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Contracting delays remain a challenge to the successful initiation of multisite clinical research in the US. The Clinical and Translational Science Awards (CTSA) Contracts Processing Study showed average contract negotiation duration of > 100 days for industry-sponsored or investigator-initiated contracts. Such delays create enormous costs to sponsors and to patients waiting to use new evidence-based treatments. With support from the National Institutes of Health’s National Center for Advancing Translational Sciences, the Accelerated Clinical Trial Agreement (ACTA) was developed by 25 major academic institutions and medical centers engaged in clinical research in collaboration with the University-Industry Demonstration Partnership and with input from pharmaceutical companies. The ACTA also informed the development of subsequent agreements, including the Federal Demonstration Partnership Clinical Trial Subaward Agreement (FDP-CTSA); both ACTA and the FDP-CTSA are largely non-negotiable agreements that represent pre-negotiated compromises in contract terms agreed upon by industry and/or medical center stakeholders. When the involved parties agree to use the CTSA-developed and supported standard agreement templates as a starting point for negotiations, there can be significant time savings for trials. Use of the ACTA resulted in an average savings of 48 days and use of the FDP-CTSA saved an average of 57 days of negotiation duration.
The IntCal family of radiocarbon (14C) calibration curves is based on research spanning more than three decades. The IntCal group have collated the 14C and calendar age data (mostly derived from primary publications with other types of data and meta-data) and, since 2010, made them available for other sorts of analysis through an open-access database. This has ensured transparency in terms of the data used in the construction of the ratified calibration curves. As the IntCal database expands, work is underway to facilitate best practice for new data submissions, make more of the associated metadata available in a structured form, and help those wishing to process the data with programming languages such as R, Python, and MATLAB. The data and metadata are complex because of the range of different types of archives. A restructured interface, based on the “IntChron” open-access data model, includes tools which allow the data to be plotted and compared without the need for export. The intention is to include complementary information which can be used alongside the main 14C series to provide new insights into the global carbon cycle, as well as facilitating access to the data for other research applications. Overall, this work aims to streamline the generation of new calibration curves.
New stalagmites from Qadisha Cave (Lebanon) located at 1720 m above sea level provide a high-resolution and well-dated record for northern Mount Lebanon. The stalagmites grew discontinuously from 9.2 to 5.7 and at 3.5 ka, and they show a tendency to move from a more negative oxygen isotope signal at ~9.1 ka to a more positive signal at ~5.8 ka. Such a trend reflects a change from a wetter to a drier climate at high altitudes. The δ13C signal shows rapid shifts throughout the record and a decreasing trend toward more negative values in the mid-Holocene, suggesting enhanced soil activity. In the short-term trend, Qadisha stalagmites record rapid dry/wet changes on centennial scales, with a tendency to more rapid dry events toward the mid-Holocene. Such changes are characterized by overall good agreement between both geochemical proxies and stalagmite growth and might be affected by the seasonal variations in snow cover. The Qadisha record is in good agreement with other Levantine records, showing more humid conditions from 9 to 7 ka. After 7 ka, a drier climate seems to affect sites at both low- and high-altitude areas. The Qadisha record reflects uniquely mountainous climate characteristics compared with other records, specifically the effect of snow cover and its duration regulating the effective infiltration.
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.
The 4.2 ka event is widely presumed to be a globally widespread aridity event and has been linked to several episodes of societal changes across the globe. Whether this climate event impacted the cultural development in south-central China remains uncertain due to a lack of regional paleorainfall records. We present here stalagmite stable carbon isotope and trace element–based reconstruction of hydroclimatic conditions from south-central China. Our data reveal a sub–millennial scale (~5.6 to 4.3 ka) drying trend in the region followed by a gradual transition to wetter conditions during the 4.2 ka event (4.3–3.9 ka). Together with the existing archaeological evidence, our data suggest that the drier climate before 4.3 ka may have promoted the Shijiahe culture, while the pluvial conditions during the 4.2 ka event may have adversely affected its settlements in low-lying areas. While military conflicts with the Wangwan III culture may have accelerated the collapse of Shijiahe culture, we suggest that the joint effects of climate and the region's topography also played important causal roles in its demise.
The Roca San Miguel (RSM) archaeological site was occupied during Mousterian times. Here we present a geoarchaeological and paleoenvironmental reconstruction of the site. Five stratigraphic units (A to E) formed by different archaeological levels are identified. Three optically stimulated luminescence (OSL) ages show that Unit A dates to between 169.6 ± 9.1 and 151.9 ± 11.1 ka, during the penultimate glacial period (PGP), and contains numerous signs of recurring hearths. Unit B is unexcavated. Unit C dates to between 118.9 ± 11.5 and 103.4 ± 6.9 ka (late Eemian–marine isotope stage (MIS) 5d) and shows an abundance of lithic remains as well as some faunal elements. Unit C is covered by Unit D, which incorporates materials moved downslope, and is dated at 81.2 ± 4.7 ka. These OSL ages concur with U/Th ages (129.3 ± 1.5 and 123.6 ± 0.6 ka) derived from a flowstone covered by both -C and D- post-flowstone units. Finally, Unit E covers the archaeological site, which was partially eroded during MIS2. The robust and well-constrained chronology of the RSM site and surroundings enables the establishment of its evolutionary model from the PGP to the last glacial cycle. The RSM site is the oldest Neanderthal occupation accurately dated in the Pre-Pyrenean region.
Clinical trials continue to face significant challenges in participant recruitment and retention. The Recruitment Innovation Center (RIC), part of the Trial Innovation Network (TIN), has been funded by the National Center for Advancing Translational Sciences of the National Institutes of Health to develop innovative strategies and technologies to enhance participant engagement in all stages of multicenter clinical trials. In collaboration with investigator teams and liaisons at Clinical and Translational Science Award institutions, the RIC is charged with the mission to design, field-test, and refine novel resources in the context of individual clinical trials. These innovations are disseminated via newsletters, publications, a virtual toolbox on the TIN website, and RIC-hosted collaboration webinars. The RIC has designed, implemented, and promised customized recruitment support for 173 studies across many diverse disease areas. This support has incorporated site feasibility assessments, community input sessions, recruitment materials recommendations, social media campaigns, and an array of study-specific suggestions. The RIC’s goal is to evaluate the efficacy of these resources and provide access to all investigating teams, so that more trials can be completed on time, within budget, with diverse participation, and with enough accrual to power statistical analyses and make substantive contributions to the advancement of healthcare.
This study examines the first precisely dated and temporally highly resolved speleothem record from Iberia that reconstructs the Oldest Dryas (OD). The onset of cold conditions in the study area, contemporary with the beginning of Heinrich Stadial 1, is recorded at 18.13 ± 0.08 ka, with a pronounced drop of 6.1‰ in δ13C in 250 years. Henceforth, stadial conditions depict a period of instability in the Atlantic Meridional Overturning Circulation, peaking in freshwater input from iceberg melting during Heinrich Event 1. Anomalies in the δ18O of the stalagmite attributed to such a freshwater event are found from 16.17 to 15.89 ka. Such absolute dates given to the onset of the OD in Iberia and to the main iceberg discharges are reliable anchor points for non-absolute chronologies. Two periods are identified in the OD: OD-a (18.13–16.17 ka) is characterized by wet conditions and a faster growth rate, and OD-b (15.89–14.81 ka) exhibits relative dryness and a slower growth rate. The sudden release of fresh water is considered to be the reason for the disruption of rainfall patterns in eastern Iberia. The present study also highlights the existence of heterogeneous and complex hydrological conditions during the OD in Iberia when both Atlantic and Mediterranean realms are considered.
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.
We describe an ultra-wide-bandwidth, low-frequency receiver recently installed on the Parkes radio telescope. The receiver system provides continuous frequency coverage from 704 to 4032 MHz. For much of the band (
), the system temperature is approximately 22 K and the receiver system remains in a linear regime even in the presence of strong mobile phone transmissions. We discuss the scientific and technical aspects of the new receiver, including its astronomical objectives, as well as the feed, receiver, digitiser, and signal processor design. We describe the pipeline routines that form the archive-ready data products and how those data files can be accessed from the archives. The system performance is quantified, including the system noise and linearity, beam shape, antenna efficiency, polarisation calibration, and timing stability.
A 230Th/U-dated stalagmite from Hulu Cave was analyzed for δ18O, δ13C, and trace elements. A ~10-yr-resolution δ18O record, spanning 51.7–42.6 ka, revealed Dansgaard-Oeschger (DO) events 14 to 11. A similar rapid transition and synchronous timing of the onset of DO 12 is evident between the Greenland and Hulu Cave records, which suggests a common forcing mechanism of DO cycles in the North Atlantic and monsoonal region of Asia. Centennial-scale monsoonal oscillations in the cave δ18O record are indicative of hydroclimatic instability during interstadials. After removing the signals of remote moisture sources, the proportion of moisture from nearby sources is found to be higher during stadials than during interstadials. To explain this, we propose that the movement of the westerly jet is an important control on the balance of nearby and distant moisture sources in East Asia. In addition, the records of δ13C and trace element ratios, which are proxies of local environmental changes, resemble the δ18O record on the scale of DO cycles, as well as on even shorter timescales. This suggests that hydrological processes and biological activity at the cave site respond sensitively to the monsoonal changes.
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.
Glyphosate-resistant (GR) Italian ryegrass is one of the most troublesome weeds in Mississippi row crop production. Fall-applied residual herbicide applications are recommended for control of GR Italian ryegrass. However, carryover of residual herbicides applied in fields for rice production can have a negative impact on rice performance. Field studies were conducted in Stoneville, MS, to determine the effects of fall-applied residual herbicides on rice growth and yield. Herbicide treatments included suggested use rates (1×) of clomazone at 840 g ai ha–1, pyroxasulfone 170 g ai ha–1, S-metolachlor 1,420 g ai ha–1, and trifluralin 1,680 g ai ha–1, and two times (2×) the suggested use rates in the fall before rice seeding. Pooled across application rate, pyroxasulfone, S-metolachlor, and trifluralin injured rice to an extent 28% to 36% greater than clomazone 14 d after emergence (DAE). Rice seedling density and height 14 DAE and rice maturity were negatively affected by all fall-applied herbicides except clomazone. Applications at 2× rates reduced rough rice yields in plots treated with pyroxasulfone, S-metolachlor, and trifluralin compared with clomazone. Pyroxasulfone applied at the 2× rate reduced rough rice yield 22% compared with the 1× rate. Rough rice yield was 90% or greater of the nontreated control in plots treated with either rate of S-metolachlor, and these were comparable with rough rice yields from plots treated with both rates of trifluralin and the 1× rate of pyroxasulfone. Early-season injury and reductions in seedling density and height 14 DAE, would preclude even 1× applications of pyroxasulfone, S-metolachlor, and trifluralin from being viable options for residual herbicide treatments targeting GR Italian ryegrass in the fall before rice seeding. Of the herbicides evaluated, only clomazone should be utilized as a fall-applied residual herbicide treatment targeting GR Italian ryegrass before seeding rice.
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, H0) 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.
New speleothem records from northeastern Iberian caves provide data to explore the climatic patterns during the Holocene. We present δ13C and Mg/Ca from three speleothems from two different caves located in the Iberian Range allowing replication of the climatic signal for several millennia. Through the integration of those stalagmites covering since the Holocene onset to 2 ka, the early Holocene (11.7–8.5 ka) appears as the wettest interval. A marked change towards aridity is observed during the middle Holocene (8.5–4.8 ka) and an increase of humidity afterwards (4.8–2 ka). This three-part pattern, contrasting with other Iberian sequences, seems to be associated with the different role that seasonality has played in the response of different proxies (or records) to changes in water availability. Interpreting our speleothem records as changes in winter-spring precipitation along the Holocene allows reconciling previous data on hydrological variability from the western Mediterranean borderlands.
A stalagmite with high 238U content from Yangkou Cave, China, revealed the evolution of the Asian summer monsoon (ASM) between 49.1 and 59.5 ka, and the δ18O values recorded Dansgaard/Oeschger (D/O) events 13–17. The Yangkou record shows a relatively gradual transition into the D/O 14 and 16 events. The discrepancy between the abrupt and gradual transitions of D/O 14 in the records from northern and southern China, respectively, suggests different responses of the ASM to climate changes in the high northern latitudes. The higher resolution δ18O record and more precise 230Th dating indicate that the timing of D/O 14 and 17 in the Hulu records at 53 and 58 ka should be shifted to 54.3 and 59 ka, respectively. The gradual strengthening of the ASM at the onsets of D/O 16 and 14 in our record is different from the abrupt temperature rise in the northern high latitudes. Some other factors must contribute to this relatively gradual ASM change in southern China, but the actual reason is still unknown.