The early life microbiota protects neonatal mice from pathological small intestinal epithelial cell shedding

The early life gut microbiota plays a crucial role in regulating and maintaining the intestinal barrier, with disturbances in these communities linked to dysregulated renewal and replenishment of intestinal epithelial cells. Here we sought to determine pathological cell shedding outcomes throughout the postnatal developmental period, and which host and microbial factors mediate these responses. Surprisingly, neonatal mice (Day 14 and 21) were highly refractory to induction of cell shedding after intraperitoneal administration of liposaccharide (LPS), with Day 29 mice showing strong pathological responses, more similar to those observed in adult mice. These differential responses were not linked to defects in the cellular mechanisms and pathways known to regulate cell shedding responses. When we profiled microbiota and metabolites, we observed significant alterations. Neonatal mice had high relative abundances of Streptococcus, Escherichia, and Enterococcus and increased primary bile acids. In contrast, older mice were dominated by Candidatus Arthromitus, Alistipes, and Lachnoclostridium, and had increased concentrations of SCFAs and methyamines. Antibiotic treatment of neonates restored LPS-induced small intestinal cell shedding, whereas adult fecal microbiota transplant alone had no effect. Our findings further support the importance of the early life window for microbiota-epithelial interactions in the presence of inflammatory stimuli and highlights areas for further investigation

Life cycle assessment and water use impacts of lithium production from salar deposits: Challenges and opportunities

This is the final version. Available from Elsevier via the DOI in this record. Lithium is a critical raw material for the energy transition and the salar brine deposits of South America host ∼70% of global resources. However, there are concerns regarding water use, and the associated impacts, of lithium production from these deposits. Life Cycle Assessment (LCA) is becoming increasingly prevalent in the analysis of raw materials sustainability, but current methods are regarded as unsatisfactory for assessing water use impacts related to lithium production from salar deposits. This work explores the challenges and opportunities for improvement in this context. We outline how the classification and assessment of water types could be improved and identify Water Availability Assessments, groundwater specific CFs, salar-specific methodologies and multiple mid-point indicators as areas for further investigation. This will aid the development of LCA methodology and enable an improved assessment of the sustainability of lithium production from salar deposits in South America and by extension help decouple decarbonisation efforts from negative impacts.Natural Environment Research Counci

Magnetic Energy Powers the Corona: How We Can Understand its 3D Storage & Release

The coronal magnetic field is the prime driver behind many as-yet unsolved mysteries: solar eruptions, coronal heating, and the solar wind, to name a few. It is, however, still poorly observed and understood. We highlight key questions related to magnetic energy storage, release, and transport in the solar corona, and their relationship to these important problems. We advocate for new and multi-point co-optimized measurements, sensitive to magnetic field and other plasma parameters, spanning from optical to $\gamma$-ray wavelengths, to bring closure to these long-standing and fundamental questions. We discuss how our approach can fully describe the 3D magnetic field, embedded plasma, particle energization, and their joint evolution to achieve these objectives.Comment: White paper submitted to the Decadal Survey for Solar and Space Physics (Heliophysics) 2024-2033; 16 pages, 3 figure

COMPLETE: A flagship mission for complete understanding of 3D coronal magnetic energy release

COMPLETE is a flagship mission concept combining broadband spectroscopic imaging and comprehensive magnetography from multiple viewpoints around the Sun to enable tomographic reconstruction of 3D coronal magnetic fields and associated dynamic plasma properties, which provide direct diagnostics of energy release. COMPLETE re-imagines the paradigm for solar remote-sensing observations through purposefully co-optimized detectors distributed on multiple spacecraft that operate as a single observatory, linked by a comprehensive data/model assimilation strategy to unify individual observations into a single physical framework. We describe COMPLETE's science goals, instruments, and mission implementation. With targeted investment by NASA, COMPLETE is feasible for launch in 2032 to observe around the maximum of Solar Cycle 26.Comment: White paper submitted to the Decadal Survey for Solar and Space Physics (Heliophysics) 2024-2033; 10 pages, 6 figures, 1 tabl

Improving Multi-Dimensional Data Formats, Access, and Assimilation Tools for the Twenty-First Century

Heliophysics image data largely relies on a forty-year-old ecosystem built on the venerable Flexible Image Transport System (FITS) data standard. While many in situ measurements use newer standards, they are difficult to integrate with multiple data streams required to develop global understanding. Additionally, most data users still engage with data in much the same way as they did decades ago. However, contemporary missions and models require much more complex support for 3D multi-parameter data, robust data assimilation strategies, and integration of multiple individual data streams required to derive complete physical characterizations of the Sun and Heliospheric plasma environment. In this white paper we highlight some of the 21$^\mathsf{st}$ century challenges for data frameworks in heliophysics, consider an illustrative case study, and make recommendations for important steps the field can take to modernize its data products and data usage models. Our specific recommendations include: (1) Investing in data assimilation capability to drive advanced data-constrained models, (2) Investing in new strategies for integrating data across multiple instruments to realize measurements that cannot be produced from single observations, (3) Rethinking old data use paradigms to improve user access, develop deep understanding, and decrease barrier to entry for new datasets, and (4) Investing in research on data formats better suited for multi-dimensional data and cloud-based computing.Comment: White paper submitted to the Decadal Survey for Solar and Space Physics (Heliophysics) 2024-2033; 9 pages, 3 figure

Reconfiguration, contestation, and decline: conceptualizing mature large technical systems

Large technical systems (LTS) are integral to modern lifestyles but arduous to analyze. In this paper, we advance a conceptualization of LTS using the notion of mature “phases,” drawing from insights into innovation studies, science and technology studies, political science, the sociology of infra- structure, history of technology, and governance. We begin by defining LTS as a unit of analysis and explaining its conceptual utility and novelty, situating it among other prominent sociotechnical theories. Next, we argue that after LTS have moved through the (overlapping) phases proposed by Thomas Hughes of invention, expansion, growth, momentum, and style,mature LTS undergo the additional (overlapping) phases of reconfiguration, contestation (subject to pressures such as drift and crisis), and eventually stagnation and decline. We illustrate these analytical phases with historical case studies and the conceptual literature, and close by suggesting future research to refine and develop the LTS framework, particularly related to more refined typologies, temporal dimensions, and a broadening of system users. We aim to contribute to theoretical debates about the coevolution of LTS as well as empirical discussions about system-related use, socio- technical change, and policy-making

Melanoma cells break down LPA to establish local gradients that drive chemotactic dispersal.

The high mortality of melanoma is caused by rapid spread of cancer cells, which occurs unusually early in tumour evolution. Unlike most solid tumours, thickness rather than cytological markers or differentiation is the best guide to metastatic potential. Multiple stimuli that drive melanoma cell migration have been described, but it is not clear which are responsible for invasion, nor if chemotactic gradients exist in real tumours. In a chamber-based assay for melanoma dispersal, we find that cells migrate efficiently away from one another, even in initially homogeneous medium. This dispersal is driven by positive chemotaxis rather than chemorepulsion or contact inhibition. The principal chemoattractant, unexpectedly active across all tumour stages, is the lipid agonist lysophosphatidic acid (LPA) acting through the LPA receptor LPAR1. LPA induces chemotaxis of remarkable accuracy, and is both necessary and sufficient for chemotaxis and invasion in 2-D and 3-D assays. Growth factors, often described as tumour attractants, cause negligible chemotaxis themselves, but potentiate chemotaxis to LPA. Cells rapidly break down LPA present at substantial levels in culture medium and normal skin to generate outward-facing gradients. We measure LPA gradients across the margins of melanomas in vivo, confirming the physiological importance of our results. We conclude that LPA chemotaxis provides a strong drive for melanoma cells to invade outwards. Cells create their own gradients by acting as a sink, breaking down locally present LPA, and thus forming a gradient that is low in the tumour and high in the surrounding areas. The key step is not acquisition of sensitivity to the chemoattractant, but rather the tumour growing to break down enough LPA to form a gradient. Thus the stimulus that drives cell dispersal is not the presence of LPA itself, but the self-generated, outward-directed gradient

Hierarchical structures in the Large and Small Magellanic Clouds

We investigate the degree of spatial correlation among extended structures in the LMC and SMC. To this purpose we work with sub-samples characterised by different properties such as age and size, taken from the updated catalogue of Bica et al. or gathered in the present work. The structures are classified as star clusters or non-clusters (basically, nebular complexes and their stellar associations). The radius distribution functions follow power-laws ($dN/dR\propto R^{-\alpha}$) with slopes and maximum radius ($R_{max}$) that depend on object class (and age). Non-clusters are characterised by $\alpha\approx1.9$ and R_{max}\la472 pc, while young clusters (age \la10 Myr) have $\alpha\approx3.6$ and R_{max}\la15 pc, and old ones (age \ga600 Myr) have $\alpha\approx2.5$ and R_{max}\la40 pc. Young clusters present a high degree of spatial self-correlation and, especially, correlate with star-forming structures, which does not occur with the old ones. This is consistent with the old clusters having been heavily mixed up, since their ages correspond to several LMC and SMC crossing times. On the other hand, with ages corresponding to fractions of the respective crossing times, the young clusters still trace most of their birthplace structural pattern. Also, small clusters ($R<10$ pc), as well as small non-clusters ($R<100$ pc), are spatially self-correlated, while their large counterparts of both classes are not. The above results are consistent with a hierarchical star-formation scenario for the LMC and SMC.Comment: Accepted by MNRA

Evaluation of a student-run smoking cessation clinic for a medically underserved population

<p>Abstract</p> <p>Background</p> <p>Smoking is common among medically underserved populations. Accessible resources to encourage and support smoking cessation among these patients are limited. Volunteer medical student-run free smoking cessation clinics may provide an effective option to help these individuals achieve smoking abstinence. In order to demonstrate the feasibility and cost-effectiveness of a student-run clinic, we analyzed a case series of patients receiving care in a medical student-run Smoking Cessation Clinic (SCC) at the Rochester, Minnesota Salvation Army Good Samaritan Health Clinic (GSHC).</p> <p>Findings</p> <p>Between January 2005 and March 2009, 282 cigarette smokers seeking care at the SCC were analyzed. Student providers at the SCC conducted 1652 weekly individual counseling sessions averaging 18 minutes per encounter. Patients were offered a choice of pharmacotherapies including nicotine replacement therapy (NRT), bupropion, and varenicline for up to 12 weeks. Smoking abstinence was confirmed with exhaled carbon monoxide (CO). Thirty-two patients completed the entire 12-week program (11.3%). At last contact, 94 patients (33.3%) abstained from smoking for ≥ 7 days and 39 patients (13.8%) were continuously abstinent for ≥ 4 weeks. The 7-day point prevalence abstinence rates at last contact were 58.6% for varenicline, 41.2% for bupropion, 33.9% for NRT, and 23.5% for bupropion and NRT. Analyzing missing patients as smoking, the 7-day point prevalence abstinence rates were 7.1%, 8.9%, and 8.2%, at 1 month, 2 months, and 3 months after program enrollment, respectively. No serious adverse drug reactions were recorded.</p> <p>Conclusions</p> <p>Our medical student-run smoking cessation clinic provided an effective and safe experience for medically underserved patients who might not otherwise have access to conventional smoking cessation programs because of high cost, lack of insurance, or other disparities. Similar medical student initiatives focusing on healthy lifestyles may be feasible and beneficial for individuals with limited access to healthcare resources.</p

Receiver operating characteristic analysis of age-related changes in lineup performance

In the basic face memory literature, support has been found for the late maturation hypothesis, which holds that face recognition ability is not fully developed until at least adolescence. Support for the late maturation hypothesis in the criminal lineup identification literature, however, has been equivocal because of the analytic approach that has been used to examine age-related changes in identification performance. Recently, receiver operator characteristic (ROC) analysis was applied for the first time in the adult eyewitness memory literature to examine whether memory sensitivity differs across different types of lineup tests. ROC analysis allows for the separation of memory sensitivity from response bias in the analysis of recognition data. Here, we have made the first ROC-based comparison of adults’ and children’s (5- and 6-year-olds and 9- and 10-year-olds) memory performance on lineups by reanalyzing data from Humphries, Holliday, and Flowe (2012). In line with the late maturation hypothesis, memory sensitivity was significantly greater for adults compared with young children. Memory sensitivity for older children was similar to that for adults. The results indicate that the late maturation hypothesis can be generalized to account for age-related performance differences on an eyewitness memory task. The implications for developmental eyewitness memory research are discussed