Finding Mutated Subnetworks Associated with Survival in Cancer

Next-generation sequencing technologies allow the measurement of somatic mutations in a large number of patients from the same cancer type. One of the main goals in analyzing these mutations is the identification of mutations associated with clinical parameters, such as survival time. This goal is hindered by the genetic heterogeneity of mutations in cancer, due to the fact that genes and mutations act in the context of pathways. To identify mutations associated with survival time it is therefore crucial to study mutations in the context of interaction networks. In this work we study the problem of identifying subnetworks of a large gene-gene interaction network that have mutations associated with survival. We formally define the associated computational problem by using a score for subnetworks based on the test statistic of the log-rank test, a widely used statistical test for comparing the survival of two populations. We show that the computational problem is NP-hard and we propose a novel algorithm, called Network of Mutations Associated with Survival (NoMAS), to solve it. NoMAS is based on the color-coding technique, that has been previously used in other applications to find the highest scoring subnetwork with high probability when the subnetwork score is additive. In our case the score is not additive; nonetheless, we prove that under a reasonable model for mutations in cancer NoMAS does identify the optimal solution with high probability. We test NoMAS on simulated and cancer data, comparing it to approaches based on single gene tests and to various greedy approaches. We show that our method does indeed find the optimal solution and performs better than the other approaches. Moreover, on two cancer datasets our method identifies subnetworks with significant association to survival when none of the genes has significant association with survival when considered in isolation.Comment: This paper was selected for oral presentation at RECOMB 2016 and an abstract is published in the conference proceeding

Skyhøyt Spill - Resilient taktikk mot dronetrusler

Formålet med denne studien, utover å undersøke operatørenes håndtering av dronetrussel høsten 2022, er å lukke et kunnskapsgap innen studie av perspektivet «resilience engineering» (RE-perspektivet). Det er få studier som har undersøkt hvordan RE perspektivet har blitt operasjonalisert i håndtering av sikringshendelser. I denne studien ønsker jeg å undersøke: Hvordan har operatørene operasjonalisert prinsippene fra «resilience engineering» i forbindelse med håndtering av dronetrusselen høsten 2022? Studien har tatt utgangspunkt i Erik Hollnagel sin definisjon av «resilience», og hans fire egenskaper som bidrar til å bygge «resilience». Det er lagt til grunn en kvalitativ metode, hvor det er gjennomført semistrukturerte intervju av seks personer som jobber i petroleumsnæringen, og som har vært aktivt involvert i håndtering av droneobservasjonene høsten 2022. Det er gjennomført en tematisk analyse av data. Det er også anvendt en deltakende observasjon ettersom jeg selv har vært deltakende i håndtering av droneobservasjonene. Operasjonaliseringen av prinsippene fra «resilience engineering» (RE) i håndtering av dronetrusselen høsten 2022 har vært en kompleks prosess for operatørene. De sentrale funn i studien er: Operatørene har lagt betydelig vekt på overvåking ved bruk av trussel- og sikringsrisikovurderinger. Selv om disse metodene er verdifulle for overvåking, er de mindre velegnet for å forutse fremtidige scenarioer. Overvåkningens avhengighet av eksterne kilder fremhever et kritisk område for forbedring. Funn tyder på at operatørene har hatt en reaktiv respons, men til tross for dette har de vist en proaktiv tilnærming til iverksettelse av tiltak. Operatørene har operasjonalisert evnen til å lære i håndtering av dronetrussel ved å dra nytte av lærdommer fra tidligere hendelser, legge vekt på trening og øvelse, samt forsterke tverrfaglig samarbeid og nettverksbygging. Funnene indikerer en blandet tilnærming til RE-prinsippene. Mens det er klare styrker i operatørenes evne til å reagere på og lære fra trusler, er det også rom for forbedring i deres evne til å forutse og overvåke slike trusler. En forståelse av disse styrkene og svakhetene kan bidra til å informere fremtidig håndtering ved å forbedre praksis i forbindelse med dronetrusler og andre komplekse utfordringer. Denne studien understreker viktigheten av en kontinuerlig evaluering og tilpasning av praksis for å håndtere komplekse trusler i en verden i stadig endring.The purpose of this study, beyond examining the petroleum operators' handling of the drone threat during autumn 2022, is to close a knowledge gap within the study of the resilience engineering (RE) perspective. Few studies have examined how the RE perspective has been operationalized in the handling of security incidents. What I want to research in this study is: How have the operators operationalized the principles of resilience engineering in addressing the drone threat in the fall of 2022? The study is based on Erik Hollnagel's definition of resilience and his four characteristics that help build resilience. A qualitative method has been used, where semi-structured interviews have been conducted of six people who work in the petroleum industry and have been actively involved in handling the drone observations in the autumn of 2022. A thematic analysis of the data has been carried out. A participatory observation has also been used, as I myself have been involved in handling the drone observations. The operationalization of resilience engineering (RE) principles in dealing with the drone threat in autumn 2022 has been a complex process for the operators. The key findings of the study are: Operators have placed considerable emphasis on surveillance using threat- and security risk assessment. While these methods are valuable for monitoring, they are less suitable for predicting future scenarios. Monitoring's reliance on external sources highlights a critical area for improvement. Findings suggest a reactive response, but despite this, they have shown a proactive approach to implementing measures. The operators have operationalized the ability to learn in dealing with drone threats by drawing on lessons learned from previous incidents, emphasizing training and exercise, as well as reinforcing interdisciplinary cooperation and networking. The findings indicate a mixed approach to the RE principles. While there are clear strengths in operators' ability to respond to and learn from threats, there is also room for improvement in their ability to anticipate and monitor such threats. An understanding of these strengths and weaknesses can help inform future management of incidents by improving practices related to drone threats and other complex challenges. This study underscores the importance of a continuous evaluation and adaptation of practices to deal with complex threats in an ever-changing world

Det gamle og nye Frederiksberg i Roskilde

Det gamle og nye Frederiksberg i Roskild

Establishing the Convergent Validity of the Travel Habit Questions in the Health Behavior in School-Aged Children Questionnaire by Quantifying Active Travel in Norwegian Adolescents

Background: Active travel (cycling or walking to school) can be a substantial part of adolescents' daily physical activity. Research on transport activities primarily relies on self-reported indices of travel mode and travel time. However, many researchers do not report the psychometric properties of their instruments. The Health Behavior in School-aged Children (HBSC) questionnaire is a commonly used instrument, but the items in this questionnaire on travel habits have not yet been validated. The present study was conducted to investigate the convergent validity and agreement between the HBSC items and a travel diary on (1) transport mode to and from school and (2) travel time to school. Methods: The study sample consisted of 50 participants in the 9th grade (15 ± 0.3 years, 62% girls) from seven Norwegian schools. Outcome variables included transport mode and travel time derived from the HBSC items and a five-day travel diary. Convergent validity was assessed by evaluating Cohen's kappa for travel mode and the correlation coefficient (Spearman Rho) for travel time. Simple agreement calculations between the two measurement methods were also conducted. Results: The association between the HBSC questionnaire and the diary for travel mode to and from school was κ = 0.63 (P < 0.001) and κ = 0.77 (P < 0.001), respectively. The total agreement between the HBSC questionnaire and the diary for was 78%. However, the agreement was higher for walking (88%) and cycling (91%) than for motorized transport (67%). For travel time, the Spearman correlation coefficient was ρ = 0.60 (P < 0.001) between the HBSC questionnaire and the diary. The total agreement on travel time was 67%; however, active commuters (86%) seemed to more accurately estimated travel time than motorized commuters (55%). Conclusion: Although the overall agreement between the HBSC questionnaire and the diary for mode of transport was 78%, the HBSC questionnaire may underestimate the prevalence of motorized transport compared to walking and cycling.publishedVersio

Semiconvergence and Relaxation Parameters for Projected SIRT Algorithms

We give a detailed study of the semiconvergence behavior of projected nonstationary simultaneous iterative reconstruction technique (SIRT) algorithms, including the projected Landweber algorithm. We also consider the use of a relaxation parameter strategy, proposed recently for the standard algorithms, for controlling the semiconvergence of the projected algorithms. We demonstrate the semiconvergence and the performance of our strategies by examples taken from tomographic imaging.Funding Agencies|Danish Research Council for Technology and Production Sciences|274-07-0065|</p

N-Losses and Energy Use in a Scenario for Conversion to Organic Farming

The aims of organic farming include the recycling of nutrients and organic matter and the minimisa-tion of the environmental impact of agriculture. Reduced nitrogen (N)-losses and energy (E)-use are therefore fundamental objectives of conversion to organic farming. However, the case is not straightforward, and different scenarios for conversion to organic farming might lead to reduced or increased N-losses and E-use. This paper presents a scenario tool that uses a Geographical Information System in association with models for crop rotations, fertilisation practices, N-losses, and E-uses. The scenario tool has been developed within the multidisciplinary research project Land Use and Landscape Development Illustrated with Scenarios (ARLAS). A pilot scenario was carried out, where predicted changes in N-losses and E-uses following conversion to organic farming in areas with special interests in clean groundwater were compared. The N-surplus and E-use were on average reduced by 10 and 54%, respectively. However, these reductions following the predicted changes in crop rotations, livestock densities, and fertilisation practices were not large enough to ensure a statistically significant reduction at the 95% level. We therefore recommend further research in how conversion to organic farming or other changes in the agricultural practice might help to reduce N-surpluses and E-uses. In that context, the presented scenario tool would be useful