Multicenter clinical trials are essential for evaluating interventions but often face significant challenges in study design, site coordination, participant recruitment, and regulatory compliance. To address these issues, the National Institutes of Health’s National Center for Advancing Translational Sciences established the Trial Innovation Network (TIN). The TIN offers a scientific consultation process, providing access to clinical trial and disease experts who provide input and recommendations throughout the trial’s duration, at no cost to investigators. This approach aims to improve trial design, accelerate implementation, foster interdisciplinary teamwork, and spur innovations that enhance multicenter trial quality and efficiency. The TIN leverages resources of the Clinical and Translational Science Awards (CTSA) program, complementing local capabilities at the investigator’s institution. The Initial Consultation process focuses on the study’s scientific premise, design, site development, recruitment and retention strategies, funding feasibility, and other support areas. As of 6/1/2024, the TIN has provided 431 Initial Consultations to increase efficiency and accelerate trial implementation by delivering customized support and tailored recommendations. Across a range of clinical trials, the TIN has developed standardized, streamlined, and adaptable processes. We describe these processes, provide operational metrics, and include a set of lessons learned for consideration by other trial support and innovation networks.

Increasing litter size has long been a goal of pig breeders and producers, and may have implications for pig (Sus scrofa domesticus) welfare. This paper reviews the scientific evidence on biological factors affecting sow and piglet welfare in relation to large litter size. It is concluded that, in a number of ways, large litter size is a risk factor for decreased animal welfare in pig production. Increased litter size is associated with increased piglet mortality, which is likely to be associated with significant negative animal welfare impacts. In surviving piglets, many of the causes of mortality can also occur in non-lethal forms that cause suffering. Intense teat competition may increase the likelihood that some piglets do not gain adequate access to milk, causing starvation in the short term and possibly long-term detriments to health. Also, increased litter size leads to more piglets with low birth weight which is associated with a variety of negative long-term effects. Finally, increased production pressure placed on sows bearing large litters may produce health and welfare concerns for the sow. However, possible biological approaches to mitigating health and welfare issues associated with large litters are being implemented. An important mitigation strategy is genetic selection encompassing traits that promote piglet survival, vitality and growth. Sow nutrition and the minimisation of stress during gestation could also contribute to improving outcomes in terms of piglet welfare. Awareness of the possible negative welfare consequences of large litter size in pigs should lead to further active measures being taken to mitigate the mentioned effects.

Background: Eye movements reveal neurodegenerative disease processes due to overlap between oculomotor circuitry and disease-affected areas. Characterizing oculomotor behaviour in context of cognitive function may enhance disease diagnosis and monitoring. We therefore aimed to quantify cognitive impairment in neurodegenerative disease using saccade behaviour and neuropsychology. Methods: The Ontario Neurodegenerative Disease Research Initiative recruited individuals with neurodegenerative disease: one of Alzheimer’s disease, mild cognitive impairment, amyotrophic lateral sclerosis, frontotemporal dementia, Parkinson’s disease, or cerebrovascular disease. Patients (n=450, age 40-87) and healthy controls (n=149, age 42-87) completed a randomly interleaved pro- and anti-saccade task (IPAST) while their eyes were tracked. We explored the relationships of saccade parameters (e.g. task errors, reaction times) to one another and to cognitive domain-specific neuropsychological test scores (e.g. executive function, memory). Results: Task performance worsened with cognitive impairment across multiple diseases. Subsets of saccade parameters were interrelated and also differentially related to neuropsychology-based cognitive domain scores (e.g. antisaccade errors and reaction time associated with executive function). Conclusions: IPAST detects global cognitive impairment across neurodegenerative diseases. Subsets of parameters associate with one another, suggesting disparate underlying circuitry, and with different cognitive domains. This may have implications for use of IPAST as a cognitive screening tool in neurodegenerative disease.

Radiocarbon (14C) ages cannot provide absolutely dated chronologies for archaeological or paleoenvironmental studies directly but must be converted to calendar age equivalents using a calibration curve compensating for fluctuations in atmospheric 14C concentration. Although calibration curves are constructed from independently dated archives, they invariably require revision as new data become available and our understanding of the Earth system improves. In this volume the international 14C calibration curves for both the Northern and Southern Hemispheres, as well as for the ocean surface layer, have been updated to include a wealth of new data and extended to 55,000 cal BP. Based on tree rings, IntCal20 now extends as a fully atmospheric record to ca. 13,900 cal BP. For the older part of the timescale, IntCal20 comprises statistically integrated evidence from floating tree-ring chronologies, lacustrine and marine sediments, speleothems, and corals. We utilized improved evaluation of the timescales and location variable 14C offsets from the atmosphere (reservoir age, dead carbon fraction) for each dataset. New statistical methods have refined the structure of the calibration curves while maintaining a robust treatment of uncertainties in the 14C ages, the calendar ages and other corrections. The inclusion of modeled marine reservoir ages derived from a three-dimensional ocean circulation model has allowed us to apply more appropriate reservoir corrections to the marine 14C data rather than the previous use of constant regional offsets from the atmosphere. Here we provide an overview of the new and revised datasets and the associated methods used for the construction of the IntCal20 curve and explore potential regional offsets for tree-ring data. We discuss the main differences with respect to the previous calibration curve, IntCal13, and some of the implications for archaeology and geosciences ranging from the recent past to the time of the extinction of the Neanderthals.

Research was conducted from 2013 to 2015 across three sites in Mississippi to evaluate corn response to sublethal paraquat or fomesafen (105 and 35 g ai ha−1, respectively) applied PRE, or to corn at the V1, V3, V5, V7, or V9 growth stages. Fomesafen injury to corn at three d after treatment (DAT) ranged from 0% to 38%, and declined over time. Compared with the nontreated control (NTC), corn height 14 DAT was reduced approximately 15% due to fomesafen exposure at V5 or V7. Exposure at V1 or V7 resulted in 1,220 and 1,110 kg ha−1 yield losses, respectively, compared with the NTC, but yield losses were not observed at any other growth stage. Fomesafen exposure at any growth stage did not affect corn ear length or number of kernel rows relative to the NTC. Paraquat injury to corn ranged from 26% to 65%, depending on growth stage and evaluation interval. Corn exposure to paraquat at V3 or V5 consistently caused greater injury across evaluation intervals, compared with other growth stages. POST timings of paraquat exposure resulted in corn height reductions of 13% to 50%, except at V7, which was most likely due to rapid internode elongation at that stage. Likewise, yield loss occurred after all exposure times of paraquat except PRE, compared with the NTC. Corn yield was reduced 1,740 to 5,120 kg ha−1 compared with the NTC, generally worsening as exposure time was delayed. Paraquat exposure did not reduce corn ear length, compared with the NTC, at any growth stage. However, paraquat exposure at V3 or V5 was associated with reduction of kernel rows by 1.1 and 1.7, respectively, relative to the NTC. Paraquat and fomesafen applications near corn should be avoided if conditions are conducive for off-target movement, because significant injury and yield loss can result.

Understanding control of glyphosate-resistant (GR) Palmer amaranth with multiple herbicide sites of action, including synthetic auxins, is crucial for growers to minimize GR Palmer amaranth interference with crops. Field studies in 2013 and 2014 and a greenhouse study in 2014 were conducted in Stoneville, MS, to evaluate POST control of GR Palmer amaranth with 2,4-D alone and in mixtures with glyphosate and/or glufosinate. In the greenhouse study, control of 5- and 10-cm GR Palmer amaranth was 87% with 2,4-D at 0.84 kg ae ha−1. Dry weight reduction of GR Palmer amaranth was ≥81% with 2,4-D at 0.84 kg ha−1. In field studies, mixtures of glufosinate at 0.59 kg ai ha−1 and 2,4-D at 0.56 or 1.12 kg ae ha−1 controlled 5- to 10-cm GR Palmer amaranth 87% at 28 d after treatment (DAT). Averaged across glyphosate treatments, glufosinate applied alone applied to 5- to 10-cm GR Palmer amaranth reduced dry weight at 28 DAT to 20 g m−2 from 82 g m−2 and was comparable with that following 2,4-D applied alone at 1.12 kg ae ha−1 and mixtures of glufosinate plus 2,4-D at 0.56 and 1.12 kg ae ha−1. Mixtures of 2,4-D plus glufosinate provided ≥92% control of 15- to 20-cm GR Palmer amaranth at 28 DAT. When applied to 15- to 20-cm plants, mixtures of 2,4-D plus glufosinate reduced GR Palmer amaranth density to ≤5 plants m−2 compared with 65 plants m−2 where no 2,4-D or glufosinate was applied. Glufosinate and 2,4-D are viable control options for 5- to 10-cm or 15- to 20-cm GR Palmer amaranth. However, 2,4-D did not improve GR Palmer amaranth control when added to any herbicide mixture except glyphosate and glufosinate applied to 15- to 20-cm plants at the 28 DAT evaluation.

Little is known about terrestrial climate dynamics in the Levant during the penultimate interglacial-glacial period. To decipher the palaeoclimatic history of the Marine Oxygen Isotope Stage (MIS) 6 glacial period, a well-dated stalagmite (~194 to ~154 ka) from Kanaan Cave on the Mediterranean coast in Lebanon was analyzed for its petrography, growth history, and stable isotope geochemistry. A resolved climate record has been recovered from this precisely U–Th dated speleothem, spanning the late MIS 7 and early MIS 6 at low resolution and the mid–MIS 6 at higher resolution. The stalagmite grew discontinuously from ~194 to ~163 ka. More consistent growth and higher growth rates between ~163 and ~154 ka are most probably linked to increased water recharge and thus more humid conditions. More distinct layering in the upper part of the speleothem suggests strong seasonality from ~163 ka to ~154 ka. Short-term oxygen and carbon isotope excursions were found between ~155 and ~163 ka. The inferred Kanaan Cave humid intervals during the mid–MIS 6 follow variations of pollen records in the Mediterranean basins and correlate well with the synthetic Greenland record and East Asian summer monsoon interstadial periods, indicating short warm/wet periods similar to the Dansgaard-Oeschger events during MIS 4–3 in the eastern Mediterranean region.

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.

Pigweeds are among the most abundant and troublesome weed species across Midwest and mid-South soybean production systems because of their prolific growth characteristics and ability to rapidly evolve resistance to several herbicide sites of action. This has renewed interest in diversifying weed management strategies by implementing integrated weed management (IWM) programs to efficiently manage weeds, increase soybean light interception, and increase grain yield. Field studies were conducted across 16 site-years to determine the effectiveness of soybean row width, seeding rate, and herbicide strategy as components of IWM in glufosinate-resistant soybean. Sites were grouped according to optimum adaptation zones for soybean maturity groups (MGs). Across all MG regions, pigweed density and height at the POST herbicide timing, and end-of-season pigweed density, height, and fecundity were reduced in IWM programs using a PRE followed by (fb) POST herbicide strategy. Furthermore, a PRE fb POST herbicide strategy treatment increased soybean cumulative intercepted photosynthetically active radiation (CIPAR) and subsequently, soybean grain yield across all MG regions. Soybean row width and seeding rate manipulation effects were highly variable. Narrow row width (≤ 38 cm) and a high seeding rate (470,000 seeds ha−1) reduced end-of-season height and fecundity variably across MG regions compared with wide row width (≥ 76 cm) and moderate to low (322,000 to 173,000 seeds ha−1) seeding rates. However, narrow row widths and high seeding rates did not reduce pigweed density at the POST herbicide application timing or at soybean harvest. Across all MG regions, soybean CIPAR increased as soybean row width decreased and seeding rate increased; however, row width and seeding rate had variable effects on soybean yield. Furthermore, soybean CIPAR was not associated with end-of-season pigweed growth and fecundity. A PRE fb POST herbicide strategy was a necessary component for an IWM program as it simultaneously managed pigweeds, increased soybean CIPAR, and increased grain yield.

Computer based mathematical models describing the aircraft evacuation process have a vital role to play in the design and development of safer aircraft, the implementation of safer and more rigorous certification criteria, in cabin crew training and post-mortem accident investigation. As the risk of personal injury and the costs involved in performing large-scale evacuation experiments for the next generation ultra high capacity aircraft (UHCA) are expected to be high, the development and use of these evacuation modelling tools may become essential if these aircraft are to prove a viable reality. This paper describes the capabilities and limitations of the airEXODUS evacuation model and some attempts at validation, including its successful application to the prediction of a recent certification trial, prior to the actual trial taking place. Also described is a newly defined performance parameter known as OPS that can be used as a measure of evacuation trial optimality. In addition, sample evacuation simulations in the presence of fire atmospheres are described.

Computer based mathematical models describing the aircraft evacuation process have a vital role to play in aviation safety. However, such models have a heavy dependency on real evacuation data in order to (a) identify the key processes and factors associated with evacuation, (b) quantify variables and parameters associated with the identified factors/processes and finally (c) validate the models. The Fire Safety Engineering Group of the University of Greenwich is undertaking a large data extraction exercise from three major data sources in order to address these issues. This paper describes the extraction and application of data from one of these sources — aviation accident reports. To aid in the storage and analysis of the raw data, a computer database known as AASK (aircraft accident statistics and knowledge) is under development. AASK is being developed to store human observational and anecdotal data contained in accident reports and interview transcripts. AASK comprises four component sub-databases. These consist of the ACCIDENT (crash details), FLIGHT ATTENDANT (observations and actions of the flight attendants), FATALS (details concerning passenger fatalities) and PAX (observations and accounts from individual passengers) databases. AASK currently contains information from 25 survivable aviation accidents covering the period 4 April 1977 to 6 August 1995, involving some 2415 passengers, 2210 survivors, 205 fatalities and accounts from 669 people. In addition to aiding the development of aircraft evacuation models, AASK is also being used to challenge some of the myths which proliferate in the aviation safety industry such as, passenger exit selection during evacuation, nature and frequency of seat jumping, speed of passenger response and group dynamics. AASK can also be used to aid in the development of a more comprehensive approach to conducting post accident interviews, and will eventually be used to store the data directly.

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.

Australia implemented conjugate meningococcal C immunization in 2003 with a single scheduled dose at age 12 months and catch-up for individuals aged 2–19 years. Several countries have recently added one or more booster doses to their programmes to maintain disease control. Australian disease surveillance and vaccine coverage data were used to assess longer term vaccine coverage and impact on invasive serogroup C disease incidence and mortality, and review vaccine failures. Coverage was 93% in 1-year-olds and 70% for catch-up cohorts. In 10 years, after adjusting for changes in diagnostic practices, population invasive serogroup C incidence declined 96% (95% confidence interval 94–98) to 0·4 and 0·6 cases/million in vaccinated and unvaccinated cohorts, respectively. Only three serogroup C deaths occurred in 2010–2012 vs. 68 in 2000–2002. Four (<1/million doses) confirmed vaccine failures were identified in 10 years with no increasing trend. Despite published evidence of waning antibody over time, an ongoing single dose of meningococcal C conjugate vaccine in the second year of life following widespread catch-up has resulted in near elimination of serogroup C disease in all age groups without evidence of vaccine failures in the first decade since introduction. Concurrently, serogroup B incidence declined independently by 55%.