We present a new approach to search for a subsurface ocean within Ganymede through observations and modeling of the dynamics of its auroral ovals. The locations of the auroral ovals oscillate due to ...Jupiter's time‐varying magnetospheric field seen in the rest frame of Ganymede. If an electrically conductive ocean is present, the external time‐varying magnetic field is reduced due to induction within the ocean and the oscillation amplitude of the ovals decreases. Hubble Space Telescope (HST) observations show that the locations of the ovals oscillate on average by 2.0° ±1.3°. Our model calculations predict a significantly stronger oscillation by 5.8° ± 1.3° without ocean compared to 2.2°±1.3° if an ocean is present. Because the ocean and the no‐ocean hypotheses cannot be separated by simple visual inspection of individual HST images, we apply a statistical analysis including a Monte Carlo test to also address the uncertainty caused by the patchiness of observed emissions. The observations require a minimum electrical conductivity of 0.09 S/m for an ocean assumed to be located between 150 km and 250 km depth or alternatively a maximum depth of the top of the ocean at 330 km. Our analysis implies that Ganymede's dynamo possesses an outstandingly low quadrupole‐to‐dipole moment ratio. The new technique applied here is suited to probe the interior of other planetary bodies by monitoring their auroral response to time‐varying magnetic fields.
Key Points
New technique to search for a subsurface ocean in Ganymede with a telescope
Ocean affects auroral oscillation caused by time‐varying external magnetic field
HST observations reveal weak auroral oscillation and imply existence of ocean
The greatest opportunity for lifelong impact of genomic sequencing is during the newborn period. The "BabySeq Project" is a randomized trial that explores the medical, behavioral, and economic ...impacts of integrating genomic sequencing into the care of healthy and sick newborns.
Families of newborns are enrolled from Boston Children's Hospital and Brigham and Women's Hospital nurseries, and half are randomized to receive genomic sequencing and a report that includes monogenic disease variants, recessive carrier variants for childhood onset or actionable disorders, and pharmacogenomic variants. All families participate in a disclosure session, which includes the return of results for those in the sequencing arm. Outcomes are collected through review of medical records and surveys of parents and health care providers and include the rationale for choice of genes and variants to report; what genomic data adds to the medical management of sick and healthy babies; and the medical, behavioral, and economic impacts of integrating genomic sequencing into the care of healthy and sick newborns.
The BabySeq Project will provide empirical data about the risks, benefits and costs of newborn genomic sequencing and will inform policy decisions related to universal genomic screening of newborns.
The study is registered in ClinicalTrials.gov Identifier: NCT02422511 . Registration date: 10 April 2015.
Communicating genetic risk information in ways that maximize understanding and promote health is increasingly important given the rapidly expanding availability and capabilities of genomic ...technologies. A well-developed literature on risk communication in general provides guidance for best practices, including presentation of information in multiple formats, attention to framing effects, use of graphics, sensitivity to the way numbers are presented, parsimony of information, attentiveness to emotions, and interactivity as part of the communication process. Challenges to communicating genetic risk information include deciding how best to tailor it, streamlining the process, deciding what information to disclose, accepting that communications may have limited influence, and understanding the impact of context. Meeting these challenges has great potential for empowering individuals to adopt healthier lifestyles and improve public health, but will require multidisciplinary approaches and collaboration.
Despite dramatic drops in DNA sequencing costs, concerns are great that the integration of genomic sequencing into clinical settings will drastically increase health care expenditures. This ...commentary presents an overview of what is known about the costs and cost-effectiveness of genomic sequencing. We discuss the cost of germline genomic sequencing, addressing factors that have facilitated the decrease in sequencing costs to date and anticipating the factors that will drive sequencing costs in the future. We then address the cost-effectiveness of diagnostic and pharmacogenomic applications of genomic sequencing, with an emphasis on the implications for secondary findings disclosure and the integration of genomic sequencing into general patient care. Throughout, we ground the discussion by describing efforts in the MedSeq Project, an ongoing randomized controlled clinical trial, to understand the costs and cost-effectiveness of integrating whole genome sequencing into cardiology and primary care settings.
Whole-genome sequencing (WGS) in asymptomatic adults might prevent disease but increase health care use without clinical value.
To describe the effect on clinical care and outcomes of adding WGS to ...standardized family history assessment in primary care.
Pilot randomized trial. (ClinicalTrials.gov: NCT01736566).
Academic primary care practices.
9 primary care physicians (PCPs) and 100 generally healthy patients recruited at ages 40 to 65 years.
Patients were randomly assigned to receive a family history report alone (FH group) or in combination with an interpreted WGS report (FH + WGS group), which included monogenic disease risk (MDR) results (associated with Mendelian disorders), carrier variants, pharmacogenomic associations, and polygenic risk estimates for cardiometabolic traits. Each patient met with his or her PCP to discuss the report.
Clinical outcomes and health care use through 6 months were obtained from medical records and audio-recorded discussions between PCPs and patients. Patients' health behavior changes were surveyed 6 months after receiving results. A panel of clinician-geneticists rated the appropriateness of how PCPs managed MDR results.
Mean age was 55 years; 58% of patients were female. Eleven FH + WGS patients (22% 95% CI, 12% to 36%) had new MDR results. Only 2 (4% CI, 0.01% to 15%) had evidence of the phenotypes predicted by an MDR result (fundus albipunctatus due to RDH5 and variegate porphyria due to PPOX). Primary care physicians recommended new clinical actions for 16% (CI, 8% to 30%) of FH patients and 34% (CI, 22% to 49%) of FH + WGS patients. Thirty percent (CI, 17% to 45%) and 41% (CI, 27% to 56%) of FH and FH + WGS patients, respectively, reported making a health behavior change after 6 months. Geneticists rated PCP management of 8 MDR results (73% CI, 39% to 99%) as appropriate and 2 results (18% CI, 3% to 52%) as inappropriate.
Limited sample size and ancestral and socioeconomic diversity.
Adding WGS to primary care reveals new molecular findings of uncertain clinical utility. Nongeneticist providers may be able to manage WGS results appropriately, but WGS may prompt additional clinical actions of unclear value.
National Institutes of Health.
Clinical use of next-generation sequencing (NGS) tests has been increasing, but few studies have examined their economic value. Several studies have noted that there are methodological challenges to ...conducting economic evaluations of NGS tests.
Our objective was to examine key methodological challenges for conducting economic evaluations of NGS tests, prioritize these challenges for future research, and identify how studies have attempted solutions to address these challenges.
We identified challenges for economic evaluations of NGS tests using prior literature and expert judgment of the co-authors. We used a modified Delphi assessment to prioritize challenges, based on importance and probability of resolution. Using a structured literature review and article extraction we then assessed whether published economic evaluations had addressed these challenges.
We identified 11 challenges for conducting economic evaluations of NGS tests. The experts identified three challenges as the top priorities for future research: complex model structure, timeframe, and type of analysis and comparators used. Of the 15 published studies included in our literature review, four studies described specific solutions relevant to five of the 11 identified challenges.
Major methodological challenges to economic evaluations of NGS tests remain to be addressed. Our results can be used to guide future research and inform decision-makers on how to prioritize research on the economic assessment of NGS tests.
Over 100 million research participants around the world have had research array-based genotyping (GT) or genome sequencing (GS), but only a small fraction of these have been offered return of ...actionable genomic findings (gRoR). Between 2017 and 2021, we analyzed genomic results from 36,417 participants in the Mass General Brigham Biobank and offered to confirm and return pathogenic and likely pathogenic variants (PLPVs) in 59 genes. Variant verification prior to participant recontact revealed that GT falsely identified PLPVs in 44.9% of samples, and GT failed to identify 72.0% of PLPVs detected in a subset of samples that were also sequenced. GT and GS detected verified PLPVs in 1% and 2.5% of the cohort, respectively. Of 256 participants who were alerted that they carried actionable PLPVs, 37.5% actively or passively declined further disclosure. 76.3% of those carrying PLPVs were unaware that they were carrying the variant, and over half of those met published professional criteria for genetic testing but had never been tested. This gRoR protocol cost approximately $129,000 USD per year in laboratory testing and research staff support, representing $14 per participant whose DNA was analyzed or $3,224 per participant in whom a PLPV was confirmed and disclosed. These data provide logistical details around gRoR that could help other investigators planning to return genomic results.
Large-scale genetics education appropriate for general practice providers is a growing priority. We describe the content and impact of a mandatory system-wide program implemented at Sanford Health.
...The Imagenetics Initiative at Sanford Health developed a 2-year genetics education program with quarterly web-based modules that were mandatory for all physicians and advanced practice providers. Scores of 0 to 5 were calculated for each module on the basis of the number of objectives that the participants reported as fulfilled. In addition, the participants completed surveys before starting and after finishing the education program, which included a 7-item measure scored 7 to 28 on the perceived preparedness to practice genetics.
Between 2252 and 2822 Sanford Health employees completed each of the 8 quarterly education modules. The ratings were highest for the module about using genomics to improve patient management (mean score = 4.3) and lowest for the module about different types of genetic tests and specialists. The mean perceived preparedness scores increased from 15.7 at pre-education to 19.1 at post-education (P < .001).
Web-based genetics education was highly effective in increasing health care providers’ confidence about using genetics. Both comfort with personal knowledge and confidence regarding access to the system’s genomic medicine experts increased significantly. The results demonstrate how scalable approaches can improve provider preparedness.
Display omitted
To examine patients' experiences with clinical use of whole-genome sequencing (WGS).
A randomized trial compared primary care and cardiology patients receiving WGS and family health history (FH) ...information or FH information alone. 202 patients were surveyed before (BL) and up to 6 months after disclosure of results (6M).
Patients (mean age = 55 years; 50% female; 81% college graduates) reported low levels of decisional regret (mean: 7.1/100) and high satisfaction with physicians' disclosure of results (median: 29/30). Compared with the FH-only arm, patients receiving WGS results were more likely to report learning accurate disease risk information (odds ratio = 7.45) and findings influential for medical treatment (odds ratio = 2.39). Sessions where WGS results were disclosed took longer (30 vs. 15 minutes), particularly for primary care patients. Patients' expected utility of sequencing at BL was higher than perceived utility at 6M in several domains, including impacting medical decision making (87% vs. 54%) and influencing medication choice (73% vs. 32%).
Patients were satisfied with their physicians' communication of WGS results and perceived them as medically useful. Discrepancies in expected versus perceived utility of WGS results suggest a need to temper patients' expectations about its potential benefits.
With increasing utility and decreasing cost of genomic sequencing, augmentation of standard newborn screening (NBS) programs with newborn genomic sequencing (nGS) has been proposed. Before nGS can be ...integrated into newborn screening, parents' perspectives must be better understood.
Using data from surveys administered to parents of healthy newborns who were enrolled in the BabySeq Project, a randomized clinical trial of nGS alongside NBS, this paper reports parents' attitudes regarding population-based NBS and nGS assessed 3 months after results disclosure.
Parental attitudes regarding whether all newborns should receive, and whether informed consent should be required for, NBS and nGS, as well as whether nGS should be mandated were assessed using 5-point scales from strongly disagree (=1) to strongly agree (=5). Parents' interest in receiving types of results from nGS was assessed on a 5-point scale from not at all interested (=1) to very interested (=5). Survey responses were analyzed using Fisher's exact tests, paired t-tests, and repeated measures ANOVA.
At 3 months post-disclosure, 248 parents of 174 healthy newborns submitted a survey. Support for every newborn receiving standard NBS (mean 4.67) was higher than that for every newborn receiving nGS (mean 3.60;
< 0.001). Support for required informed consent for NBS (mean 3.44) was lower than that for nGS (mean 4.27,
< 0.001). Parents' attitudes toward NBS and nGS were not significantly associated with self-reported political orientation. If hypothetically receiving nGS outside of the BabySeq Project, most parents reported being very interested in receiving information on their baby's risk of developing a disease in childhood that can be prevented, treated, or cured (86.8%) and their risk of developing a disease during adulthood that can be prevented, treated, or cured (84.6%).
Parents' opinions are crucial to inform design and delivery of public health programs, as the success of the program hinges on parents' trust and participation. To accommodate parents' preferences without affecting the current high participation rates in NBS, an optional add-on consent to nGS in addition to NBS may be a feasible approach. Trial Registration ClinicalTrials.gov Identifier: NCT02422511.
PDF
