How to inform at-risk relatives?:Attitudes of 1379 Dutch patients, relatives, and members of the general population

The uptake of predictive DNA testing in families with a hereditary disease is <50%. Current practice often relies on the proband to inform relatives about the possibility of predictive DNA testing, but not all relatives are informed adequately. To enable informed decision-making concerning predictive DNA testing, the approach used to inform at-risk relatives needs to be optimized. This study investigated the preferences of patients, relatives, and the general population from the Netherlands on how to inform relatives at risk of autosomal dominant diseases. Online surveys were sent to people with autosomal dominant neuro-, onco-, or cardiogenetic diseases and their relatives via patient organizations (n = 379), and to members of the general population via a commercial panel (n = 1,000). Attitudes of the patient and population samples generally corresponded. A majority believed that initially only first-degree relatives should be informed, following the principles of a cascade screening approach. Most participants also thought that probands and healthcare professionals (HCPs) should be involved in informing relatives, and a large proportion believed that HCPs should contact relatives directly in cases where patients are unwilling to inform, both for untreatable and treatable conditions. Participants from the patient sample were of the opinion that HCPs should actively offer support. Our findings show that both patients and HCPs should be involved in informing at-risk relatives of autosomal dominant diseases and suggest that relatives' 'right to know' was considered a dominant issue by the majority of participants. Further research is needed on how to increase proactive support in informing of at-risk relatives

Earthquake Rupture on Multiple Splay Faults and Its Effect on Tsunamis

Detailed imaging of accretionary wedges reveals splay fault networks that could pose a significant tsunami hazard. However, the dynamics of multiple splay fault activation during megathrust earthquakes and the consequent effects on tsunami generation are not well understood. We use a 2-D dynamic rupture model with complex topo-bathymetry and six curved splay fault geometries constrained from realistic tectonic loading modeled by a geodynamic seismic cycle model with consistent initial stress and strength conditions. We find that all splay faults rupture coseismically. While the largest splay fault slips due to a complex rupture branching process from the megathrust, all other splay faults are activated either top down or bottom up by dynamic stress transfer induced by trapped seismic waves. We ascribe these differences to local non-optimal fault orientations and variable along-dip strength excess. Generally, rupture on splay faults is facilitated by their favorable stress orientations and low strength excess as a result of high pore-fluid pressures. The ensuing tsunami modeled with non-linear 1-D shallow water equations consists of one high-amplitude crest related to rupture on the longest splay fault and a second broader wave packet resulting from slip on the other faults. This results in two episodes of flooding and a larger run-up distance than the single long-wavelength (300 km) tsunami sourced by the megathrust-only rupture. Since splay fault activation is determined by both variable stress and strength conditions and dynamic activation, considering both tectonic and earthquake processes is relevant for understanding tsunamigenesis

Compositional attribution of non-provenienced Maya polychrome vessels

Procedures and a few of the results of the Maya ceramic project are discussed from the perspective of non-provenienced vessel attribution ranging from site specific through a more inferential level to the rather hypothetical. The examples presented serve to illustrate the manner in which compositional and stylistic covariation are viewed in an investigation of Maya Ceramic art. The large data base from neutron activation analysis including archaeologically recovered pottery as well as the stylistically and iconographically elaborate vessels requires continued refinement in our methods of statistical analysis along with gaining a greater understanding of the sources of ceramic compositional variation in the Maya area. The mutually beneficial collaboration between science, art, and archaeology are emphasized

Linked 3-D modelling of megathrust earthquake-tsunami events: from subduction to tsunami run up

How does megathrust earthquake rupture govern tsunami behaviour? Recent modelling advances permit evaluation of the influence of 3-D earthquake dynamics on tsunami genesis, propagation, and coastal inundation. Here, we present and explore a virtual laboratory in which the tsunami source arises from 3-D coseismic seafloor displacements generated by a dynamic earthquake rupture model. This is achieved by linking open-source earthquake and tsunami computational models that follow discontinuous Galerkin schemes and are facilitated by highly optimized parallel algorithms and software. We present three scenarios demonstrating the flexibility and capabilities of linked modelling. In the first two scenarios, we use a dynamic earthquake source including time-dependent spontaneous failure along a 3-D planar fault surrounded by homogeneous rock and depth-dependent, near-lithostatic stresses. We investigate how slip to the trench influences tsunami behaviour by simulating one blind and one surface-breaching rupture. The blind rupture scenario exhibits distinct earthquake characteristics (lower slip, shorter rupture duration, lower stress drop, lower rupture speed), but the tsunami is similar to that from the surface-breaching rupture in run-up and length of impacted coastline. The higher tsunami-generating efficiency of the blind rupture may explain how there are differences in earthquake characteristics between the scenarios, but similarities in tsunami inundation patterns. However, the lower seafloor displacements in the blind rupture result in a smaller displaced volume of water leading to a narrower inundation corridor inland from the coast and a 15 per cent smaller inundation area overall. In the third scenario, the 3-D earthquake model is initialized using a seismo-thermo-mechanical geodynamic model simulating both subduction dynamics and seismic cycles. This ensures that the curved fault geometry, heterogeneous stresses and strength and material structure are consistent with each other and with millions of years of modelled deformation in the subduction channel. These conditions lead to a realistic rupture in terms of velocity and stress drop that is blind, but efficiently generates a tsunami. In all scenarios, comparison with the tsunamis sourced by the time-dependent seafloor displacements, using only the time-independent displacements alters tsunami temporal behaviour, resulting in later tsunami arrival at the coast, but faster coastal inundation. In the scenarios with the surface-breaching and subduction-initialized earthquakes, using the time-independent displacements also overpredicts run-up. In the future, the here presented scenarios may be useful for comparison of alternative dynamic earthquake-tsunami modelling approaches or linking choices, and can be readily developed into more complex applications to study how earthquake source dynamics influence tsunami genesis, propagation and inundation

Recovery for all in the community:Position paper on principles and key elements of community-based mental health care

Backgroud:Service providers throughout Europe have identified the need to define how high-quality community-based mental health care looks to organize their own services and to inform governments, commissioners and funders. In 2016, representatives of mental health care service providers, networks, umbrella organizations and knowledge institutes in Europe came together to establish the European Community Mental Health Services Provider (EUCOMS) Network. This network developed a shared vision on the principles and key elements of community mental health care in different contexts. The result is a comprehensive consensus paper, of which this position paper is an outline. With this paper the network wants to contribute to the discussion on how to improve structures in mental healthcare, and to narrow the gap between evidence, policy and practice in Europe.Main text:The development of the consensus paper started with an expert workshop in April 2016. An assigned writing group representing the workshop participants built upon the outcomes of this meeting and developed the consensus paper with the input from 100 European counterparts through two additional work groups, and two structured feedback rounds via email. High quality community-based mental health care: 1) protects human rights; 2) has a public health focus; 3) supports service users in their recovery journey; 4) makes use of effective interventions based on evidence and client goals; 5) promotes a wide network of support in the community and; 6) makes use of peer expertise in service design and delivery. Each principle is illustrated with good practices from European service providers that are members of the EUCOMS Network.Conclusions:Discussion among EUCOMS network members resulted in a blueprint for a regional model of integrated mental health care based upon six principles.</p

Intermediate‐Depth Earthquakes Controlled by Incoming Plate Hydration Along Bending‐Related Faults

Intermediate‐depth earthquakes (focal depths 70–300 km) are enigmatic with respect to their nucleation and rupture mechanism and the properties controlling their spatial distribution. Several recent studies have shown a link between intermediate‐depth earthquakes and the thermal‐petrological path of subducting slabs in relation to the stability field of hydrous minerals. Here we investigate whether the structural characteristics of incoming plates can be correlated with the intermediate‐depth seismicity rate. We quantify the structural characteristics of 17 incoming plates by estimating the maximum fault throw of bending‐related faults. Maximum fault throw exhibits a statistically significant correlation with the seismicity rate. We suggest that the correlation between fault throw and intermediate‐depth seismicity rate indicates the role of hydration of the incoming plate, with larger faults reflecting increased damage, greater fluid circulation, and thus more extensive slab hydration

A Framework for Online Conformance Checking

Conformance checking – a branch of process mining – focuses on establishing to what extent actual executions of a process are in line with the expected behavior of a reference model. Current conformance checking techniques only allow for a-posteriori analysis: the amount of (non-)conformant behavior is quantified after the completion of the process instance. In this paper we propose a framework for online conformance checking: not only do we quantify (non-)conformant behavior as the execution is running, we also restrict the computation to constant time complexity per event analyzed, thus enabling the online analysis of a stream of events. The framework is instantiated with ideas coming from the theory of regions, and state similarity. An implementation is available in ProM and promising results have been obtained.Peer ReviewedPostprint (author's final draft

Analyses of abdominal adiposity and metabolic syndrome as risk factors for respiratory distress in COVID-19

Background Several characteristics of the metabolic syndrome, such as obesity and hypertension, have emerged as risk factors for a poor clinical outcome in COVID-19. However, most reports lack data on the metabolic syndrome itself. This study investigated prospectively the relationship between respiratory deterioration and the presence of metabolic syndrome or abdominal adiposity in patients with COVID-19. Methods A prospective observational cohort study analysing patients with respiratory symptoms who presented at a local emergency department in the Netherlands. The influence of abdominal adiposity - assessed by an increased waist-hip ratio - and metabolic syndrome on respiratory deterioration and the length of hospital stay were analysed with multivariable logistic regressions and Kaplan-Meier analyses. Results In total, 166 patients were analysed, of whom 86 (52%) tested positive for COVID-19. The prevalence of metabolic syndrome did not differ between patients with COVID-19 with and without the need for intubation or level of supportive care (37.5% vs 48.4%, p=0.338). In contrast, abdominal adiposity is an independent risk factor for respiratory distress in COVID-19, adjusted for metabolic syndrome, age, gender and BMI (OR 1.11, 95% CI 1.02 to 1.20, p=0.014). Conclusion This study shows that abdominal adiposity, and not the presence of metabolic syndrome, is associated with clinical deterioration in COVID-19. This prospective study provides further insight into the risk stratification of patients with COVID-19 based on a simple measurement as the waist and hip circumference

Performance of BRCA1/2 mutation prediction models in male breast cancer patients

To establish whether existing mutation prediction models can identify which male breast cancer (MBC) patients should be offered BRCA1 and BRCA2 diagnostic DNA screening, we compared the performance of BOADICEA (Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm), BRCAPRO (BRCA probability) and the Myriad prevalence table ("Myriad"). These models were evaluated using the family data of 307 Dutch MBC probands tested for BRCA1/2, 58 (19%) of whom were carriers. We compared the numbers of observed vs predicted carriers and assessed the Area Under the Receiver Operating Characteristic (ROC) Curve (AUC) for each model. BOADICEA predicted the total number of BRCA1/2 mutation carriers quite accurately (observed/predicted ratio: 0.94). When a cut-off of 10% and 20% prior probability was used, BRCAPRO showed a non-significant better performance (observed/predicted ratio BOADICEA: 0.81, 95% confidence interval [CI]: [0.60-1.09] and 0.79, 95% CI: [0.57-1.09], vs. BRCAPRO: 1.02, 95% CI: [0.75-1.38] and 0.94, 95% CI: [0.68-1.31], respectively). Myriad underestimated the number of carriers in up to 69% of the cases. BRCAPRO showed a non-significant, higher AUC than BOADICEA (0.798 vs 0.776). Myriad showed a significantly lower AUC (0.671). BRCAPRO and BOADICEA can efficiently identify MBC patients as BRCA1/2 mutation carriers. Besides their general applicability, these tools will be of particular value in countries with limited healthcare resources