People with covid-19 and those self-isolating must not be denied the vote

Voting is a basic democratic right. But while many countries have put special measures in place to enable people with COVID-19 and those self-isolating to vote, some have made it impossible for them to do so. Erik Asplund, Bor Stevense (International IDEA), Toby James (University of East Anglia) and Alistair Clark (Newcastle University) look at the different approaches taken by countries holding elections in 2020. Those with elections in 2021 need to act now

This Brief Biographical Record of Rev. Albertus Van Raalte, the Father of Rev. Albertus C. Van Raalte, Was Probably Obtained by the Van Raaltes During the Summer of 1866 When They Were Visiting in the Netherlands

This brief biographical record of Rev. Albertus Van Raalte, the father of Rev. Albertus C. Van Raalte, was probably obtained by the Van Raalte during the summer of 1866 when they were visiting in the Netherlands.https://digitalcommons.hope.edu/vrp_1860s/1382/thumbnail.jp

Examining the effect of Early Life Stress on autonomic and endocrine indicators of individual stress reactivity

Early life stress (ELS) is associated with altered stress reactivity and an increased risk for the development of psychopathological conditions in later life. However, depending on whether autonomic or endocrine measures were used as indicators of stress reactivity, previous studies reported conflicting findings of either increased or decreased stress reactivity after ELS experience. In the present study we therefore aimed to investigate the effect of ELS on both autonomic and endocrine indicators (heart rate and salivary cortisol) of individual stress reactivity and applied a psychosocial stress task in a sample of healthy participants with and without exposure to mild to moderate ELS. Results showed no significant effects of ELS on autonomic and endocrine indicators of individual stress reactivity. Importantly though, heart rate proved as more sensitive than salivary cortisol with regard to differentiating between stress and control conditions and thereby as a more feasible indicator of an individual's stress reactivity. Accordingly, our data suggest that sole reliance on salivary cortisol as an indicator of stress reactivity might lead to an oversight of more subtle effects of psychosocial stress

Examining the effect of Early Life Stress on autonomic and endocrine indicators of individual stress reactivity

Early life stress (ELS) is associated with altered stress reactivity and an increased risk for the development of psychopathological conditions in later life. However, depending on whether autonomic or endocrine measures were used as indicators of stress reactivity, previous studies reported conflicting findings of either increased or decreased stress reactivity after ELS experience. In the present study we therefore aimed to investigate the effect of ELS on both autonomic and endocrine indicators (heart rate and salivary cortisol) of individual stress reactivity and applied a psychosocial stress task in a sample of healthy participants with and without exposure to mild to moderate ELS. Results showed no significant effects of ELS on autonomic and endocrine indicators of individual stress reactivity. Importantly though, heart rate proved as more sensitive than salivary cortisol with regard to differentiating between stress and control conditions and thereby as a more feasible indicator of an individual's stress reactivity. Accordingly, our data suggest that sole reliance on salivary cortisol as an indicator of stress reactivity might lead to an oversight of more subtle effects of psychosocial stress

Scientific Report 2011-2012

144 p.-MEMORIA DE LA DIRECCION: El Centro de Investigaciones Biológicas (CIB) es uno de los centros de investigación con mayor prestigio y tradición en la Agencia Estatal Consejo Superior de Investigaciones Científicas (CSIC). El CIB ha estado en la vanguardia de la investigación en Biología desde su creación en 1953. La actividad inicial del CIB estuvo fundamentalmente orientada hacia estudios en Biología y Biomedicina pero actualmente es un Centro multidisciplinar, que agrupa de la Dirección | Director’s Report investigadores de las áreas de Biología, Ciencias Agrarias y Químicas. Es un Centro activo y dinámico, en constante evolución. Durante su larga trayectoria, el CIB ha formado grandes investigadores que han sido la semilla de otros centros de prestigio como el Centro de Biología Molecular Severo Ochoa, el Instituto Cajal y el Instituto de Investigaciones Biomédicas Alberto Sols en Madrid, el Instituto de Bioquímica Vegetal y Fotosíntesis en Sevilla y el de Instituto de Microbiología Bioquímica en Salamanca (actualmente Instituto de Biología Funcional y Genómica). En la actualidad el CIB acoge alrededor de 560 profesionales incluyendo investigadores de plantilla, doctores contratados, becarios y contratados realizando su Tesis Doctoral y otros profesionales dedicados a la administración y mantenimiento del Centro. Su ubicación actual, en el Campus de Moncloa, rodeado de las Facultades de Biología, Física, Química, Farmacia y Medicina y las Escuelas de Forestales y Agrónomos, nos sitúa en un marco inigualable para establecer colaboraciones con el ámbito universitario, participando en cursos de Grado y de Máster para la formación de jóvenes científicos. Además, el CIB colabora con diferentes Escuelas para la formación de técnicos cualificados. El carácter multidisciplinar del CIB lo convierte en una referencia para la formación de nuevos científicos y técnicos, perfectamente capacitados para su integración en los laboratorios de las mejores instituciones internacionales y empresas. La financiación necesaria para las investigaciones realizadas en nuestro Centro se obtiene de diferentes agencias, tanto internacionales como nacionales, mediante concursos competitivos, así como de contratos con empresas. El CIB lleva a cabo además un importante papel en la transferencia de conocimiento, poniendo a disposición de la sociedad los resultados de la investigación científica mediante la generación de patentes, que recogen los logros del CIB en diferentes campos como el diseño de nuevos abordajes terapéuticos, vacunas, ensayos biológicos o procedimientos para el desarrollo biotecnológico o industrial. Además, en el CIB se han creado dos empresas de base tecnológica (spin-off) para potenciar el desarrollo tecnológico de estas investigaciones. Todas estas líneas de actuación se encuadran en cinco grandes programas de investigación organizados en torno a cinco Departamentos:• Biología Ambiental. Estudia como los seres vivos interaccionan con el medio ambiente que les rodea, incluyendo la relación de las plantas con el medio biótico y abiótico, nuevas estrategias para el control de plagas o la utilización de microorganismos y sus enzimas para el desarrollo sostenible de aplicaciones industriales y medioambientales. • Biología Celular y Molecular. Estudia dos aspectos diferentes y complementarios de los procesos de identidad y regulación celular en procariotas y eucariotas: i) bases moleculares de la unidad celular y su integración en tejidos y órganos y ii) aproximaciones sintéticas “bottom-up” para el diseño y microfabricación de componentes que permitan nuevas funcionalidades de las células. • Biología Físico-Química. Trata de entender problemas biológicos específicos, a distintos niveles de complejidad, a través de la química y la física de las proteínas y otras moléculas biológicas, con el fin de predecir funciones esenciales y poder proponer aplicaciones biomédicas y/o biotecnológicas. • Medicina Celular y Molecular. Su objetivo es comprender las bases moleculares de diferentes patologías humanas, enfermedades raras o comunes con gran repercusión en la sociedad, para desarrollar estrategias que ayuden a diseñar nuevas terapias combinando estudios genéticos, celulares y estructurales. • Microbiología Molecular yBiología de la Infección. Se ocupa de una manera singular de desarrollar estrategias originales para el tratamiento de enfermedades producidas por microorganismos, tras conocer los mecanismos moleculares que controlan estas infecciones. Por otro lado, es preciso destacar que el CIB está dotado de un gran número de Servicios Científicos especializados (animalario, citometría de flujo, cromatografía de gases, microscopía electrónica y confocal, secuenciación de ADN y péptidos, proteómica y genómica, resonancia magnética nuclear de biomoléculas, síntesis de péptidos u oligonucleótidos y ultracentrifugación analítica), con personal altamente cualificado, que además de prestar apoyo a los investigadores de este Centro y del CSIC, dan cobertura a otros Centros de Investigación (públicos o privados), Universidades y empresas. También contamos con una excelente biblioteca, que cuenta con uno de los fondos bibliográficos más importantes de Europa en el ámbito de la Biología y Biomedicina, y con una red de servicios de apoyo a la investigación que incluye administración, gerencia, cultivos celulares, esterilización, informática, protección radiológica y la unidad de servicios técnicos e infraestructuras. Finalmente, comentar que la multidisciplinaridad es uno de los grandes valores de nuestro Centro, permitiendo la integración de metodologías y aproximaciones experimentales distintas, en un momento en el que se hace evidente que, dada su complejidad, los procesos biológicos solo se pueden comprender mediante aproximaciones distintas y complementarias. Pero este valor se convierte en un reto en las actuales circunstancias, puesto que mantener la competitividad en áreas técnicas y científicas muy diversas exige una adaptación constante a los avances tecnológicos y una renovación y modernización continua de los grandes equipos. A pesar de la difícil situación actual, con una reducción de fondos importantes, el CIB cuenta con un gran número de profesionales expertos en áreas muy diversas, que apuestan por afrontar juntos los retos actuales y futuros para seguir siendo un centro de referencia nacional e internacional.DIRECTOR'S REPORT: The Biological Research Centre (CIB) is one of the most prestigious research centres of the Spanish National Research Council (CSIC), and has been at the forefront of biological research since its creation in 1953. The initial activity of the CIB focused primarily on studies in the fields of biology and biomedicine, but currently the CIB is a multidisciplinary centre, bringing together researchers in the areas of biology, agricultural sciences and chemistry. It is an active, dynamic centre in constant evolution. During its long history, the CIB has trained and supported outstanding researchers who have been the driving force behind the formation of other top centres such as the Severo Ochoa Molecular Biology Centre, the Cajal Institute, and the Alberto Sols Molecular Biology Centre in Madrid, the Institute of Biology and Photosynthesis in Seville, and the Institute of Microbiology and Biochemistry in Salamanca. At present, the CIB is constituted by approximately 560 professionals including staff researchers, contract researchers, scholarship and PhD students, as well as administrative and maintenance personnel. The CIB is currently located within the campus of Madrid’s Complutense and Politécnica Universities, surrounded by the Faculties of Biology, Physics, Chemistry, Pharmacy and Medicine, as well as the Schools of Forestry and Agronomy. This places it in a unique setting for collaboration with academic researchers, participating in undergraduate and graduate courses and in the training of young scientists and qualified technicians. The multidisciplinary character of the CIB has made it a recognised centre for the training of new scientists and technicians qualified for inclusion in high caliber academic and industrial laboratories. Funding for research conducted at CIB is obtained from different agencies, both national and international, through competitive funding programs and contracts with companies. Furthermore, the CIB carries out an important role in knowledge and technology transfer, making available to the society the scientific results through the generation of patents that reflect CIB achievements in different fields, such as the design of new therapeutic approaches, vaccines, biological tests or procedures for biotechnological or industrial development. Moreover, CIB has created two technology-based spin-off companies to foster the technological development of this research. All these studies are part of five major research programmes organised around five departments:• Environmental Biology. It focuses in the understanding on how living organisms interact and respond to the environment, including studies on plants and their abiotic and biotic milieu, management of insect pest populations or the use of microorganisms and their enzymes for the sustainable development of industrial and environmental applications. • Cellular and Molecular Biology. It investigates two different and complementary aspects concerning the identity and regulation of prokaryotic or eukaryotic cells: i) Molecular basis of cell development and its integration in specialized cell types, tissues and organs and ii) synthetic approximations “bottom-up” for the design and micro-production of new cell components with new functionality. • Chemical and Physical Biology. Its main research goal is to develop a quantitative understanding of specific biological problems at different levels of complexity through the physics and chemistry of proteins and other biological molecules, to predict essential biological functions and to design biomedical and/or biotechnological applications. • Cellular and Molecular Medicine. Its goal is to understand the molecular mechanisms involved in human physiopathology, rare or common illnesses with high social impact, to develop strategies to design new therapies on the basis of genetic, cellular and structural studies. • Molecular Microbiology and Infection Biology. It studies the characterization of the molecular processes that control the life cycle and functions of microorganisms, as well as the molecular mechanisms involved in the regulation of microorganism-host interactions. The CIB is equipped with a large number of specialized scientific services (animal facility, flow cytometry, gas chromatography, electronic and confocal microscopy, DNA and peptide sequencing, proteomics, nuclear magnetic resonance of biomolecules, peptide or oligonucleotide synthesis and analytical ultracentrifugation) with highly qualified personnel, that besides helping researchers of this centre and the CSIC are also available to other research centres (public or private) universities, and companies. We can also count on an excellent library, with one of the most important bibliographical collections in Europe in the area of cellular biology and biomedicine, together with a network of research support services that includes administration, management, cellular cultures, sterilization, computer science and radiological protection along with the technical service and infrastructure unit. The multi-disciplinary character of our centre is one of its great assets, facilitating the integration of different methodologies and experimental approaches at a time when it has become clear that, given their complexity, biological processes can only be understood through such distinct complementary approaches. However, under present circumstances this asset has become a challenge, since maintaining competitiveness in very diverse technical and scientific areas requires a constant adaptation to new technological advances and a continual renewal and update of highly sophisticated instrumentation. Despite the difficult current situation, with important reductions in funding, the CIB can count on a large number of professionals who are experts in very diverse fields, who are committed to facing the present and future challenges together so that the CIB can continue to be an important reference centre both nationally and internationally.Peer reviewe

ONCOR: design of the Dutch cardio-oncology registry

Background: The relative new subspecialty ‘cardio-oncology’ was established to meet the growing demand for an interdisciplinary approach to the management of cancer therapy–related cardiovascular adverse events. In recent years, specialised cardio-oncology services have been implemented worldwide, which all strive to improve the cardiovascular health of cancer patients. However, limited data are currently available on the outcomes and experiences of these specialised services, and optimal strategies for cardio-oncological care have not been established. / Aim: The ONCOR registry has been created for prospective data collection and evaluation of cardio-oncological care in daily practice. / Methods: Dutch hospitals using a standardised cardio-oncology care pathway are included in this national, multicentre, observational cohort study. All patients visiting these cardio-oncology services are eligible for study inclusion. Data collection at baseline consists of the (planned) cancer treatment and the cardiovascular risk profile, which are used to estimate the cardiotoxic risk. Information regarding invasive and noninvasive tests is collected during the time patients receive cardio-oncological care. Outcome data consist of the incidence of cardiovascular complications and major adverse cardiac events, and the impact of these events on the oncological treatment. / Discussion: Outcomes of the ONCOR registry may aid in gaining more insight into the incidence of cancer therapy–related cardiovascular complications. The registry facilitates research on mechanisms of cardiovascular complications and on diagnostic, prognostic and therapeutic strategies. In addition, it provides a platform for future (interventional) studies. Centres with cardio-oncology services that are interested in contributing to the ONCOR registry are hereby invited to participate

Distinct Genomic Profiles Are Associated with Treatment Response and Survival in Ovarian Cancer

SIMPLE SUMMARY: In most patients with ovarian cancer, their disease eventually becomes resistant to chemotherapy. The timing and type of treatment given are therefore highly important. Currently, treatment choice is mainly based on the subtype of cancer (from a histological point of view), prior response to chemotherapy, and the time it takes for the disease to recur. In this study, we combined complete genome data of the tumor with clinical data to better understand treatment responses. In total, 132 tumor samples were included, all from patients with disease that had spread beyond the primary location. By clustering the samples based on genetic characteristics, we have identified subgroups with distinct response rates and survival outcomes. We suggest that in the future, this data can be used to make more informed treatment choices for individuals with ovarian cancer. ABSTRACT: The majority of patients with ovarian cancer ultimately develop recurrent chemotherapy-resistant disease. Treatment stratification is mainly based on histological subtype and stage, prior response to platinum-based chemotherapy, and time to recurrent disease. Here, we integrated clinical treatment, treatment response, and survival data with whole-genome sequencing profiles of 132 solid tumor biopsies of metastatic epithelial ovarian cancer to explore genome-informed stratification opportunities. Samples from primary and recurrent disease harbored comparable numbers of single nucleotide variants and structural variants. Mutational signatures represented platinum exposure, homologous recombination deficiency, and aging. Unsupervised hierarchical clustering based on genomic input data identified specific ovarian cancer subgroups, characterized by homologous recombination deficiency, genome stability, and duplications. The clusters exhibited distinct response rates and survival probabilities which could thus potentially be used for genome-informed therapy stratification for more personalized ovarian cancer treatment

Hospital Variation in Cancer Treatments and Survival OutComes of Advanced Melanoma Patients:Nationwide Quality Assurance in The Netherlands

Background: To assure a high quality of care for patients treated in Dutch melanoma centers, hospital variation in treatment patterns and outcomes is evaluated in the Dutch Melanoma Treatment Registry. The aim of this study was to assess center variation in treatments and 2-year survival probabilities of patients diagnosed between 2013 and 2017 in the Netherlands.Methods: We selected patients diagnosed between 2013 and 2017 with unresectable IIIC or stage IV melanoma, registered in the Dutch Melanoma Treatment Registry. Centers' performance on 2-year survival was evaluated using Empirical Bayes estimates calculated in a random effects model. Treatment patterns of the centers with the lowest and highest estimates for 2-year survival were compared.Results: For patients diagnosed between 2014 and 2015, significant center variation in 2-year survival probabilities was observed even after correcting for case-mix and treatment with new systemic therapies. The different use of new systemic therapies partially explained the observed variation. From 2016 onwards, no significant difference in 2-year survival was observed between centers.Conclusion: Our data suggest that between 2014 and 2015, after correcting for patient case-mix, significant variation in 2-year survival probabilities between Dutch melanoma centers existed. The use of new systemic therapies could partially explain this variation. In 2013 and between 2016 and 2017, no significant variation between centers existed.</p

The unfavorable effects of COVID-19 on Dutch advanced melanoma care

The COVID-19 pandemic had a severe impact on medical care. Our study aims to investigate the impact of COVID-19 on advanced melanoma care in the Netherlands. We selected patients diagnosed with irresectable stage IIIc and IV melanoma during the first and second COVID-19 wave and compared them with patients diagnosed within the same time frame in 2018 and 2019. Patients were divided into three geographical regions. We investigated baseline characteristics, time from diagnosis until start of systemic therapy and postponement of anti-PD-1 courses. During both waves, fewer patients were diagnosed compared to the control groups. During the first wave, time between diagnosis and start of treatment was significantly longer in the southern region compared to other regions (33 vs 9 and 15 days, P-value <.05). Anti-PD-1 courses were postponed in 20.0% vs 3.0% of patients in the first wave compared to the control period. Significantly more patients had courses postponed in the south during the first wave compared to other regions (34.8% vs 11.5% vs 22.3%, P-value <.001). Significantly more patients diagnosed during the second wave had brain metastases and worse performance status compared to the control period. In conclusion, advanced melanoma care in the Netherlands was severely affected by the COVID-19 pandemic. In the south, the start of systemic treatment for advanced melanoma was more often delayed, and treatment courses were more frequently postponed. During the second wave, patients were diagnosed with poorer patient and tumor characteristics. Longer follow-up is needed to establish the impact on patient outcomes

Response to immune checkpoint inhibitors in acral melanoma:A nationwide cohort study

Background: Recent reports suggest the limited efficacy of immune checkpoints inhibitors in advanced acral melanoma (AM). This study aims to investigate the clinical outcomes of immune checkpoint inhibitors in patients with stage III and IV AM and compare them to cutaneous melanoma (CM). Methods: We included patients with advanced AM and CM treated with first-line anti-programmed cell death (PD)-1 monotherapy or ipilimumab-nivolumab registered in the prospective nationwide Dutch Melanoma Treatment Registry. Objective response rates, progression-free survival (PFS) and overall survival (OS) were calculated. A Cox proportional hazard model was used to assess the prognostic factors with PFS and OS. Results: In total, 2058 patients (88 AM and 1970 CM) with advanced melanoma were included. First-line objective response rates were 34% for AM versus 54% for CM in the advanced anti-PD-1 cohort and 33% for AM versus 53% for CM in the advanced ipilimumab-nivolumab cohort. The Median PFS was significantly shorter for anti-PD-1 treated AM patients (3.1 months; 95%CI: 2.8–5.6) than patients with CM (10.1 months; 95%CI: 8.5–12.2) (P < 0.001). In patients with advanced melanoma, AM was significantly associated with a higher risk of progression (HRadj 1.63; 95%CI: 1.26–2.11; P < 0.001) and death (HRadj 1.54; 95%CI: 1.15–2.06; P = 0.004) than CM. Conclusions: This study shows lower effectiveness of anti-PD -1 monotherapy and ipilimumab-nivolumab in AM, with lower response rates, PFS and OS than CM. This group of patients should be prioritised in the development of alternative treatment strategies