A high-resolution multi-proxy approach, integrating pollen, inorganic and organic geochemical and sedimentological analyses, has been carried out on the Holocene section of the Padul sedimentary ...record in the southern Iberian Peninsula reconstructing vegetation, environment and climate throughout the last ~ 11.6 cal kyr BP in the western Mediterranean. The study of the entire Holocene allows us to determine the significant climate shift that occurred during the middle-to-late Holocene transition. The highest occurrence of deciduous forest in the Padul area from ~ 9.5 to 7.6 cal kyr BP represents the Holocene humidity optimum probably due to enhanced winter precipitation during a phase of highest seasonal anomaly and maximum summer insolation. Locally, insolation maxima induced high evaporation, counterbalancing the effect of relatively high precipitation, and triggered very low water table in Padul and the deposition of peat sediments. A transitional environmental change towards more regional aridity occurred from ~ 7.6 to 4.7 cal kyr BP and then aridification enhanced in the late Holocene most likely related to decreasing summer insolation. This translated into higher water levels and a sedimentary change at ~ 4.7 cal kyr BP in the Padul wetland, probably related to reduced evaporation during summer in response to decreased in seasonality. Millennial-scale variability is superimposed on the Holocene long-term trends. The Mediterranean forest regional climate proxy studied here shows significant cold-arid events around ~ 9.6, 8.5, 7.5, 6.5 and 5.4 cal kyr BP with cyclical periodicities (~1100 and 2100 yr) during the early and middle Holocene. A change is observed in the periodicity of these cold-arid events towards ~1430 yr in the late Holocene, with forest declines around ~ 4.7–4, 2.7 and 1.3 cal kyr BP. The comparison between the Padul-15-05 data with published North Atlantic and Mediterranean paleoclimate records suggests common triggers for the observed climate variability, with the early and middle Holocene forest declines at least partially controlled by external forcing (i.e. solar activity) and the late Holocene variability associated with internal mechanisms (oceanic-atmospheric).
•We carried out a multi-proxy analysis for the last 11.6 cal kyr BP from a new sedimentary record from Padul (Sierra Nevada, Spain).•This record shows a long-term climate pattern mostly forced by insolation, showing a significant climate and environmental shift at 4.7 cal kyr BP.•Millennial-scale climate oscillations are also characterized in this study by the decrease in Mediterranean forest and local response in the lake level, showing possible atmospheric and climate links between the western Mediterranean and North Atlantic areas.
Padul is one of the few wetland sites in southern Europe and the Mediterranean region that exhibits an unusually large temporal span (>100 kyr) and continuous Quaternary sedimentary record. Previous ...core-based studies from Padul yielded paleoecological datasets (i.e., pollen and organic geochemistry), but with a poor age control that resulted in rather arbitrary climate inferences. Therefore, precise age control and a multidisciplinary approach is necessary to understand long-term regional environmental and climate change and the associated local response of the Padul wetland environment. Here we present a new long sediment record (Padul-15-05) from this wetland in the southern Iberian Peninsula with the aim of improving the age control of the sedimentary sequence and carrying out up-to-date high-resolution multiproxy analyses. In this study the age control is based on 61 AMS radiocarbon dates for the last ca. 50 kyr BP and on the extent of amino acid racemization (AAR) in mollusc shells extending back ∼118 kyr BP. No numerical ages are available for the bottom part of the core but the sediment accumulation rates (SAR) and the cyclostratigraphic analysis of the multiproxy data suggest that the core preserves a continuous record of the last ∼197 kyr (from late MIS 7 to present) with millennial-scale time resolution. Sedimentological (lithology, magnetic susceptibility, XRD, color), geochemical (XRF, TOC, C/N, % carbonate content) and paleontological (pollen, charophytes, gastropods) data show co-varying cyclical paleoenvironmental changes linked to orbital-scale climatic variability. Silicon, magnetic susceptibility (MS) and total organic carbon (TOC) data show periodicities between ∼26.2–19.6 kyr linked to insolation, which is strongly dominated by precession cycles at this latitude. High values of Si and MS data have been related to high siliciclastic/detrital input from Sierra Nevada range during minima in insolation due to enhanced soil weathering/erosion during regional aridity and lower forest cover recorded by the arboreal pollen, which could also be favored by a minor biogenic productivity. In addition, warm climate conditions during maxima in insolation mostly resulted in negative precipitation/evapotranspiration balance and low lake levels, while cold glacial and stadial periods were mainly characterized by positive precipitation/evapotranspiration balance, and therefore, high lake levels. The improved chronology of the Padul sedimentary sequence along with a multiproxy study permitted us to better relate environmental and vegetation changes to climatic events and to demonstrate how both local (i.e., lake level, sedimentation) and regional (i.e., vegetation) environments responded to orbital-scale climate changes.
•A new long sedimentary record from the Padul wetland (Padul-15-05) with an improved age control of the last ∼ 200,000 years.•The multiproxy analysis of the Padul record show paleoenvironmental changes related with orbital-scale climate oscillations.•The multiproxy analysis reflects regional and local environmental changes linked to precession, which influenced insolation.
A new sediment core from Padul, Padul-15-05, provides a long and continuous sedimentary and paleoenvironmental record of the last ∼200 kyr. Here we present a detailed palynological study from this ...sedimentary sequence with new vegetation and paleoenvironmental data and a climatic interpretation for the last two climatic cycles from the southern Iberian Peninsula in the western Mediterranean region. Pollen analysis from this core shows orbital-scale vegetation oscillations (mainly forced by precession and eccentricity) pointing into insolation as the principal factor controlling vegetation changes at this latitude. The last two glacial-interglacial cycles (from MIS 6 to the present) as well as stadial and interstadial phases are well represented and characterized by significant oscillations in Mediterranean forest in the area, but several differences with respect to other Mediterranean long pollen records can be recognized. Some of these disparities between regions seem to be more related to different precipitation rates linked to the specific geographical features (e.g. strong topographic relief) than to latitudinal differences between the sites. In addition, a lake level reconstruction based on palynological data was developed and compared with the previous reconstruction from this record, representing local environmental changes in the Padul wetland that seems to be related to precipitation/evapotranspiration balance, and therefore, to changes in regional climate conditions. During glacial/stadial conditions recorded by maxima in xerophytes, the p/e increased due to very low evapotranspiration, resulting in high lake levels, while during warmer interglacial/interstadial phases (except for the MIS 5e), mainly represented in this record by maxima in the Mediterranean forest, water level decreased as a result of high evapotranspiration exceeding precipitation input. The comparison of the new Padul-15-05 pollen record with the two previous palynological studies from Padul shows significant differences mainly due to disagreements in the age control of the sequences. This study shows that an accurate age-depth model becomes essential when interpreting long paleoenvironmental and paleoclimate records.
•Padul-15-05 sediment core shows paleoenvironmental and paleoclimate changes during the last ca. 200,000 years.•In this study glacial/interglacial and stadial/interstadial periods have been identified.•Vegetation changes at Padul are linked to oscillations in the elevation of the bioclimatic vegetation belts of Sierra Nevada.•Vegetation changes are related to Padul lake level oscillations, conditioned by the precipitation/evapotranspiration balance.
The fire history is determined from sediments of the Padul-15-05 sediment core recovered from southeastern Spain’s Padul peat bog. A combination of sedimentary charcoal concentrations, charcoal ...morphology characteristics, and polycyclic aromatic hydrocarbons (PAHs) were analyzed for two sections of the core spanning 136 to 112 ka (thousands of calendar years before present) and 21.5 ka to the present. These two sections were chosen to investigate two glacial terminations and two interglacial periods, one of which did not have human impact (Marine Isotope Stage (MIS) 5e), and to construct a fire history from MIS 6 and 5e, which few studies have investigated. The fire history was compared to evidence of climate, vegetation, and hydrological dynamics through analysis of sedimentary proxies of the Padul-15-05 core. The Padul-15-05 fire history primarily captures in situ activity rather than regional fire, which is controlled by hydrological changes and fuel supply. During MIS 6 (136-130 ka), low fire activity resulted from fuel load limitations and high lake levels due to low evaporation and enhanced glacial meltwater supply, and steppe vegetation dominated. Low fire activity persisted during much of MIS 5e (130-117 ka) due to high lake levels supported by enhanced precipitation, which prohibited hygrophyte growth on the bog surface. An increase in fire activity occurred ~117 ka concurrent with a decrease in lake levels, a change to palustrine conditions, and predominantly herbaceous charcoal and hygrophyte. Fire activity was low due to high lake levels, which restricted hygrophyte growth during the late Pleistocene (MIS 2 ~ 21.5-11.6 ka), concurrent with arid conditions and primarily steppe vegetation. Moderate in situ fire activity occurred from 12.3-11.6 ka due to arid conditions resulting in low lake corresponding to the Younger Dryas (12.8-11.7 ka). Increased in situ fire activity concurrent with palustrine and temperate conditions occurred during the early and middle Holocene (11.6-4.2 ka). A significant decrease in fire indicators suggests that in situ fires were limited by higher lake levels indicated by ephemeral carbonate deposition during late Holocene (4.0-0.4 ka). Agricultural pollen indicators suggest the onset of significant human influence on the landscape in the latter half of the late Holocene (1.5 ka to present). The Padul bog became fully emerged from ~0.4 ka to present, which is likely a result of human caused water diversion, and the absence of fire indicators from ~0.4-0.1 ka indicates fire suppression. Fire activity peaked from ~0.1 ka, signaling compounding anthropogenic agriculture, mining, and land use change. The Padul-15-05 fire history is primarily controlled by hydrological setting and fuel supply, which is ultimately controlled by climate variability. The Padul-15-05 environmental history is important for the Sierra Nevada National Park as Mediterranean temperature and aridity are projected to increase. The environmental history of the Padul bog clarifies the role of fire for a wetland ecosystem in an arid region. The Padul site is an important resource for paleoenvironmental research and for the preservation of a wetland ecosystem in a changing climate.
Researchers have placed emphasis on quantifying and identifying ecological thresholds to study biological responses to urbanization. As watersheds become urbanized, they exhibit a systemic pattern of ...degradation that disrupts the natural biogeochemical and geomorphologic processes, ultimately leading to a decline in freshwater biodiversity. In North Carolina, an increase in population is leading to an aquatic biodiversity crisis which can be observed in declining freshwater fish abundance and diversity. Although studies in the Eastern Piedmont and specifically North Carolina have quantified the relationship between aquatic biotic communities and urbanization, they have fallen short of identifying individual tolerances. This study uses land cover data from the National Land Cover Database and biomonitoring datasets from the North Carolina Department of Environmental Quality and Mecklenburg County Stormwater Services with the Threshold Indicator Taxa Analysis (TITAN) to quantify percent impervious cover (IC) thresholds and change points at the community and individual level to identify biological indicators and conservation priorities for watershed health. Non-parametric and pairwise testing was used to identify IC tolerance trends among ecological functional groups and pollution tolerance designations. Results of the land cover analysis reveal that IC increased by 1.73% throughout the North Carolina Piedmont in the 16-year period, but watersheds with < 15% IC decreased by 9.7% and watersheds between 45-60% increased 329%. TITAN revealed that Z- taxa experience the greatest change in frequency and abundance, also known as change point, at 6.10% IC and have an aggregate threshold of ~ 7% IC (5.79-12.78%); Z+ taxon have a change point of 16.59% and an aggregate threshold of 41.30% IC (16.07-57.37%). Kruskal-Wallis results demonstrated IC tolerance among pollution tolerance classifications and trophic guilds thresholds were significant but insignificant for spawning guilds. TITAN also revealed several taxa whose IC tolerances differentiated from their respected pollution tolerance. Overall, this study revealed that with the current NC state watershed development regulations, ~88% of the state’s watersheds could exceed IC thresholds of ~75% of taxa within the NCP fish assemblage.
Reservoirs are depositional environments for suspended sediments in river systems. Due to sediments undergoing fallout in low-flow areas, reservoirs contain 26% of all sediment and 12% of global ...river phosphorus behind dams. Despite most large rivers containing multiple dams, the connectivity of multiple reservoirs fragmenting a single stream system is still relatively unknown. For this thesis, paleolimnological techniques, sediment cores, and surface sediment samples were collected from five reservoirs along a large and fragmented river system in the Southeast United States. Reservoir location within the reservoir sequence was the primary driver for nutrient deposition with the initial reservoir downstream of the nutrient source acting as the primary site for nutrient deposition and accumulation. Residence time was a secondary driver of sediment deposition as shorter residence times prevent deposition.The spatial distributions of nutrients along and within a string of reservoirs has also received little investigation. Whereas, nutrient deposition was hypothesized to follow the three zones of reservoirs (Riverine, Transitional, Lacustrine), a two-zone switch occurred with high nutrient concentrations near the dam and deposition dramatically decreasing as traveling upstream. Nutrients are found to primarily deposit near the dam pool area and within branches and coves. Deposition in branches and coves was linked to local shoreline land use. Because reservoir placement was shown as a primary driver for nutrient deposition, the need for reservoir and watershed managers to have a fully developed understanding of nutrient sources in relation to reservoir systems is encouraged.
Urbanization, agriculture, and other land transformations can affect water quality, decrease species biodiversity, and increase metal and nutrient concentrations in aquatic systems. Metal pollution, ...in particular, is a reported consequence of elevated anthropogenic inputs, especially from urbanized areas. The objectives of this study were to quantify metal (Cu, Al, Cd, Ni, and Pb) concentrations in the waters and biota of four streams in South Georgia, USA, and relate metal concentrations to land use and abiotic and biotic stream processes. Additionally, macrophytes, invertebrates, and fish were identified to assess biodiversity at each site. Metal concentrations in the three trophic levels differed among sites and species, correlating to differences in land use surrounding the rivers. The highest metal concentrations (except Al) were found in the streams most impacted by urbanization and development. Al concentrations were highest in streams surrounded by land dominated by forested areas. Metal content in macrophytes reflected metal concentrations in the water and was at least three orders of magnitude higher than any other trophic level. Despite metal concentration differences, all four streams contained similar water quality and were healthy based on macroinvertebrate community structure. This study provides insight into the impact of urbanization and the fate and effects of metals in river ecosystems with varying degrees of anthropogenic impact.
Allogeneic stem cell transplantation (allo‐SCT) is the most successful and widely used immunotherapy for the treatment of acute myeloid leukemia (AML), as a result of its anti‐leukemic properties ...driven by T cells and natural killer (NK) cells, leading to a graft‐vs‐leukemia (GVL) effect. Despite its essential role in AML treatment, relapse after allo‐SCT is common and associated with a poor prognosis. There is longstanding interest in developing immunologic strategies to augment the GVL effect post‐transplant to prevent relapse and improve outcomes. In addition to prophylactic maintenance strategies, the GVL effect can also be used in relapsed patients to reinduce remission. While immune checkpoint inhibitors and other novel immune‐targeted agents have been successfully used in the post‐transplant setting to augment the GVL effect and induce remission in small clinical trials of relapsed patients, exacerbations of graft‐vs‐host disease (GVHD) have limited their broader use. Here we review advances in three areas of immunotherapy that have been studied in post‐transplant AML: donor lymphocyte infusion (DLI), immune checkpoint inhibitors, and other monoclonal antibodies (mAbs), including antibody‐drug conjugates (ADCs) and ligand receptor antagonists. We also discuss additional therapies with proposed immunologic mechanisms, such as hypomethylating agents, histone deacetylase inhibitors, and the FLT3 inhibitor sorafenib.
In the phase IV, open-label, single-arm study NCT01203917, first-line gefitinib 250 mg/d was effective and well tolerated in Caucasian patients with epidermal growth factor receptor (EGFR) ...mutation-positive non–small-cell lung cancer (previously published). Here, we report EGFR mutation analyses of plasma-derived, circulating-free tumor DNA.
Mandatory tumor and duplicate plasma (1 and 2) baseline samples were collected (all screened patients; n = 1060). Preplanned, exploratory analyses included EGFR mutation (and subtype) status of tumor versus plasma and between plasma samples. Post hoc, exploratory analyses included efficacy by tumor and plasma EGFR mutation (and subtype) status.
Available baseline tumor samples were 1033 of 1060 (118 positive of 859 mutation status known; mutation frequency, 13.7%). Available plasma 1 samples were 803 of 1060 (82 positive of 784 mutation status known; mutation frequency, 10.5%). Mutation status concordance between 652 matched tumor and plasma 1 samples was 94.3% (95% confidence interval CI, 92.3–96.0) (comparable for mutation subtypes); test sensitivity was 65.7% (95% CI, 55.8–74.7); and test specificity was 99.8% (95% CI, 99.0–100.0). Twelve patients of unknown tumor mutation status were subsequently identified as plasma mutation-positive. Available plasma 2 samples were 803 of 1060 (65 positive of 224 mutation status-evaluable and -known). Mutation status concordance between 224 matched duplicate plasma 1 and 2 samples was 96.9% (95% CI, 93.7–98.7). Objective response rates are as follows: mutation-positive tumor, 70% (95% CI, 60.5–77.7); mutation-positive tumor and plasma 1, 76.9% (95% CI, 65.4–85.5); and mutation-positive tumor and mutation-negative plasma 1, 59.5% (95% CI, 43.5–73.7). Median progression-free survival (months) was 9.7 (95% CI, 8.5–11.0; 61 events) for mutation-positive tumor and 10.2 (95% CI, 8.5–12.5; 36 events) for mutation-positive tumor and plasma 1.
The high concordance, specificity, and sensitivity demonstrate that EGFR mutation status can be accurately assessed using circulating-free tumor DNA. Although encouraging and suggesting that plasma is a suitable substitute for mutation analysis, tumor tissue should remain the preferred sample type when available.
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