Clinical trials are a fundamental tool in evaluating the safety and efficacy of new drugs, medical devices, and health system interventions. Clinical trial visits generally involve eligibility assessment, enrollment, intervention administration, data collection, and follow-up, with many of these steps performed during face-to-face visits between participants and the investigative team. Social distancing, which emerged as one of the mainstay strategies for reducing the spread of SARS-CoV-2, has presented a challenge to the traditional model of clinical trial conduct, causing many research teams to halt all in-person contacts except for life-saving research. Nonetheless, clinical research has continued during the pandemic because study teams adapted quickly, turning to virtual visits and other similar methods to complete critical research activities. The purpose of this special communication is to document this rapid transition to virtual methodologies at Clinical and Translational Science Awards hubs and highlight important considerations for future development. Looking beyond the pandemic, we envision that a hybrid approach, which implements remote activities when feasible but also maintains in-person activities as necessary, will be adopted more widely for clinical trials. There will always be a need for in-person aspects of clinical research, but future study designs will need to incorporate remote capabilities.

Field experiments were conducted to measure the grain yield of wheat (Triticum aestivum L. ‘ANZA’) at various wild oat (Avena fatua L. ♯ AVEFA) and wheat plant densities. Wheat yield declined as wild oat plant density increased. Wheat yield increased in wild oat-infested plots as wheat plant density increased. Regression models were developed to describe the combined effect of wheat and wild oat plant densities on wheat grain yield. Wheat yields were best described by a nonlinear regression model using the relative density of wild oat in the weed-crop stand as the dependent variable. Inclusion of crop stand as a competitive factor significantly improved the fit of all regression models tested. Wild oat were more competitive against wheat in these experiments than in experiments reported by others. Possible reasons for differences in observed competitiveness are discussed.

Field experiments were conducted to determine the effect of nitrogen fertilization on competition between wild oat (Avena fatua L. # AVEFA) and spring wheat (Triticum aestivum ‘Anza’). Nitrogen fertilizer treatments were applied over several wild oat-wheat density combinations. Wheat grain yield in wild oat-infested plots generally declined with fertilization while the density of wild oat panicles increased. Apparently, in competition with wheat, wild oat was better able to utilize the added nitrogen and thus gained a competitive advantage over the wheat. The increased competitiveness of wild oat resulted in reduced crop yields. Under the conditions of these experiments, nitrogen fertilization resulted in positive wheat yield response only when the wild oat plant density was below 1.6 percent of the total plant density.

California arrowhead is a broadleaf weed widespread in water-seeded rice. Bensulfuron is the only herbicide currently available for use throughout the California rice growing region that provides complete control of California arrowhead; however, resistance to bensulfuron has been detected in California arrowhead and in several other weed species. Growers have herbicide alternatives for weed species other than California arrowhead but continue to use bensulfuron year after year for control because they believe California arrowhead reduces rice yields. However, damage thresholds have not been determined for this weed, and the crop may be able to tolerate relatively high California arrowhead densities. In this work, the damage thresholds for California arrowhead were determined in field and greenhouse experiments. Water-seeded rice was grown in mixture with California arrowhead in a 1992 greenhouse experiment and in field experiments in 1992 and 1998. Rice tiller density and grain yields were not affected by California arrowhead densities up to 200 plants m−2 in any year. Rice was taller than California arrowhead throughout the growing season in all experiments, and the weed senesced well before rice maturity. The ability of the crop to overtop the weed and grow weed-free during the latter part of the season may explain why California arrowhead is such a weak competitor with water-seeded rice. The results suggest that growers may be able to tolerate California arrowhead densities up to 200 plants m−2 without detectable yield losses. Implications for weed management are discussed.

In the United States alone, ∼14,000 children are hospitalised annually with acute heart failure. The science and art of caring for these patients continues to evolve. The International Pediatric Heart Failure Summit of Johns Hopkins All Children’s Heart Institute was held on February 4 and 5, 2015. The 2015 International Pediatric Heart Failure Summit of Johns Hopkins All Children’s Heart Institute was funded through the Andrews/Daicoff Cardiovascular Program Endowment, a philanthropic collaboration between All Children’s Hospital and the Morsani College of Medicine at the University of South Florida (USF). Sponsored by All Children’s Hospital Andrews/Daicoff Cardiovascular Program, the International Pediatric Heart Failure Summit assembled leaders in clinical and scientific disciplines related to paediatric heart failure and created a multi-disciplinary “think-tank”. The purpose of this manuscript is to summarise the lessons from the 2015 International Pediatric Heart Failure Summit of Johns Hopkins All Children’s Heart Institute, to describe the “state of the art” of the treatment of paediatric cardiac failure, and to discuss future directions for research in the domain of paediatric cardiac failure.

The antimalarial drug artemisinin (ART) is commercially extracted from the medicinal plant Artemisia annua L. Here, we report the screening of 70 A. annua plants representing 14 diverse germplasm accessions sourced from around the world, and identify lines containing >2% ART. These extremely high-yielding individuals have been maintained as vegetative clones, and they represent promising germplasm resources for future A. annua breeding programmes.

We report a study on catalytic water oxidation by cobalt in oxygen ligand environments because such systems are as promising as any in the water oxidation component of solar fuel production. We have re-examined the catalytic activity of Co(II) in aqueous solution using either [Ru(bpy)3]3+ as a stoichiometric oxidant or in visible-light-driven reactions with persulfate as a sacrificial electron acceptor. In both systems a distinctive induction period is observed. A simple kinetic model is proposed that describes the experimental data well. The presence of an induction period is explained by relatively slow formation of the true catalyst from aquacobalt(II).

Patients with Alzheimer's disease (AD) have been reported to have a rate of nonsuppression on the dexamethasone suppression test (DST) comparable to that of patients with major depression. With symptoms of depression being increasingly recognized in patients with AD, studying their DST response may provide clues to the etiology of the abnormal response in both diagnostic groups. A correlation between dementia severity and post-dexamethasone cortisol was found within the group of male, but not female AD patients. Within the group of elderly depressives, a correlation between post-dexamethasone cortisol and ratings of depression was found. Serum dexamethasone levels were not significantly lower in the nonsuppressors as compared with suppressors in either diagnostic group.

Dietary studies are often conducted as longitudinal intervention or crossover trials using multiple days of measurement on each subject during each of several measurement periods, and determining the required numbers of days and subjects is important in designing these studies. Linear mixed statistical models were used to derive equations for precision, statistical power and sample size (number of days and number of subjects) and to obtain estimates of between-subject, period-to-period, and day-to-day variation needed to apply the equations. Two cohorts of an on-going exercise intervention study, and a crossover study of Olestra, each with 14 d of measurement/subject per period, were used to obtain estimates of variability for energy and macronutrient intake. Numerical examples illustrate how the equations for calculating the number of days or number of subjects are applied in typical situations, and sample SAS code is given. It was found that between-subject, period-to-period, and day-to-day variation all contributed significantly to the variation in energy and macronutrient intake. The ratio of period-to-period and day-to-day standard deviations controls the trade-off between the number of days and the number of subjects, and this remained relatively stable across studies and energy and macronutrient intake variables. The greatest gains in precision were seen over the first few measurement days. Greater precision and fewer required days were noted in the study (Olestra) that exerted greater control over the subjects and diets during the feeding protocol.

The “mindblindness” theory of core cognitive impairment in autism and at least one of the executive theories of the core cognitive deficit both predict that children with autism should find it difficult to report what their intention was when it diverged from an outcome. The former predicts this because it takes intention reporting to require a “theory of mind” and the latter predicts it because the theory posits an impairment in the monitoring of goal-directed actions. The latter also predicts impairments in the ability to monitor basic actions. Our three studies failed to support either of these views. Experiment 1 demonstrated intact abilities in the monitoring of basic actions (detecting which stimulus of a number of stimuli one is controlling). Experiment 2 demonstrated intact abilities in reporting an intention, both for self and for another agent, when the outcome was unintended but desired. In Experiment 3, using the novel “transparent intentions task”, we found (with a minor qualification) intact ability in reporting on nonballistic intended actions when the result that the action achieved was unexpected. The implications of these results for views of the relation between theory of mind and executive difficulties in autism are discussed.

We describe the design of Escherichia coli cells that synthesize a structurally perfect, recombinant cytochrome c from the Thermus thermophilus cytochrome c552 gene. Key features are (1) construction of a plasmid-borne, chimeric cycA gene encoding an Escherichia coli-compatible, N-terminal signal sequence (MetLysIleSerIleTyrAlaThrLeuAlaAlaLeuSerLeuAlaLeuProAlaGlyAla) followed by the amino acid sequence of mature Thermus cytochrome c552; and (2) coexpression of the chimeric cycA gene with plasmid-borne, host-specific cytochrome c maturation genes (ccmABCDEFGH). Approximately 1 mg of purified protein is obtained from 1 L of culture medium. The recombinant protein, cytochrome rsC552, and native cytochrome c552 have identical redox potentials and are equally active as electron transfer substrates toward cytochrome ba3, a Thermus heme-copper oxidase. Native and recombinant cytochromes c were compared and found to be identical using circular dichroism, optical absorption, resonance Raman, and 500 MHz 1H-NMR spectroscopies. The 1.7 Å resolution X-ray crystallographic structure of the recombinant protein was determined and is indistinguishable from that reported for the native protein (Than, ME, Hof P, Huber R, Bourenkov GP, Bartunik HD, Buse G, Soulimane T, 1997, J Mol Biol 271:629–644). This approach may be generally useful for expression of alien cytochrome c genes in E. coli.

The linear polarization of the Crab pulsar as a function of pulse phase was observed by the High Speed Photometer on the Hubble Space Telescope in March, 1993. Observations were obtained in a bandpass centered on 2770 A using a 0.25 ms sample time, corresponding to a time resolution of 0.0075 in pulse phase. The UV polarization of the pulsar [Fig. 1] is strikingly similar to that observed in the visible (cf. Smith et al. 1988). The same values of polarization and the same swing of position angle occur through the main and secondary pulses. The polarization pulse profile must be essentially wavelength independent at frequencies above the infrared.