Resistance to chemotherapy in advanced ovarian cancer: mechanisms and current strategies

Although treatment for advanced epithelial ovarian cancer has improved over recent years with the introduction of taxane–platinum chemotherapy, the majority of patients will relapse, and in most the disease remains incurable. A thorough understanding of drug resistance mechanisms is needed, as this remains the largest obstacle in treating patients with recurrent disease. Multidrug resistance proteins, mismatch repair processes and alterations in the p53 pathway are examples of properties within tumour cells that may lead to drug resistance. Novel agents designed to circumvent these mechanisms (e.g. PSC 833, ONYX-015 and ADP53) are currently being investigated for ovarian cancer patients. Further improvements may result from the optimisation of existing first-line regimens with more creative schedules, perhaps involving sequential or intraperitoneal administration of existing drugs, and the incorporation of newer noncross-resistant drugs

Dark energy FRW cosmology - dynamical system reconstruction

We develop a simple method of dark energy reconstruction using a geometrical form of the luminosity-distance relation. In this method the FRW dynamical system with dark energy is reconstructed instead of the equation of state parameter. We give several examples which illustrate the usefulness of our method in fitting the redshift transition from the decelerating to accelerating phase as the value of the Hubble function at the transition.Comment: Talk presented at Spanish Relativity Meeting 2007, Puerto de la Cruz, Tenerife, Spain, 10-14 September 200

Dark Energy Accretion onto a Black Hole in an Expanding Universe

By using the solution describing a black hole embedded in the FLRW universe, we obtain the evolving equation of the black hole mass expressed in terms of the cosmological parameters. The evolving equation indicates that in the phantom dark energy universe the black hole mass becomes zero before the Big Rip is reached.Comment: 7 pages, no figures, errors is correcte

Photometry of SN 2002ic and Implications for the Progenitor Mass-Loss History

We present new pre-maximum and late-time optical photometry of the Type Ia/IIn supernova 2002ic. These observations are combined with the published V-band magnitudes of Hamuy et al. (2003) and the VLT spectrophotometry of Wang et al. (2004) to construct the most extensive light curve to date of this unusual supernova. The observed flux at late time is significantly higher relative to the flux at maximum than that of any other observed Type Ia supernova and continues to fade very slowly a year after explosion. Our analysis of the light curve suggests that a non-Type Ia supernova component becomes prominent $\sim20$ days after explosion. Modeling of the non-Type Ia supernova component as heating from the shock interaction of the supernova ejecta with pre-existing circumstellar material suggests the presence of a $\sim1.7 10^{15}$ cm gap or trough between the progenitor system and the surrounding circumstellar material. This gap could be due to significantly lower mass-loss $\sim15 (v_w/10 km/s)^{-1}$ years prior to explosion or evacuation of the circumstellar material by a low-density fast wind. The latter is consistent with observed properties of proto-planetary nebulae and with models of white-dwarf + asymptotic giant branch star progenitor systems with the asymptotic giant branch star in the proto-planetary nebula phase.Comment: accepted for publication in Ap

Novae as a Mechanism for Producing Cavities around the Progenitors of SN 2002ic and Other SNe Ia

We propose that a nova shell ejected from a recurrent nova progenitor system created the evacuated region around the explosion center of SN 2002ic. In this picture, periodic shell ejections due to nova explosions on a white dwarf sweep up the slow wind from the binary companion, creating density variations and instabilities that lead to structure in the circumstellar medium (CSM). Our model naturally explains the observed gap between the supernova explosion center and the CSM in SN 2002ic, accounts for the density variations observed in the CSM, and resolves the coincidence problem of the timing of the explosion of SN 2002ic with respect to the apparent cessation of mass-loss in the progenitor system. We also consider such nova outburst sweeping as a generic feature of Type Ia supernovae with recurrent nova progenitors.Comment: Accepted to ApJL. 11 pages, 1 tabl

RELIABILITY OF CLINICAL ISOKINETIC DYNAMOMETRY IN PATHOLOGICAL ATHLETIC SHOULDERS

There have been relatively few studies of the reliability of isokinetic shoulder testing, and only Malerba et al. (1993) have investigated patients with shoulder joint pathology (patients ranged in activity level from sedentary to highly active). Furthermore, all existing studies have involved a level of procedural standardisation which, while desirable, cannot always be achieved in a clinical environment, that is, where most isokinetic testing is performed. Therefore, the aim of this study was to assess the reliability of isokinetic testing of pathological athletic shoulders in a clinical environment, under routine clinical conditions. Twenty-two athletic patients (mean age 26 years) presenting with a range of pathologies including post-subluxation, post-dislocation, and post-surgical reconstruction were tested. Patients were tested on two occasions, separated by a time interval during which their clinical status was not expected to change (most tests were one week apart; mean interval 10 days). Bilateral isokinetic strength of the shoulder internal and external rotators were tested on a Cybex 6000 dynamometer at 2.09 and 4.19 radianslsecond (concentric) and 2.09 radianslsecond (eccentric). Patients were tested in a seated position, in 45 degrees of shoulder abduction, and 90 degrees of elbow flexion. Tests were performed in essentially the same fashion on each occasion by the same tester. However, the constraints of a busy clinical environment meant that precise control and exact replication may not have always been achieved. Intra-class correlation coefficients (ICC) for absolute concentric peak torque, work, and average power were all above 0.9. Eccentric ICCs were generally above 0.8. These values are as high as, or higher than, those reported in the literature for studies of healthy subjects conducted under more stringent conditions than can be achieved in a clinical environment. The reliability of commonly calculated ratios, such as agonistlantagonist and involved/uninvolved, was lower than that of the constituent absolute scores, and in some cases were quite poor. Caution is therefore warranted in the use of such ratios. Malerba JL; Adam ML, Harris BA, Krebs DE (1993) Reliability of dynamic and isometric testing of shoulder external and internal rotators. Journal of Orthopaedic and Sports Physical Therapy 18543-552

Mitigating the risk of Zika virus contamination of raw materials and cell lines in the manufacture of biologicals

Ensuring the virological safety of biologicals is challenging due to the risk of viral contamination of raw materials and cell banks, and exposure during in-process handling to known and/or emerging viral pathogens. Viruses may contaminate raw materials and biologicals intended for human or veterinary use and remain undetected until appropriate testing measures are employed. The outbreak and expansive spread of the mosquito-borne flavivirus Zika virus (ZIKV) poses challenges to screening human- and animal -derived products used in the manufacture of biologicals. Here, we report the results of an in vitro study where detector cell lines were challenged with African and Asian lineages of ZIKV. We demonstrate that this pathogen is robustly detectable by in vitro assay, thereby providing assurance of detection of ZIKV, and in turn underpinning the robustness of in vitro virology assays in safety testing of biologicals