BackgroundStandard therapy for glioblastoma includes surgery, radiotherapy, and temozolomide. This Phase 3 trial evaluates the addition of an autologous tumor lysate-pulsed dendritic cell vaccine (DCVax®-L) to standard therapy for newly diagnosed glioblastoma.MethodsAfter surgery and chemoradiotherapy, patients were randomized (2:1) to receive temozolomide plus DCVax-L (n = 232) or temozolomide and placebo (n = 99). Following recurrence, all patients were allowed to receive DCVax-L, without unblinding. The primary endpoint was progression free survival (PFS); the secondary endpoint was overall survival (OS).ResultsFor the intent-to-treat (ITT) population (n = 331), median OS (mOS) was 23.1 months from surgery. Because of the cross-over trial design, nearly 90% of the ITT population received DCVax-L. For patients with methylated MGMT (n = 131), mOS was 34.7 months from surgery, with a 3-year survival of 46.4%. As of this analysis, 223 patients are ≥ 30 months past their surgery date; 67 of these (30.0%) have lived ≥ 30 months and have a Kaplan-Meier (KM)-derived mOS of 46.5 months. 182 patients are ≥ 36 months past surgery; 44 of these (24.2%) have lived ≥ 36 months and have a KM-derived mOS of 88.2 months. A population of extended survivors (n = 100) with mOS of 40.5 months, not explained by known prognostic factors, will be analyzed further. Only 2.1% of ITT patients (n = 7) had a grade 3 or 4 adverse event that was deemed at least possibly related to the vaccine. Overall adverse events with DCVax were comparable to standard therapy alone.ConclusionsAddition of DCVax-L to standard therapy is feasible and safe in glioblastoma patients, and may extend survival.Trial registration Funded by Northwest Biotherapeutics; Clinicaltrials.gov number: NCT00045968; https://clinicaltrials.gov/ct2/show/NCT00045968?term=NCT00045968&rank=1; initially registered 19 September 2002

We examine whether the provision of nonaudit services (NAS) by incumbent auditors is associated with a reduction in the extent to which earnings reflect bad news on a timely basis (that is, news‐based conservatism). Reduced conservatism is expected to occur if relatively high levels of NAS result in reduced auditor independence and, ultimately, lower‐quality auditing. Because client‐specific demand for NAS is expected to vary, our proxy for the auditor‐client economic bond is the extent to which NAS purchases (relative to audit fees) are greater or less than expected. Using several different methods for identifying news‐based conservatism, we consistently find that higher than expected levels of NAS are not associated with reduced conservatism. This result is robust to allowing for endogenous NAS demand, as well as several explicit factors that may be associated with differences in conservatism. Similar conclusions arise from tests that use alternative measures of the economic bond between auditors and their clients, as well as in tests confined to either the Big 6 or non‐Big 6 audit firms. Our results are consistent with factors such as market‐based incentives, the threat of litigation, and alternative governance mechanisms offsetting any expected benefits to the audit firm from reducing its independence. We therefore conclude that recent legislative intervention aimed at restricting the supply of NAS is unlikely to result in increased independence in fact, although independence in appearance may be improved.

IntroductionThe effectiveness of breast cancer screening programmes in reducing mortality from breast cancer is dependent on maintaining adequate attendance at screening among eligible women. Information regarding the general characteristics and health of women who do and do not attend for breast cancer screening is limited and representative data are difficult to obtain. This paper compares the characteristics of women who do and do not attend for breast cancer screening through the National Health Service Breast Screening Programme (NHSBSP), in terms of age, deprivation and prescriptions for a variety of commonly used medications. It also assesses the characteristics of women from the same population who agreed to participate in the Million Women Study, which recruits women through the NHSBSP. HRT = hormone replacement therapy; NHSBSP = National Health Service Breast Screening Programme.Available online http://breast-cancer-research.com/content/4/1/R1 Abstract Background: Information regarding the characteristics and health of women who do and do not attend for breast cancer screening is limited and representative data are difficult to obtain. Methods: Information on age, deprivation and prescriptions for various medications was obtained for all women at two UK general practices who were invited to breast cancer screening through the National Health Service Breast Screening Programme. The characteristics of women who attended and did not attend screening were compared. Results: Of the 1064 women invited to screening from the two practices, 882 (83%) attended screening. Screening attenders were of a similar age to non-attenders but came from significantly less deprived areas (30% of attenders versus 50% of non-attenders came from the most deprived areas, P < 0.0001) and were more likely to have a current prescription for hormone replacement therapy (32% versus 19%, P < 0.0001). No significant differences in recent prescriptions of medication for hypertension, heart disease, hypercholesterolaemia, diabetes mellitus, asthma, thyroid disease or depression/anxiety were observed between attenders and non-attenders. Conclusion: Women who attend the National Health Service Breast Screening Programme come from less deprived areas and are more likely to have a current prescription for hormone replacement therapy than non-attenders, but do not differ in terms of age or recent prescriptions for various other medications.

We investigate the extent to which Australian firms that report small profits and/or small increases in earnings (i.e. benchmark beaters) have done so by the upward manipulation of these earnings. Although evidence of an unusually large number of firms managing to just beat such earnings benchmarks has been interpreted as evidence of earnings management, this approach fails to identify those firms that are the manipulators from those where unbiased earnings fall naturally into the benchmark beating group. Our results suggest that caution is required in interpreting benchmark beating as an indicator of the extent of earnings management. Using several methods for estimating the unexpected accrual component of earnings, we show that although benchmark beaters have larger positive unexpected accruals than other firms, a similar result holds when firms with small losses or earnings declines (i.e. 'just miss' firms) are compared with other firms. Moreover, there is no statistically significant difference between unexpected accruals for the benchmark beating and just miss groups. At a minimum, we reject the joint hypothesis that unexpected accruals capture earnings management and that an unusual kink around zero in the distribution of earnings levels or earnings changes is caused by earnings management. Copyright 2005 Accounting and Finance Association of Australia and New Zealand..

The Ñavanol composition and ca †eine content of green tea leaf, black tea quality parameters of theaÑavins, thearubigins, liquor brightness and total colour varied more among clones than with time of the year. In green leaf, either ([)epicatechin gallate or ([)epigallocatechin gallate was the dominant Ñavanol present. Regression analysis of tastersÏ preferences for black teas against green leaf chemical components showed positive and signiÐcant correlations for ([)epicatechin gallate (r \ 0É498, P O 0É05 for taster A ; r \ 0É665, P O 0É01 for taster B, and r \ 0É678, P O 0É01 for both tastersÏ overall ranking), ([)epigallocatechin gallate (r \ 0É513, P O 0É05 for taster B ; r \ 0É532, P O 0É05 for both tastersÏ overall ranking and ca †eine (r \ 0É523, P O 0É05 for taster A ; r \ 0É657, P O 0É01 for taster B ; and r \ 0É686, P O 0É01 for both tastersÏ overall ranking). Similar regressions against black tea theaÑavins, thearubigin content, liquor brightness and total colour were not signiÐcant. The results suggest that the green leaf chemical components, ([)epicatechin gallate, ([)epigallocatechin gallate and ca †eine could be used as quality potential indicators during clonal selection and propagation.