Low-Jitter Clock Multiplication: a Comparioson between PLLs and DLLs

This paper shows that, for a given power budget, a practical phase-locked loop (PLL)-based clock multiplier generates less jitter than a delay-locked loop (DLL) equivalent. This is due to the fact that the delay cells in a PLL ring-oscillator can consume more power per cell than their counterparts in the DLL. We can show that this effect is stronger than the notorious jitter accumulation effect that occurs in the voltage-controlled oscillator (VCO) of a PLL. First, an analysis of the stochastic-output jitter of the architectures, due to the most important noise sources, is presented. Then, another important source of jitter in a DLL-based clock multiplier is treated, namely the stochastic mismatch in the delay cells which compose the DLL voltage-controlled delay line (VCDL). An analysis is presented that relates the stochastic spread of the delay of the cells to the output jitter of the clock multiplier. A circuit design technique, called impedance level scaling, is then presented which allows the designer to optimize the noise and mismatch behavior of a circuit, independently from other specifications such as speed and linearity. Applying this technique on a delay cell design yields a direct tradeoff between noise induced jitter and power usage, and between stochastic mismatch induced jitter and power usage

Nab-paclitaxel in pretreated metastatic breast cancer: evaluation of activity, safety, and quality of life

Objective: Metastatic breast cancer (MBC) is an incurable disease; the treatment of this disease prolongs survival, improving the quality of life (QoL) with a balance between efficacy and toxicity of the treatment. In recent years, treatment with nab-paclitaxel has improved the already known antitumor activity of conventional paclitaxel, in terms of increased efficacy and better tolerability. The aim of this study was to evaluate nab-paclitaxel in Italian patients with MBC. Methods: We conducted a retrospective analysis of 90 patients with histologically confirmed diagnosis of MBC. To evaluate the efficacy of nab-paclitaxel, overall survival (OS), progression-free survival (PFS), and overall response rate were the primary endpoints, whereas carbohydrate antigen 15.3 (Ca15.3) reduction, QoL, and tolerability were secondary endpoints. Results: The median OS was 10.4 months, the median PFS was 6.8 months. A considerable difference Ca15.3 before and after treatment was observed. Descriptive and regression analyses were done to examine the associations between Ca15.3 response and OS, demonstrating good correlation, revealing that Ca15.3 reduction is an important predictor of OS. Conclusion: Nab-paclitaxel is an effective and well-tolerated treatment of patients affected by MBC. The drug showed an improved tolerability profile. With all the limitations of the observational nature of our results, nab-paclitaxel has proven to be an effective and safe therapeutic option in patients with MBC

Progression-free survival as a surrogate endpoint of overall survival in patients with metastatic colorectal cancer

Background: In many clinical trials designed to assess the efficacy of anticancer treatments, overall survival (OS) is often used as a primary endpoint despite its several points of weakness. Methods: This study evaluated the role of progression-free survival (PFS) in the first three lines of treatment as a potential surrogate endpoint of OS in patients with metastatic colorectal cancer (MCRC). One hundred and twenty patients with MCRC were enrolled in this study. The median PFS of the first-, second-, and third-lines of treatment and the OS were evaluated. The correlation between the time to progression and the OS was analyzed. The median PFS of the three lines of treatment were 8.5, 5, and 3 months, respectively. Results: The median OS was 32.4 months. A modest correlation was found between the PFS to the first-line treatment with Folfox\u2013avastin and OS. Similar data were obtained with the second-line treatment. However, no correlation was found between the PFS and OS during the third-line treatment. The regression analysis revealed that PFS is predictive of OS. Conclusion: In brief, the PFS of the first- and second-lines of treatment could be a good candidate as a surrogate endpoint of OS in patients with MCRC

Eficácia da associaçao da linfocintigrafia na gama-câmara e do corante vital para identificaçao do linfonodo sentinela no câncer de mama

Orientador: Luiz Fernando Bleggi-TorresDissertaçao (mestrado) - Universidade Federal do Paraná, Setor de Ciencias da SaúdeResumo: O linfonodo sentinela e capaz de predizer o estado da axila no câncer de mama e evitar esvaziamentos axilares desnecessários. Entre as técnicas para identificação deste linfonodo, a associação do corante vital e do gama-probe e a que apresenta melhores resultados. Entretanto, o gama-probe tem custo elevado, o que limita a maior difusão da técnica nos países em desenvolvimento. O objetivo deste estudo, realizado nos Serviços de Cirurgia Oncológica, Medicina Nuclear e Anatomia Patológica do Hospital Nossa Senhora das Gracas, em Curitiba, foi avaliar a eficacia de uma técnica inédita para identificação deste linfonodo no câncer de mama. No período de outubro de 1999 a agosto de 2001, foram incluídas 52 pacientes que concordaram em participar deste estudo prospectivo, descritivo, aprovado pelo Comitê de Ética em Pesquisa independente. Todas as pacientes eram portadoras de carcinomas mamários invasores, T1 e T2 (UICC) e axila negativa ao exame clínico. A idade variou de 33 a 88 anos (media=55,4 anos) e o tamanho tumoral entre 5 e 50 mm (media=18 mm). Uma hora antes da cirurgia, as pacientes foram submetidas a linfocintigrafia na gama-câmara (ELCINT 409, 1988, Haifa, Israel), com injeção subdérmica do 99mTC-sulfeto de antimônio ou do 99mTC-fitato (0,4 ml, 0,8 microCi). A projeção do linfonodo sentinela, identificado na gama-câmara, era marcada na pele. No centro cirúrgico, apos a indução da anestesia, injetava-se na sub-derme 1 ml do azul patente 2% (Laboratoire Guerbert, Paris, France). Nas pacientes em que o azul patente não identificou o linfonodo sentinela, era realizada amostragem axilar na área marcada pela linfocintigrafia pré-operatória. O linfonodo sentinela foi identificado em 98,1% das pacientes. Em quatro pacientes em que houve falha com o azul patente, o linfonodo sentinela foi identificado através da amostragem axilar auxiliada pela gama-câmara. Além disso, em uma paciente em que o houve falha da gama-câmara, o azul patente conseguiu identificá-lo. A acurácia do linfonodo sentinela foi de 94,1%, com índice de falso-negativo de 17,6%. Estes resultados foram comparáveis aos encontrados com o gama-probe, que possui custos mais elevados. Portanto, esta técnica pode ser uma alternativa acessível para identificação do linfonodo sentinela no câncer de mama nos países em desenvolvimento.Abstract: Several reports have demonstrated the accurate prediction of axillary nodal status with sentinel lymph node biopsy in breast câncer. A wide range of different techniques have been employed for lymphatic mapping. The association of blue dye and the probe seems to be the most reliable of them. However, the probe is an expensive technique, limiting for developing countries. The purpose of this analyses, performed from October 1999 to August 2001, in the Division of Surgical Oncology, Nuclear Medicine and Anatomic Pathology, Nossa Senhora das Gracas Hospital, Curitiba, Brazil, was to determine the efficacy and viability of a new sentinel node technique in breast cancer. 52 consecutive patients were enrolled in this descriptive, prospective, review board-approved study after informed consent was obtained. Patients with clinical stage T1-2, NO, MO invasive breast cancer were eligible. The median age was 56,4 years (range, 33 to 88 years). The median tumor size was 18 mm (range, 5 to 50 mm). All patients underwent sentinel node biopsy with preoperative sub-dermal radiotracer injection ("^C-atimonium sulfide in 40 patients and "^TC-fitate in 12 patients - 0,4 ml, 0,8 pCi) in gamma-camera, one hour before surgery (ELCINT 409, 1988, Haifa, Israel), and patent blue 2% (Laboratoire Guerbert, Paris, France) 1 ml sub-dermal intra-operative. The protocol specified if blue node were not found at surgery, then axillary sampling should be done in sentinel node projection designated by gamma-camera. Sentinel node were identified in 98,1% patients. In 4 patients the axillary sampling was supported by the gamma-camera only, due to failure of the blue dye technique. At the same time, the blue dye identified the sentinel node in one gamma-camera failure. Of the patients with sentinel node identified, 56,6% had only one sentinel node removed. Overall accuracy was 94,1% and false-negative rate 17,6%. These data support this technique as reliable for developing countries, with lower costs than the probe and similar results in sentinel node identification

The patient-physician relationship in the face of oncological disease: A review of literature on the emotional and psychological reactions of patients and physician

The physician-patient relationship is daily destabilized by emotional reactions and psychic defenses that cancer arises in the two partners. Continued scientific and technological progresses which were reached by medicine in recent years, and particularly oncologic clinical discoveries, increased the chance of not only survival but also healing. Nevertheless, cancer diagnosis is still a hard existential text that destabilizes everyday life, all the psychic and relational balance, inevitably causing a psychological and social change not only in the patient who is affected but also into the wide social network around him (family, friends, doctors, healthcare team). The aim of this review is to understand how problems, feelings, emotions, distresses or defense mechanisms could garble the relation and the communication dynamics between physician and patients and then prejudicing the efficacy of oncologic therapeutic compliance. Pubmed and Scopus were searched, using strings related to "cancer", "physician-patient relations", burn-out", "compliance", and "communication", identifying literature published from 2000 to January 2015. Extracted papers were assessed for their relevance (10 of 412 papers initially reviewed). Results indicate that a good and empathetic relationship between physician and patient were related to good therapeutic adherence. In particular, a good physician-patient relation maximizes the impact of clinical therapies and reduces psychophysical implications

Use of Eribulin mesylate as second-line therapy in elderly patients with HER/2 negative metastatic breast cancer (MBC): Efficacy, tolerability and Quality of Life

OBJECTIVE: Eribulin mesylate (Halaven®) is a non-taxane inhibitor of microtubule indicated as monotherapy in patients with metastatic breast cancer (MBC), which progresses after anthracycline and taxanes therapy. In this retrospective observational study, we want to evaluate the efficacy of Eribulin in elderly women with MBC pretreated with anthracyclines and taxanes. PATIENTS AND METHODS: 40 elderly patients > 70 years of age were enrolled, and the median age was 76 years (range 70-82). Overall survival (OS), Progression Free Survival (PFS), Objective Response Rate (ORR) were primary endpoints, tolerability, carcinoembryonic antigen levels 15.3 (Ca 15.3), before and after treatment, and Quality of Life (QoL) were secondary endpoints. RESULTS: Eribulin treatment was well tolerated, produced a good level of disease control, a manageable toxicity profile and a significant impact on QoL. Median OS was 12.8 months and median PFS was 3.2 months. A significant correlation was observed between reduction of Ca 15.3 and PFS with a value of 0.59 (p = 0.002). CONCLUSIONS: Despite a limited number of patients and a modest manageable toxicity, Eribulin is a chemotherapy treatment that has showed to be an effective and well-tolerated therapeutic option in elderly patients with MBC. Further analysis should focus on the elderly patients in our setting of study

Clinical efficacy of nab-paclitaxel in patients with metastatic pancreatic cancer

Purpose: Pancreatic carcinoma is the neoplasia with the major mortality, and main standard treatments in this cancer increase survival but do not lead to complete recovery of the patient. The aim of this study was to evaluate the efficacy of Abraxane® (nab-paclitaxel) in Italian patients with metastatic pancreatic cancer (MPC). Patients and methods: We conducted a retrospective analysis of 80 patients. Overall survival (OS) was the primary end point for evaluating the efficacy of nab-paclitaxel in combination with gemcitabine treatment, while carbohydrate antigen 19-9 (CA 19-9) reduction, safety, progression-free survival (PFS), overall response rate and reduction in pain were secondary end points. Results: The median OS was 8 months, and the median PFS was 5 months. A considerable difference in CA 19-9 before and after treatment was observed. Descriptive and correlation analyses were done to examine the relationship between CA 19-9 response and OS. Linear regression analysis between OS and CA 19-9 response revealed that CA 19-9 is an important predictor of OS, showing a positive correlation. Conclusion: Nab-paclitaxel is a well-tolerated and effective treatment for patients affected by MPC. The drug showed an improved tolerability profile, significant pain relief and an increase in survival rate