PyHIST: a histological image segmentation tool

The development of increasingly sophisticated methods to acquire high resolution images has led to the generation of large collections of biomedical imaging data, including images of tissues and organs. Many of the current machine learning methods that aim to extract biological knowledge from histopathological images require several data preprocessing stages, creating an overhead before the proper analysis. Here we present PyHIST (https://github.com/manuel-munoz-aguirre/PyHIST), an easy-to-use, open source whole slide histological image tissue segmentation and preprocessing tool aimed at data preparation for machine learning applications.Peer ReviewedPreprin

Brain transcriptomic profiling reveals common alterations across neurodegenerative and psychiatric disorders

Neurodegenerative and neuropsychiatric disorders (ND-NPs) are multifactorial, polygenic and complex behavioral phenotypes caused by brain abnormalities. Large-scale collaborative efforts have tried to identify the genetic architecture of these conditions. However, the specific and shared underlying molecular pathobiology of brain illnesses is not clear. Here, we examine transcriptome-wide characterization of eight conditions, using a total of 2,633 post-mortem brain samples from patients with Alzheimer’s disease (AD), Parkinson’s disease (PD), Progressive Supranuclear Palsy (PSP), Pathological Aging (PA), Autism Spectrum Disorder (ASD), Schizophrenia (Scz), Major Depressive Disorder (MDD), and Bipolar Disorder (BP)–in comparison with 2,078 brain samples from matched control subjects. Similar transcriptome alterations were observed between NDs and NPs with the top correlations obtained between Scz-BP, ASD-PD, AD-PD, and Scz-ASD. Region-specific comparisons also revealed shared transcriptome alterations in frontal and temporal lobes across NPs and NDs. Co-expression network analysis identified coordinated dysregulations of cell-type-specific modules across NDs and NPs. This study provides a transcriptomic framework to understand the molecular alterations of NPs and NDs through their shared- and specific gene expression in the brain

The effects of death and post-mortem cold ischemia on human tissue transcriptomes

Post-mortem tissues samples are a key resource for investigating patterns of gene expression. However, the processes triggered by death and the post-mortem interval (PMI) can significantly alter physiologically normal RNA levels. We investigate the impact of PMI on gene expression using data from multiple tissues of post-mortem donors obtained from the GTEx project. We find that many genes change expression over relatively short PMIs in a tissue-specific manner, but this potentially confounding effect in a biological analysis can be minimized by taking into account appropriate covariates. By comparing ante- and post-mortem blood samples, we identify the cascade of transcriptional events triggered by death of the organism. These events do not appear to simply reflect stochastic variation resulting from mRNA degradation, but active and ongoing regulation of transcription. Finally, we develop a model to predict the time since death from the analysis of the transcriptome of a few readily accessible tissues.Peer ReviewedPostprint (published version

Evidencias morfosedimentarias del Último Máximo Interglacial en la costa de Governor’s Beach, Gibraltar

Los registros marinos, erosivo-sedimentarios, en la costa de Gibraltar son el resultado de episodios de elevaciones eustáticas, sobre los que se depositan secuencias continentales eólicas y gravitacionales de descenso eustático, en las que se intercalan paleosuelos. En la costa oriental de Governor’s Beach, se han reconocido dos altas paradas marinas durante OISs-5e. La primera transgresiva, a +5,0 m, con un amplio y marcado socave, cuevas, abrigos, cantiles y un cortejo bioerosivo de ascenso eustático; la segunda regresiva, a +1,5 m, con pequeñas rasas mareales y una secuencia sedimentaria de playa-duna-suelo rojo. Registros semejantes han sido reconocidos en otros lugares del Mediterráneo occidental a ~130 ka y ~120-110 ka. Todas estas evidencias fueron parcialmente cubiertas por episodios continentales posteriores de carácter eólico-kárstico-gravitaciona

Interpolación espacial de la precipitación media mensual en la cuenca del río Bravo/Grande

La precipitación es una de las principales variables climáticas empleadas para describir procesos hidrológicos; sin embargo, su representación espacial es difícil en áreas con efecto orográfico complejo y escasa disponibilidad de estaciones. En el presente estudio se analizaron datos mensuales de precipitación para representar de manera fiable la distribución espacial de la precipitación media mensual (PMM) en la cuenca del río Bravo/Grande (CRB). Se utilizaron datos de 201 estaciones climáticas ubicadas al interior y en los alrededores de la cuenca. Con la información del 60% de estaciones seleccionadas de forma aleatoria se ajustaron modelos de regresión múltiple para predecir la PMM a partir de la elevación, la complejidad del relieve, la proximidad de zonas marítimas y la localización geográfica de estaciones climáticas, que explicaron entre 70 y 82% la variabilidad espacial de la precipitación que ocurre durante los meses del periodo húmedo. Se obtuvieron mapas mensuales de PMM calibrados espacialmente con la interpolación de los residuales. Con el restante 40% de estaciones se llevaron a cabo pruebas de validación estadística antes y después de la calibración. Las pruebas de validación mostraron valores de eficiencia (EF) comprendidos entre 0.41 y 0.82, y valores porcentuales del error medio absoluto (%EMA) entre 19.1 y 39.5%, siendo los modelos del periodo comprendido entre mayo y agosto los de mejor capacidad predictiva. La calibración de los modelos mejoró de manera significativa la fiabilidad de las interpolaciones en la totalidad de los modelos (EF entre 0.60 y 0.90, y % EMA entre 16.2 y 30.1), permitiendo obtener coberturas geográficas fiables de alta resolución espacial y con potencial de poder considerarlas como variables de entrada en modelos orientados a evaluar procesos hidrológicos en la CRB

Adynaton 1

Revista de narrativa y poesía escrita en los talleres literarios de CETYS Universidad.Adynaton es una revista del Círculo de Letras de CETYS Universidad

Las arenas eólicas del Pleistoceno Superior en Gibraltar

During the period represented by the sandy infills of the eastern flank caves and the Catalan Sand formation, it was likely that Gibraltar was part of the mainland, including a broad coastal plain covered with transgressive wind-blown dunes. All aeolian formations originated on marine beaches, from 6 m a.s.l. to 100 m b.s.l., before being blown inland to accumulate as topographic dunes. Cliff-front aeolian accumulations comprise echo dunes, climbing dunes and sand ramps. Aeolian deposition began immediately before the last interglacial marine highstand (MIS 6-5 transition) and continued during the subsequent fall in sea level until the end of MIS 3.Ministerio de Educación y Ciencia CGL2006-01412/BT

Impact of an Antimicrobial Stewardship Program on the Incidence of Carbapenem Resistant Gram-Negative Bacilli: An Interrupted Time-Series Analysis

This article belongs to the Section Antibiotics Use and Antimicrobial Stewardship.Carbapenem-resistant Gram-negative bacilli (CR-GNB) are a critical public health threat, and carbapenem use contributes to their spread. Antimicrobial stewardship programs (ASPs) have proven successful in reducing antimicrobial use. However, evidence on the impact of carbapenem resistance remains unclear. We evaluated the impact of a multifaceted ASP on carbapenem use and incidence of CR-GNB in a high-endemic hospital. An interrupted time-series analysis was conducted one year before and two years after starting the ASP to assess carbapenem consumption, CR-GNB incidence, death rates of sentinel events, and other variables potentially related to CR-GNB incidence. An intense reduction in carbapenem consumption occurred after starting the intervention and was sustained two years later (relative effect −83.51%; 95% CI −87.23 to −79.79). The incidence density of CR-GNB decreased by −0.915 cases per 1000 occupied bed days (95% CI −1.743 to −0.087). This effect was especially marked in CR-Klebsiella pneumoniae and CR-Escherichia coli, reversing the pre-intervention upward trend and leading to a relative reduction of −91.15% (95% CI −105.53 to −76.76) and −89.93% (95% CI −107.03 to −72.83), respectively, two years after starting the program. Death rates did not change. This ASP contributed to decreasing CR-GNB incidence through a sustained reduction in antibiotic use without increasing mortality rates.This research was funded by the Plan Nacional de I + D+i 2013–2016 and Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Ciencia, Innovación y Universidades, Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/0008; RD16/0016/0009) co-financed by European Development Regional Fund ‘A way to achieve Europe’ and Operative program intelligent Growth 2014–2020, which did not participate in the development of the program or the analysis of its results

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.This work was supported by GlaxoSmithKline plc (GSK) through a contract with Medica Scientia Innovation Research (MedSIR), an academic research organization focused on independent clinical research development