150 research outputs found

    On the existence of sure profits via flash strategies

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    © Applied Probability Trust 2019. We introduce and study the notion of sure profits via flash strategies, consisting of a high-frequency limit of buy-and-hold trading strategies. In a fully general setting, without imposing any semimartingale restriction, we prove that there are no sure profits via flash strategies if and only if asset prices do not exhibit predictable jumps. This result relies on the general theory of processes and provides the most general formulation of the well-known fact that, in an arbitrage-free financial market, asset prices (including dividends) should not exhibit jumps of a predictable direction or magnitude at predictable times. We furthermore show that any price process is always right-continuous in the absence of sure profits. Our results are robust under small transaction costs and imply that, under minimal assumptions, price changes occurring at scheduled dates should only be due to unanticipated information releases

    Seksuele disfunctie en relatieproblemen na prostaatkankerbehandeling: De gewenste zorg vanuit het oogpunt van patiënt en partner

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    Erectile dysfunction (ED) is one of the most common side effects of prostate cancer (PC) treatment and may lead to changes in a relationship. The aim of this study was to identify sexual and/or relational problems and to investigate what kind of supportive care is preferred by patients and their partners. A cross-sectional survey was performed among men diagnosed with PC enrolled in active surveillance or treated with laparoscopic radical prostatectomy, brachytherapy, intensity-modulated radiotherapy or hormonal therapy. If possible, partners were included as well. Out of 250 patients, 80,5% suffered from moderate to severe erectile complaints. Half of them (53,7%) was treated for ED and a great part was partially (30,7%) up to not satisfied (25,7%). Out of 168 partners, 50,6% found it difficult to cope with changes around sexuality. The majority of men (74,7%) preferred a standard consultation with a urologist-sexologist three months after treatment to discuss sexuality

    Quantitative ultrasound of the calcaneus (QUS): A valuable tool in the identification of patients with non-metastatic prostate cancer requiring screening for osteoporosis

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    Non-metastatic prostate cancer (PCa) patients are at increased risk for osteoporosis and fractures mainly due to androgen deprivation therapy (ADT)-associated hypogonadism, but this remains largely underdiagnosed and untreated. In this study, we examine the value of pre-screening calcaneal QUS in identifying patients who should be referred for screening for osteoporosis using dual-energy X-Ray absorptiometry (DXA). In a single-center retrospective cross-sectional cohort study, we analysed data on DXA and calcaneal QUS measurements systematically collected between 2011 and 2013 in all non-metastatic PCa patients attending our Uro-Oncological Clinic at the Leiden University Medical Center. Receiver operating characteristic curves were used to assess the positive (PPV) and negative (NPV) predictive values of QUS T-scores of 0, −1.0, and − 1.8 in identifying DXA-diagnosed osteoporosis (T-scores ≤ − 2.5 and ≤ −2) at lumbar spine and/or femoral neck. Complete sets of data were available in 256 patients, median age 70.9 (53.6–89.5) years; 93.0 % had received local treatment, 84.4 % with additional ADT. Prevalence of osteoporosis and osteopenia was respectively 10.5 % and 53 %. Mean QUS T-score was −0.54 ± 1.58. Whereas PPV at any QUS T-score was <25 %, precluding the use of QUS as surrogate for DXA in screening for osteoporosis, QUS T-scores of −1.0 to 0.0 had a NPV of ≥94.5 % for DXA T-scores ≤ 2.5 and ≤ −2 at any site, confidently identifying patients least likely to have osteoporosis, thereby significantly reducing the number of patients requiring DXA screening for diagnosing osteoporosis by up to two-third. Osteoporosis screening is a significant unmet need in non-metastatic prostate cancer patients treated with ADT, and QUS may represent a valuable alternative pre-screening strategy to overcome logistics, time demands, and economic barriers encountered with current strategies for osteoporosis screening in these patients. Osteoporosis and associated increased fracture risk are common in non-metastatic prostate carcinoma, mainly due to androgen deprivation therapy, but these often remain underdiagnosed and untreated. We demonstrate that QUS is a safe, less costly pre-screen tool that reduces by up to two-third the number of patients requiring referral for DXA for osteoporosis screening

    Pelvic floor dysfunction is not a risk factor for febrile urinary tract infection in adults

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    OBJECTIVE To determine whether pelvic floor dysfunction (PFD) might be a risk factor for or consequence of febrile urinary tract infection (UTI), as UTI in adults is a common infection in which an underlying urological abnormality is often considered, and as in children, PFD is also thought to have a pathophysiological role in adults with UTI. PATIENTS AND METHODS A multicentre case-control study was conducted at 26 primary-care centres and at six Emergency Departments of regional hospitals. Cases were consecutive patients aged >= 18 years, who presented with febrile UTI. Controls were randomly selected subjects who visited their general practitioner for reasons other than UTI or fever. A validated pelvic floor questionnaire (the Pelvic Floor Inventories Leiden, PelFIs) was used to assess pelvic floor function. RESULTS Between October 2006 and December 2007, 153 cases were included; of these, the completed questionnaires of 102 (response rate 67%) were compared to those of 100 of 110 (response rate 91%) controls. The median age of cases and controls was 65 and 58 years, respectively; 40% of cases and controls were men. The percentage of PelFIs outcomes consistent with PFD were comparable between cases and controls, at 21% vs 23%, respectively (odds ratio 0.9, 95% confidence interval, CI, 0.4-1.78). In the multivariate analysis, comorbidity (odds ratio 4.9, 95% CI 2.2-11.1) and a history of UTI (odds ratio 2.5, 95% CI 1.0-6.1) were independent significant risk factors for febrile UTI, whereas PFD was not (odds ratio 1.0, 0.5-2.2). Within the group of cases, PFD was not associated with bacteriuria during assessment of PelFIs (odds ratio 1.1, 95% CI 0.4-3.5) and inversely related to a history of UTI within the previous year (odds ratio 0.2, 0.1-0.9). CONCLUSIONS PFD is common among adults but it does not seem to be a risk factor for febrile UTI.Immunogenetics and cellular immunology of bacterial infectious disease

    An ex vivo Tissue Culture Model for the Assessment of Individualized Drug Responses in Prostate and Bladder Cancer

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    Urological malignancies, including prostate and bladder carcinoma, represent a major clinical problem due to the frequent occurrence of therapy resistance and the formation of incurable distant metastases. As a result, there is an urgent need for versatile and predictive disease models for the assessment of the individualized drug response in urological malignancies. Compound testing on ex vivo cultured patient-derived tumor tissues could represent a promising approach. In this study, we have optimized an ex vivo culture system of explanted human prostate and bladder tumors derived from clinical specimens and human cancer cell lines xenografted in mice. The explanted and cultured tumor slices remained viable and tissue architecture could be maintained for up to 10 days of culture. Treatment of ex vivo cultured human prostate and bladder cancer tissues with docetaxel and gemcitabine, respectively, resulted in a dose-dependent anti-tumor response. The dose-dependent decrease in tumor cells upon administration of the chemotherapeutic agents was preceded by an induction of apoptosis. The implementation and optimization of the tissue slice technology may facilitate the assessment of anti-tumor efficacies of existing and candidate pharmacological agents in the complex multicellular neoplastic tissues from prostate and bladder cancer patients. Our model represents a versatile “near-patient” tool to determine tumor-targeted and/or stroma-mediated anti-neoplastic responses, thus contributing to the field of personalized therapeutics

    The aldehyde dehydrogenase enzyme 7A1 is functionally involved in prostate cancer bone metastasis

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    High aldehyde dehydrogenase (ALDH) activity can be used to identify tumor-initiating and metastasis-initiating cells in various human carcinomas, including prostate cancer. To date, the functional importance of ALDH enzymes in prostate carcinogenesis, progression and metastasis has remained elusive. Previously we identified strong expression of ALDH7A1 in human prostate cancer cell lines, primary tumors and matched bone metastases. In this study, we evaluated whether ALDH7A1 is required for the acquisition of a metastatic stem/progenitor cell phenotype in human prostate cancer. Knockdown of ALDH7A1 expression resulted in a decrease of the α2hi/αvhi/CD44+ stem/progenitor cell subpopulation in the human prostate cancer cell line PC-3M-Pro4. In addition, ALDH7A1 knockdown significantly inhibited the clonogenic and migratory ability of human prostate cancer cells in vitro. Furthermore, a number of genes/factors involved in migration, invasion and metastasis were affected including transcription factors (snail, snail2, and twist) and osteopontin, an ECM molecule involved in metastasis. Knockdown of ALDH7A1 resulted in decreased intra-bone growth and inhibited experimentally induced (bone) metastasis, while intra-prostatic growth was not affected. In line with these observations, evidence is presented that TGF-β, a key player in cancer invasiveness and bone metastasis, strongly induced ALDH activity while BMP7 (an antagonist of TGF-β signaling) down-regulated ALDH activity. Our findings show, for the first time, that the ALDH7A1 enzyme is functionally involved in the formation of bone metastases and that the effect appeared dependent on the microenvironment, i.e., bone versus prostate

    CRIPTO and its signaling partner GRP78 drive the metastatic phenotype in human osteotropic prostate cancer

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    CRIPTO (CR-1, TDGF1) is a cell surface/secreted oncoprotein actively involved in development and cancer. Here, we report that high expression of CRIPTO correlates with poor survival in stratified risk groups of prostate cancer (PCa) patients. CRIPTO and its signaling partner glucose-regulated protein 78 (GRP78) are highly expressed in PCa metastases and display higher levels in the metastatic ALDHhigh sub-population of PC-3M-Pro4Luc2 PCa cells compared with non-metastatic ALDHlow. Coculture of the osteotropic PC-3M-Pro4Luc2 PCa cells with differentiated primary human osteoblasts induced CRIPTO and GRP78 expression in cancer cells and increases the size of the ALDHhigh sub-population. Additionally, CRIPTO or GRP78 knockdown decreases proliferation, migration, clonogenicity and the size of the metastasis-initiating ALDHhigh sub-population. CRIPTO knockdown reduces the invasion of PC-3M-Pro4Luc2 cells in zebrafish and inhibits bone metastasis in a preclinical mouse model. These results highlight a functional role for CRIPTO and GRP78 in PCa metastasis and suggest that targeting CRIPTO/GRP78 signaling may have significant therapeutic potential.Oncogene advance online publication, 10 April 2017; doi:10.1038/onc.2017.87
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