Changing eruptive styles and textural features from phreatomagmatic to strombolian activity of basaltic littoral cones: Los Erales cinder cone, Tenerife, Canary Islands

Montaña Los Erales is a 70 m high Quaternary cinder cone in the Bandas del Sur region, south Tenerife. Field observations on excavated sections and SEM analysis of tephra samples from the cone suggest that the eruption style of this vent changed progressively from an initial hydrovolcanic phase, through a transitional stage, to one that was entirely strombolian. Clast sizes increase from ≤1 cm angular lapilli in hydrovolcanic samples to 15 cm bombs in strombolian samples. Vesicles also increase in size from 0.5 mm to 1.2 mm, becoming more rounded in the strombolian samples. Palagonitization, extensive in the hydrovolcanic deposits, becomes less noticeable in strombolian deposits. To investigate the causes for and the nature of these changes in eruptive style, products from each major unit were analysed for their morphology, using scanning electron microscopy with both SE and BSE imaging as tephra morphologies are known to reflect the eruptive regime and degree of explosivity at the time of eruption. SEM imaging of hydrovolcanic samples illustrate angular fragments that have been rapidly quenched and contain high levels of palagonitisation and zeolitisation, whereas strombolian samples appear to be less altered and display larger clast sizes and vesicles. Our results confirm that the initial phase of activity was largely driven by magma-water (coolant) interaction, where magma may have interacted with a lens of fresh ground or surface water, causing intense fragmentation of the magma. With proceeding eruptive activity the water became exhausted, giving rise to an entirely strombolian eruptive style. Additionally, fossil diatoms were found in hydrovolcanic samples, further emphasising the influence of a, probably fluvial, water source during the early phase of emplacement.La Montaña de Los Erales es un cono de cínder del Cuaternario de 70 m de altura situado en la zona de las Bandas del Sur, en el litoral meridional de la isla de Tenerife. Observaciones de campo en secciones excavadas en los flancos del cono y análisis SEM de las muestras de tefra sugieren que el estilo eruptivo de este aparato volcánico cambió progresivamente durante la erupción de una fase inicial hidrovolcánica a una final enteramente estromboliana, con estadios intermedios transicionales. El tamaño de los clastos aumenta de ≤1 cm de lapilli angular en las muestras hidrovolcánicas a bombas de 15 cm en las estrombolianas. Las vesículas también aumentan en tamaño desde 0,5 mm a 1,2 mm, volviéndose más redondeadas en las muestras estrombolianas. Los intensos procesos de palagonitización de los depósitos hidrovolcánicos son menos significativos en las fases estrombolianas. Con objeto de investigar la naturaleza y las causas de estos cambios se analizó la morfología de los productos de las principales fases. Se han utilizado para ello imágenes de microscopía electrónica (SE y BSE), ya que se sabe que las diferentes morfologías de estos piroclastos reflejan el régimen eruptivo y el grado de explosividad durante la erupción. Las imágenes SEM de las muestras hidrovolcánicas presentan fragmentos angulares que se han enfriado rápidamente y con elevado grado de palagonitización y zeolitización. Las estrombolianas, en cambio, aparecen menos alteradas y muestran mayor tamaño de clastos y vesículas. Los resultados obtenidos indican que la fase inicial de la erupción se caracteriza por una importante interacción magma-agua (refrigerante), probablemente relacionada con una cantidad limitada de agua superficial o freática que produjo la intensa fragmentación del magma. En el transcurso de la erupción la fuente de agua se agotó, dando lugar a las fases finales de carácter enteramente estromboliano. Fósiles de diatomeas, que se han encontrado asociados a las muestras hidrovolcánicas, refuerzan la posibilidad de que el agua fuera de origen superficial, probablemente el cauce de un barranco

Impact of a change of bronchodilator medications in a hospital drug formulary on intra- and out-of-hospital drug prescriptions: interrupted time series design with comparison group

BACKGROUND: Hospital drug formularies are reduced lists of drugs designed to optimise inpatient care. Adherence to the drugs included in such formularies is not always 100% but is generally very high. Little research has targeted the impact of a change in these formularies on outpatient drug prescriptions. This study therefore sought to evaluate the impact of a change affecting bronchodilator medications in a hospital drug formulary on intra- and out-of-hospital drug prescriptions in a region in north-western Spain. Two new drugs belonging to this same class were brought onto the out-of-hospital market, overlapping with the intervention. METHODS: We used a natural before-after quasi-experimental design with control group based on monthly data. The intervention evaluated was the modification of a hospital drug formulary, which involved withdrawing salmeterol/fluticasone in order to retain formoterol/budesonide as the sole inhaled corticosteroid and long-acting beta-agonist (ICS/LABA). Using official data sources, we extracted the following dependent variables: defined daily doses (DDD) per 1000 inhabitants per day, DDD per 100 bed-days, and cost per DDD. RESULTS: Intra-hospital use showed a 173.2% rise (95% CI 47.3-299.0%) in the medication retained in the formulary, formoterol/budesonide, and a 94.9% drop (95% CI 77.9-111.9%) in the medication withdrawn from the formulary, salmeterol/fluticasone. This intervention led to an immediate reduction of 75.9% (95% CI 82.8-68.9%) in the intra-hospital cost per DDD of ICS/LABA. No significant changes were observed in out-of-hospital use. CONCLUSIONS: Although this intervention was cost-effective in the intra-hospital setting, the out-of-hospital impact of a change in the drug formulary cannot be generalised to all types of medications and situations

Impact of a health alert and its implementation on flutamide prescriptions for women: an interrupted time series analysis.

BACKGROUND: Off-label drug use among ambulatory patients is often based on little or no scientific support. This paper reports the impact of a health warning about the risks of off-label flutamide use by women and the actions subsequently implemented by the public health service targeting such use. METHOD: The study was undertaken in a region in north-west Spain. We designed a segmented regression model of an interrupted time series, in which the dependent variable was the monthly value of defined daily doses of flutamide per 1000 inhabitants/day (DDD/TID), both total and stratified by sex. The following two data sources were used: flutamide prescriptions billed to the Spanish National Health Service; and flutamide deliveries made by wholesale drug distributors to pharmacies. The intervention assessed consisted of the issue of an official health warning and the actions subsequently taken to implement it. RESULTS: There was an immediate reduction of 49.33% in DDD/TID billed to the Spanish National Health Service in respect of women; the mean value of the population percentage of DDD/TID of flutamide billed in respect of women fell from 34.4% pre-intervention to 23.72% post-intervention. There was an immediate reduction of 19.92% (95%CI: 6.68-33.15%) in total DDD/TID invoiced. There were no significant changes in DDD/TID billed in respect of men or in flutamide use in the private medical sector. CONCLUSIONS: Off-label drug misuse is a reality among ambulatory patients, even after actions are implemented following a toxicity warning issued by the competent Health Authority

Neurofibromatosis without Neurofibromas: Confirmation of a Genotype-Phenotype Correlation and Implications for Genetic Testing

Neurofibromatosis type 1 (NF1) is a multisystem disease with autosomal dominant inheritance and complete penetrance diagnosed by clinical findings. Cutaneous neurofibromas are present in almost all adult patients in the dermis, epidermis or along the peripheral nerves. Plexiform neurofibromas are subcutaneous or deep lesions involving nerve plexuses or roots. Neurofibromas can degenerate into malignant tumors, with important prognostic implications. NF1 shows a broad clinic variability even within a single family. Exceptions are cases reporting the in-frame microdeletion c.2970_2972delAAT, presenting with the typical pigmentary features of NF1, but no cutaneous or plexiform neurofibromas. We report a patient with a de novo c.2970_2972delAAT mutation who had few café-au-lait spots, only 2 of which measured >15 mm, axillary and submammary freckling, a flat angioma extending over the neck, arm and trunk, a high arched palate, micrognathia, macrocephaly, pes cavus and scoliosis. There was complete absence of observable cutaneous neurofibromas as well as external plexiform neurofibromas. She had had epileptic seizures since childhood; however, a diagnosis of NF1 had not been confirmed until she was 38, partly due to the paucity of characteristic cutaneous stigmata. We confirm the association of the c.2970_2972delAAT mutation in NF1 with a particular clinical phenotype, especially with lack of detectable neurofibromas. For an appropriate management of patients and family counseling, molecular study of the NF1 gene should be considered in patients not fulfilling NIH criteria when other features suggestive of NF1 are present. In the absence of neurofibromas, starting NF1 testing with the screening of exon 17 may be worthwhile

Podoplanin expression in the development and progression of laryngeal squamous cell carcinomas

<p>Abstract</p> <p>Background</p> <p>Podoplanin expression is attracting interest as a marker for cancer diagnosis and prognosis. We therefore investigated the expression pattern and clinical significance of podoplanin during the development and progression of laryngeal carcinomas.</p> <p>Results</p> <p>Podoplanin expression was determined by immunohistochemistry in paraffin-embedded tissue specimens from 84 patients with laryngeal premalignancies and 53 patients with laryngeal squamous cell carcinomas. We found podoplanin expression extending from the basal to the suprabasal layer of the epithelium in 37 (44%) of 84 dysplastic lesions, whereas normal epithelium showed negligible expression. Patients carrying podoplanin-positive lesions had a higher laryngeal cancer incidence than those with negative expression reaching borderline statistical significance (51% <it>versus </it>30%, <it>P </it>= 0.071). Podoplanin expression in laryngeal carcinomas exhibited two distinct patterns. 20 (38%) cases showed diffuse expression in most tumour cells and 33 (62%) focal expression at the proliferating periphery of tumour nests. High podoplanin expression was inversely correlated with T classification (<it>P </it>= 0.033), disease stage (<it>P </it>= 0.006), and pathological grade (<it>P </it>= 0.04). There was a trend, although not significant, towards reduced disease-specific survival for patients with low podoplanin levels (<it>P </it>= 0.31) and diffuse expression pattern (<it>P </it>= 0.08).</p> <p>Conclusions</p> <p>Podoplanin expression increases in the early stages of laryngeal tumourigenesis and it seems to be associated with a higher laryngeal cancer risk. Podoplanin expression in laryngeal squamous cell carcinomas, however, diminishes during tumour progression. Taken together, these data support a role for podoplanin expression in the initiation but not in the progression of laryngeal cancers.</p

Mitochondrial metabolism: Yin and Yang for tumor progression

Altered metabolism is a distinct feature of cancer cells. During transformation, the entire metabolic network is rewired to efficiently convert nutrients to biosynthetic precursors to sustain cancer cell growth and proliferation. Whilst the molecular underpinnings of this metabolic reprogramming have been described, its role in tumor progression is still under investigation. Importantly, the mitochondrion is a central actor in many of the metabolic processes that are altered in tumors. Yet, we have only begun to understand the dualities of mitochondrial function during cancer metastasis and therapy resistance. Paradoxically, mitochondrial metabolism can be both advantageous and detrimental to these processes, highlighting the need for a better understanding of the molecular and microenvironmental cues that define the role of this fascinating organelle. In this review article, we present an updated view on the different mitochondrial metabolic strategies adopted by cancer cells to overcome the many hurdles faced during tumor progression.The work of A.C. is supported by the Ramón y Cajal award, the Basque Department of Industry, Tourism and Trade (Etortek) and the Department of Education (IKERTALDE IT1106-16), ISCIII (PI10/01484, PI13/00031), FERO VIII Fellowship, the BBVA Foundation, the MINECO (SAF2016-79381-R), and the European Research Council Starting Grant (336343). The participation of A.C. and V.T. as part of CIBERONC was cofunded with FEDER funds. L.V-J. is supported by Basque Government of Education. V.T. is funded by Fundación Vasca de Innovación e Investigación Sanitarias, BIOEF (BIO15/CA/052), the AECC J.P. Bizkaia, and the Basque Department of Health (2016111109). E.G. and C.F. are supported by the Medical Research Council, core fund to the MRC Cancer Unit SKAG106

A systematic review on the ecosystem services provided by green infrastructure

Urbanization and climate change are endangering the sustainability of public spaces through increased land artificialization, ecological fragmentation, reduced resource availability, and limited accessibility to natural and seminatural areas. Properly managing Green Infrastructure (GI) can contribute to mitigating these challenges by delivering multiple provisioning, regulating, supporting and cultural Ecosystem Services (ES). This would facilitate the implementation of strategically planned GI networks in cities for urban regeneration purposes. In this context, this study developed a systematic review on the ES provided by GI using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The analysis of 199 eligible articles indicated that more efforts should be made to address more ES at once, which connects to the need for conceiving GI as a strategically planned network of areas aimed at delivering diverse benefits. Based on the methods used in the items reviewed, geoprocessing tools and multi-criteria decision analysis are proposed to develop systems of indicators capable of accounting for multiple ES. These systems should also rely on multidisciplinary and participative procedures to encompass various facets of GI and represent the priorities of all relevant stakeholders

FAS system deregulation in T-cell lymphoblastic lymphoma

The acquisition of resistance towards FAS-mediated apoptosis may be required for tumor formation. Tumors from various histological origins exhibit FAS mutations, the most frequent being hematological malignancies. However, data regarding FAS mutations or FAS signaling alterations are still lacking in precursor T-cell lymphoblastic lymphomas (T-LBLs). The available data on acute lymphoblastic leukemia, of precursor origin as well, indicate a low frequency of FAS mutations but often report a serious reduction in FAS-mediated apoptosis as well as chemoresistance, thus suggesting the occurrence of mechanisms able to deregulate the FAS signaling pathway, different from FAS mutation. Our aim at this study was to determine whether FAS-mediated apoptotic signaling is compromised in human T-LBL samples and the mechanisms involved. This study on 26 T-LBL samples confirms that the FAS system is impaired to a wide extent in these tumors, with 57.7% of the cases presenting any alteration of the pathway. A variety of mechanisms seems to be involved in such alteration, in order of frequency the downregulation of FAS, the deregulation of other members of the pathway and the occurrence of mutations at FAS. Considering these results together, it seems plausible to think of a cumulative effect of several alterations in each T-LBL, which in turn may result in FAS/FASLG system deregulation. Since defective FAS signaling may render the T-LBL tumor cells resistant to apoptotic cell death, the correct prognosis, diagnosis and thus the success of anticancer therapy may require such an in-depth knowledge of the complete scenario of FAS-signaling alterations.S