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Doxorubicin (Dox), a mainstay of adjuvant breast cancer treatment, is associated with cardiac toxicity in the form of left ventricular dysfunction (LVD), LV diastolic dysfunction, or LV systolic dysfunction. Study objectives were to evaluate the prevalence of LVD in long-term breast cancer survivors treated with Dox and determine if brain-type natriuretic peptide (BNP) may help identify patients at risk for LVD. Patients who participated in prospective clinical trials of adjuvant Dox-based chemotherapy for breast cancer with a baseline left ventricular (LV) ejection fraction evaluation from 1999 to 2006 were retrospectively identified from the St Vincent's University Hospital database. Patients were invited to undergo transthoracic echocardiography, BNP analysis, and cardiovascular (CV) risk factor assessment. LVDD was defined as left atrial volume index >34 mL/m and/or lateral wall E prime <10 m/s, and LVSD as LVEF <50 %. Of 212 patients identified, 154 participated, 19 patients had died (no cardiac deaths), and 39 declined. Mean age was 60.7 [55:67] years. A majority of the patients (128, 83 %) had low CV risk (0/1 risk factors), 21 (13.6 %) had 2 RFs, and 5 (3.2 %) ≥3 RFs. BMI was 27.2 ± 4.9 kg/m. Median Dox dose was 240 mg/m [225-298]; 92 patients (59.7 %) received ≤240 mg/m and 62 (40.3 %) > 240 mg/m. Baseline LVEF was 68.2 ± 8 %. At follow-up of 10.8 ± 2.2 years, LVEF was 64.4 ± 6 %. Three (1.9 %) subjects had LVEF <50 % and one (0.7 %) had LVDD. Dox >240 mg/m2 was associated with any LVEF drop. BNP levels at follow-up were 20.3 pg/ml [9.9-36.5] and 21.1 pg/ml [9.8-37.7] in those without LVD and 61.5 pg/ml [50-68.4] in those with LVD ( p = 0.04). Long-term prospective data describing the impact of Dox on cardiotoxicity are sparse. At over 10 years of follow-up, decreases in LVEF are common, and dose related, but LVD as defined is infrequent (2.6 %). Monitoring with BNP for subclinical LVD needs further evaluation. [ABSTRACT FROM AUTHOR]

Mixing processes such as convection, overshooting and rotational mixing have long been known to affect the evolutionary properties of low-mass stars. While modeling a 1.2 M⊙ star, we encountered a semiconvective region outside the fully convective core, reminiscent of the well-known situation for massive stars. In this study we focus on low-mass stars presenting convective cores and, by applying different prescriptions for the determination of the convective boundaries and, using different mixing descriptions for the dynamical processes in the core, we look for the effects of semiconvective mixing in the interior structure of the stars and its observable quantities. With this purpose, we have constructed different sets of evolutionary models using a stellar evolution code (GARSTEC), and analyzed the models looking for imprints of these processes. [ABSTRACT FROM AUTHOR]

Background: Malignant melanoma, generally described as incurable, is notoriously refractory to chemotherapy. The mechanisms contributing to this have not yet been defined and the contributions of drug efflux pumps, implicated in chemo-resistance of many other cancer types, have not been extensively investigated in melanoma.Methods: In this study, expression of multi-drug resistant (MDR1/P-gp and MRP-1) proteins was examined, by immunohistochemistry, in archival specimens from 134 melanoma patients. This included 92 primary tumours and 42 metastases.Results: On assessing all specimens, MRP-1 and MDR1/P-gp expression was found to be common, with the majority (81%) of melanomas expressing at least one of these efflux pumps. Although there is significant association between expression of these pumps (P=0.007), MRP-1 was found to be the predominant (67% of cases) form detected. chi(2) analysis showed significant associations between expression of MRP-1 and/or MDR1/P-gp and the aggressive nature of this disease specifically increased Breslow's depth, Clark's level and spread to lymph nodes. This association with aggressiveness and spread is further supported by the observation that a significantly higher percentage of metastases, than primary tumours, express MRP-1 (91% vs 57%; P<0.0001) and MDR1/P-gp (74% vs 50%; P=0.010).Conclusion: The predominant expression of these pumps and, in particular, MRP-1 suggests that they may be important contributors to the inherent aggressive and resistant nature of malignant melanoma. [ABSTRACT FROM AUTHOR]

The solar rotation profile is well constrained down to about 0.25 R ⊙ thanks to the study of acoustic modes. Since the radius of the inner turning point of a resonant acoustic mode is inversely proportional to the ratio of its frequency to its degree, only the low-degree p modes reach the core. The higher the order of these modes, the deeper they penetrate into the Sun and thus they carry more diagnostic information on the inner regions. Unfortunately, the estimates of frequency splittings at high frequency from Sun-as-a-star measurements have higher observational errors because of mode blending, resulting in weaker constraints on the rotation profile in the inner core. Therefore inversions for the solar internal rotation use only modes below 2.4 mHz for ℓ≤3. In the work presented here, we used an 11.5-year-long time series to compute the rotational frequency splittings for modes ℓ≤3 using velocities measured with the GOLF instrument. We carried out a theoretical study of the influence of the low-degree modes in the region from 2 to 3.5 mHz on the inferred rotation profile as a function of their error bars. [ABSTRACT FROM AUTHOR]

Gravity modes are the best probes to infer the properties of the solar radiative zone, which represents 98% of the Sun’s total mass. It is usually assumed that high-frequency g modes give information about the structure of the solar interior whereas low-frequency g modes are more sensitive to the solar dynamics (the internal rotation). In this work, we develop a new methodology, based on the analysis of the almost constant separation of the dipole gravity modes, to introduce new constraints on the solar models. To validate this analysis procedure, several solar models – including different physical processes and either old or new chemical abundances (from, respectively, Grevesse and Noels ( Origin and Evolution of the Elements 199, Cambridge University Press, Cambridge, 15, ) and Asplund, Grevesse, and Sauval ( Cosmic Abundances as Records of Stellar Evolution and Nucleosynthesis CS-336, Astron. Soc. Pac., San Francisco, 25 – 38, )) – have been compared to another model used as a reference. The analysis clearly shows that this methodology has enough sensitivity to distinguish among some of the models, in particular, among those with different compositions. The comparison of the models with the g-mode asymptotic signature detected in GOLF data favors the ones with old abundances. Therefore, the physics of the core – obtained through the analysis of the g-mode properties – is in agreement with the results obtained in the previous studies based on the acoustic modes, which are mostly sensitive to more external layers of the Sun. [ABSTRACT FROM AUTHOR]

Purpose: Multi-drug resistance mediated by ATP-binding cassette trans-membrane protein pumps is an important cause of cancer treatment failure. Sulindac has been shown to be a competitive substrate for the clinically important resistance protein, multi-drug resistance protein-1 (MRP-1), and thus might enhance the anti-cancer activity of substrate chemotherapeutic agents, e.g. anthracyclines. Methods: We conducted a dose-escalating, single arm, prospective, open label, non-randomised phase I trial of epirubicin (75 mg/m2) in combination with escalating oral doses of sulindac (0–800 mg) in patients with advanced cancer to identify an appropriate dose of sulindac to use in future resistance studies. Anthracycline and sulindac pharmacokinetics were studied in cycles 1 and 3. Results: Seventeen patients (8 breast, 3 lung, 2 bowel, 1 melanoma, 1 renal, 1 ovarian and 1 of unknown primary origin, 16/17 having had prior chemotherapy) were enrolled. Eight patients received a full six cycles of treatment; 14 patients received three or more cycles. Dose-limiting toxicity was observed in two patients at 800 mg sulindac (1 renal impairment, 1 fatal haemoptysis in a patient with advanced lung cancer), and sulindac 600 mg was deemed to be the maximum tolerated dose. Sulindac had no effect on epirubicin pharmacokinetics. Among 15 patients with evaluable tumour, two partial responses were seen (malignant melanoma and breast cancer). Four others had prolonged stable disease. Conclusion: Epirubicin 75 mg/m2 and sulindac 600 mg are the recommended doses for phase II studies for these agents in combination. [ABSTRACT FROM AUTHOR]

In the modem era of helioseismology we have a wealth of high-quality data available, e.g., more than 6 years of data collected by the various instruments on board the SOHO mission, and an even more extensive ground-based set of observations covering a full solar cycle. Thanks to this effort a detailed picture of the internal rotation of the Sun has been constructed. In this paper we present some of the actions that should be done to improve our knowledge of the inner rotation profile discussed during the workshop organized at Saclay on June 2003 on this topic. In particular we will concentrate on the extraction of the rotational frequency splittings of low- and medium-degree modes and their influence on the rotation of deeper layers. Furthermore, for the first time a full set of individual /m/-component rotational splittings is computed for modes l ≤ 4 and 1 < v < 2 mHz, opening new studies on the latitudinal dependence of the rotation rate in the radiative interior. It will also be shown that these splittings have the footprints of the differential rotation of the convective zone which can be extremely useful to study the differential rotation of other stars where only these low-degree modes will be available. [ABSTRACT FROM AUTHOR]

The contributions of the minimal chiral two-pion exchange nucleon-nucleon potential for some selected observables are studied by means of the variable phase method. We conclude that chiral symmetry is responsible for important cancellations, which are related to those occurring in pion-nucleon scattering. [ABSTRACT FROM AUTHOR]

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Four-nucleon bound-state problems have been solved in the framework of the hyperspherical methods for various central N-N potentials, using the optimal subset expansion. The results are compared to variational ones. The convergence of the expansion for the binding energies is discussed. [ABSTRACT FROM AUTHOR]