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Aim: For decades, the traditional approach for ligand-binding assays has been to generate two measurements from adjacent wells on the plate. In recent years, scientists have investigated the true benefit of this ‘duplicate analysis’ by looking back at previously generated bioanalytical data with the conclusion that the benefits are negligible. Materials & methods: We demonstrated a method development approach to determine the best number of replicate measurements of an immunogenicity assay. We used an anti-pembrolizumab immunogenicity assay on Gyrolab® to challenge the traditional use of duplicate measurements as we compare it to singlet measurement and show a balanced design for assessing the cut-point in singlet. Results & conclusion: We introduced the concept of calculating the maximum drug tolerance during method development. In this method, we found no practical benefit for duplicate analysis and go further in recommending that singlet analysis should be considered the default for all ligand-binding assays.

Brain capillary integrity is compromised during stroke (Hu 2017). Re-establishing the blood-brain barrier (BBB) post-stroke requires integration of cues from endothelial cells (EC), pericytes (PC), and the extracellular matrix (ECM) to promote vessel remodeling. Two ECM components, Types III and IV Collagen (Col-III and Col-IV, respectively), support vascular growth and maintenance. Here, we utilized a murine embryonic stem cell (ESC) model to investigate how ECM mis-regulation impacts PC and EC collagen synthesis. ECM stability was targeted by administering α,α-dipyridyl (iron chelator) (Ikeda 1992) or Type IV Collagenase to ESC-derived vessels. Our aim was to establish potential mechanistic roles of both Col-III and Col-IV in promoting vascular maintenance. We observed by qRT-PCR that α,α-dipyridyl administration decreased Col3a1 expression, but not Col4a1, in a dose-dependent manner. Analysis by immunostaining and confocal microscopy revealed increases in vascular-associated and interstitial Col-IV with the lower doses of α,α-dipyridyl, but decreases in both Col-IV regions at higher doses. Preliminary imaging data for Col-III, however, suggested decreases in both vascular-associated and interstitial Col-III with lower doses, but increases in these Col-III regions with the highest α,α-dipyridyl dose. In separate experiments, Type IV Collagenase exposure reduced both vascular and interstitial Col-IV despite apparent increases in Col3a1 and Col4a1 gene expression. Taken together, these data suggest that perturbations to the ECM microenvironment surrounding developing blood vessels can elicit various compensatory responses depending on the severity and specificity of the ECM component targeted. These observations, support the idea that dynamic remodeling of the microvessel wall, and specifically the surrounding ECM, may contribute to microvascular instability, as seen in the BBB following acute ischemic stroke.

Subsea HPHT components may be evaluated utilizing a fracture mechanics-based approach as per guidelines in API RP 17TR8 and ASME Section VIII Division 3. Typically, the assessment is performed based on methods described in API 579-1/ASME FFS-1 and BS7910. The analysis is performed to determine critical flaw sizes and estimate the fatigue life of a growing crack as a means of establishing inspection intervals for the equipment. In most cases, the assessment is based on a linear elastic fracture mechanics approach. The effect of plasticity is generally included via the use of a failure assessment diagram (FAD); however, even with this approach the effect of plastic strain around the crack is not explicitly considered. The assessment standards do not provide clear guidance for cases involving a crack which is located within a region of large-scale plastic strain. For these cases, API 579, Annex 9G.5 recommends utilizing a driving force method whereby the J-integral is directly evaluated from an elastic-plastic finite element model. This paper presents such an approach. A simplified representative geometry is considered for this study. A region of a stress concentration, such as is typically encountered near an internal radius is considered. Such a region can potentially show localized plasticity. J-integral is calculated by explicitly modeling a series of cracks of increasing depth through this zone of plasticity and the results are compared to the different methodologies described in API 579-1/ASME FFS-1 and BS7910. Cracks are modeled both completely and partially enveloped within the plastic zone. Results are summarized and compared, highlighting the key differences between different analysis approaches with the aim of identifying the most conservative assessment method for different crack sizes. Additionally, the effect of large-scale plasticity on the crack driving force is determined relative to similar conditions without plasticity. The results indicate that for cracks lying within the regions of localized plasticity, using an API579 Level 2 approach coupled with extracting elastic-plastic through wall stresses from an uncracked geometry may result in significant under prediction of the driving force. Conversely, extracting linear elastic stresses from an uncracked geometry may significantly over predict the driving force and may prove too conservative for determining acceptable crack sizes. This paper presents a comprehensive comparison of different analysis approaches used for evaluating cracks in subsea equipment. The results indicate that, for HPHT equipment with increased safety implications, a detailed elastic plastic fracture mechanics evaluation of the cracked geometry should be performed for cases in which localized plasticity is expected to occur.

Fracture mechanics assessments for pressure vessels are performed to determine critical flaw sizes and/or estimate the fatigue life of a growing crack as a means of establishing inspection intervals for the equipment. In most cases the evaluation is performed based on methods described in API 579-1/ASME FFS-1 and BS7910. The approaches described in these standards are mostly based on a linear elastic fracture mechanics approach. Even though plasticity can be accounted for by using a failure assessment diagram (FAD); however, even with this approach the effect of plastic strain around the crack is not explicitly considered. This paper presents an approach as per API 579, Annex 9G.5 which recommends utilizing a driving force method whereby the J-integral is directly evaluated from an elastic-plastic finite element model. The main goal is to study differences between the FAD approach against the elastic-plastic J-integral approach wherein the crack is modeled explicitly. Simplified representative geometries are considered for this study. Two scenarios for the plastic zone are considered a) crack present during initial loading with no residual plastic strain and b) crack in a residual stress zone. Different crack sizes are considered for this comparison study ranging from small cracks completely embedded within the plastic region and larger cracks with partial embedment. The paper presents comparison studies which highlight the key differences between different analysis approaches with the aim of identifying the most conservative assessment method for different crack geometries.

Diabetic retinopathy is a potentially blinding eye disease that threatens the vision of a ninth of diabetic patients. Progression of the disease has long been attributed to an initial dropout of pericytes that enwrap the retinal microvasculature. Revealed through retinal vascular digests, a subsequent increase in basement membrane bridges is observed. Using cell-specific markers, we demonstrate that pericytes rather than endothelial cells colocalize with these bridges. We show that the density of bridges transiently increases with elevation of Ang-2, PDGF-BB, and blood sugar, is rapidly reversed on a time scale of days, and often associated with a pericyte cell body located off-vessel. Cell-specific knockout of KLF4 in pericytes fully replicates this phenotype. In vivo imaging of limbal vessels demonstrates pericyte migration off-vessel, with rapid pericyte filopodial-like process formation between adjacent vessels. Accounting for off-vessel and on-vessel pericytes, we observe no pericyte loss relative to non-diabetic control retina. These findings reveal the possibility that pericyte perturbations in location and process formation may play a role in the development of pathological vascular remodeling in diabetic retinopathy.

For biosimilar drug development programs, it is essential to demonstrate that there are no clinically significant differences between the proposed biosimilar therapeutic (biosimilar) and its reference product (originator). Based on a stepwise comprehensive comparability exercise, the biosimilar must demonstrate similarity to the originator in physicochemical characteristics, biological activity, pharmacokinetics, efficacy, and safety, including immunogenicity. The goal of the immunogenicity assessment is to evaluate potential differences between the proposed biosimilar product and the originator product in the incidence and severity of human immune responses. Establishing that there are no clinically meaningful differences in the immune response between the products is a key element in the demonstration of biosimilarity. An issue of practical, regulatory, and financial importance is to establish whether a two-assay (based on the biosimilar and originator respectively) or a one-assay approach (based on the biosimilar) is optimal for the comparative immunogenicity assessment. This paper recommends the use of a single, biosimilar-based assay for assessing immunogenic similarity in support of biosimilar drug development. The development and validation of an ADA assay used for a biosimilar program should include all the assessments recommended for an innovator program (10-16, 29). In addition, specific parameters also need to be evaluated, to gain confidence that the assay can detect antibodies against both the biosimilar and the originator. Specifically, the biosimilar and the originator should be compared in antigenic equivalence, to assess the ability of the biosimilar and the originator to bind in a similar manner to the positive control(s), as well as in the confirmatory assay and drug tolerance experiments. Practical guidance for the development and validation of anti-drug antibody (ADA) assays to assess immunogenicity of a biosimilar in comparison to the originator, using the one-assay approach, are described herein.

Marine Isotope Stage 11 (MIS 11) from ∼424,000 to 374,000 yrs ago included one of the longest and warmest interglacials of the last 800,000 yrs, and is a potential analogue for the Holocene due to the similarity of Earth's orbital configuration at this time. The question of how the El Nino–Southern Oscillation (ENSO) responds to warmer background climates remains unanswered and is critical to understand how the ENSO system will evolve under the influence of anthropogenic warming. In this study, we present a 35 yr-long, high-resolution record of MIS 11 climate variability in the Western Pacific Warm Pool (WPWP) based on coupled measurements of skeletal Mg/Ca and δ18O in giant Tridacna gigas clams from Huon Peninsula, Papua New Guinea. The δ18O of modern T. gigas from Huon Peninsula faithfully records sea surface temperature, salinity/rainfall and regional ENSO variability. The geochemical integrity of the MIS 11 T. gigas for recording paleo-ENSO events was established through trace element screening, detailed petrography and SEM analysis. The fossil T. gigas δ18O record indicates that ENSO was operating during a 35-yr window in MIS 11, but with fewer events of shorter duration compared to those experienced during the last 100 yrs. The suppressed ENSO variability in the MIS 11 T. gigas record corresponds with a reduction in the amplitude of the average annual cycle in δ18O values. Distinctive changes in local insolation seasonality, and T. gigas δ18O, brought about by changes in Earth's orbit, provide an additional geochronological constraint on the timing of reef growth at Huon Peninsula to around 402 ka during the MIS 11.3 sub-stage (∼424–395 ka).

Sediment-routing systems continuously transfer information and mass from eroding source areas to depositional sinks. Understanding how these systems alter environmental signals is critical when it comes to inferring source-area properties from the sedimentary record. We measure cosmogenic 10Be and 26Al along three large sediment-routing systems (~ 100,000 km2) in central Australia with the aim of tracking downstream variations in 26Al/10Be inventories and to identify the factors responsible. By comparing 56 new cosmogenic 10Be and 26Al measurements in stream sediments with matching data (n = 55) from source areas, we show that 26Al/10Be inventories in hillslope bedrock and soils set the benchmark for relative downstream modifications. Lithology is the primary determinant of erosion-rate variations in source areas and despite sediment mixing over hundreds of kilometres downstream a distinct lithological signal is retained. Postorogenic ranges yield catchment erosion rates of ~ 6–11 m/m.y. and silcrete-dominant areas erode as slow as ~ 0.2 m/m.y. 26Al/10Be inventories in stream-sediments reveal overall downstream-increasing minimum cumulative burial terms up to ~ 1.1 m.y. but more generally ~ 400–800 k.y. The magnitude of the burial signal correlates with increasing sediment cover downstream and reflects assimilation from storages with long exposure histories, such as alluvial fans, desert pavements, alluvial plains, and aeolian dunes. We propose that the tendency for large alluvial rivers to mask their 26Al/10Be source-area signal differs according to geomorphic setting. Signal preservation is favoured by i) high sediment supply rates, ii) high mean runoff, and iii) a thick sedimentary basin pile. Conversely, signal masking prevails in landscapes of i) low sediment supply, ii) discontinuous sediment flux, and iii) juxtaposition of sediment storages with notably different exposure histories.

For biosimilar drug development, it is critical to demonstrate similar physiochemical characteristics, efficacy, and safety of the biosimilar product compared to the reference product. Therefore, pharmacokinetic (PK) and immunogenicity (antidrug antibody, ADA) assays that allow for the demonstration of biosimilarity are critical. Under the auspices of the American Association of Pharmaceutical Scientists (AAPS) Ligand-Binding Assay Bioanalytical Focus Group (LBABFG), a Biosimilars Action Program Committee (APC) was formed in 2011. The goals of this Biosimilars APC were to provide a forum for in-depth discussions on issues surrounding the development and validation of PK and immunogenicity assays in support of biosimilar drug development and to make recommendations thereof. The Biosimilars APC's recommendations for the development and validation of ligand-binding assays (LBAs) to support the PK assessments for biosimilar drug development are presented here. Analytical recommendations for the development and validation of LBAs to support immunogenicity assessments will be the subject of a separate white paper.

Aeolian dust mantle soils are an important element of many landscapes in south-eastern Australia, though the age of these aeolian deposits has not been radiometrically determined. At Fowlers Gap in western New South Wales, surface cobbles of silcrete and quartz overlie a stone-free, aeolian dust mantle soil, which has a thickness of about 1.6 m. The clay-rich aeolian dust deposit in turn lies upon a buried silcrete and quartz stone layer. Modelling in-situ cosmogenic 26 Al and 10 Be concentrations measured in both the surface quartz stones and in the buried quartz layer of rocks, reveals that each has experienced a complex exposure-burial history. Due to the absence of quartz stones or sand at intermediate depths, our cosmogenic 26 Al and 10 Be modelling was not able to determine a definitive mechanism of stone pavement formation and stone burial. Various scenarios of stone formation, transport, burial and exhumation were tested that constrain the age of the deposit to range from 0.9 ± 0.2 Ma to 1.8 ± 0.2 Ma, based largely on different assumptions taken for the time-dependency of the net sedimentation rate. This corresponds with the initiation of the Simpson Desert dune fields and the deflation of lakes in central Australia, which probably responded to the shift to longer-wavelength, larger-amplitude Quaternary glacial cycles at around 1 Ma. Sensitivity analyses were carried out to identify those parameters which better constrained model outputs. Within model errors, which largely are the result of analytical errors in measured 26 Al and 10 Be concentrations, all three competing theories of colluvial wash, upward displacement of stones, and cumulic pedogenesis are possible mechanisms for the formation of the surface stone pavement.

Since their inception, cosmogenic nuclide methods have enhanced our understanding of Earth’s surface processes by providing a basis for directly determining surface exposure times and erosion rates of landscape elements. The ability to measure exposure ages up to several million years and erosion rates as low as a decimetre per million years means that the method is particularly useful for environments where landscapes change very slowly, such as deserts in tectonically stable regions. In this paper, we review cosmogenic nuclide studies of various aspects of desert landscapes, including regional to continental-scale landscape evolution in arid–semiarid Australia and the hyper-arid Namib, Atacama and Negev Deserts, together with mechanisms and timescales of formation of desert pavements and dune fields that have been difficult to be evaluated by other methods. The timescales revealed by these studies range beyond the Quaternary into the Miocene, and provide links between desert landscapes and late Cenozoic climate changes.

We compare monthly resolved oxygen isotope records derived from a giant bivalve shell, Tridacna gigas and massive Parkes corals collected along the northern coast of Papua New Guinea. This intercomparison study demonstrates that delta O-18 profiles obtained from these different aragonite-secreting organisms collected from within a 30 km range are correlated in great detail and record the timing and amplitude of seasonal and interannual (ENSO-related) variations in sea surface temperature (SST) and water isotopic composition which is closely related to rainfall. Furthermore, the T. gigas record is shown to be close to isotopic equilibrium with the local sea-water, in contrast to the corals which are approximately - 4 parts per thousand offset. These results reveal that living and fossil T. gigas clam shells have the potential to yield reliable records of past changes in seasonality and ENSO variability, as well as mean climate conditions. In particular, since the non-porous shells are generally more resistant to diagenesis than coral skeletons, they may provide robust estimates of past tropical climate for periods and locations where unaltered corals are absent. Crown Copyright (C) 2011 Published by Elsevier B.V. All rights reserved.

In February 2007, a single stage AMS from the National Electrostatics Corporation (NEC) was installed at the Research School of Earth Sciences at the Australian National University. This instrument is equipped with a gas/graphite hybrid ion source allowing direct analysis of CO 2 as well as traditional graphite targets. The instrument was funded by an Australian Research Council grant and by a consortium of eight universities plus the CSIRO Division of Land and Water. Its purpose is to support integrated environmental and archaeological research and access is open to the wider research community. In the first year ∼1500 samples have been analysed. A precision of ∼3‰ is routinely observed. The background for processed graphite (coal, calcite, Carrera marble) is better than 45,000 years. This paper summarizes the first year of measurements.

We report erosion rates determined from in situ produced cosmogenic 10 Be across a spectrum of Australian climatic zones, from the soil-mantled SE Australian escarpment through semi-arid bedrock ranges of southern and central Australia, to soil-mantled ridges at a monsoonal tropical site near the Arnhem escarpment. Climate has a major effect on the balance between erosion and transport and also on erosion rate: the highest rates, averaging 35 m Ma 21 , were from soil-mantled, transport-limited spurs in the humid temperate region around the base of the SE escarpment; the lowest, averaging about 1.5 m Ma 21 , were from the steep, weathering- limited, rocky slopes of Kings Canyon and Mt Sonder in semi-arid central Australia. Between these extremes, other factors come into play including rock-type, slope, and recruitment of vegetation. We measured intermediate average erosion rates from rocky slopes in the semi-arid Flinders and MacDonnell ranges, and from soil-mantled sites at both semi-arid Tyler Pass in central Australia and the tropical monsoonal site. At soil-mantled sites in both the SE and tropical north, soil production generally declines exponentially with increasing soil thickness, although at the tropical site this relationship does not persist under thin soil thicknesses and the relationship here is 'humped'. Results from Tyler Pass show uniform soil thicknesses and soil production rates of about 6.5 m Ma 21 , supporting a longstanding hypothesis that equilibrium, soil-mantled hillslopes erode in concert with stream incision and form convex-up spurs of constant curvature. Moreover, weathering-limited slopes and spurs also occur in the same region: the average erosion rate for rocky sandstone spurs at Glen Helen is 7 m Ma 21 , similar to the Tyler Pass soil-mantled slopes, whereas the average rate for high, quartzite spurs at Mount Sonder is 1.8 m Ma 21 . The extremely low rates measured across bedrock-dominated landscapes suggest that the ridge- valley topography observed today is likely to have been shaped as long ago as the Late Miocene. These rates and processes quantified across different, undisturbed landscapes provide critical data for landscape evolution models.

This study investigates the environmental and biological controls on trace element partitioning and stable isotope composition of modern giant long-lived bivalves (Tridacna gigas) with the aim to use these archives for paleoclimatic reconstructions. Firstly, the intra-shell variability is studied by measuring time equivalent profiles in the different shell layers characterised by different growth rates. Secondly, the inter-site variability is studied by comparing profiles derived from three modern specimens collected in sites across the Indo-Pacific region characterised by different ranges of temperature and productivity. These results show that δ18O profiles are highly reproducible across the shell regardless of significantly different growth rates. Shell δ18O is primarily controlled by water δ18O and temperature. Comparison of intra shell Mg/Ca profiles shows a clear and systematic partitioning where inner layer Mg/Ca values are a least 2–3 times higher than outer layer and hinge areas. Inner layer Mg/Ca shows seasonal oscillations but superimposed on an ontogenetic trend with increasing values and increasing amplitude Mg/Ca oscillations with age. The Sr/Ca profiles do not show clear reproducible seasonal trends in the different shell zones. It is concluded that Mg/Ca and Sr/Ca profiles appear to reflect a combination of biological and environmental controls that will need to be disentangled before using these proxies in paleoclimatic studies. Finally, intra shell Ba/Ca profiles are reproducible in great detail for all modern specimens studied. Inter-site comparison shows that the amplitude and the timing of the Ba/Ca peaks appear to reflect the timing and the amplitude of the chlorophyll peaks associated with phytoplankton blooms at each locality making this tracer a potential paleoproductivity indicator.

Differences in chemical weathering extent and character are expected to exist across topographic escarpments due to spatial gradients of climatic and/or tectonic forcing. The passive margin escarpment of south-eastern Australia has a debated but generally accepted model of propagation in which it retreated (within 40 Ma) to near its current position following rifting between Australia and New Zealand 85–100 Ma before present. We focus on this escarpment to quantify chemical weathering rates and processes and how they may provide insight into scarp evolution and retreat. We compare chemical weathering extents and rates above and below the escarpment using a mass balance approach coupling major and trace element analyses with previous measurements of denudation rates using cosmogenic nuclides (10Be and 26Al). We find a slight gradient in saprolite chemical weathering rate as a percentage of total weathering rate across the escarpment. The lowlands area, encompassing the region extending from the base of the escarpment to the coast, experiences a greater extent of chemical weathering than the highland region above the escarpment. Percents of denudation attributable to saprolite weathering average 57 ± 6% and 47 ± 7% at low and high sites respectively. Furthermore, the chemical index of alteration (CIA), a ratio of immobile to mobile oxides in granitic material that increases with weathering extent, have corresponding average values of 73·7 ± 3·9 and 65·5 ± 3·4, indicating lower extents of weathering above the escarpment. Finally, we quantify variations in the rates and extent of chemical weathering at the hillslope scale across the escarpment to suggest new insight into how climate differences and hillslope topography help drive landscape evolution, potentially overprinting longer term tectonic forcing. Copyright © 2009 John Wiley & Sons, Ltd.

Development of continental aridity has been linked to late Cenozoic global cooling, but the evidence is indirect, based on terrestrial loess deposits and eolian silt in marine sediments, whereas direct dating of the inception of arid landforms has been frustrated by a lack of suitable methods. Here we report the first age determination of a major arid-zone dune field, based on cosmogenic 10 Be and 26 Al measurements of drill cores from dunes in the Simpson Desert, central Australia. Results show that the dune field began to form ca. 1 Ma, whereas dating using quartz optically stimulated luminescence indicates episodic dune building during late Quaternary ice ages. Less intense desertification began earlier; the previous cosmogenic exposure dating showed that neighboring stony deserts began to form at the onset of Quaternary ice ages 2–4 Ma. Aridity deepened and the dune field formed when ice age cycles increased their amplitude and switched their periods from 40 k.y. to 100 k.y. ca. 1 Ma.

The sustainability of soil is a major issue for society. In principle, the evolution of soil resources can be constrained by comparing the rates of soil erosion and production. Cosmogenic isotopes provide one measurement of soil erosion rates. They can also be used to estimate soil production rates but only if erosion is assumed to be balanced by production. This implies that the evolution of soil resources (thinning, thickening or constant) since soil thickness is assumed to be constant with time. Here we utilise an independent method to estimate soil production rates, using uranium-series (U-series) isotopes. The study of a site in temperate Australia undisturbed by human activity shows that soil production rates inferred from U-series isotopes are similar to erosion rates derived from beryllium-10 (10Be) measurements, implying that at this site there is no net accumulation or loss of soil. Saprolite production rates (the migration rate of the weathering front into the bedrock) are also similar to erosion rates so the thickness of the entire weathering profile is effectively in steady-state. This study demonstrates that the combination of U-series and cosmogenic isotopes can be used to quantitatively assess soil evolution and the development of weathering profiles. Preliminary observations suggest that the rate of bedrock weathering (i.e. saprolite production) in temperate Australia is of the same order of magnitude as that inferred for laterites in tropical climates. This may suggest that, for thick weathering profiles, although the extent of weathering strongly differs between temperate and tropical climates, the migration of the weathering front into the bedrock occurs at a relatively uniform rate regardless of present-day climatic conditions.

Estimates of regional erosion and sediment mixing from different sources in the Yangtse River system are presented, based on sand samples collected from major tributaries and the trunk stream, at 23 sites between western Sichuan and the Yangtse Delta. Mixing is estimated from concentrations of Mg, Ca, Sr, Ti, Mn and Fe, which are substantially higher in sand from major tributaries in the western Yangtse River catchment than from tributaries in the eastern catchment. Intermediate concentrations occur in sand from the Yangtse Delta, both for modern samples from the surface and for early Holocene samples from drill holes. Mixing ratios indicate that 35 ± 5% of sand in the delta came from eastern sources. A similar result was obtained using cosmogenic 10Be in quartz grains as a tracer of mixing. Regional erosion rate estimated from 10Be in sand grains from high mountain catchments of the western Yangtse River are mostly similar to rates based on sediment gauging but are sometimes higher, and range to over 700 m Ma− 1, while 10Be measured at upper Yangtse River tributaries on the northeast Tibetan plateau gave rates of 20–30 m Ma− 1. For the eastern catchments, 10Be measurements from quartz sand and sediment gauging both gave rates of 30–70 m Ma− 1. Eroding at this rate, the eastern catchments could not supply more than 20% of the sediment in the delta, in contrast with 35% estimated from geochemical fingerprints. The relative input from eastern sources may have been higher in Late Pleistocene times, under a different climatic regime, and reworking of Pleistocene deposits may still be in progress.

Since the end of the post-glacial sea level rise 6800 years ago, progradation of river mouths into estuaries has been a global phenomenon. The responses of upstream alluvial river reaches to this progradation have received little attention. Here, the links between river mouth progradation and Holocene valley aggradation are examined for the Macdonald and Tuross Rivers in south-eastern Australia. Optical and radiocarbon dating of floodplain sediments indicates that since the mid-Holocene sea level highstand 6800 years ago vertical floodplain aggradation along the two valleys has generally been consistent with the rate at which each river prograded into its estuary. This link between river mouth progradation and alluvial aggradation drove floodplain aggradation for many tens of kilometres upstream of the estuarine limits. Both rivers have abandoned their main Holocene floodplains over the last 2000 years and their channels have contracted. A regional shift to smaller floods is inferred to be responsible for this change, though a greater relative sea level fall experienced by the Macdonald River since the mid-Holocene sea level highstand appears to have been an additional influence upon floodplain evolution in this valley. Copyright © 2006 John Wiley & Sons, Ltd.

Long-distance human migration across the Pacific Ocean occurred during the late Holocene and originated almost entirely in the west. As prevailing tradewinds blow from the east, the mechanisms of prehistoric seafaring have been debated since the sixteenth century. Inadequacies in propositions of accidental or opportunistic drifting on occasional westerlies were exposed by early computer simulation. Experimental voyaging in large, fast, weatherly (windward-sailing) double-canoes, together with computer simulation incorporating canoe performance data and modern, averaged, wind conditions, has supported the traditional notion of intentional passage-making in a widely accepted hypothesis of upwind migration by strategic voyaging. The critical assumption that maritime technology and sailing conditions were effectively the same prehistorically as in the historical and modern records is, however, open to question. We propose here that maritime technology during the late-Holocene migrations did not permit windward sailing, and show that the episodic pattern of initial island colonization, which is disclosed in recent archaeological data, matches periods of reversal in wind direction toward westerlies, as inferred from the millennial-scale history of ENSO (El Niño-Southern Oscillation).

The capabilities and potential applications of in situ dating of Quaternary materials using laser ablation-MC-ICPMS are explored. 234 U/ 238 U and 230 Th/ 234 U can be measured with precision sufficient for dating at a spatial resolution of 100mm or better in samples that contain as a little as 1 ppm uranium. Moreover, U and Th concentrations and U-series isotope ratios can be continuously profiled to determine changes in age that occur with sample growth (e.g. in speleothems). These capabilities additionally permit the dating of bones, teeth and possibly molluscs, which are subject to post-mortem open-system behaviour of Useries isotopes, and can be employed to elucidate processes of U-series migration during weathering and diagenesis. A drawback of laser ablation-MC-ICPMS is that it cannot in general provide U-series age estimates with the high precision and accuracy of conventional TIMS or solution MC-ICPMS methods. However, sample preparation is straightforward, the amount of sample consumed negligible, and it can be used to rapidly characterise or screen and select samples from which more precise and accurate dates can be obtained using conventional methods. Given further instrumental developments and the establishment of suitable matrix-matched standards for carbonates and other materials, we foresee that laser ablation-MC-ICPMS will play an increasingly important role in Quaternary dating research. r 2005 Published by Elsevier Ltd.

Closely-spaced transects measured by excimer laser ablation inductively-coupled plasma mass spectrometry (ELA-ICPMS) at 5 and 32 μm spatial resolution are used to generate trace element composition maps (Ba, Sr, Mg, U, Na, P and Al) from MND-S1, a previously studied modern stalagmite from southwest Australia ( Treble et al., 2003 : EPSL 216: 141). Rainfall at the site is highly seasonal, and trace elements in MND-S1 show strong seasonal variation. Trace element maps show that Ba, Sr, U and Na concentrations coherently follow annual growth layers identified from Scanning Electron Microscopy (SEM) images. The SEM images also reveal that stalagmite growth did not proceed uniformly: growth layers vary in thickness and locally pinch out. Highly preferential crystal growth, determined by nucleation sites left by the previous year’s growth, may be responsible for this uneven growth layering. Differential crystal growth apparently causes variability of trace element concentrations along each annual layer, although additional disequilibrium processes affect Mg, which is less distinctly banded than Ba, Sr, U and Na. Uneven and discontinuous growth layers influence the number of annual cycles, their wavelengths and seasonal amplitudes measured in any one transect. This has clear implications for studies that use annual trace element cycles as chronological markers, growth rate or seasonality proxies.

We present a record of seasonal and inter-annual oxygen (δO) and carbon (δC) isotope ratios from an 81-year-old stalagmite from Moondyne Cave, southwest Australia. The growth history of stalagmite MND-S1 is known since it grew on a cave boardwalk that was installed in 1911 and removed in 1992. This stalagmite provides an excellent test of speleothem climate proxies because the regional climate is strongly seasonal (wet winter/dry summer) and has experienced a 200 mm (20%) reduction of mean rainfall since the mid-1960s, and a 0.8 °C temperature rise since ∼ 1953. Seasonal variations in calcite δO were measured in situ by high spatial resolution ion microprobe, whilst inter-annual variations of δO and δC were measured by conventional gas-source mass spectrometry. Comparison of the speleothem stable isotopes and instrumental temperature records reveals that δO variations are too large to be driven by temperature alone, and are in the opposite sense. However, daily rainfall δO measurements show that the mean seasonal range in δO of rainfall in southwest Australia is large (2‰) and inversely correlated with rainfall amount. A rainfall driver for the speleothem δO is confirmed by the detection of seasonal shifts of 0.7-1.5‰ in speleothem δ that track rainfall δO, smoothed by storage in the overlying limestone. The seasonal range in speleothem δO is larger than any inter-annual and decadal variation observed in the record. The prominent annual cycles in speleothem δO revealed by ion microprobe analysis indicate that subtle changes in the frequency of intense winter rainfall events, or possibly also moisture sources, could produce significant changes in mean speleothem δO. The ion microprobe results also raise the possibility that the masses of speleothem calcite deposited in winter and summer could vary as a function of the seasonal drip rate and carbonate saturation state of these waters. If this is the case, then small changes in the relative masses of calcite deposited in winter and summer could produce significant shifts in mean δO and δC that have a complex relation to climate. This finding should be generally applicable to the interpretation of long-term trends in speleothem geochemical records for shallow cave sites where seasonal variations in geochemical tracers are relatively large, including most of the sub-tropical monsoon belts and mid to high latitudes with distinct rainfall seasons.

We have used helium-3 nuclear reaction analysis to study the morphology of spin-cast blends of poly(9,-dioctylfluorene) (F8) and poly(9,-dioctylfluorene-alt-benzothiadiazole) as a function of composition, casting solvent, and initial solvent concentration. In blends cast from toluene, a surface segregated layer is observed for a broad range of F8 compositions. The surface excess has a maximum of ?nm at an F8 volume fraction = 0.5, dropping down to ?2?nm for = 0.2 and?0.8. The existence of such surface segregated layers could play an important role in charge transport in optoelectronic devices made from blends of conjugated polymers. Films cast from chloroform show negligible surface segregation. Scanning probe microscopy experiments show that films cast from toluene exhibit significant in-plane structure, in contrast to those cast from chloroform, which show minimal lateral structure.