Search

Cloud properties are strongly influenced by ice formation; hence, we need to understand the sources of ice-nucleating particles (INPs) around the globe. Boreal forests are known as sources of bioaerosol, and recent work indicates that these dominate the INP spectra above −24 °C. To quantify the INP population at temperatures below −24 °C, we deployed a portable cloud expansion chamber (PINE) in a Finnish boreal forest from 13 March 2018 to 11 May 2018. Using the 6 min time resolution PINE data, we present several lines of evidence that INPs below −24 °C in this location are also from biological sources: (i) an INP parameterization developed for a pine forest site in Colorado, where many INPs were shown to be biological, produced a good fit to our measurements; a moderate correlation of INPs with aerosol concentration larger than 0.5 µm and the fluorescent bioaerosol concentration; (ii) a negative correlation with relative humidity that may relate to enhanced release of bioaerosol at low humidity from local sources such as the prolific lichen population in boreal forests; and (iii) the absence of correlation with ultra-fine particles (3.5 to 50 nm), indicating that new particle formation events are not sources of INPs. This study should motivate further work to establish whether the commonality in bioaerosol ice-nucleating properties between spring in Finland and summer in Colorado is more generally applicable to different coniferous forest locations and times and also to determine to what extent these bioaerosols are transported to locations where they may affect clouds.

Ice crystal formation in mixed-phase clouds is initiated by specific aerosol particles, termed ice-nucleating particles (INPs). Only a tiny fraction of all aerosol particles are INPs, providing a challenge for contemporary INP measurement techniques. Models have shown that the presence of INPs in clouds can impact their radiative properties and induce precipitation formation. However, for a qualified implementation of INPs in models, measurement techniques able to accurately detect the temperature-dependent INP concentration are needed. Here we present measurements of INP concentrations in ambient air under conditions relevant to mixed-phase clouds from a total of 10 INP methods over 2 weeks in October 2018 at the Puy de Dôme observatory in central France. A special focus in this intercomparison campaign was placed on having overlapping sampling periods. Although a variety of different measurement principles were used, the majority of the data show INP concentrations within a factor of 5 of one another, demonstrating the suitability of the instruments to derive model-relevant INP data. Lower values of comparability are likely due to instrument-specific features such as aerosol lamina spreading in continuous-flow diffusion chambers, demonstrating the need to account for such phenomena when interpreting INP concentration data from online instruments. Moreover, consistently higher INP concentrations were observed from aerosol filters collected on the rooftop at the Puy de Dôme station without the use of an aerosol inlet.

Polar nephelometers provide in situ measurements of aerosol angular light scattering and play an essential role in validating numerically calculated phase functions or inversion algorithms used in space-borne and land-based aerosol remote sensing. In this study, we present a prototype of a new polar nephelometer called uNeph. The instrument is designed to measure the phase function, F11, and polarized phase function, -F12/F11, over the scattering range of around 5 to 175∘, with an angular resolution of 1∘ at a wavelength of 532 nm. In this work, we present details of the data processing procedures and instrument calibration approaches. uNeph was validated in a laboratory setting using monodisperse polystyrene latex (PSL) and di-ethyl-hexyl-sebacate (DEHS) aerosol particles over a variety of sizes ranging from 200 to 800 nm. An error model was developed, and the level of agreement between the uNeph measurements and Mie theory was found to be consistent within the uncertainties in the measurements and the uncertainties in the input parameters for the theoretical calculations. The estimated measurement errors were between 5 % and 10 % (relative) for F11 and smaller than ∼ 0.1 (absolute) for -F12/F11. Additionally, by applying the Generalized Retrieval of Aerosol and Surface Properties (GRASP) inversion algorithm to the measurements conducted with broad unimodal DEHS aerosol particles, the volume concentration, size distribution, and refractive index of the ensemble of aerosol particles were accurately retrieved. This paper demonstrates that the uNeph prototype can be used to conduct accurate measurements of aerosol phase function and polarized phase function and to retrieve aerosol properties through inversion algorithms.

The formation of ice particles in Earth's atmosphere strongly influences the dynamics and optical properties of clouds and their impacts on the climate system. Ice formation in clouds is often triggered heterogeneously by ice-nucleating particles (INPs) that represent a very low number of particles in the atmosphere. To date, many sources of INPs, such as mineral and soil dust, have been investigated and identified in the low and mid latitudes. Although less is known about the sources of ice nucleation at high latitudes, efforts have been made to identify the sources of INPs in the Arctic and boreal environments. In this study, we investigate the INP emission potential from high-latitude boreal forests in the mixed-phase cloud regime. We introduce the HyICE-2018 measurement campaign conducted in the boreal forest of Hyytiälä, Finland, between February and June 2018. The campaign utilized the infrastructure of the Station for Measuring Ecosystem-Atmosphere Relations (SMEAR) II, with additional INP instruments, including the Portable Ice Nucleation Chamber I and II (PINC and PINCii), the SPectrometer for Ice Nuclei (SPIN), the Portable Ice Nucleation Experiment (PINE), the Ice Nucleation SpEctrometer of the Karlsruhe Institute of Technology (INSEKT) and the Microlitre Nucleation by Immersed Particle Instrument (µL-NIPI), used to quantify the INP concentrations and sources in the boreal environment. In this contribution, we describe the measurement infrastructure and operating procedures during HyICE-2018, and we report results from specific time periods where INP instruments were run in parallel for inter-comparison purposes. Our results show that the suite of instruments deployed during HyICE-2018 reports consistent results and therefore lays the foundation for forthcoming results to be considered holistically. In addition, we compare measured INP concentrations to INP parameterizations, and we observe good agreement with the Tobo et al. (2013) parameterization developed from measurements conducted in a ponderosa pine forest ecosystem in Colorado, USA.

Biogenic organic precursors play an important role in atmospheric new particle formation (NPF). One of the major precursor species is α-pinene, which upon oxidation can form a suite of products covering a wide range of volatilities. Highly oxygenated organic molecules (HOMs) comprise a fraction of the oxidation products formed. While it is known that HOMs contribute to secondary organic aerosol (SOA) formation, including NPF, they have not been well studied in newly formed particles due to their very low mass concentrations. Here we present gas- and particle-phase chemical composition data from experimental studies of α-pinene oxidation, including in the presence of isoprene, at temperatures (−50 and −30 ∘C) and relative humidities (20 % and 60 %) relevant in the upper free troposphere. The measurements took place at the CERN Cosmics Leaving Outdoor Droplets (CLOUD) chamber. The particle chemical composition was analyzed by a thermal desorption differential mobility analyzer (TD-DMA) coupled to a nitrate chemical ionization–atmospheric pressure interface–time-of-flight (CI-APi-TOF) mass spectrometer. CI-APi-TOF was used for particle- and gas-phase measurements, applying the same ionization and detection scheme. Our measurements revealed the presence of C8−10 monomers and C18−20 dimers as the major compounds in the particles (diameter up to ∼ 100 nm). Particularly, for the system with isoprene added, C5 (C5H10O5−7) and C15 compounds (C15H24O5−10) were detected. This observation is consistent with the previously observed formation of such compounds in the gas phase. However, although the C5 and C15 compounds do not easily nucleate, our measurements indicate that they can still contribute to the particle growth at free tropospheric conditions. For the experiments reported here, most likely isoprene oxidation products enhance the growth of particles larger than 15 nm. Additionally, we report on the nucleation rates measured at 1.7 nm (J1.7 nm) and compared with previous studies, we found lower J1.7 nm values, very likely due to the higher α-pinene and ozone mixing ratios used in the present study.

The abundance of aerosol particles and their ability to catalyze ice nucleation are key parameters to correctly understand and describe the aerosol indirect effect on the climate. Cirrus clouds strongly influence the Earth's radiative budget, but their effect is highly sensitive to their formation mechanism, which is still poorly understood. Sulfate and organics are among the most abundant aerosol components in the troposphere and have also been found in cirrus ice crystal residuals. Most of the studies on ice nucleation at cirrus cloud conditions looked at either purely inorganic or purely organic particles. However, particles in the atmosphere are mostly found as internal mixtures, the ice nucleation ability of which is not yet fully characterized. In this study, we investigated the ice nucleation ability of internally mixed particles composed of crystalline ammonium sulfate (AS) and secondary organic material (SOM) at temperatures between −50 and −65 ∘C. The SOM was generated from the ozonolysis of α-pinene. The experiments were conducted in a large cloud chamber, which also allowed us to simulate various aging processes that the particles may experience during their transport in the atmosphere, like cloud cycling and redistribution of the organic matter. We found that the ice nucleation ability of the mixed AS / SOM particles is strongly dependent on the particle morphology. Small organic mass fractions of 5 wt %–8 wt % condensed on the surface of AS crystals are sufficient to completely suppress the ice nucleation ability of the inorganic component, suggesting that the organic coating is evenly distributed on the surface of the seed particles. In this case, the ice nucleation onset increased from a saturation ratio with respect to ice Sice∼1.30 for the pure AS crystals to ≥1.45 for the SOM-coated AS crystals. However, if such SOM-coated AS crystals are subjected to the mentioned aging processes, they show an improved ice nucleation ability with the ice nucleation onset at Sice∼1.35. We suggest that the aging processes change the particle morphology. The organic matter might redistribute on the surface to form a partially engulfed structure, where the ice-nucleation-active sites of the AS crystals are no longer completely masked by the organic coating, or the morphology of the organic coating layer might transform from a compact to a porous structure. Our results underline the complexity in representing the ice nucleation ability of internally mixed particles in cloud models. They also demonstrate the need to further investigate the impact of atmospheric aging and cloud processing on the morphology and related ice nucleation ability of internally mixed particles.

Ice-nucleating particles (INPs) trigger the formation of cloud ice crystals in the atmosphere. Therefore, they strongly influence cloud microphysical and optical properties and precipitation and the life cycle of clouds. Improving weather forecasting and climate projection requires an appropriate formulation of atmospheric INP concentrations. This remains challenging as the global INP distribution and variability depend on a variety of aerosol types and sources, and neither their short-term variability nor their long-term seasonal cycles are well covered by continuous measurements. Here, we provide the first year-long set of observations with a pronounced INP seasonal cycle in a boreal forest environment. Besides the observed seasonal cycle in INP concentrations with a minimum in wintertime and maxima in early and late summer, we also provide indications for a seasonal variation in the prevalent INP type. We show that the seasonal dependency of INP concentrations and prevalent INP types is most likely driven by the abundance of biogenic aerosol. As current parameterizations do not reproduce this variability, we suggest a new mechanistic description for boreal forest environments which considers the seasonal variation in INP concentrations. For this, we use the ambient air temperature measured close to the ground at 4.2 m height as a proxy for the season, which appears to affect the source strength of biogenic emissions and, thus, the INP abundance over the boreal forest. Furthermore, we provide new INP parameterizations based on the Ice Nucleation Active Surface Site (INAS) approach, which specifically describes the ice nucleation activity of boreal aerosols particles prevalent in different seasons. Our results characterize the boreal forest as an important but variable INP source and provide new perspectives to describe these new findings in atmospheric models.

Objectives: The community-based, longitudinal, Canadian HIV Women's Sexual and Reproductive Health Cohort Study (CHIWOS) explored the experiences of women with HIV in Canada over the past decade. CHIWOS' high-impact publications document significant gaps in the provision of healthcare to women with HIV. We used concept mapping to analyse and present a summary of CHIWOS findings on women's experiences navigating these gaps., Design: Concept mapping procedures were performed in two steps between June 2019 and March 2021. First, two reviewers (AY and PM) independently reviewed CHIWOS manuscripts and conference abstracts written before 1 August 2019 to identify main themes and generate individual concept maps. Next, the preliminary results were presented to national experts, including women with HIV, to consolidate findings into visuals summarising the experiences and care gaps of women with HIV in CHIWOS., Setting: British Columbia, Ontario and Quebec, Canada., Participants: A total of 18 individual CHIWOS team members participated in this study including six lead investigators of CHIWOS and 12 community researchers., Results: Overall, a total of 60 peer-reviewed manuscripts and conference abstracts met the inclusion criteria. Using concept mapping, themes were generated and structured through online meetings. In total, six composite concept maps were co-developed: quality of life, HIV care, psychosocial and mental health, sexual health, reproductive health, and trans women's health. Two summary diagrams were created encompassing the concept map themes, one for all women and one specific to trans women with HIV. Through our analysis, resilience, social support, positive healthy actions and women-centred HIV care were highlighted as strengths leading to well-being for women with HIV., Conclusions: Concept mapping resulted in a composite summary of 60 peer-reviewed CHIWOS publications. This activity allows for priority setting to optimise care and well-being for women with HIV., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Aerosols formed and grown by gas-to-particle processes are a major contributor to smog and haze in megacities, despite the competition between growth and loss rates. Rapid growth rates from ammonium nitrate formation have the potential to sustain particle number in typical urban polluted conditions. This process requires supersaturation of gas-phase ammonia and nitric acid with respect to ammonium nitrate saturation ratios. Urban environments are inhomogeneous. In the troposphere, vertical mixing is fast, and aerosols may experience rapidly changing temperatures. In areas close to sources of pollution, gas-phase concentrations can also be highly variable. In this work we present results from nucleation experiments at -10 °C and 5 °C in the CLOUD chamber at CERN. We verify, using a kinetic model, how long supersaturation is likely to be sustained under urban conditions with temperature and concentration inhomogeneities, and the impact it may have on the particle size distribution. We show that rapid and strong temperature changes of 1 °C min -1 are needed to cause rapid growth of nanoparticles through ammonium nitrate formation. Furthermore, inhomogeneous emissions of ammonia in cities may also cause rapid growth of particles., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Background: Using data from a national cohort study and focus groups, the Women-Centred HIV Care (WCHC) Model was developed to inform care delivery for women living with HIV., Methods: Through an evidence-based, integrated knowledge translation approach, we developed 2 toolkits based on the WCHC Model for service providers and women living with HIV in English and French (Canada's national languages). To disseminate, we distributed printed advertising materials, hosted 3 national webinars and conducted 2 virtual capacity-building training series., Results: A total of 315 individuals attended the webinars, and the average WCHC knowledge increased by 29% (SD 4.3%). In total, 131 service providers engaged in 22 virtual capacity-building training sessions with 21 clinical cases discussed. Learners self-reported increased confidence in 15/15 abilities, including the ability to provide WCHC. As of December 2023, the toolkits were downloaded 7766 times., Conclusions: We successfully developed WCHC toolkits and shared them with diverse clinical and community audiences through various dissemination methods., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article.

Regular endurance exercise training is an effective intervention for the maintenance of metabolic health and the prevention of many age-associated chronic diseases. Several metabolic and inflammatory factors are involved in the health-promoting effects of exercise training, but regulatory mechanisms remain poorly understood. Cellular senescence-a state of irreversible growth arrest-is considered a basic mechanism of aging. Senescent cells accumulate over time and promote a variety of age-related pathologies from neurodegenerative disorders to cancer. Whether long-term intensive exercise training affect the accumulation of age-associated cellular senescence is still unclear. Here, we show that the classical senescence markers p16 and IL-6 were markedly higher in the colon mucosa of middle-aged and older overweight adults than in young sedentary individuals, but this upregulation was significantly blunted in age-matched endurance runners. Interestingly, we observe a linear correlation between the level of p16 and the triglycerides to HDL ratio, a marker of colon adenoma risk and cardiometabolic dysfunction. Our data suggest that chronic high-volume high-intensity endurance exercise can play a role in preventing the accumulation of senescent cells in cancer-prone tissues like colon mucosa with age. Future studies are warranted to elucidate if other tissues are also affected, and what are the molecular and cellular mechanisms that mediate the senopreventative effects of different forms of exercise training., (© 2023. The Author(s).)

The mechanistic pathway by which high relative humidity (RH) affects gas-particle partitioning remains poorly understood, although many studies report increased secondary organic aerosol (SOA) yields at high RH. Here, we use real-time, molecular measurements of both the gas and particle phase to provide a mechanistic understanding of the effect of RH on the partitioning of biogenic oxidized organic molecules (from α-pinene and isoprene) at low temperatures (243 and 263 K) at the CLOUD chamber at CERN. We observe increases in SOA mass of 45 and 85% with increasing RH from 10-20 to 60-80% at 243 and 263 K, respectively, and attribute it to the increased partitioning of semi-volatile compounds. At 263 K, we measure an increase of a factor 2-4 in the concentration of C 10 H 16 O 2-3 , while the particle-phase concentrations of low-volatility species, such as C 10 H 16 O 6-8 , remain almost constant. This results in a substantial shift in the chemical composition and volatility distribution toward less oxygenated and more volatile species at higher RH (e.g., at 263 K, O/C ratio = 0.55 and 0.40, at RH = 10 and 80%, respectively). By modeling particle growth using an aerosol growth model, which accounts for kinetic limitations, we can explain the enhancement in the semi-volatile fraction through the complementary effect of decreased compound activity and increased bulk-phase diffusivity. Our results highlight the importance of particle water content as a diluting agent and a plasticizer for organic aerosol growth.

Dimethyl sulfide (DMS) influences climate via cloud condensation nuclei (CCN) formation resulting from its oxidation products (mainly methanesulfonic acid, MSA, and sulfuric acid, H 2 SO 4 ). Despite their importance, accurate prediction of MSA and H 2 SO 4 from DMS oxidation remains challenging. With comprehensive experiments carried out in the Cosmics Leaving Outdoor Droplets (CLOUD) chamber at CERN, we show that decreasing the temperature from +25 to -10 °C enhances the gas-phase MSA production by an order of magnitude from OH-initiated DMS oxidation, while H 2 SO 4 production is modestly affected. This leads to a gas-phase H 2 SO 4 -to-MSA ratio (H 2 SO 4 /MSA) smaller than one at low temperatures, consistent with field observations in polar regions. With an updated DMS oxidation mechanism, we find that methanesulfinic acid, CH 3 S(O)OH, MSIA, forms large amounts of MSA. Overall, our results reveal that MSA yields are a factor of 2-10 higher than those predicted by the widely used Master Chemical Mechanism (MCMv3.3.1), and the NO x effect is less significant than that of temperature. Our updated mechanism explains the high MSA production rates observed in field observations, especially at low temperatures, thus, substantiating the greater importance of MSA in the natural sulfur cycle and natural CCN formation. Our mechanism will improve the interpretation of present-day and historical gas-phase H 2 SO 4 /MSA measurements.

New particle formation in the upper free troposphere is a major global source of cloud condensation nuclei (CCN) 1-4 . However, the precursor vapours that drive the process are not well understood. With experiments performed under upper tropospheric conditions in the CERN CLOUD chamber, we show that nitric acid, sulfuric acid and ammonia form particles synergistically, at rates that are orders of magnitude faster than those from any two of the three components. The importance of this mechanism depends on the availability of ammonia, which was previously thought to be efficiently scavenged by cloud droplets during convection. However, surprisingly high concentrations of ammonia and ammonium nitrate have recently been observed in the upper troposphere over the Asian monsoon region 5,6 . Once particles have formed, co-condensation of ammonia and abundant nitric acid alone is sufficient to drive rapid growth to CCN sizes with only trace sulfate. Moreover, our measurements show that these CCN are also highly efficient ice nucleating particles-comparable to desert dust. Our model simulations confirm that ammonia is efficiently convected aloft during the Asian monsoon, driving rapid, multi-acid HNO 3 -H 2 SO 4 -NH 3 nucleation in the upper troposphere and producing ice nucleating particles that spread across the mid-latitude Northern Hemisphere., (© 2022. The Author(s).)

Intense new particle formation events are regularly observed under highly polluted conditions, despite the high loss rates of nucleated clusters. Higher than expected cluster survival probability implies either ineffective scavenging by pre-existing particles or missing growth mechanisms. Here we present experiments performed in the CLOUD chamber at CERN showing particle formation from a mixture of anthropogenic vapours, under condensation sinks typical of haze conditions, up to 0.1 s -1 . We find that new particle formation rates substantially decrease at higher concentrations of pre-existing particles, demonstrating experimentally for the first time that molecular clusters are efficiently scavenged by larger sized particles. Additionally, we demonstrate that in the presence of supersaturated gas-phase nitric acid (HNO 3 ) and ammonia (NH 3 ), freshly nucleated particles can grow extremely rapidly, maintaining a high particle number concentration, even in the presence of a high condensation sink. Such high growth rates may explain the high survival probability of freshly formed particles under haze conditions. We identify under what typical urban conditions HNO 3 and NH 3 can be expected to contribute to particle survival during haze., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Background: In Canada, as is found globally, women of reproductive age are a growing demographic of persons living with HIV. Combination antiretroviral therapy (cART) treatment enables women living with HIV (WLWH) to become pregnant without perinatal transmission, and they are increasingly planning to become pregnant. Since 2014, Canadian guidelines no longer recommend routine elective cesarean birth (CB) for women who are virally suppressed and receiving cART. It is unknown whether their obstetric care has changed since this update. Our objective was to describe trends in cesarean births among WLWH in Ontario, Canada, over a 12-year period., Methods: Our research is co-led and codesigned with WLWH. We conducted a retrospective population-level cohort study using linked health administrative databases at ICES (formally, the Institute for Clinical and Evaluative Sciences). Participants were all women who gave birth in Ontario, between 2006/07 and 2017/18. We assessed their intrapartum characteristics and used multivariable regression to determine an association between HIV status and CB, controlling for sociodemographic and clinical variables., Results: Since 2014, the overall proportion of CB among WLWH remained stable and was higher than among women without HIV (39.9% vs 29.0%, P < 0.001). In addition, the proportion of primary CB decreased between 2006 and 2010 and between 2014 and 2018 (28.5%-19.3%), whereas the proportion of repeat CB increased (13.1%-20.5%, P = 0.013)., Conclusions: Because of decreasing HIV-related indications for CB, more practitioners may be following the guidelines for first-time mothers. Currently, no guidelines exist for care of WLWH with a previous CB, and opportunities for vaginal birth may be missed in this population., (© 2021 Wiley Periodicals LLC.)

Iodic acid (HIO 3 ) is known to form aerosol particles in coastal marine regions, but predicted nucleation and growth rates are lacking. Using the CERN CLOUD (Cosmics Leaving Outdoor Droplets) chamber, we find that the nucleation rates of HIO 3 particles are rapid, even exceeding sulfuric acid-ammonia rates under similar conditions. We also find that ion-induced nucleation involves IO 3 - and the sequential addition of HIO 3 and that it proceeds at the kinetic limit below +10°C. In contrast, neutral nucleation involves the repeated sequential addition of iodous acid (HIO 2 ) followed by HIO 3 , showing that HIO 2 plays a key stabilizing role. Freshly formed particles are composed almost entirely of HIO 3 , which drives rapid particle growth at the kinetic limit. Our measurements indicate that iodine oxoacid particle formation can compete with sulfuric acid in pristine regions of the atmosphere., (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Early prediction of COVID-19 in-hospital mortality relies usually on patients' preexisting comorbidities and is rarely reproducible in independent cohorts. We wanted to compare the role of routinely measured biomarkers of immunity, inflammation, and cellular damage with preexisting comorbidities in eight different machine-learning models to predict mortality, and evaluate their performance in an independent population. We recruited and followed-up consecutive adult patients with SARS-Cov-2 infection in two different Italian hospitals. We predicted 60-day mortality in one cohort (development dataset, n = 299 patients, of which 80% was allocated to the development dataset and 20% to the training set) and retested the models in the second cohort (external validation dataset, n = 402). Demographic, clinical, and laboratory features at admission, treatments and disease outcomes were significantly different between the two cohorts. Notably, significant differences were observed for %lymphocytes (p < 0.05), international-normalized-ratio (p < 0.01), platelets, alanine-aminotransferase, creatinine (all p < 0.001). The primary outcome (60-day mortality) was 29.10% (n = 87) in the development dataset, and 39.55% (n = 159) in the external validation dataset. The performance of the 8 tested models on the external validation dataset were similar to that of the holdout test dataset, indicating that the models capture the key predictors of mortality. The shap analysis in both datasets showed that age, immune features (%lymphocytes, platelets) and LDH substantially impacted on all models' predictions, while creatinine and CRP varied among the different models. The model with the better performance was model 8 (60-day mortality AUROC 0.83 ± 0.06 in holdout test set, 0.79 ± 0.02 in external validation dataset). The features that had the greatest impact on this model's prediction were age, LDH, platelets, and %lymphocytes, more than comorbidities or inflammation markers, and these findings were highly consistent in both datasets, likely reflecting the virus effect at the very beginning of the disease., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Author(s).)

A list of authors and their affiliations appears at the end of the paper New-particle formation is a major contributor to urban smog 1,2 , but how it occurs in cities is often puzzling 3 . If the growth rates of urban particles are similar to those found in cleaner environments (1-10 nanometres per hour), then existing understanding suggests that new urban particles should be rapidly scavenged by the high concentration of pre-existing particles. Here we show, through experiments performed under atmospheric conditions in the CLOUD chamber at CERN, that below about +5 degrees Celsius, nitric acid and ammonia vapours can condense onto freshly nucleated particles as small as a few nanometres in diameter. Moreover, when it is cold enough (below -15 degrees Celsius), nitric acid and ammonia can nucleate directly through an acid-base stabilization mechanism to form ammonium nitrate particles. Given that these vapours are often one thousand times more abundant than sulfuric acid, the resulting particle growth rates can be extremely high, reaching well above 100 nanometres per hour. However, these high growth rates require the gas-particle ammonium nitrate system to be out of equilibrium in order to sustain gas-phase supersaturations. In view of the strong temperature dependence that we measure for the gas-phase supersaturations, we expect such transient conditions to occur in inhomogeneous urban settings, especially in wintertime, driven by vertical mixing and by strong local sources such as traffic. Even though rapid growth from nitric acid and ammonia condensation may last for only a few minutes, it is nonetheless fast enough to shepherd freshly nucleated particles through the smallest size range where they are most vulnerable to scavenging loss, thus greatly increasing their survival probability. We also expect nitric acid and ammonia nucleation and rapid growth to be important in the relatively clean and cold upper free troposphere, where ammonia can be convected from the continental boundary layer and nitric acid is abundant from electrical storms 4,5 .

Objective: The availability of public health information for optimised supportive care is critical during the COVID-19 pandemic. We describe the first case of COVID-19 complicated by Takotsubo cardiomyopathy., Materials and Methods: We report the clinical, laboratory and radiological findings of a patient with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)., Results: The nasopharyngeal swab was positive for SARS-CoV-2 and x-ray images demonstrated pathognomonic pneumonia. The patient developed tachycardia and the echocardiogram confirmed the diagnosis of Takotsubo cardiomyopathy., Conclusions: Doctors should be aware of the need to thoroughly study this new infection in order to understand its underlying mechanisms and related complications., Learning Points: We report the first case of Takotsubo cardiomyopathy associated with COVID-19.We discuss a rare presentation in the current pandemic.COVID-19 can be associated with cardiac complications, even after the onset of pneumonia, and so strict monitoring of these patients is essential., Competing Interests: Conflicts of Interests: The Authors declare that there are no competing interests., (© EFIM 2020.)

Motivated by progressive climate-change influence on ice degradation in caves, in this paper we present a novel methodology to investigate the link between air dynamics and ice melting. Specifically, we use surveys available for the Leupa ice cave (LIC), located in the Canin-Kanin group in the southeastern Alps and a general purpose computational fluid dynamics model (CFD). Detailed numerical simulations are evaluated on the basis of well-established approaches that consider domain, grid, boundary-conditions, turbulence closure models, buoyancy effects, porous media properties and verification with measured data. External atmospheric conditions are the main trigger for internal circulation but morphology and thermal characteristics of ice and bedrock induce a dynamical process of heat exchange ultimately responsible for ice melting. This process is generally poorly documented in real conditions. Using CFD analyses we show that both in summer and winter, warm and cold air currents within the cave are "disturbed" by several vortices and stagnation zones which locally modify the energy balance. To account for this we introduce a macroscopic physical model based on energy balance between ice surfaces and the inner ice cave airflow to determine the heat exchanged between ice and air. Using this model, a prediction of ice thickness decay over time is obtained. In the case of LIC a reduction of initial 4 cm per year is first obtained with projection of a much faster increase. The methodology is general and easily extendable to other sites, proving to be a powerful method to estimate ice evolution in caves induced by external and internal forcing., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Hypertriglyceridemia is an independent risk factor for cardiovascular disease. Dietary interventions based on protein restriction (PR) reduce circulating triglycerides (TGs), but underlying mechanisms and clinical relevance remain unclear. Here, we show that 1 week of a protein-free diet without enforced calorie restriction significantly lowered circulating TGs in both lean and diet-induced obese mice. Mechanistically, the TG-lowering effect of PR was due, in part, to changes in very low-density lipoprotein (VLDL) metabolism both in liver and peripheral tissues. In the periphery, PR stimulated VLDL-TG consumption by increasing VLDL-bound APOA5 expression and promoting VLDL-TG hydrolysis and clearance from circulation. The PR-mediated increase in Apoa5 expression was controlled by the transcription factor CREBH, which coordinately regulated hepatic expression of fatty acid oxidation-related genes, including Fgf21 and Ppara. The CREBH-APOA5 axis activation upon PR was intact in mice lacking the GCN2-dependent amino acid-sensing arm of the integrated stress response. However, constitutive hepatic activation of the amino acid-responsive kinase mTORC1 compromised CREBH activation, leading to blunted APOA5 expression and PR-recalcitrant hypertriglyceridemia. PR also contributed to hypotriglyceridemia by reducing the rate of VLDL-TG secretion, independently of activation of the CREBH-APOA5 axis. Finally, a randomized controlled clinical trial revealed that 4-6 weeks of reduced protein intake (7%-9% of calories) decreased VLDL particle number, increased VLDL-bound APOA5 expression, and lowered plasma TGs, consistent with mechanistic conservation of PR-mediated hypotriglyceridemia in humans with translational potential as a nutraceutical intervention for dyslipidemia.

Calorie restriction (CR) is an effective strategy to delay the onset and progression of aging phenotypes in a variety of organisms. Several molecular players are involved in the anti-aging effects of CR, but mechanisms of regulation are poorly understood. Cellular senescence-a cellular state of irreversible growth arrest-is considered a basic mechanism of aging. Senescent cells accumulate with age and promote a number of age-related pathologies. Whether environmental conditions such as diet affect the accumulation of cellular senescence with age is still unclear. Here, we show that a number of classical transcriptomic markers of senescent cells are reduced in adult but relatively young mice under CR. Moreover, we demonstrate that such senescence markers are not induced in the colon of middle-age human volunteers under CR in comparison with age-matched volunteers consuming normal Western diets. Our data support the idea that the improvement in health span observed in different organisms under CR might be partly due to a reduction in the number of senescent cells., (© 2018 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.)

Consuming a Mediterranean diet rich in minimally processed plant foods has been associated with a reduced risk of developing multiple chronic diseases and increased life expectancy. Data from several randomized clinic trials have demonstrated a beneficial effect in the primary and secondary prevention of cardiovascular disease, type 2 diabetes, atrial fibrillation, and breast cancer. The exact mechanism by which an increased adherence to the traditional Mediterranean diet exerts its favorable effects is not known. However, accumulating evidence indicates that the five most important adaptations induced by the Mediterranean dietary pattern are: (a) lipid-lowering effect, (b) protection against oxidative stress, inflammation and platelet aggregation, (c) modification of hormones and growth factors involved in the pathogenesis of cancer, (d) inhibition of nutrient sensing pathways by specific amino acid restriction, and (e) gut microbiota-mediated production of metabolites influencing metabolic health. More studies are needed to understand how single modifications of nutrients typical of the Mediterranean diet interact with energy intake, energy expenditure, and the microbiome in modulating the key mechanisms that promote cellular, tissue, and organ health during aging.

Background: Associations between HIV-related stigma and reduced antiretroviral therapy (ART) adherence are widely established, yet the mechanisms accounting for this relationship are underexplored. There has been less attention to HIV-related stigma and its associations with ART initiation and current ART use. We examined pathways from HIV-related stigma to ART initiation, current ART use, and ART adherence among women living with HIV in Canada., Methods: We used baseline survey data from a national cohort of women living with HIV in Canada (n = 1425). Structural equation modeling using weighted least squares estimation methods was conducted to test the direct effects of HIV-related stigma dimensions (personalized, negative self-image, and public attitudes) on ART initiation, current ART use, and 90% ART adherence, and indirect effects through depression and HIV disclosure concerns, adjusting for sociodemographic factors., Results: In the final model, the direct paths from personalized stigma to ART initiation (β = -0.104, P < 0.05) and current ART use (β = -0.142, P < 0.01), and negative self-image to ART initiation (β = -0.113, P < 0.01) were significant, accounting for the mediation effects of depression and HIV disclosure concerns. Depression mediated the pathways from personalized stigma to ART adherence, and negative self-image to current ART use and ART adherence. Final model fit indices suggest that the model fit the data well [χ(25) = 90.251, P < 0.001; comparative fit index = 0.945; root-mean-square error of approximation = 0.044]., Conclusions: HIV-related stigma is associated with reduced likelihood of ART initiation and current ART use, and suboptimal ART adherence. To optimize the benefit of ART among women living with HIV, interventions should reduce HIV-related stigma and address depression.

Obesity, metabolic syndrome, and hyperleptinemia are associated with aging and age-associated diseases including prostate cancer. One experimental approach to inhibit tumor growth is to reduce dietary protein intake and hence levels of circulating amino acids. Dietary protein restriction (PR) increases insulin sensitivity and suppresses prostate cancer cell tumor growth in animal models, providing a rationale for clinical trials. We sought to demonstrate that biomarkers derived from plasma extracellular vesicles (EVs) reflect systemic leptin and insulin signaling and respond to dietary interventions. We studied plasma samples from men with prostate cancer awaiting prostatectomy who participated in a randomized trial of one month of PR or control diet. We found increased levels of leptin receptor in the PR group in total plasma EVs and in a subpopulation of plasma EVs expressing the neuronal marker L1CAM. Protein restriction also shifted the phosphorylation status of the insulin receptor signal transducer protein IRS1 in L1CAM+ EVs in a manner suggestive of improved insulin sensitivity. Dietary PR modifies indicators of leptin and insulin signaling in circulating EVs. These findings are consistent with improved insulin and leptin sensitivity in response to PR and open a new window for following physiologic responses to dietary interventions in humans., (© 2017 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.)

In 1948, the World Health Organization defined health as 'a state of complete physical, mental, and social well-being, and not merely the absence of disease or infirmity'. Detractors claim that this definition of health is utopian and unrealistic. However, accumulating evidence from experimental studies suggests that aging is not inevitably linked with the development of chronic diseases, and the age-associated accumulation of molecular damage can be prevented or greatly delayed by dietary and genetic manipulations that downregulate key cellular nutrient-sensing pathways. Nonetheless, to obtain a state of complete physical, mental, and social well-being, we as human beings need to go beyond nutrition or pharmacological treatments and implement a combination of interventions that enhance not only our metabolic health but also our psychological, emotional, intellectual and spiritual development, our social relationships and cultural well-being. This perspective highlights a range of scientific research-based interventions that can potentially be used to promote human health and longevity. We will also briefly address the importance of environmental health in achieving this goal., (© 2016 S. Karger AG, Basel.)

Protein-restricted (PR), high-carbohydrate diets improve metabolic health in rodents, yet the precise dietary components that are responsible for these effects have not been identified. Furthermore, the applicability of these studies to humans is unclear. Here, we demonstrate in a randomized controlled trial that a moderate PR diet also improves markers of metabolic health in humans. Intriguingly, we find that feeding mice a diet specifically reduced in branched-chain amino acids (BCAAs) is sufficient to improve glucose tolerance and body composition equivalently to a PR diet via metabolically distinct pathways. Our results highlight a critical role for dietary quality at the level of amino acids in the maintenance of metabolic health and suggest that diets specifically reduced in BCAAs, or pharmacological interventions in this pathway, may offer a translatable way to achieve many of the metabolic benefits of a PR diet., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Calorie restriction (CR) retards aging, acts as a hormetic intervention, and increases serum corticosterone and HSP70 expression in rodents. However, less is known regarding the effects of CR on these factors in humans. Serum cortisol and molecular chaperones and autophagic proteins were measured in the skeletal muscle of subjects on CR diets for 3-15 years and in control volunteers. Serum cortisol was higher in the CR group than in age-matched sedentary and endurance athlete groups (15.6 ± 4.6 ng/dl versus 12.3 ± 3.9 ng/dl and 11.2 ± 2.7 ng/dl, respectively; p ≤ 0.001). HSP70, Grp78, beclin-1, and LC3 mRNA and/or protein levels were higher in the skeletal muscle of the CR group compared to controls. Our data indicate that CR in humans is associated with sustained rises in serum cortisol, reduced inflammation, and increases in key molecular chaperones and autophagic mediators involved in cellular protein quality control and removal of dysfunctional proteins and organelles., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Reduced dietary protein intake and intermittent fasting (IF) are both linked to healthy longevity in rodents, and are effective in inhibiting cancer growth. The molecular mechanisms underlying the beneficial effects of chronic protein restriction (PR) and IF are unclear, but may be mediated in part by a down-regulation of the IGF/mTOR pathway. In this study we compared the effects of PR and IF on tumor growth in a xenograft mouse model of breast cancer. We also investigated the effects of PR and IF on the mechanistic Target Of Rapamycin (mTOR) pathway, inhibition of which extends lifespan in model organisms including mice. The mTOR protein kinase is found in two distinct complexes, of which mTOR complex 1 (mTORC1) is responsive to acute treatment with amino acids in cell culture and in vivo. We found that both PR and IF inhibit tumor growth and mTORC1 phosphorylation in tumor xenografts. In somatic tissues, we found that PR, but not IF, selectively inhibits the activity of the amino acid sensitive mTORC1, while the activity of the second mTOR complex, mTORC2, was relatively unaffected by PR. In contrast, IF resulted in increased S6 phosphorylation in multiple metabolic tissues. Our work represents the first finding that PR may reduce mTORC1 activity in tumors and multiple somatic tissues, and suggest that PR may represent a highly translatable option for the treatment not only of cancer, but also other age-related diseases.

We present a measurement of the spin-dependent cross sections for the 3He over -->(e over -->,e')X reaction in the quasielastic and resonance regions at a four-momentum transfer 0.1< or =Q2< or =0.9 GeV2. The spin-structure functions have been extracted and used to evaluate the nuclear Burkhardt-Cottingham and extended Gerasimov-Drell-Hearn sum rules for the first time. The data are also compared to an impulse approximation calculation and an exact three-body Faddeev calculation in the quasielastic region.

We have measured the spin structure functions g(1) and g(2) of 3He in a double-spin experiment by inclusively scattering polarized electrons at energies ranging from 0.862 to 5.058 GeV off a polarized 3He target at a 15.5 degrees scattering angle. Excitation energies covered the resonance and the onset of the deep inelastic regions. We have determined for the first time the Q2 evolution of Gamma(1)(Q2)= integral (1)(0)g(1)(x,Q2)dx, Gamma(2)(Q2)= integral (1)(0)g(2)(x,Q2)dx, and d(2)(Q2)= integral (1)(0)x(2)[2g(1)(x,Q2)+3g(2)(x,Q2)]dx for the neutron in the range 0.1< or =Q2< or =0.9 GeV2 with good precision. Gamma(1)(Q2) displays a smooth variation from high to low Q2. The Burkhardt-Cottingham sum rule holds within uncertainties and d(2) is nonzero over the measured range.

Aim: to verify the capacity of basic and instrumental activities of daily living (BADL and IADL) disability scales and of a performance-based test (Physical Performance Test; PPT) to detect the effect on the functional capacity of several common chronic conditions in elderly people., Method: a cross-sectional survey of the entire population aged 70 and over, living in Ospitaletto (Brescia, northern Italy)-549 subjects; 89.6% of the eligible population; 179 males and 370 females-was carried out in 1992. A multi-dimensional questionnaire administered at the subject's home was used to collect information on demographics, presence of several common chronic diseases and BADL and IADL. Objective physical capacity was assessed using the PPT., Results: only cognitive deterioration and depression were independently associated with disability, as detected by BADL or IADL scales. Cognitive deterioration, stroke, parkinsonism, heart disease and hearing and visual loss were independently associated with PPT. The performance at PPT remained statistically associated with most of the same diseases when the analysis was restricted to subjects with no BADL or IADL disability., Conclusion: a performance-based measure, such as PPT, may detect a functional limitation before it becomes measurable by traditional self-reported BADL and IADL scales.

In a geriatric evaluation and rehabilitation unit (GERU), 258 elderly patients (M: 71, F: 187; mean age 77.4 +/- 7.5) scoring 22 or more at Mini-Mental State Examination (MMSE) consecutively admitted were assessed in order to evaluate the effects of non-steroidal anti-inflammatory drugs (NSAID) chronic treatment on cognitive status in non-demented elderly patients. Sixty-six patients (25.6%) were considered chronic NSAID users. Patients chronically assuming NSAADs showed a significantly higher MMSE score than non-users (26.9+/-2.1 vs 25.7+/-2.5, P<0.0005 ). After controlling for potential confounders in a multivariate model, chronic NSAID use remained independently associated with MMSE score. The results support a positive association between chronic NSAID use and cognitive function in non-demented elderly patients. Randomized controlled trials will be needed to definitively prove this beneficial effect.

Factors related to length of stay were examined in 295 elderly patients (mean age = 79.0 +/- 7.3, range 65-94; males = 75, females = 220), consecutively admitted to a Geriatric Evaluation and Rehabilitation Unit (GERU, P. Richiedei Hospital, Gussago, Brescia, Italy) over a twelve-month period (November 1, 1993-October 31, 1994). Mini Mental State Examination (MMSE), Geriatric Depression Scale (GDS), Basic Activities of Daily Living (BADL), Instrumental Activities of Daily Living (IADL), Tinetti Scale, Prognostic Nutritional Index (PNI), number of diseases and number of administered drugs were evaluated. An index of Disease Severity (IDS) was utilized to estimate the level of comorbidity severity. Three comorbidity classes were thus defined: I) patients with no disease of relevant severity; II) patients with only one disease of relevant severity accompanied by clinically significant comorbidity; and III) patients with two or more relevant diseases. The variables associated with the length of stay proved to be classes of comorbidity, MMSE, dependence in BADL and IADL, Tinetti scale, and PNI. The association of longer length of stay with greater comorbidity was enhanced by impairment in gait and balance (Tinetti < 18) and malnutrition (PNI > 45). These data suggest that the length of stay in hospital is related to comorbidity in patients with conditions of physical and biomedical frailty.

Objective: To evaluate the relationship between change in depressive symptoms and in-hospital physical rehabilitation in elderly women., Design: Longitudinal study., Setting: Hospital facility (geriatric evaluation and rehabilitation unit)., Patients: One hundred twenty-three elderly inpatient women (mean age: 78.4+/-6.9 years, range 60 to 93) with good cognitive status (Mini Mental State Examination: 23.1+/-5.1) consecutively admitted over a 7-month period., Intervention: Physical therapy tailored to individual needs (five sessions a week of 30 to 45 minutes each)., Main Outcomes Measures: On admission: cognition (MMSE), depressive symptoms (Geriatric Depression Scale [GDS]), functional status (basic and instrumental activities of daily living [BADL, IADL], Tinetti scale), and somatic health. On discharge: depressive symptoms and gait and balance performances (Tinetti scale)., Results: Seventy-five patients (61%) did not show changes on Tinetti scale over the hospitalization period and 48(39%) had a change of 3 or more points. Nonresponders had no change of GDS over the hospitalization period for all levels of physical disability on admission, whereas responders had relevant improvement of depressive symptoms when markedly disabled on admission, and progressively smaller improvements of depressive symptoms with increasing function on admission., Conclusions: The study provides evidence that mood status changes synchronically with disability.

The aim of the study (part of the Progetto Longitudinale Gussago) was to evaluate the variables related to the difficulty in rising from a bed in 2 groups of elderly patients: nursing home residents, and patients admitted to a geriatric evaluation and management unit. Functional ability was tested through the bed rise difficulty scale (BRD). The version used in this study considered only those 7 items (out of 12) found to be of value. Only those patients who were able to rise from bed without help were selected in order to achieve the aim of the study (33 males, 113 females; mean age 79.6 +/- 7.3 years). Although the 146 patients assessed were considered as having a good functional level (Tinetti score 18.8 +/- 6.9, ADL Katz score 1.6 +/- 1.4), most of them had high scores on the BRD scale, indicating the ability of this scale to detect early, mild disability. The total score of the BRD scale was significantly related to the ADL Katz (r = 0.29, p = 0.000), Tinetti scale (r = -0.39, p = 0.000) and physical performance test (PTT; r = -0.47, p = 0.000). Similar results were obtained for the correlation between BRD time and ADL Katz (r = 0.033, p = 0.000), Tinetti scale (r = -0.30, p = 0.000) and PPT-(r = -0.46, p = 0.000). In a logistic regression analysis the items of the PPT scale considering upper extremity function and Tinetti balance score were significantly associated with the total bed rise time and score.