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Measurements of carbon-14-containing carbon monoxide (14CO) in glacial ice are useful for studies of the past oxidative capacity of the atmosphere as well as for reconstructing the past cosmic ray flux. The 14CO abundance in glacial ice represents the combination of trapped atmospheric 14CO and in situ cosmogenic 14CO. The systematics of in situ cosmogenic 14CO production and retention in ice are not fully quantified, posing an obstacle to interpretation of ice core 14CO measurements. Here we provide the first comprehensive characterization of 14CO at an ice accumulation site (Summit, Greenland), including measurements in the ice grains of the firn matrix, firn air and bubbly ice below the firn zone. The results are interpreted with the aid of a firn gas transport model into which we implemented in situ cosmogenic 14C. We find that almost all (≈ 99.5 %) of in situ 14CO that is produced in the ice grains in firn is very rapidly (in <1 year) lost to the open porosity and from there mostly vented to the atmosphere. The timescale of this rapid loss is consistent with what is expected from gas diffusion through ice. The small fraction of in situ 14CO that initially stays in the ice grains continues to slowly leak out to the open porosity at a rate of ≈ 0.6 % yr−1. Below the firn zone we observe an increase in 14CO content with depth that is due to in situ 14CO production by deep-penetrating muons, confirming recent estimates of 14CO production rates in ice via the muon mechanisms and allowing for narrowing constraints on these production rates.

The Pacific cold tongue annual cycle in sea surface temperature is presumed to be driven by Earth's axial tilt1-5 (tilt effect), and thus its phasing should be fixed relative to the calendar. However, its phase and amplitude change dramatically and consistently under various configurations of orbital precession in several Earth System models. Here, we show that the cold tongue possesses another annual cycle driven by the variation in Earth-Sun distance (distance effect) from orbital eccentricity. As the two cycles possess slightly different periodicities6, their interference results in a complex evolution of the net seasonality over a precession cycle. The amplitude from the distance effect increases linearly with eccentricity and is comparable to the amplitude from the tilt effect for the largest eccentricity values over the last million years (e value approximately 0.05)7. Mechanistically, the distance effect on the cold tongue arises through a seasonal longitudinal shift in the Walker circulation and subsequent annual wind forcing on the tropical Pacific dynamic ocean-atmosphere system. The finding calls for reassessment of current understanding of the Pacific cold tongue annual cycle and re-evaluation of tropical Pacific palaeoclimate records for annual cycle phase changes.

Abstract Herein, a robust microporous aluminum tetracarboxylate framework, MIL‐120(Al)‐AP, (MIL, AP: Institute Lavoisier and Ambient Pressure synthesis, respectively) is reported, which exhibits high CO2 uptake (1.9 mmol g−1 at 0.1 bar, 298 K). In situ Synchrotron X‐ray diffraction measurements together with Monte Carlo simulations reveal that this structure offers a favorable CO2 capture configuration with the pores being decorated with a high density of µ2‐OH groups and accessible aromatic rings. Meanwhile, based on calculations and experimental evidence, moderate host‐guest interactions Qst (CO2) value of MIL‐120(Al)‐AP (−40 kJ mol−1) is deduced, suggesting a relatively low energy penalty for full regeneration. Moreover, an environmentally friendly ambient pressure green route, relying on inexpensive raw materials, is developed to prepare MIL‐120(Al)‐AP at the kilogram scale with a high yield while the Metal‐ Organic Framework (MOF) is further shaped with inorganic binders as millimeter‐sized mechanically stable beads. First evidences of its efficient CO2/N2 separation ability are validated by breakthrough experiments while operando IR experiments indicate a kinetically favorable CO2 adsorption over water. Finally, a techno‐economic analysis gives an estimated production cost of ≈ 13 $ kg−1, significantly lower than for other benchmark MOFs. These advancements make MIL‐120(Al)‐AP an excellent candidate as an adsorbent for industrial‐scale CO2 capture processes.

Global emissions of the ozone-depleting gas HCFC-141b (1,1-dichloro-1-fluoroethane, CH3CCl2F) derived from measurements of atmospheric mole fractions increased between 2017 and 2021 despite a fall in reported production and consumption of HCFC-141b for dispersive uses. HCFC-141b is a controlled substance under the Montreal Protocol, and its phase-out is currently underway, after a peak in reported consumption and production in developing (Article 5) countries in 2013. If reported production and consumption are correct, our study suggests that the 2017-2021 rise is due to an increase in emissions from the bank when appliances containing HCFC-141b reach the end of their life, or from production of HCFC-141b not reported for dispersive uses. Regional emissions have been estimated between 2017-2020 for all regions where measurements have sufficient sensitivity to emissions. This includes the regions of northwestern Europe, east Asia, the United States and Australia, where emissions decreased by a total of 2.3 ± 4.6 Ggyr-1, compared to a mean global increase of 3.0 ± 1.2 Ggyr-1 over the same period. Collectively these regions only account for around 30% of global emissions in 2020. We are not able to pinpoint the source regions or specific activities responsible for the recent global emission rise.

We use global airborne observations of propane (C3H8) and ethane (C2H6) from the Atmospheric Tomography (ATom) and HIAPER Pole-to-Pole Observations (HIPPO), as well as U.S.-based aircraft and tower observations by NOAA and from the NCAR FRAPPE campaign as tracers for emissions from oil and gas operations. To simulate global mole fraction fields for these gases, we update the default emissions' configuration of C3H8 used by the global chemical transport model, GEOS-Chem v13.0.0, using a scaled C2H6 spatial proxy. With the updated emissions, simulations of both C3H8 and C2H6 using GEOS-Chem are in reasonable agreement with ATom and HIPPO observations, though the updated emission fields underestimate C3H8 accumulation in the arctic wintertime, pointing to additional sources of this gas in the high latitudes (e.g., Europe). Using a Bayesian hierarchical model, we estimate global emissions of C2H6 and C3H8 from fossil fuel production in 2016-2018 to be 13.3 ± 0.7 (95% CI) and 14.7 ± 0.8 (95% CI) Tg/year, respectively. We calculate bottom-up hydrocarbon emission ratios using basin composition measurements weighted by gas production and find their magnitude is higher than expected and is similar to ratios informed by our revised alkane emissions. This suggests that emissions are dominated by pre-processing activities in oil-producing basins.

The hydroxyl radical (OH) largely determines the atmosphere's oxidative capacity and, thus, the lifetimes of numerous trace gases, including methane (CH4). Hitherto, observation-based approaches for estimating the atmospheric oxidative capacity have primarily relied on using methyl chloroform (MCF), but as the atmospheric abundance of MCF has declined, the uncertainties associated with this method have increased. In this study, we examine the use of five hydrofluorocarbons (HFCs) (HFC-134a, HFC-152a, HFC-365mfc, HFC-245fa, and HFC-32) in multi-species inversions, which assimilate three HFCs simultaneously, as an alternative method to estimate atmospheric OH. We find robust estimates of OH regardless of which combination of the three HFCs are used in the inversions. Our results show that OH has remained fairly stable during our study period from 2004 to 2021, with variations of < 2 % and no significant trend. Inversions including HFC-32 and HFC-152a (the shortest-lived species) indicate a small reduction in OH in 2020 (1.6±0.9 % relative to the mean over 2004–2021 and 0.6±0.9 % lower than in 2019), but considering all inversions, the reduction was only 0.5±1.1 %, and OH was at a similar level to that in 2019.

Abstract Hepatic steatosis is the result of imbalanced nutrient delivery and metabolism in the liver and is the first hallmark of Metabolic dysfunction-associated steatotic liver disease (MASLD). MASLD is the most common chronic liver disease and involves the accumulation of excess lipids in hepatocytes, inflammation, and cancer. Mitochondria play central roles in liver metabolism yet the specific mitochondrial functions causally linked to MASLD remain unclear. Here, we identify Mitochondrial Fission Process 1 protein (MTFP1) as a key regulator of mitochondrial and metabolic activity in the liver. Deletion of Mtfp1 in hepatocytes is physiologically benign in mice yet leads to the upregulation of oxidative phosphorylation (OXPHOS) activity and mitochondrial respiration, independently of mitochondrial biogenesis. Consequently, liver-specific knockout mice are protected against high fat diet-induced steatosis and metabolic dysregulation. Additionally, Mtfp1 deletion inhibits mitochondrial permeability transition pore opening in hepatocytes, conferring protection against apoptotic liver damage in vivo and ex vivo. Our work uncovers additional functions of MTFP1 in the liver, positioning this gene as an unexpected regulator of OXPHOS and a therapeutic candidate for MASLD.

Abstract. The emissions of hydrofluorocarbons (HFCs) have increased significantly in the past 2 decades, primarily as a result of the phaseout of ozone-depleting substances under the Montreal Protocol and the use of HFCs as their replacements. In 2015, large increases were projected in HFC use and emissions in this century in the absence of regulations, contributing up to 0.5 ∘C to global surface warming by 2100. In 2019, the Kigali Amendment to the Montreal Protocol came into force with the goal of limiting the use of HFCs globally, and currently, regulations to limit the use of HFCs are in effect in several countries. Here, we analyze trends in HFC emissions inferred from observations of atmospheric abundances and compare them with previous projections. Total CO2 eq. inferred HFC emissions continue to increase through 2019 (to about 0.8 GtCO2eq.yr-1) but are about 20 % lower than previously projected for 2017–2019, mainly because of the lower global emissionsof HFC-143a. This indicates that HFCs are used much less in industrial and commercial refrigeration (ICR) applications than previously projected. This is supported by data reported by the developed countries and the lower reported consumption of HFC-143a in China. Because this time period preceded the beginning of the Kigali provisions, this reduction cannot be linked directly to the provisions of the Kigali Amendment. However, it could indicate that companies transitioned away from the HFC-143a with its high global warming potential (GWP) for ICR applications in anticipation of national or global mandates. There are two new HFC scenarios developed based (1) on current trends in HFC use and Kigali-independent (K-I) control policies currently existing in several countries and (2) current HFC trends and compliance with the Kigali Amendment (KA-2022). These current policies reduce projected emissions in 2050 from the previously calculated 4.0–5.3 GtCO2eq.yr-1 to 1.9–3.6 GtCO2eq.yr-1. The added provisions of the Kigali Amendment are projected toreduce the emissions further to 0.9–1.0 GtCO2eq.yr-1 in 2050. Without any controls, projections suggest a HFC contribution of0.28–0.44 ∘C to global surface warming by 2100, compared to a temperature contribution of 0.14–0.31 ∘C that is projectedconsidering the national K-I policies current in place. Warming from HFCs is additionally limited by the Kigali Amendment controls to a contribution of about 0.04 ∘C by 2100.

Abstract Objective Prognostic models in patients living with diabetes allow physicians to estimate individual risk based on medical records and biological results. Clinical risk factors are not always all available to evaluate these models so that they may be complemented with models from claims databases. The objective of this study was to develop, validate and compare models predicting the annual risk of severe complications and mortality in patients living with type 2 diabetes (T2D) from a national claims data. Research design and methods Adult patients with T2D were identified in a national medical claims database through their history of treatments or hospitalizations. Prognostic models were developed using logistic regression (LR), random forest (RF) and neural network (NN) to predict annual risk of outcome: severe cardiovascular (CV) complications, other severe T2D-related complications, and all-cause mortality. Risk factors included demographics, comorbidities, the adjusted Diabetes Severity and Comorbidity Index (aDSCI) and diabetes medications. Model performance was assessed using discrimination (C-statistics), balanced accuracy, sensibility and specificity. Results A total of 22,708 patients with T2D were identified, with mean age of 68 years and average duration of T2D of 9.7 years. Age, aDSCI, disease duration, diabetes medications and chronic cardiovascular disease were the most important predictors for all outcomes. Discrimination with C-statistic ranged from 0.715 to 0.786 for severe CV complications, from 0.670 to 0.847 for other severe complications and from 0.814 to 0.860 for all-cause mortality, with RF having consistently the highest discrimination. Conclusion The proposed models reliably predict severe complications and mortality in patients with T2D, without requiring medical records or biological measures. These predictions could be used by payers to alert primary care providers and high-risk patients living with T2D.

Cosmic rays entering the Earth's atmosphere produce showers of secondary particles such as protons, neutrons, and muons. The interaction of these particles with oxygen-16 (16O) in minerals such as ice and quartz can produce carbon-14 (14C). In glacial ice, 14C is also incorporated through trapping of 14C-containing atmospheric gases (14CO2, 14CO, and 14CH4). Understanding the production rates of in situ cosmogenic 14C is important to deconvolve the in situ cosmogenic and atmospheric 14C signals in ice, both of which contain valuable paleoenvironmental information. Unfortunately, the in situ 14C production rates by muons (which are the dominant production mechanism at depths of >6 m solid ice equivalent) are uncertain. In this study, we use measurements of in situ 14C in ancient ice (>50 ka) from the Taylor Glacier, an ablation site in Antarctica, in combination with a 2D ice flow model to better constrain the compound-specific rates of 14C production by muons and the partitioning of in situ 14C between CO2, CO, and CH4. Our measurements show that 33.7 % (±11.4 %; 95 % confidence interval) of the produced cosmogenic 14C forms 14CO and 66.1 % (±11.5 %; 95 % confidence interval) of the produced cosmogenic 14C forms 14CO2. 14CH4 represents a very small fraction (%) of the total. Assuming that the majority of in situ muogenic 14C in ice forms 14CO2, 14CO, and 14CH4, we also calculated muogenic 14C production rates that are lower by factors of 5.7 (3.6–13.9; 95 % confidence interval) and 3.7 (2.0–11.9; 95 % confidence interval) for negative muon capture and fast muon interactions, respectively, when compared to values determined in quartz from laboratory studies (Heisinger et al., 2002a, b) and in a natural setting (Lupker et al., 2015). This apparent discrepancy in muogenic 14C production rates in ice and quartz currently lacks a good explanation and requires further investigation.

Background and aims: Heterozygous familial hypercholesterolemia (HeFH) is increasingly better diagnosed and treatments can improve the cardiovascular prognosis. We evaluated the long-term cardiovascular risk of HeFH using the French REgistry of Familial hypERCHOLesterolemia (REFERCHOL). Methods: We studied HeFH patients diagnosed genetically and clinically by the Dutch Lipid Clinic Network (DLCN) criteria in all lipid clinics across the country and their 5-year risk of cardiovascular events (all fatal and non-fatal acute coronary, cerebral and peripheral arterial disease events, aortic valve replacement surgery) using the French national health data system. Results: The database comprised 3202 individuals, 2010 (62.8%) with genetically verified HeFH and 1192 (37.2%) a DLCN score ≥6. Of these individuals, 2485 (77.6%) were in primary prevention and 717 (22.4%) in secondary prevention. The incidence of cardiovascular events was 24.58 per 1000 person-years for the overall sample, 19.15 in primary prevention and 43.40 in secondary prevention. The incidence of myocardial infarction, cerebral infarction and death was 16.32 per 1000 person-years for the overall sample, 12.93 in primary prevention and 28.08 in secondary prevention. The incidence of aortic valve replacement was 1.78 per 1000 person-years. In the overall sample, at inclusion, 41% were not treated for LDL cholesterol, 48% of these in primary prevention and 20% in secondary prevention and high-dose statins were used by only 24% of individuals, 15% of these in primary prevention and 45% in secondary prevention. Conclusions: The incidence of cardiovascular events in HeFH is high and lipid-lowering treatment is far from optimal. The cardiovascular risk of HeFH is underestimated and patients are inadequately treated.

Permafrost and methane hydrates are large, climate-sensitive old carbon reservoirs that have the potential to emit large quantities of methane, a potent greenhouse gas, as the Earth continues to warm. We present ice core isotopic measurements of methane (Δ14C, δ13C, and δD) from the last deglaciation, which is a partial analog for modern warming. Our results show that methane emissions from old carbon reservoirs in response to deglacial warming were small (

Atmospheric methane (CH4) is a potent greenhouse gas, and its mole fraction has more than doubled since the preindustrial era1. Fossil fuel extraction and use are among the largest anthropogenic sources of CH4 emissions, but the precise magnitude of these contributions is a subject of debate2,3. Carbon-14 in CH4 (14CH4) can be used to distinguish between fossil (14C-free) CH4 emissions and contemporaneous biogenic sources; however, poorly constrained direct 14CH4 emissions from nuclear reactors have complicated this approach since the middle of the 20th century4,5. Moreover, the partitioning of total fossil CH4 emissions (presently 172 to 195 teragrams CH4 per year)2,3 between anthropogenic and natural geological sources (such as seeps and mud volcanoes) is under debate; emission inventories suggest that the latter account for about 40 to 60 teragrams CH4 per year6,7. Geological emissions were less than 15.4 teragrams CH4 per year at the end of the Pleistocene, about 11,600 years ago8, but that period is an imperfect analogue for present-day emissions owing to the large terrestrial ice sheet cover, lower sea level and extensive permafrost. Here we use preindustrial-era ice core 14CH4 measurements to show that natural geological CH4 emissions to the atmosphere were about 1.6 teragrams CH4 per year, with a maximum of 5.4 teragrams CH4 per year (95 per cent confidence limit)-an order of magnitude lower than the currently used estimates. This result indicates that anthropogenic fossil CH4 emissions are underestimated by about 38 to 58 teragrams CH4 per year, or about 25 to 40 per cent of recent estimates. Our record highlights the human impact on the atmosphere and climate, provides a firm target for inventories of the global CH4 budget, and will help to inform strategies for targeted emission reductions9,10.

Mitochondria power the beating heart. Here, Donnarumma et al. show that loss of the inner mitochondrial membrane protein MTFP1 in cardiomyocytes reduces bioenergetic efficiency and cell death resistance leading to heart failure in mice.

Measurement(s) atmospheric ozone • atmospheric carbon dioxide • atmospheric methane • atmospheric carbon monoxide • atmospheric nitrous oxide • atmospheric dimethylsulfide • atmospheric sulfur dioxide • atmospheric gaseous elemental mercury • volatile organic compounds Technology Type(s) ozone analyzer • carbon dioxide analyzer • methane analyzer • carbon monoxide analyzer • nitrous oxide analyzer • dimethylsulfide analyzer • sulfur dioxide analyzer • gaseous elemental mercury analyzer • gas chromatography-mass spectrometry Sample Characteristic - Environment Atmosphere Sample Characteristic - Location central Arctic

Global emissions of the ozone-depleting gas HCFC-141b (1,1-dichloro-1-fluoroethane, CH3CCl2F) derived from measurements of atmospheric mole fractions increased between 2017 and 2021 despite a fall in reported production and consumption of HCFC-141b for dispersive uses. HCFC-141b is a controlled substance under the Montreal Protocol, and its phase-out is currently underway, after a peak in reported consumption and production in developing (Article 5) countries in 2013. If reported production and consumption are correct, our study suggests that the 2017–2021 rise is due to an increase in emissions from the bank when appliances containing HCFC-141b reach the end of their life, or from production of HCFC-141b not reported for dispersive uses. Regional emissions have been estimated between 2017–2020 for all regions where measurements have sufficient sensitivity to emissions. This includes the regions of northwestern Europe, east Asia, the United States and Australia, where emissions decreased by a total of 2.3 ± 4.6 Gg yr−1, compared to a mean global increase of 3.0 ± 1.2 Gg yr−1 over the same period. Collectively these regions only account for around 30 % of global emissions in 2020. We are not able to pinpoint the source regions or specific activities responsible for the recent global emission rise.

This study analyzes future changes in population-weighted degree-days in 48 states over the contiguous U.S. Using temperature data from the NASA Earth Exchange Global Daily Downscaled Projects and population data from NASA Socioeconomic Data and Applications Center, we computed population-weighted degree-days (PHDD and PCDD) and EDD (energy degree-days, PHDD + PCDD) over the 21st century, under a business-as-usual scenario. Results show that although the rising temperature is the primary driver, population distribution and projection play undeniable roles in estimating state-level heating and cooling demand. Throughout the 21st century, the U.S. is projected to experience a heating-to-cooling shift in energy demand, with the number of heating-dominant states dropping from 37 to 17 and the length of cooling seasons extending by 2 months (indicating a corresponding reduction in heating seasons) in all states by late-century. Meanwhile, a more homogenous EDD pattern is expected due to the increasing PCDD and decreasing PHDD, and the peak EDD month will switch from winter to summer in 15 out of 48 states. Our study provides a more nuanced understanding of future heating and cooling demand by examining both annual and monthly variations in the demands and how their relative dominance in a single framework may evolve over time. The study’s state-level perspective can provide valuable insights for policymakers, energy providers, and other stakeholders regarding the forthcoming shift in demand patterns and related building operations and energy consumption at both state and regional levels.

The emissions of hydrofluorocarbons (HFCs) have increased significantly in the past 2 decades, primarily as a result of the phaseout of ozone-depleting substances under the Montreal Protocol and the use of HFCs as their replacements. In 2015, large increases were projected in HFC use and emissions in this century in the absence of regulations, contributing up to 0.5 ∘C to global surface warming by 2100. In 2019, the Kigali Amendment to the Montreal Protocol came into force with the goal of limiting the use of HFCs globally, and currently, regulations to limit the use of HFCs are in effect in several countries. Here, we analyze trends in HFC emissions inferred from observations of atmospheric abundances and compare them with previous projections. Total CO2 eq. inferred HFC emissions continue to increase through 2019 (to about 0.8 GtCO2eq.yr-1) but are about 20 % lower than previously projected for 2017–2019, mainly because of the lower global emissions of HFC-143a. This indicates that HFCs are used much less in industrial and commercial refrigeration (ICR) applications than previously projected. This is supported by data reported by the developed countries and the lower reported consumption of HFC-143a in China. Because this time period preceded the beginning of the Kigali provisions, this reduction cannot be linked directly to the provisions of the Kigali Amendment. However, it could indicate that companies transitioned away from the HFC-143a with its high global warming potential (GWP) for ICR applications in anticipation of national or global mandates. There are two new HFC scenarios developed based (1) on current trends in HFC use and Kigali-independent (K-I) control policies currently existing in several countries and (2) current HFC trends and compliance with the Kigali Amendment (KA-2022). These current policies reduce projected emissions in 2050 from the previously calculated 4.0–5.3 GtCO2eq.yr-1 to 1.9–3.6 GtCO2eq.yr-1. The added provisions of the Kigali Amendment are projected to reduce the emissions further to 0.9–1.0 GtCO2eq.yr-1 in 2050. Without any controls, projections suggest a HFC contribution of 0.28–0.44 ∘C to global surface warming by 2100, compared to a temperature contribution of 0.14–0.31 ∘C that is projected considering the national K-I policies current in place. Warming from HFCs is additionally limited by the Kigali Amendment controls to a contribution of about 0.04 ∘C by 2100.

The detection of increasing global CFC-11 emissions after 2012 alerted society to a possible violation of the Montreal Protocol on Substances that Deplete the Ozone Layer (MP). This alert resulted in parties to the MP taking urgent actions. As a result, atmospheric measurements made in 2019 suggest a sharp decline in global CFC-11 emissions. Despite the success in the detection and mitigation of part of this problem, regions fully responsible for the recent global emission changes in CFC-11 have not yet been identified. Roughly two thirds (60 ± 40 %) of the emission increase between 2008–2012 and 2014–2017 and two thirds (60 ± 30 %) of the decline between 2014–2017 and 2019 were explained by regional emission changes in eastern mainland China. Here, we used atmospheric CFC-11 measurements made from two global aircraft surveys – the HIAPER (High-performance Instrumented Airborne Platform for Environmental Research) Pole-to-Pole Observations (HIPPO) in November 2009–September 2011 and the Atmospheric Tomography Mission (ATom) in August 2016–May 2018, in combination with the global CFC-11 measurements made by the US National Oceanic and Atmospheric Administration during these two periods – to derive global and regional emission changes in CFC-11. Our results suggest Asia accounted for the largest fractions of global CFC-11 emissions in both periods: 43 (37–52) % during November 2009–September 2011 and 57 (49–62) % during August 2016–May 2018. Asia was also primarily responsible for the emission increase between these two periods, accounting for 86 (59–115) % of the global CFC-11 emission rise between the two periods. Besides eastern mainland China, temperate western Asia and tropical Asia also contributed significantly to global CFC-11 emissions during both periods and likely to the global CFC-11 emission increase. The atmospheric observations further provide strong constraints on CFC-11 emissions from North America and Europe, suggesting that each of them accounted for 10 %–15 % of global CFC-11 emissions during the HIPPO period and smaller fractions in the ATom period. For South America, Africa, and Australia, the derived regional emissions had larger dependence on the prior assumptions of emissions and emission changes due to a lower sensitivity of the observations considered here to emissions from these regions. However, significant increases in CFC-11 emissions from southern hemispheric lands were not likely due to the observed increase of north-to-south interhemispheric gradients in atmospheric CFC-11 mole fractions from 2012–2017.

Most papers on kidney stones arising from infection concentrate on the mineral struvite. In this contribution, we would like to call attention to other mineral phases such as highly carbonated calcium phosphate apatite, ammonium urate, and whitlockite, by presenting clinical and chemical data. We start with epidemiological data which emphasize the increase in the prevalence of kidney stones related to infection. Then we present a statistical analysis of more than 85,000 stones which have been analysed at the Laboratoire des Lithiases of Assistance Publique-Hôpitaux de Paris which gives insights regarding the link between urinary tract infection and struvite, carbonated calcium phosphate apatite (carbapatite), and also surprisingly whitlockite. Some information regarding the pathogenesis of kidney stones linked to infection, the nature of the bacteria which have been identified, and the approach to precisely analyse infrared spectra to identify struvite, carbapatite, and whitlockite, conclude this first part. To complete this clinical description, we describe the crystallographic structure and the chemistry of three relevant compounds namely carbonated calcium phosphate, struvite, and whitlockite. To conclude this second part, the dependence of crystallite morphology of struvite on pH and on the presence, or absence, of bacteria, is described. Based on clinical and chemical data, it is becoming clear that struvite is not the only mineral intimately related to renal infectious processes, but that whitlockite and carbapatite with a high carbonation rate are strongly associated with urinary tract infection as well.

Anthropogenic climate change is altering ecological and human systems globally, including in United States (US) national parks, which conserve unique biodiversity and resources. Yet, the magnitude and spatial patterns of climate change across all the parks have been unknown. Here, in the first spatial analysis of historical and projected temperature and precipitation across all 417 US national parks, we show that climate change exposes the national park area more than the US as a whole. This occurs because extensive parts of the national park area are in the Arctic, at high elevations, or in the arid southwestern US. Between 1895 and 2010, mean annual temperature of the national park area increased 1.0 °C ± 0.2 °C century-1 (mean ± standard error), double the US rate. Temperature has increased most in Alaska and its extensive national parks. Annual precipitation of the national park area declined significantly on 12% of national park area, compared to 3% of the US. Higher temperatures due to climate change have coincided with low precipitation in the southwestern US, intensifying droughts in the region. Physical and ecological changes have been detected and attributed mainly to anthropogenic climate change in areas of significant temperature increases in US national parks. From 2000 to 2100, under the highest emissions scenario (representative concentration pathway [RCP] 8.5), park temperatures would increase 3 °C-9 °C, with climate velocities outpacing dispersal capabilities of many plant and animal species. Even under the scenario of reduced emissions (RCP2.6), temperature increases could exceed 2 °C for 58% of national park area, compared to 22% of the US. Nevertheless, greenhouse gas emissions reductions could reduce projected temperature increases in national parks by one-half to two-thirds.

Atmospheric non-methane hydrocarbons (NMHCs) play an important role in the formation of secondary organic aerosols and ozone. After a multidecadal global decline in atmospheric mole fractions of ethane and propane – the most abundant atmospheric NMHCs – previous work has shown a reversal of this trend with increasing atmospheric abundances from 2009 to 2015 in the Northern Hemisphere. These concentration increases were attributed to the unprecedented growth in oil and natural gas (O&NG) production in North America. Here, we supplement this trend analysis building on the long-term (2008–2010; 2012–2020) high-resolution (∼3 h) record of ambient air C2–C7 NMHCs from in situ measurements at the Greenland Environmental Observatory at Summit station (GEOSummit, 72.58 ∘ N, 38.48 ∘ W; 3210 m above sea level). We confirm previous findings that the ethane mole fraction significantly increased by +69.0 [+47.4, +73.2; 95 % confidence interval] ppt yr−1 from January 2010 to December 2014. Subsequent measurements, however, reveal a significant decrease by −58.4 [−64.1, −48.9] ppt yr−1 from January 2015 to December 2018. A similar reversal is found for propane. The upturn observed after 2019 suggests, however, that the pause in the growth of atmospheric ethane and propane might only have been temporary. Discrete samples collected at other northern hemispheric baseline sites under the umbrella of the NOAA cooperative global air sampling network show a similar decrease in 2015–2018 and suggest a hemispheric pattern. Here, we further discuss the potential contribution of biomass burning and O&NG emissions (the main sources of ethane and propane) and conclude that O&NG activities likely played a role in these recent changes. This study highlights the crucial need for better constrained emission inventories.

AimWe aimed to investigate the performance of procalcitonin (PCT) assay between 12 and 36 h after onset of fever (PCT H12-H36) to predict invasive bacterial infection (IBI) (ie, meningitis and/or bacteremia) in febrile neonates.MethodsWe retrospectively included all febrile neonates hospitalized in the general pediatric department in a teaching hospital from January 2013 to December 2019. PCT assay ≤ 0.6 ng/ml was defined as negative. The primary outcome was to study the performance of PCT H12-H36 to predict IBI.ResultsOut of 385 included neonates, IBI was ascertainable for 357 neonates (92.7%). We found 16 IBI: 3 meningitis and 13 bacteremia. Sensitivity and specificity of PCT H12-H36 in the identification of IBI were, respectively, 100% [95% CI 82.9–100%] and 71.8% [95% CI 66.8–76.6%], with positive and negative predictive values of 14.3% [95% CI 8.4–22.2%] and 100% [95% CI 98.8–100%] respectively. Of the 259 neonates who had a PCT assay within the first 12 h of fever (< H12) and a PCT assay after H12-H36, 8 had IBI. Two of these 8 neonates had a negative < H12 PCT but a positive H12-H36 PCT.ConclusionsPCT H12-H36 did not miss any IBI whereas < H12 PCT could missed IBI diagnoses. PCT H12-H36 might be included in clinical decision rule to help physicians to stop early antibiotics in febrile neonates.

Abstract Background Inflammatory vascular disease of the arteries, such as inflamed atheromatous plaques or arteritis, may cause aneurysms or ischemic strokes. In this context, using positron emission tomography (PET) to image inflammation may help select patients who would benefit from appropriate therapeutic interventions. This study sought to assess the usefulness of the 18 kDa translocator protein (TSPO) tracers [11C]-PBR28 and [18F]-PBR06 for imaging inflammatory vascular disease in vitro and in vivo. Immunohistochemistry for macrophage infiltration as well as autoradiography with [18F]-PBR06 were performed on eight paraffin-embedded, formalin-fixed atherosclerosis plaques prospectively collected after carotid endarterectomy of eight patients affected by ischemic stroke. Six different patients, one of whom was also included in the in vitro study, underwent PET imaging. Two patients with carotid stenosis associated with ischemic stroke were imaged with [18F]-PBR06 PET/CT, and four other patients (three with large vessel vasculitis and one with bilateral carotid stenosis but without stroke) were imaged with [11C]-PBR28. Results All in vitro sections showed specific binding of [18F]-PBR06, which co-localized with immunohistochemistry markers for inflammation. However, in vivo TSPO imaging with either [11C]-PBR28 or [18F]-PBR06 was negative in all participants. Conclusion Despite good uptake on surgical samples in vitro, [11C]-PBR28 and [18F]-PBR06 are not viable clinical tools for imaging inflammatory vascular disease. Trial registration: NCT02513589, registered 31 July 2015 and NCT00547976, registered 23 October 2007. https://clinicaltrials.gov .

Abstract Mutations in OPA1 cause autosomal dominant optic atrophy (DOA) as well as DOA+, a phenotype characterized by more severe neurological deficits. OPA1 deficiency causes mitochondrial fragmentation and also disrupts cristae, respiration, mitochondrial DNA (mtDNA) maintenance, and cell viability. It has not yet been established whether phenotypic severity can be modulated by genetic modifiers of OPA1. We screened the entire known mitochondrial proteome (1,531 genes) to identify genes that control mitochondrial morphology using a first‐in‐kind imaging pipeline. We identified 145 known and novel candidate genes whose depletion promoted elongation or fragmentation of the mitochondrial network in control fibroblasts and 91 in DOA+ patient fibroblasts that prevented mitochondrial fragmentation, including phosphatidyl glycerophosphate synthase (PGS1). PGS1 depletion reduces CL content in mitochondria and rebalances mitochondrial dynamics in OPA1‐deficient fibroblasts by inhibiting mitochondrial fission, which improves defective respiration, but does not rescue mtDNA depletion, cristae dysmorphology, or apoptotic sensitivity. Our data reveal that the multifaceted roles of OPA1 in mitochondria can be functionally uncoupled by modulating mitochondrial lipid metabolism, providing novel insights into the cellular relevance of mitochondrial fragmentation.

Abstract Background Targeting G protein-coupled receptors on the surface of cancer cells with peptide ligands is a promising concept for the selective tumor delivery of therapeutically active cargos, including radiometals for targeted radionuclide therapy (TRT). Recently, the radiolanthanide terbium-161 (161Tb) gained significant interest for TRT application, since it decays with medium-energy β-radiation but also emits a significant amount of conversion and Auger electrons with short tissue penetration range. The therapeutic efficiency of radiometals emitting Auger electrons, like 161Tb, can therefore be highly boosted by an additional subcellular delivery into the nucleus, in order to facilitate maximum dose deposition to the DNA. In this study, we describe the design of a multifunctional, radiolabeled neuropeptide-Y (NPY) conjugate, to address radiolanthanides to the nucleus of cells naturally overexpressing the human Y1 receptor (hY1R). By using solid-phase peptide synthesis, the hY1R-preferring [F7,P34]-NPY was modified with a fatty acid, a cathepsin B-cleavable linker, followed by a nuclear localization sequence (NLS), and a DOTA chelator (compound pb12). In this proof-of-concept study, labeling was performed with either native terbium-159 (natTb), as surrogate for 161Tb, or with indium-111 (111In). Results [natTb]Tb-pb12 showed a preserved high binding affinity to endogenous hY1R on MCF-7 cells and was able to induce receptor activation and internalization similar to the hY1R-preferring [F7,P34]-NPY. Specific internalization of the 111In-labeled conjugate into MCF-7 cells was observed, and importantly, time-dependent nuclear uptake of 111In was demonstrated. Study of metabolic stability showed that the peptide is insufficiently stable in human plasma. This was confirmed by injection of [111In]In-pb12 in nude mice bearing MCF-7 xenograft which showed specific uptake only at very early time point. Conclusion The multifunctional NPY conjugate with a releasable DOTA-NLS unit represents a promising concept for enhanced TRT with Auger electron-emitting radiolanthanides. Our research is now focusing on improving the reported concept with respect to the poor plasmatic stability of this promising radiopeptide.

ABSTRACT Meningitis/encephalitis (ME) syndromic diagnostic assays can be applied for the rapid one-step detection of the most common pathogens in cerebrospinal fluid (CSF). However, the comprehensive performance of multiplex assays is still under evaluation. In our multisite university hospital of eastern Paris, France, ME syndromic testing has been gradually implemented since 2017 for patients with neurological symptoms presenting to an adult or pediatric emergency unit. We analyzed the results from the BioFire FilmArray ME panel versus standard routine bacteriology and virology techniques, together with CSF cytology and clinical data, over a 2.5-year period to compare the diagnostic accuracy of the FilmArray ME panel to that of the reference methods. In total, 1,744 CSF samples from 1,334 pediatric and 336 adult patients were analyzed. False-positive (mostly bacterial) and false-negative (mostly viral) cases were deciphered with the help of clinical data. The performance of the FilmArray ME panel in our study was better for bacterial detection (specificity >99%, sensitivity 100%) than viral detection (specificity >99%, sensitivity 75% for herpes simplex virus 1 [HSV-1] and 89% for enterovirus), our study being one of the largest, to date, concerning enteroviruses. The use of a threshold of 10 leukocytes/mm3 considerably increased the positive agreement between the results of the FilmArray ME panel and the clinical features, especially for bacterial pathogens, for which agreement increased from 58% to 87%, avoiding two-thirds of inappropriate testing. Based on this analysis, we propose an algorithm for the use of both syndromic and specific assays for the optimal management of suspected meningitis/encephalitis in adult and pediatric patients. IMPORTANCE Based on our comparative analysis of performances of the diagnostic assays, we propose an algorithm for the use of both syndromic and specific assays, for an optimal care of the meningitis/encephalitis threat in adult and pediatric patients.