Increasing emphasis on the use of real-world evidence (RWE) to support clinical policy and regulatory decision-making has led to a proliferation of guidance, advice, and frameworks from regulatory agencies, academia, professional societies, and industry. A broad spectrum of studies use real-world data (RWD) to produce RWE, ranging from randomized trials with outcomes assessed using RWD to fully observational studies. Yet, many proposals for generating RWE lack sufficient detail, and many analyses of RWD suffer from implausible assumptions, other methodological flaws, or inappropriate interpretations. The Causal Roadmap is an explicit, itemized, iterative process that guides investigators to prespecify study design and analysis plans; it addresses a wide range of guidance within a single framework. By supporting the transparent evaluation of causal assumptions and facilitating objective comparisons of design and analysis choices based on prespecified criteria, the Roadmap can help investigators to evaluate the quality of evidence that a given study is likely to produce, specify a study to generate high-quality RWE, and communicate effectively with regulatory agencies and other stakeholders. This paper aims to disseminate and extend the Causal Roadmap framework for use by clinical and translational researchers; three companion papers demonstrate applications of the Causal Roadmap for specific use cases.

Rapid whole genome sequencing (rapid WGS) is a powerful diagnostic tool that is becoming increasingly practical for widespread clinical use. However, protocols for its use are challenging to implement. A significant obstacle to clinical adoption is that laboratory certification requires an initial research development phase, which is constrained by regulations from returning results. Regulations preventing return of results have ethical implications in cases which might impact patient outcomes. Here, we describe our experience with the development of a rapid WGS research protocol, that balanced the requirements for laboratory-validated test development with the ethical needs of clinically relevant return of results.

Residual strain in electrodeposited Li films may affect safety and performance in Li metal battery anodes, so it is important to understand how to detect residual strain in electrodeposited Li and the conditions under which it arises. To explore this Li films, electrodeposited onto Cu metal substrates, were prepared under an applied pressure of either 10 or 1000 kPa and subsequently tested for the presence or absence of residual strain via sin2(ψ) analysis. X-ray diffraction (XRD) analysis of Li films required preparation and examination within an inert environment; hence, a Be-dome sample holder was employed during XRD characterization. Results show that the Li film grown under 1000 kPa displayed a detectable presence of in-plane compressive strain (−0.066%), whereas the Li film grown under 10 kPa displayed no detectable in-plane strain. The underlying Cu substrate revealed an in-plane residual strain near zero. Texture analysis via pole figure determination was also performed for both Li and Cu and revealed a mild fiber texture for Li metal and a strong bi-axial texture of the Cu substrate. Experimental details concerning sample preparation, alignment, and analysis of the particularly air-sensitive Li films have also been detailed. This work shows that Li metal exhibits residual strain when electrodeposited under compressive stress and that XRD can be used to quantify that strain.

Carbonate glasses can be formed routinely in the system K2CO3–MgCO3. The enthalpy of formation for one such 0.55K2CO3–0.45MgCO3 glass was determined at 298 K to be 115.00 ± 1.21 kJ/mol by drop solution calorimetry in molten sodium molybdate (3Na2O·MoO3) at 975 K. The corresponding heat of formation from oxides at 298 K was −261.12 ± 3.02 kJ/mol. This ternary glass is shown to be slightly metastable with respect to binary crystalline components (K2CO3 and MgCO3) and may be further stabilized by entropy terms arising from cation disorder and carbonate group distortions. This high degree of disorder is confirmed by 13C MAS NMR measurement of the average chemical shift tensor values, which show asymmetry of the carbonate anion to be significantly larger than previously reported values. Molecular dynamics simulations show that the structure of this carbonate glass reflects the strong interaction between the oxygen atoms in distorted carbonate anions and potassium cations.

Seven half-day regional listening sessions were held between December 2016 and April 2017 with groups of diverse stakeholders on the issues and potential solutions for herbicide-resistance management. The objective of the listening sessions was to connect with stakeholders and hear their challenges and recommendations for addressing herbicide resistance. The coordinating team hired Strategic Conservation Solutions, LLC, to facilitate all the sessions. They and the coordinating team used in-person meetings, teleconferences, and email to communicate and coordinate the activities leading up to each regional listening session. The agenda was the same across all sessions and included small-group discussions followed by reporting to the full group for discussion. The planning process was the same across all the sessions, although the selection of venue, time of day, and stakeholder participants differed to accommodate the differences among regions. The listening-session format required a great deal of work and flexibility on the part of the coordinating team and regional coordinators. Overall, the participant evaluations from the sessions were positive, with participants expressing appreciation that they were asked for their thoughts on the subject of herbicide resistance. This paper details the methods and processes used to conduct these regional listening sessions and provides an assessment of the strengths and limitations of those processes.

Herbicide resistance is ‘wicked’ in nature; therefore, results of the many educational efforts to encourage diversification of weed control practices in the United States have been mixed. It is clear that we do not sufficiently understand the totality of the grassroots obstacles, concerns, challenges, and specific solutions needed for varied crop production systems. Weed management issues and solutions vary with such variables as management styles, regions, cropping systems, and available or affordable technologies. Therefore, to help the weed science community better understand the needs and ideas of those directly dealing with herbicide resistance, seven half-day regional listening sessions were held across the United States between December 2016 and April 2017 with groups of diverse stakeholders on the issues and potential solutions for herbicide resistance management. The major goals of the sessions were to gain an understanding of stakeholders and their goals and concerns related to herbicide resistance management, to become familiar with regional differences, and to identify decision maker needs to address herbicide resistance. The messages shared by listening-session participants could be summarized by six themes: we need new herbicides; there is no need for more regulation; there is a need for more education, especially for others who were not present; diversity is hard; the agricultural economy makes it difficult to make changes; and we are aware of herbicide resistance but are managing it. The authors concluded that more work is needed to bring a community-wide, interdisciplinary approach to understanding the complexity of managing weeds within the context of the whole farm operation and for communicating the need to address herbicide resistance.

Perennial pepperweed is an invasive plant species in North America, native to temperate Eurasia and northern Africa. Effective biological control depends upon correct taxonomic identification. Therefore, we investigated morphological and genetic data (cpDNA sequences and amplified fragment length polymorphisms [AFLP]) in its native range, where the species is at times treated as multiple taxa (L. latifolium, L. affine and L. obtusum). We also analyzed genetic data to determine the number and distribution of haplotypes and genotypes in the invaded range. Using Bayesian analysis, we found three clusters of AFLP genotypes in the native range, but little correlation between these clusters and morphological characters used to distinguish taxa. Also, we found combinations of morphological character states within many native range plants that are incompatible with current species descriptions, offering no support for splitting L. latifolium sensu lato into three species. In North America 97% of the genetic variation was among populations and there were only eight AFLP genotypes in 288 plants, suggesting few introductions or a severe bottleneck, and little or no creation of new genotypes since introduction. We found plants in the native range that are genetically similar (88 to 99%) to six of the eight invasive AFLP genotypes, suggesting that Kazakhstan and China are origins for much of the North American invasion.

Field experiments were conducted at Belleville, Colby, Hays, Hesston, Garden City, and Manhattan, KS, to determine grain sorghum response to POST application of mesotrione at three application timings. Mesotrione was applied at 52, 105, 157, and 210 g ai/ha in combination with 280 g ai/ha atrazine to grain sorghum at heights of 5 to 8, 15 to 20, and 30 cm, which correspond to early POST (EPOST), mid-POST (MPOST), and late POST (LPOST), respectively. All mesotrione rates caused injury at all application timings. Overall, grain sorghum injury from mesotrione was greatest at 1 wk after treatment (WAT); plants partially recovered from injury by 4 WAT. Mesotrione applied EPOST injured grain sorghum more than when applied at MPOST and LPOST timings. The EPOST application injured grain sorghum 19 to 88%, whereas injury from MPOST and LPOST application was 1 to 66% and 0 to 69%, respectively, depending on rate. Mesotrione injury was least at Belleville and most at the Hesston and Garden City (irrigated) sites regardless of growth stage. Correlation coefficient analyses indicated that observed mesotrione injury symptoms were not well correlated with grain sorghum yield; thus, mesotrione injury to grain sorghum did not influence grain yield. However, initial grain sorghum injury was severe, and this will likely be a major concern to producers.

We present the results of an approximately 6 100 deg2 104–196 MHz radio sky survey performed with the Murchison Widefield Array during instrument commissioning between 2012 September and 2012 December: the MWACS. The data were taken as meridian drift scans with two different 32-antenna sub-arrays that were available during the commissioning period. The survey covers approximately 20.5 h < RA < 8.5 h, − 58° < Dec < −14°over three frequency bands centred on 119, 150 and 180 MHz, with image resolutions of 6–3 arcmin. The catalogue has 3 arcmin angular resolution and a typical noise level of 40 mJy beam− 1, with reduced sensitivity near the field boundaries and bright sources. We describe the data reduction strategy, based upon mosaicked snapshots, flux density calibration, and source-finding method. We present a catalogue of flux density and spectral index measurements for 14 110 sources, extracted from the mosaic, 1 247 of which are sub-components of complexes of sources.

Background: Cognitive dysfunction is a common complaint associated with obstructive hydrocephalus. The purpose of this study was to determine the effect of endoscopic third ventriculostomy (ETV) on the neuropsychological outcome in patients presenting with cognitive decline and obstructive hydrocephalus. Methods: A retrospective review of patients who underwent ETV at the University of Calgary and had both pre and post operative neuropsychological testing, was completed. Presenting clinical features, etiology of hydrocephalus and ventricle size utilizing frontal occipital horn ratio was obtained. Outcomes and complications of the ETV were recorded. Detailed measures of intelligence, attention and concentration, executive function, visual and verbal memory, language functions and fine motor skills were completed. Post treatment change was determined utilizing Reliable Change Index. Results: A total of 13 patients were identified. Etiology of the hydrocephalus was aqueductal stenosis in 8 and tectal glioma in 4. The majority of patients (11 of 13, 85%) demonstrated cognitive dysfunction at the borderline (≤1 SD) or impairment level (≤1.5 SDs) in at least one domain. Nine patients (69%) showed reliable improvement in at least one cognitive domain. The greatest improvement was seen with visual memory (42%). One quarter to one third of patients demonstrated improvement on tests of intelligence quotient, verbal memory, attention and concentration, and executive function. Two patients declined in executive functioning. Ventricle size improved in eight patients. Conclusions: ETV is a safe effective procedure, capable of producing reliable improvements in cognitive dysfunction with hydrocephalus. Patients with cognitive complaints alone may benefit from ETV.

We used sex, observed parenting quality at 18 months, and three variants of the catechol-O-methyltransferase gene (Val158Met [rs4680], intron1 [rs737865], and 3′-untranslated region [rs165599]) to predict mothers' reports of inhibitory and attentional control (assessed at 42, 54, 72, and 84 months) and internalizing symptoms (assessed at 24, 30, 42, 48, and 54 months) in a sample of 146 children (79 male). Although the pattern for all three variants was very similar, Val158Met explained more variance in both outcomes than did intron1, the 3′-untranslated region, or a haplotype that combined all three catechol-O-methyltransferase variants. In separate models, there were significant three-way interactions among each of the variants, parenting, and sex, predicting the intercepts of inhibitory control and internalizing symptoms. Results suggested that Val158Met indexes plasticity, although this effect was moderated by sex. Parenting was positively associated with inhibitory control for methionine–methionine boys and for valine–valine/valine–methionine girls, and was negatively associated with internalizing symptoms for methionine–methionine boys. Using the “regions of significance” technique, genetic differences in inhibitory control were found for children exposed to high-quality parenting, whereas genetic differences in internalizing were found for children exposed to low-quality parenting. These findings provide evidence in support of testing for differential susceptibility across multiple outcomes.