Numerical experiments in semi-infinite programming

A quasi-Newton algorithm for semi-infinite programming using an L∞ exact penalty function is described, and numerical results are presented. Comparisons with three Newton algorithms and one other quasi-Newton algorithm show that the algorithm is very promising in practice

A direct search conjugate directions algorithm for unconstrained minimization

A direct search algorithm for unconstrained minimization of smooth functions is described. The algorithm minimizes the function over a sequence of successively finer grids. Each grid is defined by a set of basis vectors. From time to time these basis vectors are updated to include available second derivative information by making some basis vectors mutually conjugate. Convergence to one or more stationary points is shown, and the finite termination property of conjugate direction methods on strictly convex quadratics is retained. Numerical results show that the algorithm is effective on a variety of problems including ill-conditioned problems

Effect of limited precision on the BFGS quasi-Newton algorithm

Some claim that updating approximate Hessian information via the BFGS formula with a Cholesky factorisation offers greater numerical stability than the more straightforward approach of performing the update directly. Others claim that no such advantage exists and that any such improvement is probably due to early implementations of the DFP formula in conjunction with low accuracy line searches. We find no discernible advantage in choosing factorised implementations (over non-factorised implementations) of BFGS methods when approximate Hessian information is available to full machine precision. However, the type of implementation may have significant effects when approximate Hessian information is only available to limited precision. Furthermore, a conjugate directions factorisation outperforms the other methods explored (including Cholesky factorisation)

The impacts of environmental warming on Odonata: a review

Climate change brings with it unprecedented rates of increase in environmental temperature, which will have major consequences for the earth's flora and fauna. The Odonata represent a taxon that has many strong links to this abiotic factor due to its tropical evolutionary history and adaptations to temperate climates. Temperature is known to affect odonate physiology including life-history traits such as developmental rate, phenology and seasonal regulation as well as immune function and the production of pigment for thermoregulation. A range of behaviours are likely to be affected which will, in turn, influence other parts of the aquatic ecosystem, primarily through trophic interactions. Temperature may influence changes in geographical distributions, through a shifting of species' fundamental niches, changes in the distribution of suitable habitat and variation in the dispersal ability of species. Finally, such a rapid change in the environment results in a strong selective pressure towards adaptation to cope and the inevitable loss of some populations and, potentially, species. Where data are lacking for odonates, studies on other invertebrate groups will be considered. Finally, directions for research are suggested, particularly laboratory studies that investigate underlying causes of climate-driven macroecological patterns

Astrometric and Timing Effects of Gravitational Waves from Localized Sources

A consistent approach for an exhaustive solution of the problem of propagation of light rays in the field of gravitational waves emitted by a localized source of gravitational radiation is developed in the first post-Minkowskian and quadrupole approximation of General Relativity. We demonstrate that the equations of light propagation in the retarded gravitational field of an arbitrary localized source emitting quadrupolar gravitational waves can be integrated exactly. The influence of the gravitational field on the light propagation is examined not only in the wave zone but also in cases when light passes through the intermediate and near zones of the source. Explicit analytic expressions for light deflection and integrated time delay (Shapiro effect) are obtained accounting for all possible retardation effects and arbitrary relative locations of the source of gravitational waves, that of light rays, and the observer. It is shown that the ADM and harmonic gauge conditions can both be satisfied simultaneously outside the source of gravitational waves. Their use drastically simplifies the integration of light propagation equations and those for the motion of light source and observer in the field of the source of gravitational waves, leading to the unique interpretation of observable effects. The two limiting cases of small and large values of impact parameter are elaborated in more detail. Explicit expressions for Shapiro effect and deflection angle are obtained in terms of the transverse-traceless part of the space-space components of the metric tensor. We also discuss the relevance of the developed formalism for interpretation of radio interferometric and timing observations, as well as for data processing algorithms for future gravitational wave detectors.Comment: 43 pages, 4 Postscript figures, uses revtex.sty, accepted to Phys. Rev. D, minor corrections in formulae regarding algebraic sign

Anti-cancer effects and mechanism of actions of aspirin analogues in the treatment of glioma cancer

INTRODUCTION: In the past 25 years only modest advancements in glioma treatment have been made, with patient prognosis and median survival time following diagnosis only increasing from 3 to 7 months. A substantial body of clinical and preclinical evidence has suggested a role for aspirin in the treatment of cancer with multiple mechanisms of action proposed including COX 2 inhibition, down regulation of EGFR expression, and NF-κB signaling affecting Bcl-2 expression. However, with serious side effects such as stroke and gastrointestinal bleeding, aspirin analogues with improved potency and side effect profiles are being developed. METHOD: Effects on cell viability following 24 hr incubation of four aspirin derivatives (PN508, 517, 526 and 529) were compared to cisplatin, aspirin and di-aspirin in four glioma cell lines (U87 MG, SVG P12, GOS – 3, and 1321N1), using the PrestoBlue assay, establishing IC50 and examining the time course of drug effects. RESULTS: All compounds were found to decrease cell viability in a concentration and time dependant manner. Significantly, the analogue PN517 (IC50 2mM) showed approximately a twofold increase in potency when compared to aspirin (3.7mM) and cisplatin (4.3mM) in U87 cells, with similar increased potency in SVG P12 cells. Other analogues demonstrated similar potency to aspirin and cisplatin. CONCLUSION: These results support the further development and characterization of novel NSAID derivatives for the treatment of glioma

The management and outcome for patients with chronic subdural hematoma: a prospective, multicenter, observational cohort study in the United Kingdom

Symptomatic chronic subdural hematoma (CSDH) will become an increasingly common presentation in neurosurgical practice as the population ages, but quality evidence is still lacking to guide the optimal management for these patients. The British Neurosurgical Trainee Research Collaborative (BNTRC) was established by neurosurgical trainees in 2012 to improve research by combining the efforts of trainees in each of the United Kingdom (UK) and Ireland's neurosurgical units (NSUs). The authors present the first study by the BNTRC that describes current management and outcomes for patients with CSDH throughout the UK and Ireland. This provides a resource both for current clinical practice and future clinical research on CSDH

Comprehensive molecular portraits of human breast tumours

We analysed primary breast cancers by genomic DNA copy number arrays, DNA methylation, exome sequencing, messenger RNA arrays, microRNA sequencing and reverse-phase protein arrays. Our ability to integrate information across platforms provided key insights into previously defined gene expression subtypes and demonstrated the existence of four main breast cancer classes when combining data from five platforms, each of which shows significant molecular heterogeneity. Somatic mutations in only three genes (TP53, PIK3CA and GATA3) occurred at.10% incidence across all breast cancers; however, there were numerous subtype-associated and novel gene mutations including the enrichment of specific mutations in GATA3, PIK3CA and MAP3K1 with the luminal A subtype. We identified two novel protein-expression-defined subgroups, possibly produced by stromal/microenvironmental elements, and integrated analyses identified specific signalling pathways dominant in each molecular subtype including a HER2/phosphorylated HER2/EGFR/phosphorylated EGFR signature within the HER2-enriched expression subtype. Comparison of basal-like breast tumours with high-grade serous ovarian tumours showed many molecular commonalities, indicating a related aetiology and similar therapeutic opportunities. The biological finding of the four main breast cancer subtypes caused by different subsets of genetic and epigenetic abnormalities raises the hypothesis that much of the clinically observable plasticity and heterogeneity occurs within, and not across, these major biological subtypes of breast cancer. © 2012 Macmillan Publishers Limited. All rights reserved

Outcomes following surgery in subgroups of comatose and very elderly patients with chronic subdural hematoma

Increasing age and lower pre-operative Glasgow coma score (GCS) are associated with worse outcome after surgery for chronic subdural haematoma (CSDH). Only few studies have quantified outcomes specific to the very elderly or comatose patients. We aim to examine surgical outcomes in these patient groups. We analysed data from a prospective multicentre cohort study, assessing the risk of recurrence, death, and unfavourable functional outcome of very elderly (≥ 90 years) patients and comatose (pre-operative GCS ≤ 8) patients following surgical treatment of CSDH. Seven hundred eighty-five patients were included in the study. Thirty-two (4.1%) patients had pre-operative GCS ≤ 8 and 70 (8.9%) patients were aged ≥ 90 years. A higher proportion of comatose patients had an unfavourable functional outcome (38.7 vs 21.7%; p = 0.03), although similar proportion of comatose (64.5%) and non-comatose patients (61.8%) functionally improved after surgery (p = 0.96). Compared to patients aged < 90 years, a higher proportion of patients aged ≥ 90 years had unfavourable functional outcome (41.2 vs 20.5%; p < 0.01), although approximately half had functional improvement following surgery. Mortality risk was higher in both comatose (6.3 vs 1.9%; p = 0.05) and very elderly (8.8 vs 1.1%; p < 0.01) groups. There was a trend towards a higher recurrence risk in the comatose group (19.4 vs 9.5%; p = 0.07). Surgery can still provide considerable benefit to very elderly and comatose patients despite their higher risk of morbidity and mortality. Further research would be needed to better identify those most likely to benefit from surgery in these groups