Privacy and security concerns with passively collected location data for digital contact tracing among U.S. college students.

People continue to use technology in new ways, and how governments harness digital information should consider privacy and security concerns. During COVID19, numerous countries deployed digital contact tracing that collect location data from user's smartphones. However, these apps had low adoption rates and faced opposition. We launched an interdisciplinary study to evaluate smartphone location data concerns among college students in the US. Using interviews and a large survey, we find that college students have higher concerns regarding privacy, and place greater trust in local government with their location data. We discuss policy recommendations for implementing improved contact tracing efforts.

Assessing the crash risks of evacuation: A matched case-control approach applied over data collected during Hurricane Irma.

Recent hurricane experiences have created concerns for transportation agencies and policymakers to find better evacuation strategies, especially after Hurricane Irma-which forced about 6.5 million Floridians to evacuate and caused a significant amount of delay due to heavy congestion. A major concern for issuing an evacuation order is that it may involve a high number of crashes in highways. In this study, we present a matched case-control based approach to understand the factors contributing to the increase in the number of crashes during evacuation. We use traffic data for a period of 5 to 10 min just before the crash occurred. For each crash observation, traffic data are collected from two upstream and two downstream detectors of the crash location. We estimate models for three different conditions: regular period, evacuation period, and combining both evacuation and regular period data. Model results show that, if there exist a high volume of traffic at an upstream station and a high variation of speed at a downstream station, the likelihood of crash occurrence increases. Using a panel mixed binary logit model, we also estimate the effect of evacuation itself on crash risk and find that, after controlling for traffic characteristics, during evacuation the chance of a crash is higher than in a regular period. Our findings have implications for evacuation declarations and highlight the need for better traffic management strategies during evacuation. Future studies may develop advanced real-time crash prediction models which would allow us to deploy proactive countermeasures to reduce crash occurrences during evacuation.

Road to effective data curation for translational research.

Translational research today is data-intensive and requires multi-stakeholder collaborations to generate and pool data together for integrated analysis. This leads to the challenge of harmonization of data from different sources with different formats and standards, which is often overlooked during project planning and thus becomes a bottleneck of the research progress. We report on our experience and lessons learnt about data curation for translational research garnered over the course of the European Translational Research Infrastructure & Knowledge management Services (eTRIKS) program (https://www.etriks.org), a unique, 5-year, cross-organizational, cross-cultural collaboration project funded by the Innovative Medicines Initiative of the EU. Here, we discuss the obstacles and suggest what steps are needed for effective data curation in translational research, especially for projects involving multiple organizations from academia and industry.

Quantifying the impact of daily mobility on errors in air pollution exposure estimation using mobile phone location data.

One major source of uncertainty in accurately estimating human exposure to air pollution is that human subjects move spatiotemporally, and such mobility is usually not considered in exposure estimation. How such mobility impacts exposure estimates at the population and individual level, particularly for subjects with different levels of mobility, remains under-investigated. In addition, a wide range of methods have been used in the past to develop air pollutant concentration fields for related health studies. How the choices of methods impact results of exposure estimation, especially when detailed mobility information is considered, is still largely unknown. In this study, by using a publicly available large cell phone location dataset containing over 35 million location records collected from 310,989 subjects, we investigated the impact of individual subjects' mobility on their estimated exposures for five chosen ambient pollutants (CO, NO2, SO2, O3 and PM2.5). We also estimated exposures separately for 10 groups of subjects with different levels of mobility to explore how increased mobility impacted their exposure estimates. Further, we applied and compared two methods to develop concentration fields for exposure estimation, including one based on Community Multiscale Air Quality (CMAQ) model outputs, and the other based on the interpolated observed pollutant concentrations using the inverse distance weighting (IDW) method. Our results suggest that detailed mobility information does not have a significant influence on mean population exposure estimate in our sample population, although impacts can be substantial at the individual level. Additionally, exposure classification error due to the use of home-location data increased for subjects that exhibited higher levels of mobility. Omitting mobility could result in underestimation of exposures to traffic-related pollutants particularly during afternoon rush-hour, and overestimate exposures to ozone especially during mid-afternoon. Between CMAQ and IDW, we found that the IDW method generates smooth concentration fields that were not suitable for exposure estimation with detailed mobility data. Therefore, the method for developing air pollution concentration fields when detailed mobility data were to be applied should be chosen carefully. Our findings have important implications for future air pollution health studies.

Applying machine learning approaches to analyze the vulnerable road-users' crashes at statewide traffic analysis zones.

INTRODUCTION: In this paper, we present machine learning techniques to analyze pedestrian and bicycle crash by developing macro-level crash prediction models. METHODS: We collected the 2010-2012 Statewide Traffic Analysis Zone (STAZ) level crash data and developed rigorous machine learning approach (i.e., decision tree regression (DTR) models) for both pedestrian and bicycle crash counts. To our knowledge, this is the first application of DTR models in the burgeoning macro-level traffic safety literature. RESULTS: The DTR models uncovered the most significant predictor variables for both response variables (pedestrian and bicycle crash counts) in terms of three broad categories: traffic, roadway, and socio-demographic characteristics. Additionally, spatial predictor variables of neighboring STAZs were considered along with the targeted STAZ in both DTR models. The DTR model considering spatial predictor variables (spatial DTR model) were compared without considering spatial predictor variables (aspatial DTR model) and the model comparison results discovered that the prediction accuracy of the spatial DTR model performed better than the aspatial DTR model. Finally, the current research effort contributed to the safety literature by applying some ensemble techniques (i.e. bagging, random forest, and gradient boosting) in order to improve the prediction accuracy of the DTR models (weak learner) for macro-level crash count. The study revealed that all the ensemble techniques performed slightly better than the DTR model and the gradient boosting technique outperformed other competing ensemble techniques in macro-level crash prediction models.

On the accuracy and potential of Google Maps location history data to characterize individual mobility for air pollution health studies.

Appropriately characterizing spatiotemporal individual mobility is important in many research areas, including epidemiological studies focusing on air pollution. However, in many retrospective air pollution health studies, exposure to air pollution is typically estimated at the subjects' residential addresses. Individual mobility is often neglected due to lack of data, and exposure misclassification errors are expected. In this study, we demonstrate the potential of using location history data collected from smartphones by the Google Maps application for characterizing historical individual mobility and exposure. Here, one subject carried a smartphone installed with Google Maps, and a reference GPS data logger which was configured to record location every 10 s, for a period of one week. The retrieved Google Maps Location History (GMLH) data were then compared with the GPS data to evaluate their effectiveness and accuracy of the GMLH data to capture individual mobility. We also conducted an online survey (n = 284) to assess the availability of GMLH data among smartphone users in the US. We found the GMLH data reasonably captured the spatial movement of the subject during the one-week time period at up to 200 m resolution. We were able to accurately estimate the time the subject spent in different microenvironments, as well as the time the subject spent driving during the week. The estimated time-weighted daily exposures to ambient particulate matter using GMLH and the GPS data logger were also similar (error less than 1.2%). Survey results showed that GMLH data may be available for 61% of the survey sample. Considering the popularity of smartphones and the Google Maps application, detailed historical location data are expected to be available for large portion of the population, and results from this study highlight the potential of these location history data to improve exposure estimation for retrospective epidemiological studies.

Controlled release of chlorhexidine from a HEMA-UDMA resin using a magnetic field.

OBJECTIVES: To functionalize novel chlorhexidine (CHX) particles with iron oxide (Fe3O4) nanoparticles and control their release kinetics in a dental resin using an external magnetic field. METHODS: Fe3O4 nanoparticles were synthesized and incorporated into spherical CHX particles and the powder was freeze dried. Resin disc specimens were produced using a UDMA-HEMA resin mixed with freeze dried spherical Fe3O4-CHX particles (5wt.%), which were placed into a Teflon mould (10mm diameter×1mm depth) and covered with a Mylar strip. A MACS magnet was left in contact for 0min (Group 1), 5min (Group 2) or 10min (Group 3) and the resin discs subsequently light cured (Bluedent LED pen, Bulgaria) for 60s per side. The resin discs were immersed in deionized water at various time points up to 650h. UV-Vis absorbance was used to determine the CHX content. CHX released for each time point was determined. The functionalized CHX particles and resin discs were characterized using TEM, TGA, EDX and SEM. RESULTS: Fe3O4 nanoparticles (20nm) incorporated into the spherical CHX particles led to a mean (SD) particle size reduction from 17.15 (1.99)µm to 10.39 (2.61)µm. The presence of Fe3O4 nanoparticles in the spherical CHX particles was confirmed with SEM, EDX, and TGA. SEM of Group 1 resin discs (no magnetic exposure) showed functionalized CHX spheres were homogeneously distributed within the resin discs. For resin discs which had magnetic exposure (5 or 10min) the particles started to cluster nearer the surface (Group 2: 43.7%, Group 3: 57.3%), to a depth of 94µm. UV-Vis absorbance revealed Group 1 resin discs had a cumulative CHX release of 4.4% compared to 5.9% for Group 2 and 7.4% for Group 3 resin discs, which had magnetic exposure (5, 10min). SIGNIFICANCE: Fe3O4 nanoparticle functionalized CHX spheres demonstrated a magnetic field responsive property. A magnetic field responsive release of CHX may be useful in clinical situations where the drug can be directed to give a tailored release at the site of infection.

Uncovering novel repositioning opportunities using the Open Targets platform.

The recently developed Open Targets platform consolidates a wide range of comprehensive evidence associating known and potential drug targets with human diseases. We have harnessed the integrated data from this platform for novel drug repositioning opportunities. Our computational workflow systematically mines data from various evidence categories and presents potential repositioning opportunities for drugs that are marketed or being investigated in ongoing human clinical trials, based on evidence strength on target-disease pairing. We classified these novel target-disease opportunities in several ways: (i) number of independent counts of evidence; (ii) broad therapy area of origin; and (iii) repositioning within or across therapy areas. Finally, we elaborate on one example that was identified by this approach.

Ectopic Scrotum with VACTERL Association.

Scrotal ectopia is a rare condition. Associated anomalies are common. We describe a neonate with ectopic scrotum with VACTERL association. This combination of anomalies is very rare.

Accessibility and socio-economic development of human settlements.

Access to facilities, services and socio-economic opportunities plays a critical role in the growth and decline of cities and human settlements. Previous attempts to explain changes in socio-economic indicators by differences in accessibility have not been convincing as countries with highly developed transport infrastructure have only seen marginal benefits of infrastructure improvements. Australia offers an ideal case for investigating the effects of accessibility on development since it is seen as home to some of the most liveable cities in the world while, at the same time, it also has some of the most isolated settlements. We investigate herein the connectivity and accessibility of all 1814 human settlements (population centers exceeding 200 persons) in Australia, and how they relate to the socio-economic characteristics of, and opportunities in, each population center. Assuming population as a proxy indicator of available opportunities, we present a simple ranking metric for a settlement using the number of population and the distance required to access all other settlements (and the corresponding opportunities therein). We find a strikingly unequal distribution of access to opportunities in Australia, with a marked prominence of opportunities in capital cities in four of the eight states. The two largest cities of Sydney and Melbourne have a dominant position across all socio-economic indicators, compared to all the other cities. In general, we observe across all the settlements that a decrease in access to opportunities is associated with relatively greater socio-economic disadvantage including increased median age and unemployment rate and decreased median household income. Our methodology can be used to better understand the potential benefits of improved accessibility based on infrastructure development, especially for remote areas and for cities and towns with many socio-economically disadvantaged population.

Open Targets: a platform for therapeutic target identification and validation.

We have designed and developed a data integration and visualization platform that provides evidence about the association of known and potential drug targets with diseases. The platform is designed to support identification and prioritization of biological targets for follow-up. Each drug target is linked to a disease using integrated genome-wide data from a broad range of data sources. The platform provides either a target-centric workflow to identify diseases that may be associated with a specific target, or a disease-centric workflow to identify targets that may be associated with a specific disease. Users can easily transition between these target- and disease-centric workflows. The Open Targets Validation Platform is accessible at https://www.targetvalidation.org.

Linking rare and common disease: mapping clinical disease-phenotypes to ontologies in therapeutic target validation.

BACKGROUND: The Centre for Therapeutic Target Validation (CTTV - https://www.targetvalidation.org/) was established to generate therapeutic target evidence from genome-scale experiments and analyses. CTTV aims to support the validity of therapeutic targets by integrating existing and newly-generated data. Data integration has been achieved in some resources by mapping metadata such as disease and phenotypes to the Experimental Factor Ontology (EFO). Additionally, the relationship between ontology descriptions of rare and common diseases and their phenotypes can offer insights into shared biological mechanisms and potential drug targets. Ontologies are not ideal for representing the sometimes associated type relationship required. This work addresses two challenges; annotation of diverse big data, and representation of complex, sometimes associated relationships between concepts. METHODS: Semantic mapping uses a combination of custom scripting, our annotation tool 'Zooma', and expert curation. Disease-phenotype associations were generated using literature mining on Europe PubMed Central abstracts, which were manually verified by experts for validity. Representation of the disease-phenotype association was achieved by the Ontology of Biomedical AssociatioN (OBAN), a generic association representation model. OBAN represents associations between a subject and object i.e., disease and its associated phenotypes and the source of evidence for that association. The indirect disease-to-disease associations are exposed through shared phenotypes. This was applied to the use case of linking rare to common diseases at the CTTV. RESULTS: EFO yields an average of over 80% of mapping coverage in all data sources. A 42% precision is obtained from the manual verification of the text-mined disease-phenotype associations. This results in 1452 and 2810 disease-phenotype pairs for IBD and autoimmune disease and contributes towards 11,338 rare diseases associations (merged with existing published work [Am J Hum Genet 97:111-24, 2015]). An OBAN result file is downloadable at http://sourceforge.net/p/efo/code/HEAD/tree/trunk/src/efoassociations/. Twenty common diseases are linked to 85 rare diseases by shared phenotypes. A generalizable OBAN model for association representation is presented in this study. CONCLUSIONS: Here we present solutions to large-scale annotation-ontology mapping in the CTTV knowledge base, a process for disease-phenotype mining, and propose a generic association model, 'OBAN', as a means to integrate disease using shared phenotypes. AVAILABILITY: EFO is released monthly and available for download at http://www.ebi.ac.uk/efo/.

ADME SARfari: comparative genomics of drug metabolizing systems.

MOTIVATION: ADME SARfari is a freely available web resource that enables comparative analyses of drug-disposition genes. It does so by integrating a number of publicly available data sources, which have subsequently been used to build data mining services, predictive tools and visualizations for drug metabolism researchers. The data include the interactions of small molecules with ADME (absorption, distribution, metabolism and excretion) proteins responsible for the metabolism and transport of molecules; available pharmacokinetic (PK) data; protein sequences of ADME-related molecular targets for pre-clinical model species and human; alignments of the orthologues including information on known SNPs (Single Nucleotide Polymorphism) and information on the tissue distribution of these proteins. In addition, in silico models have been developed, which enable users to predict which ADME relevant protein targets a novel compound is likely to interact with.

Location contexts of user check-ins to model urban geo life-style patterns.

Geo-location data from social media offers us information, in new ways, to understand people's attitudes and interests through their activity choices. In this paper, we explore the idea of inferring individual life-style patterns from activity-location choices revealed in social media. We present a model to understand life-style patterns using the contextual information (e. g. location categories) of user check-ins. Probabilistic topic models are developed to infer individual geo life-style patterns from two perspectives: i) to characterize the patterns of user interests to different types of places and ii) to characterize the patterns of user visits to different neighborhoods. The method is applied to a dataset of Foursquare check-ins of the users from New York City. The co-existence of several location contexts and the corresponding probabilities in a given pattern provide useful information about user interests and choices. It is found that geo life-style patterns have similar items-either nearby neighborhoods or similar location categories. The semantic and geographic proximity of the items in a pattern reflects the hidden regularity in user preferences and location choice behavior.

HIV-1 transmission patterns in antiretroviral therapy-naïve, HIV-infected North Americans based on phylogenetic analysis by population level and ultra-deep DNA sequencing.

Factors that contribute to the transmission of human immunodeficiency virus type 1 (HIV-1), especially drug-resistant HIV-1 variants remain a significant public health concern. In-depth phylogenetic analyses of viral sequences obtained in the screening phase from antiretroviral-naïve HIV-infected patients seeking enrollment in EPZ108859, a large open-label study in the USA, Canada and Puerto Rico (ClinicalTrials.gov NCT00440947) were examined for insights into the roles of drug resistance and epidemiological factors that could impact disease dissemination. Viral transmission clusters (VTCs) were initially predicted from a phylogenetic analysis of population level HIV-1 pol sequences obtained from 690 antiretroviral-naïve subjects in 2007. Subsequently, the predicted VTCs were tested for robustness by ultra deep sequencing (UDS) using pyrosequencing technology and further phylogenetic analyses. The demographic characteristics of clustered and non-clustered subjects were then compared. From 690 subjects, 69 were assigned to 1 of 30 VTCs, each containing 2 to 5 subjects. Race composition of VTCs were significantly more likely to be white (72% vs. 60%; p = 0.04). VTCs had fewer reverse transcriptase and major PI resistance mutations (9% vs. 24%; p = 0.002) than non-clustered sequences. Both men-who-have-sex-with-men (MSM) (68% vs. 48%; p = 0.001) and Canadians (29% vs. 14%; p = 0.03) were significantly more frequent in VTCs than non-clustered sequences. Of the 515 subjects who initiated antiretroviral therapy, 33 experienced confirmed virologic failure through 144 weeks while only 3/33 were from VTCs. Fewer VTCs subjects (as compared to those with non-clustering virus) had HIV-1 with resistance-associated mutations or experienced virologic failure during the course of the study. Our analysis shows specific geographical and drug resistance trends that correlate well with transmission clusters defined by HIV sequences of similarity. Furthermore, our study demonstrates the utility of molecular and epidemiological analysis of VTCs for identifying population-specific risks associated with HIV-1 transmission and developing effective local healthcare strategies.

Minipig and beagle animal model genomes aid species selection in pharmaceutical discovery and development.

Improving drug attrition remains a challenge in pharmaceutical discovery and development. A major cause of early attrition is the demonstration of safety signals which can negate any therapeutic index previously established. Safety attrition needs to be put in context of clinical translation (i.e. human relevance) and is negatively impacted by differences between animal models and human. In order to minimize such an impact, an earlier assessment of pharmacological target homology across animal model species will enhance understanding of the context of animal safety signals and aid species selection during later regulatory toxicology studies. Here we sequenced the genomes of the Sus scrofa Göttingen minipig and the Canis familiaris beagle, two widely used animal species in regulatory safety studies. Comparative analyses of these new genomes with other key model organisms, namely mouse, rat, cynomolgus macaque, rhesus macaque, two related breeds (S. scrofa Duroc and C. familiaris boxer) and human reveal considerable variation in gene content. Key genes in toxicology and metabolism studies, such as the UGT2 family, CYP2D6, and SLCO1A2, displayed unique duplication patterns. Comparisons of 317 known human drug targets revealed surprising variation such as species-specific positive selection, duplication and higher occurrences of pseudogenized targets in beagle (41 genes) relative to minipig (19 genes). These data will facilitate the more effective use of animals in biomedical research.

Social contagion process in informal warning networks to understand evacuation timing behavior.

Individual evacuation decisions are often characterized by the influence of one's social network, referred to as informal warning network. In this article, a threshold model of social contagion, originally introduced in the network science literature, is proposed to characterize this social influence in the evacuation decision-making process, in particular the timing of evacuation decision. Simulation models are developed to investigate the effects of community mixing patterns and the strength of ties on timing of evacuation decision.

Prevalent polymorphisms in wild-type HIV-1 integrase are unlikely to engender drug resistance to dolutegravir (S/GSK1349572).

The majority of HIV-1 integrase amino acid sites are highly conserved, suggesting that most are necessary to carry out the critical structural and functional roles of integrase. We analyzed the 34 most variable sites in integrase (>10% variability) and showed that prevalent polymorphic amino acids at these positions did not affect susceptibility to the integrase inhibitor dolutegravir (S/GSK1349572), as demonstrated both in vitro (in site-directed mutagenesis studies) and in vivo (in a phase IIa study of dolutegravir monotherapy in HIV-infected individuals). Ongoing clinical trials will provide additional data on the virologic activity of dolutegravir across subject viruses with and without prevalent polymorphic substitutions.

Exploring the determinants of pedestrian-vehicle crash severity in New York City.

Pedestrian-vehicle crashes remain a major concern in New York City due to high percentage of fatalities. This study develops random parameter logit models for explaining pedestrian injury severity levels of New York City accounting for unobserved heterogeneity in the population and across the boroughs. A log-likelihood ratio test for joint model suitability suggests that separate models for each of the boroughs should be estimated. Among many variables, road characteristics (e.g., number of lanes, grade, light condition, road surface, etc.), traffic attributes (e.g., presence of signal control, type of vehicle, etc.), and land use (e.g., parking facilities, commercial and industrial land use, etc.) are found to be statistically significant in the estimated model. The study also suggests that the set of counter measures should be different for different boroughs in the New York City and the priority ranks of countermeasures should be different as well.

Network analysis has diverse roles in drug discovery.

Computational biologists use network analysis to uncover relationships between various data types of interest for drug discovery. For example, signalling and metabolic pathways are commonly used to understand disease states and drug mechanisms. However, several other flavours of network analysis techniques are also applicable in a drug discovery context. Recent advances include networks that encompass relationships between diseases, molecular mechanisms and gene targets. Even social networks that mirror interactions within the scientific community are helping to foster collaborations and novel research. We review how these different types of network analysis approaches facilitate drug discovery and their associated challenges.