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Oxygen isotopes (δ18O) are the most commonly utilized speleothem proxy and have provided many foundational records of paleoclimate. Thus, understanding processes affecting speleothem δ18O is crucial. Yet, prior calcite precipitation (PCP), a process driven by local hydrology, is a widely ignored control of speleothem δ18O. Here we investigate the effects of PCP on a stalagmite δ18O record from central Vietnam, spanning 45 - 4 ka. We employ a geochemical model that utilizes speleothem Mg/Ca and cave monitoring data to correct the δ18O record for PCP effects. The resulting record exhibits improved agreement with regional speleothem δ18O records and climate model simulations, suggesting that the corrected record more accurately reflects precipitation δ18O (δ18Op). Without considering PCP, our interpretations of the δ18O record would have been misleading. To avoid misinterpretations of speleothem δ18O, our results emphasize the necessity of considering PCP as a significant driver of speleothem δ18O.

The Asian monsoon region is highly dependent on boreal summer rainfall, which directly impacts the socio-economic stability and welfare of billions of people each year. Precipitation variability over East China has been extensively studied and is known to be characterized by meridional tripole and dipole precipitation structures. In contrast, few studies have focused on precipitation variability over Mainland Southeast Asia (MSEA) and the possible relationship with the variability over East China. Here we focus on how interannual precipitation variability across MSEA during 1983–2017 may be associated with the tripole or dipole patterns using an empirical orthogonal function (EOF) analysis. The first EOF shows a meridional tripole pattern in East China summer precipitation and an in-phase relationship between MSEA and South China precipitation. In contrast, the second EOF shows a meridional dipole pattern in East China precipitation and an out-of-phase relationship between MSEA and South China precipitation. We show that the first EOF mode is a delayed precipitation response to the El Niño-Southern Oscillation (ENSO), while the second EOF mode is a simultaneous precipitation response to the remote influence of the North Atlantic Oscillation (NAO). Therefore, the in-phase or out-of-phase variations in precipitation between MSEA and South China may be used to gauge the relative importance of local Pacific and remote Atlantic influences on Asian monsoon climate.

The generation and transport of mineral dust is strongly related to climate on seasonal, year-to-year, and glacial-interglacial timescales. The modern dust cycle is influenced by soil moisture, which is partly a function of drought duration and severity. The production and transport of dust can therefore be amplified by global and regional droughts, thereby moderating ecosystem vulnerability to disturbance through the influence of dust on nutrient delivery to ecosystems. In this work, we use strontium and neodymium isotopes in combination with trace element concentrations in modern dust samples collected in 2015 to quantify the role of regionally versus globally supplied dust in nutrient delivery to a montane ecosystem. The study sites lie along an elevational transect in the southern Sierra Nevada, USA, with samples spanning the dry seasons of 2014 (Aciego et al., 2017) and 2015 (this study), when the region was experiencing a historic drought. The goal of our research was to quantify the spatial and temporal variability and sensitivity of the dust cycle to short term changes at nutrient-limited sites. We find that, during the dry season of 2015, Asian sources contributed between 10 and 40% of dust to sites located along this elevational transect, and importantly increased in importance during the summer growing season compared to regional dust sources. These changes are likely related to the prolonged drought in Asia in 2015, highlighting both the sensitivity of dust production and transport to drought and the teleconnections of dust transport in terrestrial ecosystems.

Orbital to millennial-scale variations in Asian monsoon speleothem δ18O have been widely interpreted as records of monsoon intensity and/or rainfall amount. To assess the influence of these and other mechanisms on higher-frequency δ18O variability, we utilize simulations from a spectrally nudged isotope-enabled general circulation model coupled with instrumental climate data to investigate the climatic controls on interannual precipitation δ18O (δ18Op) variability at four key cave locations affected by the Asian monsoon: Qunf Cave, Oman; Mawmluh Cave, India; Tham Mai Cave, Laos; and Dongge Cave, China. Comparison with instrumental climate data shows that interannual δ18Op variations are only weakly related to local precipitation amount at the four sites and are instead controlled primarily by large-scale monsoon intensity and upstream precipitation over the tropical Indo-Pacific region, which influence the δ18O of incoming moisture. Spatial correlations with sea surface temperature and precipitation, composite analyses, and time series analyses show that the El Niño-Southern Oscillation (ENSO) also plays a key role in modulating interannual precipitation δ18Op variability in the region, especially in northern India and Southeast Asia, with positive δ18Op anomalies during El Niño years reflecting increased contribution of high δ18O moisture from the nearby Bay of Bengal. Coherent interannual to decadal δ18O variations seen in high-resolution proxy records from across the Asian monsoon region, likely record monsoon intensity and upstream rainout, whereas ENSO related variability is likely to be strongest in records from northern India and Southeast Asia, with the largest anomalies expected when weak monsoons and El Niño occur together.

Extreme precipitation events, commonly associated with “Atmospheric Rivers,” are projected to increase in frequency and severity in western North America; however, the intensity and landfall position are difficult to forecast accurately. As the isotopic signature of precipitation has been widely utilized as a tracer of the hydrologic cycle and could potentially provide information about key physical processes, we utilize both climate and precipitation isotope data to investigate these events in California from 2001 to 2011. Although individual events have extreme isotopic signatures linked to associated circulation anomalies, the composite across all events unexpectedly resembles the weighted mean for the entire study period, reflecting diverse moisture trajectories and associated teleconnection phases. We document that 90% of events reaching this location occurred during the negative Arctic Oscillation, suggesting a possible link with higher-latitude warming. We also utilize precipitation data of extreme precipitation events across the entire western U.S. to investigate the relationships between key tropical and Arctic climate modes known to influence precipitation in this region. Results indicate that the wettest conditions occur when the negative Arctic Oscillation, negative Pacific/North American pattern, and positive Southern Oscillation are in sync and that precipitation has increased in the southwestern U.S. and decreased in the northwestern U.S. relative to this phase combination’s 1979-2011 climatology. Furthermore, the type of El Niño-Southern Oscillation event, Central Pacific or Eastern Pacific, influences the occurrence, landfall location, and isotopic composition of precipitation.

Several recent studies have used records of the radiocarbon (14C) bomb peak in speleothems to inversely model the soil a14CO2 and the age distribution of soil organic material (SOM) above caves, in part to investigate the potential of speleothems as sensitive records of past SOM dynamics. The results of these modeling studies have suggested that soil CO2 at karst sites is derived primarily from the decomposition of SOM with turnover times on the order of decades to centuries. This result is in stark contrast with observations of soil a14CO2 at non-karst sites, which indicate that soil CO2 is derived primarily from root respiration and decomposition of SOM with much shorter turnover times. This discrepancy suggests that SOM in karst settings may have a very different age distribution than sites that have been studied previously and/or that soil CO2 is not the main source of speleothem carbon. To help resolve this discrepancy, we present an improved inverse model which we use to estimate the age of CO2 above several caves. We also present results from a detailed case study of soil carbon dynamics at Heshang Cave, China. This work demonstrates that SOM in karst sites may be much older than SOM in non-karst soils that have been studied previously, but that CO2 produced in the shallow soil zone is unlikely to be the main source of speleothem carbon. A review of the literature suggests that the most likely explanation for the aforementioned discrepancy is that decomposition of down-washed SOM in the vadose zone is the dominant source of speleothem carbon.

East Asian summer monsoon (EASM) rainfall impacts the world’s most populous regions. Accurate EASM rainfall prediction necessitates robust paleoclimate reconstructions from proxy data and quantitative linkage to modern climatic conditions. Many precisely dated oxygen isotope records from Chinese stalagmites have been interpreted as directly reflecting past EASM rainfall amount variability, but recent research suggests that such records instead integrate multiple hydroclimatic processes. Using a Lagrangian precipitation moisture source diagnostic, we demonstrate that EASM rainfall is primarily derived from the Indian Ocean. Conversely, Pacific Ocean moisture export peaks during winter, and the moisture uptake area does not differ significantly between summer and winter and is thus a minor contributor to monsoonal precipitation. Our results are substantiated by an accurate reproduction of summer and winter spatial rainfall distributions across China. We also correlate modern EASM rainfall oxygen isotope ratios with instrumental rainfall amount and our moisture source data. This analysis reveals that the strength of the source effect is geographically variable, and differences in atmospheric moisture transport may significantly impact the isotopic signature of EASM rainfall at the Hulu, Dongge, and Wanxiang Cave sites. These results improve our ability to isolate the rainfall amount signal in paleomonsoon reconstructions and indicate that precipitation across central and eastern China will directly respond to variability in Indian Ocean moisture supply.

Recently, it has been shown that U-Th dated speleothems may provide a valuable archive of atmospheric radiocarbon (14C), but the reliability of these records is dependent upon the stability of the dead carbon proportion (DCP) derived from the soil and bedrock. In order to assess climatic influences on speleothem DCP, we have investigated DCP variability over the Holocene interval where atmospheric 14C is well known based on dendrochronologically dated tree rings by conducting 14C measurements on a U-Th dated stalagmite (HS4) from Heshang Cave, Hubei Province, China (30°27 'N, 110°25 'E; 294 m) spanning 0.5-9.6 ka. We investigated climatic controls on DCP, and found that DCP in HS4 has an average value over the Holocene of 10.3 ± 1.5%, with an average age offset from atmospheric radiocarbon of 875 ± 130 years, and displays a response to both precipitation increases and decreases. HS4 DCP increases during the wetter mid-Holocene interval (~5.5-7.1 ka), likely reflecting a shift to more closed-system dissolution in response to increased soil moisture. DCP decreases during the 8.2 ka event, a time period of dry conditions at Heshang Cave, though the lower amplitude of this shift indicates that DCP may be less sensitive to dry events. Speleothems are potentially valuable archives of atmospheric radiocarbon, especially in older portions of the 14C calibration curve where knowledge of atmospheric 14C is limited, however minor climatic influences on DCP could introduce uncertainties of several hundred years to calibrated ages. © 2014 Elsevier B.V.

© 2014 University of Washington. In North America, terrestrial records of biodiversity and climate change that span Marine Oxygen Isotope Stage (MIS) 5 are rare. Where found, they provide insight into how the coupling of the ocean-atmosphere system is manifested in biotic and environmental records and how the biosphere responds to climate change. In 2010-2011, construction at Ziegler Reservoir near Snowmass Village, Colorado (USA) revealed a nearly continuous, lacustrine/wetland sedimentary sequence that preserved evidence of past plant communities between ~. 140 and 55. ka, including all of MIS 5. At an elevation of 2705. m, the Ziegler Reservoir fossil site also contained thousands of well-preserved bones of late Pleistocene megafauna, including mastodons, mammoths, ground sloths, horses, camels, deer, bison, black bear, coyotes, and bighorn sheep. In addition, the site contained more than 26,000 bones from at least 30 species of small animals including salamanders, otters, muskrats, minks, rabbits, beavers, frogs, lizards, snakes, fish, and birds. The combination of macro- and micro-vertebrates, invertebrates, terrestrial and aquatic plant macrofossils, a detailed pollen record, and a robust, directly dated stratigraphic framework shows that high-elevation ecosystems in the Rocky Mountains of Colorado are climatically sensitive and varied dramatically throughout MIS 5.

Precipitation in southwestern North America has exhibited significant natural variability over the past few thousand years. This variability has been attributed to sea surface temperature regimes in the Pacific and Atlantic oceans, and to the attendant shifts in atmospheric circulation patterns. In particular, decadal variability in the North Pacific has influenced precipitation in this region during the twentieth century, but links to earlier droughts and pluvials are unclear. Here we assess these links using δ 18 O data from a speleothem from southern California that spans AD 854-2007. We show that variations in the oxygen isotopes of the speleothem correlate to sea surface temperatures in the Kuroshio Extension region of the North Pacific, which affect the atmospheric trajectory and isotopic composition of moisture reaching the study site. Interpreting our speleothem data as a record of sea surface temperatures in the Kuroshio Extension, we find a strong 22-year periodicity, suggesting a persistent solar influence on North Pacific decadal variability. A comparison with tree-ring records of precipitation during the past millennium shows that some droughts occurred during periods of warmth in the Kuroshio Extension, similar to the instrumental record. However, other droughts did not and instead must have been influenced by other factors. Finally, we find a significant increase in sea surface temperature variability over the past 150 years, which may reflect an influence of greenhouse gas concentrations on variability in the North Pacific.

An abrupt cooling event in the North Atlantic region 8,200 years ago affected climate throughout the Northern Hemisphere. The event is well constrained in Greenland ice cores, but lack of resolution in records from other regions has challenged our understanding of the timing and nature of the associated teleconnections. Speleothem records from East Asia have suggested monsoonal changes associated with the 8,200 year event, but the nature of these changes remains controversial. Here we assess changes in East Asian precipitation during the event from a sub-annually resolved stalagmite record from central China. Using δ 18 O and Mg/Ca measurements of the speleothem carbonate, we show that climate dried significantly about 8,200 years ago. Based on our annual-layer-counted chronology, we show that the dry event lasted 150 years, with a central period of pronounced aridity that lasted 70 years. The duration and evolution of the event is indistinguishable from that observed in the Greenland ice cores. We therefore conclude that an effective and rapid atmospheric teleconnection exists between the North Atlantic and the monsoon system in warm climates similar to today's. © 2013 Macmillan Publishers Limited. All rights reserved.

Over the past decade, a number of speleothem studies have used radiocarbon (14C) to address a range of palaeoclimate problems. These have included the use of the bomb pulse 14C to anchor chronologies over the last 60 years, the combination of U-Th and 14C measurements to improve the radiocarbon age-calibration curve, and linking atmospheric 14C variations with climate change. An issue with a number of these studies is how to constrain, or interpret, variations in the amount of radioactively dead carbon (i.e. the dead carbon fraction, or DCF) that reduces radiocarbon concentrations in speleothems. In this study, we use 14C, stable-isotopes, and trace-elements in a U-Th dated speleothem from Flores, Indonesia, to examine DCF variations and their relationship with above-cave climate over the late Holocene and modern era. A strong association between the DCF and hydrologically-controlled proxy data suggests that more dead carbon was being delivered to the speleothem during periods of higher cave recharge (i.e. lower δ18O, δ13C and Mg/Ca values), and hence stronger summer monsoon. To explore this relationship, we used a geochemical soil-karst model coupled with 14C measurements through the bomb pulse to disentangle the dominant components governing DCF variability in the speleothem. We find that the DCF is primarily controlled by limestone dissolution associated with changes in open- versus closed-system conditions, rather than kinetic fractionation and/or variations in the age spectrum of soil organic matter above the cave. Therefore, we infer that periods of higher rainfall resulted in a higher DCF because the system was in a more closed state, which inhibited carbon isotope exchange between the karst water dissolved inorganic carbon and soil-gas CO2, and ultimately led to a greater contribution of dead carbon from the bedrock. © 2012.

A reconstruction of Holocene rainfall is presented for southwest China - an area prone to drought and flooding due to variability in the East Asian monsoon. The reconstruction is derived by comparing a new high-resolution stalagmite δ18O record with an existing record from the same moisture transport pathway. The new record is from Heshang Cave (30°27′N, 110°25′E; 294 m) and shows no sign of kinetic or evaporative effects so can be reliably interpreted as a record of local rainfall composition and temperature. Heshang lies 600 km downwind from Dongge Cave which has a published high-resolution δ18O record (Wang, Y.J., Cheng, H., Edwards, R.L., He, Y.Q., Kong, X.G., An, Z.S., Wu, J.Y., Kelly, M.J., Dykoski, C.A., Li, X.D., 2005. The Holocene Asian monsoon: links to solar changes and North Atlantic climate. Science 308, 854-857). By differencing co-eval δ18O values for the two caves, secondary controls on δ18O (e.g. moisture source, moisture transport, non-local rainfall, temperature) are circumvented and the resulting Δδ18O signal is controlled directly by the amount of rain falling between the two sites. This is confirmed by comparison with rainfall data from the instrumental record, which also allows a calibration of the Δδ18O proxy. The calibrated Δδ18O record provides a quantitative history of rainfall in southwest China which demonstrates that rainfall was 8% higher than today during the Holocene climatic optimum (≈ 6 ka), but only 3% higher during the early Holocene. Significant multi-centennial variability also occurred, with notable dry periods at 8.2 ka, 4.8-4.1 ka, 3.7-3.1 ka, 1.4-1.0 ka and during the Little Ice Age. This Holocene rainfall record provides a good target with which to test climate models. The approach used here, of combining stalagmite records from more than one location, will also allow quantification of rainfall patterns for past times in other regions. © 2008.

Speleothems from Wanxiang Cave, China (33°19′ N, 105°00′ E), located near the northern limit of the East Asian summer monsoon, provide high-resolution records of paleomonsoon variability. We present a simple model for interpreting δ18O shifts in speleothems from this region in which the δ18O of speleothem calcite is inversely related to monsoon intensity. In contrast to observations at higher latitudes, atmospheric temperature has little effect on δ18O of precipitation near Wanxiang Cave. Furthermore, the temperature dependence of calcite-water δ18O fractionation acts in the opposite sense, most likely canceling out the effect of local temperature variations on speleothem δ18O. Given this, the maximum δ18O shift that could occur due only to changes in the composition of the oceanic source region, the amount of rainfall, and the amount of evaporation between full glacial conditions with a weak summer monsoon and full interglacial conditions with a strong summer monsoon is 5.5‰. Accordingly, it is necessary to invoke changes in past atmospheric circulation patterns and in the ratio of summer to winter precipitation to explain the nearly 7‰ range observed in fossil Wanxiang Cave speleothems. Two stalagmites, WXSM 51 and WXSM 52, exhibit more positive δ18O during stadial periods (marine isotope stages [MIS] 8, 6, 5d, 5b, and 2) than during interstadial periods (MIS 9, 5a, 5c, 5e). Thus, East Asian summer monsoon intensity is generally decreased during globally cooler periods and increased during globally warmer periods. We present detailed δ18O records from MIS 5a-5b and 5c-5d. During the MIS 5d-5c transition, summer monsoon intensity increased steadily from 117.6 ka, with a peak in intensity occurring at 106.8 ka, concurrent with Greenland Interstadial 24. During the MIS 5b-5a transition, monsoon intensity increased abruptly at about 85.7 ka, when δ18O decreased by approximately 4‰ in 200 years. Monsoon variability, inferred from the MIS 5c-5d and MIS 5a-5b records, closely coincides with global climate changes observed in the GISP2, Vostok, and SPECMAP records, and with the Northern Hemisphere insolation curve. This suggests that East Asian summer monsoon intensity varies in phase with global climate fluctuations and is largely controlled by variations in Northern Hemisphere incident solar radiation. The MIS 5a-5b and 5c-5d paleomonsoon records from Wanxiang Cave also agree well with other records of Asian monsoon variability indicating that δ18O of speleothems from Wanxiang Cave is a valid proxy for past changes in monsoon intensity. © 2006 Elsevier B.V. All rights reserved.

We report the presence of clear annual cycles in trace-element (Mg/Ca, Sr/Ca, Ba/Ca, and U/Ca) and stable-isotope (δ18O and δ13C) composition in an annually banded stalagmite from Heshang Cave, Hubei Province, China (30.44°N, 110.42°E). Through a combination of micromilling and in situ analysis (LA-MC-CPMS), we measured geochemical variations across 16 annual growth bands, to assess their potential as seasonal resolution paleomonsoon proxies. To facilitate comparison with modern climatic and environmental data we created composite annual cycles for each proxy by stacking 6 well-defined years. Speleothem δ18O variations (- 10.8‰ to - 8.5‰) are controlled by seasonal variations in temperature and drip-water δ18O which lead to maximum values during May, around the time of summer monsoon onset. This provides a chronological marker which can be used to constrain the timing of the other geochemical cycles. The composite cycles reveal a strong positive correlation between Mg/Ca, Sr/Ca, Ba/Ca, and δ13C values in the micromilled section (R2 = 0.65-0.98), with minimum values occurring around May. Maximum U/Ca values occur at the same time. We present simple models which show that these correlations, as well as the observed ranges of Mg/Ca (14.1 to 22.4 mmol/mol), Sr/Ca (0.2 to 0.4 mmol/mol), and δ13C (- 12.5 ‰ to - 10.7-), may be fully explained by progressive CO2 degassing and calcite precipitation from an initially saturated solution. Using realistic initial conditions for Heshang Cave (T = 18 °C, Mg/Casolution = 0.84 mol/mol, Sr/Casolution = 0.69 mmol/mol, δ13CTDIC = - 16.75‰), we find that the observed relationships can be produced by using DMg = 0.016 and DSr = 0.30, within the range of expected values. The model suggests that the fraction of Ca removed from the solution ranges from 0 to 30% to produce the observed seasonal cycles. This variation may be due to two related processes which occur during drier periods: (1) increased prior precipitation of calcite in the epikarst or on the cave ceiling, and/or (2) a greater degree of CO2 degassing and calcite precipitation on stalagmite surfaces when drip-rates are lower. Both mechanisms would have the effect of enriching speleothem Mg/Ca, Sr/Ca, Ba/Ca, and δ13C values during drier periods. Past variations in Heshang carbonate chemistry may therefore be useful as seasonal resolution proxies for past rainfall. © 2006 Elsevier B.V. All rights reserved.

The stable isotopic composition of materials such as glacial ice, tree rings, lake sediments, and speleothems from low-to-mid latitudes contains information about past changes in temperature (T) and precipitation amount (P). However, the transfer functions which link δ18Op to changes in T or P, dδ18Op/d T and dδ18Op/d P , can exhibit significant temporal and spatial variability in these regions. In areas affected by the Southeast Asian monsoon, past variations in δ18O and δD of precipitation have been attributed to variations in monsoon intensity, storm tracks, and/or variations in temperature. Proper interpretation of past δ18Op variations here requires an understanding of these complicated stable isotope systematics. Since temperature and precipitation are positively correlated in China and have opposite effects on δ18Op, it is necessary to determine which of these effects is dominant for a specific region in order to perform even qualitative paleoclimate reconstructions. Here, we evaluate the value of the transfer functions in modern precipitation to more accurately interpret the paleorecord. The strength of these transfer functions in China is investigated using multiple regression analysis of data from 10 sites within the Global Network for Isotopes in Precipitation (GNIP). δ18Op is modeled as a function of both temperature and precipitation. The magnitude and signs of the transfer functions at any given site are closely related to the degree of summer monsoon influence. δ18Op values at sites with intense summer monsoon precipitation are more dependent on the amount of precipitation than on temperature, and therefore exhibit more negative values in the summer. In contrast, δ18Op values at sites that are unaffected by summer monsoon precipitation exhibit strong relationships between δ18Op and temperature. The sites that are near the northern limit of the summer monsoon exhibit dependence on both temperature and amount of precipitation. Comparison with simple linear models (δ18Op as a function of T or P) and a geographic model (δ18Op as a function of latitude and altitude) shows that the multiple regression model is more successful at reproducing δ18Op values at sites that are strongly influenced by the summer monsoon. The fact that the transfer function values are highly spatially variable and closely related to the degree of summer monsoon influence suggests that these values may also vary temporally. Since the Southeast Asian monsoon intensity is known to exhibit large variations on a number of timescales (annual to glacial-interglacial), and the magnitude and sign of the transfer functions is related to monsoon intensity, we suggest that as monsoon intensity changes, the magnitude and possibly even the sign of the transfer functions may vary. Therefore, quantitative paleoclimate reconstructions based on δ18Op variations may not be valid. © 2004 Elsevier B.V. All rights reserved.

BACKGROUND: The duration and cost of cancer clinical trials could be reduced if a surrogate endpoint were used in place of survival. We did a meta-analysis to assess the extent to which two surrogates, tumour response and time to progression, are predictive of mortality in metastatic colorectal cancer and non-small-cell lung cancer. METHODS: Summary data (median time to progression, proportion of patients responding to treatment, and median overall survival) from randomised trials of first-line treatment in colorectal cancer (146 trials) and lung cancer (191 trials) were identified. Data were extracted and analysed by linear regression. We used prediction bands for trials with 250, 500, and 750 patients to identify the surrogate threshold effect that would predict a significant difference in survival. FINDINGS: Response to treatment and time to progression correlated with improvement in survival for both lung cancer (p<0.0001 and p=0.0003, respectively) and colorectal cancer (p<0.0001 for both). To predict a significant survival gain in colorectal cancer trials, an improvement of 20% in the number of patients responding to treatment was required in trials with 750 patients, increasing to 26% in trials with 500 patients and 38% in trials with 250 patients. In lung cancer trials, the same prediction required differences in response of 18% for 750 patients, 21% for 500 patients, and 30% for 250 patients. For time to progression for both cancer types, the incremental gain needed to predict a survival improvement was a median of 1.8 months for trials with 750 patients, 2.2 months for 500 patients, and 3.3 months for 250 patients. INTERPRETATION: Irrespective of trial size, large differences in tumour response rate are needed to predict a significant survival benefit. If surrogates are chosen as the primary endpoint in a clinical trial, time to progression is the preferred measure because more modest and achievable differences are needed for a significant survival benefit. Trials in metastatic lung cancer and colorectal cancer should measure survival as their primary outcome unless the surrogate outcome difference is anticipated to exceed the threshold effect size. [ABSTRACT FROM AUTHOR]

Costly organization-based leadership/management development training gives little evidence that such training affects long-term changes in nurse manager leader style adaptability in meeting situations and staff needs. [ABSTRACT FROM AUTHOR]

Abstract Background We conducted Geographic Information System (GIS) habitat analyses for lesser prairie-chicken (LPCH, Tympanuchus pallidicinctus) conservation planning. The 876,799 ha study area included most of the occupied habitat for the LPCH in New Mexico. The objectives were to identify and quantify: 1. suitable LPCH habitat in New Mexico, 2. conversion of native habitats, 3. potential for habitat restoration, and 4. unsuitable habitat available for oil and gas activities. Results We found 16% of suitable habitat (6% of the study area) distributed in 13 patches of at least 3,200 ha and 11% of suitable habitat (4% of the study area) distributed in four patches over 7,238 ha. The area converted from native vegetation types comprised 17% of the study area. Ninety-five percent of agricultural conversion occurred on private lands in the northeastern corner of the study area. Most known herbicide-related conversions (82%) occurred in rangelands in the western part of the study area, on lands managed primarily by the US Bureau of Land Management (BLM). We identified 88,190 ha (10% of the study area) of habitats with reasonable restoration potential. Sixty-two percent of the primary population area (PPA) contained occupied, suitable, or potentially suitable habitat, leaving 38% that could be considered for oil and gas development. Conclusion Although suitable LPCH habitat appears at first glance to be abundant in southeastern New Mexico, only a fraction of apparently suitable vegetation types constitute quality habitat. However, we identified habitat patches that could be restored through mesquite control or shin-oak reintroduction. The analysis also identified areas of unsuitable habitat with low restoration potential that could be targeted for oil and gas exploration, in lieu of occupied, high-quality habitats. Used in combination with GIS analysis and current LPCH population data, the habitat map represents a powerful conservation and management tool.

During nuclear fuel reprocessing, radioiodine, can be released. The speciation of iodine drives its volatility, and partitioning processes are highly variable because they depend on facility operating conditions. Starting from iodine behavior in the fuel and progressing to its behavior in the environment, this review article describes the current understanding of iodine partitioning during aqueous fuel reprocessing. This review outlines knowledge gaps and describes the effects of state-of-the-art reprocessing techniques on iodine speciation and volatility. Whereas many review articles have described iodine behavior during specific reprocessing steps, this review provides a holistic overview of radioiodine, from the forms of iodine in different types of irradiated fuel to the forms of iodine released into the environment. The resultant behavior of radioiodine compared with stable iodine in the environment is also described., Competing Interests: There are no conflicts of interest to declare., (This journal is © The Royal Society of Chemistry.)

Mitochondrial dysfunction causes devastating disorders, including mitochondrial myopathy, but how muscle senses and adapts to mitochondrial dysfunction is not well understood. Here, we used diverse mouse models of mitochondrial myopathy to show that the signal for mitochondrial dysfunction originates within mitochondria. The mitochondrial proteins OMA1 and DELE1 sensed disruption of the inner mitochondrial membrane and, in response, activated the mitochondrial integrated stress response (mt-ISR) to increase the building blocks for protein synthesis. In the absence of the mt-ISR, protein synthesis in muscle was dysregulated causing protein misfolding, and mice with early-onset mitochondrial myopathy failed to grow and survive. The mt-ISR was similar following disruptions in mtDNA maintenance (Tfam knockout) and mitochondrial protein misfolding (CHCHD10 G58R and S59L knockin) but heterogenous among mitochondria-rich tissues, with broad gene expression changes observed in heart and skeletal muscle and limited changes observed in liver and brown adipose tissue. Taken together, our findings identify that the DELE1 mt-ISR mediates a similar response to diverse forms of mitochondrial stress and is critical for maintaining growth and survival in early-onset mitochondrial myopathy., Competing Interests: Disclosure and competing interests statement The authors declare no competing interests., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Context: Chronic ankle instability (CAI) is associated with motor-behavioral and sensory-perceptual impairments, including reduced balance performance, hip strength, and ankle function, and increased disablement, and injury-related fear. Progressive balance training (BAL) and hip strengthening (HIP) can both improve balance and function, but their comparative effects are unknown. Our objective was to compare the effects of progressive BAL and HIP on balance, hip strength, and patient-reported outcomes in those with CAI., Methods: Forty-five individuals with CAI volunteered for this randomized control study. Participants were randomly allocated to BAL, HIP, and control (CON) groups (n = 15 per group). BAL and HIP each participated in 8-week interventions while CON did not. Participants' involved limbs underwent testing of patient-reported outcomes (Foot and Ankle Ability Measure [FAAM-ADL, FAAM-S], modified Disablement in the Physically Active Scale [mDPA], Tampa Scale of Kinesiophobia-11 [TSK-11], Fear-Avoidance Beliefs Questionnaire [FABQ], and Self-Efficacy of Balance Scale [SEBS]), Star Excursion Balance Test (SEBT), and isometric hip strength (extension [EXT], abduction [ABD], and external rotation [ER]) before and after the intervention. Multiple imputation was used for missing data. Multivariate repeated-measures analyses of variance analyzed effects of the interventions., Results: A significant group × time interaction existed for psychosocial outcomes (P = .008), but not for balance (P = .159), strength (P = .492), or ankle function and disability (P = .128). Time main effects existed for balance (P = .003), strength (P < .001), function and disability (P < .001), and psychosocial outcomes (P = .006). BAL significantly improved in SEBT, EXT, ABD, and all patient-reported outcomes. HIP significantly improved in EXT, ABD, ER, FAAM-S, mDPA, FABQ, and SEBS., Conclusions: Balance training and hip strengthening can both improve motor-behavioral and sensory-perceptual impairments in individuals with CAI; however, balance training remains the most effective option for clinicians.

Neuregulin1 (Nrg1) signaling is critical for neuronal development and function from fate specification to synaptic plasticity. Type III Nrg1 is a synaptic protein which engages in bidirectional signaling with its receptor ErbB4. Forward signaling engages ErbB4 phosphorylation, whereas back signaling engages two known mechanisms: (1) local axonal PI3K-AKT signaling and (2) cleavage by γ-secretase resulting in cytosolic release of the intracellular domain (ICD), which can traffic to the nucleus (Bao et al., 2003; Hancock et al., 2008). To dissect the contribution of these alternate signaling strategies to neuronal development, we generated a transgenic mouse with a missense mutation (V 321 L) in the Nrg1 transmembrane domain that disrupts nuclear back signaling with minimal effects on forward signaling or local back signaling and was previously found to be associated with psychosis (Walss-Bass et al., 2006). We combined RNA sequencing, retroviral fate mapping of neural stem cells, behavioral analyses, and various network analyses of transcriptomic data to investigate the effect of disrupting Nrg1 nuclear back signaling in the dentate gyrus (DG) of male and female mice. The V 321 L mutation impairs nuclear translocation of the Nrg1 ICD and alters gene expression in the DG. V 321 L mice show reduced stem cell proliferation, altered cell cycle dynamics, fate specification defects, and dendritic dysmorphogenesis. Orthologs of known schizophrenia (SCZ)-susceptibility genes were dysregulated in the V 321 L DG. These genes coordinated a larger network with other dysregulated genes. Weighted gene correlation network analysis and protein interaction network analyses revealed striking similarity between DG transcriptomes of V 321 L mouse and humans with SCZ., Competing Interests: The authors declare no competing financial interests., (Copyright © 2024 Rajebhosale et al.)

Oxygen isotopes (δ 18 O) are the most commonly utilized speleothem proxy and have provided many foundational records of paleoclimate. Thus, understanding processes affecting speleothem δ 18 O is crucial. Yet, prior calcite precipitation (PCP), a process driven by local hydrology, is a widely ignored control of speleothem δ 18 O. Here we investigate the effects of PCP on a stalagmite δ 18 O record from central Vietnam, spanning 45 - 4 ka. We employ a geochemical model that utilizes speleothem Mg/Ca and cave monitoring data to correct the δ 18 O record for PCP effects. The resulting record exhibits improved agreement with regional speleothem δ 18 O records and climate model simulations, suggesting that the corrected record more accurately reflects precipitation δ 18 O (δ 18 O p ). Without considering PCP, our interpretations of the δ 18 O record would have been misleading. To avoid misinterpretations of speleothem δ 18 O, our results emphasize the necessity of considering PCP as a significant driver of speleothem δ 18 O., (© 2024. The Author(s).)

Substance Use Disorders (SUDs) manifest as persistent drug-seeking behavior despite adverse consequences, with Alcohol Use Disorder (AUD) and Opioid Use Disorder (OUD) representing prevalent forms associated with significant mortality rates and economic burdens. The co-occurrence of AUD and OUD is common, necessitating a deeper comprehension of their intricate interactions. While the causal link between these disorders remains elusive, shared genetic factors are hypothesized. Leveraging public datasets, we employed genomic and transcriptomic analyses to explore conserved and distinct molecular pathways within the dorsolateral prefrontal cortex associated with AUD and OUD. Our findings unveil modest transcriptomic overlap at the gene level between the two disorders but substantial convergence on shared biological pathways. Notably, these pathways predominantly involve inflammatory processes, synaptic plasticity, and key intracellular signaling regulators. Integration of transcriptomic data with the latest genome-wide association studies (GWAS) for problematic alcohol use (PAU) and OUD not only corroborated our transcriptomic findings but also confirmed the limited shared heritability between the disorders. Overall, our study indicates that while alcohol and opioids induce diverse transcriptional alterations at the gene level, they converge on select biological pathways, offering promising avenues for novel therapeutic targets aimed at addressing both disorders simultaneously., (© 2024. The Author(s).)