Exposed ice-wedge sublimation proceeds ~4× faster than predicted from analogy to heat loss by buoyant convection, a theory frequently employed in Mars studies. Our results can be used to map near-surface ice-content differences, identify surface processes controlling landform formation and morphology, and identify target landing sites for human exploration of Mars.Sublimation of ice is rate-controlled by vapor transport away from its outer surface and may have generated landforms on Mars. In ice-cemented ground (permafrost), the lag of soil particles remaining after ice loss decreases subsequent sublimation. Varying soil-ice ratios lead to differential lag development. Here we report 52 years of sublimation measurements from a permafrost tunnel near Fairbanks, Alaska, and constrain models of sublimation, diffusion through porous soil, and lag formation. We derive the first long-term in situ effective diffusion coefficient of ice-free loess, a Mars analog soil, of 9.05 × 10 2 atmosphere.Sublimation of ice is believed to have generated a variety of landforms on Mars and other planetary bodies. Here the authors show the first long-term in situ effective diffusion coefficient of terrestrial ice-free loess , scaled to Mars average pressure, temperature and CO A range of dramatic landforms are thought to have developed from or been modified by ice sublimation and lag formation  limiting our ability to characterize, model, or predict landscape changes by sublimation. Sublimation-based processes are fundamental to geologic evolution elsewhere in the solar system, particularly on Mars14, emphasizing the importance of Earth-analog studies.On Earth, meteorologic conditions favorable for sublimation are sensitive to air temperature and humidity and are overshadowed by snowfall and melt events, so few locations provide an opportunity for long-term  sublimation measurements15. No other tunnel provides similar access to a more than 50-year record of permafrost sublimation. The inside of the Tunnel provides a location with a stable air temperature (−4.1 ± 1.4 °C) and relative humidity (91 ± 3%) and no wind to remobilize sediment particles. Multiple periods of Tunnel excavation provide access to exposed surfaces where sublimation can be accurately quantified over a variety of exposure times. From these observations we are able to quantify water-vapor diffusion through undisturbed loess , and sublimation of clean ice by free convection.To better understand how sublimation can develop landscape features in permafrost terrains on Mars we measured sublimation along the walls of the U.S. Army Cold Regions Research and Engineering Laboratory’s Permafrost Tunnel near Fairbanks, Alaska (hereafter referred to as the Tunnel). The Tunnel is a 250 m long underground research facility excavated through syngenetic ice-rich permafrost since the mid-1960s and is unique on EarthWe measured the rates of ice sublimation and ice-free lag formation at multiple locations within the Tunnel through two experimental campaigns. In the first campaign we repeatedly measured sublimation of freshly exposed ice and adjacent ice-cemented loess at one location over a 386 day period. For the second campaign we measured sublimation from these same two types of ice featured at various locations throughout the Tunnel representing exposure initiated at different times during the Tunnel’s (then) 52-year record. From these measurements we constrain models of sublimation through soil pores and lag formation and derive the first long term in situ effective diffusion coefficient through ice-free loess, a Mars analog soil.For the first experimental campaign we selected a location 32 m into the main Tunnel where an ice wedge and the surrounding ice-cemented loess are present at a shallow  angle for which slumping and sediment detachments were not commonplace. This area was initially excavated in the mid-1960s. The ice-rich study feature is 1.5 m tall and 2 m wide . Values ranged from 0.6 to 2.1 g of water (ice) per gram of dried loess. Based on an intrinsic density of 2.56 g cc−1, these values translate to 63 to 85% ice by volume, at the low end consistent with high-porosity loess previously measured from the Tunnel18 and at the high end consistent with the presence of ice lenses  and other locations throughout the Tunnel (n = 30). The gravimetric moisture content of the wedge ice ranged from 250 to 810 g of water per gram of dried loess, less than 0.4% wt. soil content. There was no statistically significant difference between the gravimetric moisture contents at the 386 day measurement location and the remainder of the Tunnel for either the wedge ice or the loess .At the conclusion of this 386-day experiment we extracted twelve 15 cm long by 7 cm diameter SIPRE cores from the ice-cemented loess adjacent to the ice wedge to measure the gravimetric moisture content and soil compositionFor the second experimental campaign we examined the long-term development of ice-free dry-loess lag and ice-wedge ice retreat at locations throughout the Tunnel. Several sections of the wall had been cleared of dry-loess lag at different times in the Tunnel’s history for a variety of small experiments and excavations 10, 11, and 18 years ago, exposing fresh ice-cemented loess surfaces to sublimation Fig. . Two majIn 2015 we made lag thickness measurements overlying ice-cemented loess at multiple locations throughout the Tunnel where excavation occurred along main wall sections at known times of Tunnel excavation. These sites represent elapsed times since 1964, 1998, 2011, and 2013. A graduated steel rod was pushed into the sediment to refusal and the depth of the rod was noted. Fifty of these measurements were made from each of the different aged walls representing the four time periods since excavation. Additionally, we repeated these four measurement sets in 2016 after one year of additional lag was allowed to develop.The Tunnel has a cooling system to ensure temperatures remain below freezing through the summer months. An array of thermistors reporting real time temperature and relative humidity has been operated in the Tunnel since the mid-1960s. In 2008 a system of thermistors and automatically recording dataloggers were installed to record hourly measurements of air temperature and relative humidity. A mean air temperature of −4.1 °C  and relative humidity of 91% (SD of 3%) were recorded in the main tunnel between 2008 and 2016. These values are similar to the real time measurements made since the mid-1960s. The standard deviations in the datalogger values are due to real temporal changes in environmental conditions as the cooling system varied during seasonal changes or thermal experiments were performed in the Tunnel. Mean temperatures also vary by +/−0.7 °C between different locations within the tunnel with a slight stratification of colder denser air near the floor. Deviations from the mean, typically for no more than 1–5 days, are associated with focused heating and cooling experiments in the Tunnel and they are not long lasting. Since 2008 the air temperature and relative-humidity deviations have ranged from 0 to −11.3 °C and 65% to 99%, respectively. Knowledge of the long-term temperature of the icy permafrost walls is limited (discussed below).−3 (SD of 0.4 g m−3). At different locations within the tunnel, the mean absolute humidity varied by about +/−0.16 g m−3. During 2008–2009 we measured the temperatures and humidity profile from floor to ceiling (0–4 m) at the location of the 386-day experiment and found that air near the floor was 8% drier than air above 1.5 m, consistent with the buoyancy of humid air.Since sublimation and vapor-diffusion processes are dependent largely on gradients in the water-vapor concentration, and since the relative humidity has an added dependence on temperature, we report the absolute humidity in terms of a water-vapor density. The average vapor density recorded between 2008 and 2016 was 3.2 g mr2 = 0.90), and has resulted in nearly 10 cm of weakly cohesive dry-loess lag over 52.5 years. It is clear that in ice-cemented loess the rate of sublimation decreases over time as sublimation leaves an increasingly thicker protective dry-loess lag. In comparison, the rate of sublimation loss of wedge ice was 1.21 m over the 52-year record with a linear fit of the rate of ice loss with time (r2 = 0.98).As shown in Fig. 20. The sublimation rate decreases proportionally to the growing lag thickness  can be expressed asZ. D is the effective diffusion coefficient of the dry lag, which depends on the pore structure via D12 is the binary diffusion coefficient of water vapor in air, 20. D12 is proportional to temperature and air pressure as Sublimation and desiccation of ice-cemented loess occurs by vapor diffusion through the porous-soil lag left behind as ice is lost and residual mineral and soil particles remainess Fig. , as goveThis flux of water being lost can also be expressed in terms of the lag growth rate Integrating Eqs.  and 2)  2) yield−6 m2 s−1 (r2 = 0.96), representing the first determination of the diffusion coefficient in a terrestrial field setting.Equation  can be f22. The temperature history of the wall-ice surface (the wedge-ice surface or the interface between dry-loess and ice-rich loess) has not been measured. We expect the bulk permafrost at the depth of the tunnel to reflect the local mean surface temperature over the past 30 to 100 years, estimated to be in the range of −5 to −3 °C24. However, the active cooling of air within the tunnel will slowly effect the wall surfaces such that the wall temperatures will gradually warm or cool toward the mean air temperature; large swings in air temperature will be greatly subdued by the large thermal mass of the permafrost, compounded by any insulating dry-loess layer; and latent heat of sublimation of wall ice will further cool the walls. As such −4.1 °C is a reasonable mean wall temperature, but may deviate slightly, the sensitivity of which is discussed below.In these calculations we assumed the wall temperature is isothermal with the measured average air temperature of −4.1 °C, consistent with reported subsurface temperatures in the area−3, and a lag porosity of 68% based on previous laboratory measurements In examining the overall lag growth over the 52.5-year history of the Tunnel we assumed constant environmental conditions. This assumption is supported by the linearity of exposed wedge ice loss  change with respect to sublimation and given by −(Δρ/ΔC)/ρ, ΔC = Cs – C∞ is the water vapor concentration gradient, and ν is the kinematic viscosity of air.In Eq.  hm is thC = 0.59 and m = 1/4, which are derived empirically30. Equation  and is linear in time  combined with Eq.  we then obtain a sublimation rate of 10.2 kg m−2 yr−1, still 2× smaller than our observation. However, this scenario is weakened by the fact that this rising air would encounter more humid conditions as it convects to a position above the floor. This would rapidly reduce any buoyancy advantage that might have resulted from a drier source. Therefore, the discrepancy between the standard model and our observation is closer to 4×.If we consider a scenario where drier air near the floor is buoyantly convected up the face of the ice wedge  samples of Tunnel loess18 yielded an effective diffusion coefficient of 7.35 × 10−6 m2 s−1, about 1.23× smaller than our in situ diffusion coefficient. This difference suggests that in situ cohesive loess retains a more openly-connected pore structure  than the disturbed loess samples with the same porosity. Such open structure may result from ice growth and soil freezing processes occurring when the wet loess initially froze within the pores 11,000–40,000 years ago. The process likely increased pore-to-pore connectivity, either through the expansion of water upon freezing within existing pores, or by grain-scale ice segregation cause by thin film migration along grain32. Such a grain-scale expanded structure could be retained after desiccation, supported by remaining grain contacts and mild cohesion.We have derived the vapor-diffusion coefficient of the intact Tunnel loess to be 9.05 × 1033. Several studies of Dry Valley ground-ice stability and ice loss have used theory-based estimates of the effective diffusion coefficient of the ice-free permafrost till and report values of ~2–6.3 × 10–6 m2 s−1 refs. ,13,29),2913,29]. These Antarctic soils have generally lower porosity and tortuosity compared to Tunnel loess18. Accounting for these differences, our results suggest that an appropriate diffusion coefficient for Antarctic applications lies at the high end of this range, especially when examining permafrost desiccation and vapor diffusion through the desiccated lag (sublimation till).The Antarctic Dry Valleys represent a rare natural permafrost setting on Earth where sublimation and vapor diffusion are dominant and liquid water is virtually absent34. In this scenario, desiccation of ice-rich permafrost retains a high-porosity and low-thermal-conductivity structure analogous to Tunnel loess. In experiments conducted with sublimation of clay and ice mixtures, a high-porosity lag was produced and termed filamentary sublimation residue, which was proposed as an analog to sublimation lags formed on Mars and comets35.The results from this study can also help to develop better predictive physical and conceptual models of the role of sublimation in the formation and evolution of geomorphologic features in permafrost terrains on Mars. Our measurements provide a useful analog for various studies of Mars ice sublimation, permafrost desiccation, glacial-ice stability, and responses to climate changes. Fine-grained martian soils may exhibit a similar high-porosity structure to that of Tunnel loess after desiccation of interstitial ice. This analogy has been proposed as an explanation for a continental-scale deposit of low-thermal-inertia surface soil found in the southern high latitudes of MarsT3/2 and P−1, as noted above. On Mars, the mean temperature is −68 °C (205 K) and atmospheric pressure is 600 Pa, such that the diffusion coefficient for this same soil would be ~109× larger. However, the difference in diffusion through air (Earth atmosphere) and carbon dioxide (Mars atmosphere)20 reduces this scaling by a factor of 1.65 to give a Mars effective diffusion coefficient of 5.99 × 10−4 m2 s−1, ~66× larger. This value is similar to laboratory measurements conducted with glass spheres at Mars pressures36. This value is also 4 to 5 times larger than has been utilized previously in Mars theoretical studies38, which can be mainly attributed to the high-porosity and low tortuosity structure of this analog to martian soil.Based on the kinetic theory of gases, the binary diffusion coefficient scales as 38, along with associated loss (or gain) of ground ice as stability conditions change3. Relict ice (unstable ice left over a past climate state) may persist if a sufficient delay of ice-loss follows the most recent period of stability. Rapid diffusion of sublimated water vapor decreases the potential for relict ice to occur. Sublimation till and karst landforms may form from the loss of a massive subsurface ice matrix, resulting in visible differential subsidence which may be linked to lag thickness and lag growth, and to contrasting ice-soil ratios33. Glacial ablation, thermokarst pits and scarps, high-relief patterned ground, and curvilinear ridge-and-trough textures resembling brain coral may all form rapidly in the current martian climate.The larger diffusion coefficient we derive for Mars would yield higher rates of sublimation of unstable ground ice and rapid diffusive exchange of water between the martian regolith and atmosphere. Orbital cycles and resulting climate change on Mars have been previously examined25. Subsequent studies have further explored water stability and melting potential32, the lifetime of surface ice39, and the stability of polar ice caps in relation to climate change40. Each of these studies have employed a variant of Eq. . The main tunnel (adit), roughly 90 m long, was excavated horizontally into a gently sloping northwestward facing hill from 1963 to 1966. The Tunnel is 4 to 5 m tall and 5 to 6 m wide. Groove marks from the mining machine used in the 1960s excavation are still readily visible in many locations and are evidence of original wall and ceiling locations representing the 52-year record presented in this study. A gently sloping 50-m long ramp (winze) was excavated from 1968 to 1969. Unique experiments in 1999 and 2006 led to clearing of dry loess from multiple 10 m long by 2 m high exposures along the Tunnel walls. An additional 35 m of Tunnel was excavated in 2011 and 40 m more in 2013. All of these sections contain ice wedges and ice-cemented loess and the different excavation periods provide additional clean walls on which sublimation has acted since excavation. The temperature and relative humidity within the Tunnel have been maintained since the mid-1960s for Tunnel stability.23. The Fairbanks area has a continental climate with a current mean annual temperature of −3.3 °C24. Paleoclimate temperatures in this area are less constrained, but have remained below freezing throughout the Holocene as evidenced by stable Tunnel sediments. Permafrost in the area is discontinuous and is predominantly present in valley bottoms, on north-facing slopes, and in poorly drained soils47. Permafrost exposed in the Tunnel is syngenetic48 with ice wedges, segregated ice, reticulate-chaotic ice, and thermokarst cave ice15. Ice wedges are up to 3 m wide and some, covering the entire vertical distance of the walls, are more than 5 m tall. Sequences preserved in the Tunnel have radiocarbon ages between ~11,000 and 40,000 years BP50 and are overlain by Holocene deposits23.The Tunnel provides access to Late Pleistocene-aged aeolian loess, reworked loess, and alluvium and colluvium of the Goldstream FormationPeer Review File


Urticaria (hives) is a highly prevalent skin disorder that can occur with or without associated angioedema. Chronic spontaneous urticaria (CSU) is a condition which persists for more than 6 weeks in duration and occurs in the absence of an identifiable provoking factor. CSU results from pathogenic activation of mast cells and basophils, which gives rise to the release of proinflammatory mediators that support the generation of urticaria. Several theories have been put forth regarding the pathogenesis of CSU with much evidence pointing toward a potential autoimmune etiology in up to 50% of patients with this condition. In this review, we highlight the evidence surrounding the autoimmune pathogenesis of chronic urticaria including recent data which suggests that CSU may involve contributions from both immunoglobin G (IgG)-specific and immunoglobulin E (IgE)-specific autoantibodies against a vast array of antigens that can span beyond those found on the surface of mast cells and basophils. Urticaria, more commonly known as “hives”, is a prevalent disorder that affects between 15 and 25% of the population at some point during their lifetimes . Urticarin vivo studies suggesting that CD301b+ dermal dendritic cells (DCs) are actually first to sample antigen and then relay it to nearby mast cells through secreted microvesicles  have been observed within the inflammatory infiltrates of patients with CSU, it is well-established that histamine and other mast cell products are predominantly responsible for development of this condition [note that skin biopsies are seldom needed for the diagnosis but are occasionally useful to distinguish CSU from other inflammatory conditions such as urticarial vasculitis ]. The phvesicles . HoweverTwo major mechanisms have been put forward with regards to the pathogenesis of chronic urticaria. The first is not autoimmune in nature, but involves dysregulation of intracellular signaling pathways within mast cells and basophils that lead to defects in trafficking or function of these cells. The second involves the development of autoantibodies to FcεRIα or IgE on both mast cells and basophils and will be discussed in more detail in the following sections . Both ofin vitro than their healthy counterparts -containing inositol phosphatases SHIP-1 and SHIP-2 associate with the FcεR1 β subunit and are activated upon stimulation with IgE or antigen . It is lWhile cellular signaling defects may account for some cases of CSU, the autoimmune theory is the more widely accepted hypothesis to explain the inappropriate activation of mast cells and basophils in patients with chronic spontaneous urticaria. Up to 45% of cases of CSU are thought to be autoimmune in etiology. In a sentinel study conducted by Grattan et al., 12 patients with chronic urticaria were subjected to intradermal autologous serum injection . Seven oin vivo assay of mast cell activation that is induced by intradermal injection of a patient's serum into self. It has now been accepted that nearly 50% of patients with CSU will have a positive test in response to factors present within their own serum within 30 min of injection. Additional groups have suggested that such “factors” are indeed autoantibodies or histamine-releasing factors that are capable of inducing mast cell degranulation. Unfortunately, these data have been somewhat difficult to interpret, as positive ASSTs are not unique to patients with CSU and have been noted in a substantial proportion of patients with allergic or non-allergic rhinitis, multiple drug allergy syndrome, and even in healthy control subjects  were able to elicit histamine release from healthy donor peripheral blood leukocytes with similar kinetics as anti-IgE antibodies . IntriguIn addition to the aforementioned findings, the authors astutely noted that histamine release could be elucidated when chronic urticarial serum was incubated with basophils from donors with very low serum IgE concentrations but not with anti-IgE . These din vitro basophil activation and subsequent histamine-releasing activity fails to correlate with the presence of autoantibodies to FcεR1α even among patients with chronic urticarial   antibodies relative to healthy controls, though this distribution was found to be bimodal with 39% of CSU patients exhibiting IgE anti-TPO levels similar to control subjects (IgE anti-TPOlow) . It is tlow) . Rorsmanlow) . Autoalllow) , 46 and low) . In suchs of CSU . Recent s of CSU . These rs of CSU . Howeverin vitro analyses demonstrated that IL-24 contributes to histamine release from human mast cells sensitized with IgE from CSU but not control subjects and that IgE-anti-IL-24 levels have reasonable predictive value for disease activity. The questions of why and how IgE autoantibodies develop and to what degree they contribute to CSU pathogenesis when compared to IgG autoantibodies has yet to be determined and is likely to be the focus of many future studies in this field.IgE-mediated autoimmunity is becoming increasingly recognized as a possible contributor to the pathogenesis of a variety of systemic conditions including systemic lupus erythematosus and rheumatoid arthritis . A multi2LEN/EDF/WAO remain the most popular among practicing clinicians  should first be undertaken  Multipleinicians . If caseOmalizumab is an IgG monoclonal antibody against the Fc portion of the IgE antibody and prevents free IgE from binding to high-affinity FcεR1 receptors on mast cells and basophils. The first multicenter, placebo-controlled study evaluating omalizumab use in CSU examined efficacy of this therapy in subjects with IgE autoantibodies and found that 70% of omalizumab-treated patients who were otherwise refractory to standard antihistamine therapy were completely protected against wheal development (vs. 4.5% of placebo-treated subjects) . AnotherPost hoc analysis of randomized clinical trial data have demonstrated that omalizumab increases peripheral blood basophil counts by likely reducing recruitment of these cells to the skin  vs. a type II hypersensitivity reaction (autoimmunity) is still largely unclear, however, it does appear that patients with autoallergy experience faster response times when treated with omalizumab. In one study, subjects refractory to standard antihistamine therapy with IgE anti-TPO antibodies were randomized to receive omalizumab in 2 or 4 week intervals for a span of 24 weeks. Patients with anti-IgE TPO antibodies experienced early responses to omalizumab, suggesting that rapid neutralization of IgE is the major mechanism by which omalizumab benefits this particular cohort . On the Chronic spontaneous urticaria is a common and complex disorder that occurs in the absence of any identifiable provoking factor. While there are many aspects regarding CSU that have yet to be understood, it is becoming increasingly clear that both autoimmunity (IgG-mediated disease) and autoallergy (IgE-mediated disease) can contribute to the pathogenesis of this disorder and predispose subjects to the development of additional autoimmune diseases. Subjects with IgE autoantibody-mediated CSU appear to have a faster onset of improvement in response to omalizumab than those with IgG-mediated disease due to the unique mechanisms by which this drug sequentially affects IgE levels and FcεR1 status. Further investigation is required to determine how the presence of unique autoantibodies can predict the disease course and comorbidities associated with various subtypes of CSU as well as overall responsiveness to therapy.SB and ASM conceptualized the topic of the review article and wrote the review. SA and ASM supervised the writing of this review.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Allergic diseases are among major pediatric issues as they are highly prevalent and chronic. Therefore, identification of factors contributing to allergic disease could play a significant role in prevention of these conditions. This study aimed at investigating the IgE level in newborn’s umbilical cord blood and its relationship with some maternal factors.A cross-sectional study was conducted in 101 mothers and their newborns in Babol, Iran 2016. The samples were selected using non-probability convenience sampling. Information including newborn sex, gravidity, history of allergy before and during pregnancy , family history of allergy among mothers, history of exposure to secondhand smoke and pets, and delivery techniques was recorded. The IgE levels in newborn umbilical cord blood and maternal serum were measured using an IgE kit and ELISA technique.The newborns included 53 females (52.5%) and 29 mothers had vaginal birth (28.7%). History of exposure to secondhand smoke was found in 15 samples (14.9%), and 18 participants reported exposure to pets (17.8%). The median IgE levels in newborns and their mothers were 0.41 and 98.6, respectively. In general, IgE level in all newborns was within the normal range, but, it was higher than normal in 15 mothers (14.9%). The IgE level was significantly higher in male newborns than that of the female newborns (p = 0.011). There were no significant differences in the IgE levels of mothers and their newborns on the basis of delivery technique and history of exposure to pets (p > 0.05).In this study, the IgE level in all newborns was within the normal range, and sex was found to be an effective factor in IgE levels. TherThis study aimed at investigating the IgE level in umbilical cord blood of a population of newborns in Babol, Iran to specify the relationship between this level and some maternal variables.This cross-sectional study was conducted in the mothers and their newborns, attending Babol Rouhani Hospital for giving birth during the fall and winter of 2016–2017. The participants were selected using non-probability convenience sampling. The minimum sample size estimation was approximately 100 patients based on p = 0.6, a = 0.05, and d = 0.1. Data was collected by recording the following information: demographic information , history of allergy before and during the pregnancy , mother with a family history of allergy, history of exposure to secondhand smoke and pets, and delivery method. After obtaining the informed consent from parents, 1 cc of maternal serum and newborn umbilical cord blood samples were taken. The sampling was done using a 2 cc syringe. The samples were stored at 2–8 °C and then delivered to the laboratory for measurement of the total IgE. The IgE level in umbilical cord blood samples was examined using an IgE kit and nephelometry technique. High IgE level suggested that the mother and newborn blood cells were mixed. Therefore, cases with high IgE levels (n = 3) were excluded. The IgE levels in newborn umbilical cord blood and mother serum were measured using an IgE kit and ELISA technique. Based on kit handbook, IgE less than 13, 81 and 127 (IU/ml) for age less than 1, 1–7 years and more than 8 years, respectively, was considered as normal level. Parents provided informed consent for umbilical cord blood sampling. Data were analyzed in SPSS16 and Mann–Whitney U test was applied to compare the IgE level in mothers and their newborns based on different variables. In this study, the significance level was set at lower than 0.05. The one sample Kolmogorov–Smirnov test was used to investigate normal distribution of IgE level.This study was conducted in 101 mothers and 101 newborns. The mean age of mothers was 30.7 ± 5.2 (17–41 years old). The mean maternal age of the participants was 38.4 ± 0.9 years old. Data about the distribution of sex, gravidity, and delivery technique is presented in Table There were three mothers with allergic problems during labor (3%), one had a history of allergy (1%), and one mother was found with a family history of allergy (1%). Nine people had a history of underlying diseases (8.9%), including blood pressure disorder (n = 1), diabetes (n = 2), diabetes with blood pressure (n = 2), hypothyroidism (n = 2), and sarcoidosis (n = 2). There was a history of exposure to secondhand smoke in 15 participants (14.9%), and 18 reported exposure to pets (17.8%).The median IgE levels (IU/ml) in newborns and their mothers were 0.41 and 98.6, respectively. In general, IgE level of all newborns was within the normal range; whereas, it was higher than normal level in 15 mothers (14.9%).The distribution of IgE level in mothers and their newborns is presented in Table In present study, the IgE level of all newborns was within a normal range, but it was higher than normal range in 15 mothers (14.9%). In an investigation of 763 childbirths, including 724 term births and 39 preterm births 14% of mothers had high levels of IgE . This isIn current study, significantly higher levels of IgE were seen in male newborns p = 0.011). Consistent with our findings, Petrovičová et al. also found that the IgE level in umbilical cord blood was higher in male newborns , so, the. ConsistIn current study, delivery method did not significantly influence the IgE levels of mothers and their newborns. But Nabavi et al. showed a relationship between the umbilical cord blood IgE and delivery method . SimilarThe IgE level was found to be significantly lower in newborns of 15 mothers (14.9%) with a history of exposure to secondhand smoke (p = 0.014). In contrast, Gurbuz et al. showed no significant correlation between exposure to secondhand smoke and umbilical cord IgE level .In the current study, the IgE levels of mothers and their newborns was not significantly different based on the childbirth method Two studies investigating the relationship between prenatal exposure to pets and IgE level in newborn umbilical cord revealed different results. Hernandez et al. showed that having pets could influence the umbilical cord IgE level , but GurThis study was associated with some limitations, including lack of a control group. The researchers suggest further studies with greater sample size, as of longitudinal studies into the effect of IgE level in newborns with allergic diseases during childhood.Results showed that the IgE level in all newborns was within the normal range, but sex was found to be an effective factor.


Later birth order, being male, maternal illiteracy, short maternal stature, lack of improved water source, and household poverty were also associated with wasting in various countries, but not systematically in all. Seasonality was also not consistently associated with wasting in the final models. These findings suggest that pre-conception (adolescence), pregnancy and early postpartum, represent windows of opportunity for tackling child wasting, not only stunting. Our analysis suggests that the underlying determinants of wasting and stunting in South Asia are similar, but not universal across geographies. Cost-effective interventions to prevent both stunting and wasting, and to treat severe wasting, need to be scaled up urgently. Separating these two manifestations of child undernutrition in conceptual and programmatic terms may unnecessarily impair progress to reach the Sustainable Development Goals targets aimed at addressing both child stunting and wasting.South Asia continues to carry the greatest share and number of wasted children worldwide. Understanding the determinants of wasting is important as policymakers renew efforts to tackle this persistent public health and development problem. Using data from national surveys in Bangladesh, India, the Maldives, Nepal, Pakistan and Afghanistan, this analysis explores factors associated with wasting among children aged 0 to 59 months . We conducted multivariate mixed logistic regression and backwards stepwise methods to identify parsimonious models for each country separately . Younger children (0 to 5 months), and those whose mothers had a low body mass index (<18.5 kg/m Approximately 52 million children worldwide suffered from wasting in 2016, defined as a weight-for-height Z-score (WHZ) < -2 of WHO’s Child Growth Standards , 4. WastA large body of literature has highlighted the mortality and morbidity consequences of wasting –8. RarelDespite these risks, wasting has been reduced only slowly at a global level over the past 40 years, with some countries, such as India and Sri Lanka, recently noting rising prevalence rates , 14. ForThe continued high burden of child wasting represents an urgent policy priority . The gloYet, while there is growing global agreement on the need for action, there remain many gaps in our understanding first, of the drivers of wasting specific to different geographies of the world, and second, how to prevent wasting as compared to stunting. For example, it was shown in the 1990s that national factors explained “almost all of the differences” in wasting across regions, and that “the prevalence of wasting relative to that of stunting was higher in Asia than in Africa when adjusting for national factors” . But detThis study seeks to shed more light on the determinants of wasting across South Asia to support more effective local and regional action. Better policies and investments aimed at wasting have to be informed by evidence of current determinants across contexts. We use the most recent cross-sectional survey data from Afghanistan, Bangladesh, India, the Maldives, Nepal and Pakistan, dating from 2009 to 2016. These data are used to assess wasting disparities across the region and within countries, and to determine the individual, maternal, household, and environmental level factors that may explain such patterns. The co-occurrence of stunting and wasting in each country is also presented.S1 Table. Due to a lack of comparable accessible data, Bhutan and Sri Lanka were not be included in this analysis.The Afghanistan National Nutrition Survey (NNS) 2013, Bangladesh Demographic and Health Survey (DHS) 2014, India NFHS 2016, the Maldives DHS 2009, Nepal DHS 2016, and Pakistan DHS 2013 were used in this analysis. Each survey is described in All surveys used multistage cluster sampling, with some variation by country. In general, households from selected clusters, or enumeration areas, were included, some surveys used stratification. All surveys included sample weights in the dataset. However, sample weights for Afghanistan were not provided on the same scale as those used in the DHSs and NFHS. Therefore weights were included in by-country summaries, but not included in the pooled summarized for this regional analysis. Detailed study designs have been published elsewhere –26. DataChildren under 5 years of age were included in the analysis if they had a plausible value for WHZ (i.e. ranging from -5 to 5) and their mother was not pregnant at the time of the survey, as maternal body-mass index was explored as a factor associated with child wasting.zscore06 ), Nangarhar , Laghman , Paktia , Khost , Kunar , Nuristan , Urozgan , Zabul , and Helmand  which have been largely inaccessible to development or humanitarian actors for many years.In Bangladesh, divisions were the region of residence unit analyzed. Children in Barisal  and Rajshahi  were more likely to be wasted compared with children in Dhaka. Similarly, in India, the likelihood of wasting was significantly higher in five states , compared with New Delhi, while in thirteen states the likelihood was significantly lower . In Pakistan, where Islamabad was the reference region, the adjusted odds ratio for child wasting for all other regions were not significant.Fig 3). When the process of identifying factors associated with wasting was repeated using urban/rural stratification some distinct differences emerged, as summarized in Table 4. For example, child’s age was not significantly associated with wasting in urban households in the Maldives or Nepal, and only marginally significant in Pakistan. Being male was no longer associated with wasting in urban Afghanistan or Bangladesh, nor in rural Pakistan. Stunting was inversely associated with wasting among rural Afghani children, but positively associated with wasting in urban Afghanistan, and birth order was no longer associated with wasting in the Maldives or Nepal, but was positively associated with wasting in urban India.The prevalence of wasting, severe wasting and the co-occurrence of being wasted and stunted, was higher in rural areas than in urban areas in all countries , whereas the lack of access to improved water was associated with increased odds of child wasting among rural children in India. Less household wealth was associated with increased odds of wasting among children in rural India and Nepal , and the rainy season was also associated with increased odds of wasting among children in rural Nepal.The prevalence of wasting across the 6 countries considered in this analysis ranged from 9% in Afghanistan to 21% in India. According to WHO thresholds, a level above 10% represents a “serious public health emergency”, and rates above 15% amount to a critical situation [While this study identified country-specific predictors of child wasting, several commonalities are apparent across the region. For instance, wasting was consistently highest among children aged 0 to 5 months, ranging between 13% and 31%, and typically lowest among older children aged 48 to 59 months. In other words, infants are very vulnerable to wasting, while stunting generally increase with age from early childhood to around 24 to 35 months, as described globally by Victora et al. (2010).Low maternal BMI was significantly associated with wasting across all countries considered in our analysis and maternal thinness ranged from 8% in the Maldives to 25% in India. The relationship between low maternal BMI and child wasting may be mediated through poor birth outcomes that have been associated with low maternal BMI previously, such as a recent study conducted in Bangladesh .Boys were 16% to 36% more likely to be wasted than girls in Afghanistan, Bangladesh, India and Pakistan. This runs counter to some early literature on child undernutrition in South Asia that has reported girls being more likely to be stunted or wasted than boys , 33. HowThe high prevalence of children who are both wasted and stunted requires urgent attention. The fact that over 5% of Bangladeshi, Indian and Pakistani children exhibit both manifestations of undernutrition simultaneously is a serious concern; the combined effects of wasting and stunting are likely to amplify the risks associated with each condition separately . Both coWe did not find a strong pattern of wasting in relation to season or wealth. Household wealth has been widely referenced as a determinant of wasting , 37. HowIt is also possible that the socioeconomic inequalities in child wasting in South Asia have attenuated over time, as seen with anemia among women of reproductive age in India . For exaHowever, while the distribution of wasting across income groups has fallen in several parts of South Asia, the absolute number of children affected remains unacceptably high. If nations across this region are to achieve the wasting reduction targets embedded in the SDGs, they will have to quickly scale up strategies for the prevention of child wasting in the context of broader nutrition investments while strengthening the scale and effectiveness of programmes for the treatment of severe wasting in children. Evidence-based interventions to treat severe wasting are known, but coverage in South Asia remains low. At a cost of roughly US$ 200 per treatment , WHO deeThere are undoubtedly operational problems that need to be overcome if child wasting is to be appropriately prevented and treated. Integrating community-based management of severe wasting into health service delivery at a national level is challenging, primarily because of organizational and financial weaknesses in most national and sub-national health systems, particularly in rural settings, including challenges in ensuring adequate long-term funding to scale up training, staffing and regular provision of supplies. As a result, the current effective coverage of these programmes in less than 20% across Bangladesh, India, Nepal, Pakistan, and Sri Lanka .Importantly, while treatment programmes will save lives, the current scale of wasting in South Asia requires attention to preventive programmes. Many of the underlying determinants of wasting overlap with those of stunting, which has become the primary focus of nutrition programming in recent years. Emphasis has appropriately come to be placed on the “first 1,000 days”, that is, the period from conception through two years of life, as the critical window of opportunity where substantial impacts can be achieved on child physical growth and brain development , 41, 42.These overlaps argue strongly for joint attention to the drivers of wasting and stunting, with a view to better prevent both. WHO (2014) notes that “programmes, policy, research and financing for wasting and stunting have been separate. Both wasting and stunting (…) share causal pathways, which suggest that action on one is very likely to impact the other” . InvestmThere are a number of limitations to this analysis. Comparable data were not accessible for Bhutan and Sri Lanka, limiting our analysis to six of the eight South Asian countries. The analysis presented here provides a cross-sectional view of wasting by country, and therefore is limited to interpretation of factors associated with wasting rather than inferring causality. Similarly, given the nature of the datasets included in this study, many covariates that have previously been linked to wasting (e.g. food security and child’s energy expenditure) were not measured and therefore not included in this analysis. While we document the prevalence of the coexistence of wasting and stunting, the cross sectoral nature of the dataset limits our ability to draw conclusions about the directionality of the relationship between wasting and stunting.Despite these limitations, our analysis has a number of important strengths. It provides standardized analyses of factors associated with wasting across South Asian countries using comparable datasets. The prevalence of the co-occurrence of wasting and stunting is calculated, shedding light on a combined problem that is not commonly considered. Finally, the differential manifestation of wasting across urban and rural populations is presented. Urbanization is occurring rapidly in South Asia and designing context-specific interventions for these changing demographics is increasingly necessary.South Asia has been home to the largest proportion and number of wasted children in the world for decades . This reAs argued by WHO (2014), targets to reduce wasting can only be achieved if “high-burden countries take stock of their current prevalence, projected population growth, underlying causes of wasting and the resources available to address them; set target annual reduction rates to guide intervention efforts; mobilize necessary resources; and develop and implement systematic plans for the reduction of wasting” . Using dThis study highlights the scale of wasting in South Asia, and its several links to stunting. We note that the underlying determinants of wasting and stunting are similar. With well-known and cost-effective interventions to prevent stunting and manage wasting, the raising number of wasted children is unacceptable. Policymakers and program designers should broaden their perspectives on nutrition interventions to ensure that investments aimed at addressing single nutrition condition (like stunting) are tailored in ways that will also contribute to tackling wasting. Separating these two manifestations of undernutrition in conceptual and programmatic terms is unnecessarily impairing progress on both fronts.S1 Table(DOCX)Click here for additional data file.


The accumulation of cAMP was quantified in HeLa cells. The presence of PDE-4B2 and phosphorylated myosin light-chain (pMLC), in addition to the effect of thalidomide analogs on oxytocin-induced pMLC, were assessed in human uterine myometrial cells (UtSMCs). Thalidomide analogs had concentration-dependent inhibitory effects on spontaneous and tonic contractions and inhibited Ca2+-induced responses. Tonic contraction was equipotently inhibited by 4APDPMe and rolipram . Rolipram and the thalidomide analogs inhibited spontaneous and tonic contractions equieffectively. Both analogs increased cAMP accumulation in a concentration-dependent manner (p < 0.05) and induced changes in the subcellular localization of oxytocin-induced pMLC in UtSMCs. The inhibitory effects of thalidomide analogs on the contractions of pregnant human myometrium tissue may be due to their PDE-4 inhibitory effect and novel mechanism as calcium-channel blockers.Uterine relaxation is crucial during preterm labor. Phosphodiesterase-4 (PDE-4) inhibitors have been proposed as tocolytics. Some thalidomide analogs are PDE-4 inhibitors. The aim of this study was to assess the uterus-relaxant properties of two thalidomide analogs, methyl 3--3--propanoate (4NO2PDPMe) and methyl 3--3--propanoate (4APDPMe) and were compared to rolipram in functional studies of spontaneous phasic, K Preterm (premature) labor is the major cause of neonatal morbidity and mortality, with a worldwide average rate of 12% that includes low and high income countries and accounts for 75%–85% of all neonatal deaths ,4. Prete2+]i. The uterus also responds to many agonists; thus, changes in the expression of receptors and the activation of signaling pathways in myocytes may be involved in the regulation of uterine contractility i, a phenomenon known as “calcium-sensitization” [2+]i; indeed, contractions induced by KCl are completely driven by membrane depolarization and Ca2+ entry through voltage-operated Ca2+ channels i and/or MLC phosphorylation; nevertheless, cAMP concentrations can lead to the relaxation of tonic smooth muscle by mechanisms that are independent of changes in [Ca2+]i or in the state of myosin light chain phosphorylation -cAMP (10 nM). After 2.5 h at 4 °C, the reactions were terminated by filtration over GF/B filters pre-soaked in 0.3% polyethylenimine, followed by three washes with 1 mL of ice-cold deionized water. The retained radioactivity was measured by liquid scintillation, and the amount of endogenous cAMP present in each sample was calculated using a standard cAMP curve (10–10−6 M) . Data fo2.Normal human uterine myometrial cells (UtSMCs) were purchased from Clonetics  and grown in medium containing supplements and fetal bovine serum from a SmGM-2 Bullet Kit . UtSMC cells were trypsinized and seeded onto glass coverslips 2 days prior to use to achieve a confluence of 80% at the time of experimentation. The cells were maintained in a humidified 37 °C incubator with 95% air and 5% COw/v) and 1.5% fetal bovine serum (FBS) in PBS and incubated overnight at 4 °C with p-MLC  and PDE4B2  antibodies . The final concentration of both antibodies was 1:25. The cells were then washed with PBS and incubated for 1 h at 4 °C with fluorescein-conjugated donkey anti-goat IgG (Santa Cruz Biotechnology). 4′,6-diamidino-2-phenylindole (DAPI) was used to stain nuclei (blue). The cell preparations were washed again with PBS and mounted on microscope slides with VectaShield ; the samples were visualized on a confocal laser scanning microscope  using a Plan Neo Fluor 63× (NA = 1.4) oil-immersion objective.To assess the level of the resultant pMLC, UtSMCs plated on coverslips were incubated for 30 min in the absence and presence of 1 mM 4NO2FDPMe or 4AFDPMe . Later, depending on the experiment, the cells were or were not exposed to oxytocin  to provoke the phosphorylation of MLC because OT is the most potent biological inducer for this cell type . After tn = 6). The differences in IC50 (potency) and Emax (efficacy) among the compounds were determined by one-way ANOVA followed by a post hoc Bonferroni test using Sigma Stat software version 3.1 . In all cases, p < 0.05 was considered statistically significant.The data are expressed as the means ± SEM from determinations for each concentration (2+ entry blockade effect of rolipram and these analogs. Although further studies are required, the immunomodulatory, anti-inflammatory, and uterus-relaxant properties of these non-teratogenic thalidomide analogs position them as potentially safe and effective tocolytic agents in a field that urgently needs improved pharmacological treatments, as in cases of preterm labor.In this work, the thalidomide analogs 4NO2PDPMe and 4APDPMe showed inhibitory effects on the spontaneous and tonic contractions of pregnant human myometrium, likely due to their inhibitory effect on PDE-4 and to their novel mechanism as calcium-channel blockers. This is the first report to propose a Ca


This article contains visualization data on concentrating apple juice with a trinitarian suspension crystallization freeze concentrator, which integrates scraped-surface heat exchanger, suspension crystallizer and wash-column into one piece of equipment. The visualization data on ice accumulation, ice bed development and consolidation in the crystallizer/wash-column of the freeze concentrator are presented in a set of photographs in chronological order and videos attached as appendix materials. These data refer to the related research article entitled “Concentration of Apple Juice with an Intelligent Freeze Concentrator” Ding et al., 2019. They have been edited to give captions.23456The following are the supplementary data related to this article:2® brand  purchased in a local market.The apple juice used in this study was HuiyuanThe apple juice was cooled and frozen to produce ice slurry by a scraped-surface heat exchanger below a 2.5-L suspension crystallizer. As the content of ice accumulated in the apple juice, a tightly packed ice bed was formed at the end, and the crystallizer then converted to a wash column that was used for separate the ice with the concentrated apple juice


The onset of deglaciation in the Southern Hemisphere mid-latitudes has been attributed to the southward transmission of climate anomalies in response to slow-down of Atlantic meridional overturning circulation (AMOC) during Heinrich Stadial 1 . However, inferences on the response of former ice sheets to sub-millennial palaeoclimate shifts are limited by a shortage of high-resolution terrestrial archives. Here we use a ~1000-year duration, annually-resolved lake sediment record to investigate the deglacial retreat dynamics of the Lago General Carrera–Buenos Aires ice lobe (46.5°S) of the former Patagonian Ice Sheet. We attribute the onset of glacier retreat at 18.0 ± 0.14 cal ka BP to abrupt southward migration of the Southern Westerly Winds that enhanced solar radiation receipt (and ablation) at the ice sheet surface. We infer that accelerated retreat from 17.77 ± 0.13 cal ka BP represents a lagged Southern Hemisphere response to gradual ocean-atmosphere warming associated with the centennial-scale transmission of Northern Hemisphere climate anomalies through the oceanic bipolar seesaw. By 17.38 ± 0.12 cal ka BP, the glacier margin had receded into a deepening proglacial lake, instigating sustained calving losses and more rapid ice recession. In particular, the southern mid-latitude region is strongly influenced by variations in the strength and position of the Southern Westerly Winds (SWWs)5 and Southern Ocean fronts8. Physical changes in this coupled system play an important role in major climate transitions, influencing ocean circulation9 and the global carbon cycle10, and transmitting climate anomalies between regions, on timescales of centuries to decades13. Constraining the dynamics of former mid-latitude ice sheets through such transitions therefore offers important insight into cryosphere response to regional and hemispheric climate drivers14. However, owing to the chronological uncertainties associated with radiometric dating of former glacier margins, chronologies of ice recession often overlap intervals of rapid climate transition17. Whether former mid-latitude ice sheets bear the imprint of (sub-)centennial, as well as millennial-scale climate variability, therefore, remains uncertain, precluding empirical assessments of (i) the intra- and interhemispheric phasing of palaeoclimate between the poles20 and mid-latitudes; and (ii) theoretical22 and simulated23 models of climate reorganisation during glacial-to-interglacial transitions. Incremental dating techniques, however, such as annual-layer counting of varved lake sediment sequences, offer palaeoenvironmental data with the potential to resolve sub-centennial climate variability (e.g. ref.24).The mid-latitude ice masses of Patagonia and New Zealand are ideally located to investigate the response of the cryosphere to climatic changes that occurred during the global Last Glacial Maximum (LGM) and succeeding deglacial period25, the largest conduit of former Patagonian Ice Sheet (PIS) discharge in central Patagonia 26. The 994 ± 36 varve year (vyr) record is anchored to the calendar-year timescale through the presence of the precisely-dated Ho tephra from Cerro Hudson  and records the initial stages (~18–17 ka) of PIS deglaciation at 46.5°S25. Glaciolacustrine varved sediments accumulated in an ice-contact proglacial lake that formed and expanded as the LGC–BA ice lobe retreated from the local LGM terminal ice limit25. Through detailed sedimentological investigation of these sequences, Bendle et al. (ref.25) developed the Fenix Chico Master Varve Chronology (FCMC17), a composite record derived from five varve series located in the eastern parts of the LGC–BA basin. The FCMC17 varves are composed of two main sedimentary layers  of outlet glacier retreat dynamics from the Lago General Carrera (Chile)–Buenos Aires (Argentina) basin . Over multi-decadal to centennial timescales, meltwater and sediment fluxes are modulated by glacial extent, where a more proximal  ice margin leads to increased (decreased) sediment flux and varve thickness36. Over decadal scales, the controls on varve thickness are more complex. Increased varve thickness has been linked to transitional periods of (i) rapid glacier advance (i.e. increased ice-margin proximity) or (ii) the initial phases (one-to-two decades) of glacier retreat (i.e. enhanced glacier ablation and meltwater/sediment flux)36. Using these established glacier-varve relationships, high-resolution  analyses of glaciolacustrine sediment flux (i.e. varve thickness) are related to changes in former ice-margin position .Prior to retreat, the LGC-BA ice lobe remained stable at the local Last Glacial Maximum (LGM) Fenix I moraine for ~700 modelled years, between 18,778 ± 615 and 18,086 ± 214 cal yr BP Fig. 25. Upon −1 As we were unable to identify ‘basal varves’  in this area, the calculated retreat rate may be an overestimate. However, the very thick varves observed in these sequences are typical of ice-proximal sedimentation during the earliest decades of ice-retreat28, likely making this overestimate minor  and represents a ~2 km terminus retreat from the Fenix I to Menucos moraine Fig. . We idennor Fig. .36. We also invoke this interpretation, which would suggest that varves started to accumulate almost immediately behind the ice-contact face of the Menucos moraine. The subsequent decrease in varve thickness through the rest of Phase 2  increase in varve thickness from 17,768 ± 127 cal yr BP  established during Phase 3 cannot yet be definitively confirmed. However, a subaqueous moraine complex on the southern shoreline of LGC–BA (see Supplementary Information) provides a minimum constraint on the distance (6.0–9.0 km) of ice recession during Phase 3, which yields a mean ice-margin retreat rate of ~19.0 m yr−1  with a 123 ± 3 vyr period of abruptly decreasing varve thickness. Subsequently, the rate of varve thickness decrease slows at 17,255 ± 122 cal yr BP and remains relatively constant until the end of the FCMC17 record at 16,982 ± 127 cal yr BP  values  concentration in the WDC record 42, SSTs of ~5–6 °C begin to increase at 18.2 ka, before a further 3–4 °C of warming through the rest of the time-window. Palaeoecological temperature reconstructions from TN57-21 in the Southeast Atlantic7 support a comparable subsurface warming of ~9–13 °C between 18.1 and 17.5 ka  and acceleration (17.77 ± 0.13 ka) of PIS ice lobe retreat at 46.5°S Fig.  were pha ka Fig. , highlig ka Fig. 2,3,15–17ere Fig.  cooling4nse Fig.  to inter48. Marine SST records from the South Atlantic7, Southeast Pacific42, and Southwest Pacific49 record a concurrent poleward migration of the Subtropical Front (STF), and a strengthening of ACC flow through the Drake Passage50, consistent with southward-shifted westerlies. A sustained poleward shift of westerly circulation provides a likely trigger for mid-latitude glacier retreat, as southward-shifted storms tracks would decrease cloud cover over Patagonia and enhance solar radiation receipt51 at the ice sheet surface, increasing melting and (together with reduced accumulation) driving negative mass balance. Conceptually, this process is similar to a positive state in the Southern Annular Mode (the leading mode of tropospheric circulation variability south of 20°S), whereby high mid-latitude surface pressure forces a poleward contraction of the SWWs52 and increased surface air temperature south of 40°S, due to a combination of horizontal advection, subsidence and enhanced solar radiation53. The broadly synchronous timing of deglaciation in New Zealand  for heat to accumulate in the South Atlantic, and for warm anomalies to be propagated around the Southern Ocean via Kelvin and Rossby waves, or with the ACC flow23. This produces modelled Pacific sector warm anomalies of ~1–1.5 °C, both north and south of the ACC, within 100–200 years of AMOC collapse, and with a synchronous surface air-temperature increase of ~1 °C in both Patagonia and Antarctica23. 500 years after AMOC collapse, a mid- and high-latitude warming of ~2 °C is simulated, sufficient to explain around half the glaciologically-modelled (summer) atmospheric warming (~4.5 °C) that drove mountain glacier retreat in the Southern Alps of New Zealand during HS-13. This modelled process is empirically supported by analyses of isotopic changes recorded in time-synchronised polar ice cores55, which evidence a consistent ~200-year lag between Northern Hemisphere climate and Antarctic temperature response owing to the timescales of anomaly transmission through the oceanic bipolar seesaw.Second, we consider the processes driving synchronous acceleration of WDC warming Fig.  and mid-23. Together with a wind-driven southward shift of the STF7, this process would deliver warm waters to the sea ice zone, driving sea ice retreat and meridional atmospheric heat fluxes both poleward (>70°S) over Antarctica, and equatorward (<50°S) to the mid-latitudes23. Southern Ocean deep convection may have further amplified both mid- and high-latitude warming through heat release from intermediate depths57, forced by either wind-driven upwelling 25, the PIS at 46.5°S responded rapidly to interlocked southward migration of the SWWs and STF at ~18.0 ka15. This circulation shift, which modulated the mid-latitude glaciological surface energy budget, regional atmospheric temperature, and moisture distribution, was likely zonally symmetric, as mountain glaciers in New Zealand also started to recede at ~18.0 ka  to southward-shifted westerlies, the rate of retreat was steady for ~200 years  and ocean (lagged) change during HS-1 ka Fig. 3,54. Thoars Fig. . We prop19 between ~18.0 and 17.4 ka. Specifically, the timing of major shifts in outlet glacier retreat, inferred from the FCMC17 varve thickness record, support both modelled23 and empirical55 data in favour of a sequence of interhemispheric ocean-atmosphere changes driven by perturbed AMOC in HS-1. The high-precision and incremental FCMC17 record25 shows a phased ice-sheet response to (i) rapid  coupled migration of the SWW and STF at 18.0 ± 0.13 cal ka; (ii) lagged  ocean–atmosphere warming from 17.77 ± 0.13 cal ka, transmitted through the oceanic bipolar seesaw, and (iii) a combination of continued warming and local calving dynamics from 17.38 ± 0.12 cal ka.We have presented an annually-resolved terrestrial archive from the Southern Hemisphere mid-latitude region that, for the first time, allows exploration of the phasing of mid-latitude ice-sheet dynamics and hemispheric palaeoclimate at the end of the last glaciation (~18–17 ka). Our results reveal close synchronicity between regional PIS retreat dynamics and West Antarctic warming and sea-ice trends25. Varve counts and thickness measurements were generated from field (macroscopic) outcrops  or microscopic analyses of petrographic thin sections . Site records were correlated on a varve-to-varve basis using prominent marker layers as definitive tie-points between sequences, alongside distinctive trends in varve thickness. Varve count uncertainties were estimated through repeat measurements, although local disturbances were often bridged by better preserved sequences during the correlation process. This process yielded a composite chronology of 994 ± 36 varve years (vyrs)25.This study was carried out on a composite varve thickness record and chronology (FCMC17) established from five individual site varve records in the Río Fenix Chico valley, at the eastern end of LGC–BA25. Samples from three sites were sieved at 125 µm and 15 µm, and an optimum glass fraction extracted using sodium polytungstate (SPT) at 2.55 g cm−3 density58. Glass shards were mounted in probe stubs, carbon coated, and major element analyses obtained for 195 individual glass shards using a Cameca-SX100 WDS-EPMA at the Tephra Analytical Unit, University of Edinburgh. Analyses were undertaken using a beam diameter of 5 μm and at 15 keV; a 2 nA beam current was employed for Na, Al, Si, Fe, K, Ca, Mg and a 80 nA beam current for Mn, Cl and Ti59. The uncertainty on this analysis is <1%, and international standards Lipari 1 (rhyolitic) and BCR2G  were analysed frequently to monitor for instrument drift. In addition, five bulk tephra samples (~10–12 g) were prepared for trace element analyses. Samples were sieved at 15 µm to remove the fine silt and clay fraction, and powdered in a tungsten carbide mill. Powered samples were pressed into pellets and analysed using a PANalytical Axios Sequential X-ray Fluorescence Spectrometer at Royal Holloway, University of London. Matrix corrections were applied using the major element chemical dataset obtained using the WDS-EMPA analysis, and Limits of Detection (LoD) were calculated using long-term data collected using the same equipment25. Geochemical correlations with published tephrochronological datasets determined an origin as the Ho tephra from Cerro Hudson60, and eight published radiocarbon determinations61 were remodeled in Oxcal v4.362 to 17,378 ± 118 cal yr BP. This age was inserted at vyr 605 ± 27 and calendar years extrapolated for the remaining varves. Varve counting errors were propagated backwards and forwards from vyr 605 and summed with the uncertainty of the Ho tephra age25.A prominent time marker was established at vyr 605 ± 27 in the composite record, through geochemical fingerprinting of a visible tephra layer (see Supplementary Information)−1) for three main recessional phases. These phases are also evident as prominent changes in the trend of varve thickness. The number of varves deposited between former ice-margin positions was deduced from site varve records, which were strategically located with respect to temporary ice lobe positions (see Supplementary Information). The age-estimate uncertainty associated with the Ho tephra  permitted absolute dating of ice-lobe retreat dynamics at centennial resolution. However, the continuous FCMC17, with low internal varve count uncertainty (994 ± 36 vyr), enabled the characterisation of former ice-dynamics at centennial, and even decadal, resolution, and permitted comparison with other high-resolution incremental climate records (e.g. refs19).The number of varves deposited between geomorphologically (i.e. moraines) or stratigraphically defined ice limits enabled calculation of average ice-lobe retreat rates (m yrSupplementary Information


Sea ice is an important transport vehicle for gaseous, dissolved and particulate matter in the Arctic Ocean. Due to the recently observed acceleration in sea ice drift, it has been assumed that more matter is advected by the Transpolar Drift from shallow shelf waters to the central Arctic Ocean and beyond. However, this study provides first evidence that intensified melt in the marginal zones of the Arctic Ocean interrupts the transarctic conveyor belt and has led to a reduction of the survival rates of sea ice exported from the shallow Siberian shelves (−15% per decade). As a consequence, less and less ice formed in shallow water areas (<30 m) has reached Fram Strait (−17% per decade), and more ice and ice-rafted material is released in the northern Laptev Sea and central Arctic Ocean. Decreasing survival rates of first-year ice are visible all along the Russian shelves, but significant only in the Kara Sea, East Siberian Sea and western Laptev Sea. Identified changes affect biogeochemical fluxes and ecological processes in the central Arctic: A reduced long-range transport of sea ice alters transport and redistribution of climate relevant gases, and increases accumulation of sediments and contaminates in the central Arctic Ocean, with consequences for primary production, and the biodiversity of the Arctic Ocean. Under modern  conditions, in particular the Transpolar Drift . The analysis of 20 years (1998–2017) of backward trajectories starting in Fram Strait reveals that less and less ice formed in shallow water areas (<30 m) has reached Fram Strait  and to identify regions of most pronounced melt, a second experiment was carried out. Again, we used the Lagrangian approach to trace ice forward in time from 32 points located along the Siberian coast at a water depth favorable for suspension freezing Fig. , 25–30 m26, the thinning FYI cover is the consequence of enhanced offshore-directed transport  from the ESA Climate Change Initiative (CCI) indicates a decreasing winter mean ice thickness in the past 15 years Fig. . Followi27. To identify potential sites of melt out and intensified release of biogeochemical matter, we used a simple thermodynamic model. The model calculated level ice growth and melt along trajectories based on surface temperatures, ocean heat flux assumptions and a snow climatology . Figure The evolution of sea ice, namely, growth from the underside in winter, and sea ice melt at the top in summer causes ice-rafted particles to migrate towards the ice floe surface28 of their arctic-wide spatial coverage with a constant temporal resolution, low-resolution sea ice motion products from satellites have been widely used in sea ice studies and for model assimilation30. It stands to reason that validity and reliability of the presented results from trajectory studies depend on the accuracy of the applied sea ice motion product. Therefore, tracking experiments were repeated using different combinations of motion products, as well as higher ice concentration thresholds (e.g. 40%), but a reduced long-range transport was observed independent of the forcing dataset and the chosen setup.Because33. Restrictions may arise from the coarse resolution of the sensors in near-shore regions characterized by a complex coastline, extensive fast ice areas, and polynyas31. However, a cross-comparsion with drift estimates obtained from long-term moorings deployed on the Laptev Sea shelf shows that CERSAT motion products are capable of reproducing sea ice drift in near-shore areas correctly17.In this study, we primarily use the CERSAT drift dataset to calculate trajectories, because it provides the most consistent time series of motion vectors starting from 1991 to present. Comparisons with buoys and high resolution SAR images indicate that in particular during winter months, when the atmospheric moisture content is low and surface melt processes are absent, the quality of motion products from low resolution satellites is high28. This effect is particularly pronounced at the ice edge and in Fram Strait. Because CERSAT drift estimates are not available between June and August, motion information is bridged with OSISAF or NSIDC data . At this point, it should be noted that the lack of temporally consistent climate data records of sea ice drift covering all seasons makes it difficult to carry out, validate and compare studies such as this one. To quantify uncertainties of sea ice trajectories, we therefore reconstructed the pathways of 57 drifting buoys obtained from the SeaIcePortal.de  and considered to be in an acceptable range. Moreover, Fig. During summer months, strong surface melt processes and high moisture content in the atmosphere further reduces accuracy of motion vectors and lead to an underestimation of the ice drift.de Fig. 34. Overa35. However, consequences for the sedimentary budget, biogeochemical and ecological effects can be assessed for some materials that are studied more regularly.By combining Lagrangian trajectories with other state-of-the-art satellite and model products, we established a new tool to investigate changing Arctic sea ice and processes acting on the ice cover along pathways. In this study we show that long-range transport from shelf seas towards Fram Strait declines. Instead, there is evidence of intensified melt in the central Arctic Ocean and north of the Laptev Sea. To assess related changes in sedimentation rates of ice-rafted materials, reliable estimates of material uptake in shallow waters are needed. At present, estimates are still scarce – particularly because incorporation of ice-rafted materials into sea ice during formation or at a later stage is a very complex process that depends on the entrainment process itself, water masses, depth and stratification, and the presence of emitting sources  in the surrounding waters37. Following12, the annual sea ice sediment uptake in the Kara Sea, Laptev Sea and East Siberian Sea is around ~34 × 106 t y−1  more sediments are released in the marginal ice zones and central Arctic Ocean due to intensified melt of FYI. The largest part is released close to where the ice was formed  that traces sea ice backward or forward in time using a combination of satellite-derived low resolution drift products. So far, ICETrack has been used in a number of publications to examine sea ice sources, pathways, thickness changes and atmospheric processes acting on the ice cover30. In this study we apply a combination of three different products: (i) motion estimates based on a combination of scatterometer and radiometer data provided by the Center for Satellite Exploitation and Research (CERSAT)32, (ii) the OSI-405-c motion product from the Ocean and Sea Ice Satellite Application Facility (OSISAF)33, and (iii) Polar Pathfinder Daily Motion Vectors from the National Snow and Ice Data Center (NSIDC)48.Sea ice motion information is provided by different institutions, obtained from different sensors, and for different time intervals31. During summer months (June–August) when drift estimates from CERSAT are missing, motion information is bridged with OSISAF (2012 to present). Prior 2012, or if no valid OSISAF motion vector is available within the search range, NSIDC data is applied. For a detailed description of the differences between the CERSAT, OSISAF and NSIDC products we refer to28.The tracking approach works as follows: An ice parcel is traced backward or forward in time on a daily basis. Tracking is stopped if a) ice hits the coastline or fast ice edge, or b) ice concentration at a specific location drops below 20% and we assume the ice to be melted (forward tracking) or formed (backward tracking). A weighted approach is used to determine the motion product that is applied for the tracking: The algorithm first checks for the availability of CERSAT motion data within a predefined search range. CERSAT provides the most consistent time series of motion vectors starting from 1991 to present and has shown good performance on the Siberian shelvesIn order to determine drift patterns and source areas of sea ice that exits the Arctic between Greenland and Svalbard, backward trajectories were calculated starting from six positions located in northern Fram Strait  algorithm. The product is available on a 12.5 km × 12.5 km grid50. Sea ice thickness information of the winter month between October and April ril Fig.  is based53 and has been used by54 to reconstruct the surface hydrography of the Arctic Ocean interior. Here we use the model output to number accumulated melt rates and identify potential sites where intensified sedimentation on Siberian Shelf Seas and in the central Arctic Ocean takes place  data were obtained using an instrument pulled on a sledge across the ice60. In 2004, measurements were made with an airborne EM (AEM) system towed by a helicopter 20 m above the ice surface. Surveys performed after 2010 were conducted with the research aircraft Polar-5 or Polar-6 operating from the Danish Station Nord in Nord-East Greenland20. The accuracy of the EM measurements is in the order of ±0.1 m over level sea ice61. The AEM thickness data enables us to determine the general thermodynamic and dynamic boundary conditions of ice formation63. The most frequently occurring ice thickness, the mode of the distribution, represents level ice thickness and is the result of winter accretion and summer ablation. We assume the bias that arises from the unknown snow thickness to be negligible, since temperatures above freezing had certainly led to a significantly reduced snow cover or no snow cover at all56. For details about data processing and handling we refer to59.Electromagnetic (EM) ice thickness observations were carried out during summer in northern Fram Strait and the southern part of the Nansen Basin within the framework of the AWI IceBird program. Measurements , but a more recent study of 8 could show that values are much larger and roughly 20–30 × 106 t y−1 may be exported from the Laptev Sea towards the central Arctic Ocean. Estimates are based on particle concentrations in ice samples from near-coastal sites and quantifications of new ice formation rates in winter. The authors assume that most sediment-laden ice produced in leads and polynyas reach areas north of the mean multiyear ice edge, and thus will not melt during summer.Followingsee Fig. . The Lap8 to quantify the amount of sediments released in the marginal shelf seas and central Arctic Ocean before and after 2004 (Fig. 6 t y−1 of mainly fine-grained material with high silt content12.Here we use our estimates of FYI survival rate from the forward tracking approach Tables  and S2 t004 Fig. . AssuminSupplementary Info


Due to the profound impact of El Niño-Southern Oscillation (ENSO) on global climate and weather, extensive research has been devoted to its prediction. However, prediction accuracy based on observation is still insufficient and largely limited to less than one year of lead time. In this study, we demonstrate the possibility that anomalous sea surface temperature (SST) warming (cooling) in the Western Hemisphere Warm Pool  near the Intra-Americas Sea (IAS), which is the second largest warm pool on the planet, contributes to the initiation of La Niña (El Niño) with a 17-month lag time. SST anomalies in WHWP in late boreal summer contribute significantly to the emergence of the Pacific meridional mode (PMM) via interaction between the ocean and atmosphere over the subtropical North Pacific during the subsequent winter and spring. Near-equatorial surface wind anomalies associated with the PMM can further trigger ENSO through the dynamics of the equatorial oceanic waves. Thus, this observational analysis presents a clear step-by-step explanation about the influence of WHWP on ENSO development with a 17-month lead time. Hence, extensive studies have been conducted based on observational data to better understand the triggering mechanisms of El Niño6 (a positive phase of ENSO) and associated precursors8 that help in anticipating the El Niño occurrence and its accompanied extreme climate events. For instance, some previous studies emphasized the role of warm water volume (WWV)9 in the equatorial Pacific as an essential precondition of ENSO. Since the ocean’s memory is dependent on the wave adjustment process according to the delayed oscillator theory10 or the recharge oscillatory theory12, a WWV peak usually precedes the El Niño by approximately eight months13. In addition, precursory signals from extratropical Pacific regions, such as the North Pacific Oscillation during boreal winter , can also lead to subsequent El Niño development via a seasonal foot-printing mechanism14 (SFM). Similarly, the Pacific meridional mode (PMM)16 in the subtropical North Pacific and its related trade winds can induce a charging mechanism18, which is known as another precursor that will often trigger El Niño events.The El Niño-Southern Oscillation (ENSO) exerts considerable influence on weather and climate around the world via atmospheric teleconnection21. Ham et al.20 proposed that a negative sea surface temperature (SST) anomaly in the tropical North Atlantic (TNA) during early spring could induce El Niño development via Rossby wave response to an anomalous heat source in the TNA and local air–sea interactions along the intertropical convective zone (ITCZ) in the subtropical North Pacific, which could be used to predict El Niño with a three-season lead time. Regarding the influence of the TNA, Yu et al.21 mentioned that a cold SST anomaly (SSTA) in the TNA in summer could force a remote westerly anomaly response in the equatorial Pacific through atmospheric Kelvin wave response and the Indian Ocean relaying effect.Atmospheric teleconnection from other oceans may also help to trigger El Niño. For example, Atlantic Niño, which peaks in summer, may independently enhance El Niño development by modulating the Walker Circulation in the Atlantic and eastern Pacific sectoret al.22 argued that the Indian Ocean dipole (IOD)23, which has a peak phase in fall, may trigger El Niño by modulating surface wind anomalies over the western equatorial Pacific in the following spring and summer. It was emphasized that the effect of IOD could help predict El Niño events with a 13 to 15-month lead time. These results imply that interbasin interaction can play a key role in El Niño prediction beyond one year. Such a long-lead relation is of great importance as it overcomes the spring predictability barrier of El Niño24 which makes El Niño predictions beyond one year very difficult.Izumo 25. These observational and modeling studies motivated us to consider other possible precursors in the Atlantic Ocean that could extend El Niño prediction lead time. In this light, we suggest that an SSTA in the Western Hemisphere Warm Pool26 , which is located in the Intra-Americas Sea (IAS), is a new independent precursor of El Niño with a forecast lead time of 17 months.In addition, some forecast experiments have shown that the interbasin interactions with the Indian and Atlantic Oceans can improve ENSO prediction27 (refer to Methods). Figure 28.A lead-lag correlation analysis with Niño3.4 index from December 1) to February (2) JF(2), where the number denotes the sequential order of year) revealed that there is a significant positive correlation between SST and heat content (HC) anomalies over the tropical western Pacific ~17 months prior ) to an El Niño peak in winter , which is in the middle of developing  process into a peak phase of the IOD in fall29. According to the previous studies31, the IOD evolves into a basin-wide cooling pattern during the following winter. The basin-wide cooling in the Indian Ocean persists from winter to the following summer, and it induces anomalous westerly winds in the western equatorial Pacific through Kelvin wave response32 and establishes a low-level cyclonic circulation anomaly. Since the westerly wind anomalies over the western equatorial Pacific is known to provide favorable conditions for El Niño development, an IOD may be regarded as a potential long-lead precursor of El Niño. However, it should be emphasized that during JAS(0) an SSTA over the western Indian Ocean, rather than the eastern Indian Ocean, plays a more significant role in subsequent El Niño development or phase transition30, as inferred in Fig. In addition to the Pacific signal, a significant SST cooling signal appears in the western Indian Ocean, a region often used to represent the western pole of the IOD26, which is the second largest warm pool on the planet. The statistical significance of this long-lead (about six seasons) correlation between WHWP and El Niño suggests that interbasin interaction exists between the Pacific and Atlantic Oceans, as well as the Pacific and Indian Oceans. It is necessary to consider significant SST signals over the subtropical eastern South Pacific and tropical Atlantic. However, since the signals are small and possibly related to WHWP through atmospheric circulation, we focus on WHWP. Therefore, WHWP–El Niño connection provides an additional precursory signal for possible prediction of El Niño with a lead time greater than one year. It should be noted that the long-lead relation between WHWP and El Niño has become significant during the past three decades  over the subtropical northeastern Pacific35. Note that SST amplitude and areal expansion of WHWP are climatologically greatest during JAS season. Thus, influence of WHWP on the atmospheric circulation is expected to be greatest during this season. If one considers JJA (June to August) or ASO (August to October) instead of JAS, a similar result can be obtained.The abovementioned observational results point out three key precursory signals for El Niño with ~17-month lead time. The first is the HC over the western equatorial Pacific. The second and the third are IOD and WHWP, respectively. Since the relation between precursory HC and IOD signals and El Niño have been previously reporteddex Fig. . As illu36  SSTA belt to the west (east). The subtropical dipole SSTA pattern becomes strongest in MAM(1) (March to May), resembling a typical PMM pattern  ) onto the observed SSTA (D(1)JF(2)), SSTA fields are reconstructed. Then, the correlation is calculated at each grid point between the observed and reconstructed SSTA, as shown in Fig. Lastly, the effect of WHWP is incorporated into the multiple regression model Fig.  and then41. Because the western North Pacific is recognized as a key region that conveys El Niño impacts, the WHWP effect appears to provide an additional benefit in the prediction of El Niño.It is worth noting that the increase in the correlation coefficient appears not only in the equatorial Pacific but also in the subtropical western North Pacific. This is understandable because the two regions are dynamically linked via westward propagating Rossby wavesBased on the significant relation between WHWP and ENSO, we examined how WHWP is related to the ENSO event, combined with the IOD and HC in the CMIP5 long-term simulations. For this, the same calculation applied to the observation is repeated. Figure 18. Thus, the occurrence of a PMM-like pattern in the northeastern subtropical Pacific plays a key role in linking WHWP to ENSO.By analyzing observational and model simulation data, we showed a significant influence of WHWP on El Niño with a 17-month lead time. Results of our evaluation indicated an increase of an SSTA in the WHWP in mid-summer to early-fall induces a northerly wind anomaly over the North Pacific as a result of Rossby wave propagation, which in turn generates a cold SSTA and a high SLPA in the subtropical northeastern Pacific. The cold SSTA and high SLPA together with associated anomalous low-level anticyclone persist through the subsequent winter and spring due to positive air–sea feedback. The equatorward expansion of the cold SSTA and the anomalous circulation in the subtropical North Pacific lead to the generation of a PMM-like pattern in the spring, triggering a La Niña through induced equatorial easterlies that force upwelling Kelvin waves and trade-wind discharging of equatorial heat contentet al.22 that emphasized the effect of the IOD). A multiple regression model was constructed to demonstrate the significant value added to El Niño prediction by including WHWP influence. It has been shown that the combination of the WHWP signal with equatorial HC and IOD signals leads to much better predictions throughout the entire tropical Pacific basin  version 2.4. Atmospheric data, including wind and SLP fields, were obtained from the NCEP/NCAR Reanalysis 1 (NCEP-R1)45. The precipitation data were from the Global Precipitation Climatology Project version 2.1 (GPCPv2.1)46, which has a horizontal resolution of 2.5° × 2.5°. For subsurface oceanic data, Global Ocean Data Assimilation System is used47 (ftp://ftp.cdc.noaa.gov/Datasets/godas). Using this data, HCs were calculated.In this study, several reanalysis datasets were used to analyze the relation between WHWP and El Niño. The analysis covers the period from 1985 to 2016. The SST data used in this analysis were the Extended Reconstructed Sea Surface Temperature version 3 (ERSSTv3)27. We defined the HC index as an area average of the HC anomaly in the western Pacific  during the JAS season. For the IOD index, the areas for the IOD are 50°–70°E within 10°S–10°N for west and 90°–110°E within 10°S-0° for east in JAS season, and the IOD index is defined as an areal-averaged SST difference (west minus east). The WHWP index is obtained by areal average of SSTA in 60°–105°W within 10°–35°N during the JAS season. With respect to WHWP and IOD indices, previous El Niño signal (Niño3.4 in DJF season) is removed by partial regression since previous ENSO is able to affect the subsequent SSTA in the Atlantic and the Indian Oceans.HC is defined as a vertical average of oceanic temperature within upper 300 mThe outputs of 33 CMIP5 models from historical 1970–2000) experiments (with one ensemble member each) were used (Supplementary Table 970–2000 Supplementary information