Search

Abstract Asthma-related mortality is high in low- and middle-income countries. Little is known about public perceptions of inhaled medicines. We conducted semi-structured interviews with asthma patients and healthcare workers at three secondary care facilities in The Gambia, between August and November 2022. Thematic analysis was used to interpret these data. A total of 20 patients and 15 healthcare workers were interviewed. Both groups noted limited access to inhalers was an issue resulting in continued use of oral medications. Some patients recognised the benefits of inhalers, yet beliefs that inhalers were dangerous were common. Reliance on oral short-acting beta agonists meant patients saw asthma as a recurrent acute condition resulting in an emphasis on hospital management with little awareness of inhaled preventative medicines. Increasing access to inhaled medicines has the potential to reduce costly avoidable admissions, but socio-cultural factors, in addition to medication supply, need addressing.

Nurses around the globe have been impacted psychologically and emotionally during and after the COVID-19 pandemic. The purpose of this study was to describe nurses’ perspectives on the concepts of compassion fatigue, second victimhood, burnout, and moral injury. Eight nurses were interviewed either individually or in groups of two. Data were analyzed using conventional content analysis. The following themes were identified: waves of compassion fatigue, traumatization within second victimhood, never the same after chronic burnout, moral injury: nurses couldn’t do their best, and connections across concepts. Results showed nurses were most familiar with burnout and compassion fatigue, which remain chronic struggles. Second victimhood and moral injury were more distinct experiences related to traumatic or morally distressing events and likely contributed to experiencing burnout or compassion fatigue. Nurses’ suffering heightened during the COVID-19 pandemic and remains prominent three years later. Future research and interventions are urgently needed globally to reduce workplace stressors and promote nurse well-being.

Abstract Satellite imagery provides a global perspective for studying river hydrology and water quality, but clouds remain a fundamental limitation of optical sensors. Explicit studies of this problem were limited to specific locations or regions. In this study, we characterize the global severity of this limitation by analyzing 22 years of daily satellite cloud cover data and modeled river discharge for a global sample 21,642 river reaches of diverse sizes and climates. Our results show that the bias in observed river discharge is highly organized in space, particularly affecting Tropical and Arctic rivers. Given the fundamental nature of this cloud limitation, optical satellites will always provide a biased representation of river conditions. We discuss several strategies to mitigate bias, including modeling, data fusion, and temporal averaging, yet these methods introduce their own challenges and uncertainties.

Adequate concentrations of human milk (HM) nutrients, including macro- and trace-elements, are essential for healthy growth and development of exclusively breastfed (EBF) infants. To monitor potential risk of deficiencies, and evaluate the effects of interventions like supplementation, accurate analysis is crucial. Even recent methods reporting on HM macro- and/or trace-elements describe multiple methodological approaches and the need for several milliliters. We optimized and validated a comprehensive method for simultaneous analysis of 13 macro- and trace-elements for simultaneous analysis by inductively-coupled plasma-mass spectrometry. 100–600 μL HM were microwave digested with ≤1.5 mL HNO3 (70 %). The digest was diluted to 5 % final acid concentration. He-Kinetic Energy Discrimination (KED; Na, K, P, Ca, Mg, Fe, Cu, Zn, Cr, Mo) and O2-Dynamic Reaction Cell (DRC; As, Mn, Se) modes minimized remaining interferences. Accuracy (NIST SRM 1869 infant formula; n = 15, 4 weeks) varied from 93.2 to 103 % (CV: 2.8–8.5 %) with trueness ranging from 93.9 to 104 %. Inter-day variation of a HM-pool (n = 20, 3 weeks) varied between 4.1 and 8.5 % for most elements; Cr, Mo, Mn (all80 %) with concentrations below the Adequate Intake. Our method allows for simultaneous and reproducible analysis of macro- and trace-elements with concentrations ranging over 6 orders of magnitude, without the need for separate analytics and sample preparations, and requiring only sub-milliliter amounts of HM. Additional elements may be included after optimization and validation. The results from Bangladeshi HM samples indicate selective supplementation effects and concerningly low concentrations for some elements, which could adversely affect the EBF infant.

Abstract Background The FROM-16 is a generic family quality of life (QoL) instrument that measures the QoL impact of patients’ disease on their family members/partners. The study aimed to assess the responsiveness of FROM-16 to change and determine Minimal Important Change (MIC). Methods Responsiveness and MIC for FROM-16 were assessed prospectively with patients and their family members recruited from outpatient departments of the University Hospital Wales and University Hospital Llandough, Cardiff, United Kingdom. Patients completed the EQ-5D-3L and a global severity question (GSQ) online at baseline and at 3-month follow-up. Family members completed FROM-16 at baseline and a Global Rating of Change (GRC) in addition to FROM-16 at follow-up. Responsiveness was assessed using the distribution-based (effect size-ES, standardized response mean -SRM) and anchor-based (area under the receiver operating characteristics curve ROC-AUC) approaches and by testing hypotheses on expected correlation strength between FROM-16 change score and patient assessment tools (GSQ and EQ-5D). Cohen’s criteria were used for assessing ES. The AUC ≥ 0.7 was considered a good measure of responsiveness. MIC was calculated using anchor-based (ROC analysis and adjusted predictive modelling) and distribution methods based on standard deviation (SD) and standard error of the measurement (SEM). Results Eighty-three patients with 15 different health conditions and their relatives completed baseline and follow-up questionnaires and were included in the responsiveness analysis. The mean FROM-16 change over 3 months = 1.43 (SD = 4.98). The mean patient EQ-5D change over 3 months = −0.059 (SD = 0.14). The responsiveness analysis showed that the FROM-16 was responsive to change (ES = 0.2, SRM = 0.3; p

Our understanding and predictive capability of streamflow processes largely rely on high-quality datasets that depict a river's upstream basin characteristics. Recent proliferation of large sample hydrology (LSH) datasets has promoted model parameter estimation and data-driven analyses of hydrological processes worldwide, yet existing LSH is still insufficient in terms of sample coverage, uncertainty estimates, and dynamic descriptions of anthropogenic activities. To bridge the gap, we contribute the synthesis of Global Streamflow characteristics, Hydrometeorology, and catchment Attributes (GSHA) to complement existing LSH datasets, which covers 21 568 watersheds from 13 agencies for as long as 43 years based on discharge observations scraped from the internet. In addition to annual and monthly streamflow indices, each basin's daily meteorological variables (i.e., precipitation, 2 m air temperature, longwave/shortwave radiation, wind speed, actual and potential evapotranspiration), daily–weekly water storage terms (i.e., snow water equivalence, soil moisture, groundwater percentage), and yearly dynamic descriptors of the land surface characteristics (i.e., urban/cropland/forest fractions, leaf area index, reservoir storage and degree of regulation) are also provided by combining openly available remote sensing and reanalysis datasets. The uncertainties in all meteorological variables are estimated with independent data sources. Our analyses reveal the following insights: (i) the meteorological data uncertainties vary across variables and geographical regions, and the revealed pattern should be accounted for by LSH users; (ii) ∼6 % watersheds shifted between human-managed and natural states during 2001–2015, e.g., basins with environmental recovery projects in northeast China, which may be useful for hydrologic analysis that takes the changing land surface characteristics into account; and (iii) GSHA watersheds showed a more widespread declining trend in runoff coefficient than an increasing trend, pointing towards critical water availability issues. Overall, GSHA is expected to serve hydrological model parameter estimation and data-driven analyses as it continues to improve. GSHA v1.1 can be accessed at https://doi.org/10.5281/zenodo.8090704 and https://doi.org/10.5281/zenodo.10433905 (Yin et al., 2023a, b).

Background: There is limited information on relationships among biomarkers of thiamine status (whole blood thiamine diphosphate [ThDP], erythrocyte transketolase activity coefficient [ETKac], and human milk thiamine [MTh]) and clinical manifestations of thiamine deficiency. Objectives: This study aimed to explore correlations among these biomarkers and thiamine responsive disorders (TRDs), a diagnosis based on favorable clinical response to thiamine. Methods: Hospitalized infants and young children (aged 21 d to 1.25 were explored using area under the receiver operating characteristic curve framework. Results: Thiamine biomarkers were available for 287 hospitalized children and 228 community children (mean age 4.7 mo; 59.4% male). Median (interquartile range [IQR]) ThDP and ETKac were 66.9 nmol/L (IQR: 41.4, 96.9 nmol/L) and 1.25 nmol/L (IQR: 1.11, 1.48 nmol/L), respectively, among hospitalized children, and 64.1 nmol/L (IQR: 50.0, 85.3 nmol/L) and 1.22 nmol/L (IQR: 1.12, 1.37 nmol/L) among 228 community children (P > 0.05 for both). Forty-five percent of breastfeeding mothers of infants

ABSTRACT: Flue Gas Desulfurization (FGD) gypsum is a byproduct of the coal-fired power plant process commonly used to remove sulfur dioxide emissions from the flue gas. FGD gypsum has numerous industrial, agricultural, and environmental applications. This study aimed to explore a novel approach involving the use of FGD gypsum combined with different litter treatments as bedding for broiler production. It focused on performance metrics, including adjusted feed conversion ratio (AFCR) and average body weight (BW), foot pad dermatitis (FPD), and fear response over 5 consecutive flocks. A total of 1,800 one-day-old Ross 708 chicks were randomly assigned to 24 pens (75 birds/pen), divided into 6 treatment groups (4 pens/treatment), with 5 replications and raised until 42 d old (d). Treatments were gypsum that was decaked (D), rotovated (E), and rotovated then windrowed (F) between flocks. Control treatments using pine shavings were decaked (A), rotovated (B), and windrowed postrotovating (C). AFCR, average BW, and mortality were used as a measure of production. Foot pad dermatitis scores were taken on d42 using a scale of 0 (absence), 1 (mild), and 2 (severe). Response to observer and human approach test were used to measure fear response. Data were analyzed as a 2-way ANOVA (Proc Glimmix) for the main effects of bedding type and litter treatment. Means were identified using Tukey's HSD. No effect of bedding type or litter treatment was found for AFCR, BW, or mortality. FPD scores 2 and 1, were higher with pine shavings than gypsum (P = 0.01 and P = 0.01, respectively). While FPD scores 0 were higher for gypsum than the pine shaving (P = 0.01). No difference in fear response was found among birds raised on any of the gypsum litter treatments and any of the pine shaving litter treatments. Overall, the use of gypsum as bedding results in equivalent production and fear response to pine shavings, while increasing FPD quality when compared to pine shaving.

It is estimated that billions of people around the world are affected by micronutrient deficiencies. Madagascar is considered to be particularly nutritionally vulnerable, with nearly half of the population stunted, and parts of the country facing emergency, near famine-like conditions (IPC4). Although Madagascar is generally considered among the most undernourished of countries, empirical data in the form of biological samples to validate these claims are extremely limited. Our research drew data from three studies conducted between 2013–2020 and provided comprehensive biomarker profile information for 4,710 individuals from 30 communities in five different ecological regions during at least one time-point. Estimated prevalences of nutrient deficiencies and inflammation across various regions of rural Madagascar were of concern for both sexes and across all ages, with 66.5% of the population estimated to be deficient in zinc, 15.6% depleted in vitamin B12 (3.6% deficient), 11.6% deficient in retinol, and lower levels of iron deficiency (as indicated by 11.7% deficient in ferritin and 2.3% deficient assessed by soluble transferrin receptors). Beyond nutrient status biomarkers, nearly one quarter of the population (24.0%) exhibited chronic inflammation based on high values of α-1-acid glycoprotein, and 12.3% exhibited acute inflammation based on high values of C-reactive protein. There is an 8-fold difference between the lowest and highest regional observed prevalence of vitamin B12 deficiency, a 10-fold difference in vitamin A deficiency (based on retinol), and a 2-fold difference in acute inflammation (CRP) and deficiencies of zinc and iron (based on ferritin), highlighting strong geographical variations in micronutrient deficiencies across Madagascar.

Abstract Background There is limited research to determine whether vitamin B12 (B12) supplementation during pregnancy and lactation is protective against oxidative stress and pro-inflammatory cytokines and whether this effect is transferred to breastfed infants via milk. In addition, associations among maternal plasma/ milk and infant B12 status and immune function markers are poorly characterized. Objectives To evaluate effects of oral B12 supplementation during pregnancy and postpartum on maternal and infant 8-hydroxy-2′-deoxyguanosine (8-OH-dG, an oxidative stress marker) and proinflammatory cytokine levels, and examine associations between maternal plasma, breastmilk and infant B12 status as well as immune function markers. Method In a blinded, placebo-controlled trial, Bangladeshi women (n = 68, 18–35 years, hemoglobin

Extensive airborne measurements of non-methane organic gases (NMOGs), methane, nitrogen oxides, reduced nitrogen species, and aerosol emissions from US wild and prescribed fires were conducted during the 2019 NOAA/NASA Fire Influence on Regional to Global Environments and Air Quality campaign (FIREX-AQ). Here, we report the atmospheric enhancement ratios (ERs) and inferred emission factors (EFs) for compounds measured on board the NASA DC-8 research aircraft for nine wildfires and one prescribed fire, which encompass a range of vegetation types. We use photochemical proxies to identify young smoke and reduce the effects of chemical degradation on our emissions calculations. ERs and EFs calculated from FIREX-AQ observations agree within a factor of 2, with values reported from previous laboratory and field studies for more than 80 % of the carbon- and nitrogen-containing species. Wildfire emissions are parameterized based on correlations of the sum of NMOGs with reactive nitrogen oxides (NOy) to modified combustion efficiency (MCE) as well as other chemical signatures indicative of flaming/smoldering combustion, including carbon monoxide (CO), nitrogen dioxide (NO2), and black carbon aerosol. The sum of primary NMOG EFs correlates to MCE with an R2 of 0.68 and a slope of −296 ± 51 g kg−1, consistent with previous studies. The sum of the NMOG mixing ratios correlates well with CO with an R2 of 0.98 and a slope of 137 ± 4 ppbv of NMOGs per parts per million by volume (ppmv) of CO, demonstrating that primary NMOG emissions can be estimated from CO. Individual nitrogen-containing species correlate better with NO2, NOy, and black carbon than with CO. More than half of the NOy in fresh plumes is NO2 with an R2 of 0.95 and a ratio of NO2 to NOy of 0.55 ± 0.05 ppbv ppbv−1, highlighting that fast photochemistry had already occurred in the sampled fire plumes. The ratio of NOy to the sum of NMOGs follows trends observed in laboratory experiments and increases exponentially with MCE, due to increased emission of key nitrogen species and reduced emission of NMOGs at higher MCE during flaming combustion. These parameterizations will provide more accurate boundary conditions for modeling and satellite studies of fire plume chemistry and evolution to predict the downwind formation of secondary pollutants, including ozone and secondary organic aerosol.

Abstract Background Incarcerated youth are characterized by particularly high rates of childhood trauma, a significant risk factor for outcomes including risky behaviors and recidivism. Trauma-based interventions can ameliorate the negative effects of childhood trauma; however, a critical part of success is careful trauma screening. Due to the limitations associated with commonly used self-report trauma assessments, our team developed the Trauma Checklist (TCL), a trained-rater assessment of childhood trauma specifically created for use with forensic populations. The TCL is designed to provide a more comprehensive assessment of trauma, incorporating categories that are of specific relevance for incarcerated individuals (e.g., traumatic loss). Here, we discuss the continued development made to our original trauma assessment and explore the psychometric properties of this expanded assessment (herein termed the TCL 2.0). Method We examined relationships between TCL 2.0 scores, measures of psychopathology, and psychopathic traits in a sample of incarcerated male juvenile offenders (n = 237). In addition, we examined whether TCL 2.0 scores were associated with time to felony re-offense via Cox proportional-hazard regression analyses. Results We examined dimensionality of the TCL 2.0 using a principal component analysis (PCA), the results of which were confirmed via exploratory structural equation modeling; the PCA yielded a two-component solution (i.e., PC1 and PC2). We observed that PC1 (Experienced Trauma) scores were positively correlated with mood disorder diagnoses. TCL 2.0 total scores were positively correlated with post-traumatic stress disorder symptomatology and psychopathic traits. Finally, higher PC2 (Community Trauma) scores were associated with faster time to felony re-offending. Conclusions These results suggest that the TCL 2.0 may be a beneficial screening tool to provide high-risk youth with appropriate trauma-informed treatment.

Lakes and reservoirs are ubiquitous across global landscapes, functioning as the largest repository of liquid surface freshwater, hotspots of carbon cycling, and sentinels of climate change. Although typically considered lentic (hydrologically stationary) environments, lakes are an integral part of global drainage networks. Through perennial and intermittent hydrological connections, lakes often interact with each other, and these connections actively affect water mass, quality, and energy balances in both lacustrine and fluvial systems. Deciphering how global lakes are hydrologically interconnected (or the so-called “lake drainage topology”) is not only important for lake change attribution but also increasingly critical for discharge, sediment, and carbon modeling. Despite the proliferation of river hydrography data, lakes remain poorly represented in routing models, partially because there has been no global-scale hydrography dataset tailored to lake drainage basins and networks. Here, we introduce the global Lake drainage Topology and Catchment database (Lake-TopoCat), which reveals detailed lake hydrography information with careful consideration of possible multifurcation. Lake-TopoCat contains the outlet(s) and catchment(s) of each lake; the interconnecting reaches among lakes; and a wide suite of attributes depicting lake drainage topology such as upstream and downstream relationship, drainage distance between lakes, and a priori drainage type and connectivity with river networks. Using the HydroLAKES v1.0 (Messager et al., 2016) global lake mask, Lake-TopoCat identifies ∼ 1.46 million outlets for ∼ 1.43 million lakes larger than 10 ha and delineates 77.5×106 km2 of lake catchments covering 57 % of the Earth's landmass except Antarctica. The global lakes are interconnected by ∼ 3 million reaches, derived from MERIT Hydro v1.0.1 (Yamazaki et al., 2019), stretching a total distance of ∼10×106 km, of which ∼ 80 % are shorter than 10 km. With such unprecedented lake hydrography details, Lake-TopoCat contributes towards a globally coupled lake–river routing model. It may also facilitate a variety of limnological applications such as attributing water quality from lake scale to basin scale, tracing inter-lake fish migration due to changing climate, monitoring fluvial–lacustrine connectivity, and improving estimates of terrestrial carbon fluxes. Lake-TopoCat is freely accessible at https://doi.org/10.5281/zenodo.7916729 (Sikder et al., 2023).

Abstract Surface water reservoirs are increasingly being relied upon to meet rising demands in the context of growing population and changing climate. However, the amount of water available in reservoirs (and the corresponding trends) have not been well quantified at the global scale. Here we use satellite observations to estimate the storage variations of 7245 global reservoirs from 1999 to 2018. Total global reservoir storage has increased at a rate of 27.82 ± 0.08 km3/yr, which is mainly attributed to the construction of new dams. However, the normalized reservoir storage (NS)—the ratio of the actual storage to the storage capacity—has declined by 0.82 ± 0.01%. The decline of NS values is especially pronounced in the global south, while the global north mainly exhibits an NS increase. With predicted decreasing runoff and increasing water demand, these observed diminishing storage returns of reservoir construction will likely persist into the future.

Background: Multiple sclerosis (MS) is a clinically heterogeneous disease underpinned by inflammatory, demyelinating and neurodegenerative processes, the extent of which varies between individuals and over the course of the disease. Recognising the clinicopathological features that most strongly associate with disease outcomes will inform future efforts at patient phenotyping. Aims: We used a digital pathology workflow, involving high-resolution image acquisition of immunostained slides and opensource software for quantification, to investigate the relationship between clinical and neuropathological features in an autopsy cohort of progressive MS. Methods: Sequential sections of frontal, cingulate and occipital cortex, thalamus, brain stem (pons) and cerebellum including dentate nucleus (n = 35 progressive MS, females = 28, males = 7; age died = 53.5 years; range 38–98 years) were immunostained for myelin (anti-MOG), neurons (anti-HuC/D) and microglia/macrophages (anti-HLA). The extent of demyelination, neurodegeneration, the presence of active and/or chronic active lesions and quantification of brain and leptomeningeal inflammation was captured by digital pathology. Results: Digital analysis of tissue sections revealed the variable extent of pathology that characterises progressive MS. Microglia/macrophage activation, if found at a higher level in a single block, was typically elevated across all sampled blocks. Compartmentalised (perivascular/leptomeningeal) inflammation was associated with age-related measures of disease severity and an earlier death. Conclusion: Digital pathology identified prognostically important clinicopathological correlations in MS. This methodology can be used to prioritise the principal pathological processes that need to be captured by future MS biomarkers.

L 98-59 d is a Super-Earth planet orbiting an M-type star. We performed retrievals on the transmission spectrum of L 98-59 d obtained using NIRSpec G395H during a single transit, from JWST Cycle 1 GTO 1224. The wavelength range of this spectrum allows us to detect the presence of several atmospheric species. We found that the spectrum is consistent with a high mean molecular weight atmosphere. The atmospheric spectrum indicates the possible presence of the sulfur-bearing species H _2 S and SO _2 , which could hint at active volcanism on this planet if verified by future observations. We also tested for signs of stellar contamination in the spectrum and found signs of unocculted faculae on the star. The tentative signs of an atmosphere on L 98-59 d presented in this work from just one transit bodes well for possible molecular detections in the future, particularly as it is one of the best targets among small exoplanets for atmospheric characterization using JWST.

Detecting atmospheres around planets with a radius below 1.6 R _⊕ , commonly referred to as rocky planets, has proven to be challenging. However, rocky planets orbiting M dwarfs are ideal candidates due to their favorable planet-to-star radius ratio. Here, we present one transit observation of the Super-Earth L98-59 d (1.58 R _⊕ and 2.31 M _⊕ ), at the limit of rocky/gas-rich, using the JWST NIRSpec G395H mode covering the 2.8–5.1 μ m wavelength range. The extracted transit spectrum from a single transit observation deviates from a flat line by 2.6 σ –5.6 σ , depending on the data reduction and retrieval setup. The hints of an atmospheric detection are driven by a large absorption feature between 3.3 and 4.8 μ m. A stellar contamination retrieval analysis rejected the source of this feature as being due to stellar inhomogeneities, making the best fit an atmospheric model including sulfur-bearing species, suggesting that the atmosphere of L98-59 d may not be at equilibrium. This result will need to be confirmed by the analysis of the second NIRSpec G395H visit in addition to the NIRISS SOSS transit observation.

Abstract Rivers are among the most diverse, dynamic, and productive ecosystems on Earth. River flow regimes are constantly changing, but characterizing and understanding such changes have been challenging from a long-term and global perspective. By analyzing water extent variations observed from four-decade Landsat imagery, we here provide a global attribution of the recent changes in river regime to morphological dynamics (e.g., channel shifting and anabranching), expansion induced by new dams, and hydrological signals of widening and narrowing. Morphological dynamics prevailed in ~20% of the global river area. Booming reservoir constructions, mostly skewed in Asia and South America, contributed to ~32% of the river widening. The remaining hydrological signals were characterized by contrasting hotspots, including prominent river widening in alpine and pan-Arctic regions and narrowing in the arid/semi-arid continental interiors, driven by varying trends in climate forcing, cryospheric response to warming, and human water management. Our findings suggest that the recent river extent dynamics diverge based on hydroclimate and socio-economic conditions, and besides reflecting ongoing morphodynamical processes, river extent changes show close connections with external forcings, including climate change and anthropogenic interference.

BackgroundConditions in utero influence intrauterine and postnatal infant growth and a few studies indicate that maternal inflammation and insulin resistance might affect birth and breastfeeding outcomes. Furthermore, hormones in human milk (HM) may influence infant appetite-regulation and thereby milk intake, but the associations are less understood.Objective(1) To investigate associations between maternal inflammatory, lipid and metabolic markers and birth and breastfeeding outcomes, and (2) to assess predictors of maternal inflammatory, lipid and metabolic markers in pregnancy.MethodsSeventy-one mother-infant dyads participating in the Mothers, Infants and Lactation Quality (MILQ) study were included in the present study. Fasting blood samples were collected around 28th gestational week, and HM samples at three time points from 1.0 to 8.5 months, where milk intake was assessed using 24-h test weighing. Maternal plasma inflammatory, lipid and metabolic markers included high-sensitive C-reactive protein (hs-CRP), tumor-necrosis factor-α (TNFα), interferon-γ (IFNγ), Interleukin (IL)-6, IL-8, high-, low-, and very-low-density lipoprotein (HDL, LDL, VLDL), total-cholesterol, triglycerides, leptin, adiponectin, insulin, C-peptide, the homeostasis model assessment of insulin resistance (HOMA-IR) and glucose concentration at t = 120 min following an oral glucose tolerance test. Of these, TNFα, IFNγ, IL-6, IL-8, leptin, adiponectin and insulin were also measured in HM samples.ResultsHDL in pregnancy was inversely associated with gestational age (GA) at birth and GA-adjusted birthweight z-score, whereas triglycerides and glucose (t = 120) were positively associated with GA-adjusted birthweight z-score. Higher hs-CRP, VLDL and triglycerides were associated with a higher placental weight. Furthermore, higher HDL, insulin, leptin and HOMA-IR were associated with longer duration of exclusive breastfeeding (EBF). Higher pre-pregnancy BMI was the main predictor of higher levels of hs-CRP, log-TNFα, leptin, insulin, C-peptide, and HOMA-IR.ConclusionMaternal lipid and metabolic markers influenced birthweight z-score and placental weight as well as duration of EBF. Furthermore, pre-pregnancy BMI and maternal age predicted levels of several inflammatory and metabolic markers during pregnancy. Our findings indicate that maternal lipid and metabolic profiles in pregnancy may influence fetal growth and breastfeeding, possibly explained by overweight and/or higher placental weight.Clinical trial registrationhttps://clinicaltrials.gov/, identifier NCT03254329.

Previous work in incarcerated boys and adult men and women suggest that individuals scoring high on psychopathic traits show altered resting-state limbic/paralimbic, and default mode functional network properties. However, it is unclear whether similar results extend to high-risk adolescent girls with elevated psychopathic traits. This study examined whether psychopathic traits [assessed via the Hare Psychopathy Checklist: Youth Version (PCL:YV)] were associated with altered inter-network connectivity, intra-network connectivity (i.e., functional coherence within a network), and amplitude of low-frequency fluctuations (ALFFs) across resting-state networks among high-risk incarcerated adolescent girls (n = 40). Resting-state networks were identified by applying group independent component analysis (ICA) to resting-state fMRI scans, and a priori regions of interest included limbic, paralimbic, and default mode network components. We tested the association of psychopathic traits (PCL:YV Factor 1 measuring affective/interpersonal traits and PCL:YV Factor 2 assessing antisocial/lifestyle traits) to these three resting-state measures. PCL:YV Factor 1 scores were associated with increased low-frequency and decreased high-frequency fluctuations in components corresponding to the default mode network, as well as increased intra-network FNC in components corresponding to cognitive control networks. PCL:YV Factor 2 scores were associated with increased low-frequency fluctuations in sensorimotor networks and decreased high-frequency fluctuations in default mode, sensorimotor, and visual networks. Consistent with previous analyses in incarcerated adult women, our results suggest that psychopathic traits among incarcerated adolescent girls are associated with altered intra-network ALFFs—primarily that of increased low-frequency and decreased high-frequency fluctuations—and connectivity across multiple networks including paralimbic regions. These results suggest stable neurobiological correlates of psychopathic traits among women across development.

Interest in improving the long-term sustainability of agricultural production systems has focused on identifying management practices that promote soil health. No tillage, cover cropping, and amending soils with broiler (Gallus gallus domesticus L.) litter are commonly adopted conservation practices that have been shown to improve soil fertility and crop yield. However, the overall influence of these conservation practices on soil health in the southeastern US are not well understood. Thus, a study was conducted to evaluate the influence of tillage, broiler litter (BL) applications, and cropping systems on soil biochemical properties. Soils were collected from field research plots under long-term management (>than 25 years of tillage, 15 years of broiler litter application, and 15 years of cropping system). Soil microbial biomass, C, N, and P, amidohydrolases, and dissolved organic matter (DOM) were evaluated as indicators of soil health. Adopting tillage and BL into the agricultural management system modified the biochemical parameters of the soils evaluated. Most of these modifications occurred in the 0–5 cm depth. Higher microbial biomass carbon (MBC; 85%) and nitrogen (MBN; 10%) and enzyme activities of asparaginase (65%) and glutaminase (70%) were observed in the 0–5 cm depth under no tillage (NT) compared to conventional tillage (CT), indicating greater biological activities were established in these soil ecosystems. Broiler litter applications increased microbial biomass N and activities of asparaginase and glutaminase in both soil depths. In addition, microbial biomass phosphorus (MBP) was increased following BL application in the 0–5 cm depth. The results suggest that long-term management of NT and BL additions can improve the health of eroded southeastern US soils by altering the soil biochemical parameters.

Effects of rising atmospheric CO2 concentration [CO2] on pastures and grazing lands are beginning to be researched, but these important systems remain understudied compared to other agronomic and forest ecosystems. Therefore, we conducted a long-term (2005–2015) study of bahiagrass (Paspalum notatum Flüggé) response to elevated [CO2] and fertility management. The study was conducted at the USDA-ARS, National Soil Dynamics Laboratory open-top field chamber facility, Auburn, AL. A newly established bahiagrass pasture was exposed to either ambient or elevated (ambient + 200 µmol mol−1) [CO2]. Following one year of pasture establishment, half the plots received a fertilizer treatment [N at 90 kg ha−1 three times yearly plus P, K, and lime as recommended by soil testing]; the remaining plots received no fertilization. These treatments were implemented to represent managed (M) and unmanaged (U) pastures; both are common in the southeastern US. Root cores (0–60 cm depth) were collected annually in October and processed using standard procedures. Fertility additions consistently increased both root length density (53.8%) and root dry weight density (68.2%) compared to unmanaged plots, but these root variables were generally unaffected by either [CO2] or its interaction with management. The results suggest that southern bahiagrass pastures could benefit greatly from fertilizer additions. However, bahiagrass pasture root growth is unlikely to be greatly affected by rising atmospheric [CO2], at least by those levels expected during this century.

Abstract Rivers and lakes are intrinsically connected waterbodies yet they are rarely used to hydrologically constrain one another with remote sensing. Here we begin to bridge the gap between river and lake hydrology with the introduction of the LakeFlow algorithm. LakeFlow uses river‐lake mass conservation and observations from the Surface Water and Ocean Topography (SWOT) satellite to provide river discharge estimates of lake and reservoir inflows and outflows. We test LakeFlow performance at three lakes using a synthetic SWOT data set assuming the maximum measurement errors defined by the mission science requirements, and we include modeled lateral inflow and lake evaporation data to further constrain the mass balance. We find that LakeFlow produces promising discharge estimates (median Nash‐Sutcliffe efficiency = 0.88, relative bias = 14%). LakeFlow can inform water resources management by providing global lake inflow and outflow estimates, highlighting a path for recognizing rivers and lakes as an interconnected system.

Rent control is a highly controversial housing policy. For Vienna, Austria, we show how rent control impacts block-group income distributions as the share of residents with rental contracts subject to a cap increase. Using regression with spatial fixed effects, we find that a 1 %-point increase in residents with rental contracts subject to a cap reduces the average net income of the block-group by 52.70 Euro/year. For the typical block-group containing 861 residents, this implies a reduction in total block-group income of 45,375 Euro/year. This suggests increasing numbers of lower income residents are locating in block-groups with rental caps. We further show the effect of capped rents on average income is heterogeneous across and within block-groups, with greater reductions in higher income block-groups compared to lower income block-groups. Our results demonstrate that the rent control policy in Vienna impacts residents' location choice and the resulting spatial income distribution despite the lack of means testing. [ABSTRACT FROM AUTHOR]

In 2021 JET exploited its unique capabilities to operate with T and D–T fuel with an ITER-like Be/W wall (JET-ILW). This second major JET D–T campaign (DTE2), after DTE1 in 1997, represented the culmination of a series of JET enhancements—new fusion diagnostics, new T injection capabilities, refurbishment of the T plant, increased auxiliary heating, in-vessel calibration of 14 MeV neutron yield monitors—as well as significant advances in plasma theory and modelling in the fusion community. DTE2 was complemented by a sequence of isotope physics campaigns encompassing operation in pure tritium at high T-NBI power. Carefully conducted for safe operation with tritium, the new T and D–T experiments used 1 kg of T (vs 100 g in DTE1), yielding the most fusion reactor relevant D–T plasmas to date and expanding our understanding of isotopes and D–T mixture physics. Furthermore, since the JET T and DTE2 campaigns occurred almost 25 years after the last major D–T tokamak experiment, it was also a strategic goal of the European fusion programme to refresh operational experience of a nuclear tokamak to prepare staff for ITER operation. The key physics results of the JET T and DTE2 experiments, carried out within the EUROfusion JET1 work package, are reported in this paper. Progress in the technological exploitation of JET D–T operations, development and validation of nuclear codes, neutronic tools and techniques for ITER operations carried out by EUROfusion (started within the Horizon 2020 Framework Programme and continuing under the Horizon Europe FP) are reported in (Litaudon et al Nucl. Fusion accepted), while JET experience on T and D–T operations is presented in (King et al Nucl. Fusion submitted).

JET, the world’s largest operating tokamak with unique Be/W wall and tritium handling capability, completed a Deuterium-Tritium (D-T) campaign in 2021 (Maggi et al 29th Fusion Energy Conf. ) following a decade of preparatory experiments, dedicated enhancements, technical rehearsals and training (Horton et al 2016 Fusion Eng. Des. 109–111 925). Operation with tritium raises significant technical, safety and scientific challenges not encountered in standard protium or deuterium operation. This contribution describes the tritium operational requirements, pulses and technical preparations, new operating procedures, lessons learned and details on the achieved operational availability and performance. The preparation and execution of the recent JET tritium experiments benefitted from the previous experience in 1991 (Preliminary Tritium Experiment), 1997 (DTE1 campaign) and 2003 (Trace Tritium Campaigns) and consisted of the following five phases: technical rehearsals and scenario preparation, tritium commissioning, 100% tritium campaign, D-T campaign (DTE2), tritium clean-up. Following the clean-up JET resumed normal operation and is currently undertaking a further D-T campaign (DTE3).

We present the first spectroscopic characterization of the dayside atmosphere of WASP-17b in the mid-infrared using a single JWST MIRI/LRS eclipse observation. From forward-model fits to the 5–12 μ m emission spectrum, we tightly constrain the heat redistribution factor of WASP-17b to be 0.92 ± 0.02 at the pressures probed by this data, indicative of inefficient global heat redistribution. We also marginally detect a supersolar abundance of water, consistent with previous findings for WASP-17b, but note our weak constraints on this parameter. These results reflect the thermodynamically rich but chemically poor information content of MIRI/LRS emission data for high-temperature hot Jupiters. Using the eclipse mapping method, which utilizes the signals that the spatial emission profile of an exoplanet imprints on the eclipse light curve during ingress/egress due to its partial occultation by the host star, we also construct the first eclipse map of WASP-17b, allowing us to diagnose its multidimensional atmospheric dynamics for the first time. We find a day–night temperature contrast of order 1000 K at the pressures probed by this data, consistent with our derived heat redistribution factor, along with an eastward longitudinal hotspot offset of ${18.7}_{-3.8}^{+11.1\circ }$ , indicative of the presence of an equatorial jet induced by day–night thermal forcing being the dominant redistributor of heat from the substellar point. These dynamics are consistent with general circulation model predictions for WASP-17b. This work is part of a series of studies by the JWST Telescope Scientist Team, in which we use Guaranteed Time Observations to perform Deep Reconnaissance of Exoplanet Atmospheres through Multi-instrument Spectroscopy.

The Hubble Space Telescope (HST) has been our most prolific tool to study exoplanet atmospheres. As the age of JWST begins, there are a wealth of HST archival data that are useful to strengthen our inferences from JWST. Notably, HST/Space Telescope Imaging Spectrograph (STIS), with its 0.3–1 μ m wavelength coverage, extends past JWST’s 0.6 μ m wavelength cutoff and holds an abundance of potential information: alkali (Na, K) and molecular (TiO, VO) species opacities, aerosol information, and the presence of stellar contamination. However, time-series observations with HST suffer from significant instrumental systematics and can be highly dependent on choices made during the transit fitting process. This makes comparing transmission spectra of planets with different data reduction methodologies challenging, as it is difficult to discern whether an observed trend is caused by differences in data reduction or underlying physical processes. Here we present the Sculpting Hubble’s Exoplanet Legacy (SHEL) program, which aims to build a consistent data reduction and light-curve analysis methodology and associated database of transmission spectra from archival HST observations. In this paper, we present the SHEL analysis framework for HST/STIS and its low-resolution spectroscopy modes, G430L and G750L. We apply our methodology to four notable hot Jupiters, WASP-39 b, WASP-121 b, WASP-69 b, and WASP-17 b, and use these examples to discuss nuances behind analysis with HST/STIS. Our results for WASP-39 b, WASP-121 b, and WASP-17 b are consistent with past publications, but our analysis of WASP-69 b differs and shows evidence of either a strong scattering slope or stellar contamination. The data reduction pipeline and tutorials are available on Github and Zenodo.

The JWST NIRSpec integral field unit (IFU) presents a unique opportunity to observe directly imaged exoplanets from 3 to 5 μ m at moderate spectral resolution ( R ∼ 2700) and thereby better constrain the composition, disequilibrium chemistry, and cloud properties of their atmospheres. In this work, we present the first NIRSpec IFU high-contrast observations of a substellar companion that requires starlight suppression techniques. We develop specific data-reduction strategies to study faint companions around bright stars and assess the performance of NIRSpec at high contrast. First, we demonstrate an approach to forward model the companion signal and the starlight directly in the detector images, which mitigates the effects of NIRSpec’s spatial undersampling. We demonstrate a sensitivity to planets that are 3 × 10 ^−6 fainter than their stars at 1″, or 3 × 10 ^−5 at 0.″3. Then, we implement a reference star point-spread function subtraction and a spectral extraction that does not require spatially and spectrally regularly sampled spectral cubes. This allows us to extract a moderate resolution ( R ∼ 2,700) spectrum of the faint T dwarf companion HD 19467 B from 2.9 to 5.2 μ m with a signal-to-noise ratio of ∼10 per resolution element. Across this wavelength range, HD 19467 B has a flux ratio varying between 10 ^−5 and 10 ^−4 and a separation relative to its star of 1.″6. A companion paper by Hoch et al. more deeply analyzes the atmospheric properties of this companion based on the extracted spectrum. Using the methods developed here, NIRSpec’s sensitivity may enable direct detection and spectral characterization of relatively old (∼1 Gyr), cool (∼250 K), and closely separated (∼3–5 au) exoplanets that are less massive than Jupiter.

Studies have reported positive associations between youth psychopathy scores and measures of ‘fearlessness’. However, prior studies modified fearlessness items to be age appropriate, shifting from assessing hypothetical, extreme forms of physical risk-taking (e.g., flying an airplane) to normative risk-taking (e.g., riding bicycles downhill). We hypothesize that associations between youth psychopathy scores and alternative forms of sensation seeking (i.e., Disinhibition) have been conflated under a false fearlessness label. We tested this hypothesis among incarcerated male adolescents, investigating whether youth psychopathy scores were significantly associated with two different forms of sensation seeking: Disinhibition and Thrill and Adventure Seeking (TAS). Youth psychopathic traits were assessed using the Psychopathy Checklist: Youth Version (PCL:YV), Antisocial Process Screening Device (APSD), Child Psychopathy Scale (CPS), Inventory of Callous and Unemotional Traits (ICU), and Youth Psychopathic Traits Inventory (YPI). Disinhibition and fearlessness (i.e., TAS) were assessed using an unmodified version of the Zuckerman Sensation Seeking Scales (SSS). Consistent with hypotheses, youth psychopathy scores were associated with higher Disinhibition and lower TAS scores. Our results contribute to a growing body of literature suggesting that psychopathic traits, including among adolescents, are not concomitant with physical risk-taking and descriptions of psychopathy including fearlessness distort a precise understanding of psychopathy’s core features.

Dams and reservoirs are among the most widespread human-made infrastructures on Earth. Despite their societal and environmental significance, spatial inventories of dams and reservoirs, even for the large ones, are insufficient. A dilemma of the existing georeferenced dam datasets is the polarized focus on either dam quantity and spatial coverage (e.g., GlObal geOreferenced Database of Dams, GOODD) or detailed attributes for a limited dam quantity or region (e.g., GRanD (Global Reservoir and Dam database) and national inventories). One of the most comprehensive datasets, the World Register of Dams (WRD), maintained by the International Commission on Large Dams (ICOLD), documents nearly 60 000 dams with an extensive suite of attributes. Unfortunately, the WRD records provide no geographic coordinates, limiting the benefits of their attributes for spatially explicit applications. To bridge the gap between attribute accessibility and spatial explicitness, we introduce the Georeferenced global Dams And Reservoirs (GeoDAR) dataset, created by utilizing the Google Maps geocoding application programming interface (API) and multi-source inventories. We release GeoDAR in two successive versions (v1.0 and v1.1) at https://doi.org/10.5281/zenodo.6163413 (Wang et al., 2022). GeoDAR v1.0 holds 22 560 dam points georeferenced from the WRD, whereas v1.1 consists of (a) 24 783 dam points after a harmonization between GeoDAR v1.0 and GRanD v1.3 and (b) 21 515 reservoir polygons retrieved from high-resolution water masks based on a one-to-one relationship between dams and reservoirs. Due to geocoding challenges, GeoDAR spatially resolved ∼ 40 % of the records in the WRD, which, however, comprise over 90 % of the total reservoir area, catchment area, and reservoir storage capacity. GeoDAR does not release the proprietary WRD attributes, but upon individual user requests we may provide assistance in associating GeoDAR spatial features with the WRD attribute information that users have acquired from ICOLD. Despite this limit, GeoDAR, with a dam quantity triple that of GRanD, significantly enhances the spatial details of smaller but more widespread dams and reservoirs and complements other existing global dam inventories. Along with its extended attribute accessibility, GeoDAR is expected to benefit a broad range of applications in hydrologic modeling, water resource management, ecosystem health, and energy planning.

Targeted biologic therapies can elicit an undesirable host immune response characterized by the development of antidrug antibodies (ADA), an important cause of treatment failure. The most widely used biologic across immune-mediated diseases is adalimumab, a tumor necrosis factor inhibitor. This study aimed to identify genetic variants that contribute to the development of ADA against adalimumab, thereby influencing treatment failure. In patients with psoriasis on their first course of adalimumab, in whom serum ADA had been evaluated 6–36 months after starting treatment, we observed a genome-wide association with ADA against adalimumab within the major histocompatibility complex (MHC). The association signal mapped to the presence of tryptophan at position 9 and lysine at position 71 of the HLA-DR peptide-binding groove, with both residues conferring protection against ADA. Underscoring their clinical relevance, these residues were also protective against treatment failure. Our findings highlight antigenic peptide presentation via MHC class II as a critical mechanism in the development of ADA against biologic therapies and downstream treatment response.

Clouds are prevalent in many of the exoplanet atmospheres that have been observed to date. For transiting exoplanets, we know if clouds are present because they mute spectral features and cause wavelength-dependent scattering. While the exact composition of these clouds is largely unknown, this information is vital to understanding the chemistry and energy budget of planetary atmospheres. In this work, we observe one transit of the hot Jupiter WASP-17b with JWST’s Mid-Infrared Instrument Low Resolution Spectrometer and generate a transmission spectrum from 5 to 12 μ m. These wavelengths allow us to probe absorption due to the vibrational modes of various predicted cloud species. Our transmission spectrum shows additional opacity centered at 8.6 μ m, and detailed atmospheric modeling and retrievals identify this feature as SiO _2 (s) (quartz) clouds. The SiO _2 (s) clouds model is preferred at 3.5–4.2 σ versus a cloud-free model and at 2.6 σ versus a generic aerosol prescription. We find the SiO _2 (s) clouds are composed of small ∼0.01 μ m particles, which extend to high altitudes in the atmosphere. The atmosphere also shows a depletion of H _2 O, a finding consistent with the formation of high-temperature aerosols from oxygen-rich species. This work is part of a series of studies by our JWST Telescope Scientist Team (JWST-TST), in which we will use Guaranteed Time Observations to perform Deep Reconnaissance of Exoplanet Atmospheres through Multi-instrument Spectroscopy (DREAMS).

BackgroundGlobally, almost 15 million infants are born prematurely each year, disproportionately affecting low and middle-income countries. In the absence of mother's milk, the World Health Organization recommends using donor human milk (DHM) due to its protective effect against necrotizing enterocolitis, a life-threatening intestinal disorder. The use of DHM is increasing globally, with many low and middle-income countries integrating donor milk banks into their public health strategies to reduce neonatal mortality, yet very little is known about the nutritional composition of DHM. Additional knowledge gaps include how DHM composition is influenced by milk banking practices, and whether preterm nutrient recommendations are achieved when DHM is used with commercially available fortifiers.MethodsWe designed a multi-site study with eight geographically diverse milk bank partners in high, middle, and low-income settings that will examine and compare a broad range of nutrients and bioactive factors in human milk from 600 approved milk bank donors around the world to create comprehensive, geographically diverse nutrient profiles for DHM. We will then simulate the random pooling of 2 to 10 donors to evaluate the impact of pooling as a potential strategy for milk banks to manage nutrient variability in DHM. Finally, we will evaluate whether commercially available fortifiers meet nutrient recommendations when used with DHM.DiscussionWe expect that results from this study will improve nutritional care globally for the growing number of preterm infants who receive donor human milk.

Live coral cover has declined precipitously on Caribbean reefs in recent decades. Acropora cervicornis coral has been particularly decimated, and few Western Atlantic Acropora spp. refugia remain. Coral Gardens, Belize, was identified in 2020 as a long-term refugium for this species. This study assesses changes in live A. cervicornis coral abundance over time at Coral Gardens to monitor the stability of A. cervicornis corals, and to explore potential threats to this important refugium. Live coral cover was documented annually from 2012-2019 along five permanent transects. In situ sea-surface temperature data were collected at Coral Gardens throughout the study period and compared with calibrated satellite data to calculate Maximum Monthly Mean (MMM) temperatures and Degree Heating Weeks (DHW). Data on bathymetry, sediment, substrate, herbivore abundance, and macroalgal abundance were collected in 2014 and 2019 to assess potential threats to Coral Gardens. Live coral cover declined at all five transect sites over the study period. The greatest loss of live coral occurred between 2016 and 2017, coincident with the earliest and highest maximum average temperatures recorded at the study site, and the passage of a hurricane in 2016. Structural storm damage was not observed at Coral Gardens, though live coral cover declined after the passage of the storm. Uranium-thorium (230Th) dating of 26 dead in situ fragments of A. cervicornis collected in 2015 from Coral Gardens revealed no correlation between coral mortality and tropical storms and hurricanes in the recent past. Our data suggest that several other common drivers for coral decline (i.e. herbivory, predation, sedimentation, pH) may likely be ruled out for Coral Gardens. At the end of the study period, Coral Gardens satisfied most criteria for refugium status. However, the early onset, higher mean, and longer duration of above-average temperatures, as well as intermittent temperature anomalies likely played a critical role in the stability of this refugium. We suggest that temperature stress in 2016 and perhaps 2015 may have increased coral tissue vulnerability at Coral Gardens to a passing hurricane, threatening the status of this unique refugium.

Individuals with history of childhood trauma are characterized by aberrant resting-state limbic and paralimbic functional network connectivity. However, it is unclear whether specific subtypes of trauma (i.e., experienced vs observed or community) showcase differential effects. This study examined whether subtypes of childhood trauma (assessed via the Trauma Checklist [TCL] 2.0) were associated with aberrant intra-network amplitude of fluctuations and connectivity (i.e., functional coherence within a network), and inter-network connectivity across resting-state networks among incarcerated juvenile males (n = 179). Subtypes of trauma were established via principal component analysis of the TCL 2.0 and resting-state networks were identified by applying group independent component analysis to resting-state fMRI scans. We tested the association of subtypes of childhood trauma (i.e., TCL Factor 1 measuring experienced trauma and TCL Factor 2 assessing community trauma), and TCL Total scores to the aforementioned functional connectivity measures. TCL Factor 2 scores were associated with increased high-frequency fluctuations and increased intra-network connectivity in cognitive control, auditory, and sensorimotor networks, occurring primarily in paralimbic regions. TCL Total scores exhibited similar neurobiological patterns to TCL Factor 2 scores (with the addition of aberrant intra-network connectivity in visual networks), and no significant associations were found for TCL Factor 1. Consistent with previous analyses of community samples, our results suggest that childhood trauma among incarcerated juvenile males is associated with aberrant intra-network amplitude of fluctuations and connectivity across multiple networks including predominately paralimbic regions. Our results highlight the importance of accounting for traumatic loss, observed trauma, and community trauma in assessing neurobiological aberrances associated with adverse experiences in childhood, as well as the value of trained-rater trauma assessments compared to self-report.

BackgroundAppetite-regulating hormones (ARH) in human milk (HM) are suggested to affect infants’ milk intake and possibly infant growth. Maternal adiposity might contribute to higher levels of ARH in HM, either from the mammary gland or from raised circulating levels due to higher adiposity. Counterfactual-based mediation analysis can define indirect and direct effects between HM ARH and maternal and infant factors, and might be an important tool when investigating the mother-milk-infant triad.ObjectiveWe aim to investigate whether potential associations between (1) maternal adiposity and HM ARH and (2) HM ARH and infant milk intake and growth are mediated through maternal and infant plasma ARH, respectively.Materials and methodsMaternal and infant anthropometry and body composition, HM and blood samples were collected from 223 mother-infant dyads participating in the Mother, Infant and Lactation Quality study at three postpartum visits from 1 to 8.49 months. Leptin, insulin and adiponectin were analyzed using immunoassays. Mediation analyses using linear mixed-effect models were applied to investigate the direct and indirect effects through maternal and infant plasma hormone concentrations.ResultsA positive association between maternal body-mass-index (BMI) and HM leptin was mediated by maternal plasma leptin by 29% when fixing BMI to < 25 kg/m2, and through 51% when fixing BMI to ≥ 25 kg/m2 (pinteraction < 0.01). There was no mediated effect through plasma insulin in the association between BMI and HM insulin (p = 0.068). We found negative and positive associations between HM insulin and total milk intake and infant weight, respectively, however, these diminished in mediation analyses with reduced sample sizes.ConclusionOur main results suggest that the association between maternal adiposity and HM leptin was mediated through circulating leptin to a stronger degree for mothers with overweight compared to mothers with normal-weight. This indicates that excess maternal adiposity, and the resulting rise of circulating leptin and possible concomitant low-grade inflammation, may be reflected in HM composition.Clinical trials registry numberNCT03254329.

Producers are looking for more sustainable methods of producing fresh vegetables. No-till systems that use cover crops to keep the soil surface covered can increase sustainability by reducing soil erosion, reducing weed pressure, and retaining soil moisture compared to bare soil cropping systems. Cover crop termination methods along with planting equipment modifications required to work in high residue planting systems are often areas of interest to farmers prior to adopting no-till systems. The objectives of this experiment are to compare the effects of two different cover crops, iron clay pea (Vigna unguiculata L.), and pearl millet (Pennisetum glaucum L.), using three different termination methods (rolled/crimped, mowed, and mowed + incorporated via tillage) and two no-till transplanter configurations (with and without residue manager) on soil properties and collard (Brassica oleracea L. var. viridis) yield. Results show that biomass production for pearl millet was greater, with a three-season average of 8461 kg ha−1 compared to 6465 kg ha−1 for iron clay pea. Rolled cover crops under drier weather conditions retained more volumetric soil moisture compared to other methods for both cover crops. Increases in total soil carbon and nitrogen concentration in the top 15 cm ranged from 8 to 11% and 23 to 35%, respectively. Collards grown in an iron clay pea cover crop produced greater weight and height per plant for all growing seasons compared to those grown in pearl millet. Collard yield was affected by cover crop type as reported with iron clay peas ranging from 2881–13,168 kg ha−1 compared to lower yield for the pearl millet cover crop with a range of 1354–8943 kg ha−1. Overall, both cover crops showed the ability to improve soil health by increasing total soil carbon, but collard production was better in the iron clay pea cover crop.

Novel therapeutic approaches are much needed for the treatment of osteosarcoma. Targeted radionuclide therapy (TRT) and radioimmunotherapy (RIT) are promising approaches that deliver therapeutic radiation precisely to the tumor site. We have previously developed a fully human antibody, named IF3, that binds to insulin-like growth factor 2 receptor (IGF2R). IF3 was used in TRT to effectively inhibit tumor growth in osteosarcoma preclinical models. However, IF3’s relatively short half-life in mice raised the need for improvement. We generated an Fc-engineered version of IF3, termed IF3δ, with amino acid substitutions known to enhance antibody half-life in human serum. In this study, we confirmed the specific binding of IF3δ to IGF2R with nanomolar affinity, similar to wild-type IF3. Additionally, IF3δ demonstrated binding to human and mouse neonatal Fc receptors (FcRn), indicating the potential for FcRn-mediated endocytosis and recycling. Biodistribution studies in mice showed a higher accumulation of IF3δ in the spleen and bone than wild-type IF3, likely attributed to abnormal spleen expression of IGF2R in mice. Therefore, the pharmacokinetics data from mouse xenograft models may not precisely reflect their behavior in canine and human patients. However, the findings suggest both IF3 and IF3δ as promising options for the RIT of osteosarcoma.

Helicobacter pylori is a major human pathogen that colonizes the gastric mucosa and plays a causative role in development of peptic ulcers and gastric cancer. Neutrophils are heavily infected with this organism in vivo and play a prominent role in tissue destruction and disease. Recently, we demonstrated that H. pylori exploits neutrophil plasticity as part of its virulence strategy eliciting N1-like subtype differentiation that is notable for profound nuclear hypersegmentation. We undertook this study to test the hypothesis that hypersegmentation may enhance neutrophil migratory capacity. However, EZ-TAXIScan™ video imaging revealed a previously unappreciated and progressive chemotaxis defect that was apparent prior to hypersegmentation onset. Cell speed and directionality were significantly impaired to fMLF as well as C5a and IL-8. Infected cells oriented normally in chemotactic gradients, but speed and direction were impaired because of a uropod retraction defect that led to cell elongation, nuclear lobe trapping in the contracted rear and progressive narrowing of the leading edge. In contrast, chemotactic receptor abundance, adhesion, phagocytosis and other aspects of cell function were unchanged. At the molecular level, H. pylori phenocopied the effects of Blebbistatin as indicated by aberrant accumulation of F-actin and actin spikes at the uropod together with enhanced ROCKII-mediated phosphorylation of myosin IIA regulatory light chains at S19. At the same time, RhoA and ROCKII disappeared from the cell rear and accumulated at the leading edge whereas myosin IIA was enriched at both cell poles. These data suggest that H. pylori inhibits the dynamic changes in myosin IIA contractility and front-to-back polarity that are essential for chemotaxis. Taken together, our data advance understanding of PMN plasticity and H. pylori pathogenesis.

Objectives Recreational off-road vehicle crashes can produce severe injury and death among children, often from head trauma sustained while riding unhelmeted. Although required for competition, recreational riders commonly forego helmets. This study aimed to identify socioeconomic factors associated with unhelmeted injuries among children riding all-terrain vehicles (ATVs) and dirt bikes recreationally, thus informing injury prevention efforts.Methods A retrospective review was completed of patients younger than 18 years who presented after recreational ATV or dirt bike crash to a single American College of Surgeons-verified level 1 pediatric trauma center (2010–2019). Demographic, injury, and outcome data were collected. US Census data regarding median and per capita income, poverty prevalence, and scholastic graduation rates were recorded for each patient’s home county. Relationships between helmet use at the time of injury, demographics, and socioeconomic variables were examined.Results The cohort comprised 680 injured recreational ATV (n=510; 75%) and dirt bike (170; 25%) riders. Unhelmeted riders (n=450) were significantly older (median age 13 vs 11 years; p=0.008) and more often rode ATVs (n=399). Significantly greater percentages of females (77.9%; p

Background: Osteosarcoma (OS) represents the most common primary bone tumor in humans and in companion dogs, being practically phenotypically identical. There is a need for effective treatments to extend the survival of patients with OS. Here, we examine the dosimetry in beagle dogs and cross-reactivity with human tissues of a novel human antibody, IF3, that targets the insulin growth factor receptor type 2 (IGF2R), which is overexpressed on OS cells, making it a candidate for radioimmunotherapy of OS. Methods: [89Zr]Zr-DFO-IF3 was injected into three healthy beagle dogs. PET/CT was conducted at 4, 24, 48, and 72 h. RAPID analysis was used to determine the dosimetry of [177Lu]Lu-CHXA”-IF3 for a clinical trial in companion dogs with OS. IF3 antibody was biotinylated, and a multitude of human tissues were assessed with immunohistochemistry. Results: PET/CT revealed that only the liver, bone marrow, and adrenal glands had high uptake. Clearance was initially through renal and hepatobiliary excretion in the first 72 h followed by primarily physical decay. RAPID analysis showed bone marrow to be the dose-limiting organ with a therapeutic range for 177Lu calculated to be 0.487–0.583 GBq. Immunohistochemistry demonstrated the absence of IGF2R expression on the surface of healthy human cells, thus suggesting that radioimmunotherapy with [177Lu]Lu-CHXA”-IF3 will be well tolerated. Conclusions: Image-based dosimetry has defined a safe therapeutic range for canine clinical trials, while immunohistochemistry has suggested that the antibody will not cross-react with healthy human tissues.