The nexus of immigration regulation and health governance: a scoping review of the extent to which right to access healthcare by migrants, refugees and asylum seekers was upheld in the United Kingdom during COVID-19.

OBJECTIVES: Complementing the well-established evidence base on health inequalities experienced by migrants, refugees and asylum seekers in the UK; we examined the extent to which their right to equal non-discriminatory access to health services (promotive, preventive, curative) was upheld during the COVID-19 pandemic. STUDY DESIGN: Arksey and O'Malley's scoping review framework. METHODS: A comprehensive search was conducted on Medline, PubMed, and CINAHL using detailed MESH terms, for literature published between 01 January 2020 and 01 January 2024. The process was supported by a ten-page Google search and hand searching of reference lists. 42 records meeting the inclusion criteria were charted, coded inductively and analysed thematically in an integrated team-based approach. RESULTS: Dissonance between immigration regulation and health governance is illustrated in four themes: Health systems leveraged to (re)enforce the hostile environment; Dissonance between health rights on paper and in practice; Structural failures to overcome communication and digital exclusion; and COVID-19 vaccine (in)equity exacerbated fear, mistrust and exclusion. Migrants, refugees and asylum seekers encountered substantial individual, structural and policy-level barriers to accessing healthcare in the UK during COVID-19. Insecure immigration status, institutional mistrust, data-sharing and charging fears, communication challenges and digital exclusion impacted heavily on their ability to access healthcare in an equitable non-discriminatory manner. CONCLUSIONS: An inclusive and innovative health equity and rights-based responses reaching all migrants, refugees and asylum seekers are warranted if the National Health Service is to live up to its promise of 'leaving no one behind' in post-pandemic and future responses.

Metal bioaccumulation and effects of olivine sand exposure on benthic marine invertebrates.

Due to the anthropogenic increase of atmospheric CO2 emissions, humanity is facing the negative effects of rapid global climate change. Both active emission reduction and carbon dioxide removal (CDR) technologies are needed to meet the Paris Agreement and limit global warming to 1.5 °C by 2050. One promising CDR approach is coastal enhanced weathering (CEW), which involves the placement of sand composed of (ultra)mafic minerals like olivine in coastal zones. Although the large-scale placement of olivine sand could beneficially impact the planet through the consumption of atmospheric CO2 and reduction in ocean acidification, it may also have physical and geochemical impacts on benthic communities. The dissolution of olivine can release dissolved constituents such as trace metals that may affect marine organisms. Here we tested acute and chronic responses of marine invertebrates to olivine sand exposure, as well as examined metal accumulation in invertebrate tissue resulting from olivine dissolution. Two different ecotoxicological experiments were performed on a range of benthic marine invertebrates (amphipod, polychaete, bivalve). The first experiment included acute and chronic survival and growth tests (10 and 20 days, respectively) of olivine exposure while the second had longer (28 day) exposures to measure chronic survival and bioaccumulation of trace metals (e.g. Ni, Cr, Co) released during olivine sand dissolution. Across all fauna we observed no negative effects on acute survival or chronic growth resulting solely from olivine exposure. However, over 28 days of exposure, the bent-nosed clam Macoma nasuta experienced reduced burrowing and accumulated 4.2 ± 0.7 µg g ww-1 of Ni while the polychaete Alitta virens accumulated 3.5 ± 0.9 µg g ww-1 of Ni. No significant accumulation of any other metals was observed. Future work should include longer-term laboratory studies as well as CEW field studies to validate these findings under real-world scenarios.

Microbial Catalysis for CO2 Sequestration: A Geobiological Approach.

One of the greatest threats facing the planet is the continued increase in excess greenhouse gasses, with CO2 being the primary driver due to its rapid increase in only a century. Excess CO2 is exacerbating known climate tipping points that will have cascading local and global effects including loss of biodiversity, global warming, and climate migration. However, global reduction of CO2 emissions is not enough. Carbon dioxide removal (CDR) will also be needed to avoid the catastrophic effects of global warming. Although the drawdown and storage of CO2 occur naturally via the coupling of the silicate and carbonate cycles, they operate over geological timescales (thousands of years). Here, we suggest that microbes can be used to accelerate this process, perhaps by orders of magnitude, while simultaneously producing potentially valuable by-products. This could provide both a sustainable pathway for global drawdown of CO2 and an environmentally benign biosynthesis of materials. We discuss several different approaches, all of which involve enhancing the rate of silicate weathering. We use the silicate mineral olivine as a case study because of its favorable weathering properties, global abundance, and growing interest in CDR applications. Extensive research is needed to determine both the upper limit of the rate of silicate dissolution and its potential to economically scale to draw down significant amounts (Mt/Gt) of CO2 Other industrial processes have successfully cultivated microbial consortia to provide valuable services at scale (e.g., wastewater treatment, anaerobic digestion, fermentation), and we argue that similar economies of scale could be achieved from this research.

Scintillation light detection in the 6-m drift-length ProtoDUNE Dual Phase liquid argon TPC.

DUNE is a dual-site experiment for long-baseline neutrino oscillation studies, neutrino astrophysics and nucleon decay searches. ProtoDUNE Dual Phase (DP) is a 6  ×  6  ×  6 m 3 liquid argon time-projection-chamber (LArTPC) that recorded cosmic-muon data at the CERN Neutrino Platform in 2019-2020 as a prototype of the DUNE Far Detector. Charged particles propagating through the LArTPC produce ionization and scintillation light. The scintillation light signal in these detectors can provide the trigger for non-beam events. In addition, it adds precise timing capabilities and improves the calorimetry measurements. In ProtoDUNE-DP, scintillation and electroluminescence light produced by cosmic muons in the LArTPC is collected by photomultiplier tubes placed up to 7 m away from the ionizing track. In this paper, the ProtoDUNE-DP photon detection system performance is evaluated with a particular focus on the different wavelength shifters, such as PEN and TPB, and the use of Xe-doped LAr, considering its future use in giant LArTPCs. The scintillation light production and propagation processes are analyzed and a comparison of simulation to data is performed, improving understanding of the liquid argon properties.

Robust but weak winter atmospheric circulation response to future Arctic sea ice loss.

The possibility that Arctic sea ice loss weakens mid-latitude westerlies, promoting more severe cold winters, has sparked more than a decade of scientific debate, with apparent support from observations but inconclusive modelling evidence. Here we show that sixteen models contributing to the Polar Amplification Model Intercomparison Project simulate a weakening of mid-latitude westerlies in response to projected Arctic sea ice loss. We develop an emergent constraint based on eddy feedback, which is 1.2 to 3 times too weak in the models, suggesting that the real-world weakening lies towards the higher end of the model simulations. Still, the modelled response to Arctic sea ice loss is weak: the North Atlantic Oscillation response is similar in magnitude and offsets the projected response to increased greenhouse gases, but would only account for around 10% of variations in individual years. We further find that relationships between Arctic sea ice and atmospheric circulation have weakened recently in observations and are no longer inconsistent with those in models.

Prospects for beyond the Standard Model physics searches at the Deep Underground Neutrino Experiment: DUNE Collaboration.

The Deep Underground Neutrino Experiment (DUNE) will be a powerful tool for a variety of physics topics. The high-intensity proton beams provide a large neutrino flux, sampled by a near detector system consisting of a combination of capable precision detectors, and by the massive far detector system located deep underground. This configuration sets up DUNE as a machine for discovery, as it enables opportunities not only to perform precision neutrino measurements that may uncover deviations from the present three-flavor mixing paradigm, but also to discover new particles and unveil new interactions and symmetries beyond those predicted in the Standard Model (SM). Of the many potential beyond the Standard Model (BSM) topics DUNE will probe, this paper presents a selection of studies quantifying DUNE's sensitivities to sterile neutrino mixing, heavy neutral leptons, non-standard interactions, CPT symmetry violation, Lorentz invariance violation, neutrino trident production, dark matter from both beam induced and cosmogenic sources, baryon number violation, and other new physics topics that complement those at high-energy colliders and significantly extend the present reach.

Forecasting extreme stratospheric polar vortex events.

Extreme polar vortex events known as sudden stratospheric warmings can influence surface winter weather conditions, but their timing is difficult to predict. Here, we examine factors that influence their occurrence, with a focus on their timing and vertical extent. We consider the roles of the troposphere and equatorial stratosphere separately, using a split vortex event in January 2009 as the primary case study. This event cannot be reproduced by constraining wind and temperatures in the troposphere alone, even when the equatorial lower stratosphere is in the correct phase of the quasi biennial oscillation. When the flow in the equatorial upper stratosphere is also constrained, the timing and spatial evolution of the vortex event is captured remarkably well. This highlights an influence from this region previously unrecognised by the seasonal forecast community. We suggest that better representation of the flow in this region is likely to improve predictability of extreme polar vortex events and hence their associated impacts at the surface.

Potential for large-scale CO2 removal via enhanced rock weathering with croplands.

Enhanced silicate rock weathering (ERW), deployable with croplands, has potential use for atmospheric carbon dioxide (CO2) removal (CDR), which is now necessary to mitigate anthropogenic climate change1. ERW also has possible co-benefits for improved food and soil security, and reduced ocean acidification2-4. Here we use an integrated performance modelling approach to make an initial techno-economic assessment for 2050, quantifying how CDR potential and costs vary among nations in relation to business-as-usual energy policies and policies consistent with limiting future warming to 2 degrees Celsius5. China, India, the USA and Brazil have great potential to help achieve average global CDR goals of 0.5 to 2 gigatonnes of carbon dioxide (CO2) per year with extraction costs of approximately US$80-180 per tonne of CO2. These goals and costs are robust, regardless of future energy policies. Deployment within existing croplands offers opportunities to align agriculture and climate policy. However, success will depend upon overcoming political and social inertia to develop regulatory and incentive frameworks. We discuss the challenges and opportunities of ERW deployment, including the potential for excess industrial silicate materials (basalt mine overburden, concrete, and iron and steel slag) to obviate the need for new mining, as well as uncertainties in soil weathering rates and land-ocean transfer of weathered products.

Increased yield and CO2 sequestration potential with the C4 cereal Sorghum bicolor cultivated in basaltic rock dust-amended agricultural soil.

Land-based enhanced rock weathering (ERW) is a biogeochemical carbon dioxide removal (CDR) strategy aiming to accelerate natural geological processes of carbon sequestration through application of crushed silicate rocks, such as basalt, to croplands and forested landscapes. However, the efficacy of the approach when undertaken with basalt, and its potential co-benefits for agriculture, require experimental and field evaluation. Here we report that amending a UK clay-loam agricultural soil with a high loading (10 kg/m2 ) of relatively coarse-grained crushed basalt significantly increased the yield (21 ± 9.4%, SE) of the important C4 cereal Sorghum bicolor under controlled environmental conditions, without accumulation of potentially toxic trace elements in the seeds. Yield increases resulted from the basalt treatment after 120 days without P- and K-fertilizer addition. Shoot silicon concentrations also increased significantly (26 ± 5.4%, SE), with potential benefits for crop resistance to biotic and abiotic stress. Elemental budgets indicate substantial release of base cations important for inorganic carbon removal and their accumulation mainly in the soil exchangeable pools. Geochemical reactive transport modelling, constrained by elemental budgets, indicated CO2 sequestration rates of 2-4 t CO2 /ha, 1-5 years after a single application of basaltic rock dust, including via newly formed soil carbonate minerals whose long-term fate requires assessment through field trials. This represents an approximately fourfold increase in carbon capture compared to control plant-soil systems without basalt. Our results build support for ERW deployment as a CDR technique compatible with spreading basalt powder on acidic loamy soils common across millions of hectares of western European and North American agriculture.

Long-term treatment with kefir probiotics ameliorates cardiac function in spontaneously hypertensive rats.

This work evaluated the effects of long-term kefir treatment in cardiac function (cardiac contractility and calcium-handling proteins) and the central nervous system (CNS) control of the sympathetic signaling in spontaneously hypertensive rats (SHR). Male normotensive rats [Wistar Kyoto rats (WKYs)] and SHRs were divided into three groups: WKYs and SHRs treated with vehicle, and SHRs treated with milk fermented by the grains of kefir (5%; SHR-Kefir; oral gavage, 0.3 ml/100 g daily/9 weeks). At the end of treatment, mean arterial pressure (MAP) and heart rate (HR) were measured by direct arterial catheterization. Hemodynamic parameters (left ventricular systolic pressure, left ventricular isovolumetric relaxation time constant, maximal and minimal pressure decay) were acquired through a left ventricular catheter implantation. Left ventricle protein expressions of phospholamban (PLB), its phosphorylated form (p-PLB) and sarcoplasmic reticulum Ca2+-ATPase (SERCA2a) were determined by Western blot. Tyrosine hydroxylase (TH) protein expression was evaluated via immunofluorescence within the paraventricular nucleus (PVN) of the hypothalamus and the rostral ventrolateral medulla (RVLM). SHR-Kefir group presented lower MAP and HR compared to SHRs. Kefir treatment ameliorated cardiac hypertrophy and promoted reduced expression of PLB, p-PLB and SERCA2a contractile proteins. Within the PVN and RVML, TH protein overexpression observed in SHRs was reduced by probiotic treatment. In addition, kefir improved cardiac hemodynamic parameters in SHR-treated animals. Altogether, the data show that long-term kefir treatment reduced blood pressure by mechanisms involving reduction of cardiac hypertrophy, improvement of cardiac contractility and calcium-handling proteins, and reduction in the CNS regulation of the sympathetic activity.

Transplantation of mesenchymal stem cells genetically engineered to overexpress interleukin-10 promotes alternative inflammatory response in rat model of traumatic brain injury.

BACKGROUND: Traumatic brain injury (TBI) is a major cause for long-term disability, yet the treatments available that improve outcomes after TBI limited. Neuroinflammatory responses are key contributors to determining patient outcomes after TBI. Transplantation of mesenchymal stem cells (MSCs), which release trophic and pro-repair cytokines, represents an effective strategy to reduce inflammation after TBI. One such pro-repair cytokine is interleukin-10 (IL-10), which reduces pro-inflammatory markers and trigger alternative inflammatory markers, such as CD163. In this study, we tested the therapeutic effects of MSCs that were engineered to overexpress IL-10 when transplanted into rats following TBI in the medial frontal cortex. METHODS: Thirty-six hours following TBI, rats were transplanted with MSCs and then assessed for 3 weeks on a battery of behavioral tests that measured motor and cognitive abilities. Histological evaluation was then done to measure the activation of the inflammatory response. Additionally, immunomodulatory effects were evaluated by immunohistochemistry and Western blot analyses. RESULTS: A significant improvement in fine motor function was observed in rats that received transplants of MSCs engineered to overexpress IL-10 (MSCs + IL-10) or MSCs alone compared to TBI + vehicle-treated rats. Although tissue spared was unchanged, anti-inflammatory effects were revealed by a reduction in the number of glial fibrillary acidic protein cells and CD86 cells in both TBI + MSCs + IL-10 and TBI + MSC groups compared to TBI + vehicle rats. Microglial activation was significantly increased in the TBI + MSC group when compared to the sham + vehicle group. Western blot data suggested a reduction in tumor necrosis factor-alpha in the TBI + MSCs + IL-10 group compared to TBI + MSC group. Immunomodulatory effects were demonstrated by a shift from classical inflammation expression (CD86) to an alternative inflammation state (CD163) in both treatments with MSCs and MSCs + IL-10. Furthermore, co-labeling of both CD86 and CD163 was detected in the same cells, suggesting a temporal change in macrophage expression. CONCLUSIONS: Overall, our findings suggest that transplantation of MSCs that were engineered to overexpress IL-10 can improve functional outcomes by providing a beneficial perilesion environment. This improvement may be explained by the shifting of macrophage expression to a more pro-repair state, thereby providing a possible new therapy for treating TBI.

Expression of genes associated with inflammation and iron metabolism in 3T3-L1 cells induced with macrophages-conditioned medium, glucose and iron.

Obesity is characterized by a chronic inflammatory process, with an increased volume of total adipose tissue, especially visceral, which secretes pro-inflammatory cytokines such as TNF-α and IL-6. Hepcidin (Hpc), a main iron metabolism regulator, is synthetized by an IL-6 stimuli, among others, in liver and adipose tissue, favoring an association between the inflammatory process and iron metabolism. Still there are questions remain regarding the interaction of these factors. Our aim was to study the effect of a macrophage-conditioned medium (MCM) on adipocyte cells challenged with glucose and/or iron. We studied the mRNA relative abundance of genes related to inflammation in differentiated 3T3-L1 cells challenged with Fe (40 µM), glucose (20 mM) or Fe/glucose (40 µM/20 mM) with or without MCM for 24 h. We also measured the intracellular iron levels under these conditions. Our results showed that when adipocytes were challenged with MCM, glucose and/or Fe, the intracellular iron and mRNA levels of pro-inflammatory cytokines increased. These responses were higher when all the stimuli were combined with MCM from macrophages. Thus, we showed that combined high glucose/high Fe alone or with MCM may contribute to an increase on intracellular iron and inflammatory response in 3T3-L1 differentiated cells, by increased mRNA levels of IL-6, TNF-α, MCP-1, Hpc and reducing adiponectin levels, enhancing the inflammatory processes.

Modulation of the carboxamidine redox potential through photoinduced spiropyran or fulgimide isomerisation.

Carboxamidines functionalized with either a spiropyran or fulgimide photoswitch were prepared on multigram scales. The thermal, electrochemical, and photochemical ring isomerizations of these compounds were studied and the results compared with related systems. The photochemical isomerisations were found to be reversible and could be followed by 1H NMR and UV-vis spectroscopy. The spiropyran/merocyanine couple was thermally active and an activation enthalpy of 116 kJ mol-1 was measured for ring-opening. These measurements yielded an enthalpy difference of 25 kJ mol-1 between the open and closed states which is consistent with DFT calculations. DFT calculations predicted a charge transfer to the carboxamidine group upon ring closure in the fulgimide and a charge transfer from the carboxamidine group upon switching the spiropyran to the merocyanine form. This was confirmed experimentally by monitoring the change in the oxidation potential assigned to the carboxamidine group. The potential of these molecules to therefore act as a new class of photoresponsive ligands that can modulate the ligand field of a complex is discussed.

Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients.

Preclinical mouse models suggest that the gut microbiome modulates tumor response to checkpoint blockade immunotherapy; however, this has not been well-characterized in human cancer patients. Here we examined the oral and gut microbiome of melanoma patients undergoing anti-programmed cell death 1 protein (PD-1) immunotherapy (n = 112). Significant differences were observed in the diversity and composition of the patient gut microbiome of responders versus nonresponders. Analysis of patient fecal microbiome samples (n = 43, 30 responders, 13 nonresponders) showed significantly higher alpha diversity (P < 0.01) and relative abundance of bacteria of the Ruminococcaceae family (P < 0.01) in responding patients. Metagenomic studies revealed functional differences in gut bacteria in responders, including enrichment of anabolic pathways. Immune profiling suggested enhanced systemic and antitumor immunity in responding patients with a favorable gut microbiome as well as in germ-free mice receiving fecal transplants from responding patients. Together, these data have important implications for the treatment of melanoma patients with immune checkpoint inhibitors.

Cancer Evolution during Immunotherapy.

Immune checkpoint blockade has revolutionized cancer treatment. In this issue of Cell, insights from a longitudinal multi-omics analysis of the largest yet-reported cohort of melanoma patients reveal how tumor and immunity co-evolve during anti-PD-1 therapy.

Opportunity for interprofessional collaborative care-findings from a sample of federally qualified health center patients in the Midwest.

OBJECTIVES: Federally qualified health centers (FQHCs) frequently serve more socio-economically disadvantaged populations; existing literature suggests that underserved groups are more likely to experience various chronic physical and mental health conditions. FQHC patients may have significant needs for various specialty services that are beyond common FQHC providers. This study examines chronic condition prevalence, healthcare satisfaction, and use of multiprovider services in a Midwest FQHC patient population. We also evaluated the potential of interprofessional collaborative practices in FQHC settings. STUDY DESIGN: Cross-sectional study. METHODS: A total of 232 participants were recruited prior to or immediately after their scheduled clinic visit within an FQHC located on the fringes of an urban area. Respondents were invited to complete a brief questionnaire and grant access to their electronic medical records. RESULTS: Nearly half of participants were covered by Medicaid, private insurance carriers (19.4%), or Medicare (17.7%). The most prevalent chronic conditions included diabetes, depression, anxiety, and chronic pain. Almost half (46.6%) of participants were seen by two or three providers; 20% had 7+ office visits in the last year. While 35.3% reported health dissatisfaction, 30.6% reported health satisfaction. When asked if they were satisfied with their health care, nearly 70% reported satisfaction with health care, while only 4.7% reported healthcare dissatisfaction. CONCLUSIONS: The authors of this study recommend an interprofessional collaborate healthcare model be explored to address the complex and multifaceted healthcare needs of this population. Future research in this area should prospectively examine the utility of monitoring patient satisfaction in a collaborative practice setting.