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This work aims to investigate the correlation between the painting materials used by Picasso to create four artworks in Barcelona in 1917 and their actual conditions. Specifically, a range of crack types and patterns was observed in the painted layers. The paintings, kept together in Picasso’s family house until they were donated to the Museu Picasso in 1970, had significant differences in their condition, even though they present several similarities in the choice of materials, technique and in their conservation history. A multi-analytical approach was adopted to characterise the painted layers by X-ray fluorescence spectroscopy, fibre optic reflectance spectroscopy in the 350–2200 nm range, gas chromatography-mass spectrometry, and Fourier transform infrared spectroscopy. The obtained results have been combined with those from a previous analytical campaign focused on the study of grounds and canvases of these four paintings and with visual examination of the cracks to establish hypotheses about the differences in degradation. This combined overview of non-invasive documentation techniques, chemical analysis and observations of the mechanical damage has provided an insight into the possible contribution each layer could have played in the damage observed in the four canvas paintings.

Bevacizumab is approved in combination with chemotherapy for the treatment of ovarian cancer, either in first-line therapy or for patients with recurrent disease not previously treated with the same drug. We aimed to test the value of continuing bevacizumab beyond progression after first-line treatment with the same drug. In our open-label, randomised, phase 3 trial done at 82 sites in four countries, we enrolled women (aged ≥18 years) who had previously received first-line platinum-based therapy including bevacizumab, and had recurrent (≥6 months since last platinum dose), International Federation of Gynaecology and Obstetrics stage IIIB–IV ovarian cancer with an Eastern Cooperative Oncology Group performance status 0–2. Patients were randomly assigned (1:1) to receive a carboplatin-based doublet intravenously (carboplatin area under the concentration curve [AUC] 5 on day 1 plus paclitaxel 175 mg/m2 on day 1, every 21 days; carboplatin AUC 4 on day 1 plus gemcitabine 1000 mg/m2 on days 1 and 8, every 21 days; or carboplatin AUC 5 on day 1 plus pegylated liposomal doxorubicin 30 mg/m2 on day 1, every 28 days), or a carboplatin-based doublet plus bevacizumab (10 mg/kg intravenous every 14 days combined with pegylated liposomal doxorubicin–carboplatin, or 15 mg/kg every 21 days combined with gemcitabine–carboplatin or paclitaxel–carboplatin). Evaluable disease according to RECIST 1.1 guidelines was required before randomisation. Randomisation was done through the trial website with a minimisation procedure, stratified by centre, time of recurrence, performance status, and type of second-line chemotherapy. The primary endpoint was investigator-assessed progression-free survival, analysed on an intention-to-treat basis. Safety was assessed in all participants who received at least one dose. This trial is registered with ClinicalTrials.gov, NCT01802749 and EudraCT 2012-004362-17. Between Dec 6, 2013, and Nov 11, 2016, 406 patients were recruited (203 [50%] assigned to the bevacizumab group and 203 [50%] to the standard chemotherapy group). 130 patients (64%) in the bevacizumab group and 131 (65%) in the standard chemotherapy group had progressed after receiving a last dose of platinum more than 12 months before, and 146 patients (72%) in the bevacizumab group and 147 (72%) in the standard chemotherapy group had progressed after completion of first-line bevacizumab maintenance. 161 participants (79%) progressed in the standard chemotherapy group, as did 143 (70%) in the bevacizumab group. Median progression-free survival was 8·8 months (95% CI 8·4–9·3) in the standard chemotherapy group and 11·8 months (10·8–12·9) in the bevacizumab group (hazard ratio 0·51, 95% CI 0·41–0·65; log-rank p<0·0001). Most common grade 3–4 adverse events were hypertension (20 [10%] in the standard chemotherapy group vs 58 (29%) in the bevacizumab group), neutrophil count decrease (81 [41%] vs 80 [40%]), and platelet count decrease (43 [22%] vs 61 [30%]). 68 patients (33%) died in the standard chemotherapy group and 79 (39%) died in the bevacizumab group; two deaths (1%) in the standard chemotherapy group and one death (<1%) in the bevacizumab group were deemed to be treatment-related. Continuing bevacizumab beyond progression combined with chemotherapy in patients with platinum-sensitive recurrent ovarian cancer improves progression-free survival compared with standard chemotherapy alone and might be considered in clinical practice. Hoffmann–La Roche and Associazione Italiana per la Ricerca sul Cancro.

Background: Intraperitoneal (IP) perioperative chemotherapy with cisplatin is an interesting option in ovarian cancer treatment. A combination of cisplatin with IP epinephrine (already shown to improve IP and decrease systemic platinum (Pt) exposure) was evaluated using a population pharmacokinetic analysis. Methods: Data from 55 patients treated with cisplatin-based IP perioperative chemotherapy with ( n =26) or without ( n =29) epinephrine were analysed using NONMEM. Results: Epinephrine halves clearance between peritoneum and serum (IPCL) and increases the Pt central volume of distribution, IP exposure and penetration in tissue. IPCL has a better predictive value than any other parameter with respect to renal toxicity. Conclusion: This confirms that IPCL could be useful in assessing renal toxicity. As IPCL is also linked to tissue penetration and IP exposure, it may be proposed as biomarker. In addition to a Bayesian estimation, we propose a single-sample calculation-way to assess it. Prospective studies are needed to validate IPCL as a biomarker in this context.

The COVID-19 pandemic has been associated with substantial reduction in screening, case identification, and hospital referrals among patients with cancer. However, no study has quantitatively examined the implications of this correlation for cancer patient management. To evaluate the association of the COVID-19 pandemic lockdown with the tumor burden of patients who were diagnosed with metastatic colorectal cancer (mCRC) before vs after lockdown. This cohort study analyzed participants in the screening procedure of the PANIRINOX (Phase II Randomized Study Comparing FOLFIRINOX + Panitumumab vs FOLFOX + Panitumumab in Metastatic Colorectal Cancer Patients Stratified by RAS Status from Circulating DNA Analysis) phase 2 randomized clinical trial. These newly diagnosed patients received care at 1 of 18 different clinical centers in France and were recruited before or after the lockdown was enacted in France in the spring of 2020. Patients underwent a blood-sampling screening procedure to identify their RAS and BRAF tumor status. mCRC. Circulating tumor DNA (ctDNA) analysis was used to identify RAS and BRAF status. Tumor burden was evaluated by the total plasma ctDNA concentration. The median ctDNA concentration was compared in patients who underwent screening before (November 11, 2019, to March 9, 2020) vs after (May 14 to September 3, 2020) lockdown and in patients who were included from the start of the PANIRINOX study. A total of 80 patients were included, of whom 40 underwent screening before and 40 others underwent screening after the first COVID-19 lockdown in France. These patients included 48 men (60.0%) and 32 women (40.0%) and had a median (range) age of 62 (37-77) years. The median ctDNA concentration was statistically higher in patients who were newly diagnosed after lockdown compared with those who were diagnosed before lockdown (119.2 ng/mL vs 17.3 ng/mL; P < .001). Patients with mCRC and high ctDNA concentration had lower median survival compared with those with lower concentration (14.7 [95% CI, 8.8-18.0] months vs 20.0 [95% CI, 14.1-32.0] months). This finding points to the potential adverse consequences of the COVID-19 pandemic and related lockdown. This cohort study found that tumor burden differed between patients who received an mCRC diagnosis before vs after the first COVID-19 lockdown in France. The findings of this study suggest that CRC is a major area for intervention to minimize pandemic-associated delays in screening, diagnosis, and treatment.

The purpose of our study was to determine the clinical prognostic factors for the duration of the overall survival from recurrence (OSR) in patients with recurrent head and neck squamous-cell carcinoma. We performed a retrospective analysis on 496 patients treated between 1982 and 1993 at the Antoine Lacassagne Center. The significant favorable prognostic factors for the OSR were: initial T 1–2 (p = 0.008), no initial nodal involvement (p = 0.002), no initial chemotherapy exposure (p = 0.002), induction chemotherapy response (p = 0.001), duration of disease-free interval (DFI; p = 0.0001), performance status (PS) 0–1 (p = 0.004) and local-regional recurrence (p = 0.001). In the multivariate analysis, the apparent nonsignificance of all factors apart from the DFI suggested that relevant prognostic factors could be embedded in the DFI. Multivariate analysis was performed after excluding the DFI. The results indicated that local-regional recurrence, PS 0–1 and no initial chemotherapy exposure remained significant favorable prognostic factors for the OSR. The advantages of taking into account such prognostic factors are to eliminate the patient selection bias and to ensure a fairer comparative evaluation of new or already existing agents in recurrent head and neck cancer.

Objective: Twenty-seven patients with recurrent squamous cell carcinoma of the head and neck were entered in a multicenter study to determine the efficacy of the paclitaxel-carboplatin association. Methods: Standard eligibility criteria applied, i.e. measurable disease, and chemotherapy given as induction treatment or concomitant chemoradiotherapy was allowed if completed more than 6 months prior to the study. Every 21 days, paclitaxel 175 mg/m 2 and carboplatin AUC 6 were administered. The patient group included 3 females and 24 males with a median age of 61 years (range 39–75 years). Results: All patients were assessable for toxicity and 24 for responses. Main grade 3–4 toxicities were: neutropenia (62.9%), febrile neutropenia (18.5%), anemia (11.1%), thrombocytopenia (14.8%), mucositis (7.4%) and vomiting (7.4%). Among the intent-to-treat population, 29.6% of patients had an objective response, with a median response duration of 4.2 months (range 1–5.7 months). Stable and progressive disease were observed in 11.1 and 48.1% of patients, respectively. The median overall survival was 7.2 months (range 0.5–10.9 months). Conclusion: From these data, paclitaxel-carboplatin seems to have an activity in recurrent squamous cell carcinoma of the head and neck, but the high level of toxicity highlights the need to search for a safer chemotherapy combination.

Anaemia is a common toxicity in cancer patients and epoetins (EPOs) are now an established treatment. The economic profile of EPO treatment was assessed in patients with breast cancer treated by adjuvant-chemotherapy. Two strategies were compared: without treatment by EPO and with the possible use of treatment by EPO (epoetin alfa) when required. The clinical effectiveness criterion was time adjusted to quality of life and economic data included only direct medical costs. One hundred ninety-two patients were included. In the group with the strategy containing the possible use of EPO, 45.5% of patients effectively received EPO. A significant difference in the haemoglobin level profile over time was observed which provided a significant overall benefit of 0.0052 (p<10(-4)) quality-adjusted life year (QALY) associated with an extra cost of 1,615 (p<10(-4)). In the base case analysis, the cost per added QALY was estimated as 310,577 with the strategy containing the possible use of EPO. This robust result seems to be unacceptable, but the only relevant point of discussion might be the level of acceptable incremental cost-effectiveness ratio (ICER) for a patient.

Introducción. Se han realizado estudios que analizan los artículos científicos españoles publicados en el área de la dependencia de drogas, pero en ellos no se incluían los libros. Se estudió la publicación de libros en España sobre este tema.Material y métodos. Se identificaron los libros incluidos en la base de datos de la Agencia Española ISBN que trataban de dependencia de drogas. Se analizaron: año de publicación, autor, idioma (original y de publicación), institución editora, lugar de publicación, materia ISBN y temática. Se realizó un análisis estadístico descriptivo de los datos.Resultados. Se analizaron 879 libros. Los años en que se publicaron más libros fueron 1995 (n=108), 1994 (n=91) y 1993 (n=80). Se observó un importante incremento a partir de 1985. El 64% estaba firmado por autores personales (429 por un solo autor). El idioma de publicación más frecuente fue el castellano (94%); 132 libros eran traducciones. Las editoriales comerciales publicaron el 43% de los libros. Las comunidades en que se publicaron más libros fueron Madrid (40%) y Cataluña (25%). Las materias ISBN más frecuentes fueron: ciencias aplicadasmedicina- técnica (43%) y ciencias sociales en general (37%). La clasificación temática mostró un predominio de los libros de información general (24%), de los que tratan de prevención (23%), y de los de medicina y psicología (18%).Conclusiones. Se observa un aumento en el número de libros publicados en España sobre dependencia de drogas, que coincide con el incremento en la publicación de artículos científicos sobre este tema.

Objective: To analyse scientific literature on drug dependence (DD). Method: Spanish articles about DD published in 1976- 2000 as indexed by PsycINFO were analysed, and compared with the rest of European Union (EU) countries in 2000. Results and Discussion: PsycINFO is useful to compare countries because it includes the name of institution and country. The number of publications on DD from EU and Spain increased between 1976 and 2000. The Spanish scientific production on DD has increased more than that of the EU. 501 references of Spain and 4,324 of the other 14 EU countries were collected. From 1990, the Spanish production stands for about 10% of that of the EU. EU articles were published in 13 languages and those from Spain in three: Spanish, English and French. Apart from English, Spanish was the only language with an increase in use. EU works were published in 521 journals and those from Spain in 100; in both cases, they tended to concentrate in journals specialised in DD and psychiatry. Foreign journals that published more articles by Spanish authors have a high impact factor. In 1996-2000, the collaboration index of authors was 3.24 in the EU and 3.49 in Spain. The Autonomous Communities with more production were Catalonia, Madrid, Galicia, and Andalucia. The University was the most represented institution, followed by hospitals and alcohol and drug addiction treatment centres.