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Glaciers are retreating globally and are projected to continue to lose mass in the coming decades, directly affecting downstream ecosystems through changes in glacier runoff. Estimating the future evolution of glacier runoff involves several sources of data uncertainty, which to date have not been comprehensively assessed on a regional scale. In this study, we used the Open Global Glacier Model (OGGM) to estimate the evolution of each glacier (with area > 1 km2) in the Patagonian Andes (40–56° S). As sources of uncertainty, we used different glacier inventories (n = 2), ice thickness datasets (n = 2), historical climate datasets (n = 4), general circulation models (GCMs; n = 10), emission scenarios (Shared Socioeconomic Pathways, SSPs; n = 4) and bias correction methods (BCMs; n = 3) to generate 1920 possible scenarios over the period of 1980–2099. In each scenario, glacier runoff and melt time series were characterised by 10 glacio-hydrological signatures (i.e. metrics). We used the permutation feature importance of random forest regression models to assess the relative importance of each source of uncertainty on the signatures of each catchment. Considering all scenarios, 34 % ± 13 % (mean ± 1 standard deviation) of the glacier area has already peaked in terms of glacier melt (the year 2020), and 68 % ± 21 % of the glacier area will lose more than 50 % of its volume this century. Considering the glacier melt signatures, the future sources of uncertainty (GCMs, SSPs and BCMs) were the main source in only 17 % ± 21 % of the total glacier area. In contrast, the reference climate was the main source in 69 % ± 22 % of the glacier area, highlighting the impact of calibration choices on baseline conditions, model parameters and the initial starting geometry for future projections. The results provide a basis for prioritising future efforts (e.g. the improvement of reference climate characterisation) to reduce glacio-hydrological modelling gaps in poorly instrumented regions such as the Patagonian Andes.

The Patagonian Icefields (Northern and Southern Patagonian Icefield) are the largest ice masses in the Andes Cordillera. Despite its importance, little is known about the main mechanisms that underpin the interaction between these ice masses and climate. Furthermore, the nature of large-scale climatic control over the surface mass variations of the Patagonian Icefields still remains unclear. The main aim of this study is to understand the present-day climatic control of the surface mass balance (SMB) of the Patagonian Icefields at interannual timescales, especially considering large-scale processes. We modeled the present-day (1980–2015) glacioclimatic surface conditions for the southern Andes Cordillera by statistically downscaling the output from a regional climate model (RegCMv4) from a 10 km spatial resolution to a 450 m resolution grid and then using the downscaled fields as input for a simplified SMB model. Series of spatially averaged modeled fields over the Patagonian Icefields were used to derive regression and correlation maps against fields of climate variables from the ERA-Interim reanalysis. Years of relatively high SMB are associated with the establishment of an anomalous low-pressure center near the Drake Passage, the Drake low, that induces an anomalous cyclonic circulation accompanied with enhanced westerlies impinging on the Patagonian Icefields, which in turn leads to increases in the precipitation and the accumulation over the icefields. Also, the Drake low is thermodynamically maintained by a core of cold air that tends to reduce the ablation. Years of relatively low SMB are associated with the opposite conditions. We found low dependence of the SMB on main atmospheric modes of variability (El Niño–Southern Oscillation, Southern Annular Mode), revealing a poor ability of the associated indices to reproduce the interannual variability of the SMB. Instead, this study highlights the Drake Passage as a key region that has the potential to influence the SMB variability of the Patagonian Icefields.

Glaciers and ice caps are thinning and retreating along the entire Andes ridge, and drivers of this mass loss vary between the different climate zones. The southern part of the Andes (Wet Andes) has the highest abundance of glaciers in number and size, and a proper understanding of ice dynamics is important to assess their evolution. In this contribution, we apply the ice-sheet model SICOPOLIS (SImulation COde for POLythermal Ice Sheets) to the Mocho-Choshuenco ice cap in the Chilean Lake District (40∘ S, 72∘ W; Wet Andes) to reproduce its current state and to project its evolution until the end of the 21st century under different global warming scenarios. First, we create a model spin-up using observed surface mass balance data on the south-eastern catchment, extrapolating them to the whole ice cap using an aspect-dependent parameterization. This spin-up is able to reproduce the most important present-day glacier features. Based on the spin-up, we then run the model 80 years into the future, forced by projected surface temperature anomalies from different global climate models under different radiative pathway scenarios to obtain estimates of the ice cap's state by the end of the 21st century. The mean projected ice volume losses are 56±16 % (RCP2.6), 81±6 % (RCP4.5), and 97±2 % (RCP8.5) with respect to the ice volume estimated by radio-echo sounding data from 2013. We estimate the uncertainty of our projections based on the spread of the results when forcing with different global climate models and on the uncertainty associated with the variation of the equilibrium line altitude with temperature change. Considering our results, we project a considerable deglaciation of the Chilean Lake District by the end of the 21st century.

The surface energy fluxes of glaciers determine surface melt, and their adequate parametrization is one of the keys to a successful prediction of future glacier mass balance and freshwater discharge. Chile hosts glaciers in a large range of latitudes under contrasting climatic settings: from 18∘ S in the Atacama Desert to 55∘ S on Tierra del Fuego. Using three different methods, we computed surface energy fluxes for five glaciers which represent the main glaciological zones of Chile. We found the main energy sources for surface melt change from the Central Andes, where the net shortwave radiation is driving the melt, to Patagonia, where the turbulent fluxes are an important source of energy. We inferred higher surface melt rates for Patagonian glaciers as compared to the glaciers of the Central Andes due to a higher contribution of the turbulent sensible heat flux, less negative net longwave radiation and a positive contribution of the turbulent latent heat flux. The variability in the atmospheric emissivity was high and not able to be explained exclusively by the variability in the inferred cloud cover. The influence of the stability correction and the roughness length on the magnitude of the turbulent fluxes in the different climate settings was examined. We conclude that, when working towards physical melt models, it is not sufficient to use the observed melt as a measure of model performance; the model parametrizations of individual components of the energy balance have to be validated individually against measurements.

Mobility is becoming more and more important to society and hence air transportation is expected to grow further over the next decades. Reducing anthropogenic climate impact from aviation emissions and building a climate-friendly air transportation system are required for a sustainable development of commercial aviation. A climate optimized routing, which avoids climate-sensitive regions by re-routing horizontally and vertically, is an important measure for climate impact reduction. The idea includes a number of different routing strategies (routing options) and shows a great potential for the reduction. To evaluate this, the impact of not only CO2 but also non-CO2 emissions must be considered. CO2 is a long-lived gas, while non-CO2 emissions are short-lived and are inhomogeneously distributed. This study introduces AirTraf (version 1.0) that performs global air traffic simulations, including effects of local weather conditions on the emissions. AirTraf was developed as a new submodel of the ECHAM5/MESSy Atmospheric Chemistry (EMAC) model. Air traffic information comprises Eurocontrol's Base of Aircraft Data (BADA Revision 3.9) and International Civil Aviation Organization (ICAO) engine performance data. Fuel use and emissions are calculated by the total energy model based on the BADA methodology and Deutsches Zentrum für Luft- und Raumfahrt (DLR) fuel flow method. The flight trajectory optimization is performed by a genetic algorithm (GA) with respect to a selected routing option. In the model development phase, benchmark tests were performed for the great circle and flight time routing options. The first test showed that the great circle calculations were accurate to −0.004 %, compared to those calculated by the Movable Type script. The second test showed that the optimal solution found by the algorithm sufficiently converged to the theoretical true-optimal solution. The difference in flight time between the two solutions is less than 0.01 %. The dependence of the optimal solutions on the initial set of solutions (called population) was analyzed and the influence was small (around 0.01 %). The trade-off between the accuracy of GA optimizations and computational costs is clarified and the appropriate population and generation (one iteration of GA) sizing is discussed. The results showed that a large reduction in the number of function evaluations of around 90 % can be achieved with only a small decrease in the accuracy of less than 0.1 %. Finally, AirTraf simulations are demonstrated with the great circle and the flight time routing options for a typical winter day. The 103 trans-Atlantic flight plans were used, assuming an Airbus A330-301 aircraft. The results confirmed that AirTraf simulates the air traffic properly for the two routing options. In addition, the GA successfully found the time-optimal flight trajectories for the 103 airport pairs, taking local weather conditions into account. The consistency check for the AirTraf simulations confirmed that calculated flight time, fuel consumption, NOx emission index and aircraft weights show good agreement with reference data.

We present surface mass balance simulations of the Southern Patagonia Icefield (SPI) driven by downscaled reanalysis data. The simulations were evaluated and interpreted using geodetic mass balances, measured point balances and a complete velocity field of the icefield for spring 2004. The high measured accumulation of snow of up to 15.4 m w.e. yr−1 (meters water equivalent per year) as well as the high measured ablation of up to 11 m w.e. yr−1 is reproduced by the model. The overall modeled surface mass balance was positive and increasing during 1975–2011. Subtracting the surface mass balance from geodetic balances, calving fluxes were inferred. Mass losses of the SPI due to calving were strongly increasing from 1975–2000 to 2000–2011 and higher than losses due to surface melt. Calving fluxes were inferred for the individual glacier catchments and compared to fluxes estimated from velocity data. Measurements of ice thickness and flow velocities at the glaciers' front and spatially distributed accumulation measurements can help to reduce the uncertainties of the different terms in the mass balance of the Southern Patagonia Icefield.

Background: Patient-reported outcome measures (PROMs) have gained increased importance in assessing outcomes after reconstructive surgery. This also applies to the reconstruction of vulvoperineal defects after resection of gynecological or colorectal cancers in women. The objective of this study is to analyze the current state of PROM tool use within this patient population. Methods: By systematic literature searches in Embase, Medline, and Web of Science, English-language studies published after 1980, including randomized controlled trials, cohort studies, and case series reporting on vulvoperineal defect reconstruction, which were included if they also analyzed quality of life (QoL) and/or PROMs. The PROM tools used by each study were extracted, analyzed, and compared. Results: The primary search yielded 2576 abstracts, of which 395 articles were retrieved in full text. Of these, 50 reported on vulvoperineal defect reconstruction, among which 27 studies analyzing QoL were found. Of those, 17 met the inclusion criteria for this systematic review. After full-text screening, 14 different PROM tools and 5 individual, non-standardized questionnaires were identified. Only 22% of studies used a validated PROM tool. Conclusion: Far too few studies currently use PROM tools to assess outcomes in oncological vulvoperineal defect reconstruction. Less than half of the used PROMs are validated. No PROM was designed to specifically measure QoL in this patient population. The standardized implementation of a validated PROM tool in the clinical treatment of this patient population is an essential step to improve outcomes, enable the comparison of research, and support evidence-based treatment approaches.

We present 40 new 10Be exposure ages of moraines and other glacial deposits left behind by the southeastern sector of the Laurentide Ice Sheet (LIS) in southern New England and New York, summarize the regional moraine record, and interpret the dataset in the context of previously published deglaciation chronologies. The regional moraine record spans the Last Glacial Maximum (LGM), with the outermost ridge of the terminal complex dating to ∼ 26–25 ka, the innermost ridge of the terminal complex dating to ∼ 22 ka, and a series of smaller recessional limits within ∼ 50 km of the terminal complex dating to ∼ 21–20.5 ka. The chronology generally agrees with independent age constraints from radiocarbon and glacial varves. A few inconsistencies between ages from cosmogenic-nuclide measurements and those from other dating methods are explained by geological scatter, where several bedrock samples and boulders from the outer terminal moraine exhibit nuclide inheritance, while some exposure ages of large moraines are likely affected by postdepositional disturbance. The exposure age chronology places the southeastern sector of the LIS at or near its maximum extent, from ∼ 26 to 21 ka, which is broadly consistent with the LGM sea-level lowstand, local and regional temperature indicators, and local summer insolation. The net change in LIS extent, represented by this chronology, occurred more slowly (< 5 to 25 m yr−1) than the subsequent retreat through the rest of New England, consistent with a slow general rise in insolation and modeled summer temperature. We conclude that the major pulse of LIS deglaciation and accelerated recession, recorded by dated glacial deposits north of the moraines discussed here, did not begin until after atmospheric CO2 increased around 18 ka, marking the onset of Termination I.

The fungal pathogen Candida albicans transforms arachidonic acid (AA) into 3-hydroxyarachidonic acid [3(R)-HETE], and we investigated if its nonpathogenic and 3(R)-HETE-producing close relative, Dipodascopsis uninucleata, could similarly transform the endocannabinoid/endovanilloid anandamide into 3-hydroxyanandamide (3-HAEA). We found that D. uninucleata converts anandamide into 3-HAEA, and we therefore developed an enantiodivergent synthesis for this compound to study its pharmacological activity. Both enantiomers of 3-HAEA were as active as anandamide at elevating intracellular Ca2+ via TRPV1 receptors overexpressed in HEK-293 cells, while a∼70–90-fold and ∼45–60-fold lower affinity at cannabinoid CB1 and CB2 receptors was instead observed. Patch clamp recordings showed that 3(R)-HAEA activates a TRPV1-like current in TRPV1-expressing HEK-293 cells. Thus, 3(R)-HETE-producing yeasts might convert anandamide released by host cells at the site of infection into 3(R)-HAEA, and this event might contribute to the inflammatory and algogenous responses associated to fungal diseases.

Abstract An ideal tumor‐specific immunomodulatory therapy should both preferentially target the tumor, while simultaneously reduce the immunosuppressive environment within the tumor. This guiding principle led us to explore engineering Siglec‐15 (S15) targeted bispecific antibody (bsAb) to enhance therapy against triple negative breast cancer (TNBC). S15 appears to be exclusively expressed on macrophages and diverse tumor cells, including human and mouse 4T1 TNBC. TGF‐β is a growth hormone frequently associated with increased tumor invasiveness, including in TNBC. Here, to overcome the immune‐suppressive environment within TNBC tumors to enable more effective cancer therapy, we engineered a bispecific antibody (bsAb) targeting both Siglec15 and TGF‐β. In mice engrafted with orthotopic 4T1 tumors, S15/TGF‐β bsAb treatment was highly effective in suppressing tumor growth, not only compared to control monoclonal antibody (mAb) but also markedly more effective than mAbs against S15 alone, against TGF‐β alone, as well as a cocktail of both anti‐S15 and anti‐TGF‐β mAbs. We did not detect liver and lung metastasis in mice treated with S15/TGF‐β bsAb, unlike all other treatment groups at the end of the study. The enhanced anti‐tumor response observed with S15/TGF‐β bsAb correlated with a less immunosuppressive environment in the tumor. These results underscore S15‐targeted bsAb as a promising therapeutic strategy for TNBC, and possibly other S15 positive solid tumors.

Abstract NADH autofluorescence imaging is a promising approach for visualizing energy metabolism at the single-cell level. However, it is sensitive to the redox ratio and the total NAD(H) amount, which can change independently from each other, for example with aging. Here, we evaluate the potential of fluorescence lifetime imaging microscopy (FLIM) of NADH to differentiate between these modalities. We perform targeted modifications of the NAD(H) pool size and ratio in cells and mice and assess the impact on NADH FLIM. We show that NADH FLIM is sensitive to NAD(H) pool size, mimicking the effect of redox alterations. However, individual components of the fluorescence lifetime are differently impacted by redox versus pool size changes, allowing us to distinguish both modalities using only FLIM. Our results emphasize NADH FLIM’s potential for evaluating cellular metabolism and relative NAD(H) levels with high spatial resolution, providing a crucial tool for our understanding of aging and metabolism.

Alpine glacier-based temperature reconstructions spanning the last deglaciation provide critical constraints on local to regional climate change and have been reported from several formerly glaciated regions around the world yet remain sparse from high-northern-latitude regions. Using newly and previously 10Be-dated moraines, we report paleo-glacier equilibrium line altitudes (ELAs) for 15 time slices spanning the Last Glacial Maximum (LGM) to the Little Ice Age (LIA) for a valley in the western Alaska Range. We translate our ELA reconstructions into a proxy for summer temperature by applying a dry adiabatic lapse rate at each reconstructed ELA relative to the outermost LIA moraine. We observe ∼4 °C warming through the last deglaciation at our site that took place in two steps following initial gradual warming: ∼1.5 °C abrupt warming at 16 ka, ∼2 kyr after the onset of global CO2 rise, and ∼2 °C warming at ∼15 ka, near the start of the Bølling. Moraine deposition and modest summer cooling during Heinrich Stadial 1 and the early Younger Dryas (YD) suggest that despite these events being expressed more strongly in wintertime, the classic blueprint of North Atlantic climate variability extends to the western Arctic region.

Abstract Bivalent molecules consisting of groups connected through bridging linkers often exhibit strong target binding and unique biological effects. However, developing bivalent inhibitors with the desired activity is challenging due to the dual motif architecture of these molecules and the variability that can be introduced through differing linker structures and geometries. We report a set of alternatively linked bivalent EGFR inhibitors that simultaneously occupy the ATP substrate and allosteric pockets. Crystal structures show that initial and redesigned linkers bridging a trisubstituted imidazole ATP-site inhibitor and dibenzodiazepinone allosteric-site inhibitor proved successful in spanning these sites. The re-engineered linker yielded a compound that exhibited significantly higher potency (~60 pM) against the drug-resistant EGFR L858R/T790M and L858R/T790M/C797S, which was superadditive as compared with the parent molecules. The enhanced potency is attributed to factors stemming from the linker connection to the allosteric-site group and informs strategies to engineer linkers in bivalent agent design.

Abstract Background Information on social media may affect peoples’ contraceptive decision making. We performed an exploratory analysis of contraceptive content on Twitter (recently renamed X), a popular social media platform. Methods We selected a random subset of 1% of publicly available, English-language tweets related to reversible, prescription contraceptive methods posted between January 2014 and December 2019. We oversampled tweets for the contraceptive patch to ensure at least 200 tweets per method. To create the codebook, we identified common themes specific to tweet content topics, tweet sources, and tweets soliciting information or providing advice. All posts were coded by two team members, and differences were adjudicated by a third reviewer. Descriptive analyses were reported with accompanying qualitative findings. Results During the study period, 457,369 tweets about reversible contraceptive methods were published, with a random sample of 4,434 tweets used for final analysis. Tweets most frequently discussed contraceptive method decision-making (26.7%) and side effects (20.5%), particularly for long-acting reversible contraceptive methods and the depot medroxyprogesterone acetate shot. Tweets about logistics of use or adherence were common for short-acting reversible contraceptives. Tweets were frequently posted by contraceptive consumers (50.6%). A small proportion of tweets explicitly requested information (6.2%) or provided advice (4.2%). Conclusions Clinicians should be aware that individuals are exposed to information through Twitter that may affect contraceptive perceptions and decision making, particularly regarding long-acting reversible contraceptives. Social media is a valuable source for studying contraceptive beliefs missing in traditional health research and may be used by professionals to disseminate accurate contraceptive information.

Antibiotic resistance (AR) is a growing health concern worldwide and the Arctic represents an understudied region in terms of AR. This study aimed to quantify AR genes (ARGs) from effluent released from a wastewater treatment plant (WWTP) in Iqaluit, Nunavut, Canada, thus creating a baseline reference for future evaluations. Water, sediment, and truncate softshell clam (Mya truncata) tissue samples were compared from the wastewater, the receiving environment of Frobisher Bay, and nearby undisturbed freshwaters. The pharmaceuticals and personal care products (PPCPs) atenolol, carbamazepine, metoprolol, naproxen, sulfapyridine, and trimethoprim were found in the wastewater, but the PPCPs were undetectable in the receiving environment. However, the relative abundances of ARGs were significantly higher in wastewater than in the receiving environment or reference sites. Abundances did not significantly differ in Frobisher Bay compared to undisturbed reference sites. ARGs in clams near the WWTP had similar relative abundances as those from pristine areas. The lack of ARG detection is likely due to Frobisher Bay tides flushing inputs to levels below detection. These data suggest that the WWTP infrastructure does not influence the receiving environment based on the measured parameters; more importantly, further research must elucidate the impact and fate of AR and PPCPs in Arctic communities.

Abstract Background Eating disorders (EDs) are serious, complex disorders for which broad-based clinical training is lacking. This study aimed to evaluate the efficacy of a free, brief, web-based curriculum, PreparED, in increasing comfort and confidence with, and knowledge about EDs in healthcare trainees, and to obtain program feedback from key stakeholders (i.e., learners). Methods This programmatic evaluation study was designed as a quantitative, repeated measures (i.e., pre- and post-test intervention) investigation. A convenience sample of two groups of healthcare trainees across geographically diverse training sites completed an anonymous survey pre- and post- engagement with PreparED. The survey included items to assess prior exposure to EDs, as well as program feasibility. The main educational outcomes included (1) Confidence and Comfort with EDs and (2) Knowledge of EDs. User experience variables of interest were likeability, usability, and engagement with the training modules. Mixed effects linear regression was used to assess the association between PreparED and educational outcome variables. Results Participants (N = 67) included 41 nutrition graduate students and 26 nurse practitioner students recruited from Teacher’s College/Columbia University in New York, NY, USA, Columbia University School of Nursing in New York, NY, USA and North Dakota State University School of Nursing in Fargo, ND, USA. Confidence/Comfort scores and Knowledge scores significantly improved following engagement with PreparED (β = for effect of intervention = 1.23, p

Myoclonic status epilepticus (MSE) is a sign of severe neurologic injury in cardiac arrest patients. To our knowledge, MSE has not been described as a result of prolonged hyperpyrexia. A 56-year-old man with coronavirus disease 2019 presented with acute respiratory distress syndrome, septic/hypovolemic shock, and presumed community-acquired pneumonia. Five days after presentation, he developed a sustained fever of 42.1°C that did not respond to acetaminophen or ice water gastric lavage. After several hours, he was placed on surface cooling. Three hours after fever resolution, new multifocal myoclonus was noted in the patient’s arms and trunk. Electroencephalography showed midline spikes consistent with MSE, which resolved with 40 mg/kg of levetiracetam. This case demonstrates that severe hyperthermia can cause cortical injury significant enough to trigger MSE and should be treated emergently using the most aggressive measures available. Providers should have a low threshold for electroencephalography in intubated patients with a recent history of hyperpyrexia.

Abstract Background Dementia is a common disease with around 55 million cases worldwide. Therefore, dietary changes and lifestyle interventions are important approaches to delay the progress of a decline in cognitive function. The study aims to explore the association of various sources of free sugars (FS) and intrinsic sugars with dementia risk in the prospective population-based UK Biobank cohort. Methods Sugar consumption was assessed in 186,622 UK Biobank participants with at least one web-based dietary questionnaire (Oxford WebQ). Over a mean follow-up of 10.6 (standard deviation 1.1) years, 1498 incident dementia cases occurred. The hazard ratios (HR) for incident dementia were assessed with Cox proportional hazard regression models including sugar intake from different sources as penalized cubic splines to allow for non-linear predictor effects. Results The intake of FS and intrinsic sugar was significantly associated with dementia risk in a J-shaped fashion with the HR-nadir observed at 9% and 8% total energy (%E), respectively. FS in beverages were significantly associated with dementia risk in an ascending approximately linear way, whereas no significant association was found for FS in solids. Assessing beverage subtypes, FS in soda/fruit drinks, milk-based drinks and to a lesser extent in juice were significantly and positively related to dementia risk, whereas no association was found for FS in tea/coffee. The association between sugar subtype consumption and dementia risk remained consistent in most sensitivity analyses but changed from a J-shape to a more linear shape when the analysis was restricted to participants with at least two Oxford WebQs. Conclusions A linear-shaped association between sugar subtype intake and dementia risk is most consistently found for FS in beverages and more specifically for FS in soda/fruit drinks, as well as in milk-based drinks. Graphical Abstract

IntroductionA greater sense of purpose in life is associated with several health benefits relevant for active aging, but the mechanisms remain unclear. We evaluated if purpose in life was associated with indices of brain health.MethodsWe examined data from the Midlife in the United States (MIDUS) Neuroscience Project. Diffusion weighted magnetic resonance imaging data (n=138; mean age 65.2 years, age range 48-95; 80 females; 37 black, indigenous, and people of color) were used to estimate microstructural indices of brain health such as axonal density, and axonal orientation. The seven-item purpose in life scale was used. Permutation analysis of linear models was used to examine associations between purpose in life scores and the diffusion metrics in white matter and in the bilateral hippocampus, adjusting for age, sex, education, and race.Results and discussionGreater sense of purpose in life was associated with brain microstructural features consistent with better brain health. Positive associations were found in both white matter and the right hippocampus, where multiple convergent associations were detected. The hippocampus is a brain structure involved in learning and memory that is vulnerable to stress but retains the capacity to grow and adapt through old age. Our findings suggest pathways through which an enhanced sense of purpose in life may contribute to better brain health and promote healthy aging. Since purpose in life is known to decline with age, interventions and policy changes that facilitate a greater sense of purpose may extend and improve the brain health of individuals and thus improve public health.

Abstract Respiratory syncytial virus (RSV) causes substantial morbidity and mortality in infants, the immunocompromised, and the elderly. RSV infects the airway epithelium via the apical membrane and almost exclusively sheds progeny virions back into the airway mucus (AM), making RSV difficult to target by systemically administered therapies. An inhalable “muco‐trapping” variant of motavizumab (Mota‐MT), a potent neutralizing mAb against RSV F is engineered. Mota‐MT traps RSV in AM via polyvalent Fc‐mucin bonds, reducing the fraction of fast‐moving RSV particles in both fresh pediatric and adult AM by ≈20–30‐fold in a Fc‐glycan dependent manner, and facilitates clearance from the airways of mice within minutes. Intranasal dosing of Mota‐MT eliminated viral load in cotton rats within 2 days. Daily nebulized delivery of Mota‐MT to RSV‐infected neonatal lambs, beginning 3 days after infection when viral load is at its maximum, led to a 10 000‐fold and 100 000‐fold reduction in viral load in bronchoalveolar lavage and lung tissues relative to placebo control, respectively. Mota‐MT‐treated lambs exhibited reduced bronchiolitis, neutrophil infiltration, and airway remodeling than lambs receiving placebo or intramuscular palivizumab. The findings underscore inhaled delivery of muco‐trapping mAbs as a promising strategy for the treatment of RSV and other acute respiratory infections.

Here, we present cosmogenic-10Be and cosmogenic-3He data from Ferrar dolerite pyroxenes in surficial rock samples and a bedrock core from the McMurdo Dry Valleys, Antarctica, with the goal of refining the laboratory methods for extracting beryllium from pyroxene, further estimating the 10Be production rate in pyroxene and demonstrating the applicability of 10Be–3He in mafic rock. The ability to routinely measure cosmogenic 10Be in pyroxene will open new opportunities for quantifying exposure durations and Earth surface processes in mafic rocks. We describe scalable laboratory methods for isolating beryllium from pyroxene, which include a simple hydrofluoric acid leaching procedure for removing meteoric 10Be and the addition of a pH 8 precipitation step to reduce the cation load prior to ion exchange chromatography. 10Be measurements in pyroxene from the surface samples have apparent 3He exposure ages of 1–6 Myr. We estimate a spallation production rate for 10Be in pyroxene, referenced to 3He, of 3.6 ± 0.2 atoms g−1 yr−1. 10Be and 3He measurements in the bedrock core yield initial estimates for parameters associated with 10Be and 3He production by negative-muon capture (f10∗=0.00183 and f3∗fCfD=0.00337). Next, we demonstrate that the 10Be–3He pair in pyroxene can be used to simultaneously resolve erosion rates and exposure ages, finding that the measured cosmogenic-nuclide concentrations in our surface samples are best explained by 2–8 Myr of exposure at erosion rates of 0–35 cm Myr−1. Finally, given the low 10Be in our laboratory blanks (average of 5.7 × 103 atoms), the reported measurement precision, and our estimated production rate, it should be possible to measure 2 g samples with 10Be concentrations of 6 × 104 and 1.5 × 104 atoms g−1 with 5 % and 15 % uncertainty, respectively. With this level of precision, Last Glacial Maximum to Late Holocene surfaces can now be dated with 10Be in pyroxene. Application of 10Be in pyroxene, alone or in combination with 3He, will expand possibilities for investigating glacial histories and landscape change in mafic rock.

Introduction Pregnancy is a known independent risk factor for a severe course of COVID-19. The relationship of SARS-CoV-2 infection and gestational diabetes mellitus (GDM) on neonatal outcomes is unclear. Our aim was to determine if SARS-CoV-2 infection represents an independent risk factor for adverse perinatal outcomes in pregnancy with GDM.Research design and methods We compared data from two German registries including pregnant women with GDM, established during the SARS-CoV-2 pandemic (COVID-19-Related Obstetric and Neonatal Outcome Study (CRONOS), a multicenter prospective observational study) and already existing before the pandemic (German registry of pregnant women with GDM; GestDiab). In total, 409 participants with GDM and SARS-CoV-2 infection and 4598 participants with GDM, registered 2018–2019, were eligible for analyses. The primary fetal and neonatal outcomes were defined as: (1) combined: admission to neonatal intensive care unit, stillbirth, and/or neonatal death, and (2) preterm birth before 37+0 weeks of gestation. Large and small for gestational age, maternal insulin therapy, birth weight >4500 g and cesarean delivery were considered as secondary outcomes.Results Women with SARS-CoV-2 infection were younger (32 vs 33 years) and had a higher median body mass index (28 vs 27 kg/m²). In CRONOS, more neonates developed the primary outcome (adjusted OR (aOR) 1.48, 95% CI 1.11 to 1.97) and were born preterm (aOR 1.50, 95% CI 1.07 to 2.10). Fasting glucose was higher in women in CRONOS versus GestDiab (5.4 vs 5.3 mmol/L) considering each 0.1 mmol/L increase was independently associated with a 5% higher risk of preterm birth among women in CRONOS only (aOR 1.05, 95% CI 1.01 to 1.09).Conclusions GDM with SARS-CoV-2 infection in pregnancy is associated with an increased risk of adverse fetal and neonatal outcomes as compared with GDM without SARS-CoV-2 infection.

Abstract Topoisomerase 3α (TOP3A) is an enzyme that removes torsional strain and interlinks between DNA molecules. TOP3A localises to both the nucleus and mitochondria, with the two isoforms playing specialised roles in DNA recombination and replication respectively. Pathogenic variants in TOP3A can cause a disorder similar to Bloom syndrome, which results from bi‐allelic pathogenic variants in BLM, encoding a nuclear‐binding partner of TOP3A. In this work, we describe 11 individuals from 9 families with an adult‐onset mitochondrial disease resulting from bi‐allelic TOP3A gene variants. The majority of patients have a consistent clinical phenotype characterised by bilateral ptosis, ophthalmoplegia, myopathy and axonal sensory‐motor neuropathy. We present a comprehensive characterisation of the effect of TOP3A variants, from individuals with mitochondrial disease and Bloom‐like syndrome, upon mtDNA maintenance and different aspects of enzyme function. Based on these results, we suggest a model whereby the overall severity of the TOP3A catalytic defect determines the clinical outcome, with milder variants causing adult‐onset mitochondrial disease and more severe variants causing a Bloom‐like syndrome with mitochondrial dysfunction in childhood.

We demonstrate that a gradual interface between gold and silver supports the propagation of a novel kind of surface electromagnetic wave, which is different from the more well-known surface plasmon polaritons. The existence of such surface waves leads to a paradoxical situation in which a continuous metal barrier which does not have any pinholes may exhibit considerably increased light transmission if the barrier is made of two different metals. A spectroscopic study of this effect is reported.

Greater cortisol reactivity to stress is often assumed to lead to heightened negative affective reactivity to stress. Conversely, a growing body of evidence demonstrates mood-protective effects of cortisol elevations in the context of acute stress. We administered a laboratory-based stressor, the Trier Social Stress Test (TSST), and measured cortisol and emotional reactivity in 68 adults (48 women) between the ages of 25 and 65. In accordance with our pre-registered hypothesis (https://osf.io/t8r3w) and prior research, negative affective reactivity was inversely related to cortisol reactivity assessed immediately after the stressor. We found that greater cortisol response to acute stress is associated with smaller increases in negative affect, consistent with mood-protective effects of cortisol elevations in response to acute stress.

Background Mitochondrial disorders are known to cause diverse neurological phenotypes which cause a diagnostic challenge to most neurologists. Pathogenic polymerase gamma (POLG) variants have been described as a cause of chronic progressive external ophthalmoplegia, which manifests with ptosis, horizontal and vertical eye movement restriction and myopathy. Autosomal dominant progressive external ophthalmoplegia is rarely associated with Parkinsonism responsive to levodopa.Methods We report a case of a 58-year-old man who presented with an eye movement disorder then Parkinsonism who made his way through the myasthenia then the movement disorder clinic.Results A diagnostic right tibialis anterior biopsy revealed classical hallmarks of mitochondrial disease, and genetic testing identified compound heterozygous pathogenic gene variants in the POLG gene. The patient was diagnosed with autosomal recessive POLG disease.Conclusions It is important to maintain a high index of suspicion of pathogenic POLG variants in patients presenting with atypical Parkinsonism and ophthalmoplegia. Patients with POLG-related disease will usually have ptosis, and downgaze is typically preserved until late in the disease. Accurate diagnosis is essential for appropriate prognosis and genetic counselling.

The preservation of cosmogenic nuclides that accumulated during periods of prior exposure but were not subsequently removed by erosion or radioactive decay complicates interpretation of exposure, erosion, and burial ages used for a variety of geomorphological applications. In glacial settings, cold-based, non-erosive glacier ice may fail to remove inventories of inherited nuclides in glacially transported material. As a result, individual exposure ages can vary widely across a single landform (e.g., moraine) and exceed the expected or true depositional age. The surface processes that contribute to inheritance remain poorly understood, thus limiting interpretations of cosmogenic nuclide datasets in glacial environments. Here, we present a compilation of new and previously published exposure ages of multiple lithologies in local Last Glacial Maximum (LGM) and older Pleistocene glacial sediments in the McMurdo Sound region of Antarctica. Unlike most Antarctic exposure chronologies, we are able to compare exposure ages of local LGM sediments directly against an independent radiocarbon chronology of fossil algae from the same sedimentary unit that brackets the age of the local LGM between 12.3 and 19.6 ka. Cosmogenic exposure ages vary by lithology, suggesting that bedrock source and surface processes prior to, during, and after glacial entrainment explain scatter. 10Be exposure ages of quartz in granite, sourced from the base of the stratigraphic section in the Transantarctic Mountains, are scattered but young, suggesting that clasts entrained by sub-glacial plucking can generate reasonable apparent exposure ages. 3He exposure ages of pyroxene in Ferrar Dolerite, which crops out above outlet glaciers in the Transantarctic Mountains, are older, which suggests that clasts initially exposed on cliff faces and glacially entrained by rock fall carry inherited nuclides. 3He exposure ages of olivine in basalt from local volcanic bedrock in the McMurdo Sound region contain many excessively old ages but also have a bimodal distribution with peak probabilities that slightly pre-date and post-date the local LGM; this suggests that glacial clasts from local bedrock record local landscape exposure. With the magnitude and geological processes contributing to age scatter in mind, we examine exposure ages of older glacial sediments deposited by the most extensive ice sheet to inundate McMurdo Sound during the Pleistocene. These results underscore how surface processes operating in the Transantarctic Mountains are expressed in the cosmogenic nuclide inventories held in Antarctic glacial sediments.

Microcystins are toxic chemicals generated by certain freshwater cyanobacteria. These chemicals can accumulate to dangerous levels during harmful algal blooms. When exposed to microcystins, humans are at risk of hepatic injury, including liver failure. Here, we describe a method to detect microcystins in human plasma by using immunocapture followed by a protein phosphatase inhibition assay. At least 279 microcystins have been identified, and most of these compounds share a common amino acid, the Adda side chain. We targeted this Adda side chain using a commercial antibody and extracted microcystins from human samples for screening and analysis. To quantitate the extracted microcystins, we fortified plasma with microcystin-LR, one of the most well-studied, commonly detected, and toxic microcystin congeners. The quantitation range for the detection of microcystin in human plasma using this method is 0.030–0.50 ng/mL microcystin-LR equivalents. This method detects unconjugated and conjugated forms (cysteine and glutathione) of microcystins. Quality control sample accuracies varied between 98.9% and 114%, with a precision of 7.18–15.8%. Finally, we evaluated plasma samples from a community health surveillance project of Florida residents living or working near harmful algae blooms.

Objective Regular cardiac surveillance is advocated for patients with primary mitochondrial DNA disease. However, there is limited information to guide clinical practice in mitochondrial conditions caused by nuclear DNA defects. We sought to determine the frequency and spectrum of cardiac abnormalities identified in adult mitochondrial disease originated from the nuclear genome.Methods Adult patients with a genetically confirmed mitochondrial disease were identified and followed up at the national clinical service for mitochondrial disease in Newcastle upon Tyne, UK (January 2009 to December 2018). Case notes, molecular genetics reports, laboratory data and cardiac investigations, including serial electrocardiograms and echocardiograms, were reviewed.Results In this cohort-based observational study, we included 146 adult patients (92 women) (mean age 53.6±18.7 years, 95% CI 50.6 to 56.7) with a mean follow-up duration of 7.9±5.1 years (95% CI 7.0 to 8.8). Eleven different nuclear genotypes were identified: TWNK, POLG, RRM2B, OPA1, GFER, YARS2, TYMP, ETFDH, SDHA, TRIT1 and AGK. Cardiac abnormalities were detected in 14 patients (9.6%). Seven of these patients (4.8%) had early-onset cardiac manifestations: hypertrophic cardiomyopathy required cardiac transplantation (AGK; n=2/2), left ventricular (LV) hypertrophy and bifascicular heart block (GFER; n=2/3) and mild LV dysfunction (GFER; n=1/3, YARS2; n=1/2, TWNK; n=1/41). The remaining seven patients had acquired heart disease most likely related to conventional cardiovascular risk factors and presented later in life (14.6±12.8 vs 55.1±8.9 years, p

Background Glass slide preparations from a variety of specimens (blood, masses, effusions) are commonly made as part of the diagnostic work-up, however the effects of various drying methods in veterinary practice and diagnostic laboratory settings is not clear. Objective Compare the effects of four drying methods on results of microscopic examination of canine blood smears and direct smears of pleural or peritoneal effusion fluid. Methods Twelve canine blood samples (6 from healthy dogs, 6 from sick dogs) and 6 canine peritoneal or pleural effusion samples. Four smears were prepared from each of the 18 samples and dried using the following methods: air-dry, hair dryer with or without heat, and heat block at 58 °C. Observers, blinded to the drying method, independently reviewed the slides microscopically, using a scoring system to evaluate cell morphology and (for blood smears) echinocyte numbers; scoring results were analyzed statistically. Results For blood smears, several comparisons showed more adverse effects on morphology using the heat block method than for one or more other drying methods. For effusion fluid smears, RBCs dried with the heat block or air-dry methods had more poorly preserved morphology than RBCs dried by the hair dryer method without heat. Conclusions and clinical relevance The results (1) indicate that different drying methods had a significant effect, (2) support using a hair dryer without heat for both blood smears and effusion fluid smears, and (3) discourage using a 58 °C heat block.

Purpose One of the main pathophysiological mechanisms of chronic obstructive pulmonary disease is inflammation, which has been associated with lymphadenopathy. Intrapulmonary lymph nodes can be identified on CT as perifissural nodules (PFN). We investigated the association between the number and size of PFNs and measures of COPD severity. Materials and Methods CT images were obtained from COPDGene. 50 subjects were randomly selected per GOLD stage (0 to 4), GOLD-unclassified, and never-smoker groups and allocated to either “Healthy,” “Mild,” or “Moderate/severe” groups. 26/350 (7.4%) subjects had missing images and were excluded. Supported by computer-aided detection, a trained researcher prelocated non-calcified opacities larger than 3 mm in diameter. Included lung opacities were classified independently by two radiologists as either “PFN,” “not a PFN,” “calcified,” or “not a nodule”; disagreements were arbitrated by a third radiologist. Ordinal logistic regression was performed as the main statistical test. Results A total of 592 opacities were included in the observer study. A total of 163/592 classifications (27.5%) required arbitration. A total of 17/592 opacities (2.9%) were excluded from the analysis because they were not considered nodular, were calcified, or all three radiologists disagreed. A total of 366/575 accepted nodules (63.7%) were considered PFNs. A maximum of 10 PFNs were found in one image; 154/324 (47.5%) contained no PFNs. The number of PFNs per subject did not differ between COPD severity groups (p = 0.50). PFN short-axis diameter could significantly distinguish between the Mild and Moderate/severe groups, but not between the Healthy and Mild groups (p = 0.021). Conclusions There is no relationship between PFN count and COPD severity. There may be a weak trend of larger intrapulmonary lymph nodes among patients with more advanced stages of COPD.

Abstract Mitochondrial disease associated with the pathogenic m.3243A>G variant is a common, clinically heterogeneous, neurogenetic disorder. Using multiple linear regression and linear mixed modelling, we evaluated which commonly assayed tissue (blood N = 231, urine N = 235, skeletal muscle N = 77) represents the m.3243A>G mutation load and mitochondrial DNA (mtDNA) copy number most strongly associated with disease burden and progression. m.3243A>G levels are correlated in blood, muscle and urine (R2 = 0.61–0.73). Blood heteroplasmy declines by ~2.3%/year; we have extended previously published methodology to adjust for age. In urine, males have higher mtDNA copy number and ~20% higher m.3243A>G mutation load; we present formulas to adjust for this. Blood is the most highly correlated mutation measure for disease burden and progression in m.3243A>G‐harbouring individuals; increasing age and heteroplasmy contribute (R2 = 0.27, P G heteroplasmy is the most convenient and reliable measure for routine clinical assessment, additional factors such as mtDNA copy number may also influence disease severity.

Background Organ cross-talk describes interactions between a primary affected organ and a secondarily injured remote organ, particularly in lung-brain interactions. A common theory is the systemic distribution of inflammatory mediators that are released by the affected organ and transferred through the bloodstream. The present study characterises the baseline immunogenic effects of a novel experimental model of random allogeneic blood transfusion in pigs designed to analyse the role of the bloodstream in organ cross-talk. Methods After approval of the State and Institutional Animal Care Committee, 20 anesthetized pig were randomized in a donor and an acceptor (each n = 8): the acceptor animals each received high-volume whole blood transfusion from the donor (35–40 ml kg−1). Four animals received balanced electrolyte solution instead of blood transfusion (control group; n = 4). Afterwards the animals underwent extended cardiorespiratory monitoring for eight hours. Post mortem assessment included pulmonary, cerebral and systemic mediators of early inflammatory response (IL-6, TNF-alpha, iNOS), wet to dry ratio, and lung histology. Results No adverse events or incompatibilities occurred during the blood transfusion procedures. Systemic cytokine levels and pulmonary function were unaffected. Lung histopathology scoring did not display relevant intergroup differences. Neither within the lung nor within the brain an up-regulation of inflammatory mediators was detected. High volume random allogeneic blood transfusion in pigs neither impaired pulmonary integrity nor induced systemic, lung, or brain inflammatory response. Conclusion This approach can represent a novel experimental model to characterize the blood-bound transmission in remote organ injury.

Clinical signs of photosensitivity in cattle can occur sporadically and unpredictably. It is believed that cases of photosensitivity may be underreported, causing inaccurate and inflated reports of mortality. Additionally, because secondary photosensitization in grazing cattle occurs with liver damage or dysfunction, photosensitivity can have many potential or associated causes. This case links a previous occurrence of coccidiosis to an outbreak of photosensitivity in grazing Holstein steers. Grazing management staff first observed clinical signs of photosensitivity 17 days after an outbreak of coccidiosis and subsequent turnout to spring pastures. Clinical signs were observed in 25% of the population. The severity of photosensitivity was variable and ranged from blistered skin on the muzzle to sloughing of unpigmented epidermis and thinly haired regions. Severely affected cattle were removed from pasture, housed under shade, monitored for infection, and recovered without treatment. Mild cases remained on pasture and recovered without treatment. Photosensitivity did not reoccur in the cattle that remained on pasture or in mildly affected cattle returned to pasture. Photosensitivity did not appear to be associated with pasture weeds, a specific forage species, or variable or extreme weather conditions that could have resulted in mycotoxin production. The occurrence appears to have been a result of a previous and concurrent coccidiosis outbreak that caused secondary photosensitization through hepatic lipidosis caused by anorexia and dehydration associated with the severe coccidiosis. Although clinical signs appeared suddenly, cattle recovered quickly and without treatment.

A description of vertical habitat use by yellowfin tuna, Thunnus albacares, captured and released with archival tags in the Revillagigedo Archipelago Biosphere Reserve, Mexico, during the 2006–2011 period is given. An analysis was made of internal and ambient temperatures, depth, and time of day registered in 68 archival tags recovered from tuna caught mostly in sets associated with dolphins by Mexican purse-seine vessels. Tuna were classified into 3 age groups (I, II, and III) for analyses. Vertical movements were analyzed by dividing the water column into 10 depth strata. The 3 age groups remained the longest in the uppermost stratum (0–25 m), and their presence began to diminish in subsequent strata, with some occasional visits at >500-m depths. In the >500 m stratum, age group III was the one with the longest time investment with 45 min on average. Presence at different depths throughout the day showed significant differences among age groups (Wald’s test expressed as χ2, P < 0.05). The physiological adaptation of yellowfin tuna to maintain minimal changes in its internal temperature at different depths gives it the advantage to expand its food search to deep zones where temperature oscillates around 5 ºC.

Background. The kidney transplant evaluation process for older candidates is complex due to the presence of multiple comorbid conditions. Methods. We retrospectively reviewed patients ≥60 years referred to our center for kidney transplantation over a 3-year period. Variables were collected to identify reasons for patients being turned down and to determine the number of unnecessary tests performed. Statistical analysis was performed to estimate the association between clinical predictors and listing status. Results. 345 patients were included in the statistical analysis. 31.6% of patients were turned down: 44% due to coronary artery disease (CAD), peripheral vascular disease (PVD), or both. After adjustment for patient demographics and comorbid conditions, history of CAD, PVD, or both (OR = 1.75, 95% CI (1.20, 2.56), p=0.004), chronic obstructive pulmonary disease (OR = 8.75, 95% CI (2.81, 27.20), p=0.0002), and cancer (OR 2.59, 95% CI (1.18, 5.67), p=0.02) were associated with a higher risk of being turned down. 14.8% of patients underwent unnecessary basic testing and 9.6% underwent unnecessary supplementary testing with the charges over a 3-year period estimated at $304,337. Conclusion. A significant number of older candidates are deemed unacceptable for kidney transplantation with primary reasons cited as CAD and PVD. The overall burden of unnecessary testing is substantial and potentially avoidable.

Armadillos are prehistoric-looking animals that belong to a family of mammals found primarily in Central and South America. The earliest fossil ancestor of our North American armadillo occurred about 60 million years ago; it was as large as a rhinoceros. Our present-day nine-banded or long-nosed armadillo, Dasypus novemcinctus, is much smaller; adults normally weigh from 8-17 pounds (3.5-8 kilograms). This species occurs in Texas and east, throughout the South. It occasionally is found in Missouri and South Carolina. However, cold weather limits the northern boundary of the armadillo's range. This document is WEC 76 and was previously published under the title "Control of Armadillos." It is one of a series of the Department of Wildlife Ecology and Conservation, Florida Cooperative Extension Service, Institute of Food and Agricultural Sciences (IFAS), University of Florida. First published: January 1998. Reviewed: 2001. Major revision: October 2003. WEC 76/UW082: The Nine-Banded Armadillo (Dasypus novemcinctus) (ufl.edu)

The wood duck (Aix sponsa) is known in Florida as the "summer duck" and the "acorn duck." It is one of the most colorful of all North American waterfowl. Its coloration has made it the most sought-after duck by hunters and birdwatchers. By the early 1900s, this highly desirable species was near extinction because of improper hunting regulations and habitat loss. With the Federal Migratory Bird Treaty Act in 1918, hunting of these birds was restricted. Also, wildlife officials developed a management program to increase wood duck numbers. Due to the success of this program, the wood duck is now one of the most abundant waterfowl species in North America.This document is WEC 168, one of a series of the Department of Wildlife Ecology and Conservation, Florida Cooperative Extension Service, Institute of Food and Agricultural Sciences, University of Florida. First published in April 2003. WEC 168/UW180: The Wood Duck (ufl.edu)

Abstract Background Accruing evidence suggests that personality-based approaches to eating disorder classification may offer several advantages over current diagnostic models, with prior research consistently identifying three personality-based groups characterized by either (1) high levels of impulsivity and dysregulation (termed the “undercontrolled” group), (2) high levels of rigidity and avoidance (termed the “overcontrolled” group), or (3) relatively normative levels of personality functioning (termed the “low psychopathology” group). Cognitive inflexibility (i.e., difficulty adjusting thoughts or behaviors) has theorized relevance to eating disorders. However, prior research has frequently failed to observe differences in cognitive inflexibility across eating disorder diagnostic groups. The present study aimed to identify personality-based groups in an eating disorder sample, and then to examine the relations between these groups and behavioral measures of cognitive inflexibility. Method 83 men and women who met DSM-5 criteria for anorexia nervosa or bulimia nervosa completed self-report questionnaires to assess trait-level approach/avoidance behaviors and impulsivity, as well as behavioral tasks assessing attentional set-shifting and reversal learning, two facets of cognitive inflexibility. Results Latent profile analysis of measures assessing approach/avoidance behaviors and impulsivity supported a three-class model replicating the undercontrolled, overcontrolled, and low psychopathology groups. Notably, the low psychopathology group was characterized by elevated reward responding. One-way ANOVAs indicated that the low psychopathology group demonstrated heightened perseverative errors (an indicator of impaired reversal learning) relative to the other groups. No group differences were observed for attentional set-shifting errors or probabilistic switch errors. Discussion Findings from the present study provide additional support for personality-based classification approaches identifying undercontrolled, overcontrolled, and low psychopathology eating disorder groups. Results also suggest that reward-related processes may contribute to disorder maintenance in the low psychopathology group, indicating potentially meaningful targets for intervention.

Over the last century, northwestern Canada experienced some of the highest rates of tropospheric warming globally, which caused glaciers in the region to rapidly retreat. Our study seeks to extend the record of glacier fluctuations and assess climate drivers prior to the instrumental record in the Mackenzie and Selwyn mountains of northwestern Canada. We collected 27 10Be surface exposure ages across nine cirque and valley glacier moraines to constrain the timing of their emplacement. Cirque and valley glaciers in this region reached their greatest Holocene extents in the latter half of the Little Ice Age (1600–1850 CE). Four erratic boulders, 10–250 m distal from late Holocene moraines, yielded 10Be exposure ages of 10.9–11.6 ka, demonstrating that by ca. 11 ka, alpine glaciers were no more extensive than during the last several hundred years. Estimated temperature change obtained through reconstruction of equilibrium line altitudes shows that since ca. 1850 CE, mean annual temperatures have risen 0.2–2.3 ∘C. We use our glacier chronology and the Open Global Glacier Model (OGGM) to estimate that from 1000 CE, glaciers in this region reached a maximum total volume of 34–38 km3 between 1765 and 1855 CE and had lost nearly half their ice volume by 2019 CE. OGGM was unable to produce modeled glacier lengths that match the timing or magnitude of the maximum glacier extent indicated by the 10Be chronology. However, when applied to the entire Mackenzie and Selwyn mountain region, past millennium OGGM simulations using the Max Planck Institute Earth System Model (MPI-ESM) and the Community Climate System Model 4 (CCSM4) yield late Holocene glacier volume change temporally consistent with our moraine and remote sensing record, while the Meteorological Research Institute Earth System Model 2 (MRI-ESM2) and the Model for Interdisciplinary Research on Climate (MIROC) fail to produce modeled glacier change consistent with our glacier chronology. Finally, OGGM forced by future climate projections under varying greenhouse gas emission scenarios predicts 85 % to over 97 % glacier volume loss by the end of the 21st century. The loss of glaciers from this region will have profound impacts on local ecosystems and communities that rely on meltwater from glacierized catchments.

Glacial erosion creates diagnostic landscapes and vast amounts of sediment. However, knowledge about the rate at which glaciers erode and sculpt bedrock and the proportion of quarried (plucked) versus abraded material is limited. To address this, we quantify subglacial erosion rates and constrain the ratio of quarrying to abrasion during a recent, ∼ 200-year long overriding of a bedrock surface fronting, Sermeq Kujalleq (Jakobshavn Isbræ), Greenland, by combining 10Be analyses, a digital terrain model, and field observations. Cosmogenic 10Be measurements along a 1.2 m tall quarried bedrock step reveal a triangular wedge of quarried rock. Using individual 10Be measurements from abraded surfaces across the study area, we derive an average abrasion rate of 0.13 ± 0.08 mm yr−1. By applying this analysis across a ∼ 1.33 km2 study area, we estimate that the Greenland Ice Sheet quarried 378 ± 45 m3 and abraded 322 ± 204 m3 of material at this site. These values result in an average total erosion rate of 0.26 ± 0.16 mm yr−1, with abrasion and quarrying contributing in roughly equal proportions within uncertainty. Additional cosmogenic 10Be analysis and surface texture mapping indicate that many lee steps are relicts from the prior glaciation and were not re-quarried during the recent overriding event. These new observations of glacier erosion in a recently exposed landscape provide one of the first direct measurements of quarrying rates and indicate that quarrying accounts for roughly half of the total glacial erosion in representative continental shield lithologies.

Direct observations of the size of the Greenland Ice Sheet during Quaternary interglaciations are sparse yet valuable for testing numerical models of ice-sheet history and sea level contribution. Recent measurements of cosmogenic nuclides in bedrock from beneath the Greenland Ice Sheet collected during past deep-drilling campaigns reveal that the ice sheet was significantly smaller, and perhaps largely absent, sometime during the past 1.1 million years. These discoveries from decades-old basal samples motivate new, targeted sampling for cosmogenic-nuclide analysis beneath the ice sheet. Current drills available for retrieving bed material from the US Ice Drilling Program require < 700 m ice thickness and a frozen bed, while quartz-bearing bedrock lithologies are required for measuring a large suite of cosmogenic nuclides. We find that these and other requirements yield only ∼ 3.4 % of the Greenland Ice Sheet bed as a suitable drilling target using presently available technology. Additional factors related to scientific questions of interest are the following: which areas of the present ice sheet are the most sensitive to warming, where would a retreating ice sheet expose bare ground rather than leave a remnant ice cap, and which areas are most likely to remain frozen bedded throughout glacial cycles and thus best preserve cosmogenic nuclides? Here we identify locations beneath the Greenland Ice Sheet that are best suited for potential future drilling and analysis. These include sites bordering Inglefield Land in northwestern Greenland, near Victoria Fjord and Mylius-Erichsen Land in northern Greenland, and inland from the alpine topography along the ice margin in eastern and northeastern Greenland. Results from cosmogenic-nuclide analysis in new sub-ice bedrock cores from these areas would help to constrain dimensions of the Greenland Ice Sheet in the past.

Abstract Acute kidney injury (AKI) is common in patients hospitalized for COVID-19, complicating their clinical course and contributing to worse outcomes. Animal studies show that adenosine, inosine and guanosine protect the kidney against some types of AKI. However, until now there was no evidence in patients supporting the possibility that abnormally low kidney levels of adenosine, inosine and guanosine contribute to AKI. Here, we addressed the question as to whether these renoprotective purines are altered in the urine of COVID-19 patients with AKI. Purines were measured by employing ultra-high-performance liquid chromatography-tandem mass spectrometry with stable-isotope-labeled internal standards for each purine of interest. Compared with COVID-19 patients without AKI (n = 23), COVID-19 patients with AKI (n = 20) had significantly lower urine levels of adenosine (P

Abstract Climate is currently warming due to anthropogenic impact on the Earth’s atmosphere. To better understand the processes and feedbacks within the climate system that underlie this accelerating warming trend, it is useful to examine past periods of abrupt climate change that were driven by natural forcings. Glaciers provide an excellent natural laboratory for reconstructing the climate of the past as they respond sensitively to climate oscillations. Therefore, we study glacier systems and their behavior during the transition from colder to warmer climate phases, focusing on the period between 15 and 10 ka. Using a combination of geomorphological mapping and beryllium-10 surface exposure dating, we reconstruct ice extents in two glaciated valleys of the Silvretta Massif in the Austrian Alps. The mountain glacier record shows that general deglaciation after the Last Glacial Maximum (LGM) was repeatedly interrupted by glacier stabilization or readvance, perhaps during the Oldest Dryas to Bølling transition (landform age: 14.4 ± 1.0 ka) and certainly during the Younger Dryas (YD; 12.9–11.7 ka) and the Early Holocene (EH; 12–10 ka). The oldest landform age indicates a lateral ice margin that postdates the ‘Gschnitz’ stadial (ca. 17–16 ka) and predates the YD. It shows that local inner-alpine glaciers were more extensive until the onset of the Bølling warm phase (ca. 14.6 ka), or possibly even into the Bølling than during the subsequent YD. The second age group, ca. 80 m below the (pre-)Bølling ice margin, indicates glacier extents during the YD cold phase and captures the spatial and temporal fine structure of glacier retreat during this period. The ice surface lowered approximately 50–60 m through the YD, which is indicative of milder climate conditions at the end of the YD compared to its beginning. Finally, the third age group falls into a period of more substantial warming, the YD–EH transition, and shows discontinuous glacier retreat during the glacial to interglacial transition. The new geochronologies synthesized with pre-existing moraine records from the Silvretta Massif evidence multiple cold phases that punctuated the general post-LGM warming trend and illustrate the sensitive response of Silvretta glaciers to abrupt climate oscillations in the past.

Abstract The Last Glacial Termination (T1) featured major changes in global circulation systems that led to a shift from glacial to interglacial climate. While polar ice cores attest to an antiphased thermal pattern at millennial timescales, recent well-dated moraine records from both hemispheres suggest in-phase fluctuations in glaciers through T1, which is inconsistent with the bipolar see-saw paradigm. Here, we present a glacier chronology based on 30 new 10Be surface exposure ages from well-preserved moraines in the Lago Palena/General Vintter basin in northern Patagonia (~ 44°S). We find that the main glacier lobe underwent profound retreat after 19.7 ± 0.7 ka. This recessional trend led to the individualization of the Cerro Riñón glacier by ~ 16.3 ka, which underwent minor readvances at 15.9 ± 0.5 ka during Heinrich Stadial 1, during the Antarctic Cold Reversal with successive maxima at 13.5 ± 0.4, 13.1 ± 0.4, and 13.1 ± 0.5 ka, and a minor culmination at 12.5 ± 0.4 ka during Younger Dryas time. We conclude that fluctuations of Patagonian glaciers during T1 were controlled primarily by climate anomalies brought by shifts in the Southern Westerly Winds (SWW) locus. We posit that the global covariation of mountain glaciers during T1 was linked to variations in atmospheric CO2 (atmCO2) promoted by the interplay of the SWW-Southern Ocean system at millennial timescales.

Abstract Background Sonography based estimate of fetal weight is a considerable issue for delivery planning. The study evaluated the influence of diabetes, obesity, excess weight gain, fetal and neonatal anthropometrics on accuracy of estimated fetal weight with respect to the extent of the percent error of estimated fetal weight to birth weight for different categories. Methods Multicenter retrospective analysis from 11,049 term deliveries and fetal ultrasound biometry performed within 14 days to delivery. Estimated fetal weight was calculated by Hadlock IV. Percent error from birth weight was determined for categories in 250 g increments between 2500 g and 4500 g. Estimated fetal weight accuracy was categorized as accurate ≤ 10% of birth weight, under- and overestimated by > ± 10% – ± 20% and > 20%. Results Diabetes was diagnosed in 12.5%, obesity in 12.6% and weight gain exceeding IOM recommendation in 49.1% of the women. The percentage of accurate estimated fetal weight was not significantly different in the presence of maternal diabetes (70.0% vs. 71.8%, p = 0.17), obesity (69.6% vs. 71.9%, p = 0.08) or excess weight gain (71.2% vs. 72%, p = 0.352) but of preexisting diabetes (61.1% vs. 71.7%; p = 0.007) that was associated with the highest macrosomia rate (26.9%). Mean percent error of estimated fetal weight from birth weight was 2.39% ± 9.13%. The extent of percent error varied with birth weight with the lowest numbers for 3000 g–3249 g and increasing with the extent of birth weight variation: 5% ± 11% overestimation in the lowest and 12% ± 8% underestimation in the highest ranges. Conclusion Diabetes, obesity and excess weight gain are not necessarily confounders of estimated fetal weight accuracy. Percent error of estimated fetal weight is closely related to birth weight with clinically relevant over- and underestimation at both extremes. This work provides detailed data regarding the extent of percent error for different birth weight categories and may therefore improve delivery planning.

Mid-latitude mountain glaciers are sensitive to local summer temperature changes. Chronologies of past glacier fluctuations based on the investigation of glacial landforms therefore allow for a better understanding of natural climate variability at local scale, which is relevant for the assessment of the ongoing anthropogenic climate warming. In this study, we focus on the Holocene, the current interglacial of the last 11 700 years, which remains a matter of dispute regarding its temperature evolution and underlying driving mechanisms. In particular, the nature and significance of the transition from the early to mid-Holocene and of the Holocene Thermal Maximum (HTM) are still debated. Here, we apply an emerging approach by combining in situ cosmogenic 10Be moraine and 10Be–14C bedrock dating from the same site, the forefield of Steingletscher (European Alps), and reconstruct the glacier's millennial recession and advance periods. The results suggest that, subsequent to the final deglaciation at ∼10 ka, the glacier was similar to or smaller than its 2000 CE extent for ∼7 kyr. At ∼3 ka, Steingletscher advanced to an extent slightly outside the maximum Little Ice Age (LIA) position and until the 19th century experienced sizes that were mainly confined between the LIA and 2000 CE extents. These findings agree with existing Holocene glacier chronologies and proxy records of summer temperatures in the Alps, suggesting that glaciers throughout the region were similar to or even smaller than their 2000 CE extent for most of the early and mid-Holocene. Although glaciers in the Alps are currently far from equilibrium with the accelerating anthropogenic warming, thus hindering a simple comparison of summer temperatures associated with modern and paleo-glacier sizes, our findings imply that the summer temperatures during most of the Holocene, including the HTM, were similar to those at the end of the 20th century. Further investigations are necessary to refine the magnitude of warming and the potential HTM seasonality.

Glaciers preserve climate variations in their geological and geomorphological records, which makes them prime candidates for climate reconstructions. Investigating the glacier–climate system over the past millennia is particularly relevant first because the amplitude and frequency of natural climate variability during the Holocene provides the climatic context against which modern, human-induced climate change must be assessed. Second, the transition from the last glacial to the current interglacial promises important insights into the climate system during warming, which is of particular interest with respect to ongoing climate change. Evidence of stable ice margin positions that record cooling during the past 12 kyr are preserved in two glaciated valleys of the Silvretta Massif in the eastern European Alps, the Jamtal (JAM) and the Laraintal (LAR). We mapped and dated moraines in these catchments including historical ridges using beryllium-10 surface exposure dating (10Be SED) techniques and correlate resulting moraine formation intervals with climate proxy records to evaluate the spatial and temporal scale of these cold phases. The new geochronologies indicate the formation of moraines during the early Holocene (EH), ca. 11.0 ± 0.7 ka (n = 19). Boulder ages along historical moraines (n = 6) suggest at least two glacier advances during the Little Ice Age (LIA; ca. 1250–1850 CE) around 1300 CE and in the second half of the 18th century. An earlier advance to the same position may have occurred around 500 CE. The Jamtal and Laraintal moraine chronologies provide evidence that millennial-scale EH warming was superimposed by centennial-scale cooling. The timing of EH moraine formation coincides with brief temperature drops identified in local and regional paleoproxy records, most prominently with the Preboreal Oscillation (PBO) and is consistent with moraine deposition in other catchments in the European Alps and in the Arctic region. This consistency points to cooling beyond the local scale and therefore a regional or even hemispheric climate driver. Freshwater input sourced from the Laurentide Ice Sheet (LIS), which changed circulation patterns in the North Atlantic, is a plausible explanation for EH cooling and moraine formation in the Nordic region and in Europe.

Abstract Seasonal subsidence induced by ground ice melt can be measured by interferometric synthetic aperture radar (InSAR) techniques to infer active layer thickness (ALT) in permafrost regions. The magnitude of subsidence depends on both how deep the soil thawed and how much ice/water content existed in the active layer soil. To provide the later, P‐band polarimetric synthetic aperture radar (PolSAR) backscatter is used due to its sensitivity to subsurface soil moisture and freeze/thaw conditions. In this study, which is the second in a two‐part series of Permafrost Dynamics Observatory (PDO), we exploit L‐band InSAR subsidence and P‐band PolSAR backscatter in a joint retrieval scheme to simultaneously estimate ALT and soil moisture profile of permafrost active layer. Both subsidence and backscatter are explicitly characterized by physics‐based models and share a common set of soil parameters including porosity and water saturation profiles. The PDO joint retrieval has been applied to the L‐ and P‐band SAR data acquired by National Aeronautics and Space Administration/Jet Propulsion Laboratory's Uninhabited Aerial Vehicle Synthetic Aperture Radar over Alaska and western Canada during the 2017 Arctic‐Boreal Vulnerability Experiment (ABoVE) airborne campaign. This high‐resolution (30 m) regional estimates of ALT and soil moisture profile spanning over the ABoVE study domain can help link the ground‐based field surveys with satellite observations to further understand the permafrost and active layer soil process dynamics to disturbances and climate change occurring across the northern circumpolar region.