Validation of the geographic position of EPER-Spain industries

BACKGROUND: The European Pollutant Emission Register in Spain (EPER-Spain) is a public inventory of pollutant industries created by decision of the European Union. The location of these industries is geocoded and the first published data correspond to 2001. Publication of these data will allow for quantification of the effect of proximity to one or more such plant on cancer and all-cause mortality observed in nearby towns. However, as errors have been detected in the geocoding of many of the pollutant foci shown in the EPER, it was decided that a validation study should be conducted into the accuracy of these co-ordinates. EPER-Spain geographic co-ordinates were drawn from the European Environment Agency (EEA) server and the Spanish Ministry of the Environment (MOE). The Farm Plot Geographic Information System (Sistema de Información Geográfica de Parcelas Agrícolas) (SIGPAC) enables orthophotos (digitalized aerial images) of any territorial point across Spain to be obtained. Through a search of co-ordinates in the SIGPAC, all the industrial foci (except farms) were located. The quality criteria used to ascertain possible errors in industrial location were high, medium and low quality, where industries were situated at a distance of less than 500 metres, more than 500 metres but less than 1 kilometre, and more than 1 kilometre from their real locations, respectively. RESULTS: Insofar as initial registry quality was concerned, 84% of industrial complexes were inaccurately positioned (low quality) according to EEA data versus 60% for Spanish MOE data. The distribution of the distances between the original and corrected co-ordinates for each of the industries on the registry revealed that the median error was 2.55 kilometres for Spain overall (according to EEA data). The Autonomous Regions that displayed most errors in industrial geocoding were Murcia, Canary Islands, Andalusia and Madrid. Correct co-ordinates were successfully allocated to 100% of EPER-Spain industries. CONCLUSION: Knowing the exact location of pollutant foci is vital to obtain reliable and valid conclusions in any study where distance to the focus is a decisive factor, as in the case of the consequences of industrial pollution on the health of neighbouring populations.This study was funded by grant FIS 040041 from the Health Research Fund (Fondo de Investigación Sanitaria)S

Biofluid Biomarkers in the Prognosis of Amyotrophic Lateral Sclerosis: Recent Developments and Therapeutic Applications

Amyotrophic lateral sclerosis; Biomarker; PrognosisEsclerosi lateral amiotròfica; Biomarcador; PronòsticEsclerosis lateral amiotrófica; Biomarcador; PronósticoAmyotrophic lateral sclerosis is a neurodegenerative disease characterized by the degeneration of motor neurons for which effective therapies are lacking. One of the most explored areas of research in ALS is the discovery and validation of biomarkers that can be applied to clinical practice and incorporated into the development of innovative therapies. The study of biomarkers requires an adequate theoretical and operational framework, highlighting the “fit-for-purpose” concept and distinguishing different types of biomarkers based on common terminology. In this review, we aim to discuss the current status of fluid-based prognostic and predictive biomarkers in ALS, with particular emphasis on those that are the most promising ones for clinical trial design and routine clinical practice. Neurofilaments in cerebrospinal fluid and blood are the main prognostic and pharmacodynamic biomarkers. Furthermore, several candidates exist covering various pathological aspects of the disease, such as immune, metabolic and muscle damage markers. Urine has been studied less often and should be explored for its possible advantages. New advances in the knowledge of cryptic exons introduce the possibility of discovering new biomarkers. Collaborative efforts, prospective studies and standardized procedures are needed to validate candidate biomarkers. A combined biomarkers panel can provide a more detailed disease status.This study has been funded by Instituto de Salud Carlos III through the project “PI19/0593” (co-funded by European Regional Development Fund: “A way to make Europe “)

Deciphering intrafamilial phenotypic variability by exome sequencing in a Bardet–Biedl family

Bardet–Biedl syndrome (BBS) is a model ciliopathy characterized by a wide range of clinical variability. The heterogeneity of this condition is reflected in the number of underlying gene defects and the epistatic interactions between the proteins encoded. BBS is generally inherited in an autosomal recessive trait. However, in some families, mutations across different loci interact to modulate the expressivity of the phenotype. In order to investigate the magnitude of epistasis in one BBS family with remarkable intrafamilial phenotypic variability, we designed an exome sequencing–based approach using SOLID 5500xl platform. This strategy allowed the reliable detection of the primary causal mutations in our family consisting of two novel compound heterozygous mutations in McKusick–Kaufman syndrome (MKKS) gene (p.D90G and p.V396F). Additionally, exome sequencing enabled the detection of one novel heterozygous NPHP4 variant which is predicted to activate a cryptic acceptor splice site and is only present in the most severely affected patient. Here, we provide an exome sequencing analysis of a BBS family and show the potential utility of this tool, in combination with network analysis, to detect disease-causing mutations and second-site modifiers. Our data demonstrate how next-generation sequencing (NGS) can facilitate the dissection of epistatic phenomena, and shed light on the genetic basis of phenotypic variability

Gemini multi-conjugate adaptive optics system review II: Commissioning, operation and overall performance

The Gemini Multi-conjugate Adaptive Optics System - GeMS, a facility instrument mounted on the Gemini South telescope, delivers a uniform, near diffraction limited images at near infrared wavelengths (0.95 microns- 2.5 microns) over a field of view of 120 arc seconds. GeMS is the first sodium layer based multi laser guide star adaptive optics system used in astronomy. It uses five laser guide stars distributed on a 60 arc seconds square constellation to measure for atmospheric distortions and two deformable mirrors to compensate for it. In this paper, the second devoted to describe the GeMS project, we present the commissioning, overall performance and operational scheme of GeMS. Performance of each sub-system is derived from the commissioning results. The typical image quality, expressed in full with half maximum, Strehl ratios and variations over the field delivered by the system are then described. A discussion of the main contributor to performance limitation is carried-out. Finally, overheads and future system upgrades are described.Comment: 20 pages, 11 figures, accepted for publication in MNRA

Biomass Accumulation and Carbon Storage in Pinus maximinoi, Quercus robur, Quercus rugosa, and Pinus patula from Village- Forests of Chiapas, Mexico

The Frailesca region (Chiapas, Mexico) presents a lack of forest studies and its environmental contribution. This chapter displays a first case study with preliminary research information regarding the identification of main forest trees and rural villages with best potential for biomass production and carbon storage management. Twenty two plots of 500 m2 were selected in 11 villages of the region, in order to identify the main and dominant forest trees species and then to estimate the biomass production and carbon storage in pine (Pinus maximinoi), oak (Quercus robur), holm oak (Quercus rugosa) and Mexican weeping pine (Pinus patula) species. This study shows that the largest accumulation of both biomass and carbon occurred in the pine forests and the lowest in the oak forests. Pine trees showed carbon storage of 516.75 Mg ha−1, followed by holm oaks, with 297.21 Mg ha−1; the species with the lowest value was oak, with 75.02 Mg ha−1. The forests of the 24 de Febrero villages had the highest potential for carbon storage. Deep studies are being conducted in relation to the aboveground biomass, carbon contents in trees stem, branches and leaves, and the relation to biomass dynamics and carbon stocks and other ecological aspects of village-forests

Epidemiological situation of breast cancer in spain.

Title and summary, also in English.El cáncer de mama es el tumor más frecuente en Europa. Según la Agencia Internacional de Investigación del Cáncer, en 2006 se diagnosticaron unos 429.900 casos nuevos de cáncer de mama en Europa, con una tasa estandarizada de incidencia de 110 casos por 100.000 mujeres. También es la localización más frecuente en mujeres españolas: supone casi la cuarta parte de los casos de cáncer femeninos, y su incidencia está aumentando entre un 2-3% anual. Entre las posibles causas de este incremento están los cambios en los patrones reproductivos y en los hábitos de vida y la introducción de la terapia hormonal sustitutiva. Nuestro país, con una tasa de incidencia estandarizada estimada de 93,6 casos por 100.000 mujeres-año para 2006, ocupa una posición intermedia entre los países de Europa occidental y los del este. Es también una importante causa de mortalidad femenina. En 2005 causó la muerte de 5.703 mujeres españolas, con una tasa de mortalidad estandarizada de 18,6 por 100.000 mujeres-año. Desde los años 90 la mortalidad por cáncer de mama está descendiendo debido al diagnóstico precoz por programas de cribado y a los avances terapéuticos. En España esta tendencia decreciente se observa a partir de 1993, con un descenso de un 2,4% anual.La supervivencia global en Europa a los 5 años es cercana al 79%, inferior a la observada en EEUU (90%), y ha aumentado en los últimos años. En España, se sitúa en un 83%, significativamente más alta que la media europea. Breast cancer is the most frequent neoplasm in Europe. According to the International Agency for Research on Cancer, there were an estimated 429,900 cases diagnosed in Europe in 2006, with an age-standardised incidence rate of 110 cases per 100,000 women.It is also the most frequent cancer in Spanish women, accounting for one forth of female cancer cases, and its incidence is increasing around 2-3% per year. Changes in reproductive behaviour and life style along with the introduction of hormone replacement therapy are partially responsible of this trend. Our country, with an estimated age-standardised incidence rate of 93.6 cases per 100,000 women-year in 2006, occupies an intermediate position between Western and Eastern European countries.This tumour also represents an important cause of female mortality. In 2005, it caused 5,703 deaths in Spanish women, with an age-standardised mortality rate of 18.6 per 100,000 women-year. However, since the 90’s, breast cancer mortality is declining thanks to earlier diagnosis derived from population screening programs and to therapeutical advances. In Spain this downward trend has started in 1993, declining a 2.4% per year.In Europe, 5-year global survival is close to 79%, lower than EEUU survival estimates (90%). Breast cancer survival has risen in recent years. In Spain, 5-year survival is around 83%, significantly higher than European average.S

RET Fusion Testing in Patients With NSCLC: The RETING Study

Introduction: RET inhibitors with impressive overall response rates are now available for patients with NSCLC, yet the identi fication of RET fusions remains a dif ficult challenge. Most guidelines encourage the upfront use of next -generation sequencing (NGS), or alternatively, fluorescence in situ hybridization (FISH) or reverse transcriptase-polymerase chain reaction (RT-PCR) when NGS is not possible or available. Taken together, the suboptimal performance of single-analyte assays to detect RET fusions, although consistent with the notion of encouraging universal NGS, is currently widening some of the clinical practice gaps in the implementation of predictive biomarkers in patients with advanced NSCLC. Methods: This situation prompted us to evaluate several RET assays in a large multicenter cohort of RET fusion -positive NSCLC (n 1 / 4 38) to obtain real -world data. In addition to RNA -based NGS (the criterion standard method), all positive specimens underwent break -apart RET FISH with two different assays and were also tested by an RT-PCR assay. Results: The most common RET partners were KIF5B (78.9%), followed by CCDC6 (15.8%). The two RET NGSpositive but FISH -negative samples contained a KIF5B(15)RET(12) fusion. The three RET fusions not identi fied with RT-PCR were AKAP13(35)-RET(12) , KIF5B(24)-RET(9) and KIF5B(24)-RET(11) . All three false -negative RT-PCR cases were FISH -positive, exhibited a typical break -apart pattern, and contained a very high number of positive tumor cells with both FISH assays. Signet ring cells, psammoma bodies, and pleomorphic features were frequently observed (in 34.2%, 39.5%, and 39.5% of tumors, respectively). Conclusions: In-depth knowledge of the advantages and disadvantages of the different RET testing methodologies could help clinical and molecular tumor boards implement and maintain sensible algorithms for the rapid and effective detection of RET fusions in patients with NSCLC. The likelihood of RET false -negative results with both FISH and RT-PCR reinforces the need for upfront NGS in patients with NSCLC. (c) 2024 The Authors. Published by Elsevier Inc. on behalf of the International Association for the Study of Lung Cancer. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)

Safety and efficacy of ribociclib plus letrozole in patients with HR+, HER2– advanced breast cancer: Results from the Spanish sub-population of the phase 3b CompLEEment-1 trial

Background: Breast cancer is the most common malignancy and the second leading cause of cancer-related mortality in Spanish women. Ribociclib in combination with endocrine therapy (ET) has shown superiority in prolonging survival in patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC) vs. ET alone.Methods: CompLEEment-1 is a single-arm, open-label phase 3b trial evaluating ribociclib plus letrozole in a broad population of patients with HR+, HER2- ABC. The primary endpoints were safety and tolerability. Here we report data for Spanish patients enrolled in CompLEEment-1.Results: A total of 526 patients were evaluated (median follow-up: 26.97 months). Baseline characteristics showed a diverse population with a median age of 54 years. At study entry, 56.5% of patients had visceral metastases and 8.7% had received prior chemotherapy for advanced disease. Rates of all-grade and Grade >= 3 adverse events (AEs) were 99.0% and 76.2%, respectively; 21.3% of patients experienced a serious AE, and 15.8% of AEs led to treatment discontinuation. AEs of special interest of neutropenia, increased alanine aminotransferase, increased aspartate aminotransferase and QTcF prolongation occurred in 77.8%, 14.8%, 11.4% and 4.0% of patients, respectively. Patients aged >70 years experienced increased rates of all-grade and Grade >= 3 neutropenia and anemia. Efficacy results were consistent with the global study.Conclusions: Results from Spanish patients enrolled in CompLEEment-1 are consistent with global data showing efficacy and a manageable safety profile for ribociclib plus letrozole treatment in patients with HR+, HER2-ABC, including populations of interest (NCT02941926).Trial registration: ClinicalTrials.gov NCT0294192

Kidney cancer mortality in Spain: geographic patterns and possible hypotheses

<p>Abstract</p> <p>Background</p> <p>Since the second half of the 1990s, kidney cancer mortality has tended to stabilize and decline in many European countries, due to the decrease in the prevalence of smokers. Nevertheless, incidence of kidney cancer is rising across the sexes in some of these countries, a trend which may possibly reflect the fact that improvements in diagnostic techniques are being outweighed by the increased prevalence of some of this tumor's risk factors. This study sought to: examine the geographic pattern of kidney cancer mortality in Spain; suggest possible hypotheses that would help explain these patterns; and enhance existing knowledge about the large proportion of kidney tumors whose cause remains unknown.</p> <p>Methods</p> <p>Smoothed municipal relative risks (RRs) for kidney cancer mortality were calculated in men and women, using the conditional autoregressive model proposed by Besag, York and Molliè. Maps were plotted depicting smoothed relative risk estimates, and the distribution of the posterior probability of RR>1 by sex.</p> <p>Results</p> <p>Municipal maps displayed a marked geographic pattern, with excess mortality in both sexes, mainly in towns along the Bay of Biscay, including areas of Asturias, the Basque Country and, to a lesser extent, Cantabria. Among women, the geographic pattern was strikingly singular, not in evidence for any other tumors, and marked by excess risk in towns situated in the Salamanca area and Extremaduran Autonomous Region. This difference would lead one to postulate the existence of different exposures of environmental origin in the various regions.</p> <p>Conclusion</p> <p>The reasons for this pattern of distribution are not clear, and it would thus be of interest if the effect of industrial emissions on this disease could be studied. The excess mortality observed among women in towns situated in areas with a high degree of natural radiation could reflect the influence of exposures which derive from the geologic composition of the terrain and then become manifest through the agency of drinking water.</p