 Thank you. I wanted to give you a little bit of a background about our project and see nexus North Carolina newborn exome sequencing for universal screening and then I'm going to turn it over to Dr. Ryan Paikwin from RTI International who were Research partners with us in this study So newborn screening you've already heard about a bit about it We think of traditional newborn screening as the test that's done Where they come in and prick the heel of a newborn and put several Spots of blood on a on a piece of paper that's sent to the newborn screening lab But there's also a newborn screening that's done in every infant born in the US To test their hearing before they're discharged from the hospital as well as most states are now screening for critical congenital heart disease by testing the Pulse oximeter or the amount of oxygen in a baby to pick up congenital heart defects the recommended uniform screening panel that's recommended Conditions that every state should include in their newborn screening program currently includes 35 core conditions So the criteria of for deciding what would be a Condition that should be screened for has been taken from criteria originally published by Wilson and Youngner in 1968 and it includes that there is a treatment available that early treatment before symptoms appear is better That the condition otherwise would not be identifiable in a newborn So a test is required and that you also need a rapid and inexpensive lab test That's highly sensitive no false negatives and reasonably specific few if any false positives So now that we understand the genetic etiology of many Mendelian conditions theoretically Barriers to screening for any disorder in a newborn may now be overcome if there is a known genetic cause for a condition but should we do this and So that was really one of the main areas of interest for our project The aims included to evaluate how next generation Sequencing newborn screening or what we call NGS NBS can extend the utility of current newborn screening and To devise and evaluate a clinically oriented framework for analyzing Information from next generation sequencing newborn screening and to develop best practices for potentially incorporating this into clinical care So we examined what information should be reported to parents do parents want this information How do parents decide if they want this information? Do they agree with each other or not if they're a couple and for our study we utilized cheek swabs or saliva samples from newborns instead of the dried blood spot and We looked at Mendelian conditions So conditions that are known to have a genetic etiology a single gene etiology and broke it down into basically four different quadrants based on the the age of an individual Whether it had onset in infancy or childhood or adolescence or not until adulthood and Also, whether or not we could treat the condition or could we screen for the condition potentially if you knew For example that that a person was at risk for a tumor. Let's say a cancer could there be a screening Option available so we broke that down into the what's called the action ability of a condition So in the upper left-hand corner is what we call our NGS NBS category That includes conditions many of which are currently on the recommended uniform screening panel With onset in childhood and medical action ability you can put a child on a special diet You can give them a medication Etc. And then adult onset medically actionable conditions such as conditions causing risk of breast and ovarian cancer or colon cancer and Then Conditions that would have onset in childhood but for which there's no treatment at least in the traditional sense childhood onset non medically actionable and Finally the fourth quadrant conditions with adult onset and non medical action ability for example early onset Alzheimer disease so we have 466 conditions that were in our NGS NBS category and these were analyzed and returned if there were any Pathogenic or likely pathogenic variants in any of these genes Returned to all families whose children were in the study and We base that Scoring system in order to determine which genes made it into that NGS NBS category by looking at the severity of the outcome the likelihood that there would be a severe outcome How effective was the intervention available? What's the acceptability of families to having This condition known about and the intervention Undertaken and then what's the knowledge base for conditions? There's many conditions there where there may be just one Publication so that there's a little evidence that really this gene is associated with the condition And then we had two different cohort groups. We had one group whose parents were Assertained and recruited during their pregnancy normal pregnancy and then we had another whose children were diagnosed through traditional newborn screening and had metabolic conditions or hearing loss all Families of children in the diagnosed cohort Received diagnostic results related to the underlying condition and then as I said everyone got back any findings in this NGS Category and then two-thirds of the families were randomized Into a group we call the decision group and they were able to receive additional information In other categories if they were interested And those would include childhood onset non medically actionable conditions adult onset medically actionable and then carrier status The category of adult onset non medically actionable conditions were not reported to any Participants that was not an option So now I'm going to turn it over to Ryan and