Children who receive cochlear implants develop spoken language on a protracted timescale. The home environment facilitates speech-language development, yet it is relatively unknown how the environment differs between children with cochlear implants and typical hearing. We matched eighteen preschoolers with implants (31-65 months) to two groups of children with typical hearing: by chronological age and hearing age. Each child completed a long-form, naturalistic audio recording of their home environment (appx. 16 hours/child; >730 hours of observation) to measure adult speech input, child vocal productivity, and caregiver-child interaction. Results showed that children with cochlear implants and typical hearing were exposed to and engaged in similar amounts of spoken language with caregivers. However, the home environment did not reflect developmental stages as closely for children with implants, or predict their speech outcomes as strongly. Home-based speech-language interventions should focus on the unique input-outcome relationships for this group of children with hearing loss.

In 2016, the National Center for Advancing Translational Science launched the Trial Innovation Network (TIN) to address barriers to efficient and informative multicenter trials. The TIN provides a national platform, working in partnership with 60+ Clinical and Translational Science Award (CTSA) hubs across the country to support the design and conduct of successful multicenter trials. A dedicated Hub Liaison Team (HLT) was established within each CTSA to facilitate connection between the hubs and the newly launched Trial and Recruitment Innovation Centers. Each HLT serves as an expert intermediary, connecting CTSA Hub investigators with TIN support, and connecting TIN research teams with potential multicenter trial site investigators. The cross-consortium Liaison Team network was developed during the first TIN funding cycle, and it is now a mature national network at the cutting edge of team science in clinical and translational research. The CTSA-based HLT structures and the external network structure have been developed in collaborative and iterative ways, with methods for shared learning and continuous process improvement. In this paper, we review the structure, function, and development of the Liaison Team network, discuss lessons learned during the first TIN funding cycle, and outline a path toward further network maturity.

Improving the quality and conduct of multi-center clinical trials is essential to the generation of generalizable knowledge about the safety and efficacy of healthcare treatments. Despite significant effort and expense, many clinical trials are unsuccessful. The National Center for Advancing Translational Science launched the Trial Innovation Network to address critical roadblocks in multi-center trials by leveraging existing infrastructure and developing operational innovations. We provide an overview of the roadblocks that led to opportunities for operational innovation, our work to develop, define, and map innovations across the network, and how we implemented and disseminated mature innovations.

Many factors affect patient outcome after congenital heart surgery, including the complexity of the heart disease, pre-operative status, patient specific factors (prematurity, nutritional status and/or presence of comorbid conditions or genetic syndromes), and post-operative residual lesions. The Residual Lesion Score is a novel tool for assessing whether specific residual cardiac lesions after surgery have a measurable impact on outcome. The goal is to understand which residual lesions can be tolerated and which should be addressed prior to leaving the operating room. The Residual Lesion Score study is a large multicentre prospective study designed to evaluate the association of Residual Lesion Score to outcomes in infants undergoing surgery for CHD. This Pediatric Heart Network and National Heart, Lung, and Blood Institute-funded study prospectively enrolled 1,149 infants undergoing 5 different congenital cardiac surgical repairs at 17 surgical centres. Given the contribution of echocardiographic measurements in assigning the Residual Lesion Score, the Residual Lesion Score study made use of a centralised core lab in addition to site review of all data. The data collection plan was designed with the added goal of collecting image quality information in a way that would permit us to improve our understanding of the reproducibility, variability, and feasibility of the echocardiographic measurements being made. There were significant challenges along the way, including the coordination, de-identification, storage, and interpretation of very large quantities of imaging data. This necessitated the development of new infrastructure and technology, as well as use of novel statistical methods. The study was successfully completed, but the size and complexity of the population being studied and the data being extracted required more technologic and human resources than expected which impacted the length and cost of conducting the study. This paper outlines the process of designing and executing this complex protocol, some of the barriers to implementation and lessons to be considered in the design of future studies.

Paleoproterozoic massive Cu-Zn±Pb±Au±Ag sulphide deposits metamorphosed to the middle-upper amphibolite facies in central-south Colorado formed in a volcanic arc setting on the edge of the Yavapai crustal province. Previously published U-Pb ages on spatially related granitoids range from ∼1.9 to ∼1.1 Ga, while Pb isotope studies on galena from massive sulphides suggest mineralization formed at around 1.8–1.7 Ga. Some deposits in the Dawson-Green Mountain trend (DGMT) and the Gunnison belt are composed of Cu-Zn-Au-(Pb-Ag) mineralization that were overprinted by later Au-(Ag-Cu-Bi-Se-Te) mineralization. Sulphide mineralization is spatially related to amphibolite and bimodal, mafic-felsic volcanic rocks (gabbro, amphibolite, rhyolite and dacite) and granitoids, but it occurs mostly in biotite-garnet-quartz±sillimanite±cordierite schists and gneisses, spatially related to nodular sillimanite rocks, and in some locations, exhalative rocks (iron formations, gahnite-rich rocks and quartz-garnetite). The major metallic minerals of the massive sulphides include chalcopyrite, sphalerite, pyrite, pyrrhotite, and magnetite, with minor galena and gahnite. Altered rocks intimately associated with mineralization primarily consist of various amphiboles (gedrite, tremolite and hornblende), gahnite, biotite, garnet, cordierite, carbonate and rare högbomite. The Zn/Cd ratios of sphalerite (44 to 307) in deposits in the DGMT fall within the range of global volcanogenic massive sulphide (VMS) deposits but overlap with sphalerite from sedimentary exhalative (Sedex) deposits. Sulphur isotope values of sulphides (δ34S = −3.3 to +6.5) suggest sulphur was largely derived from magmatic sources, and that variations in isotopic values resulting from thermochemical sulphate reduction are due to small differences in physicochemical conditions. The preferred genetic model is for the deposits to be bimodal-mafic (Gunnison) to mafic-siliciclastic VMS deposits (Cotopaxi, Cinderella-Bon Ton, DGMT).

New technologies and disruptions related to Coronavirus disease-2019 have led to expansion of decentralized approaches to clinical trials. Remote tools and methods hold promise for increasing trial efficiency and reducing burdens and barriers by facilitating participation outside of traditional clinical settings and taking studies directly to participants. The Trial Innovation Network, established in 2016 by the National Center for Advancing Clinical and Translational Science to address critical roadblocks in clinical research and accelerate the translational research process, has consulted on over 400 research study proposals to date. Its recommendations for decentralized approaches have included eConsent, participant-informed study design, remote intervention, study task reminders, social media recruitment, and return of results for participants. Some clinical trial elements have worked well when decentralized, while others, including remote recruitment and patient monitoring, need further refinement and assessment to determine their value. Partially decentralized, or “hybrid” trials, offer a first step to optimizing remote methods. Decentralized processes demonstrate potential to improve urban-rural diversity, but their impact on inclusion of racially and ethnically marginalized populations requires further study. To optimize inclusive participation in decentralized clinical trials, efforts must be made to build trust among marginalized communities, and to ensure access to remote technology.

One challenge for multisite clinical trials is ensuring that the conditions of an informative trial are incorporated into all aspects of trial planning and execution. The multicenter model can provide the potential for a more informative environment, but it can also place a trial at risk of becoming uninformative due to lack of rigor, quality control, or effective recruitment, resulting in premature discontinuation and/or non-publication. Key factors that support informativeness are having the right team and resources during study planning and implementation and adequate funding to support performance activities. This communication draws on the experience of the National Center for Advancing Translational Science (NCATS) Trial Innovation Network (TIN) to develop approaches for enhancing the informativeness of clinical trials. We distilled this information into three principles: (1) assemble a diverse team, (2) leverage existing processes and systems, and (3) carefully consider budgets and contracts. The TIN, comprised of NCATS, three Trial Innovation Centers, a Recruitment Innovation Center, and 60+ CTSA Program hubs, provides resources to investigators who are proposing multicenter collaborations. In addition to sharing principles that support the informativeness of clinical trials, we highlight TIN-developed resources relevant for multicenter trial initiation and conduct.

Scanning transmission electron microscopy (STEM) allows for imaging, diffraction, and spectroscopy of materials on length scales ranging from microns to atoms. By using a high-speed, direct electron detector, it is now possible to record a full two-dimensional (2D) image of the diffracted electron beam at each probe position, typically a 2D grid of probe positions. These 4D-STEM datasets are rich in information, including signatures of the local structure, orientation, deformation, electromagnetic fields, and other sample-dependent properties. However, extracting this information requires complex analysis pipelines that include data wrangling, calibration, analysis, and visualization, all while maintaining robustness against imaging distortions and artifacts. In this paper, we present py4DSTEM, an analysis toolkit for measuring material properties from 4D-STEM datasets, written in the Python language and released with an open-source license. We describe the algorithmic steps for dataset calibration and various 4D-STEM property measurements in detail and present results from several experimental datasets. We also implement a simple and universal file format appropriate for electron microscopy data in py4DSTEM, which uses the open-source HDF5 standard. We hope this tool will benefit the research community and help improve the standards for data and computational methods in electron microscopy, and we invite the community to contribute to this ongoing project.

In this study, we use aerial photographs, satellite imagery and field observations to quantify changes in the area, terminus length, snowline elevation and surface elevation of eight glaciers in the Alexandra Fiord region, eastern Ellesmere Island, between 1959 and 2019. Comparisons to written and pictorial descriptions from the British Arctic Expedition extend the record of change in terminus position and surface elevation to 1875 for Twin Glacier. Glacier area at Alexandra Fiord decreased by a total of 15.77 ± 0.65 km2 (11.77 ± 0.49%) between 1959 and 2019, the mean end of summer snowline increased in elevation by 360 ± 84 m (8 ± 2 m a−1) between 1974 and 2019, and the glaciers thinned at an average rate of 0.60 ± 0.06 m a−1 between 2001 and 2018. Annual rates of terminus retreat were ~3–5 times higher over the period 1974–2019 compared to 1875–1974, and rates of thinning were ~2–3 times higher over 2001–18 compared to 1875–2001. Our results are consistent with rates of change determined for other glaciers of similar size on Ellesmere Island, and with accelerated rates of ice loss coincident with regional increases in air temperature of ~1.5°C since the early 1980s.

This study examined a potential lexicality advantage in young children's early speech production: do children produce sound sequences less accurately in nonwords than real words? Children aged 3;3-4;4 completed two tasks: a real word repetition task and a corresponding nonword repetition task. Each of the 23 real words had a paired consonant-vowel sequence in the nonword in word-initial position (e.g., ‘su’ in [ˈsutkes] ‘suitcase’ and [ˈsudrɑs]). The word-initial consonant-vowel sequences were kept constant between the paired words. Previous work on this topic compared different sequences of paired sounds, making it hard to determine if those results were due to a lexical or phonetic effect. Our results show that children reliably produced consonant-vowel sequences in real words more accurately than nonwords. The effect was most pronounced in children with smaller receptive vocabularies. Together, these results reinforce theories arguing for interactions between vocabulary size and phonology in language development.

Surgical site infections (SSIs) are among the most common healthcare-associated infections in low- and middle-income countries. To encourage establishment of actionable and standardized SSI surveillance in these countries, we propose simplified surveillance case definitions. Here, we use NHSN reports to explore concordance of these simplified definitions to NHSN as ‘reference standard.’

This study investigated whether individual differences in receptive vocabulary, speech perception and production, and nonword repetition at age 2 years, 4 months to 3 years, 4 months predicted phonological awareness 2 years later. One hundred twenty-one children were tested twice. During the first testing period (Time 1), children’s receptive vocabulary, speech perception and production, and nonword repetition were measured. Nonword repetition accuracy in the present study was distinct from other widely used measures of nonword repetition in that it focused on narrow transcription of diphone sequences in each nonword that differed systematically in phonotactic probability. At the second testing period (Time 2), children’s phonological awareness was measured. The best predictors of phonological awareness were a measure of speech production and a measure of phonological processing derived from performance on the nonword repetition task. The results of this study suggest that nonword repetition accuracy provides an implicit measure of phonological skills that are indicative of later phonological awareness at an age when children are too young to perform explicit phonological awareness tasks reliably.