UV stalled replication forks restart by re-priming in human fibroblasts

Restarting stalled replication forks is vital to avoid fatal replication errors. Previously, it was demonstrated that hydroxyurea-stalled replication forks rescue replication either by an active restart mechanism or by new origin firing. To our surprise, using the DNA fibre assay, we only detect a slightly reduced fork speed on a UV-damaged template during the first hour after UV exposure, and no evidence for persistent replication fork arrest. Interestingly, no evidence for persistent UV-induced fork stalling was observed even in translesion synthesis defective, Polηmut cells. In contrast, using an assay to measure DNA molecule elongation at the fork, we observe that continuous DNA elongation is severely blocked by UV irradiation, particularly in UV-damaged Polηmut cells. In conclusion, our data suggest that UV-blocked replication forks restart effectively through re-priming past the lesion, leaving only a small gap opposite the lesion. This allows continuation of replication on damaged DNA. If left unfilled, the gaps may collapse into DNA double-strand breaks that are repaired by a recombination pathway, similar to the fate of replication forks collapsed after hydroxyurea treatment

BioSense 2.0 Governance: Surveying Users and Stakeholders for Continued Development

To set appropriate priorities in the development of BioSense 2.0, its governance body understand the needs and requests of users and stakeholders. The Governance Group has surveyed this community several times, refining its methods along they way. There is now a clearer understanding of the appropriate priorities for developing BioSense 2.0

BioSense 2.0 Governance: Surveying Users and Stakeholders for Continued Development

To set appropriate priorities in the development of BioSense 2.0, its governance body understand the needs and requests of users and stakeholders. The Governance Group has surveyed this community several times, refining its methods along they way. There is now a clearer understanding of the appropriate priorities for developing BioSense 2.0

Washington’s Methods for Analytics Interoperability and Metrics (AIM), Approaches to Data Integration and Dissemination in Population Health

Healthier Washington's Innovation Plan leverages "big data" analytics to combine different data sources providing a local picture of health including geo-mapping at census tract level and hot-spotting disease burden estimates. These approaches ensure robust availability of information that enables communities to address health inequities through targeted initiatives to improve the health of those most in need, and effectively measure progress over time. Washington's State Medicaid program, Department of Health, and Public Health Seattle & King County are working with the University of Washington to inform best practices in application of these methodologies. This panel will review some approaches under consideratio

Using Health Information Exchange to Improve Use of Prescription Monitoring Data

ObjectiveDemonstrate that use of the Washington State health informationexchange (HIE) to facilitate access to prescription monitoringprogram (PMP) data enhances the effectiveness of a PMP. Theincreased accessibility will lead to improved patient care by givingproviders more complete and recent data on patients’ controlledsubstance prescriptions.IntroductionWashington State experienced a five-fold increase in deaths fromunintentional drug overdoses between 1998 and 2014. The PMPcollects data on controlled substances prescribed to patients andmakes the data available to healthcare providers, giving providersanother tool for patient care and safety. Optimal impact for theprogram depends on providers regularly accessing the information toreview patients’ dispensing history. We have found through providersurveys and work with stakeholders that the best way to increase useis to make data seamlessly accessible through electronic health recordsystems (EHRs). This approach does not require a separate login tothe PMP portal. This linkage works through the Health InformationExchange (HIE) to make PMP data available to providers via EHRs.The HIE facilitates electronic communication of patient informationamong organizations including hospitals and providers. In additionto the PMP, another resource to address the prescription drug abuseproblem is the Emergency Department Information Exchange(EDIE), a web-based technology that specifically connects emergencydepartments statewide to track patients who visit multiple EDs.We also developed a connection between EDIE and PMP datathrough the HIE.MethodsIncreased provider utilization of the PMP will be achieved byusing the HIE to create more seamless access to PMP data throughproviders’ EHRs and through the EDIE system. This will be done bycompleting the build out of a transaction using NCPCP 10.6, pilotingthe connection with healthcare systems and EHR vendors, and bycontinuing to promote and encourage the PMP to remain an MUoption through recent rule changes being proposed by CMS/ONC.The pilot with Epic was conducted in 2015 from April to October.Epic has released an update, available to Washington customers, thatincludes the connection between EHR and PMP. PMP data is alsoconnected to EDIE. That connection is now live in 80 of 93 acute carehospital emergency departments.ResultsTo date the transaction is in production with 80 emergencydepartments and achieving positive results. In 2015 the PMP receivedmore than 2 million queries from the EDIE system via the HIE,compared to 900,000 queries via the online PMP portal in the yearbefore the link through the HIE was available. We have also finisheda pilot with a major EHR vendor and are working to on-board theircustomers. We are also working directly with healthcare systems, andas of September 2016 there are 3 healthcare facilities in testing thatare expected to go live by the end of the year. Over 90 registrationsfor meaningful use of the PMP have been received, representing morethan 1000 clinics. Improved access to PMP data benefits providers byallowing them to check the history of transactions linked to their DEAnumbers, which can alert them to fraudulent prescriptions.ConclusionsIntegration of PMP data with other information systems will greatlyenhance the accessibility and impact of the data. Making a connectionto EDIE alone more than doubled the number of queries we receivedfrom providers in 2015. We anticipate even more inquiries onceadditional care settings are connected. We hope from this to see acontinued decline in unintentional poisonings due to prescriptiondrugs

Using Health Information Exchange to Improve Use of Prescription Monitoring Data

ObjectiveDemonstrate that use of the Washington State health informationexchange (HIE) to facilitate access to prescription monitoringprogram (PMP) data enhances the effectiveness of a PMP. Theincreased accessibility will lead to improved patient care by givingproviders more complete and recent data on patients’ controlledsubstance prescriptions.IntroductionWashington State experienced a five-fold increase in deaths fromunintentional drug overdoses between 1998 and 2014. The PMPcollects data on controlled substances prescribed to patients andmakes the data available to healthcare providers, giving providersanother tool for patient care and safety. Optimal impact for theprogram depends on providers regularly accessing the information toreview patients’ dispensing history. We have found through providersurveys and work with stakeholders that the best way to increase useis to make data seamlessly accessible through electronic health recordsystems (EHRs). This approach does not require a separate login tothe PMP portal. This linkage works through the Health InformationExchange (HIE) to make PMP data available to providers via EHRs.The HIE facilitates electronic communication of patient informationamong organizations including hospitals and providers. In additionto the PMP, another resource to address the prescription drug abuseproblem is the Emergency Department Information Exchange(EDIE), a web-based technology that specifically connects emergencydepartments statewide to track patients who visit multiple EDs.We also developed a connection between EDIE and PMP datathrough the HIE.MethodsIncreased provider utilization of the PMP will be achieved byusing the HIE to create more seamless access to PMP data throughproviders’ EHRs and through the EDIE system. This will be done bycompleting the build out of a transaction using NCPCP 10.6, pilotingthe connection with healthcare systems and EHR vendors, and bycontinuing to promote and encourage the PMP to remain an MUoption through recent rule changes being proposed by CMS/ONC.The pilot with Epic was conducted in 2015 from April to October.Epic has released an update, available to Washington customers, thatincludes the connection between EHR and PMP. PMP data is alsoconnected to EDIE. That connection is now live in 80 of 93 acute carehospital emergency departments.ResultsTo date the transaction is in production with 80 emergencydepartments and achieving positive results. In 2015 the PMP receivedmore than 2 million queries from the EDIE system via the HIE,compared to 900,000 queries via the online PMP portal in the yearbefore the link through the HIE was available. We have also finisheda pilot with a major EHR vendor and are working to on-board theircustomers. We are also working directly with healthcare systems, andas of September 2016 there are 3 healthcare facilities in testing thatare expected to go live by the end of the year. Over 90 registrationsfor meaningful use of the PMP have been received, representing morethan 1000 clinics. Improved access to PMP data benefits providers byallowing them to check the history of transactions linked to their DEAnumbers, which can alert them to fraudulent prescriptions.ConclusionsIntegration of PMP data with other information systems will greatlyenhance the accessibility and impact of the data. Making a connectionto EDIE alone more than doubled the number of queries we receivedfrom providers in 2015. We anticipate even more inquiries onceadditional care settings are connected. We hope from this to see acontinued decline in unintentional poisonings due to prescriptiondrugs

Roundtable on Bioterrorism Detection: Information System–based Surveillance

During the 2001 AMIA Annual Symposium, the Anesthesia, Critical Care, and Emergency Medicine Working Group hosted the Roundtable on Bioterrorism Detection. Sixty-four people attended the roundtable discussion, during which several researchers discussed public health surveillance systems designed to enhance early detection of bioterrorism events. These systems make secondary use of existing clinical, laboratory, paramedical, and pharmacy data or facilitate electronic case reporting by clinicians. This paper combines case reports of six existing systems with discussion of some common techniques and approaches. The purpose of the roundtable discussion was to foster communication among researchers and promote progress by 1) sharing information about systems, including origins, current capabilities, stages of deployment, and architectures; 2) sharing lessons learned during the development and implementation of systems; and 3) exploring cooperation projects, including the sharing of software and data. A mailing list server for these ongoing efforts may be found at http://bt.cirg.washington.edu

Aquaporin water channels: New perspectives on the potential role in inflammation

Aquaporins (AQPs) are a family of membrane water channel proteins that osmotically modulate water fluid homeostasis in several tissues; some of them also transport small solutes such as glycerol. At the cellular level, the AQPs regulate not only cell migration and transepithelial fluid transport across membranes, but also common events that are crucial for the inflammatory response. Emerging data reveal a new function of AQPs in the inflammatory process, as demonstrated by their dysregulation in a wide range of inflammatory diseases including edematous states, cancer, obesity, wound healing and several autoimmune diseases. This chapter summarizes the discoveries made so far about the structure and functions of the AQPs and provides updated information on the underlying mechanisms of AQPs in several human inflammatory diseases. The discovery of new functions for AQPs opens new vistas offering promise for the discovery of mechanisms and therapeutic opportunities in inflammatory disorders