The COVID-19 pandemic accelerated the development of decentralized clinical trials (DCT). DCT’s are an important and pragmatic method for assessing health outcomes yet comprise only a minority of clinical trials, and few published methodologies exist. In this report, we detail the operational components of COVID-OUT, a decentralized, multicenter, quadruple-blinded, randomized trial that rapidly delivered study drugs nation-wide. The trial examined three medications (metformin, ivermectin, and fluvoxamine) as outpatient treatment of SARS-CoV-2 for their effectiveness in preventing severe or long COVID-19. Decentralized strategies included HIPAA-compliant electronic screening and consenting, prepacking investigational product to accelerate delivery after randomization, and remotely confirming participant-reported outcomes. Of the 1417 individuals with the intention-to-treat sample, the remote nature of the study caused an additional 94 participants to not take any doses of study drug. Therefore, 1323 participants were in the modified intention-to-treat sample, which was the a priori primary study sample. Only 1.4% of participants were lost to follow-up. Decentralized strategies facilitated the successful completion of the COVID-OUT trial without any in-person contact by expediting intervention delivery, expanding trial access geographically, limiting contagion exposure, and making it easy for participants to complete follow-up visits. Remotely completed consent and follow-up facilitated enrollment.

Invasive species can have disastrous effects on the ecosystems they invade, requiring costly, labour-intensive mitigation. Public awareness campaigns are often used as a tool to reduce these species’ impacts. While heralded as useful and cost-effective, little evidence suggests that these campaigns contribute to meaningful biological outcomes. Furthermore, awareness campaigns are relatively understudied despite their usage as a common approach to mitigating invasive species. We conducted a literature review to assess publications that evaluated the efficacy of public awareness campaigns for managing invasive species. Out of 4382 papers initially extracted for analysis, we determined that 24 of them included studies conducted on awareness campaigns for invasive species. Four public awareness campaigns were deemed a ‘success’, and the other campaigns’ success was indeterminable due to study design. Our study revealed that inconsistencies in defined end points, unclear procedures and variability of campaigns contribute to there being insufficient evidence to determine the efficacy of public awareness campaigns. To evaluate the true efficacy of public awareness campaigns, we recommend that organizations conducting such campaigns implement rigorous and standardized assessments (e.g., Before–After Control–Impact designs or Bayesian analyses) that include measures of not just changes in the knowledge and behaviour of target audiences, but also relevant biological outcomes.

In this study, we propose a scale-by-scale (SBS) energy budget equation for flows with homogeneity in at least one direction. This SBS budget represents a modified form of the equation first proposed by Danaila et al. (J. Fluid Mech., vol. 430, 2001, pp. 87–109) for the channel centreline – the primary difference is that, here, we consider the role of pressure along with the errors associated with the isotropic approximations of the interscale divergence and Laplacian of the squared velocity increment. The term encompassing the effects of mean shear is also characterised such that the present analysis can be extended straightforwardly to locations away from the centreline. We show, based on a detailed analysis of previously published channel flow direct numerical simulations and pipe flow experiments near the centreline, how several terms in the present SBS budget equation (including the third-order velocity structure function) behave with increasing Reynolds number. The behaviour of these terms is shown to imply a rate of emergence and subsequent growth of the 4/3 law scale subrange at the channel centreline and pipe axis. The analysis also suggests that the peak magnitude of the third-order velocity structure function occurs at a scale that is fixed in proportion to the Taylor microscale at sufficiently high Reynolds number.

Leafy spurge is a troublesome, exotic weed in the northern Great Plains of the United States. Leafy spurge produces showy yellow bracts during June that give this weed a conspicuous appearance. A study was conducted to determine the feasibility of using remote sensing techniques to detect leafy spurge in this phenological stage. Study sites were located in North Dakota and Montana. Plant canopy reflectance measurements showed that leafy spurge had higher visible (0.63- to 0.69-μm) reflectance than several associated plant species. The conspicuous yellow bracts of leafy spurge gave it distinct yellow-green and pink images on conventional color and color-infrared aerial photographs, respectively. Leafy spurge also could be distinguished on conventional color video imagery where it had a golden yellow image response. Quantitative data obtained from digitized video images showed that leafy spurge had statistically different digital values from those of associated vegetation and soil. Computer analyses of video images showed/that light reflected from leafy spurge populations could be quantified from associated vegetation. This technique permits area estimates of leafy spurge populations. Large format conventional color photographs of Theodore Roosevelt National Park near Medora, ND were digitized and integrated with a geographic information system to produce a map of leafy spurge populations within the park that can be useful to monitor the spread or decline of leafy spurge.

A plausible mechanism underlying flavonoid-associated cognitive effects is increased cerebral blood flow (CBF). However, behavioural and CBF effects following flavanone-rich juice consumption have not been explored. The aim of this study was to investigate whether consumption of flavanone-rich juice is associated with acute cognitive benefits and increased regional CBF in healthy, young adults. An acute, single-blind, randomised, cross-over design was applied with two 500-ml drink conditions – high-flavanone (HF; 70·5 mg) drink and an energy-, and vitamin C- matched, zero-flavanone control. A total of twenty-four healthy young adults aged 18–30 years underwent cognitive testing at baseline and 2-h after drink consumption. A further sixteen, healthy, young adults were recruited for functional MRI assessment, whereby CBF was measured with arterial spin labelling during conscious resting state at baseline as well as 2 and 5 h after drink consumption. The HF drink was associated with significantly increased regional perfusion in the inferior and middle right frontal gyrus at 2 h relative to baseline and the control drink. In addition, the HF drink was associated with significantly improved performance on the Digit Symbol Substitution Test at 2 h relative to baseline and the control drink, but no effects were observed on any other behavioural cognitive tests. These results demonstrate that consumption of flavanone-rich citrus juice in quantities commonly consumed can acutely enhance blood flow to the brain in healthy, young adults. However, further studies are required to establish a direct causal link between increased CBF and enhanced behavioural outcomes following citrus juice ingestion.

Effects of a marine oil-based n-3 LCPUFA supplement (mLCPUFA) fed from weaning until the end of the next lactation to sows with a predicted low litter birth weight (LBW) phenotype on growth performance and carcass quality of litters born to these sows were studied, based on the hypothesis that LBW litters would benefit most from mLCPUFA supplementation. Sows were allocated to be fed either standard corn/soybean meal-based gestation and lactation diets (CON), or the same diets enriched with 0.5% of the mLCPUFA supplement at the expense of corn. The growth performance from birth until slaughter of the litters with the lowest average birth weight in each treatment (n=24 per treatment) is reported in this paper. At weaning, each litter was split between two nursery pens with three to six pigs per pen. At the end of the 5-week nursery period, two barrows and two gilts from each litter that had individual birth weights closest to their litter average birth weight, were moved to experimental grow–finish pens (barn A), where they were housed as two pigs per pen, sorted by sex within litter. Remaining pigs in each litter were moved to another grow–finish barn (barn B) and kept in mixed-sex pens of up to 10 littermates. After 8 weeks, one of the two pigs in each pen in barn A was relocated to the pens holding their respective littermates in barn B. The remaining barrows and gilts were individually housed in the pens in barn A until slaughter. Maternal mLCPUFA supplementation increased docosahexaenoic acid (DHA) concentration in the brain, liver and Semitendinosus muscle of stillborn pigs (P<0.01), did not affect eicosapentaenoic acid and DHA concentrations in sow serum at the end of lactation, and did not affect average daily gain, average daily feed intake or feed utilization efficiency of the offspring. BW was higher (P<0.01) in the second half of the grow–finish phase in pigs from mLCPUFA sows compared with controls in barn A, where space and competition for feed was minimal, but not barn B. Carcass quality was not affected by treatment for pigs from barn A, but maternal mLCPUFA supplementation negatively affected carcass quality in pigs from barn B. Collectively, these results suggest that nutritional supplementation of sows can have lasting effects on litter development, but that feeding mLCPUFA to sows during gestation and lactation was not effective in improving growth rates or carcass quality of LBW litters.

The first clinical trials of gene therapy in the 1990s offered the promise of a new paradigm for the treatment of genetic diseases. Over the decades that followed the challenges and setbacks which gene therapy faced often overshadowed any successes. Despite this, recent years have seen cause for renewed optimism. In 2012 Glybera™, an adeno-associated viral vector expressing lipoprotein lipase, became the first gene therapy product to receive marketing authorisation in Europe, with a licence to treat familial lipoprotein lipase deficiency. This followed the earlier licensing in China of two gene therapies: Gendicine™ for head and neck squamous cell carcinoma and Oncorine™ for late-stage nasopharyngeal cancer. By this stage over 1800 clinical trials had been, or were being, conducted worldwide, and the therapeutic targets had expanded far beyond purely genetic disorders. So far no trials of gene therapy have been carried out in pregnancy, but an increasing understanding of the molecular mechanisms underlying obstetric diseases means that it is likely to have a role to play in the future. This review will discuss how gene therapy works, its potential application in obstetric conditions and the risks and limitations associated with its use in this setting. It will also address the ethical and regulatory issues that will be faced by any potential clinical trial of gene therapy during pregnancy.

The effects of a marine oil-based n-3 long-chain polyunsaturated fatty acid (mLCPUFA) supplement fed to the sow from weaning, through the rebreeding period, during gestation and until end of lactation on litter characteristics from birth until weaning were studied in sows with known litter birth weight phenotypes. It was hypothesized that low birth weight (LBW) litters would benefit more from mLCPUFA supplementation than high birth weight litters. A total of 163 sows (mean parity=4.9±0.9) were rebred after weaning. Sows were pair-matched by parity and litter average birth weight of the previous three litters. Within pairs, sows were allocated to be fed either standard corn/soyabean meal-based gestation and lactation diets (CON), or the same diets enriched with 0.5% of the mLCPUFA supplement at the expense of corn. Each litter between 9 and 16 total pigs born was classified as LBW or medium/high average birth weight (MHBW) litter and there was a significant correlation (P<0.001) between litter average birth weight of the current and previous litters within sows (r=0.49). Sow serum was harvested at day 113 of gestation for determination of immunoglobulin G (IgG) concentrations. The number of pigs born total and alive were lower (P=0.01) in mLCPUFA than CON sows, whereas the number of stillborn and mummified pigs were similar between treatments. Number of stillborns (trend) and mummies (P<0.01) were higher in LBW than MHBW litters. Tissue weights and brain : tissue weight ratios were similar between treatments, but LBW litters had decreased tissue weights and increased brain : tissue weight ratios compared with MHBW litters. Placental weight was lower (P=0.01) in LBW than MHBW litters, but was not different between treatments. Average and total litter weight at day 1 was similar between treatments. mLCPUFA increased weaning weight (P=0.08) and average daily gain (P<0.05) in MHBW litters, but not in LBW litters. Pre-weaning mortality was similar between treatments, but was higher (P<0.01) in LBW than MHBW litters. IgG concentration in sow serum was similar between treatments and litter birth weight categories. In conclusion, litter birth weight phenotype was repeatable within sows and LBW litters showed the benchmarks of intra-uterine growth retardation (lower placental weight and brain sparing effects). As maternal mLCPUFA supplementation decreased litter size overall, only improved litter growth rate until weaning in MHBW litters, and did not affect pre-weaning mortality, maternal mLCPUFA supplementation was not an effective strategy in our study for mitigating negative effects of a LBW litter phenotype.

Anti-black prejudice affects how some citizens evaluate black candidates. What does it take to reduce the role of prejudice in these evaluations? Using logical implications of relevant psychological phenomena, this article shows that repeated exposure to counter-stereotypical information is insufficient to reduce evaluative prejudice. Instead, citizens must associate this prejudice with adverse effects for themselves in contexts that induce them to rethink their existing racial beliefs. These findings explain important disagreements in empirical prejudice research, as only some empirical research designs supply the conditions for prejudice reduction predicted here. This study also clarifies why similarly situated citizens react so differently to counter-stereotypical information. In sum, we find that prejudice change is possible, but in a far narrower set of circumstances than many scholars claim.