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.

The elm zigzag sawfly, Aproceros leucopoda Takeuchi (Hymenoptera: Argidae), was reported for the first time in North America during the summer of 2020. Characteristic zigzag defoliation was reported in the province of Québec, Canada, on the community science website, iNaturalist. Field trips conducted to the site resulted in the collection of live specimens (a few larvae and a cocoon from which an adult emerged) and onsite observation of diagnostic defoliation and empty cocoons, confirming the presence of this exotic species in Canada. Subsequent inspection of elm trees by naturalists and scientists in the south of the province led to the conclusion that the species is more widely distributed than first expected and that the invasion is not localised to a small area. Preliminary genetic data pointed to a possible European origin of the Canadian population, but conclusive assignment to source will require examination of more specimens and the collection of reference sequences from different European and Asian populations. This is a good example of the importance of community science in the detection of new invasive species.

Objectives: Preterm children demonstrate deficits in executive functions including inhibition, working memory, and cognitive flexibility; however, their goal setting abilities (planning, organization, strategic reasoning) remain unclear. This study compared goal setting abilities between very preterm (VP: <30 weeks/<1250 grams) and term born controls during late childhood. Additionally, early risk factors (neonatal brain abnormalities, medical complications, and sex) were examined in relationship to goal setting outcomes within the VP group. Methods: Participants included 177 VP and 61 full-term born control children aged 13 years. Goal setting was assessed using several measures of planning, organization, and strategic reasoning. Parents also completed the Behavior Rating Inventory of Executive Function. Regression models were performed to compare groups, with secondary analyses adjusting for potential confounders (sex and social risk), and excluding children with major neurosensory impairment and/or IQ<70. Within the VP group, regression models were performed to examine the relationship between brain abnormalities, medical complications, and sex, on goal setting scores. Results: The VP group demonstrated a clear pattern of impairment and inefficiency across goal setting measures, consistent with parental report, compared with their full-term born peers. Within the VP group, moderate/severe brain abnormalities on neonatal MRI predicted adverse goal setting outcomes at 13. Conclusions: Goal setting difficulties are a significant area of concern in VP children during late childhood. These difficulties are associated with neonatal brain abnormalities, and are likely to have functional consequences academically, socially and vocationally. (JINS, 2018, 24, 372–381)

Firn-densification modeling based on hot isostatic pressing with power-law creep is investigated using depth–density data from 38 sites that collectively have mean annual temperatures ranging from 216 to 256 K and accumulation rates ranging from 0.022 to 1.2 m w.e. a−1. We use an inverse technique to obtain free parameters in a simple physical model for different stages of time-dependent firn densification. Our model works as well as or slightly better than previous models interpolating within the data range, but extrapolating would require additional physics.

The WAIS (West Antarctic Ice Sheet) Divide deep ice core was recently completed to a total depth of 3405 m, ending 50 m above the bed. Investigation of the visual stratigraphy and grain characteristics indicates that the ice column at the drilling location is undisturbed by any large-scale overturning or discontinuity. The climate record developed from this core is therefore likely to be continuous and robust. Measured grain-growth rates, recrystallization characteristics, and grain-size response at climate transitions fit within current understanding. Significant impurity control on grain size is indicated from correlation analysis between impurity loading and grain size. Bubble-number densities and bubble sizes and shapes are presented through the full extent of the bubbly ice. Where bubble elongation is observed, the direction of elongation is preferentially parallel to the trace of the basal (0001) plane. Preferred crystallographic orientation of grains is present in the shallowest samples measured, and increases with depth, progressing to a vertical-girdle pattern that tightens to a vertical single-maximum fabric. This single-maximum fabric switches into multiple maxima as the grain size increases rapidly in the deepest, warmest ice. A strong dependence of the fabric on the impurity-mediated grain size is apparent in the deepest samples.

δ18O values of sulfate minerals from a 186-m core (past 200,000 years) in Death Valley varied from +9 to +23‰ (V-SMOW). Sulfates that accumulated in the past ephemeral saline lake, salt pans, and mud flats have relatively low δ18O values similar to those of present-day local inflows. Sulfates that accumulated during two perennial lake intervals, however, have higher δ18O values, reflecting changes in temperature, lake water levels, and/or sulfur redox reactions. Over the same time interval, the δ18O record for sulfate had excursions that bear similarities to those found for carbonate in the Death Valley core, marine carbonate (SPECMAP), and polar ice in the Summit ice core, Greenland. The δ18O record differed considerably from the records reported for carbonate at Owens Lake and Devils Hole, which probably relates to different water sources. Death Valley, Owens Lake, and Devils Hole are responding to the same climatic changes but manifesting them differently. In Death Valley sediments, the isotopic composition of sulfate may have potential as an indicator of paleoenvironmental changes.

Finch trichomonosis, caused by Trichomonas gallinae, emerged in the Canadian Maritime provinces in 2007 and has since caused ongoing mortality in regional purple finch (Carpodacus purpureus) and American goldfinch (Carduelis tristis) populations. Trichomonas gallinae was isolated from (1) finches and rock pigeons (Columbia livia) submitted for post-mortem or live-captured at bird feeding sites experiencing trichomonosis mortality; (2) bird seed at these same sites; and (3) rock pigeons live-captured at known roosts or humanely killed. Isolates were characterized using internal transcribed spacer (ITS) region and iron hydrogenase (Fe-hyd) gene sequences. Two distinct ITS types were found. Type A was identical to the UK finch epidemic strain and was isolated from finches and a rock pigeon with trichomonosis; apparently healthy rock pigeons and finches; and bird seed at an outbreak site. Type B was obtained from apparently healthy rock pigeons. Fe-hyd sequencing revealed six distinct subtypes. The predominant subtype in both finches and the rock pigeon with trichomonosis was identical to the UK finch epidemic strain A1. Single nucleotide polymorphisms in Fe-hyd sequences suggest there is fine-scale variation amongst isolates and that finch trichomonosis emergence in this region may not have been caused by a single spill-over event.

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 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.

The consequences of a low litter average birth weight phenotype for postnatal growth performance and carcass quality of all progeny, and testicular development in male offspring, were investigated. Using data from 25 sows with one, and 223 sows with two consecutive farrowing events, individual birth weight (BW) was measured and each litter between 9 and 16 total pigs born was classified as low (LBW), medium (MBW) or high (HBW) birth weight: low and high BW being defined as >1 standard deviation below or above, respectively, the population mean for each litter size. Litter average BW was repeatable within sows. At castration, testicular tissue was collected from 40 male pigs in LBW and HBW litters with individual BW close to their litter average BW and used for histomorphometric analysis. LBW piglets had a lower absolute number of germ cells, Sertoli cells and Leydig cells in their testes and a higher brain : testis weight ratio than HBW piglets. Overall, LBW litters had lower placental weight and higher brain : liver, brain : intestine and brain : Semitendinosus muscle weight ratios than MBW and HBW litters. In the nursery and grow–finish (GF) phase, pigs were kept in pens by BW classification (9 HBW, 17 MBW and 10 LBW pens) with 13 males and 13 females per pen. Average daily gain tended to be lower in LBW than HBW litters in lactation (P = 0.06) and throughout the nursery and GF phases (P < 0.01), resulting in an increasing difference in body weight between LBW, MBW and HBW litters (P < 0.05). Average daily feed intake was lower (P < 0.001) in LBW than HBW litters in the nursery and GF phases. Feed utilization efficiency (feed/gain) was similar for LBW and HBW litters in the nursery, but was lower (P < 0.001) in HBW than LBW litters in the GF phase. By design, slaughter weight was similar between BW classifications; however, LBW litters needed 9 more days to reach the same slaughter weight than HBW litters (P < 0.001). BW classification did not affect carcass composition traits. In conclusion, LBW litters showed benchmarks of intrauterine growth retardation, LBW had a negative impact on testicular development and germ and somatic cell populations, and was associated with decreased postnatal growth during all phases of production; however, no measurable effect on carcass composition traits was established.

Feeding n-3 long-chain polyunsaturated fatty acids (LCPUFA) to gilts or sows has shown different responses to litter growth, pre-weaning mortality and subsequent reproductive performance of the sow. Two hypotheses were tested: (1) that feeding a marine oil-based supplement rich in protected n-3 LCPUFAs to gilts in established gestation would improve the growth performance of their litters; and (2) that continued feeding of the supplement during lactation and after weaning would offset the negative effects of lactational catabolism induced, using an established experimental model involving feed restriction of lactating primiparous sows. A total of 117 primiparous sows were pair-matched at day 60 of gestation by weight, and when possible, litter of origin, and were allocated to be either control sows (CON) fed standard gestation and lactation diets, or treated sows (LCPUFA) fed the standard diets supplemented with 84 g/day of a n-3 LCPUFA rich supplement, from day 60 of first gestation, through a 21-day lactation, and until euthanasia at day 30 of their second gestation. All sows were feed restricted during the last 7 days of lactation to induce catabolism, providing a background challenge against which to determine beneficial effects of n-3 LCPUFA supplementation on subsequent reproduction. In the absence of an effect on litter size or birth weight, n-3 LCPUFA tended to improve piglet BW gain from birth until 34 days after weaning (P = 0.06), while increasing pre-weaning mortality (P = 0.05). It did not affect energy utilization by the sow during lactation, thus not improving the catabolic state of the sows. Supplementation from weaning until day 30 of second gestation did not have an effect on embryonic weight, ovulation rate or early embryonic survival, but did increase corpora lutea (CL) weight (P = 0.001). Eicosapentaenoic acid and docosahexaenoic acid (DHA) levels were increased in sow serum and CL (P < 0.001), whereas only DHA levels increased in embryos (P < 0.01). In conclusion, feeding n-3 LCPUFA to gilts tended to improve litter growth, but did not have an effect on overall subsequent reproductive performance.