Search Results (22)

The Module-0 Demonstrator is a single-phase 600 kg liquid argon time projection chamber operated as a prototype for the DUNE liquid argon near detector. Based on the ArgonCube design concept, Module-0 features a novel 80k-channel pixelated charge readout and advanced high-coverage photon detection system. In this paper, we present an analysis of an eight-day data set consisting of 25 million cosmic ray events collected in the spring of 2021. We use this sample to demonstrate the imaging performance of the charge and light readout systems as well as the signal correlations between the two. We also report argon purity and detector uniformity measurements and provide comparisons to detector simulations. Full article

Globally, children are exposed to multiple health risks associated with diet and nutrition. Rather than simply being a condition of having too much or too little food, malnutrition is more a syndrome comprising multiple burdens of coexisting and reciprocal malnutrition, infection, or other conditions. Importantly, children with such syndromes (e.g., stunting and anemia, which are neither specific nor necessarily sensitive to nutritional status) are more likely to also have irreversible functional outcomes such as poor growth, impaired immune function, or cognitive delays. The global health community has identified nutrition-related targets (e.g., Sustainable Development Goals (SDGs) and World Health Organization (WHO) Global Nutrition Targets) that, for multiple reasons, are difficult to address. Moreover, as the complexity of the global health context increases with persistent pandemics of infectious diseases and the rising prevalence of noncommunicable diseases, there is a growing appreciation that conditions selected as nutrition/health targets indeed represent syndromes for which nutritional status serves as both an input and outcome. In recognition of the impact of these combined challenges and the role of the multiple manifestations of malnutrition, we suggest an approach to nutritional assessment that is intended to improve the precision of context-specific, equitable approaches to health promotion, disease prevention, and treatment. Full article

(1) Background: Clinical results on the effects of excess sugar consumption on insulin sensitivity are conflicting, possibly due to differences in sugar type and the insulin sensitivity index (ISI) assessed. Therefore, we compared the effects of consuming four different sugars on insulin sensitivity indices derived from oral glucose tolerance tests (OGTT). (2) Methods: Young adults consumed fructose-, glucose-, high-fructose corn syrup (HFCS)-, sucrose-, or aspartame-sweetened beverages (SB) for 2 weeks. Participants underwent OGTT before and at the end of the intervention. Fasting glucose and insulin, Homeostatic Model Assessment-Insulin Resistance (HOMA-IR), glucose and insulin area under the curve, Surrogate Hepatic Insulin Resistance Index, Matsuda ISI, Predicted M ISI, and Stumvoll Index were assessed. Outcomes were analyzed to determine: (1) effects of the five SB; (2) effects of the proportions of fructose and glucose in all SB. (3) Results: Fructose-SB and the fructose component in mixed sugars negatively affected outcomes that assess hepatic insulin sensitivity, while glucose did not. The effects of glucose-SB and the glucose component in mixed sugar on muscle insulin sensitivity were more negative than those of fructose. (4) Conclusion: the effects of consuming sugar-SB on insulin sensitivity varied depending on type of sugar and ISI index because outcomes assessing hepatic insulin sensitivity were negatively affected by fructose, and outcomes assessing muscle insulin sensitivity were more negatively affected by glucose. Full article

The impact of the ethylene inhibitor, 1-methylcyclopropene (1-MCP), on four apple cultivars (Braeburn, Fuji, Jazz and Golden Delicious) over 150 days of storage at 2 °C was assessed. Proton transfer reaction quadrupole mass spectrometry (PTR-QUAD-MS) was used to monitor changes in VOC composition, while texture analysis and X-ray microcomputer tomography (µ-CT) scanning were used to study microstructural changes. The application of 1-MCP on apples reduced VOC emissions, concurrently maintaining a firmer texture compared to the untreated apples at each time point. The µ-CT scanning revealed how changes in specific morphological characteristics such as anisotropy, connectivity and porosity, size and shape, as well as the interconnectivity of intracellular spaces (IS) influenced texture even when porosity was similar. Additionally, this study showed that the porosity and connectivity of IS were associated with VOC emission and increased simultaneously. This study highlights how the morphological parameters of an apple can help explain their ripening process during long-term storage and how their microstructure can influence the release of VOCs. Full article

Malignancies can cause severe stenosis of the biliary tract and therefore predispose a patient to bacterial cholangitis. Upon endoscopic drainage, antibiotic therapy (AT) is performed according to individual clinical judgement, as the optimal duration of AT is unclear to date, especially in the case of multidrug-resistant organisms (MDROs). In a case-based retrospective study, patients with malignant biliary strictures and acute cholangitis were included upon endoscopic retrograde cholangiography (ERC). The outcome of cases treated with short AT (≤6 days) was compared to that of long AT (≥7 days). Recurrent cholangitis (RC) before scheduled stent exchange was the primary end point. In total, 124 patients were included, with 183 cases of proven cholangitis in total. The overall median duration of AT was 7 days (range 1–20), with 74 cases (40%) receiving short AT and 109 (60%) receiving long AT. Short AT was not an independent risk factor for RC (HR = 0.66, p > 0.2), while colonization with MDROs was associated with a higher risk of RC (HR = 2.21, p = 0.005). Placement of a metal stent was associated with minor risk of RC (HR = 0.4, p = 0.038). In conclusion, short AT is possible in selected patients with non-severe cholangitis and malignant biliary strictures. Scheduled screening for MDROs is recommended and placement of a metal stent should be performed if possible. Full article

Changes in our climate and physical environments are having profound effects on all aspects of human existence, and the ability to develop sustainable and resilient food systems is critical not just to the environment but to all aspects of human health. The Pediatric Growth and Nutrition Branch (PGNB) of the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the US National Institutes of Health has adopted a new paradigm to undergird the study of nutrition that recognizes the complex and reciprocal nature of the relationships between nutrition and health outcomes. This conceptual framework, termed the “nutritional ecology,” views humans as complex biological systems interacting with both their internal and external environments. Herein, we focus on: (i) the reciprocal relationship between climate and environmental changes and food systems and their impact on food/nutrition security and health; and (ii) how PGNB is utilizing the “nutritional ecology” framework to support science addressing the interactions among health, nutrition, food systems, climate, and the environment. Full article

The consumer rejection threshold (RjT) method was applied to determine the total microbial numbers (TMNs) where consumers find that the quality of whole fresh chilled pasteurised milk (WFCPM) and skim milk (Trim) stored at 4.5 ± 0.5 °C is no longer acceptable. Food spoilage progression was supported by measurements of VOCs and the terms consumers used to describe the ageing fresh chilled pasteurised milk (FCPM). RjTs for TMN of 7.43 and 7.34 log10 CFU.mL⁻¹ for WFCPM and Trim, respectively were derived using Hill’s equation from a series of paired preference tests comparing fresh and aged milks (3–26 days) assessed by consumers (WFCPM, n = 55; Trim, n = 52). A poor relationship between storage time and TMN was found, owing mainly to batch-to-batch and within-batch variation in the milk’s post-pasteurization contamination (PPC) levels. At the RjT, there was a significant change in the signal intensities for a number of spoilage-related VOCs that occurred in the FCPM headspace (p ≤ 0.05), which were measured using proton transfer reaction–mass spectrometry (PTR-MS), including m/z 33, 45, 47, 61, 63, 69, 71, 87, and 89, tentatively identified as methanol; acetaldehyde; ethanol; acetate (acetic acid and acetate esters); dimethyl sulphide (DMS); isoprene, furan, and aldehydes; 2-butanone; and pentanal and butyrates (butyric acid and butyrate esters), respectively. Consumers described the milks at TMN greater than the RjTs using terms like off, expired, sour, spoilt or rancid. This multidisciplinary study has provided data on the importance of PPC and subsequent increases in TMN on VOCs associated with FCPM and consumer’s preferences and highlighted the value of measuring a range of variables when investigating consumer’s perception of food quality and shelf-life. Full article

Computed tomography perfusion (CTP) is frequently used in the triage of ischemic stroke patients for endovascular thrombectomy (EVT). We aimed to quantify the volumetric and spatial agreement of the CTP ischemic core estimated with different thresholds and follow-up MRI infarct volume on diffusion-weighted imaging (DWI). Patients treated with EVT between November 2017 and September 2020 with available baseline CTP and follow-up DWI were included. Data were processed with Philips IntelliSpace Portal using four different thresholds. Follow-up infarct volume was segmented on DWI. In 55 patients, the median DWI volume was 10 mL, and median estimated CTP ischemic core volumes ranged from 10–42 mL. In patients with complete reperfusion, the intraclass correlation coefficient (ICC) showed moderate-good volumetric agreement (range 0.55–0.76). A poor agreement was found for all methods in patients with successful reperfusion (ICC range 0.36–0.45). Spatial agreement (median Dice) was low for all four methods (range 0.17–0.19). Severe core overestimation was most frequently (27%) seen in Method 3 and patients with carotid-T occlusion. Our study shows moderate–good volumetric agreement between ischemic core estimates for four different thresholds and subsequent infarct volume on DWI in EVT-treated patients with complete reperfusion. The spatial agreement was similar to other commercially available software packages. Full article

The perception of hop-derived flavour in beer is not well understood, particularly regarding the effect that different yeast strains and fermentation parameters have on perceived hop aroma and the mechanisms responsible for these changes. To evaluate the influence of yeast strain on the sensory properties and volatile composition of beer, a standard wort, late-hopped with New Zealand Motueka hops (5 g·L⁻¹), was fermented with one of twelve yeast strains under constant conditions (temperature and yeast inoculation rate). The bottled beers were evaluated using a free sorting sensory methodology, and their volatile organic compounds (VOC) were assessed using gas chromatography mass spectrometry (GC/MS) with headspace solid-phase microextraction (SPME) sampling. Beer fermented with SafLager W-34/70 yeast was associated with a hoppy flavour attribute, whereas WY1272 and OTA79 beers were sulfury, and WY1272 was also metallic. WB06 and WLP730 beers were perceived to be spicy, with WB06 beer also perceived as estery, whereas VIN13 beer was sour, and the WLP001 beer was astringent. Beers fermented using the twelve yeast strains had clearly distinct VOC profiles. Beer made with WLP730, OTA29, SPH, and WB06 yeasts had the highest 4-vinylguaiacol levels, which contributed to their spicy attribute. Beer made with W3470 had high levels of nerol, geraniol, and citronellol, which supported its sensory characterisation as being ‘hoppy’. This research has illustrated the important role that yeast strain has on modulating hop flavour in beer. Full article

Increased hepatic lipid content and decreased insulin sensitivity have critical roles in the development of cardiometabolic diseases. Therefore, our objective was to investigate the dose-response effects of consuming high fructose corn syrup (HFCS)-sweetened beverages for two weeks on hepatic lipid content and insulin sensitivity in young (18–40 years) adults (BMI 18–35 kg/m²). In a parallel, double-blinded study, participants consumed three beverages/day providing 0% (aspartame: n = 23), 10% (n = 18), 17.5% (n = 16), or 25% (n = 28) daily energy requirements from HFCS. Magnetic resonance imaging for hepatic lipid content and oral glucose tolerance tests (OGTT) were conducted during 3.5-day inpatient visits at baseline and again at the end of a 15-day intervention. During the 12 intervening outpatient days participants consumed their usual diets with their assigned beverages. Significant linear dose-response effects were observed for increases of hepatic lipid content (p = 0.015) and glucose and insulin AUCs during OGTT (both p = 0.0004), and for decreases in the Matsuda (p = 0.0087) and Predicted M (p = 0.0027) indices of insulin sensitivity. These dose-response effects strengthen the mechanistic evidence implicating consumption of HFCS-sweetened beverages as a contributor to the metabolic dysregulation that increases risk for nonalcoholic fatty liver disease and type 2 diabetes. Full article

Identification of human cancer-reactive CD8+ T cells is crucial for the stratification of patients for immunotherapy and determination of immune-therapeutic effects. To date, these T cells have been identified mainly based on cell surface expression of programmed cell death protein 1 (PD-1) or co-expression of CD103 and CD39. A small subset of CD103− CD39+ CD8+ T cells is also present in tumors, but little is known about these T cells. Here, we report that CD103− CD39+ CD8+ T cells from mismatch repair-deficient endometrial tumors are activated and characterized predominantly by expression of TNFRSF9. In vitro, transforming growth factor-beta (TGF-β) drives the disappearance of this subset, likely through the conversion of CD103− CD39+ cells to a CD103+ phenotype. On the transcriptomic level, T cell activation and induction of CD39 was associated with a number of tissue residence and TGF-β responsive transcription factors. Altogether, our data suggest CD39+ CD103− CD8+ tumor-infiltrating T cells are recently activated and likely rapidly differentiate towards tissue residence upon exposure to TGF-β in the tumor micro-environment, explaining their relative paucity in human tumors. Full article

Epidermolysis bullosa is a group of genetic skin conditions characterized by abnormal skin (and mucosal) fragility caused by pathogenic variants in various genes. The disease severity ranges from early childhood mortality in the most severe types to occasional acral blistering in the mildest types. The subtype and severity of EB is linked to the gene involved and the specific variants in that gene, which also determine its mode of inheritance. Current treatment is mainly focused on symptomatic relief such as wound care and blister prevention, because truly curative treatment options are still at the preclinical stage. Given the current level of understanding, the broad spectrum of genes and variants underlying EB makes it impossible to develop a single treatment strategy for all patients. It is likely that many different variant-specific treatment strategies will be needed to ultimately treat all patients. Antisense-oligonucleotide (ASO)-mediated exon skipping aims to counteract pathogenic sequence variants by restoring the open reading frame through the removal of the mutant exon from the pre-messenger RNA. This should lead to the restored production of the protein absent in the affected skin and, consequently, improvement of the phenotype. Several preclinical studies have demonstrated that exon skipping can restore protein production in vitro, in skin equivalents, and in skin grafts derived from EB-patient skin cells, indicating that ASO-mediated exon skipping could be a viable strategy as a topical or systemic treatment. The potential value of exon skipping for EB is supported by a study showing reduced phenotypic severity in patients who carry variants that result in natural exon skipping. In this article, we review the substantial progress made on exon skipping for EB in the past 15 years and highlight the opportunities and current challenges of this RNA-based therapy approach. In addition, we present a prioritization strategy for the development of exon skipping based on genomic information of all EB-involved genes. Full article

The Deep Underground Neutrino Experiment (DUNE) is an international, world-class experiment aimed at exploring fundamental questions about the universe that are at the forefront of astrophysics and particle physics research. DUNE will study questions pertaining to the preponderance of matter over antimatter in the early universe, the dynamics of supernovae, the subtleties of neutrino interaction physics, and a number of beyond the Standard Model topics accessible in a powerful neutrino beam. A critical component of the DUNE physics program involves the study of changes in a powerful beam of neutrinos, i.e., neutrino oscillations, as the neutrinos propagate a long distance. The experiment consists of a near detector, sited close to the source of the beam, and a far detector, sited along the beam at a large distance. This document, the DUNE Near Detector Conceptual Design Report (CDR), describes the design of the DUNE near detector and the science program that drives the design and technology choices. The goals and requirements underlying the design, along with projected performance are given. It serves as a starting point for a more detailed design that will be described in future documents. Full article

As the extent of secondary forests continues to expand throughout the tropics, there is a growing need to better understand the ecosystem services, including carbon (C) storage provided by these ecosystems. Despite their spatial extent, there are limited data on how the ecosystem services provided by secondary forest may be enhanced through the restoration of both ecological and agroecological functions in these systems. This study quantifies the above- and below-ground C stocks in a non-native secondary forest in Hawaiʻi where a community-based non-profit seeks to restore a multi-strata agroforestry system for cultural and ecological benefits. For soil C, we use the equivalent soil mass method both to estimate stocks and examine spatial heterogeneity at high resolution (eg. sub 5 m) to define a method and sampling design that can be replicated to track changes in C stocks on-site and elsewhere. The assessed total ecosystem C was ~388.5 Mg C/ha. Carbon stock was highest in trees (~192.4 Mg C/ha; ~50% of total C); followed by soil (~136.4 Mg C/ha; ~35% of total C); roots (~52.7 Mg C/ha; ~14% of total C); and was lowest in coarse woody debris (~4.7 Mg C/ha; ~1% of total C) and litter (~2.3 Mg C/ha; <1% of total C). This work provides a baseline carbon assessment prior to agroforest restoration that will help to better quantify the contributions of secondary forest transitions and restoration efforts to state climate policy. In addition to the role of C sequestration in climate mitigation, we also highlight soil C as a critical metric of hybrid, people-centered restoration success given the role of soil organic matter in the production of a suite of on- and off-site ecosystem services closely linked to local sustainable development goals. Full article

Sugar-sweetened beverage (sugar-SB) consumption is associated with body weight gain. We investigated whether the changes of (Δ) circulating leptin contribute to weight gain and ad libitum food intake in young adults consuming sugar-SB for two weeks. In a parallel, double-blinded, intervention study, participants (n = 131; BMI 18–35 kg/m²; 18–40 years) consumed three beverages/day containing aspartame or 25% energy requirement as glucose, fructose, high fructose corn syrup (HFCS) or sucrose (n = 23–28/group). Body weight, ad libitum food intake and 24-h leptin area under the curve (AUC) were assessed at Week 0 and at the end of Week 2. The Δbody weight was not different among groups (p = 0.092), but the increases in subjects consuming HFCS- (p = 0.0008) and glucose-SB (p = 0.018) were significant compared with Week 0. Subjects consuming sucrose- (+14%, p < 0.0015), fructose- (+9%, p = 0.015) and HFCS-SB (+8%, p = 0.017) increased energy intake during the ad libitum food intake trial compared with subjects consuming aspartame-SB (−4%, p = 0.0037, effect of SB). Fructose-SB decreased (−14 ng/mL × 24 h, p = 0.0006) and sucrose-SB increased (+25 ng/mL × 24 h, p = 0.025 vs. Week 0; p = 0.0008 vs. fructose-SB) 24-h leptin AUC. The Δad libitum food intake and Δbody weight were not influenced by circulating leptin in young adults consuming sugar-SB for 2 weeks. Studies are needed to determine the mechanisms mediating increased energy intake in subjects consuming sugar-SB. Full article