A retrospective, multicenter study of the efficacy of lapatinib plus trastuzumab in HER2-positive metastatic breast cancer patients previously treated with trastuzumab, lapatinib, or both: the Trastyvere study.

PURPOSE: To evaluate the efficacy and safety of lapatinib (L) and trastuzumab (T) combination in HER2-positive metastatic breast cancer (MBC) patients previously treated with T and/or L. MATERIALS AND METHODS: We conducted a retrospective, post-authorized, multicenter study including patients with HER2-positive MBC or locally advanced breast cancer (ABC) treated with the combination of L-T. Concomitant endocrine therapy, as well as brain metastasis and/or prior exposure to L, were allowed. RESULTS: One hundred and fifteen patients from 14 institutions were included. The median age was 59.8 years. The median number of prior T regimens in the advanced setting was 3 and 73 patients had received a prior L regimen. The clinical benefit rate (CBR) was 34.8% (95% CI 26.1-43.5). Among other efficacy endpoints, the overall response rate was 21.7%, and median progression-free survival (PFS) and overall survival were 3.9 and 21.6 months, respectively. Heavily pretreated and ≥ 3 metastatic organ patients showed lower CBR and PFS than patients with a low number of previous regimens and < 3 metastatic organs. Moreover, CBR did not significantly change in L-pretreated compared with L-naïve patients (31.5% versus 40.5% for L-pretreated versus L-naïve). Grade 3/4 adverse events were reported in 19 patients (16.5%). CONCLUSION: The combination of L-T is an effective and well-tolerated regimen in heavily pretreated patients and remains active among patients progressing on prior L-based therapy. Our study suggests that the L-T regimen is a safe and active chemotherapy-free option for MBC patients previously treated with T and/or L.

The CODATwins Project: The Current Status and Recent Findings of COllaborative Project of Development of Anthropometrical Measures in Twins.

The COllaborative project of Development of Anthropometrical measures in Twins (CODATwins) project is a large international collaborative effort to analyze individual-level phenotype data from twins in multiple cohorts from different environments. The main objective is to study factors that modify genetic and environmental variation of height, body mass index (BMI, kg/m2) and size at birth, and additionally to address other research questions such as long-term consequences of birth size. The project started in 2013 and is open to all twin projects in the world having height and weight measures on twins with information on zygosity. Thus far, 54 twin projects from 24 countries have provided individual-level data. The CODATwins database includes 489,981 twin individuals (228,635 complete twin pairs). Since many twin cohorts have collected longitudinal data, there is a total of 1,049,785 height and weight observations. For many cohorts, we also have information on birth weight and length, own smoking behavior and own or parental education. We found that the heritability estimates of height and BMI systematically changed from infancy to old age. Remarkably, only minor differences in the heritability estimates were found across cultural-geographic regions, measurement time and birth cohort for height and BMI. In addition to genetic epidemiological studies, we looked at associations of height and BMI with education, birth weight and smoking status. Within-family analyses examined differences within same-sex and opposite-sex dizygotic twins in birth size and later development. The CODATwins project demonstrates the feasibility and value of international collaboration to address gene-by-exposure interactions that require large sample sizes and address the effects of different exposures across time, geographical regions and socioeconomic status.

No evidence of association of oxytocin polymorphisms with breastfeeding in 2 independent samples.

Oxytocin has an important function in breastfeeding via its role in the milk ejection reflex and in attachment and bonding processes. Genetic factors account for a significant part of the individual differences in breastfeeding behavior. OXT and OXTR have been proposed as gene candidates for breastfeeding. Previous studies have focused on certain single-nucleotide polymorphisms (SNPs) within these genes, finding null or inconsistent results. The present study analyses the associations between a wide coverage of polymorphisms in OXT and OXTR and breastfeeding duration from 2 large and independent unselected samples comprising a total of 580 and 2112 female twin mothers from the Murcia Twin Registry (Spain) and QIMR Berghofer Medical Research Institute (Australia), respectively. A total of 19 SNPs in OXT and 137 in OXTR SNPs were covered in both samples. Effects of the OXT and OXTR polymorphisms on breastfeeding duration were calculated by means of linear regression controlling for age at survey time, educational level, interaction between age and educational level and principal components of genetic ancestry. The analyses were conducted independently in the 2 samples and also meta-analyzed. Although some SNPs were associated at an alpha level of .05 with breastfeeding, they did not survive multiple testing correction. We conclude that SNPs within or nearby OXT and OXTR are unlikely to have large effects on breastfeeding behavior.

Automatic control of pollutant on a shallow river using surface water systems: application to the Ebro River.

In this paper, the problem of automatic control of pollutant on a shallow river using surface water systems is addressed using a benchmark test case based in the Ebro River. The Ebro River presents flooding episodes in the city of Zaragoza in Spring when snow melts in the Pyrenees. To avoid flooding and high pollutant levels in living areas, some lands outside the city are prepared to be flooded. Going one step further, this paper is focused on the pollutant level control at a certain point downstream of the river under flooding episodes, and several control strategies for that purpose are presented and tested.

Update on adjuvant hormonal treatment of early breast cancer.

Clinical trials conducted over the last two decades have demonstrated that 5 years of treatment with tamoxifen (TAM) after local treatment in postmenopausal patients with positive hormone receptor early breast cancer improves disease-free survival and overall survival. More recently, aromatase inhibitors (AI) have been tested in several randomized clinical trials in this setting. The studies have tested either AI versus TAM or different sequential approaches combining the two agents. While the most effective strategy remains to be determined, overall, incorporation of AI resulted in better disease-free survival, particularly in the worst-prognosis subgroup of patients. In addition, long-term treatment with AI was, in general, well tolerated. However, mature results are needed in order to be able to assess the effect in overall survival. The authors of this supplement paper include the key points of roundtable presentations and discussions of hormonal therapy in breast cancer by topic.

Optimal predictive control of water transport systems: Arrêt-Darré/Arros case study.

This paper proposes the use of predictive optimal control as a suitable methodology to manage efficiently transport water networks. The predictive optimal controller is implemented using MPC control techniques. The Arrêt-Darré/Arros dam-river system located in the Southwest region of France is proposed as case study. A high-fidelity dynamic simulator based on the full Saint-Venant equations and able to reproduce this system is developed in MATLAB/SIMULINK to validate the performance of the developed predictive optimal control system. The control objective in the Arrêt-Darré/Arros dam-river system is to guarantee an ecological flow rate at a control point downstream of the Arrêt-Darré dam by controlling the outflow of this dam in spite of the unmeasured disturbances introduced by rainfalls incomings and farmer withdrawals.

Predictive optimal control of sewer networks using CORAL tool: application to Riera Blanca catchment in Barcelona.

This paper deals with the global control of the Riera Blanca catchment in the Barcelona sewer network using a predictive optimal control approach. This catchment has been modelled using a conceptual modelling approach based on decomposing the catchments in subcatchments and representing them as virtual tanks. This conceptual modelling approach allows real-time model calibration and control of the sewer network. The global control problem of the Riera Blanca catchment is solved using a optimal/predictive control algorithm. To implement the predictive optimal control of the Riera Blanca catchment, a software tool named CORAL is used. The on-line control is simulated by interfacing CORAL with a high fidelity simulator of sewer networks (MOUSE). CORAL interchanges readings from the limnimeters and gate commands with MOUSE as if it was connected with the real SCADA system. Finally, the global control results obtained using the predictive optimal control are presented and compared against the results obtained using current local control system. The results obtained using the global control are very satisfactory compared to those obtained using the local control.

Documento de Consenso sobre Tratamiento Extrahospitalario de la Trombosis Venosa / No disponible

No disponible

Approach to the synthesis of antitumor quassinoids from labdane diterpenes: an efficient synthesis of a picrasane-related intermediate.

[structure: see text]. The tetracyclic ketal 24, a suitable intermediate for the synthesis of antitumor pentacyclic quassinoids, has been efficiently prepared from communic acids (5a-c), via methyl ketone 9. The synthetic sequence from 9 to 24 consists of 15 steps in 12% overall yield.

Determination of pantothenic acid in infant milk formulas by high performance liquid chromatography.

A reverse-phase liquid chromatographic method was adapted for the assay of pantothenic acid in infant milk formulas. Sample preparation consisted of deproteination with acetic acid and sodium acetate solutions, followed by centrifugation and filtration. The chromatographic system included a C-18 column and a mobile phase consisting of a sodium phosphate buffer and acetonitrile (97:3, vol/vol). The column effluent was monitored by UV detection at 197 nm. The system was linear from 50 to 800 ng. The recoveries of pantothenic acid from augmented samples ranged from 89 to 98%, and the coefficients of variation ranged from 1.17 to 3.20%. The results obtained with the HPLC and a microbiological method were highly correlated for starting infant formula, follow-up infant formula, and formula for infants of low birth weight from four different manufactures. All formulas analyzed contained pantothenic acid at concentrations higher than those declared on their nutritional labels and were in compliance with international recommendations.

A rapid gas-liquid chromatography method for the determination of lactulose and mannitol in urine: clinical application in studies of intestinal permeability.

OBJECTIVE: The purpose of this study was to develop a gas-liquid chromatography method for the determination of the urinary excretion of two nonmetabolizable sugars (lactulose and mannitol) to estimate the intestinal permeability. METHODS: Two internal standards (alpha-methyl-D-glucopyranosyde and sucrose) were added to the urine samples prior to derivatization with the aid of a solution of pyridine, [N, O-bis (trimethylsilyl)]-acetamide and chlorotrimethylsilan. Sample preparation was simpler and faster than in other previous methods and the four sugars were resolved within 27 min. RESULTS: The inclusion of internal standards reduced the coefficient of variation from 9.44% to 4.78%. The method provided better sensitivity, range of analysis, and linearity than a previously published HPLC method reducing variances in the recovery of lactulose and mannitol added to urine. The clinical application of this method was tested in preterm infants fed human milk or cow's milk based formula and in breast fed term infants. CONCLUSION: The method described here for the determination of urinary lactulose and mannitol is more rapid, simpler, and more accurate than other previously published methods.