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[cat]El principal objectiu del present article consisteix en plantejar les possibles relacions entre Die Balearen i la historiografia mallorquina contemporània, per la via de mostrar com la informació que proporciona aquesta obra ha constituït i pot ser encara constitueix una excel·lent base documental per als estudis històrics, especialment per aquells que enfoquen la segona meitat del segle XIX; com també perquè de la descripció realitzada per Lluís Salvador es deriven alguns dels temes que resulten especialment interessants per a la historiografia mallorquina de l’època contemporània. A més, tant l’obra com el seu autor són mereixedors de formar part de la Història de Mallorca., [eng]The main aim of the present article points out to the possible relations between Die Balearen and the contemporary Majorcan historiography, by means to show how the information provided by this work has constituted and it still constitutes an excellent documentary base for the historical studies, especially for those that focus the second half of the 19th century. Besides, some of the most interesting subjects for the Majorcan modern historiography spring from the description of the Balearic Island done by Lluís Salvador; and also much of this work and the author himself do deserve to form part of the History of Majorca.

BACKGROUND: Despite limited clinical efficacy, treatment with dacarbazine or temozolomide (TMZ) remains the standard therapy for metastatic melanoma. In glioblastoma, promoter methylation of the counteracting DNA repair enzyme O-6-methylguanine-DNA-methyltransferase (MGMT) correlates with survival of patients exposed to TMZ in combination with radiotherapy. For melanoma, data are limited and controversial. METHODS: Biopsy samples from 122 patients with metastatic melanoma being treated with TMZ in two multicenter studies of the Dermatologic Cooperative Oncology Group were investigated for MGMT promoter methylation. We used the COBRA (combined bisulphite restriction analysis) technique to determine aberrant methylation of CpG islands in small amounts of genomic DNA isolated from paraffin-embedded tissue sections. To detect aberrant methylation, bisulphite-treated DNA was amplified by PCR, enzyme restricted, and visualised by gel electrophoresis. RESULTS: Correlation with clinical data from 117 evaluable patients in a best-response evaluation indicated no statistically significant association between MGMT promoter methylation status and response. A methylated MGMT promoter was observed in 34.8% of responders and 23.4% of non-responders (P = 0.29). In addition, no survival advantage for patients with a methylated MGMT promoter was detectable (P = 0.79). Interestingly, we found a significant correlation between MGMT methylation and tolerance of therapy. Patients with a methylated MGMT promoter had more severe adverse events, requiring more TMZ dose reductions or discontinuations (P = 0.007; OR 2.7 (95% CI: 1.32-5.7)). Analysis of MGMT promoter methylation comparing primaries and different metastases over the clinical course revealed no statistical difference (P = 0.49). CONCLUSIONS: In advanced melanoma MGMT promoter, methylation correlates with tolerance of therapy, but not with clinical outcome. British Journal of Cancer (2010) 103, 820-826. doi:10.1038/sj.bjc.6605796

BACKGROUND: Despite limited clinical efficacy, treatment with dacarbazine or temozolomide (TMZ) remains the standard therapy for metastatic melanoma. In glioblastoma, promoter methylation of the counteracting DNA repair enzyme O-6-methylguanine-DNA-methyltransferase (MGMT) correlates with survival of patients exposed to TMZ in combination with radiotherapy. For melanoma, data are limited and controversial. METHODS: Biopsy samples from 122 patients with metastatic melanoma being treated with TMZ in two multicenter studies of the Dermatologic Cooperative Oncology Group were investigated for MGMT promoter methylation. We used the COBRA (combined bisulphite restriction analysis) technique to determine aberrant methylation of CpG islands in small amounts of genomic DNA isolated from paraffin-embedded tissue sections. To detect aberrant methylation, bisulphite-treated DNA was amplified by PCR, enzyme restricted, and visualised by gel electrophoresis. RESULTS: Correlation with clinical data from 117 evaluable patients in a best-response evaluation indicated no statistically significant association between MGMT promoter methylation status and response. A methylated MGMT promoter was observed in 34.8% of responders and 23.4% of non-responders (P = 0.29). In addition, no survival advantage for patients with a methylated MGMT promoter was detectable (P = 0.79). Interestingly, we found a significant correlation between MGMT methylation and tolerance of therapy. Patients with a methylated MGMT promoter had more severe adverse events, requiring more TMZ dose reductions or discontinuations (P = 0.007; OR 2.7 (95% CI: 1.32-5.7)). Analysis of MGMT promoter methylation comparing primaries and different metastases over the clinical course revealed no statistical difference (P = 0.49). CONCLUSIONS: In advanced melanoma MGMT promoter, methylation correlates with tolerance of therapy, but not with clinical outcome. British Journal of Cancer (2010) 103, 820-826. doi:10.1038/sj.bjc.6605796

Measurements of ionic concentrations in skin have traditionally been performed with an array of methods which either did not reveal detailed localization information, or only provided qualitative, not quantitative information. FLIM combines a number of advantages into a method ideally suited to visualize concentrations of ions such as FT in intact, unperturbed epidermis and stratum corneum (SC). Fluorescence lifetime is dye concentration- independent, the method requires only low light intensities and is therefore not prone to photobleaching or phototoxic artifacts, and because multiphoton lasers of IR wavelength are used, light penetrates deep into intact tissue. The standard method to measure SC pH is the flat pH electrode, which provides reliable information only about surface pH changes, without further vertical or subcellular spatial resolution; i.e., specific microdomains such as the corneocyte interstices are not resolved, and the deeper SC is inaccessible without resorting to inherently disruptive stripping methods. Furthermore, the concept of a gradient of pH through the SC stems from such stripping experiments, but other confirmation for this concept is lacking. Our investigations into the SC pH distribution so far have revealed the crucial role of the Sodium/Hydrogen Antiporter NHE1 in generation of SC acidity, the colocalization of enzymatic lipid processing activity in the SC with acidic domains of the SC, and the timing and localization of emerging acidity in the SC of newborns. Together, these results have led to an improved understanding of the SC pH, its distribution, origin, and regulation. Future uses for this method include measurements of other ions important for epidermal processes, such as Ca2+, and a quantitative approach to topical drug penetration.

Measurements of ionic concentrations in skin have traditionally been performed with an array of methods which either did not reveal detailed localization information, or only provided qualitative, not quantitative information. FLIM combines a number of advantages into a method ideally suited to visualize concentrations of ions such as FT in intact, unperturbed epidermis and stratum corneum (SC). Fluorescence lifetime is dye concentration- independent, the method requires only low light intensities and is therefore not prone to photobleaching or phototoxic artifacts, and because multiphoton lasers of IR wavelength are used, light penetrates deep into intact tissue. The standard method to measure SC pH is the flat pH electrode, which provides reliable information only about surface pH changes, without further vertical or subcellular spatial resolution; i.e., specific microdomains such as the corneocyte interstices are not resolved, and the deeper SC is inaccessible without resorting to inherently disruptive stripping methods. Furthermore, the concept of a gradient of pH through the SC stems from such stripping experiments, but other confirmation for this concept is lacking. Our investigations into the SC pH distribution so far have revealed the crucial role of the Sodium/Hydrogen Antiporter NHE1 in generation of SC acidity, the colocalization of enzymatic lipid processing activity in the SC with acidic domains of the SC, and the timing and localization of emerging acidity in the SC of newborns. Together, these results have led to an improved understanding of the SC pH, its distribution, origin, and regulation. Future uses for this method include measurements of other ions important for epidermal processes, such as Ca2+, and a quantitative approach to topical drug penetration.

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Este volumen, escrito por el eclesiástico Joan Binimelis (1538/9-1616), constituye la primera edición crítica del Libro V de la Història general del Regne de Mallorca en la versión catalana que, como es sabido, es la original. Sin duda, esta parte de la obra, dedicada a la descripción geográfica de Mallorca y de carácter autónomo respecto a la narración histórica y cronística, representa la aportación más original del autor y la que mantiene más vigencia e interés hoy en día, tanto por la modernidad de su planteamiento, como por la diversidad de los aspectos que son objeto de su metódica atención: situación geográfica, límites, abastecimiento de agua, calas e idoneidad para desembarcos, capacidad y posibilidades de anclaje, demografía, datos económicos -producciones agrícolas y ganaderas-, datos históricos, régimen jurídico, instituciones, monumentos y otras informaciones relevantes de las poblaciones isleñas.

Este volumen, escrito por el eclesiástico Joan Binimelis (1538/9-1616), constituye la primera edición crítica del Libro V de la Història general del Regne de Mallorca en la versión catalana que, como es sabido, es la original. Sin duda, esta parte de la obra, dedicada a la descripción geográfica de Mallorca y de carácter autónomo respecto a la narración histórica y cronística, representa la aportación más original del autor y la que mantiene más vigencia e interés hoy en día, tanto por la modernidad de su planteamiento, como por la diversidad de los aspectos que son objeto de su metódica atención: situación geográfica, límites, abastecimiento de agua, calas e idoneidad para desembarcos, capacidad y posibilidades de anclaje, demografía, datos económicos -producciones agrícolas y ganaderas-, datos históricos, régimen jurídico, instituciones, monumentos y otras informaciones relevantes de las poblaciones isleñas.

Este volumen, escrito por el eclesiástico Joan Binimelis (1538/9-1616), constituye la primera edición crítica del Libro V de la Història general del Regne de Mallorca en la versión catalana que, como es sabido, es la original. Sin duda, esta parte de la obra, dedicada a la descripción geográfica de Mallorca y de carácter autónomo respecto a la narración histórica y cronística, representa la aportación más original del autor y la que mantiene más vigencia e interés hoy en día, tanto por la modernidad de su planteamiento, como por la diversidad de los aspectos que son objeto de su metódica atención: situación geográfica, límites, abastecimiento de agua, calas e idoneidad para desembarcos, capacidad y posibilidades de anclaje, demografía, datos económicos -producciones agrícolas y ganaderas-, datos históricos, régimen jurídico, instituciones, monumentos y otras informaciones relevantes de las poblaciones isleñas.

Este volumen, escrito por el eclesiástico Joan Binimelis (1538/9-1616), constituye la primera edición crítica del Libro V de la Història general del Regne de Mallorca en la versión catalana que, como es sabido, es la original. Sin duda, esta parte de la obra, dedicada a la descripción geográfica de Mallorca y de carácter autónomo respecto a la narración histórica y cronística, representa la aportación más original del autor y la que mantiene más vigencia e interés hoy en día, tanto por la modernidad de su planteamiento, como por la diversidad de los aspectos que son objeto de su metódica atención: situación geográfica, límites, abastecimiento de agua, calas e idoneidad para desembarcos, capacidad y posibilidades de anclaje, demografía, datos económicos -producciones agrícolas y ganaderas-, datos históricos, régimen jurídico, instituciones, monumentos y otras informaciones relevantes de las poblaciones isleñas.