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Background:Calcium electroporation is a novel anticancer treatment, which utilizes high voltage pulses to permeabilize cell membranes and expose the cell to supraphysiological doses of calcium. Preclinical studies on calcium electroporation have shown strikingly high tumor response with cell necrosis. Calcium electroporation builds on the treatment electrochemotherapy, where chemotherapeutic drugs, mostly bleomycin, are internalized by electroporation. This double-blinded randomized study compared calcium electroporation to electrochemotherapy in terms of objective response measured 6 months after treatment. Methods:Seven patients with a total of 47 cutaneous metastases from breast cancer and malignant melanoma were included in the protocol. A total of 37 metastases were randomized and evaluated for response, another 10 metastases were used for biopsy. This was a non-inferiority trial and metastases were randomized individually in each patient to either intratumoral calcium or bleomycin followed by application of electric pulses to tumor site. All metastases were treated once, and after 6-months of follow-up, the randomization code was revealed. Results:Objective response of calcium electroporation was 72% (13/18) with complete response in 66% (12/18). For electrochemotherapy, objective response was 84% (16/19) with complete response in 68% (13/19). There was no statistically significant difference between the two treatments (p = 0.5). After 1 year, only three out of 25 metastases had relapsed. Ulceration, itching and exudation were reported slightly more frequently in metastases treated with bleomycin, and hyperpigmentation was only seen in metastases treated with bleomycin. Conclusion:This study shows that calcium electroporation is feasible and effective in patients with cutaneous metastases. [ABSTRACT FROM AUTHOR]

Background and Purpose: Guideline adherence in radiotherapy is crucial for maintaining treatment quality and consistency, particularly in non-trial patient settings where most treatments occur. The study aimed to assess the impact of guideline changes on treatment planning practices and compare manual registry data accuracy with treatment planning data., Materials and Methods: This study utilised the DBCG RT Nation cohort, a collection of breast cancer radiotherapy data in Denmark, to evaluate adherence to guidelines from 2008 to 2016. The cohort included 7448 high-risk breast cancer patients. National guideline changes included, fractionation, introduction of respiratory gating, irradiation of the internal mammary lymph nodes, use of the simultaneous integrated boost technique and inclusion of the Left Anterior Descending coronary artery in delineation practice. Methods for structure name mapping, laterality detection, detection of temporal changes in population mean lung volume, and dose evaluation were presented and applied. Manually registered treatment characteristic data was obtained from the Danish Breast Cancer Database for comparison., Results: The study found immediate and consistent adherence to guideline changes across Danish radiotherapy centres. Treatment practices before guideline implementation were documented and showed a variation among centres. Discrepancies between manual registry data and actual treatment planning data were as high as 10% for some measures., Conclusion: National guideline changes could be detected in the routine treatment data, with a high degree of compliance and short implementation time. Data extracted from treatment planning data files provides a more accurate and detailed characterisation of treatments and guideline adherence than medical register data., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Influenza virus infections are a major public health threat. Vaccination is available, but unpredictable antigenic changes in circulating strains require annual modification of seasonal influenza vaccines. Vaccine effectiveness has proven limited, particularly in certain groups, such as the elderly. Moreover, preparedness for upcoming pandemics is challenging because we can predict neither the strain that will cause the next pandemic nor the severity of the pandemic. The European Union fosters research and innovation to develop novel vaccines that evoke broadly protective and long-lasting immune responses against both seasonal and pandemic influenza, underpinned by a political commitment to global public health.

The Innovative Medicines Initiative is a public-private partnership between the European Union and the pharmaceuticals industry that was established in 2008, with an overall budget of €5.3 billion from 2008 until 2024. The objective of the initiative is to boost pharmaceutical innovation in Europe and speed up the development of innovative medicines, vaccines and medical technologies, in particular in areas with high unmet needs. This article discusses the objectives of the initiative, its governance and main results and impact. The initiative has proved to be a unique platform for multi-stakeholder collaborations across Europe. It has contributed to the acceleration of the development process for medicines, from drug discovery to clinical development. The initiative has made important steps towards accessing and using real-world evidence for pharmaceutical research and development, and for healthcare decision-making. Several projects have contributed to a better understanding of the causes of diseases, and some are already delivering results, such as a vaccine against Ebola virus. The initiative has also significantly contributed to building capacity and resources for open use by the broader research and innovation community., Competing Interests: Irene Norstedt is a member of the Innovative Medicines Initiative Governing Board, representing the European Commission, and Line Matthiessen has been member until 30 June 2018. Tomasz Dyląg and Jean-Emmanuel Faure are observers at the Innovative Medicines Initiative Governing Board meetings, representing the European Commission.

Immunisation efforts save millions of lives every year, but vaccines hold the potential to deliver even greater health benefits for mankind. Vaccine research and development is highly complex, and it requires concerted public funding efforts to support. In this paper we discuss EU funding priorities and the resulting recent advancements in European vaccine research, and we lay out the EU strategy for aiding promising vaccine candidates to successfully reach the market., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

The European Commission has defined the Knowledge-Based Bio-Economy (KBBE) as the process of transforming life science knowledge into new, sustainable, eco-efficient and competitive products. The term "Bio-Economy" encompasses all industries and economic sectors that produce, manage and otherwise exploit biological resources and related services. Over the last decades biotechnologies have led to innovations in many agricultural, industrial, medical sectors and societal activities. Biotechnology will continue to be a major contributor to the Bio-Economy, playing an essential role in support of economic growth, employment, energy supply and a new generation of bio-products, and to maintain the standard of living. The paper reviews some of the main biotechnology-related research activities at European level. Beyond the 7th Framework Program for Research and Technological Development (FP7), several initiatives have been launched to better integrate FP7 with European national research activities, promote public-private partnerships and create better market and regulatory environments for stimulating innovation.

The requirements for neuroinformatics to make a significant impact on neuroscience are not simply technical--the hardware, software, and protocols for collaborative research--they also include the legal and policy frameworks within which projects operate. This is not least because the creation of large collaborative scientific databases amplifies the complicated interactions between proprietary, for-profit R&D and public "open science." In this paper, we draw on experiences from the field of genomics to examine some of the likely consequences of these interactions in neuroscience. Facilitating the widespread sharing of data and tools for neuroscientific research will accelerate the development of neuroinformatics. We propose approaches to overcome the cultural and legal barriers that have slowed these developments to date. We also draw on legal strategies employed by the Free Software community, in suggesting frameworks neuroinformatics might adopt to reinforce the role of public-science databases, and propose a mechanism for identifying and allowing "open science" uses for data whilst still permitting flexible licensing for secondary commercial research.

There is significant interest amongst neuroscientists in sharing neuroscience data and analytical tools. The exchange of neuroscience data and tools between groups affords the opportunity to differently re-analyze previously collected data, encourage new neuroscience interpretations and foster otherwise uninitiated collaborations, and provide a framework for the further development of theoretically based models of brain function. Data sharing will ultimately reduce experimental and analytical error. Many small Internet accessible database initiatives have been developed and specialized analytical software and modeling tools are distributed within different fields of neuroscience. However, in addition large-scale international collaborations are required which involve new mechanisms of coordination and funding. Provided sufficient government support is given to such international initiatives, sharing of neuroscience data and tools can play a pivotal role in human brain research and lead to innovations in neuroscience, informatics and treatment of brain disorders. These innovations will enable application of theoretical modeling techniques to enhance our understanding of the integrative aspects of neuroscience. This article, authored by a multinational working group on neuroinformatics established by the Organization for Economic Co-operation and Development (OECD), articulates some of the challenges and lessons learned to date in efforts to achieve international collaborative neuroscience.

Objective: To try out a collection of a standard set of data from computerised medical records., Design: Retrospective extraction of ordinary patient record information put into the computer by general practitioners., Setting: Encounters in office hours in strategically selected practices or health centres in Denmark, Finland, Iceland, Norway and Sweden., Subjects: 59 general practitioners and a total study population of 97475 persons., Main Outcome Measures: Proportions, crude and specific rates of encounters, diagnoses and processes., Results: In a 4-week period there was a threefold difference in the office encounter rates between the participating sites in the Nordic countries. Gender and age patterns were similar despite these differences. An access to several different denominators revealed diverse patterns of referring to the specialist, prescribing, ordering blood tests, X-rays and physiotherapy. Data from computerised medical records agree well with earlier studies in the Nordic countries using other methods., Conclusions: This survey demonstrates that valid and reliable data for routine statistics are available from computerised medical records in general practice. The major obstacle extracting more epidemiological data from computerised medical records is caused by information in the databases not being uniquely linked to episodes of care.

The serotonin 5-HT1A receptors were visualized in the cerebellar vermis of 8-day-old and adult rats by immunocytochemistry using anti-5-HT1A receptor antibodies raised against a synthetic peptide corresponding to a highly selective portion of the receptor amino acid sequence (El Mestikawy et al, Neurosci Lett 118, 189-192, 1990). The 5-HT1A receptor-like immunoreactivity was particularly abundant in the posterior lobules (IXB-X) of the immature vermis where it was found in the molecular-Purkinje cell layers. Immunostaining was confined to the plasmic membrane of the Purkinje cell somas, dendrites and perhaps axons (at their somatic emergence) suggesting that 5-HT receptors might participate in non-junctional 5-HT neurotransmission in the immature cerebellum.

Bone marrow biopsies from 125 patients at different stages of HIV infection were examined and the histopathological changes are described. Indications for biopsy included peripheral blood abnormalities, search for opportunistic pathogens, a suspected lymphoma or evaluation of its progression. Common histopathological features, suggestive of HIV infection but non-pathognomonic, were: severe hypercellularity (43.2%), myelodysplasia (74.4%), plasmocytosis (86.4%), and lymphocytic (36.8%) and histiocytic infiltrates with or without granulomas (20%). Reticular fibrosis (58.6%), iron deposits (59.2%), vascular congestion and mucoid degeneration of fat (18.4%) were frequently observed. Hypoplasia was usually a late-occurring event and/or may have been iatrogenic. Opportunistic infections were detected in 8 patients: Mycobacterium avium intracellulare (4 cases), Mycobacterium tuberculosis (1 case), Cryptococcus neoformans (1 case), and Leishmania (1 case). Neoplastic complications were found in 3 patients: Burkitt's lymphoma (1 case) and Hodgkin's disease (2 cases). The pathophysiological mechanisms envisaged include the effect of HIV infection on precursor cells in the bone marrow.

The histopathologic changes of bone marrow during infection with the human immunodeficiency virus type 1 (HIV-1) are described. Bone marrow biopsies from 73 patients at different stages of HIV-1 infection were studied. Indications for biopsy included peripheral blood abnormalities, suspicion of lymphoma, or search for specific pathogens. Common histopathological features, suggestive of HIV-1 infection but nonpathognomonic were hypercellularity (67%), myelodysplasia (86.1%), plasmacytosis (98.6%), lymphocytic infiltration (31.1%) and histiocytic infiltration with or without granulomata (13.7%). Increases in reticulin fibers (54.7%), and stainable iron deposits, vascular congestion and serous atrophy of fat were frequent features. Opportunistic infections and neoplastic complications were detected in 7 cases: pathogens were demonstrated in 4 cases (Mycobacterium avium intracellulare (MAI), Cryptococcus neoformans, Toxoplasma gondii and Leishmania) and lymphoma in 3 cases (1 Burkitt lymphoma and 2 Hodgkin's disease). Bone marrow hypoplasia is usually a terminal event in AIDS and may be iatrogenic.