Optimal sequential fingerprinting: Wald vs. Tardos

We study sequential collusion-resistant fingerprinting, where the fingerprinting code is generated in advance but accusations may be made between rounds, and show that in this setting both the dynamic Tardos scheme and schemes building upon Wald's sequential probability ratio test (SPRT) are asymptotically optimal. We further compare these two approaches to sequential fingerprinting, highlighting differences between the two schemes. Based on these differences, we argue that Wald's scheme should in general be preferred over the dynamic Tardos scheme, even though both schemes have their merits. As a side result, we derive an optimal sequential group testing method for the classical model, which can easily be generalized to different group testing models.Comment: 12 pages, 10 figure

High Multiplicity Scheduling with Switching Costs for few Products

We study a variant of the single machine capacitated lot-sizing problem with sequence-dependent setup costs and product-dependent inventory costs. We are given a single machine and a set of products associated with a constant demand rate, maximum loading rate and holding costs per time unit. Switching production from one product to another incurs sequencing costs based on the two products. In this work, we show that by considering the high multiplicity setting and switching costs, even trivial cases of the corresponding "normal" counterparts become non-trivial in terms of size and complexity. We present solutions for one and two products.Comment: 10 pages (4 appendix), to be published in Operations Research Proceedings 201

Curcumin as Treatment for Bladder Cancer : A Preclinical Study of Cyclodextrin-Curcumin Complex and BCG as Intravesical Treatment in an Orthotopic Bladder Cancer Rat Model

Objective. To evaluate the antitumor effect of cyclodextrin-curcumin complex (CDC) on human and rat urothelial carcinoma cells in vitro and to evaluate the effect of intravesical instillations of CDC, BCG, and the combination in vivo in the AY-F344 orthotopic bladder cancer rat model. Curcumin has anticarcinogenic activity on urothelial carcinoma and is therefore under investigation for the treatment of non-muscle invasive bladder cancer. Curcumin and BCG share immunomodulating pathways against urothelial carcinoma. Methods. Curcumin was complexed with cyclodextrin to improve solubility. Four human urothelial carcinoma cell lines and the AY-27 rat cell line were exposed to various concentrations of CDC in vitro. For the in vivo experiment, the AY-27 orthotopic bladder cancer F344 rat model was used. Rats were treated with consecutive intravesical instillations of CDC, BCG, the combination of CDC+BCG, or NaCl as control. Results. CDC showed a dose-dependent antiproliferative effect on all human urothelial carcinoma cell lines tested and the rat AY-27 urothelial carcinoma cell line. Moreover, intravesical treatment with CDC and CDC+BCG results in a lower percentage of tumors (60% and 68%, respectively) compared to BCG (75%) or control (85%). This difference with placebo was not statistically significant (p=0.078 and 0.199, respectively). However, tumors present in the placebo and BCG-treated rats were generally of higher stage. Conclusions. Cyclodextrin-curcumin complex showed an antiproliferative effect on human and rat urothelial carcinoma cell lines in vitro. In the aggressive orthotopic bladder cancer rat model, we observed a promising effect of CDC treatment and CDC in combination with BCG.Peer reviewe

Hereditary Breast-Ovarian Cancer Team of the University Medical Centre Groningen (UMCG):a Report

Female carriers of a germline BRCA1 or BRCA2 mutation have a cumulative lifetime ovarian cancer risk of 39-54 % or 11-23%, respectively [1, 2]. Preventive health strategies for these women include gynaecological screening aiming at early cancer detection and prophylactic salpingo-ophorectomy aiming at cancer risk reduction. However, it is becoming increasingly clear that (bi) annual gynaecological screening by transvaginal ultrasonography and serum CA125 estimation in women at increased risk of ovarian cancer is ineffective in detecting presymptomatic ovarian cancer [4]. In a recent publication a positive predictive value of 17 % and a sensitivity of less than 50 % were found for screening for ovarian cancer in a high-risk population [3]. Preventive bilateral salpingo-oophorectomy (BSO) reduces ovaria

Exposure to low-dose radiation and the risk of breast cancer among women with a familial or genetic predisposition:a meta-analysis

Women with familial or genetic aggregation of breast cancer are offered screening outside the population screening programme. However, the possible benefit of mammography screening could be reduced due to the risk of radiation-induced tumours. A systematic search was conducted addressing the question of how low-dose radiation exposure affects breast cancer risk among high-risk women. A systematic search was conducted for articles addressing breast cancer, mammography screening, radiation and high-risk women. Effects of low-dose radiation on breast cancer risk were presented in terms of pooled odds ratios (OR). Of 127 articles found, 7 were selected for the meta-analysis. Pooled OR revealed an increased risk of breast cancer among high-risk women due to low-dose radiation exposure (OR = 1.3, 95% CI: 0.9- 1.8). Exposure before age 20 (OR = 2.0, 95% CI: 1.3-3.1) or a mean of a parts per thousand yen5 exposures (OR = 1.8, 95% CI: 1.1-3.0) was significantly associated with a higher radiation-induced breast cancer risk. Low-dose radiation increases breast cancer risk among high-risk women. When using low-dose radiation among high-risk women, a careful approach is needed, by means of reducing repeated exposure, avoidance of exposure at a younger age and using non-ionising screening techniques

Genetic counseling of patients with ovarian carcinoma:acceptance, timing, and psychological wellbeing

The new Dutch guidelines on hereditary and familial ovarian carcinoma recommend genetic testing of all patients with epithelial ovarian cancer (EOC). With this study, we aimed to obtain insight into (1) the acceptance and timing of the offer of genetic counseling in women with EOC, (2) reasons for accepting or declining genetic counseling, and (3) psychological differences between women who did and did not have genetic counseling. A multicenter questionnaire survey was performed in patients with EOC in four Dutch oncology centers. The questionnaire addressed whether, how, and when genetic counseling was offered, women's arguments to accept or decline genetic counseling, and included the Cancer Worry Scale (CWS) and the Hospital Anxiety and Depression Scale (HADS). A total of 67 women completed the questionnaire, of which 43 had genetic counseling. Despite a wide variability in the timing of the offer of genetic counseling, 89% of the women were satisfied with the timing. No significant differences were found between the CWS and HADS scores for the timing of the offer of genetic counseling and whether or not women had genetic counseling. Taking the small sample size into account, the results tentatively suggest that genetic counseling may have limited impact on the psychosocial wellbeing of women with EOC. Therefore, we assume that implementation of the new guidelines offering genetic counseling to all patients with EOC will not cause considerable additional burden to these patients

Diagnostic DNA Methylation Biomarkers for Renal Cell Carcinoma:A Systematic Review

CONTEXT: The 5-yr survival of early-stage renal cell carcinoma (RCC) is approximately 93%, but once metastasised, the 5-yr survival plummets to 12%, indicating that early RCC detection is crucial to improvement in survival. DNA methylation biomarkers have been suggested to be of potential diagnostic value; however, their current state of clinical translation is unclear and a comprehensive overview is lacking. OBJECTIVE: To systematically review and summarise all literature regarding diagnostic DNA methylation biomarkers for RCC. EVIDENCE ACQUISITION: We performed a systematic literature review of PubMed, EMBASE, Medline, and Google Scholar up to January 2019, according to the Preferred Reporting Items for Systematic Review and Meta-Analysis of Diagnostic Test Accuracy Studies (PRISMA-DTA) guidelines. Included studies were scored according to the Standards for Reporting of Diagnostic Accuracy Studies (STARD) criteria. Forest plots were generated to summarise diagnostic performance of all biomarkers. Level of evidence (LoE) and potential risk of bias were determined for all included studies. EVIDENCE SYNTHESIS: After selection, 19 articles reporting on 44 diagnostic DNA methylation biomarkers and 11 multimarker panels were included; however, only 15 biomarkers were independently validated. STARD scores varied from 4 to 13 out of 23 points, with a median of 10 points. Large variation in subgroups, methods, and primer locations was observed. None of the reported biomarkers exceeded LoE III, and the majority of studies reported inadequately. CONCLUSIONS: None of the reported biomarkers exceeded LoE III, indicating their limited clinical utility. Moreover, study reproducibility and further development of these RCC biomarkers are greatly hampered by inadequate reporting. PATIENT SUMMARY: In this report, we reviewed whether specific biomarkers could be used to diagnose the most common form of kidney cancer. We conclude that due to limited evidence and reporting inconsistencies, none of these biomarkers can be used in clinical practice, and further development towards clinical use is hindered

Cognitive modeling of mindfulness therapy by autogenic training

In this paper, the effect of a mindfulness therapy based on a Network-Oriented Modeling approach is addressed. The considered therapy is Autogenic Training that can be used when under stress; it has as two main goals to achieve feeling heavy and warm body parts (limbs). Mantras have been used in therapies since long ago to make stressed individuals more relaxed, and they are also used in Autogenic Training. The presented cognitive temporal-causal network model addresses the modeling of Autogenic Training asking this into account. In the first phase a strong stress-inducing stimulus causes the individual to develop an extreme stressful emotion. In the second phase, the therapy with the two goals is shown to make the stressed individual relaxed. Hebbian learning is used to increase the influence of the therapy.</p

Bone mineral density and fractures after risk-reducing salpingo-oophorectomy in women at increased risk for breast and ovarian cancer

AbstractAimRisk-reducing salpingo-oophorectomy (RRSO) reduces ovarian cancer risk in BRCA mutation carriers. RRSO is assumed to decrease bone mineral density (BMD) and increase fracture risk more than natural menopause. We aimed to compare BMD and fracture incidence after premenopausal RRSO to general population data and identify risk factors for low BMD and fractures after RRSO.MethodsIn 212 women with RRSO at premenopausal age, BMD was measured by dual energy X-ray absorptiometry. Fractures and risk factors were assessed by self-administered questionnaire. Fracture incidence after RRSO was compared to general practitioner data by using standardised incidence ratios (SIRs). Risk factors for low standardised BMD-scores and fractures were identified by regression analyses.ResultsMedian age at RRSO was 42years (range 35–65) and duration of follow-up 5years (2–8). Standardised lumbar spine (Z=0.01, p=0.870) and femoral neck BMD (Z=0.15, p=0.019) were not lower than population BMD. Higher age at time of RRSO and use of hormonal replacement therapy were associated with higher, and current smoking with lower standardised BMD-scores. Sixteen women reported 22 fractures. Fracture incidence was not higher than expected from the general population (all fractures: 25–44years: SIR 2.12 [95% confidence interval (CI) 0.85–4.37]; 45–64years: SIR 1.65 [95% CI 0.92–2.72]).ConclusionFive years after RRSO, BMD and fracture incidence were not different than expected from the general population. Based on these data it appears safe not to intensively screen for osteoporosis within five years after RRSO, although prospective research on the long-term effects of RRSO on bone is warranted

Death and the Erotic Woman: the European Gendering of Mortality in time of Religious Change

This paper explores the use of European erotic death imagery produced in the Death and the Maiden (D&M) genre in two time periods. It compares and contrasts D&M imagery produced by the Germanic-speaking proto/early-Reformation artists, Hans Baldung (alias Grien) (c1484–1545), Niklaus Manuel (known as Deutsch) (c1484–1530) and Sebald Beham (known as Hans Sebald Beham) (1500–1550) which highlighted the folly, futility and transience of earthly vanities during the transition from Roman Catholic to Protestant Christianity, with contemporary calendar art produced by Cofani Funebri (from 2003) and Lindner (from 2010) which advertise coffins manufactured in the increasingly secular countries of Italy and Poland. Drawing on Biblical narrative, Augustinian theology and European socio-cultural perceptions of gender, this paper argues that these D&M images are highly eroticised and place woman as signifiers of transcient life (vanitas) and earthly pleasure (voluptas), juxtaposing her with a masculine/male representation of death; Death being imaged as an individual in the sixteenth century, and as a coffin in the contemporary works. The paper also contextualises the imagery in terms of traditional European Christian notions of life and death, as informed by the Biblical Fall narrative, with its elucidations of sin, concupiscence and punishment. It thus asserts that both socio-cultural and religious attitudes towards gender are highly significant in D&M imagery and indeed in terms of the artworks, argues that the masculine signifier of Death can be placed as Adam, whilst the Maiden, as fecund life, represents Eve. However, the overt eroticism of both sets of artworks also allows for a reading that draws on Messaris' [(1997). Visual persuasion; the role of images in advertising. London: Sage] notion that visual images ‘make a persuasive communication due to iconicity; the emotional response to the visual image presented’. Thus, this paper contrasts D&M imagery produced over 400 years apart to examine consciously erotic gendered thanantological allegories of women as vanitas and voluptas, and the male/masculine as representations of Death