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

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

Status of the 80Mbit/s Receiver for the CMS digital optical link

The first prototype of the 80Mbit/s optical receiver ASIC for the CMS digital optical link has been manufactured in a 0.25µm commercial CMOS process. The circuit design has been made using radiation tolerant layout techniques. Its performance satisfies the low power, wide dynamic range, sensitivity and speed specifications. The radiation hardness of the receiver has been verified irradiating the diode with 6 MeV neutrons (up to 6.5·1014 n/cm2) and the receiver circuit with 10KeV X-rays (up to 20 Mrad). A second prototype has been submitted for fabrication in the same commercial CMOS process. I

First-line chemotherapy for ovarian cancer – the controversy continues

British Journal of Cancer (2002) 87, 813–814. doi:10.1038/sj.bjc.6600568 www.bjcancer.co

Precision measurements of large scale structure with future type Ia supernova surveys

Type Ia supernovae are currently the best known standard candles at cosmological distances. In addition to providing a powerful probe of dark energy they are an ideal source of information about the peculiar velocity field of the local universe. Even with the very small number of supernovae presently available it has been possible to measure the dipole and quadrupole of the local velocity field out to z~0.025. With future continuous all-sky surveys like the LSST project the luminosity distances of tens of thousands of nearby supernovae will be measured accurately. This will allow for a determination of the local velocity structure of the universe as a function of redshift with unprecedented accuracy, provided the redshifts of the host galaxies are known. Using catalogues of mock surveys we estimate that future low redshift supernova surveys will be able to probe sigma-8 to a precision of roughly 5% at 95% C.L. This is comparable to the precision in future galaxy and weak lensing surveys and with a relatively modest observational effort it will provide a crucial cross-check on future measurements of the matter power spectrum.Comment: 18 pages, 9 figures, submitted to JCA

A dose-finding study of carboplatin–epirubicin–docetaxel in advanced epithelial ovarian cancer

The docetaxel–carboplatin combination is active and well tolerated in patients with epithelial ovarian cancer. We added epirubicin to this combination to investigate additional benefits of anthracyclines in epithelial ovarian cancer. Twenty-one patients, FIGO Ic-IV, performance status 0–1, were treated in four dose cohorts. Docetaxel was fixed at 75 mg m−2, carboplatin doses were AUC 4–5 and epirubicin doses were 50–60 mg m−2. Drugs were given on day 1, every 3 weeks, except in cohort 3, where epirubicin was given on day 8. Dexamethasone was given prophylactically. One dose-limiting toxicity occurred in cohorts 1, 2 and 4, two occurred in cohort 3. Complicated neutropenia occurred in two patients in cohorts 1 and 2 and one patient in cohorts 3 and 4. Two patients experienced grade III diarrhoea or stomatitis in cohort 1 and two in cohort 3. There were no treatment-related deaths. Grade II sensory neuropathy occurred in one patient. No cardiac toxicity or significant oedema was observed. The overall response rate was 36%, and 62% were CA125 responders. The predefined maximum tolerated dose was exceeded in cohort 3. The cohort 4 dose level (epirubicin 50 mg m−2, carboplatin AUC 4, docetaxel 75 mg m−2), warrants further study

Multi-color Optical and NIR Light Curves of 64 Stripped-Envelope Core-Collapse Supernovae

We present a densely-sampled, homogeneous set of light curves of 64 low redshift (z < 0.05) stripped-envelope supernovae (SN of type IIb, Ib, Ic and Ic-bl). These data were obtained between 2001 and 2009 at the Fred L. Whipple Observatory (FLWO) on Mt. Hopkins in Arizona, with the optical FLWO 1.2-m and the near-infrared PAIRITEL 1.3-m telescopes. Our dataset consists of 4543 optical photometric measurements on 61 SN, including a combination of UBVRI, UBVr'i', and u'BVr'i', and 2142 JHKs near-infrared measurements on 25 SN. This sample constitutes the most extensive multi-color data set of stripped-envelope SN to date. Our photometry is based on template-subtracted images to eliminate any potential host galaxy light contamination. This work presents these photometric data, compares them with data in the literature, and estimates basic statistical quantities: date of maximum, color, and photometric properties. We identify promising color trends that may permit the identification of stripped-envelope SN subtypes from their photometry alone. Many of these SN were observed spectroscopically by the CfA SN group, and the spectra are presented in a companion paper (Modjaz et al. 2014). A thorough exploration that combines the CfA photometry and spectroscopy of stripped-envelope core-collapse SN will be presented in a follow-up paper.Comment: 26 pages, 17 figures, 8 tables. Revised version resubmitted to ApJ Supplements after referee report. Additional online material is available through http://cosmo.nyu.edu/SNYU

Offspring Production among the Extended Relatives of Samoan Men and Fa'afafine

Androphilia refers to sexual attraction to adult males, whereas gynephilia refers to sexual attraction to adult females. Male androphilia is an evolutionary paradox. Its development is at least partially influenced by genetic factors, yet male androphiles exhibit lower reproductive output, thus raising the question of how genetic factors underlying its development persist. The sexual antagonism hypothesis posits that the fitness costs associated with genetic factors underlying male androphilia are offset because these same factors lead to elevated reproduction on the part of the female relatives of androphilic males. Western samples drawn from low fertility populations have yielded inconsistent results when testing this hypothesis. Some studies documented elevated reproduction among the matrilineal female kin of androphilic males, whereas others found such effects in the paternal line. Samoa is a high-fertility population in which individuals reproduce closer to their maximum capacities. This study compared the reproductive output of the paternal and maternal line grandmothers, aunts, and uncles of 86 Samoan androphilic males, known locally as fa'afafine, and 86 Samoan gynephilic males. Reproductive output was elevated in the paternal and maternal line grandmothers, but not aunts or uncles, of fa'afafine. These findings are consistent with the sexual antagonism hypothesis and suggest that male androphilia is associated with elevated reproduction among extended relatives in both the maternal and paternal line. Discussion focuses on how this study, in conjunction with the broader literature, informs various models for the evolution of male androphilia via elevated reproduction on the part of female kin