ERANET JTC 2011: Submission and Activation of an International Academic Translational Project in Advanced Breast Cancer. Experience From the ET-FES Study

Background: Academic research is important to face unmet medical needs. The Oncological community encounters many hurdles in setting up multicenter investigator-driven trials mainly due to administrative complexity. The purpose of a network organization at a multinational level is to facilitate clinical trials through standardization, coordination, and education for drug development and regulatory approval.Methods: The application of an European grant foresees the creation of a consortium which aims at facilitating multi-center academic clinical trials.Results: The ERA-NET TRANSCAN Call 2011 on “Validation of biomarkers for personalized cancer medicine” was released on December 2011. This project included Italian, Spanish, French and German centers. The approval process included Consortium constitution, project submission, Clinical Trial Submission, and activation on a national level. The different timescales for submitting study documents in each Country and the misalignment of objections by each Competent Authority CA, generated several requests for changes to the study documents which meant amendments had to be made; as requested by the 2001/20/EC Directive, the alignment of core documents is mandatory. This procedure impacted significantly on study activation timelines. Time to first patient in was 14, 10, 28, and 31 months from the date of submission in Italy, France, Spain, and Germany, respectively. Accrual was stopped on 22nd January 2021 due to an 18F FES shortage as the primary reason but also for having exceeded the project deadlines with consequent exhaustion of the funds allocated for the project.Conclusions: Pharmaceutical companies might be reluctant to fund research projects aimed at treatment individualization if the approval for a wider indication has already been achieved. Academic trials therefore become fundamental for promoting trials which are not attractive to big pharma. It was very difficult and time consuming to activate an academic clinical trial, for this reason, a study may become “old” as new drugs entered into the market. National institutions should promote the development of clinical research infrastructures and network with competence in regulatory, ethical, and legal skills to speed up academic research.

Building a Nuclear Security Regime: Questions to Be Asked

This chapter outlines some of the key questions to be asked by a State when considering a nuclear programme and thus a nuclear security regime. In the context of globalization and the emergence of a world in which States are interdependent, it is recognized that the way one State carries out its mission to protect nuclear materials and nuclear activities concerns other States also. In response to this, and despite the reluctance of States to expose their sovereign security practices, an international framework, composed of legally binding or non-binding tools, has been built up with the idea of promoting greater consistency and thus providing guarantees to all States. It is also important, for this one State, to comprehend the national and international context beyond nuclear security within which it falls. This State has then to question itself, in the light of security issues and the fundamental principle of State sovereignty, on the essential concepts that are found in certain components of the nuclear field, such as the positioning of the competent authority, the protection of information, transparency or the place of the operator.

Perlindungan Hukum Terhadap Notaris dalam Pelaksanaan Jabatan Notaris Berdasarkan Teori Keseimbangan Berbasis Keadilan

<span>Notary has two sides were attached, namely as an individual Indonesian citizens and public officials appointed by the competent authority. As a Notary as a holder of the office of Notary who performs duties as a public official appointed by an authorized official. Notary as an individual has a position as an Indonesian Citizen based on his personal identity as an Indonesian Citizen. The legal protection provided to the Notary is based on the position of the Notary as a public official appointed by an authorized public official, not legal protection as an individual Indonesian Citizen. Although the two are attached together but related to legal protection, there is a separation of the two positions. Legal protection of Notaries as individual Indonesian Citizens has been regulated by regulations already in Indonesia and related to the human rights of individual Indonesian Citizens while legal protection of Notaries as public officials is a topic of discussion that will be discussed further. Discuss the legal protection for Notaries in the performance of their duties by reviewing based on the principle of proportionality. Legal protection for Notaries in the performance of their office is now something important because many Notaries are criminalized in the performance of their office. The research method used for this research is normative research. This research is a <em>prescriptive analysis. </em>In this research, using the approach, the approach of legislation <em>(Statue Approach)</em> and conceptual approach (<em>Conceptual Approach</em>).</span>

Handling of Incidents in the Clinical Application of Ionizing Radiation in Diagnostic and Interventional Radiology – a Multi-center Study

Purpose According to the German legislation and regulation of radiation protection, i. e. Strahlenschutzgesetz und Strahlenschutzverordnung (StrlSchG and StrlSchV), which came into force on 31st December 2018, significant unintended or accidential exposures have to be reported to the competent authority. Furthermore, facilities have to implement measures to prevent and to recognize unintended or accidental exposures as well as to reduce their consequences. We developed a process to register incidents and tested its application in the framework of a multi-center-study. Materials and Methods Over a period of 12 months, 16 institutions for x-ray diagnostics and interventions, documented their incidents. Documentation of the incidents was conducted using the software CIRSrad, which was developed, released for testing purposes and implemented in the frame of the study. Reporting criteria of the project were selected to be more sensitive compared to the legal criteria specifying “significant incidents”. Reported incidents were evaluated after four, eight, and twelve months. Finally, all participating institutions were interviewed on their experience with the software and the correlated effort. Results The rate of reported incidents varied between institutions as well as between modalities. The majority of incidents were reported in conventional x-ray imaging, followed by computed tomography and therapeutic interventions. Incidents were attributed to several different causes, amongst others to the technical setup and patient positioning (19 %) and patient movement or insufficient cooperativeness of the patient (18 %). Most incidents were below corresponding thresholds stated in StrlSchV. The workload for documenting the incidents was rated as appropriate. Conclusion It is possible to monitor and handle incidents complient with legal requirements with an acceptable effort. The number of reported incidents can be increased by frequent trainings on the detection and the processing workflow, on the software and legal regulation as well as by a transparent error handling within the institution. Key Points: Citation Format

Measures and applications of the Turkish Ice Hockey Federation during the COVID-19 pandemic

COVID-19 virus, which broke out in Wuhan city of China in 2019 and has nearly brought the sports industry to a standstill, has spread to all stages within the organizational structure of sports. In this period, it can be said that sports clubs were affected economically, and coaches, managers and other stakeholders remained inactive. In this period, issues such as the creation of financial support packages for sports clubs and online education came to the fore. Therefore, strategies and applications of sports federations which are the competent authority of sports in the national platform, in this process have become a determinant for most work areas such as sports clubs, coaches, executives and referees to sustain their activities. This study was conducted to examine the education, development and health applications followed by the Turkish Ice Hockey Federation during the COVID-19 pandemic. In this study, the general screening method was used. It is expected that the applications carried out in the 2019-2020 and 2020-2021 seasons will set an example for other sports organizations.

ANALISIS MAQASID SYARIAH JASSER AUDA TERHADAP COUNTER LEGAL DRAFT KOMPILASI HUKUM ISLAM

Islamic law transformative bid is made to replace the Islamic Law Compilation (KHI) in the form of Counter Legal Draft Compilation of Islamic Law (CLD-KHI), attracted the attention of academics, scholars and jurists of Islam in Indonesia. Many of those who reject and not infrequently also agree with the offer. This formulation is a challenge to bring order to respect Indonesia by Islamic law to all national character, culture and progress in democratization and upholding human rights, including women's rights. This study aims to answer the question (a) how is the legal istinbath method used in formulating the Counter Legal Draft Compilation of Islamic Law? (b) What is the formulation of the Counter Legal Draft Compilation of Islamic Law from the perspective of Jasser Auda's sharia maqasid? Library research using qualitative approach suggests that (a) the CLD-KHI is a legal draft in the form of provisions, so that in the process of its formulation is done through a procedural step that is done gradually, systematically, and involve several competent authority (b) Formulation of family law Islam offered in CLD-KHI in law istinbath method is not contrary to the concept of maqasid syariah Jasser Auda. However, the application instead of KHI still hindered political factor, because there are chapters that are considered controversial.

Territorial impact of the COVID-19 pandemic in Galicia (Spain): a geographical approach

The coronavirus pandemic is causing a huge impact around the world. Its real magnitude presents very important regional differences, which are appreciable in the number of infected and victims in the different countries. The outbreak of the pandemic and the ignorance of the virus mean that, even today, there are many unknowns about essential aspects related to it. In this sense, geographic knowledge can help answer many questions from the territorial analysis of the data. The objective of this article will be to analyze the behavior of the coronavirus pandemic within the Spanish region of Galicia. The authors of this study propose a multiscale analysis that allows deciphering the most common propagation patterns. For this, we have high spatial resolution data that has been provided by the competent authority under confidentiality. The results of this work allow us to represent and interpret the territorial impact of the pandemic, understanding its behavior as far as possible, allowing future dynamics to be predicted.

NOVEL ANIMAL WELL BEING CENTRIC ZOO LAYOUT MODEL AND ITS APPLICATION AT DHAULADHAR NATURE PARK (A SMALL ZOOLOGICAL PARK)

Zoological parks are the ex-situ conservation facilities to complement and strengthen the national efforts in conservation and strengthen the rich biodiversity of the country, particularly the fauna.[1]The architectural design or the map of the zoo depicting location and dimensions of the office,exhibit area, indoor holding area, visitor paths etc are some of the major components of Master (Layout) Plan of the Zoo. Central Zoo Authority is the competent authority to approve the Master (Layout) Plan of the recognized zoological parks recognized by CZA. This Master (Layout) Plan model design takes into account of 3 key parameters that one should keep in mind while designing the zoo: Animal welfare (i.e., making animal housing facility as comfortable as possible), seamless visitor experience and smooth working of zoo management personnel.

Assessing the safety, tolerability and efficacy of PLGA-based immunomodulatory nanoparticles in patients with advanced NY-ESO-1-positive cancers: a first-in-human phase I open-label dose-escalation study protocol

IntroductionThe undiminished need for more effective cancer treatments stimulates the development of novel cancer immunotherapy candidates. The archetypical cancer immunotherapy would induce robust, targeted and long-lasting immune responses while simultaneously circumventing immunosuppression in the tumour microenvironment. For this purpose, we developed a novel immunomodulatory nanomedicine: PRECIOUS-01. As a PLGA-based nanocarrier, PRECIOUS-01 encapsulates a tumour antigen (NY-ESO-1) and an invariant natural killer T cell activator to target and augment specific antitumour immune responses in patients with NY-ESO-1-expressing advanced cancers.Methods and analysisThis open-label, first-in-human, phase I dose-escalation trial investigates the safety, tolerability and immune-modulatory activity of increasing doses of PRECIOUS-01 administered intravenously in subjects with advanced NY-ESO-1-expressing solid tumours. A total of 15 subjects will receive three intravenous infusions of PRECIOUS-01 at a 3-weekly interval in three dose-finding cohorts. The trial follows a 3+3 design for the dose-escalation steps to establish a maximum tolerated dose (MTD) and/or recommended phase II dose (RP2D). Depending on the toxicity, the two highest dosing cohorts will be extended to delineate the immune-related parameters as a readout for pharmacodynamics. Subjects will be monitored for safety and the occurrence of dose-limiting toxicities. If the MTD is not reached in the planned dose-escalation cohorts, the RP2D will be based on the observed safety and immune-modulatory activity as a pharmacodynamic parameter supporting the RP2D. The preliminary efficacy will be evaluated as an exploratory endpoint using the best overall response rate, according to Response Evaluation Criteria in Solid Tumors V.1.1.Ethics and disseminationThe Dutch competent authority (CCMO) reviewed the trial application and the medical research ethics committee (CMO Arnhem-Nijmegen) approved the trial under registration number NL72876.000.20. The results will be disseminated via (inter)national conferences and submitted for publication to a peer-reviewed journal.Trial registration numberNCT04751786.

Qualitative Evaluation of Causes for Routine Salmonella Monitoring False-Positive Test Results in Dutch Poultry Breeding Flocks

The Salmonella monitoring program, as outlined in the EU Commission regulation 200/2010, asks for repeated sampling in order to ascertain progress in achievement of the EU target. According to Article 2.2.2.2.c of this regulation, the competent authority may decide to do a resample and retest when it has reasons to question the results of initial testing. In the Netherlands, the competent authorities have been resampling and retesting all initial positive samplings for several years because of doubts about false positive initial test results. An analysis of population data in the period 2015–2019 indicates that 48% of initial samplings at the farm were classified as false positive after resampling and retesting by the competent authorities. A qualitative analysis, assessing factors that could be associated with the occurrence of false positives, indicates that cross-contamination during the sampling process by the poultry farmer is probably the most likely source. Cross-contamination of samples during transport from the farm to the laboratory and/or cross-contamination at the laboratory are also considered possible sources. Given the slightly non-optimal system-specificity of the Salmonella monitoring program, there is good reason to make, or consider, standard resampling and retesting of initial positive results by the competent veterinary authorities possible within the EU.