While cyberspace as a globally interconnected network offers economic, social and informational potential, at the same time this space also produces a wide variety of risks, for which no easy... Show moreWhile cyberspace as a globally interconnected network offers economic, social and informational potential, at the same time this space also produces a wide variety of risks, for which no easy solutions exist. For the international community, for nation states, for organizations and even for individuals, uncertainty is a common thread for interaction, communication and the general use of (systems connected to) cyberspace. This research shows that there are five different common reactions to dealing with this uncertainty in cyberspace: (1) using risk management to control uncertainty; (2) recovering from uncertainty through resilience; (3) influencing uncertainty with laws and regulation; suspending uncertainty by engaging in trust; and (5) ignoring uncertainty through inaction. Some of these approaches are used more often than others. For instance, risk management is currently the dominant way of responding to uncertainty in cyberspace, with resilience gaining prominence. Other strategies, such as relying on trust or inaction, are less common. Oftentimes, using a mixture of strategies may be helpful, because some strategies may strengthen one another, for instance when a combination of risk management and resilience approaches is used. Each strategy has particular use for specific contexts, but since we lack an overview of which strategies are being used, we also cannot establish under which conditions which strategy is most beneficial. Solving this lack of knowledge can help us be more effective in dealing with uncertainties of a wide variety in cyberspace. Show less
Speight, B.; Colvin, E.; Epurescu, E.D.; Drummond, J.; Verhoef, S.; Pereira, M.; ... ; Tischkowitz, M. 2022
Germline pathogenic variants in BRCA1 and BRCA2 cause hereditary breast and ovarian cancer. The vast majority of these variants are inherited from a parent. De novo constitutional pathogenic... Show moreGermline pathogenic variants in BRCA1 and BRCA2 cause hereditary breast and ovarian cancer. The vast majority of these variants are inherited from a parent. De novo constitutional pathogenic variants are rare. Even fewer cases of constitutional mosaicism have been reported and these have mostly been described in women with breast cancer. Here we report low-level constitutional mosaicism identified by Next Generation Sequencing in two women with ovarian cancer. A BRCA1 c.5074G > A p.(Asp1692Asn) variant detected in the first female at 42 years, classed as likely pathogenic, was found in similar to 52% of reads in DNA extracted from tumour, similar to 10% of reads in DNA extracted from peripheral blood leukocytes and similar to 10% of reads in DNA extracted from buccal mucosa. The second BRCA c.2755_2758dupCCTG p.(Val920AlafsTer6) variant was detected in a female aged 53 years, classed as pathogenic, and was found in similar to 59% of reads in DNA extracted from tumour, similar to 14% of reads in DNA extracted from peripheral blood leukocytes and similarly in similar to 14% of reads in both DNA extracted from buccal mucosa and urine sample. Sanger sequencing confirmed the presence of these variants at a corresponding low level consistent with mosaicism that may not have been detected by this method alone. This report demonstrates the clinical benefit for two women of BRCA1/BRCA2 germline NGS testing at a depth that can detect low-level mosaicism. As well as informing appropriate treatments, tumour sequencing results may facilitate the detection and interpretation of low-level mosaic variants in the germline. Both results have implications for other cancer risks and for relatives when providing a family cancer risk assessment and reproductive risk. The implications for laboratory practice, clinical genetics management and genetic counselling for constitutional mosaicism of BRCA1/BRCA2 are discussed. Show less
This research revealed the role of leaders in relation to incident prevention in organisations. The acquired data showed that Dominance-oriented leaders have a negative influence on safety.... Show moreThis research revealed the role of leaders in relation to incident prevention in organisations. The acquired data showed that Dominance-oriented leaders have a negative influence on safety. Relation-oriented leaders appeared to be friendly people with no real influence on safety. Production-oriented leaders are real achievers, committed to meeting production targets. A new character emerged during our research: the Process-oriented leader. This leader proved a dedicated safety minded leader, who fulfils his production duties in a responsible way, taking care of the reliability of production without compromising the safety of his team members. Also, we developed a Risk Reduction Cycle, showing the risk reduction process. This model revealed that the recognition of risks and implementation of remedial actions are the weakest links. In conclusion, we argue that this research revealed that the effectiveness of incident prevention depends predominantly on the individual behaviour of their leaders. Consequently, in order to foster Process-oriented Safety Leadership, we recommend not to focus on operational safety practices to be carried out by the workforce. Instead, we deliberately emphasise the influential power of their leaders, and propose a set of Process-oriented Safety Leadership Principles, directed at the board room level of organisations and three external parties. Show less
Berger, F.A.; Sijs, H. van der; Gelder, T. van; Kuijper, A.F.M.; Bemt, P.M.L.A. van den; Becker, M.L. 2021
Background: QTc-prolongation is an independent risk factor for developing life-threatening arrhythmias. Risk management of drug-induced QTc-prolongation is complex and digital support tools could... Show moreBackground: QTc-prolongation is an independent risk factor for developing life-threatening arrhythmias. Risk management of drug-induced QTc-prolongation is complex and digital support tools could be of assistance. Bindraban et al. and Berger et al. developed two algorithms to identify patients at risk for QTc-prolongation.Objective: The main aim of this study was to compare the performances of these algorithms for managing QTcprolonging drug-drug interactions (QT-DDIs).Materials and Methods: A retrospective data analysis was performed. A dataset was created from QT-DDI alerts generated for inand outpatients at a general teaching hospital between November 2016 and March 2018. ECGs recorded within 7 days of the QT-DDI alert were collected. Main outcomes were the performance characteristics of both algorithms. QTc-intervals of > 500 ms on the first ECG after the alert were taken as outcome parameter, to which the performances were compared. Secondary outcome was the distribution of risk scores in the study cohort.Results: In total, 10,870 QT-DDI alerts of 4987 patients were included. ECGs were recorded in 26.2 % of the QT-DDI alerts. Application of the algorithms resulted in area under the ROC-curves of 0.81 (95 % CI 0.79-0.84) for Bindraban et al. and 0.73 (0.70-0.75) for Berger et al. Cut-off values of >= 3 and >= 6 led to sensitivities of 85.7 % and 89.1 %, and specificities of 60.8 % and 44.3 % respectively.Conclusions: Both algorithms showed good discriminative abilities to identify patients at risk for QTcprolongation when using >= 2 QTc-prolonging drugs. Implementation of digital algorithms in clinical decision support systems could support the risk management of QT-DDIs. Show less
The number of anthropogenic chemicals, manufactured, by-products, metabolites and abiotically formed transformation products, counts to hundreds of thousands, at present. Thus, humans and wildlife... Show moreThe number of anthropogenic chemicals, manufactured, by-products, metabolites and abiotically formed transformation products, counts to hundreds of thousands, at present. Thus, humans and wildlife are exposed to complex mixtures, never one chemical at a time and rarely with only one dominating effect. Hence there is an urgent need to develop strategies on how exposure to multiple hazardous chemicals and the combination of their effects can be assessed. A workshop, "Advancing the Assessment of Chemical Mixtures and their Risks for Human Health and the Environment" was organized in May 2018 together with Joint Research Center in Ispra, EU-funded research projects and Commission Services and relevant EU agencies. This forum for researchers and policy-makers was created to discuss and identify gaps in risk assessment and governance of chemical mixtures as well as to discuss state of the art science and future research needs. Based on the presentations and discussions at this workshop we want to bring forward the following Key Messages:• We are at a turning point: multiple exposures and their combined effects require better management to protect public health and the environment from hazardous chemical mixtures.• Regulatory initiatives should be launched to investigate the opportunities for all relevant regulatory frameworks to include prospective mixture risk assessment and consider combined exposures to (real-life) chemical mixtures to humans and wildlife, across sectors.• Precautionary approaches and intermediate measures (e.g. Mixture Assessment Factor) can already be applied, although, definitive mixture risk assessments cannot be routinely conducted due to significant knowledge and data gaps.• A European strategy needs to be set, through stakeholder engagement, for the governance of combined exposure to multiple chemicals and mixtures. The strategy would include research aimed at scientific advancement in mechanistic understanding and modelling techniques, as well as research to address regulatory and policy needs. Without such a clear strategy, specific objectives and common priorities, research, and policies to address mixtures will likely remain scattered and insufficient. Show less
In the past decades a growing body of literature has been dedicated to explain desistance from offending behaviour, or to answer the question why some offenders quit crime and others do not.... Show moreIn the past decades a growing body of literature has been dedicated to explain desistance from offending behaviour, or to answer the question why some offenders quit crime and others do not. Currently, more psychological explanations infuse a prominent line of research emphasizing the importance of subjective, individual factors coming from within the offender, such as developing a new sense of self-identity. The aim of this study was to gain more insight into different dimensions of desistance, focusing on two aspects of identity: future expectations and conventional aspirations, and investigated how these related to (non-)criminal behaviour over time. Furthermore, this study examined how the parole experience interacted with the different dimensions of desistance. This qualitative, longitudinal study followed 28 male prisoners serving a long-term sentence in the Netherlands during their transition from prison to society. Findings illustrated the importance of individual factors such as believing in one’s own abilities in the context of pre-release expectations, the lack of conventional scripts and role models, and the contribution of parole supervision to the desistance process. Yet, it also revealed the pain of failure for men attempting to refrain from crime, mostly relating to structural support such as employment or housing issues. Show less
ederland is een van de weinige Europese landen waar voorspellende modellen een rol spelen in het beheer van archeologisch erfgoed. Deze modellen worden gebruikt om de locatie van archeologische... Show moreederland is een van de weinige Europese landen waar voorspellende modellen een rol spelen in het beheer van archeologisch erfgoed. Deze modellen worden gebruikt om de locatie van archeologische vindplaatsen te voorspellen. Ze spelen zo een rol in toekomstige ontwikkelingen van het moderne landschap. Voor veel onderzoekers is het gebruik van voorspellende modellen in de monumentenzorg omstreden. Tussen 2002 en 2006 onderzocht een team van Nederlandse onderzoekers het gebruik van deze modellen in de Nederlandse archeologische monumentenzorg. Een van de doelen was het ontwikkelen van een best practice voor het maken en gebruiken van deze modellen. Dit boek is hier het resultaat van, het bevat naast technische bijdragen artikelen over hoe de modellen gebruikt moeten. Meer informatie over het onderzoeksproject Predictive Modelling for Archaeological Heritage Management kunt u "http://archaeology.leiden.edu/research/computerapplications/bbopredmod.html">hier vinden. The Netherlands are one of the few countries in Europe where predictive models play an important role in cultural heritage management. The models are used to predict archaeological site location in order to guide future developments in the modern landscape. Many scholars however consider the application of predictive models for this purpose highly controversial. Between 2002 and 2006 a team of Dutch researchers conducted strategic research into predictive modelling on behalf of Dutch cultural resource management. One of the goals was to develop best practices for the production and application of these models. This book is the second and final edited volume of publications of this Predictive Modelling project. It brings together technical papers on developing new methods for predictive modelling and applied, interdisciplinary 'action research' focusing on how the models are, or should be, used by stakeholders in cultural heritage management in the Netherlands. For more information on the researchproject, please click "http://archaeology.leiden.edu/research/computerapplications/bbopredmod.html">here Show less
