Technical note: Analytical formulae for the critical supersaturations and droplet diameters of CCN containing insoluble material

International audienceIn this paper, we consider the cloud drop activation of aerosol particles consisting of water soluble material and an insoluble core. Based on the Köhler theory, we derive analytical equations for the critical diameters and supersaturations of such particles. We demonstrate the use of the equations by comparing the critical supersaturations of particles composed of ammonium sulfate and insoluble substances with those of model organic particles with varying molecular sizes

Serum MMP-8 and TIMP-1 as prognostic biomarkers in gastric cancer

Despite gastric cancer being rare nowadays in Western countries, it remains one of the leading causes of cancer death worldwide. The course of the disease varies, so the individual gastric cancer patient’s prognosis is difficult to determine. The need for new biomarkers is crucial. The aim of this study was to evaluate the prognostic value of serum matrix metalloproteinase-8, serum tissue inhibitor of metalloproteinase-1, and tissue matrix metalloproteinase-8 in patients with gastric cancer. Preoperative serum samples from 233 patients with gastric cancer were retrospectively analyzed. Serum levels of matrix metalloproteinase-8 were analyzed with immunofluorometric assay, and tissue inhibitor of metalloproteinase-1 levels were determined by enzyme-linked immunosorbent assay. We also determined the tissue expression of matrix metalloproteinase-8 in 276 gastric cancer samples by immunohistochemistry. Survival data and death causes came from patient records, the Population Register Center of Finland, and Statistics Finland. Patients with a low (131 ng/mL) serum matrix metalloproteinase-8 level had a considerably unfavorable prognosis (p = 0.002). Those patients with a high (≥170 ng/mL) serum tissue inhibitor of metalloproteinase-1 level also had a poor prognosis (p <0.001), and the latter remained significant in multivariable analysis (hazard ratio = 1.85; 95% confidence interval: 1.26–2.72; p = 0.002). The molar ratio of serum matrix metalloproteinase-8 and tissue inhibitor of metalloproteinase-1 levels with low (0.30) molar ratios predicted a worse prognosis (p = 0.020). Tissue matrix metalloproteinase-8 did not influence prognosis. These results suggest that serum matrix metalloproteinase-8, tissue inhibitor of metalloproteinase-1, and the ratio of matrix metalloproteinase-8/ tissue inhibitor of metalloproteinase-1 may prove useful biomarkers for prediction of prognosis in patients with gastric cancer. © The Author(s) 2018.Peer reviewe

Diagnosis, natural course and treatment outcomes of groove pancreatitis

Background: Groove pancreatitis (GP) is a rare form of chronic pancreatitis with limited data on its diagnostics and treatment outcomes. The aim of this study was to assess its diagnostics, natural course, and treatment options. Methods: The study is a retrospective population-based study from Southern Finland, including all patients with suspected GP between January 2005 and December 2015. Two certified gastrointestinal radiologists re-reviewed the imaging studies. The radiological re-review, clinical judgment, and final histopathology confirmed the GP diagnoses. Results: Out of 67 patients with possible GP, 39 patients were considered to have high radiological certainty of GP. Out of these 39, five patients had cancer instead. Thirty-three patients with confirmed GP formed the final study cohort. Patients with GP were mostly middle-aged (median 55 years) men. All had at least moderate alcohol consumption. No intervention was needed in 14 patients. In five-year follow-up all conservatively treated patients became asymptomatic, while 10 out of 16 patients undergoing at least one intervention were asymptomatic at five years. Conclusion: The radiological diagnosis of GP is difficult, and a low threshold for cancer suspicion should be kept. Symptoms of GP decrease with time and suggest conservative treatment as the first-line option.Peer reviewe

S-Nitrosothiols modulate G protein-coupled receptor signaling in a reversible and highly receptor-specific manner

BACKGROUND: Recent studies indicate that the G protein-coupled receptor (GPCR) signaling machinery can serve as a direct target of reactive oxygen species, including nitric oxide (NO) and S-nitrosothiols (RSNOs). To gain a broader view into the way that receptor-dependent G protein activation – an early step in signal transduction – might be affected by RSNOs, we have studied several receptors coupling to the G(i )family of G proteins in their native cellular environment using the powerful functional approach of [(35)S]GTPγS autoradiography with brain cryostat sections in combination with classical G protein activation assays. RESULTS: We demonstrate that RSNOs, like S-nitrosoglutathione (GSNO) and S-nitrosocysteine (CysNO), can modulate GPCR signaling via reversible, thiol-sensitive mechanisms probably involving S-nitrosylation. RSNOs are capable of very targeted regulation, as they potentiate the signaling of some receptors (exemplified by the M2/M4 muscarinic cholinergic receptors), inhibit others (P2Y(12 )purinergic, LPA(1)lysophosphatidic acid, and cannabinoid CB(1 )receptors), but may only marginally affect signaling of others, such as adenosine A(1), μ-opioid, and opiate related receptors. Amplification of M2/M4 muscarinic responses is explained by an accelerated rate of guanine nucleotide exchange, as well as an increased number of high-affinity [(35)S]GTPγS binding sites available for the agonist-activated receptor. GSNO amplified human M4 receptor signaling also under heterologous expression in CHO cells, but the effect diminished with increasing constitutive receptor activity. RSNOs markedly inhibited P2Y(12 )receptor signaling in native tissues (rat brain and human platelets), but failed to affect human P2Y(12 )receptor signaling under heterologous expression in CHO cells, indicating that the native cellular signaling partners, rather than the P2Y(12 )receptor protein, act as a molecular target for this action. CONCLUSION: These in vitro studies show for the first time in a broader general context that RSNOs are capable of modulating GPCR signaling in a reversible and highly receptor-specific manner. Given that the enzymatic machinery responsible for endogenous NO production is located in close proximity with the GPCR signaling complex, especially with that for several receptors whose signaling is shown here to be modulated by exogenous RSNOs, our data suggest that GPCR signaling in vivo is likely to be subject to substantial, and highly receptor-specific modulation by NO-derived RSNOs

Outcomes of High-Frequency Gastric Electric Stimulation for the Treatment of Severe, Medically Refractory Gastroparesis in Finland

Background and Aims: Severe, medically uncontrollable gastroparesis is a rare entity, which can be treated using a high-frequency gastric electric stimulator implanted surgically. Previous follow-ups have proven positive outcomes with gastric electric stimulator in patients with gastroparesis. The aim of this study was to evaluate the efficacy and safety of gastric electric stimulator in patients, in whom gastroparesis could not be controlled by conservative means in our country. Materials and Methods: This is a retrospective multi-center cohort comprising all patients who had been implanted gastric electric stimulator for severe, medically refractory gastroparesis during 2007-2015 in Finland. Results: Fourteen patients underwent implantation of gastric electrical stimulator without any postoperative complications. Laparoscopic approach was used in 13 patients (93%). Prior implantation, all patients needed frequent hospitalization for parenteral feeding, 13 had severe nausea, 11 had severe vomiting, 10 had notable weight loss, and 6 had frequent abdominal pain. After operation, none of the patients required parenteral feeding, 11 patients (79%) gained median of 5.1 kg in weight (P <0.01), and symptoms were relieved markedly in 8 and partially in 3 patients (79%). Of partial responders, two continued to experience occasional vomiting and one mild nausea. Five patients needed medication for gastroparesis after the operation. One patient did not get any relief of symptoms, but gained 6 kg in weight. No major late complications occurred. Conclusion: Gastric electrical stimulator seems to improve the nutritional status and give clear relief of the symptoms of severe, medically uncontrollable gastroparesis. Given the low number of operations, gastric electrical stimulator seems to be underused in Finland.Peer reviewe

Novel cerebrospinal fluid biomarkers correlating with shunt responsiveness in patients with idiopathic normal pressure hydrocephalus

BACKGROUND: Idiopathic Normal pressure hydrocephalus (iNPH) is a form of adult hydrocephalus that is clinically characterized by progressive gait impairment, cognitive dysfunction, and urinary incontinence. The current standard method of treatment involves surgical installation of a CSF diversion shunt. However, only a fraction of patients shows an alleviation of symptoms from shunt surgery. Thus, the purpose of this prospective explorative proteomic study was to identify prognostic CSF biomarkers to predict shunt responsiveness in iNPH patients. Further, we evaluated the ability of the core Alzheimer's disease (AD) CSF biomarkers phosphorylated (p)-tau, total (t)-tau, and amyloid-β 1-42 (Aβ1-42) to serve as predictors of shunt response. METHODS: We conducted a tandem mass tag (TMT) proteomic analysis of lumbar CSF from 68 iNPH patients, sampled pre-shunt surgery. Tryptic digests of CSF samples were labelled with TMTpro reagents. The TMT multiplex samples were fractionated in 24 concatenated fractions by reversed-phase chromatography at basic pH and analysed by liquid chromatography coupled to mass spectrometry (LC-MS) on an Orbitrap Lumos mass spectrometer. The relative abundances of the identified proteins were correlated with (i) iNPH grading scale (iNPHGS) and (ii) gait speed change 1 year after surgery from baseline to identify predictors of shunt responsiveness. RESULTS: We identified four CSF biomarker candidates which correlated most strongly with clinical improvement on the iNPHGS and were significantly changed in shunt-responsive compared to shunt-unresponsive iNPH patients 1 year post-surgery: FABP3 (R = - 0.46, log2(fold change (FC)) = - 0.25, p < 0.001), ANXA4 (R = 0.46, log2(FC) = 0.32, p < 0.001), MIF (R = -0.49, log2(FC) =  - 0.20, p < 0.001) and B3GAT2 (R = 0.54, log2(FC) = 0.20, p < 0.001). In addition, five biomarker candidates were selected based on their strong correlation with gait speed change 1 year after shunt installation: ITGB1 (R = - 0.48, p < 0.001), YWHAG (R = - 0.41, p < 0.01), OLFM2 (R = 0.39, p < 0.01), TGFBI (R = - 0.38, p < 0.01), and DSG2 (R = 0.37, p < 0.01). Concentrations of the CSF AD core biomarkers did not differ significantly with shunt responsiveness. CONCLUSION: FABP3, MIF, ANXA4, B3GAT2, ITGB1, YWHAG, OLFM2, TGFBI and DSG2 in CSF are promising prognostic biomarker candidates to predict shunt responsiveness in iNPH patients

UCLALES–SALSA v1.0: a large-eddy model with interactive sectional microphysics for aerosol, clouds and precipitation

Challenges in understanding the aerosol–cloud interactions and their impacts on global climate highlight the need for improved knowledge of the underlying physical processes and feedbacks as well as their interactions with cloud and boundary layer dynamics. To pursue this goal, increasingly sophisticated cloud-scale models are needed to complement the limited supply of observations of the interactions between aerosols and clouds. For this purpose, a new large-eddy simulation (LES) model, coupled with an interactive sectional description for aerosols and clouds, is introduced. The new model builds and extends upon the well-characterized UCLA Large-Eddy Simulation Code (UCLALES) and the Sectional Aerosol module for Large-Scale Applications (SALSA), hereafter denoted as UCLALES-SALSA. Novel strategies for the aerosol, cloud and precipitation bin discretisation are presented. These enable tracking the effects of cloud processing and wet scavenging on the aerosol size distribution as accurately as possible, while keeping the computational cost of the model as low as possible. The model is tested with two different simulation set-ups: a marine stratocumulus case in the DYCOMS-II campaign and another case focusing on the formation and evolution of a nocturnal radiation fog. It is shown that, in both cases, the size-resolved interactions between aerosols and clouds have a critical influence on the dynamics of the boundary layer. The results demonstrate the importance of accurately representing the wet scavenging of aerosol in the model. Specifically, in a case with marine stratocumulus, precipitation and the subsequent removal of cloud activating particles lead to thinning of the cloud deck and the formation of a decoupled boundary layer structure. In radiation fog, the growth and sedimentation of droplets strongly affect their radiative properties, which in turn drive new droplet formation. The size-resolved diagnostics provided by the model enable investigations of these issues with high detail. It is also shown that the results remain consistent with UCLALES (without SALSA) in cases where the dominating physical processes remain well represented by both models

Modelling mixed-phase clouds with the large-eddy model UCLALES-SALSA

The large-eddy model UCLALES-SALSA, with an exceptionally detailed aerosol description for both aerosol number and chemical composition, has been extended for ice and mixed-phase clouds. Comparison to a previous mixed-phase cloud model intercomparison study confirmed the accuracy of newly implemented ice microphysics. A further simulation with a heterogeneous ice nucleation scheme, in which ice-nucleating particles (INPs) are also a prognostic variable, captured the typical layered structure of Arctic mid-altitude mixed-phase cloud: a liquid layer near cloud top and ice within and below the liquid layer. In addition, the simulation showed a realistic freezing rate of droplets within the vertical cloud structure. The represented detailed sectional ice microphysics with prognostic aerosols is crucially important in reproducing mixed-phase clouds

SALSA - a sectional aerosol module for large scale applications

"The sectional aerosol module SALSA is introduced. The model has been designed to be implemented in large scale climate models, which require both accuracy and computational efficiency. We have used multiple methods to reduce the computational burden of different aerosol processes to optimize the model performance without losing physical features relevant to problematics of climate importance. The optimizations include limiting the chemical compounds and physical processes available in different size sections of aerosol particles; division of the size distribution into size sections using size sections of variable width depending on the sensitivity of microphysical processing to the particles sizes; the total amount of size sections to describe the size distribution is kept to the minimum; furthermore, only the relevant microphysical processes affecting each size section are calculated. The ability of the module to describe different microphysical processes was evaluated against explicit microphysical models and several microphysical models used in air quality models. The results from the current module show good consistency when compared to more explicit models. Also, the module was used to simulate a new particle formation event typical in highly polluted conditions with comparable results to more explicit model setup.""The sectional aerosol module SALSA is introduced. The model has been designed to be implemented in large scale climate models, which require both accuracy and computational efficiency. We have used multiple methods to reduce the computational burden of different aerosol processes to optimize the model performance without losing physical features relevant to problematics of climate importance. The optimizations include limiting the chemical compounds and physical processes available in different size sections of aerosol particles; division of the size distribution into size sections using size sections of variable width depending on the sensitivity of microphysical processing to the particles sizes; the total amount of size sections to describe the size distribution is kept to the minimum; furthermore, only the relevant microphysical processes affecting each size section are calculated. The ability of the module to describe different microphysical processes was evaluated against explicit microphysical models and several microphysical models used in air quality models. The results from the current module show good consistency when compared to more explicit models. Also, the module was used to simulate a new particle formation event typical in highly polluted conditions with comparable results to more explicit model setup.""The sectional aerosol module SALSA is introduced. The model has been designed to be implemented in large scale climate models, which require both accuracy and computational efficiency. We have used multiple methods to reduce the computational burden of different aerosol processes to optimize the model performance without losing physical features relevant to problematics of climate importance. The optimizations include limiting the chemical compounds and physical processes available in different size sections of aerosol particles; division of the size distribution into size sections using size sections of variable width depending on the sensitivity of microphysical processing to the particles sizes; the total amount of size sections to describe the size distribution is kept to the minimum; furthermore, only the relevant microphysical processes affecting each size section are calculated. The ability of the module to describe different microphysical processes was evaluated against explicit microphysical models and several microphysical models used in air quality models. The results from the current module show good consistency when compared to more explicit models. Also, the module was used to simulate a new particle formation event typical in highly polluted conditions with comparable results to more explicit model setup."Peer reviewe

Isoprene-derived secondary organic aerosol in the global aerosol–chemistry–climate model ECHAM6.3.0–HAM2.3–MOZ1.0

Within the framework of the global chemistry climate model ECHAM–HAMMOZ, a novel explicit coupling between the sectional aerosol model HAM-SALSA and the chemistry model MOZ was established to form isoprene-derived secondary organic aerosol (iSOA). Isoprene oxidation in the chemistry model MOZ is described by a semi-explicit scheme consisting of 147 reactions embedded in a detailed atmospheric chemical mechanism with a total of 779 reactions. Semi-volatile and low-volatile compounds produced during isoprene photooxidation are identified and explicitly partitioned by HAM-SALSA. A group contribution method was used to estimate their evaporation enthalpies and corresponding saturation vapor pressures, which are used by HAM-SALSA to calculate the saturation concentration of each iSOA precursor. With this method, every single precursor is tracked in terms of condensation and evaporation in each aerosol size bin. This approach led to the identification of dihydroxy dihydroperoxide (ISOP(OOH)2) as a main contributor to iSOA formation. Further, the reactive uptake of isoprene epoxydiols (IEPOXs) and isoprene-derived glyoxal were included as iSOA sources. The parameterization of IEPOX reactive uptake includes a dependency on aerosol pH value. This model framework connecting semi-explicit isoprene oxidation with explicit treatment of aerosol tracers leads to a global annual average isoprene SOA yield of 15&thinsp;% relative to the primary oxidation of isoprene by OH, NO3 and ozone. With 445.1&thinsp;Tg (392.1&thinsp;Tg&thinsp;C) isoprene emitted, an iSOA source of 138.5&thinsp;Tg (56.7&thinsp;Tg&thinsp;C) is simulated. The major part of iSOA in ECHAM–HAMMOZ is produced by IEPOX at 42.4&thinsp;Tg (21.0&thinsp;Tg&thinsp;C) and ISOP(OOH)2 at 78.0&thinsp;Tg (27.9&thinsp;Tg&thinsp;C). The main sink process is particle wet deposition, which removes 133.6 (54.7&thinsp;Tg&thinsp;C). The average iSOA burden reaches 1.4&thinsp;Tg (0.6&thinsp;Tg&thinsp;C) in the year 2012.</p