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At the starting point of this case study, a garrison hospital performed an assessment of the need for treatment when the number of conscripts queuing at reception is at its highest level. The research aims to find out the reasons for conscripts' perceived long waiting times, which causes absence from the conscripts' training. According to the predictions made by the queuing simulation, the hospital's staff are able to receive patients arriving at reception in the morning without the queue time causing undue harm to training. However, during large congestion peaks, the waiting times may become unreasonable, which would require an increase in human resources. Peaks of congestion usually occur at the beginning of the week, as well as on days with heavy military training. [ABSTRACT FROM AUTHOR]

We compile and analyze all available geothermal heat flow measurements collected in and around Greenland into a new database of 419 sites and generate an accompanying spatial map. This database includes 290 sites previously reported by the International Heat Flow Commission (IHFC), for which we now standardize measurement and metadata quality. This database also includes 129 new sites, which have not been previously reported by the IHFC. These new sites consist of 88 offshore measurements and 41 onshore measurements, of which 24 are subglacial. We employ machine learning to synthesize these in situ measurements into a gridded geothermal heat flow model that is consistent across both continental and marine areas in and around Greenland. This model has a native horizontal resolution of 55 km. In comparison to five existing Greenland geothermal heat flow models, our model has the lowest mean geothermal heat flow for Greenland onshore areas. Our modeled heat flow in central North Greenland is highly sensitive to whether the NGRIP (North GReenland Ice core Project) elevated heat flow anomaly is included in the training dataset. Our model's most distinctive spatial feature is pronounced low geothermal heat flow (< 40 mW m -2) across the North Atlantic Craton of southern Greenland. Crucially, our model does not show an area of elevated heat flow that might be interpreted as remnant from the Icelandic plume track. Finally, we discuss the substantial influence of paleoclimatic and other corrections on geothermal heat flow measurements in Greenland. The in situ measurement database and gridded heat flow model, as well as other supporting materials, are freely available from the GEUS Dataverse (10.22008/FK2/F9P03L; Colgan and Wansing, 2021). [ABSTRACT FROM AUTHOR]

We compile, analyse and map all available geothermal heat flow measurements collected in and around Greenland into a new database of 419 sites and generate an accompanying spatial map. This database includes 290 sites previously reported by the International Heat Flow Commission (IHFC), for which we now standardize measurement and metadata quality. This database also includes 129 new sites, which have not been previously reported by the IHFC. These new sites consist of 88 offshore measurements and 41 onshore measurements, of which 24 are subglacial. We employ machine learning to synthesize these in situ measurements into a gridded geothermal heat flow model that is consistent across both continental and marine areas in and around Greenland. This model has a native horizontal resolution of 55 km. In comparison to five existing Greenland geothermal heat flow models, our model has the lowest mean geothermal heat flow for Greenland onshore areas (44 mW m-2). Our model's most distinctive spatial feature is pronounced low geothermal heat flow (< 40 mW m-2) across the North Atlantic Craton of southern Greenland. Crucially, our model does not show an area of elevated heat flow that might be interpreted as remnant from the Icelandic Plume track. Finally, we discuss the substantial influence of paleoclimatic and other corrections on geothermal heat flow measurements in Greenland. The in-situ measurement database and gridded heat flow model, as well as other supporting materials, are freely available from the GEUS DataVerse (https://doi.org/10.22008/FK2/F9P03L; Colgan and Wansing, 2021). [ABSTRACT FROM AUTHOR]

Wildfire occurrence is influenced by climate, vegetation and human activities. A key challenge for understanding the risk of fires is quantifying the mediating effect of vegetation on fire regimes. Here, we explore the relative importance of Holocene land cover, land use, dominant functional forest type, and climate dynamics on biomass burning in temperate and boreo-nemoral regions of central and eastern Europe over the past 12 kyr. We used an extensive data set of Holocene pollen and sedimentary charcoal records, in combination with climate simulations and statistical modelling. Biomass burning was highest during the early Holocene and lowest during the mid-Holocene in all three ecoregions (Atlantic, continental and boreo-nemoral) but was more spatially variable over the past 3–4 kyr. Although climate explained a significant variance in biomass burning during the early Holocene, tree cover was consistently the highest predictor of past biomass burning over the past 8 kyr. In temperate forests, biomass burning was high at ∼45 % tree cover and decreased to a minimum at between 60 % and 70 % tree cover. In needleleaf-dominated forests, biomass burning was highest at ∼ 60 %–65 % tree cover and steeply declined at >65 % tree cover. Biomass burning also increased when arable lands and grasslands reached ∼ 15 %–20 %, although this relationship was variable depending on land use practice via ignition sources, fuel type and quantities. Higher tree cover reduced the amount of solar radiation reaching the forest floor and could provide moister, more wind-protected microclimates underneath canopies, thereby decreasing fuel flammability. Tree cover at which biomass burning increased appears to be driven by warmer and drier summer conditions during the early Holocene and by increasing human influence on land cover during the late Holocene. We suggest that long-term fire hazard may be effectively reduced through land cover management, given that land cover has controlled fire regimes under the dynamic climates of the Holocene. [ABSTRACT FROM AUTHOR]

Wildfire occurrence is influenced by climate, vegetation and human activities. A key challenge for understanding fire-climate-vegetation interactions is to quantify the effect vegetation has in mediating fire regime. Here, we explore the relative importance of Holocene land cover and dominant functional forest type, and climate dynamics on biomass burned in temperate and boreo-nemoral regions of Central and Eastern Europe over the past 12 ka BP years. We used an extensive data set of Holocene pollen and sedimentary charcoal records, in combination with climate simulations and novel statistical modelling. Biomass burned was highest during the early Holocene and lowest during the mid Holocene in all three ecoregions, but diverged more markedly over the past 3-4 ka BP. Although the climate was an important driver of fire hazard during the warm and dry early Holocene, tree cover was consistently the strongest predictor of past biomass burning. In temperate forests, biomass burned was high at ~ 45 % tree cover and decreased strongly towards 60 % tree cover. In needleleaf dominated forests, biomass burned was highest at ~ 60-65 % tree cover and abruptly declined at > 65 % tree cover. Biomass burned also increased when arable lands and grasslands reached ~ 15-20 %, although this relationship was highly dynamic depending on land use intensity throughout ignition and fuel type and availability. Our observations cover the full range of Holocene climate variability and land cover changes and illustrates that percentages of land cover is a key predictor of the probability of fire occurrence over timescales of centuries to millennia. We suggest that long-term fire risk may be effectively reduced through land cover management, given that land cover has controlled fire regimes under the dynamic climates of the Holocene. [ABSTRACT FROM AUTHOR]

Vegetation is crucial for modulating rates of denudation and landscape evolution, as it stabilizes and protects hillslopes and intercepts rainfall. Climate conditions and the atmospheric CO2 concentration, hereafter [CO2], influence the establishment and performance of plants; thus, these factors have a direct influence on vegetation cover. In addition, vegetation dynamics (competition for space, light, nutrients, and water) and stochastic events (mortality and fires) determine the state of vegetation, response times to environmental perturbations and successional development. In spite of this, state-of-the-art reconstructions of past transient vegetation changes have not been accounted for in landscape evolution models. Here, a widely used dynamic vegetation model (LPJ-GUESS) was used to simulate vegetation composition/cover and surface runoff in Chile for the Last Glacial Maximum (LGM), the mid-Holocene (MH) and the present day (PD). In addition, transient vegetation simulations were carried out from the LGM to PD for four sites in the Coastal Cordillera of Chile at a spatial and temporal resolution adequate for coupling with landscape evolution models. A new landform mode was introduced to LPJ-GUESS to enable a better simulation of vegetation dynamics and state at a sub-pixel resolution and to allow for future coupling with landscape evolution models operating at different spatial scales. Using a regionally adapted parameterization, LPJ-GUESS was capable of reproducing PD potential natural vegetation along the strong climatic gradients of Chile, and simulated vegetation cover was also in line with satellite-based observations. Simulated vegetation during the LGM differed markedly from PD conditions. Coastal cold temperate rainforests were displaced northward by about 5° and the tree line and vegetation zones were at lower elevations than PD. Transient vegetation simulations indicate a marked shift in vegetation composition starting with the past glacial warming that coincides with a rise in [CO2]. Vegetation cover between the sites ranged from 13% (LGM: 8 %) to 81% (LGM: 73 %) for the northern Pan de Azúcar and southern Nahuelbuta sites, respectively, but did not vary by more than 10% over the 21 000 year simulation. A sensitivity study suggests that [CO2] is an important driver of vegetation changes and, thereby, potentially landscape evolution. Comparisons with other paleoclimate model drivers highlight the importance of model input on simulated vegetation. In the near future, we will directly couple LPJ-GUESS to a landscape evolution model (see companion paper) to build a fully coupled dynamic-vegetation/landscape evolution model that is forced with paleoclimate data from atmospheric general circulation models. [ABSTRACT FROM AUTHOR]

It is well known that ice sheet-climate feedbacks are essential for realistically simulating the spatiotemporal evolution of continental ice sheets over glacial-interglacial cycles. However, many of these feedbacks are dependent on the ice sheet thickness, which is poorly constrained by proxy data records. For example, height estimates of the Laurentide Ice Sheet (LIS) topography at the Last Glacial Maximum (LGM; ~ 21 000 years ago) vary by more than 1 km among different ice sheet reconstructions. In order to better constrain the LIS elevation it is therefore important to understand how the mean climate is influenced by elevation discrepancies of this magnitude. Here we use an atmospheric circulation model coupled to a slab-ocean model to analyze the LGM surface temperature response to a broad range of LIS elevations (from 0 to over 4 km). We find that raising the LIS topography induces a widespread surface warming in the Arctic region, amounting to approximately 1.5 °C per km of elevation increase, or about 6.5 °C for the highest LIS. The warming is attributed to an increased poleward energy flux by atmospheric stationary waves, amplified by surface albedo and water vapor feedbacks, which account for about two-thirds of the total temperature response. These results suggest a strong feedback between continental-scale ice sheets and the Arctic temperatures that may help constrain LIS elevation estimates for the LGM and explain differences in ice distribution between the LGM and earlier glacial periods. [ABSTRACT FROM AUTHOR]

It is well known that ice sheet-climate feedbacks are essential for realistically simulating the spatio-temporal evolution of continental ice sheet over glacial-interglacial cycles. However, many of these feedbacks are dependent on the ice sheet thickness, which is poorly constrained by proxy data records. For example, height estimates of the Laurentide Ice Sheet (LIS) topography at the Last Glacial Maximum (LGM; ~ 21,000 years ago) vary by more than 1 km between different ice-sheet reconstructions. In order to better constrain the LIS elevation it is therefore important to understand how the mean climate is influenced by elevation discrepancies of this magnitude. Here we use an atmospheric model coupled to a slab-ocean model to analyze the LGM surface temperature response to a broad range of LIS elevations (from 0 to over 4 km). We find that raising the LIS topography induces a widespread surface warming in the Arctic region, amounting to approximately 1.5 °C per km elevation increase, or about 6.5 °C for the highest LIS. The warming is attributed to an increased northward energy flux by atmospheric stationary waves, reinforced by surface albedo and water vapor feedbacks, which account for about two-thirds of the total temperature response. These results suggest a positive feedback between continental-scale ice sheets and the Arctic temperatures that may help constrain LIS elevation estimates for the LGM and explain differences in ice distribution between the LGM and earlier glacial periods. [ABSTRACT FROM AUTHOR]

Coupled climate-ice sheet simulations have been growing in popularity in recent years. Experiments of this type are however challenging as ice sheets evolve over multimillennial timescales, which is beyond the practical integration limit of most Earth system models. A common method to increase model throughput is to trade resolution for computational efficiency (compromise accuracy for speed). Here we analyze how the resolution of an atmospheric general circulation model (AGCM) influences the simulation quality in a stand-alone ice sheet model. Four identical AGCM simulations of the Last Glacial Maximum (LGM) were run at different horizontal resolutions: T85 (1.4°), T42 (2.8°), T31 (3.8°), and T21 (5.6°). These simulations were subsequently used as forcing of an ice sheet model. While the T85 climate forcing reproduces the LGM ice sheets to a high accuracy, the intermediate resolution cases (T42 and T31) fail to build the Eurasian ice sheet. The T21 case fails in both Eurasia and North America. Sensitivity experiments using different surface mass balance parameterizations improve the simulations of the Eurasian ice sheet in the T42 case, but the compromise is a substantial ice buildup in Siberia. The T31 and T21 cases do not improve in the same way in Eurasia, though the latter simulates the continent-wide Laurentide ice sheet in North America. The difficulty to reproduce the LGM ice sheets in the T21 case is in broad agreement with previous studies using low-resolution atmospheric models, and is caused by a substantial deterioration of the model climate between the T31 and T21 resolutions. It is speculated that this deficiency may demonstrate a fundamental problem with using low-resolution atmospheric models in these types of experiments. [ABSTRACT FROM AUTHOR]

Objective: Intrinsic inflammatory characteristics play a pivotal role in stem cell recruitment and homing through migration where the subsequent change in niche has been shown to alter these characteristics. The bone marrow mesenchymal stem cells (bmMSCs) have been demonstrated to migrate to the endometrium contributing to the stem cell reservoir and regeneration of endometrial tissue. Thus, the aim of the present study was to compare the inflammation-driven migration and cytokine secretion profile of human bmMSCs to endometrial mesenchymal stem cells (eMSCs) and endometrial fibroblasts (eSFs). Materials and methods: The bmMSCs were isolated from bone marrow aspirates through culturing, whereas eMSCs and eSFs were FACS-isolated. All cell types were tested for their surface marker, proliferation profiles and migration properties towards serum and inflammatory attractants. The cytokine/chemokine secretion profile of 35 targets was analysed in each cell type at basal level along with lipopolysaccharide (LPS)-induced state. Results: Both stem cell types, bmMSCs and eMSCs, presented with similar stem cell surface marker profiles as well as possessed high proliferation and migration potential compared to eSFs. In multiplex assays, the secretion of 16 cytokine targets was detected and LPS stimulation expanded the cytokine secretion pattern by triggering the secretion of several targets. The bmMSCs exhibited higher cytokine secretion of vascular endothelial growth factor (VEGF)-A, stromal cell-derived factor-1 alpha (SDF)-1α, interleukin-1 receptor antagonist (IL-1RA), IL-6, interferon-gamma inducible protein (IP)-10, monocyte chemoattractant protein (MCP)-1, macrophage inflammatory protein (MIP)1α and RANTES compared to eMSCs and/or eSFs after stimulation with LPS. The basal IL-8 secretion was higher in both endometrial cell types compared to bmMSCs. Conclusion: Our results highlight that similar to bmMSCs, the eMSCs possess high migration activity while the differentiation process towards stromal fibroblasts seemed to result in loss of stem cell surface markers, minimal migration activity and a subtler cytokine profile likely contributing to normal endometrial function. [ABSTRACT FROM AUTHOR]

Modeling studies have shown that the continental-scale ice sheets in North America and Eurasia in the last glacial cycle had a large influence on the atmospheric circulation and thus yielded a climate distinctly different from the present. However, to what extent the two ice sheets influenced each others' growth trajectories remains largely unexplored. In this study we investigate how an ice sheet in North America influences the downstream evolution of the Eurasian ice sheet, using a thermomechanical ice-sheet model forced by climate data from atmospheric snapshot experiments of three distinctly different phases of the last glacial cycle: the Marine Isotope Stages 5b, 4, and 2 (Last Glacial Maximum - LGM). Owing to the large uncertainty associated with glacial changes in the Atlantic meridional overturning circulation, each atmospheric snapshot experiment was conducted using two distinctly different ocean heat transport representations. Our results suggest that changes in the North American paleo-topography may have largely controlled the zonal distribution of the Eurasian ice sheet. In the MIS4 and LGM experiments, the Eurasian ice sheet migrates westward towards the Atlantic sector - largely consistent with geological data and contemporary ice-sheet reconstructions - due to a low wave number stationary wave response, which yields a cooling in Europe and a warming in northeastern Siberia. The expansion of the North American ice sheet between MIS4 and the LGM amplifies the Siberian warm anomaly, which limits the glaciation there and may therefore help explain the progressive westward migration of the Eurasian ice sheet in this time period. The ocean heat transport only has a small influence on the stationary wave response to the North American glacial topography; however, because temperature anomalies have a smaller influence on an ice sheet's ablation in a colder climate than in a warmer one, the impact of the North American glacial topography on the Eurasian ice-sheet evolution is reduced for colder surface conditions in the North Atlantic. While the Eurasian ice sheet in the MIS4 and the LGM experiments appears to be in equilibrium with the simulated climate conditions, the MIS5b climate forcing is too warm to grow an ice sheet in Eurasia. First-order sensitivity experiments suggest that the MIS5b ice sheet was established during preceding colder stages. [ABSTRACT FROM AUTHOR]

This study examines the evolution of a continental-scale ice sheet on a triangular representation of North America, with and without the influence of the Cordilleran region. Simulations are conducted using a comprehensive atmospheric general circulation model asynchronously coupled to a three-dimensional thermomechanical ice-sheet model. The atmospheric state is updated for every 2 × 106 km3 increase in ice volume, and the coupled model is integrated to steady state. In the first experiment a flat continent with no background topography is used. The ice sheet evolves fairly zonally symmetric, and the equilibrium state is continent-wide and has the highest point in the center of the continent. This equilibrium ice sheet forces an anticyclonic circulation that results in relatively warmer (cooler) summer surface temperatures in the northwest (southeast), owing to warm (cold) air advection and radiative heating due to reduced cloudiness. The second experiment includes a simplified representation of the Cordilleran region. The ice sheet's equilibrium state is here structurally different from the flat continent case; the center of mass is strongly shifted to the east and the interior of the continent remains ice free-an outline broadly resembling the geologically determined ice margin in Marine Isotope Stage 4. The limited glaciation in the continental interior is the result of warm summer surface temperatures primarily due to stationary waves and radiative feedbacks. [ABSTRACT FROM AUTHOR]

Proxy-based reconstructions of climate variability over the last millennium provide important insights for understanding current climate change within a long-term context. Past hydrological changes are particularly difficult to reconstruct, yet rainfall patterns and variability are among the most critical environmental variables. Ombrotrophic bogs, entirely dependent on water from precipitation and sensitive to changes in the balance between precipitation and evapotranspiration, are highly suitable for such hydro-climate reconstructions. We present a multi-proxy analysis (testate amoebae, plant macrofossils, stable carbon isotopes in Sphagnum, pollen, spores and macroscopic charcoal) from an ombrotrophic peat profile from the Rodna Mountains (northern Romania) to establish a quantitative record of hydro-climatic changes. We identify five main stages: wet surface mire conditions between AD 800 and 1150 and AD 1800 and 1950, and drying of the mire surface between AD 1300 and 1450, AD 1550 and 1750 and AD 1950 and 2012. Our multi-proxy reconstructions suggest that conditions during the Medieval Climate Anomaly (MCA) period (AD 900–1150) were considerably wetter than today, while during most of the ‘Little Ice Age’ (LIA; AD 1500–1850), they were dry. Mire surface conditions in the Rodna Mountains have dried markedly over the last 40 years mainly as a result of anthropogenic climate change approaching the driest conditions seen over the last 1000 years. There is a marked difference between current hydro-climatic conditions (dry mire) and those of the MCA (wet mire). This implies that for the study region, the MCA cannot provide analogous climatic conditions to the contemporary situation. Our reconstructions are in partial agreement with water table estimates elsewhere in central and eastern Europe but generally contrast with those from NW Europe, especially during LIA. We suggest that these distinctive regional differences result from fluctuations in large-scale atmospheric circulation, which determine the relative influences of continental and oceanic air masses. [ABSTRACT FROM AUTHOR]

Aim The forest steppe of the Transylvanian Plain is a landscape of exceptionally diverse steppe-like and semi-natural grasslands. Is this vegetation a remnant of a once continuous temperate forest extensively cleared by humans, or has the area, since the last glacial, always been a forest steppe? Understanding the processes that drive temperate grassland formation is important because effective management of this biome is critical to the conservation of the European cultural landscape. Location Lake Stiucii, north-western Romania, central-eastern Europe. Methods We analysed multi-proxy variables (pollen, coprophilous fungi, plant macroremains, macrocharcoal) from a 55,000 year discontinuous sequence ( c. 55,000-35,000; 13,000-0 cal. yr bp), integrating models of pollen-based vegetation cover, biome reconstruction, global atmospheric simulations and archaeological records. Results Needleleaf woodland occurred during glacial Marine Isotope Stage ( MIS) 3, but contracted at the end of this period. Forest coverage of c. 55% (early Holocene) and 65% (mid-Holocene) prevailed through the Holocene, but Bronze Age humans extensively cleared forests after 3700 cal. yr bp. Forest coverage was most widespread between 8600 and 3700 cal. yr bp, whereas grasses, steppe and xerothermic forbs were most extensive between 11,700 and 8600 cal. yr bp and during the last 3700 cal. yr bp. Cerealia pollen indicate the presence of arable agriculture by c. 7000 cal. yr bp. Main conclusions We have provided the first unequivocal evidence for needleleaf woodland during glacial MIS 3 in this region. Extensive forests prevailed prior to 3700 cal. yr bp, challenging the hypothesis that the Transylvanian lowlands were never wooded following the last glaciation. However, these forests were never fully closed either, reflecting dry growing season conditions, recurrent fires and anthropogenic impacts, which have favoured grassland persistence throughout the Holocene. The longevity of natural and semi-natural grasslands in the region may explain their current exceptional biodiversity. This longer-term perspective implies that future climatic warming and associated fire will maintain these grasslands. [ABSTRACT FROM AUTHOR]

STUDY QUESTIONS: DO endometrial stromal fibroblasts (eSF) in women with polycystic ovary syndrome (PCOS) (Esfpcos) exhibit altered estrogen and/or progesterone (P4) responses, which may explain some of the adverse reproductive outcomes and endometrial pathologies in these women? SUMMARY ANSWER: In vitro, eSF from women with PCOS exhibit an aberrant decidualization response and concomitant changes in pro-inflammatory cytokine, chemokine and matrix metalloproteinase (MMP) release and immune cell chemo attraction. In vivo these aberrations may result in suboptimal implantation and predisposition to endometrial cancer. WHAT IS KNOWN ALREADY: The endometrium in women with PCOS has several abnormalities including progesterone (P4) resistance at the gene expression level, likely contributing to subfertility, pregnancy complications and increased endometrial cancer risk in PCOS women. STUDY DESIGN, SIZE, DURATION: Prospective, university-based, case-control, in vitro study. PARTICIPANTS/MATERIALS, SETTING, METHODS: Cultures of eSFPCOS (n = 12, Rotterdam and NIH criteria) and eSFControl (Ctrl) (n = 6, regular cycle length, no signs of hyperandrogenism) were treated with vehicle, estradiol (E2, 10 nM) or E2P4 (10 nM/1 µM) for 14 days. Progesterone receptor (PGR)mRNA was assessed with quantitative real-time PCR(qRT-PCR) and eSF decidualization was confirmed by insulin-like growth factor-binding protein-1 (IGFBP-1) transcript and protein expression. Fractalkine(CX3CL1),granulocyte-macrophagecolony-stimu-latingfactor(GM-CSF),interleukin (IL)6,8and 1 1,macrophagechemoattractantprotein (MCP) 1 and3,CCL5 (RANTES) and MMPs(MMP1,2, 3,7,9, 10 and 12) were measured in conditioned media by Luminex multiplex assays, and chemotactic activity of the conditioned media was tested in a migration assay using CD 14+ monocyte and CD4+ T-cell migration assay. Effects of IL-6 (0.02, 0.2,2 or 20 ng/ml) or IL-8 (0.04, 0.4,4, or 40 ng/ml) or combination (0.2 ng/ml IL-6 and 4.0 ng/ml IL-8) on 14-d decidualization were also tested. ANOVA with pre-planned contrasts was used for statistical analysis. MAIN RESULTS AND THE ROLE OF CHANCE: Hormonal challenge with E2P4 to induce decidualization revealed two distinctsubsets of eSFPCOS. Eight eSFPCOS (dPCOS) and all eSFCtrl (dCtrl) cultures showed a normal decidualization response to E2P4 as determined by morphology and IGFBP-1 secretion. However, 4 eSFPCOS cultures showed blunted decidualization (ndPCOS) in morphological assessment and low IGFBP-1 levels even though all three groups exhibited normal estrogen-mediated increase in PGR expression. Interestingly dPCOS had decreased IL-6 and GM-SCF secretion compared with dCtrl, whereas the ndPCOS cultures showed increased IL-6 and 8, MCP1, RANTES and GM-CSF secretion at base-line and/or in response to E2 or E2P4 compared with dCtrl and/or dPCOS. Furthermore, even though PGR expression was similar in all three groups, P4 inhibition of MM Psecretion was attenuated in ndPCOS resulting in higher MMP2 and 3 levels. The conditioned media from ndPCOS had increased chemoattractic activity compared with dCtrl and dPCOS media. Exogenously added IL-6 and/or 8 did not inhibit decidualization in eSFCtrl indicating that high levels of these cytokines in ndPCOS samples were not likely a cause for the aberrant decidualization. LIMITATIONS, REASONS FOR CAUTION: This is an in vitro study with a small sample size, utilizing stromal cell cultures from proliferative and secretory phase endometrium. The effect of PCOS on endometrial epithelium, another major histoarchitectural cell compartment of the endometrium, was not evaluated and should be considered in future studies. Furthermore, results obtained should also be confirmed in a larger data set and with mid/late secretory phase in vivo samples and models. WIDER IMPLICATIONS OF THE FINDINGS: The alterations seen in ndPCOS may contribute to endometrial dysfunction, subfertility and pregnancy complications in PCOS women. The results emphasize the importance of understanding immune responses related to the implantation process and normal endometrial homeostasis in women with PCOS. [ABSTRACT FROM AUTHOR]

The combined use of proxy records and climate modelling is invaluable for obtaining a better understanding of past climates. However, many methods of model-proxy comparison in the literature are fundamentally problematic because larger errors in the proxy tend to yield a "better" agreement with the model. Here we quantify model-proxy agreement as a function to proxy uncertainty using the overlapping coefficient OVL, which measures the similarity between two probability distributions. We found that the model-proxy agreement is poor (OVL < 50%) if the proxy uncertainty (σp) is greater than three times the model variability (σm), even if the model and proxy have similar mean estimates. Hence only proxies that fulfil the condition σp < 3σm should be used for detailed quantitative evaluation of the model performance. [ABSTRACT FROM AUTHOR]

This study examines the mutual interaction between topographically-forced atmospheric stationary waves and continental-scale ice sheets using a thermomechanical ice-sheet model coupled to a linear as well as a fully-nonlinear dry atmospheric primitive equation model. The focus is on how the stationary-wave induced ablation feeds back on the ice sheet. Simulations are conducted in which an embryonal ice mass, on an idealised 'North American' continent, evolves to an equilibrium ice sheet. Under the coupling to the linear atmospheric model, the equilibrium ice sheet is primarily controlled by the ratio between the wavelength of the stationary waves and the zonal continental extent. When this ratio is near two, the ice sheet has its center of mass shifted far eastward and its shape is broadly reminiscent of the Laurentide ice sheet at LGM. For wavelengths comparable to the continental extent, however, the ice margin extends far equatorward on the central continent but is displaced poleward near the eastern coast. Remarkably, the coupling to the nonlinear atmospheric model yields equilibrium ice sheets that are virtually identical to the ones obtained in uncoupled simulations, i.e. a symmetric ice sheet with a zonal southern margin. Thus, the degree of linearity of the atmospheric response should control to what extent topographically-forced stationary waves can reorganise the structure of ice sheets. If the stationary-wave response is linear, the present results suggest that spatial reconstructions of past ice sheets can provide some information on the zonal-mean atmospheric circulation that prevailed. [ABSTRACT FROM AUTHOR]

BACKGROUND Anti-Müllerian hormone (AMH) is secreted by ovarian granulosa cells and its serum levels reflect ovarian follicle reserve. The main objective of this study was to test the use of AMH assay in identifying women with primary amenorrhea (PA) and existing follicles and to study follicle phase dependent AMH secretion. METHODS Serum levels of AMH were measured in subjects with FSH-resistant ovaries (FSHRO, n= 12), primary ovarian insufficiency (POI) with PA (n= 11) or secondary amenorrhea (SA n= 20) of unknown etiology, and controls (n= 23), and in Turner syndrome (TS) [45,X (n= 18), mosaicism (n= 7), structural X chromosome abnormalities (SCA, n= 10)], and healthy controls (n= 34). RESULTS Serum levels of AMH in women with FSHRO were comparable with those in control women (2.76 ± 2.37 versus 3.77 ± 2.36 ng/ml) and significantly higher than in women with PA (0.05 ± 0.04 ng/ml; P < 0.001) or SA of unknown origin (0.12 ± 0.20 ng/ml; P < 0.001). TS girls/women with 45,X or SCA had low serum AMH levels (0.13 ± 0.09 and 0.27 ± 0.19 ng/ml) compared with their controls (3.34 ± 2.23 ng/ml) or subjects with mosaicism (2.33 ± 2.81 ng/ml). AMH expression was detected in granulosa cells of women with FSHRO but not in any of the 45,X fetal ovarian specimens. CONCLUSIONS A serum AMH assay could be used to identify patients with decreasing ovarian reserves and POI. Moreover, our results support the notion that AMH is secreted mainly by small non-selected follicles, since follicular granulosa cells were AMH-positive and serum AMH levels were normal/low normal in women with FSHRO, who lack follicle development beyond the small antral stage. [ABSTRACT FROM AUTHOR]

This study examines mutualinteractions between stationary waves and ice sheets using a dry atmospheric primitive-equation model coupled to a three-dimensional thermomechanical ice-sheet model. The emphasis is on how non-linear interactions between thermal and topographical forcing of the stationary waves influence the ice-sheet evolution by changing the ablation. Simulations are conducted in which a small ice cap, on an idealised Northern Hemisphere continent, evolves to an equilibrium continental-scale ice sheet. In the absence of stationary waves, the equilibrium ice sheet arrives at symmetric shape with a zonal equatorward margin. In isolation, the topographically induced stationary waves have essentially no impact on the equilibrium features of the ice sheet. The reason is that the temperature anomalies are located far from the equatorward ice margin. When forcing due to thermal cooling is added to the topographical forcing, thermally induced perturbation winds amplify the topographically induced stationary-wave response, which that serves to increase both the equatorward extent and the volume of the ice sheet. Roughly, a 10% increase in the ice volume is reported here. Hence, the present study suggests that the topographically induced stationary-wave response can be substantially enhanced by the high albedo of ice sheets. [ABSTRACT FROM AUTHOR]

This work focuses on the Late Saalian (140 ka) Eurasian ice sheets' surface mass balance (SMB) sensitivity to changes in sea surface temperatures (SST). An Atmospheric General Circulation Model (AGCM), forced with two preexisting Last Glacial Maximum (LGM, 21 ka) SST reconstructions, is used to compute climate at 140 and 21 ka (reference glaciation). Contrary to the LGM, the ablation almost stopped at 140 ka due to the climatic cooling effect from the large ice sheet topography. Late Saalian SST are simulated using an AGCM coupled with a mixed layer ocean. Compared to the LGM, these 140 ka SST show an inter-hemispheric asymmetry caused by the larger ice-albedo feedback, cooling climate. The resulting Late Saalian ice sheet SMB is smaller due to the extensive simulated sea ice reducing the precipitation. In conclusion, SST are important for the stability and growth of the Late Saalian Eurasian ice sheet. [ABSTRACT FROM AUTHOR]

The article discusses a study which investigated the influence ice-sheet topography has had on atmospheric stationary waves using a linear two-level atmospheric model. Information is presented on the development of the model for calculating the ice-sheet profile and experimental design. A qualitative analysis of the manner in which temperature and snowfall anomalies induced by the ice sheet can affect its mass balance and evolution is discussed. The article also examines the stationary-wave influence on the temperature over an equatorward-expanding ice sheet.

Endometriosis, a relatively common disease generally affecting women in the reproductive age group, is mostly found in the pelvic organs. Although endometriosis is a benign disease, some malignant tumors have been reported to develop in endometriotic lesions, most commonly in the ovary. The relationship between endometriosis and malignancy is not well known, but the majority of endometriosis-associated ovarian malignancies are usually endometrioid adenocarcinomas and clear cell carcinomas. The sex cord-like variant of endometrioid adenocarcinoma is a rare tumor that histologically closely resembles the sex cord-stromal tumor. Despite its rarity, the correct histological diagnosis of the sex cord-like variant of endometrioid adenocarcinoma is crucial to avoid misdiagnosis of a less aggressive tumor. We here report a 53-year-old woman who was diagnosed as having this very rare subtype of endometroid adenocarcinoma curiously arising from an endometriotic lesion at the site of previous salpingo-oophorectomy. The tumor was diagnosed based on light microscopy and immunohistochemistry. [ABSTRACT FROM AUTHOR]

Basement membranes (BMs) play an important role in anchoring epithelial cells and separating them from the adjacent stroma. Altered composition and assembly of BMs may influence carcinoma cell growth and invasion. Using immunohistochemistry and in situ hybridization, we investigated the expressions of the BMs components laminin-5 (Ln-5) subunits and collagen types IV, VII and XVII in normal endometrium and compared them to the expression pattern in hyperplastic and neoplastic endometrium. Chains of Ln-5 ( α3 β3 γ2) and types IV, VII and XVII collagens were observed in normal endometrium. In hyperplastic endometrium, laminin γ2 chain and type XVII collagen showed intensified expression in foci of dispersed epithelial cells. Individual carcinoma cells in adenocarcinomas of low differentiation grade displayed increased laminin γ2 chain and type XVII collagen immunoreactivity and mRNA synthesis, whereas type VII collagen usually showed decreased expression. Laminin and type IV collagen showed BM disruptions, especially in tumors with low differentiation. Our results indicate that all the BM anchoring molecules investigated are expressed in normal endometrium, but the expression of laminin γ2 chain and collagen type XVII is altered in endometrial adenocarcinomas, which support their role in malignant growth. [ABSTRACT FROM AUTHOR]

In an attempt to develop a gene therapy method for splenic and systemic diseases, an evaluation was made of surgical methods for gene transfer into porcine spleen. We have developed a continuous closed-circuit organ perfusion method for gene transfer into porcine spleen. For gene transfer, we used a type-5 replication defective adenovirus vector expressing the E. coli beta-galactosidase gene as a reporter gene. In eight young 22-35 kg farm pigs, the spleen was perfused in vivo with the viral solution via laparotomy, for 30 or 60 min. Gene transfer was determined visually on histological cryosections after X-gal and PAS staining. Infusion of the viral solution through the splenic artery did not result in gene expression. Perfusion of spleen in vivo resulted in beta-galactosidase reporter gene expression in the macrophages located around capillaries terminating in the perifollicular zone and in the red pulp examined after four days. The present results suggest that the surgically performed spleen perfusion method can be used for gene transfer in the treatment of diseases having splenic manifestations and in systemic diseases. [ABSTRACT FROM AUTHOR]

In an attempt to develop a gene therapy method for splenic and systemic diseases, an evaluation was made of surgical methods for gene transfer into porcine spleen. We have developed a continuous closed-circuit organ perfusion method for gene transfer into porcine spleen. For gene transfer, we used a type-5 replication defective adenovirus vector expressing the E. coli β-galactosidase gene as a reporter gene. In eight young 22-35 kg farm pigs, the spleen was perfused in vivo with the viral solution via laparotomy, for 30 or 60 min. Gene transfer was determined visually on histological cryosections after X-gal and PAS staining. Infusion of the viral solution through the splenic artery did not result in gene expression. Perfusion of spleen in vivo resulted in β-galactosidase reporter gene expression in the macrophages located around capillaries terminating in the perifollicular zone and in the red pulp examined after four days. The present results suggest that the surgically performed spleen perfusion method can be used for gene transfer in the treatment of diseases having splenic manifestations and in systemic diseases. [ABSTRACT FROM AUTHOR]

The distribution of the extracellular matrix proteins types III pN-collagen and IV collagen, laminin and tenascin was investigated in fetal, infant, and adult human spleens by using immuno-electron microscopy. The presence of type III pN-collagen was assessed by using an antibody against the aminoterminal propeptide of type III procollagen. All the proteins other than type III pN-collagen were found in reticular fibers throughout development. In the white pulp of the fetus aged 16 gestational weeks, only an occasional type III pN-collagen-containing fibril was present, although type III pN-collagen was abundant in the reticular fibers of the red pulp. Conversely, in adults, most of the reticular fibers of the white pulp, but not of the red pulp, were immunoreactive for type III pN-collagen. Ring fibers, the basement membranes of venous sinuses, were well developed in both infant and adult spleens. The first signs of their formation could be seen as a discontinuous basement membrane, which was immunoreactive for type IV collagen, laminin, and tenascin in the fetus aged 20 gestational weeks. Intracytoplasmic immunoreactivity for all the proteins studied was visible in the mesenchymal cells of the fetus aged 16 gestational weeks and in the reticular cells of the older fetuses, which also showed labeling for type IV collagen and laminin in the endothelial cells. The results suggest that proteins of the extracellular matrix are produced by these stationary cells. [ABSTRACT FROM AUTHOR]

The immunohistochemical distribution of the basement membrane (BM) proteins, laminin and type IV collagen, and interstitial type III collagen was investigated in 12 fetal spleens at the 15th-38th gestational weeks (g.w.) and in spleens of 8 infants from term to 4 years. The results were compared with the distribution of the same proteins in adult human spleen. BM proteins were found to be abundantly present in the red pulp of all spleens during the whole of development. The content of type III collagen gradually decreased with advancing age and, in adult spleen, there were only occasional positively staining fibers in Billroth's cords. This finding indicates that the composition of reticular fibers in the red pulp of spleen is different from the reticular fibers elsewhere in lymphoreticular tissue. Early signs of ring fiber formation in the walls of venous sinuses were detectable at the 15th-19th g.w., although their more complete development occurred relatively late from the 36th g.w. onwards. Ring fibers contained both laminin and type IV collagen in all the investigated spleens. They never stained for type III collagen. The developing white pulp was positive for BM proteins, but showed no staining for type III collagen at the 15th g.w. At later ages, the white pulp stained similarly for both BM proteins and type III collagen. [ABSTRACT FROM AUTHOR]

Reports a case of multiple progressive pulmonary leiomyomatous metastases treated with tamoxifen. Thoracoscopy; Immunohistochemical analysis; Pathogenesis of the disease.