Consensus Panel for Assessing Usability and Acceptability of Mobile Health Autism Screeners

Abstract: Background: Parents go online to assess whether their child has symptoms of autism. Though early autism identification is important, language, cultural, and technological barriers may impede equitable access to online autism screening tools. Objective: To create consensus recommendations for equitable design of autism screening apps and websites using an online panel of parents, autistic self-advocates, health and educational providers, autism researchers, and online screening tool developers. Methods: We invited 6 parents (4 of autistic and 2 of typically-developing children), 2 autistic adults, 3 early intervention providers, 3 pediatric primary care providers, and 3 autism online screening app/website developers to participate in a consensus panel, using a Modified Delphi design. The panel includes 3 asynchronous rounds of online discussion and voting and one live online videoconference. Participants initially received a multimedia summary (written summaries, videos, interactive polls) of prior research on screening tool usability/accessibility, and a list of preliminary design recommendations. In each round, participants discuss recommendations, make suggestions for alternative or additional recommendations, and vote for most important recommendations. The list of recommendations is iteratively revised and reduced after each round. In the final videoconference discussion, a consensus guideline will be created based on the recommendations vetted by panel participants. Anticipated results: The consensus panel is currently in process. Some example recommendations include: Screener should be accessible on multiple platforms (e.g., iOS, Android) parents should be able to complete screener inminutes Conclusion: A multidisciplinary panel can help translate research findings to actionable recommendations for equitable autism screening

Use of the i2b2 research query tool to conduct a matched case–control clinical research study: advantages, disadvantages and methodological considerations

Background: A major aim of the i2b2 (informatics for integrating biology and the bedside) clinical data informatics framework aims to create an efficient structure within which patients can be identified for clinical and translational research projects. Our objective was to describe the respective roles of the i2b2 research query tool and the electronic medical record (EMR) in conducting a case-controlled clinical study at our institution. Methods: We analyzed the process of using i2b2 and the EMR together to generate a complete research database for a case–control study that sought to examine risk factors for kidney stones among gastrostomy tube (G-tube) fed children. Results: Our final case cohort consisted of 41/177 (23%) of potential cases initially identified by i2b2, who were matched with 80/486 (17%) of potential controls. Cases were 10 times more likely to be excluded for inaccurate coding regarding stones vs. inaccurate coding regarding G-tubes. A majority (67%) of cases were excluded due to not meeting clinical inclusion criteria, whereas a majority of control exclusions (72%) occurred due to inadequate clinical data necessary for study completion. Full dataset assembly required complementary information from i2b2 and the EMR. Conclusions: i2b2 was critical as a query analysis tool for patient identification in our case–control study. Patient identification via procedural coding appeared more accurate compared with diagnosis coding. Completion of our investigation required iterative interplay of i2b2 and the EMR to assemble the study cohort

Climate change impacts on streamflow, sediment load and carbon fluxes in the Lena River delta

Water and sediment supply are essential to the health of deltaic ecosystems. Diverse datasets were integrated to better understand how climate change is shifting the supply of water and sediment to the largest polar distributary channel pattern – the Lena River Delta. Here the increase in warming rate from an average air temperature is from 4.1 °C for the period 1950–99 to 6.1 °C during 2000–21, which is higher than in the adjacent polar regions. Streamflow and sediment yield entering the Lena Delta have increased since 1988 by 56.3 km3 and 6.1×106 t, respectively; meanwhile, the Lena River’s increases in water temperature in June, July–August and September were found to be as much as 1.1, 0.6 and 0.05 °C. These changes have a pronounced effect on sediment regimes in particular parts of the delta. Based on analyses of correlations between various hydroclimatic drivers and sediment concentration changes across particular distributaries of the Lena Delta extracted from Landsat datasets, bank degradation driven by thermal erosional processes (which are in turn related to air and soil temperature increases) is proved to be the primary factor of the sediment regime in the delta. The study also highlights that sediment load changes are sensitive to wind speed due to remobilization of bottom sediment. Sums of daily air temperature and wind speed over 3 days are correlated with sediment concentration changes in the delta. The results also indicate that carbon transport across the delta (both POC and DOC) depends on sediment transport conditions and water discharge and might increase by up to 10 %. We conclude that the Lena Delta can be recognized as the global hot spot in terms of the hydrological consequences of climate change, which is altering sediment regimes, stream hydromorphology and carbon transport

Machine learning-derived baseline visual field patterns predict future glaucoma onset in the Ocular Hypertension Treatment Study

PURPOSE: The Ocular Hypertension Treatment Study (OHTS) identified risk factors for primary open-angle glaucoma (POAG) in patients with ocular hypertension, including pattern standard deviation (PSD). Archetypal analysis, an unsupervised machine learning method, may offer a more interpretable approach to risk stratification by identifying patterns in baseline visual fields (VFs). METHODS: There were 3272 eyes available in the OHTS. Archetypal analysis was applied using 24-2 baseline VFs, and model selection was performed with cross-validation. Decomposition coefficients for archetypes (ATs) were calculated. A penalized Cox proportional hazards model was implemented to select discriminative ATs. The AT model was compared to the OHTS model. Associations were identified between ATs with both POAG onset and VF progression, defined by mean deviation change per year. RESULTS: We selected 8494 baseline VFs. Optimal AT count was 19. The highest prevalence ATs were AT9, AT11, and AT7. The AT-based prediction model had a C-index of 0.75 for POAG onset. Multivariable models demonstrated that a one-interquartile range increase in the AT5 (hazard ratio [HR] = 1.14; 95% confidence interval [CI], 1.04-1.25), AT8 (HR = 1.22; 95% CI, 1.09-1.37), AT15 (HR = 1.26; 95% CI, 1.12-1.41), and AT17 (HR = 1.17; 95% CI, 1.03-1.31) coefficients conferred increased risk of POAG onset. AT5, AT10, and AT14 were significantly associated with rapid VF progression. In a subgroup analysis by high-risk ATs (\u3e95th percentile or \u3c75th percentile coefficients), PSD lost significance as a predictor of POAG in the low-risk group. CONCLUSIONS: Baseline VFs, prior to detectable glaucomatous damage, contain occult patterns representing early changes that may increase the risk of POAG onset and VF progression in patients with ocular hypertension. The relationship between PSD and POAG is modified by the presence of high-risk patterns at baseline. An AT-based prediction model for POAG may provide more interpretable glaucoma-specific information in a clinical setting

CRISPR-Cas9–based treatment of myocilin-associated glaucoma

Primary open-angle glaucoma (POAG) is a leading cause of irreversible vision loss worldwide, with elevated intraocular pressure (IOP) a major risk factor. Myocilin (MYOC) dominant gain-of-function mutations have been reported in ∼4% of POAG cases. MYOC mutations result in protein misfolding, leading to endoplasmic reticulum (ER) stress in the trabecular meshwork (TM), the tissue that regulates IOP. We use CRISPR-Cas9–med iated genome editing in cultured human TM cells and in a MYOC mouse model of POAG to knock down expression of mutant MYOC, resulting in relief of ER stress. In vivo genome editing results in lower IOP and prevents further glaucomatous damage. Importantly, using an ex vivo human organ culture system, we demonstrate the feasibility of human genome editing in the eye for this important disease. Keywords: myocilin; CRISPR; glaucoma; trabecular meshwork; genome editingNational Institutes of Health (U.S.) (Grant R01 EY024259)National Institutes of Health (U.S.) (Grant R01 EY026177)National Institutes of Health (U.S.) (Grant R00 EY022077

Exfoliation syndrome: assembling the puzzle pieces

PURPOSE: To summarize various topics and the cutting edge approaches to refine XFS pathogenesis that were discussed at the 21st annual Glaucoma Foundation Think Tank meeting in New York City, Sept. 19-20, 2014. METHODS: The highlights of three categories of talks on cutting edge research in the field were summarized. RESULTS: Exfoliation syndrome (XFS) is a systemic disorder with a substantial ocular burden, including high rates of cataract, cataract surgery complications, glaucoma and retinal vein occlusion. New information about XFS is akin to puzzle pieces that do not quite join together to reveal a clear picture regarding how exfoliation material (XFM) forms. CONCLUSION: Meeting participants concluded that it is unclear how the mild homocysteinemia seen in XFS might contribute to the disarrayed extracellular aggregates characteristic of this syndrome. Lysyl oxidase-like 1 (LOXL1) variants are unequivocally genetic risk factors for XFS but exactly how these variants contribute to the assembly of exfoliation material (XFM) remains unclear. Variants in a new genomic region, CACNA1A associated with XFS, may alter calcium concentrations at the cell surface and facilitate XFM formation but much more work is needed before we can place this new finding in proper context. It is hoped that various animal model and ex vivo systems will emerge that will allow for proper assembly of the puzzle pieces into a coherent picture of XFS pathogenesis. A clear understanding of XFS pathogenesis may lead to 'upstream solutions' to reduce the ocular morbidity produced by XFS