Making ERP research more transparent: Guidelines for preregistration

A combination of confirmation bias, hindsight bias, and pressure to publish may prompt the (unconscious) exploration of various methodological options and reporting only the ones that lead to a (statistically) significant outcome. This undisclosed analytic flexibility is particularly relevant in EEG research, where a myriad of preprocessing and analysis pipelines can be used to extract information from complex multidimensional data. One solution to limit confirmation and hindsight bias by disclosing analytic choices is preregistration: researchers write a time-stamped, publicly accessible research plan with hypotheses, data collection plan, and the intended preprocessing and statistical analyses before the start of a research project. In this manuscript, we present an overview of the problems associated with undisclosed analytic flexibility, discuss why and how EEG researchers would benefit from adopting preregistration, provide guidelines and examples on how to preregister data preprocessing and analysis steps in typical ERP studies, and conclude by discussing possibilities and limitations of this open science practice

UK adaptive radiotherapy practices for head and neck cancer patients

Objective: To provide evidence on the extent and manner in which adaptive practices have been employed in the UK and identify the main barriers for the clinical implementation of adaptive radiotherapy (ART) in head and neck (HN) cancer cases. Methods: In December 2019, a Supplementary Material 1, of 23 questions, was sent to all UK radiotherapy centres (67). This covered general information to current ART practices and perceived barriers to implementation. Results: 31 centres responded (46%). 56% responding centres employed ART for between 10 and 20 patients/annum. 96% of respondents were using CBCT either alone or with other modalities for assessing "weight loss" and "shell gap," which were the main reasons for ART. Adaptation usually occurs at week three or four during the radiotherapy treatment. 25 responding centres used an online image-guided radiotherapy (IGRT) approach and 20 used an offline ad hoc ART approach, either with or without protocol level. Nearly 70% of respondents required 2 to 3 days to create an adaptive plan and 95% used 3-5 mm adaptive planning target volume margins. All centres performed pre-treatment QA. "Limited staff resources" and "lack of clinical relevance" were identified as the two main barriers for ART implementation. Conclusion: There is no consensus in adaptive practice for HN cancer patients across the UK. For those centres not employing ART, similar clinical implementation barriers were identified. Advances in knowledge: An insight into contemporary UK practices of ART for HN cancer patients indicating national guidance for ART implementation for HN cancer patients may be required

Reconstruction of a Segment of the UNESCO World Heritage Hadrian’s Villa Tunnel Network by Integrated GPR, Magnetic–Paleomagnetic, and Electric Resistivity Prospections

The authors are grateful to the Director of the Villa Adriana and Villa d’Este, Andrea Bruciati, for kindly allowing us to survey the archaeological area and to Benedetta Adembri for facilitating the research on site. We are also grateful to Francesco Ferruti and the students that helped us in the data acquisition. Finally, we thank Alessandro Bertani for his help in the acquisition and formal analysis of aerial photogrammetry data. This paper also benefited from four accurate reviews that allowed us to improve the manuscript.The following are available online at https://zenodo.org/record/3351757#.XVIUHdIRWUl, Figure S1: Local reference frames used for the acquisition of GPR data, Figure S2: UAV orthophoto of the study area (Plutonium−Inferi complex) with indication of the excavated areas, Tables S1–S13: Relevant migrated and unmigrated GPR profiles for areas 1 through 13, Table S10A, transversal migrated and unmigrated GPR profiles for Areas 10.Hadrian’s Villa is an ancient Roman archaeological site built over an ignimbritic tuff and characterized by abundant iron oxides, strong remnant magnetization, and elevated magnetic susceptibility. These properties account for the high-amplitude magnetic anomalies observed in this site and were used as a primary tool to detect deep archaeological features consisting of air-filled and soil-filled cavities of the tuff. An integrated magnetic, paleomagnetic, radar, and electric resistivity survey was performed in the Plutonium-Inferi sector of Hadrian’s Villa to outline a segment of the underground system of tunnels that link different zones of the villa. A preliminary paleomagnetic analysis of the bedrock unit and a high-resolution topographic survey by aerial photogrammetry allowed us to perform a computer-assisted modelling of the observed magnetic anomalies, with respect to the archaeological sources. The intrinsic ambiguity of this procedure was reduced through the analysis of ground penetrating radar and electric resistivity profiles, while a comprehensive picture of the buried archaeological features was built by integration of the magnetization model with radar amplitude maps. The final subsurface model of the Plutonium-Inferi complex shows that the observed anomalies are mostly due to the presence of tunnels, skylights, and a system of ditches excavated in the tuff.This research was funded by the Università degli Studi di Camerino, grants FAR Schettino 2016–2018 and FAR Pierantoni 2016–2018, and by the University of Oxford, Eugene Ludwig Fund, New College

Novel anticancer and treatment sensitizing compounds against pancreatic cancer

The isolation of chemical compounds from natural origins for medical application has played an important role in modern medicine with a range of novel treatments having emerged from various natural forms over the past decades. Natural compounds have been exploited for their antioxidant, antimicrobial and antitumor capabilities. Specifically, 60% of today’s anticancer drugs originate from natural sources. Moreover, the combination of synthetic and natural treatments has shown applications for (i) reduced side effects, (ii) treatment sensitization and (iii) reduction in treatment resistance. This review aims to collate novel and natural compounds that are being explored for their preclinical anticancer, chemosensitizing and radiosensitizing effects on Pancreatic Ductal Adenocarcinoma (PDAC), which is a lethal disease with current treatments being inefficient and causing serve side effects. Two key points are highlighted by this work: (i) the availability of a range of natural compounds for potentially new therapeutic approaches for PDAC, (ii) potential synergetic impact of natural compounds with advanced chemo-and radio-therapeutic modalities for PDAC

On the Evaluation of a Novel Hypoxic 3D Pancreatic Cancer Model as a Tool for Radiotherapy Treatment Screening

Tissue engineering is evolving to mimic intricate ecosystems of tumour microenvironments (TME) to more readily map realistic in vivo niches of cancerous tissues. Such advanced cancer tissue models enable more accurate preclinical assessment of treatment strategies. Pancreatic cancer is a dangerous disease with high treatment resistance that is directly associated with a highly complex TME. More specifically, the pancreatic cancer TME includes (i) complex structure and complex extracellular matrix (ECM) protein composition; (ii) diverse cell populations (e.g., stellate cells), cancer associated fibroblasts, endothelial cells, which interact with the cancer cells and promote resistance to treatment and metastasis; (iii) accumulation of high amounts of (ECM), which leads to the creation of a fibrotic/desmoplastic reaction around the tumour; and (iv) heterogeneous environmental gradients such as hypoxia, which result from vessel collapse and stiffness increase in the fibrotic/desmoplastic area of the TME. These unique hallmarks are not effectively recapitulated in traditional preclinical research despite radiotherapeutic resistance being largely connected to them. Herein, we investigate, for the first time, the impact of in vitro hypoxia (5% O2) on the radiotherapy treatment response of pancreatic cancer cells (PANC-1) in a novel polymer (polyurethane) based highly macroporous scaffold that was surface modified with proteins (fibronectin) for ECM mimicry. More specifically, PANC-1 cells were seeded in fibronectin coated macroporous scaffolds and were cultured for four weeks in in vitro normoxia (21% O2), followed by a two day exposure to either in vitro hypoxia (5% O2) or maintenance in in vitro normoxia. Thereafter, in situ post-radiation monitoring (one day, three days, seven days post-irradiation) of the 3D cell cultures took place via quantification of (i) live/dead and apoptotic profiles and (ii) ECM (collagen-I) and HIF-1a secretion by the cancer cells. Our results showed increased post-radiation viability, reduced apoptosis, and increased collagen-I and HIF-1a secretion in in vitro hypoxia compared to normoxic cultures, revealing hypoxia-induced radioprotection. Overall, this study employed a low cost, animal free model enabling (i) the possibility of long-term in vitro hypoxic 3D cell culture for pancreatic cancer, and (ii) in vitro hypoxia associated PDAC radio-protection development. Our novel platform for radiation treatment screening can be used for long-term in vitro post-treatment observations as well as for fractionated radiotherapy treatment

Obtenção e Caracterização de Nanopartículas Magnéticas Inseridas em Materiais Carbonosos Porosos a partir da Decomposição do Pentacarbonil Ferro.

Este trabalho é dedicado à síntese e caracterização de nanopartículas de óxidos de ferro dispersas na estrutura porosa de um carvão ativado, originando nanocompósitos com propriedades magnéticas. As amostras foram preparadas a partir da mistura do organometálico pentacarbonil ferro com o carvão ativado, em diferentes proporções e sob as atmosferas ambiente e de argônio. As técnicas experimentais utilizadas para a caracterização foram: espectroscopia Mössbauer, difração de raios-X convencional e com luz síncrotron , espectroscopia de fotoelétrons excitados por raios-X, microscopia eletrônica de varredura, análise textural por adsorção de nitrogênio, medidas de propriedades magnéticas, análise elementar e termogravimetria. Os resultados mostraram que os teores de ferro nas amostras como preparadas atingiram valores de até 33 % em massa, aproximadamente. As nanopartículas foram identificadas como óxidos de ferro dispersos de forma homogênea no carvão ativado, com tamanho médio de cristalito na faixa 4-6nm e apresentando comportamento superparamagnético em temperatura ambiente. As amostras preparadas sob atmosfera ambiente apresentaram predominantemente as fases hematita e magnetita e nas amostras preparadas sob atmosfera de argônio foi encontrada apenas a magnetita. A área superficial específica e o volume total de poros do carvão ativado foram reduzidos em torno de 40 e 50%, respectivamente, com a formação das nanopartículas. A execução de tratamentos térmicos em atmosfera inerte levou ao crescimento do tamanho médio de cristalito; para temperaturas a partir de 400 oC, aproximadamente, teve início o processo de redução do estado de oxidação do ferro, até temperaturas em torno de 700 oC. Nas amostras tratadas em 900 oC foi observada a predominância de ferro metálico, além da formação de carbetos de ferro. Na análise de difração de raios-X in situ durante o aquecimento das amostras, foi observada a formação da wustita como um composto intermediário antes da formação do ferro metálico. Os valores dos coeficientes de expansão térmica para os óxidos de ferro nanocristalinos foram consideravelmente maiores do que os esperados para as fases cristalinas massivas, um efeito associado à elevada fração de átomos de superfície nas nanopartículas. Os resultados deste trabalho mostraram que os métodos empregados de síntese e posterior tratamento térmico possibilitam a obtenção de nanopartículas magnéticas contendo ferro dispersas na matriz do carvão ativado; a natureza e o tamanho médio dessas partículas dependem das condições experimentais envolvidas, tais como atmosfera de síntese, temperatura e tempo de tratamento térmico