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.

This study used a short-term longitudinal design with theoretically derived preregistered hypotheses and analyses to examine the role of temperament in the development of forms (i.e., physical and relational) and functions (i.e., proactive and reactive) of aggressive behavior in early childhood (N = 300, M age = 44.70 months, SD = 4.38, 44% girls). Temperament was measured via behavioral reports of emotional dysregulation, fearlessness/daring, and rule internalization/empathy and, in a subsample that completed a physiological assessment, via skin conductance and respiratory sinus arrhythmia. Emotion dysregulation generally served as a risk factor for all subtypes of aggression, with evidence of stronger associations with reactive as compared to proactive functions of relational aggression for girls. Daring predicted increases in physical aggression, especially among boys, and rule internalization predicted decreases in relational aggression, especially among girls. Rule internalization mediated longitudinal associations between daring and proactive relational aggression for girls. Some evidence also emerged supporting associations between adaptive functioning (i.e., high empathy, high respiratory sinus arrhythmia) and proactive functions of aggression. Findings highlight distinct temperamental risk factors for physical versus relational aggression and provide partial support for gender-linked theories of the development of aggression.

Seed retention, and ultimately seed shatter, are extremely important for the efficacy of harvest weed seed control (HWSC) and are likely influenced by various agroecological and environmental factors. Field studies investigated seed-shattering phenology of 22 weed species across three soybean [Glycine max (L.) Merr.]-producing regions in the United States. We further evaluated the potential drivers of seed shatter in terms of weather conditions, growing degree days, and plant biomass. Based on the results, weather conditions had no consistent impact on weed seed shatter. However, there was a positive correlation between individual weed plant biomass and delayed weed seed–shattering rates during harvest. This work demonstrates that HWSC can potentially reduce weed seedbank inputs of plants that have escaped early-season management practices and retained seed through harvest. However, smaller individuals of plants within the same population that shatter seed before harvest pose a risk of escaping early-season management and HWSC.

Potential effectiveness of harvest weed seed control (HWSC) systems depends upon seed shatter of the target weed species at crop maturity, enabling its collection and processing at crop harvest. However, seed retention likely is influenced by agroecological and environmental factors. In 2016 and 2017, we assessed seed-shatter phenology in 13 economically important broadleaf weed species in soybean [Glycine max (L.) Merr.] from crop physiological maturity to 4 wk after physiological maturity at multiple sites spread across 14 states in the southern, northern, and mid-Atlantic United States. Greater proportions of seeds were retained by weeds in southern latitudes and shatter rate increased at northern latitudes. Amaranthus spp. seed shatter was low (0% to 2%), whereas shatter varied widely in common ragweed (Ambrosia artemisiifolia L.) (2% to 90%) over the weeks following soybean physiological maturity. Overall, the broadleaf species studied shattered less than 10% of their seeds by soybean harvest. Our results suggest that some of the broadleaf species with greater seed retention rates in the weeks following soybean physiological maturity may be good candidates for HWSC.

Seed shatter is an important weediness trait on which the efficacy of harvest weed seed control (HWSC) depends. The level of seed shatter in a species is likely influenced by agroecological and environmental factors. In 2016 and 2017, we assessed seed shatter of eight economically important grass weed species in soybean [Glycine max (L.) Merr.] from crop physiological maturity to 4 wk after maturity at multiple sites spread across 11 states in the southern, northern, and mid-Atlantic United States. From soybean maturity to 4 wk after maturity, cumulative percent seed shatter was lowest in the southern U.S. regions and increased moving north through the states. At soybean maturity, the percent of seed shatter ranged from 1% to 70%. That range had shifted to 5% to 100% (mean: 42%) by 25 d after soybean maturity. There were considerable differences in seed-shatter onset and rate of progression between sites and years in some species that could impact their susceptibility to HWSC. Our results suggest that many summer annual grass species are likely not ideal candidates for HWSC, although HWSC could substantially reduce their seed output during certain years.

This paper updates Living with Mortality published in 2006. It describes how the longevity risk transfer market has developed over the intervening period, and, in particular, how insurance-based solutions – buy-outs, buy-ins and longevity insurance – have triumphed over capital markets solutions that were expected to dominate at the time. Some capital markets solutions – longevity-spread bonds, longevity swaps, q-forwards and tail-risk protection – have come to market, but the volume of business has been disappointingly low. The reason for this is that when market participants compare the index-based solutions of the capital markets with the customised solutions of insurance companies in terms of basis risk, credit risk, regulatory capital, collateral and liquidity, the former perform on balance less favourably despite a lower potential cost. We discuss the importance of stochastic mortality models for forecasting future longevity and examine some applications of these models, e.g. determining the longevity risk premium and estimating regulatory capital relief. The longevity risk transfer market is now beginning to recognise that there is insufficient capacity in the insurance and reinsurance industries to deal fully with demand and new solutions for attracting capital markets investors are now being examined – such as longevity-linked securities and reinsurance sidecars.

The Taipan galaxy survey (hereafter simply ‘Taipan’) is a multi-object spectroscopic survey starting in 2017 that will cover 2π steradians over the southern sky (δ ≲ 10°, |b| ≳ 10°), and obtain optical spectra for about two million galaxies out to z < 0.4. Taipan will use the newly refurbished 1.2-m UK Schmidt Telescope at Siding Spring Observatory with the new TAIPAN instrument, which includes an innovative ‘Starbugs’ positioning system capable of rapidly and simultaneously deploying up to 150 spectroscopic fibres (and up to 300 with a proposed upgrade) over the 6° diameter focal plane, and a purpose-built spectrograph operating in the range from 370 to 870 nm with resolving power R ≳ 2000. The main scientific goals of Taipan are (i) to measure the distance scale of the Universe (primarily governed by the local expansion rate, H 0) to 1% precision, and the growth rate of structure to 5%; (ii) to make the most extensive map yet constructed of the total mass distribution and motions in the local Universe, using peculiar velocities based on improved Fundamental Plane distances, which will enable sensitive tests of gravitational physics; and (iii) to deliver a legacy sample of low-redshift galaxies as a unique laboratory for studying galaxy evolution as a function of dark matter halo and stellar mass and environment. The final survey, which will be completed within 5 yrs, will consist of a complete magnitude-limited sample (i ⩽ 17) of about 1.2 × 106 galaxies supplemented by an extension to higher redshifts and fainter magnitudes (i ⩽ 18.1) of a luminous red galaxy sample of about 0.8 × 106 galaxies. Observations and data processing will be carried out remotely and in a fully automated way, using a purpose-built automated ‘virtual observer’ software and an automated data reduction pipeline. The Taipan survey is deliberately designed to maximise its legacy value by complementing and enhancing current and planned surveys of the southern sky at wavelengths from the optical to the radio; it will become the primary redshift and optical spectroscopic reference catalogue for the local extragalactic Universe in the southern sky for the coming decade.

Degradation of 3-amino-l,2,4-triazole-5-C14 (amitrole-5-C14) in autoclaved, potassium azide, ethylene oxide, and dry-heat sterilized soil was compared with that observed in nonsterile soils by measuring evolved C14O2. Amitrole degradation occurred in azide and ethylene oxide-sterilized and nonsterile soils but not in autoclaved soils. Only slight degradation occurred in autoclaved soil re-inoculated with mixed cultures of soil microorganisms isolated from soil in which amitrole had been rapidly degraded. Addition of EDTA-Na to nonsterile and ethylene oxide sterilized soils reduced amitrole degradation. Addition of organic amendments to amitrole treated soil stimulated microbial activity but reduced amitrole degradation. Addition of specific metallic salts to certain soils increased the rate of amitrole degradation. Amitrole degradation occurred rapidly in several free radical generating chemical systems. These results and additional observations indicate that amitrole degradation, at least in three soils examined, was largely a chemical process, and that microbial involvement was only indirect.

This paper examines the influence of exit separation, exit availability and seating configuration on aircraft evacuation efficiency and evacuation time. The purpose of this analysis is to explore how these parameters influence the 60-foot exit separation requirement found in aircraft certification rules. The analysis makes use of the airEXODUS evacuation model and is based on a typical wide-body aircraft cabin section involving two pairs of Type-A exits located at either end of the section with a maximum permissible loading of 220 passengers located between the exits. The analysis reveals that there is a complex relationship between exit separation and evacuation efficiency. A main finding of this work is that for the cabin section examined, with a maximum passenger load of 220 and under certification conditions, exit separations up to 170ft will result in approximately constant total evacuation times and average personal evacuation times. This practical exit separation threshold is decreased to 114ft if another combination of exits is selected. While other factors must also be considered when determining maximum allowable exit separations, these results suggest it is not possible to mandate a maximum exit separation without taking into consideration exit type, exit availability and aircraft configuration.

Very Large Transport Aircraft (VLTA) pose considerable challenges to designers, operators and certification authorities. Questions concerning seating arrangement, nature and design of recreational space, the number, design and location of internal staircases, the number of cabin crew required and the nature of the cabin crew emergency procedures are just some of the issues that need to be addressed. Other more radical concepts such as blended wing body (BWB) design, involving one or two decks with possibly four or more aisles offer even greater challenges. Can the largest exits currently available cope with passenger flow arising from four or five aisles? Do we need to consider new concepts in exit design? Should the main aisles be made wider to accommodate more passengers? In this paper we demonstrate how computer based evacuation models can be used to investigate these issues through examination of staircase evacuation procedures for VLTA and aisle/exit configuration for BWB cabin layouts.

Cellulose nanocrystals (CNCs) are high-strength sustainable nanomaterials, theincorporation of which to a host polymer matrix can potentially lead tonanocomposites with superior mechanical properties. However, the mismatch insurface energy of CNCs and common structural polymers is a challenge that needsto be overcome to prevent the aggregation of CNCs and ensure the robustintegration of CNCs into a polymer matrix. Herein, we report an approachinvolving the functionalization of CNCs with maleated-anhydride polypropylene(MAPP) through diethylenetriamine (DETA) linkers to significantly enhance thecompatibility between CNCs and polypropylene. Polypropylene/modified CNCnanocomposites displayed 74% and 76% increase in elastic modulus in comparisonto neat polypropylene and polypropylene/untreated CNC nanocomposites,respectively. The tensile strength was also higher for nanocomposites withmodified CNC than neat polypropylene, as well as nanocomposites with untreatedCNCs. The tensile strength at 5.5% strain of polypropylene/modified CNCnanocomposites was 32% and 28% larger that of polypropylene andpolypropylene/untreated CNC nanocomposites, respectively. Finally, suchCNC-based nanocomposites have a lower density than many competitive systemsresulting in opportunities to propagate this environmentally-responsibletechnology to nanocomposites used in additive manufacturing, automotiveapplications, construction materials and consumer products.

We investigate why the Supreme Court grants a smaller percentage of cases at the first conference of each term compared to other conferences. According to received wisdom, Supreme Court law clerks are overly cautious at the beginning of their tenure because they receive only a brief amount of training. Reputational concerns motivate clerks to provide fewer recommendations to grant review in cert. pool memos written over the summer months. Using a random sample of petitions from the Blackmun Archives, we code case characteristics, clerk recommendation, and the Court's decision on cert. Nearest neighbor matching suggests clerks are 36 percent less likely to recommend grants in their early cert. pool memos. Because of this temporal discrepancy, petitions arriving over the summer have a 16 percent worse chance of being granted by the Court. This seasonal variation in access to the Court's docket imposes a legally irrelevant burden on litigants who have little control over the timing of their appeal.

Currently developments in two bodies of literature address the determination of optimum levels of storage. One approach, the use of inventory models, has developed as a generalization of the familiar lot size problem in management science models [9, 17]. The decision unit in these models is the firm or frequently a decentralized management unit or authority [4, 12, 15].

Two community-based density case-control studies were performed to assess risk factors for cholera transmission during inter-peak periods of the ongoing epidemic in two Haitian urban settings, Gonaives and Carrefour. The strongest associations were: close contact with cholera patients (sharing latrines, visiting cholera patients, helping someone with diarrhoea), eating food from street vendors and washing dishes with untreated water. Protective factors were: drinking chlorinated water, receiving prevention messages via television, church or training sessions, and high household socioeconomic level. These findings suggest that, in addition to contaminated water, factors related to direct and indirect inter-human contact play an important role in cholera transmission during inter-peak periods. In order to reduce cholera transmission in Haiti intensive preventive measures such as hygiene promotion and awareness campaigns should be implemented during inter-peak lulls, when prevention activities are typically scaled back.

In this paper we examine the dynamics of an initially stable bubble due to ultrasonic forcing by an acoustic wave. A tissue layer is modelled as a density interface acted upon by surface tension to mimic membrane effects. The effect of a rigid backing to the thin tissue layer is investigated. We are interested in ultrasound contrast agent type bubbles which have immediate biomedical applications such as the delivery of drugs and the instigation of sonoporation. We use the axisymmetric boundary integral technique detailed in Curtiss et al. (J. Comput. Phys., 2013, submitted) to model the interaction between a single bubble and the tissue layer. We have identified a new peeling mechanism whereby the re-expansion of a toroidal bubble can peel away tissue from a rigid backing. We explore the problem over a large range of parameters including tissue layer depth, interfacial tension and ultrasonic forcing.

This paper provides a new explanation for why closed-end bond funds coexist along with otherwise identical open-end bond funds. Closed-end bond funds offer investors the opportunity to leverage their fixed income investment at very low borrowing rates and are attractive to investors for this reason. We find that differences in leverage are reflected in the discount on closed-end bond funds in a manner consistent with the advantage of leverage.