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.

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.

Gatherings where people are eating and drinking can increase the risk of getting and spreading SARS-CoV-2 among people who are not fully vaccinated; prevention strategies like wearing masks and physical distancing continue to be important for some groups. We conducted an online survey to characterise fall/winter 2020–2021 holiday gatherings, decisions to attend and prevention strategies employed during and before gatherings. We determined associations between practicing prevention strategies, demographics and COVID-19 experience. Among 502 respondents, one-third attended in person holiday gatherings; 73% wore masks and 84% practiced physical distancing, but less did so always (29% and 23%, respectively). Younger adults were 44% more likely to attend gatherings than adults ≥35 years. Younger adults (adjusted prevalence ratio (aPR) 1.53, 95% CI 1.19–1.97), persons who did not experience COVID-19 themselves or have relatives/close friends experience severe COVID-19 (aPR 1.56, 95% CI 1.18–2.07), and non-Hispanic White persons (aPR 1.57, 95% CI 1.13–2.18) were more likely to not always wear masks in public during the 2 weeks before gatherings. Public health messaging emphasizing consistent application of COVID-19 prevention strategies is important to slow the spread of COVID-19.

Clinical trials continue to face significant challenges in participant recruitment and retention. The Recruitment Innovation Center (RIC), part of the Trial Innovation Network (TIN), has been funded by the National Center for Advancing Translational Sciences of the National Institutes of Health to develop innovative strategies and technologies to enhance participant engagement in all stages of multicenter clinical trials. In collaboration with investigator teams and liaisons at Clinical and Translational Science Award institutions, the RIC is charged with the mission to design, field-test, and refine novel resources in the context of individual clinical trials. These innovations are disseminated via newsletters, publications, a virtual toolbox on the TIN website, and RIC-hosted collaboration webinars. The RIC has designed, implemented, and promised customized recruitment support for 173 studies across many diverse disease areas. This support has incorporated site feasibility assessments, community input sessions, recruitment materials recommendations, social media campaigns, and an array of study-specific suggestions. The RIC’s goal is to evaluate the efficacy of these resources and provide access to all investigating teams, so that more trials can be completed on time, within budget, with diverse participation, and with enough accrual to power statistical analyses and make substantive contributions to the advancement of healthcare.

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 recent years, a variety of efforts have been made in political science to enable, encourage, or require scholars to be more open and explicit about the bases of their empirical claims and, in turn, make those claims more readily evaluable by others. While qualitative scholars have long taken an interest in making their research open, reflexive, and systematic, the recent push for overarching transparency norms and requirements has provoked serious concern within qualitative research communities and raised fundamental questions about the meaning, value, costs, and intellectual relevance of transparency for qualitative inquiry. In this Perspectives Reflection, we crystallize the central findings of a three-year deliberative process—the Qualitative Transparency Deliberations (QTD)—involving hundreds of political scientists in a broad discussion of these issues. Following an overview of the process and the key insights that emerged, we present summaries of the QTD Working Groups’ final reports. Drawing on a series of public, online conversations that unfolded at www.qualtd.net, the reports unpack transparency’s promise, practicalities, risks, and limitations in relation to different qualitative methodologies, forms of evidence, and research contexts. Taken as a whole, these reports—the full versions of which can be found in the Supplementary Materials—offer practical guidance to scholars designing and implementing qualitative research, and to editors, reviewers, and funders seeking to develop criteria of evaluation that are appropriate—as understood by relevant research communities—to the forms of inquiry being assessed. We dedicate this Reflection to the memory of our coauthor and QTD working group leader Kendra Koivu.1

In the two decades or so since ancient sedimentary DNA (sedaDNA) took its place as a new Quaternary paleo-proxy, there have been large advances in the scope of its applications and its reliability. The two main approaches, metabarcoding and shotgun sequencing, have contributed exciting insights into areas such as floristic diversity change, plant-herbivore interactions, extinction, conservation baselines and impacts of invasive species. Early doubts as to its potential to contribute novel information have been dispelled; more is now understood about the passage of sedaDNA from the original organism to a component of soil or sediment and about the range of uncertainties that must be addressed in the interpretation of data. With its move into the mainstream, it is now time to develop effective data archives for sedaDNA, refine our understanding of central issues such as taphonomy, and further expand the potential for describing, both qualitatively and quantitatively, the history of past ecosystems.

One major challenge in the study of late-Quaternary extinctions (LQEs) is providing better estimates of past megafauna abundance. To show how megaherbivore population size varied before and after the last extinctions in interior Alaska, we use both a database of radiocarbon-dated bone remains (spanning 25–0 ka) and spores of the obligate dung fungus, Sporormiella, recovered from radiocarbon-dated lake-sediment cores (spanning 17–0 ka). Bone fossils show that the last stage of LQEs in the region occurred at about 13 ka ago, but the number of megaherbivore bones remains high into the Holocene. Sporormiella abundance also remains high into the Holocene and does not decrease with major vegetation changes recorded by arboreal pollen percentages. At two sites, the interpretation of Sporormiella was enhanced by additional dung fungal spore types (e.g., Sordaria). In contrast to many sites where the last stage of LQEs is marked by a sharp decline in Sporormiella abundance, in interior Alaska our results indicate the continuance of megaherbivore abundance, albeit with a major taxonomic turnover (including Mammuthus and Equus extinction) from predominantly grazing to browsing dietary guilds. This new and robust evidence implies that regional LQEs were not systematically associated with crashes of overall megaherbivore abundance.

The nature of air-snow exchange processes depends upon both the physical characteristics of the snow and forcing from the atmosphere. An understanding of snow-air transport processes and models of these processes are important for interpreting ice cores and for predicting remotely sensed snow-surface characteristics. Accurate modeling requires knowledge of the physical characteristics of the snow and firn. In this paper, measurements of snow and firn permeability from the surface down to 12 m depth at Siple Dome, Antarctica, are presented. The permeability varies greatly as a function of layer and depth, generally increasing to approximately 3 m, and generally decreasing below that. The maximum permeability,280 × 10–10 1 0 m2, occurs at approximately 3 m depth. The lowest permeability in the top 12 m of snow and firn, 10 × 10–10w m2, was measured in the surface wind pack/The measurements show that layering and microstructure have large effects on permeability A mathematical expression for the overall variation of permeability with depth is presented It is shown that snow density is a poor indicator of permeability Quantitative microscopy may be helpful in relating observed snow characteristics to permeability, and useful in modeling firnification and chemical-species transport.

Holocene tephrostratigraphy in Alaska provides independent chronology and stratigraphic correlation in a region where reworked old (Holocene) organic carbon can significantly distort radiocarbon chronologies. Here, we present new glass chemistry and chronology for Holocene tephras preserved in three Alaskan lakes: one in the eastern interior and two in the southern Brooks Range. Tephra beds in the eastern interior lake-sediment core are correlated with the White River Ash and the Hayes tephra set H (~4200–3700 cal yr BP), and an additional discrete tephra bed is likely from the Aleutian arc/Alaska Peninsula. Cryptotephras (nonvisible tephras) found in the Brooks Range include the informally named “Ruppert tephra” (~2700–2300 cal yr BP) and the Aniakchak caldera-forming event II (CFE II) tephra (~3600 cal yr BP). A third underlying Brooks Range cryptotephra is chemically indistinguishable from the Aniakchak CFE II tephra (4070–3760 cal yr BP) and is likely to be from an earlier eruption of the Aniakchak volcano.

A megaslump at Batagaika, in northern Yakutia, exposes a remarkable stratigraphic sequence of permafrost deposits ~50–80 m thick. To determine their potential for answering key questions about Quaternary environmental and climatic change in northeast Siberia, we carried out a reconnaissance study of their cryostratigraphy and paleoecology, supported by four rangefinder 14C ages. The sequence includes two ice complexes separated by a unit of fine sand containing narrow syngenetic ice wedges and multiple paleosols. Overall, the sequence developed as permafrost grew syngenetically through an eolian sand sheet aggrading on a hillslope. Wood remains occur in two forest beds, each associated with a reddened weathering horizon. The lower bed contains high amounts of Larix pollen (>20%), plus small amounts of Picea and Pinus pumila, and is attributed to interglacial conditions. Pollen from the overlying sequence is dominated by herbaceous taxa (~70%–80%) attributed to an open tundra landscape during interstadial climatic conditions. Of three hypothetical age schemes considered, we tentatively attribute much of the Batagaika sequence to Marine Oxygen Isotope Stage (MIS) 3. The upper and lower forest beds may represent a mid–MIS 3 optimum and MIS 5, respectively, although we cannot discount alternative attributions to MIS 5 and 7.

Five pollen diagrams reveal late Wisconsin and Holocene vegetation changes in the Walker Lake/Alatna Valley region of the central Brooks Range, approximately 100 km west of the area studied by D. A. Livingstone (1955, Ecology 36, 587–600). New insights into the vegetation history of this region are provided by calculations of pollen influx and by the use of linear discriminant analysis to separate Picea glauca and P. mariana pollen. Three major pollen zones are identified: (1) a basal herb zone, characterized by high percentages of Cyperaceae, Gramineae, Salix, and Artemisia, and low total pollen influx; (2) a shrub Betula zone with increased total pollen influx and very high percentages of Betula pollen, predominantly in the size range of B. nana and B. glandulosa; and (3) and Alnus zone dominated by Alnus pollen. Lakes currently within the boreal forest or near tree line show relatively high percentages of Picea pollen in the Alnus zone. Several striking vegetation changes occurred between ca. 10,000 and 7000 yr B.P. Between ca. 11,000 and 10,000 yr B.P., Populus balsamifera pollen percentages as great as 30% indicate that this species was present at low-elevation sites near Walker Lake. These populations declined abruptly ca. 10,000 yr ago and have never regained prominence. About 8500 yr B.P., Picea glauca pollen reached 10–15%, indicating the arrival of P. glauca in or near the study area. P. glauca populations evidently decreased ca. 8000 yr ago, when Picea pollen percentages and influx fell to low values. About 7000 yr B.P., Alnus pollen percentages and influx rose sharply as alder shrubs became established widely. Picea once more expanded ca. 5000 yr ago, but these populations were dominated by P. mariana rather than P. glauca, which increased slowly at this time and may still be advancing northward. Some vegetation changes have been remarkably synchronous over wide areas of interior Alaska, and probably reflect responses of in situ vegetation to environmental changes, but others may reflect the lagged responses of species migrating into new areas.

A 12-m sequence of lake sediment and peat in a 45-m high exposure on Birch Creek, northeast Alaska, contains pollen of Picea, Betula, Alnus and Populus, and wood of Picea and Populus. This sequence, which may represent 10,000 yr of more of accumulation, is beyond the limit of radiocarbon dating. It lies between two units of loess; the underlying loess lies above the Old Crow Tephra, recently dated at 149,000 ± 13,000 yr B.P. The lake sediments probably were deposited during the last interglaciation (isotope substage 5e) and subsequently buried by Wisconsinan loess. Analogs for the ancient lake may be deep, long-lived thaw lakes that are present in the modern landscape. When Birch Creek is correlated with other sites across nonglaciated Alaska and northwest Canada, there appears to be a common interglacial signal in sediments overlying the Old Crow Tephra.

Weed science has contributed much to agriculture, forestry and natural resource management during its history. However, if it is to remain relevant as a scientific discipline, it is long past time for weed scientists to move beyond a dominating focus on herbicide efficacy testing and address the basic science underlying complex issues in vegetation management at many levels of biological organization currently being solved by others, such as invasion ecologists and molecular biologists. Weed science must not be circumscribed by a narrowly-defined set of tools but rather be seen as an integrating discipline. As a means of assessing current and future research interests and funding trends among weed scientists, the Weed Science Society of America conducted an online survey of its members in summer of 2007. There were 304 respondents out of a membership of 1330 at the time of the survey, a response rate of 23%. The largest group of respondents (41%) reported working on research problems primarily focused on herbicide efficacy and maintenance, funded mainly by private industry sources. Another smaller group of respondents (22%) reported focusing on research topics with a complex systems focus (such as invasion biology, ecosystem restoration, ecological weed management, and the genetics, molecular biology, and physiology of weedy traits), funded primarily by public sources. Increased cooperation between these complementary groups of scientists will be an essential step in making weed science increasingly relevant to the complex vegetation management issues of the 21st century.

Burial Lake in northwest Alaska records changes in water level and regional vegetation since ∼ 39,000 cal yr BP based on terrestrial macrofossil AMS radiocarbon dates. A sedimentary unconformity is dated between 34,800 and 23,200 cal yr BP. During all or some of this period there was a hiatus in deposition indicating a major drop in lake level and deflation of lacustrine sediments. MIS 3 vegetation was herb-shrub tundra; more xeric graminoid-herb tundra developed after 23,200 cal yr BP. The tundra gradually became more mesic after 17,000 cal yr BP. Expansions of Salix then Betula, at 15,000 and 14,000 cal yr BP, respectively, are coincident with a major rise in lake level marked by increasing fine-grained sediment and higher organic matter content. Several sites in the region display disrupted sedimentation and probable hiatuses during the last glacial maximum (LGM); together regional data indicate an arid interval prior to and during the LGM and continued low moisture levels until ∼ 15,000 cal yr BP. AMS 14C dates from Burial Lake are approximately synchronous with AMS 14C dates reported for the Betula expansion at nearby sites and sites across northern Alaska, but 1000–2000 yr younger than bulk-sediment dates.

Paleoenvironmental conditions are reconstructed from soils buried under volcanic ash ca. 21,500 years ago on the Seward Peninsula. Soil development was minimal, reflecting the continuous regional deposition of loess, which originated from river floodplains and the exposed Chukchi shelf. Cryoturbated soil horizons, ice wedges, and ice-lens formation indicate a permafrost environment and mean annual temperatures below −6° to −8°C. Shallow active layers (average 45 cm), minimal evidence for chemical leaching of soils, and the presence of earthen hummocks indicate a cold and seasonally dry climate. Neither steppe nor polar desert soils are appropriate analogues for these zonal soils of loess-covered central Beringia. No exact analogues are known; however, soils underlying dry tundra near the arctic coast of northern Yakutia, Russia, and under moist, nonacidic tundra of the Alaskan North Slope have properties in common with the buried soils.

Calibration of the radiocarbon timescale of paleoecological records is essential if they are to be explained correctly in terms of their governing ecological or climatological controls. The differences between calendar ages and radiocarbon ages that arise from variations in 14C production through time can distort the chronologies of individual records and the interpretations based on them. Misleading impressions of synchrony or diachrony of events among multiple records can result, and estimates of the apparent duration of episodes and rates of sedimentation and local population changes can be biased. Displays of the temporal patterns of migration or extinction may also be affected. Spurious correlations may arise between records with radiocarbon-controlled chronologies and time series of potential controls that are expressed on a calendar time scale. Support for particular explanations of features in a paleoecological record may vary depending on whether radiocarbon ages are calibrated or not. This situation is illustrated using the eastern Beringian Populus subzone as an example. When the radiocarbon ages that control the timing of the Populus subzone are calibrated, the contemporaneous decrease in ice volume and increase in summer insolation are implicated as the ultimate controls of the occurrence of the subzone.