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Objective: To assess the relationship between MRI-derived changes in whole-brain and ventricular volume with change in cognitive scores in Alzheimer's disease (AD), mild cognitive impairment (MCI) and control subjects.Material and Methods: In total 131 control, 231 MCI and 99 AD subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort with T1-weighted volumetric MRIs from baseline and 12-month follow-up were used to derive volume changes. Mini mental state examination (MMSE), Alzheimer's disease assessment scale (ADAS)-cog and trails test changes were calculated over the same period.Results: Brain atrophy rates and ventricular enlargement differed between subject groups (p < 0.0005) and in MCI and AD were associated with MMSE changes. Both measures were additionally associated with ADAS-cog and trails-B in MCI patients, and ventricular expansion was associated with ADAS-cog in AD patients. Brain atrophy (p < 0.0005) and ventricular expansion rates (p = 0.001) were higher in MCI subjects who progressed to AD within 12 months of follow-up compared with MCI subjects who remained stable. MCI subjects who progressed to AD within 12 months had similar atrophy rates to AD subjects.Conclusion: Whole-brain atrophy rates and ventricular enlargement differed between patient groups and healthy controls, and tracked disease progression and psychological decline, demonstrating their relevance as biomarkers. [ABSTRACT FROM AUTHOR]

Alkaline gases such as NH 3 and amines play important roles in neutralizing acidic particles in the atmosphere. Here, two common gaseous amines (dimethylamine (DMA) and trimethylamine (TMA)), NH 3 , and their corresponding ions in PM 2.5 were measured semicontinuously using an ambient ion monitor-ion chromatography (AIM-IC) system in marine air during a round-trip cruise of approximately 4000 km along the coastline of eastern China. The concentrations of particulate DMA, detected as DMAH + , varied from <4 to 100 ng m -3 and generally decreased with increasing atmospheric NH 3 concentrations. Combining observations with thermodynamic equilibrium calculations using the extended aerosol inorganics model (E-AIM) indicated that the competitive uptake of DMA against NH 3 on acidic aerosols generally followed thermodynamic equilibria and appeared to be sensitive to DMA/NH 3 molar ratios, resulting in molar ratios of DMAH + to DMA + DMAH + of 0.31 ± 0.16 (average ± standard deviation) at atmospheric NH 3 concentrations over 1.8 μg m -3 (with a corresponding DMA/NH 3 ratio of (1.8 ± 1.0) × 10 -3 ), 0.80 ± 0.15 at atmospheric NH 3 concentrations below 0.3 μg m -3 (with a corresponding DMA/NH 3 ratio of (1.3 ± 0.6) × 10 -2 ), and 0.56 ± 0.19 in the remaining cases. Particulate TMA concentrations, detected as TMAH + , ranged from <2 to 21 ng m -3 and decreased with increasing concentrations of atmospheric NH 3 . However, TMAH + was depleted concurrently with the formation of NH 4 NO 3 under low concentrations of atmospheric NH 3 , contradictory to the calculated increase in the equilibrated concentration of TMAH + by the E-AIM.

Chemical thermodynamic models of solvent and solute activities predict the equilibrium behavior of aqueous solutions. However, these models are semi-empirical. They represent micro-scale ion and solvent behaviors controlling the macroscopic properties using small numbers of parameters whose values are obtained by fitting to activities and other partial derivatives of the Gibbs energy measured for the bulk solutions. We have conducted atomistic simulations of aqueous electrolyte solutions (MgCl 2 and CaCl 2 ) to determine the parameters of thermodynamic hydration models. We have implemented a cooperative hydration model to categorize the water molecules in electrolyte solutions into different subpopulations. The value of the electrolyte-specific parameter, k, was determined from the ion-affected subpopulation with the lowest absolute value of the free energy of removing the water molecule. The other equilibrium constant parameter, K 1 , associated with the first degree of hydration, was computed from the free energy of hydration of hydrated clusters. The hydration number, h, was determined from a reorientation dynamic analysis of the water subpopulations compared to bulk-like behavior. The reparameterized models [R. H. Stokes and R. H. Robinson, J. Solution Chem. 2, 173 (1973) and Balomenos et al., Fluid Phase Equilib. 243, 29 (2006)] using the computed values of the parameters lead to the osmotic coefficients of MgCl 2 solutions that are consistent with measurements. Such an approach removes the dependence on the availability of experimental data and could lead to aqueous thermodynamic models capable of estimating the values of solute and solvent activities as well as thermal and volumetric properties for a wide range of compositions and concentrations.

Background: Drugs modifying angiotensin II signalling could reduce Alzheimer's disease pathology, thus decreasing the rate of disease progression. We investigated whether the angiotensin II receptor antagonist losartan, compared with placebo, could reduce brain volume loss, as a measure of disease progression, in clinically diagnosed mild-to-moderate Alzheimer's disease., Methods: In this double-blind, multicentre, randomised controlled trial, eligible patients aged 55 years or older, previously untreated with angiotensin II drugs and diagnosed (National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association criteria) with mild-to-moderate Alzheimer's disease, and who had capacity to consent, were recruited from 23 UK National Health Service hospital trusts. After undergoing a 4-week, open-label phase of active treatment then washout, participants were randomly assigned (1:1) oral over-encapsulated preparations of either 100 mg losartan (after an initial two-dose titration stage) or matched placebo daily for 12 months. Randomisation, minimised by age and baseline medial temporal lobe atrophy score, was undertaken online or via pin-access service by telephone. Participants, their study companions, and study personnel were masked to group assignment. The primary outcome, analysed by the intention-to-treat principle (ie, participants analysed in the group to which they were randomised, without imputation for missing data), was change in whole brain volume between baseline and 12 months, measured using volumetric MRI and determined by boundary shift interval (BSI) analysis. The trial is registered with the International Standard Randomised Controlled Trial Register (ISRCTN93682878) and the European Union Drug Regulating Authorities Clinical Trials Database (EudraCT 2012-003641-15), and is completed., Findings: Between July 22, 2014, and May 17, 2018, 261 participants entered the open-label phase. 211 were randomly assigned losartan (n=105) or placebo (n=106). Of 197 (93%) participants who completed the study, 171 (81%) had complete primary outcome data. The mean brain volume (BSI) reduction was 19·1 mL (SD 10·3) in the losartan group and 20·0 mL (10·8) in the placebo group. The difference in total volume reduction between groups was -2·29 mL (95% CI -6·46 to 0·89; p=0·14). The number of adverse events was low (22 in the losartan group and 20 in the placebo group) with no differences between treatment groups. There was one treatment-related death per treatment group., Interpretation: 12 months of treatment with losartan was well tolerated but was not effective in reducing the rate of brain atrophy in individuals with clinically diagnosed mild-to-moderate Alzheimer's disease. Further research is needed to assess the potential therapeutic benefit from earlier treatment in patients with milder cognitive impairment or from longer treatment periods., Funding: Efficacy and Mechanism Evaluation Programme (UK Medical Research Council and National Institute for Health Research)., Competing Interests: Declaration of interests PGK reports grants from the National Institute of Health Research (NIHR), during the conduct of the study; being a non-funded co-investigator of the ongoing Alzheimer's Association-funded HEART phase 1b study of telmisartan and its use as an intervention against the renin–angiotensin system in African American people at risk of developing dementia by parental history; and having previously undertaken advisory work for Novartis in their development and intended trialling of dual acting inhibitors of Angiotensin Receptor Blockers and neprilysin (LCZ696) for the treatment of heart failure. NT, BH, LJ, SLB, IBM, CN, NJT, PSB, JAL, PP, JT, DLT, IW, and YBS report grants from the NIHR, during the conduct of the study. JB reports grants from Alzheimer's Research UK, outside the submitted work. CHS reports grants for the Alzheimer's Society, during the conduct of the study. EC reports grants from the NIHR, during the conduct of the study; and received payment from Biogen, Novartis, and Union Chimique Belge for providing educational resources or consultancy around Alzheimer's Disease trials. NCF reports other funding from Roche, personal fees from Biogen, and non-financial support from Lilly and Ionis, outside the submitted work. AW and H-JM declare no competing interests., (Copyright © 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

We present an atomistic simulation scheme for the determination of the hydration number (h) of aqueous electrolyte solutions based on the calculation of the water dipole reorientation dynamics. In this methodology, the time evolution of an aqueous electrolyte solution generated from ab initio molecular dynamics simulations is used to compute the reorientation time of different water subpopulations. The value of h is determined by considering whether the reorientation time of the water subpopulations is retarded with respect to bulk-like behavior. The application of this computational protocol to magnesium chloride (MgCl 2 ) solutions at different concentrations (0.6-2.8 mol kg -1 ) gives h values in excellent agreement with experimental hydration numbers obtained using GHz-to-THz dielectric relaxation spectroscopy. This methodology is attractive because it is based on a well-defined criterion for the definition of hydration number and provides a link with the molecular-level processes responsible for affecting bulk solution behavior. Analysis of the ab initio molecular dynamics trajectories using radial distribution functions, hydrogen bonding statistics, vibrational density of states, water-water hydrogen bonding lifetimes, and water dipole reorientation reveals that MgCl 2 has a considerable influence on the hydrogen bond network compared with bulk water. These effects have been assigned to the specific strong Mg-water interaction rather than the Cl-water interaction., (© 2020 The Authors. Published by Wiley-VCH GmbH.)

We present an ab initio molecular dynamics study of the alkali metal ions Li+, Na+, K+ and Cs+, and of the alkaline earth metal ions Mg2+ and Ca2+ in both pure water and electrolyte solutions containing the counterions Cl- and SO42-. Simulations were conducted using different density functional theory methods (PBE, BLYP and revPBE), with and without the inclusion of dispersion interactions (-D3). Analysis of the ion-water structure and interaction strength, water exchange between the first and second hydration shell, and hydrogen bond network and low-frequency reorientation dynamics around the metal ions have been used to characterise the influence of solution composition on the ionic solvation shell. Counterions affect the properties of the hydration shell not only when they are directly coordinated to the metal ion, but also when they are at the second coordination shell. Chloride ions reduce the sodium hydration shell and expand the calcium hydration shell by stabilizing under-coordinated hydrated Na(H2O)5+ complexes and over-coordinated Ca(H2O)72+. The same behaviour is observed in CaSO4(aq), where Ca2+ and SO42- form almost exclusively solvent-shared ion pairs. Water exchange between the first and second hydration shell around Ca2+ in CaSO4(aq) is drastically decelerated compared with the simulations of the hydrated metal ion (single Ca2+, no counterions). Velocity autocorrelation function analysis, used to probe the strength of the local ion-water interaction, shows a smoother decay of Mg2+ in MgCl2(aq), which is a clear indication of a looser inter-hexahedral vibration in the presence of chloride ions located in the second coordination shell of Mg2+. The hydrogen bond statistics and orientational dynamics in the ionic solvation shell show that the influence on the water-water network cannot only be ascribed to the specific cation-water interaction, but also to the subtle interplay between the level of hydration of the ions, and the interactions between ions, especially those of opposite charge. As many reactive processes involving solvated metal ions occur in environments that are far from pure water but rich in ions, this computational study shows how the solution composition can result in significant differences in behaviour and function of the ionic solvation shell.

Acidity, defined as pH, is a central component of aqueous chemistry. In the atmosphere, the acidity of condensed phases (aerosol particles, cloud water, and fog droplets) governs the phase partitioning of semi-volatile gases such as HNO 3 , NH 3 , HCl, and organic acids and bases as well as chemical reaction rates. It has implications for the atmospheric lifetime of pollutants, deposition, and human health. Despite its fundamental role in atmospheric processes, only recently has this field seen a growth in the number of studies on particle acidity. Even with this growth, many fine particle pH estimates must be based on thermodynamic model calculations since no operational techniques exist for direct measurements. Current information indicates acidic fine particles are ubiquitous, but observationally-constrained pH estimates are limited in spatial and temporal coverage. Clouds and fogs are also generally acidic, but to a lesser degree than particles, and have a range of pH that is quite sensitive to anthropogenic emissions of sulfur and nitrogen oxides, as well as ambient ammonia. Historical measurements indicate that cloud and fog droplet pH has changed in recent decades in response to controls on anthropogenic emissions, while the limited trend data for aerosol particles indicates acidity may be relatively constant due to the semi-volatile nature of the key acids and bases and buffering in particles. This paper reviews and synthesizes the current state of knowledge on the acidity of atmospheric condensed phases, specifically particles and cloud droplets. It includes recommendations for estimating acidity and pH, standard nomenclature, a synthesis of current pH estimates based on observations, and new model calculations on the local and global scale., Competing Interests: Competing interests. The authors declare that they have no conflict of interest.

Atmospheric sulfate aerosols have important impacts on air quality, climate, and human and ecosystem health. However, current air-quality models generally underestimate the rate of conversion of sulfur dioxide (SO 2 ) to sulfate during severe haze pollution events, indicating that our understanding of sulfate formation chemistry is incomplete. This may arise because the air-quality models rely upon kinetics studies of SO 2 oxidation conducted in dilute aqueous solutions, and not at the high solute strengths of atmospheric aerosol particles. Here, we utilize an aerosol flow reactor to perform direct investigation on the kinetics of aqueous oxidation of dissolved SO 2 by hydrogen peroxide (H 2 O 2 ) using pH-buffered, submicrometer, deliquesced aerosol particles at relative humidity of 73 to 90%. We find that the high solute strength of the aerosol particles significantly enhances the sulfate formation rate for the H 2 O 2 oxidation pathway compared to the dilute solution. By taking these effects into account, our results indicate that the oxidation of SO 2 by H 2 O 2 in the liquid water present in atmospheric aerosol particles can contribute to the missing sulfate source during severe haze episodes., Competing Interests: The authors declare no competing interest.

Using a comparative evaporation kinetics approach, we describe a new and accurate method for determining the equilibrium hygroscopic growth of aerosol droplets. The time-evolving size of an aqueous droplet, as it evaporates to a steady size and composition that is in equilibrium with the gas phase relative humidity, is used to determine the time-dependent mass flux of water, yielding information on the vapor pressure of water above the droplet surface at every instant in time. Accurate characterization of the gas phase relative humidity is provided from a control measurement of the evaporation profile of a droplet of know equilibrium properties, either a pure water droplet or a sodium chloride droplet. In combination, and by comparison with simulations that account for both the heat and mass transport governing the droplet evaporation kinetics, these measurements allow accurate retrieval of the equilibrium properties of the solution droplet (i.e., the variations with water activity in the mass fraction of solute, diameter growth factor, osmotic coefficient or number of water molecules per solute molecule). Hygroscopicity measurements can be made over a wide range in water activity (from >0.99 to, in principle, <0.05) on time scales of <10 s for droplets containing involatile or volatile solutes. The approach is benchmarked for binary and ternary inorganic solution aerosols with typical uncertainties in water activity of <±0.2% at water activities >0.9 and ∼±1% below 80% RH, and maximum uncertainties in diameter growth factor of ±0.7%. For all of the inorganic systems examined, the time-dependent data are consistent with large values of the mass accommodation (or evaporation) coefficient (>0.1).

Measurements of the hygroscopic response of aerosol and the particle-to-gas partitioning of semivolatile organic compounds are crucial for providing more accurate descriptions of the compositional and size distributions of atmospheric aerosol. Concurrent measurements of particle size and composition (inferred from refractive index) are reported here using optical tweezers to isolate and probe individual aerosol droplets over extended timeframes. The measurements are shown to allow accurate retrievals of component vapor pressures and hygroscopic response through examining correlated variations in size and composition for binary droplets containing water and a single organic component. Measurements are reported for a homologous series of dicarboxylic acids, maleic acid, citric acid, glycerol, or 1,2,6-hexanetriol. An assessment of the inherent uncertainties in such measurements when measuring only particle size is provided to confirm the value of such a correlational approach. We also show that the method of molar refraction provides an accurate characterization of the compositional dependence of the refractive index of the solutions. In this method, the density of the pure liquid solute is the largest uncertainty and must be either known or inferred from subsaturated measurements with an error of <±2.5% to discriminate between different thermodynamic treatments.

Background: Rare TREM2 variants are significant risk factors for Alzheimer's disease (AD)., Methods: We used next generation sequencing of the whole gene (n = 700), exon 2 Sanger sequencing (n = 2634), p.R47H genotyping (n = 3518), and genome wide association study imputation (n = 13,048) to determine whether TREM2 variants are risk factors or phenotypic modifiers in patients with AD (n = 1002), frontotemporal dementia (n = 358), sporadic (n = 2500), and variant (n = 115) Creutzfeldt-Jakob disease (CJD)., Results: We confirm only p.R47H as a risk factor for AD (odds ratio or OR = 2.19; 95% confidence interval or CI = 1.04-4.51; P = .03). p.R47H does not significantly alter risk for frontotemporal dementia (OR = 0.81), variant or sporadic CJD (OR = 1.06 95%CI = 0.66-1.69) in our cohorts. Individuals with p.R47H associated AD (n = 12) had significantly earlier symptom onset than individuals with no TREM2 variants (n = 551) (55.2 years vs. 61.7 years, P = .02). We note that heterozygous p.R47H AD is memory led and otherwise indistinguishable from "typical" sporadic AD., Conclusion: We find p.R47H is a risk factor for AD, but not frontotemporal dementia or prion disease., (Copyright © 2014 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.)

Formation of new particles through clustering of molecules from condensable vapors is a significant source for atmospheric aerosols. The smallest clusters formed in the very first steps of the condensation process are, however, not directly observable by experimental means. We present here a comprehensive series of electronic structure calculations on the hydrates of clusters formed by up to four molecules of sulfuric acid, and up to two molecules of ammonia or dimethylamine. Though clusters containing ammonia, and certainly dimethylamine, generally exhibit lower average hydration than the pure acid clusters, populations of individual hydrates vary widely. Furthermore, we explore the predictions obtained using a thermodynamic model for the description of these hydrates. The similar magnitude and trends of hydrate formation predicted by both methods illustrate the potential of combining them to obtain more comprehensive models. The stabilization of some clusters relative to others due to their hydration is highly likely to have significant effects on the overall processes that lead to formation of new particles in the atmosphere.

In previous studies (Dutcher et al. J. Phys. Chem. C 2011, 115, 16474-16487; 2012, 116, 1850-1864), we derived equations for the Gibbs energy, solvent and solute activities, and solute concentrations in multicomponent liquid mixtures, based upon expressions for adsorption isotherms that include arbitrary numbers of hydration layers on each solute. In this work, the long-range electrostatic interactions that dominate in dilute solutions are added to the Gibbs energy expression, thus extending the range of concentrations for which the model can be used from pure liquid solute(s) to infinite dilution in the solvent, water. An equation for the conversion of the reference state for solute activity coefficients to infinite dilution in water has been derived. A number of simplifications are identified, notably the equivalence of the sorption site parameters r and the stoichiometric coefficients of the solutes, resulting in a reduction in the number of model parameters. Solute concentrations in mixtures conform to a modified Zdanovskii-Stokes-Robinson mixing rule, and solute activity coefficients to a modified McKay-Perring relation, when the effects of the long-range (Debye-Hückel) term in the equations are taken into account. Practical applications of the equations to osmotic and activity coefficients of pure aqueous electrolyte solutions and mixtures show both satisfactory accuracy from low to high concentrations, together with a thermodynamically reasonable extrapolation (beyond the range of measurements) to extreme concentration and to the pure liquid solute(s).

Calculations of the size and density of atmospheric aerosols are complicated by the fact that they can exist at concentrations highly supersaturated with respect to dissolved salts and supercooled with respect to ice. Densities and apparent molar volumes of solutes in aqueous solutions containing the solutes H(2)SO(4), HNO(3), HCl, Na(2)SO(4), NaNO(3), NaCl, (NH(4))(2)SO(4), NH(4)NO(3), and NH(4)Cl have been critically evaluated and represented using fitted equations from 0 to 50 °C or greater and from infinite dilution to concentrations saturated or supersaturated with respect to the dissolved salts. Using extrapolated densities of high-temperature solutions and melts, the relationship between density and concentration is extended to the hypothetical pure liquid solutes. Above a given reference concentration of a few mol kg(-1), it is observed that density increases almost linearly with decreasing temperature, and comparisons with available data below 0 °C suggest that the fitted equations for density can be extrapolated to very low temperatures. As concentration is decreased below the reference concentration, the variation of density with temperature tends to that of water (which decreases as temperature is reduced below 3.98 °C). In this region below the reference concentration, and below 0 °C, densities are calculated using extrapolated apparent molar volumes which are constrained to agree at the reference concentrations with an equation for the directly fitted density. Calculated volume properties agree well with available data at low temperatures, for both concentrated and dilute solutions. Comparisons are made with literature data for temperatures of maximum density. Apparent molar volumes at infinite dilution are consistent, on a single ion basis, to better than ±0.1 cm(3) mol(-1) from 0 to 50 °C. Volume properties of aqueous NaHSO(4), NaOH, and NH(3) have also been evaluated, at 25 °C only. In part 2 of this work (ref 1 ) an ion interaction (Pitzer) model has been used to calculate apparent molar volumes of H(2)SO(4) in 0-3 mol kg(-1) aqueous solutions of the pure acid and to represent directly the effect of the HSO(4)(-) ↔ H(+) + SO(4)(2-) reaction. The results are incorporated into the treatment of aqueous H(2)SO(4) density described here. Densities and apparent molar volumes from -20 to 50 °C, and from 0 to 100 wt % of solute, are tabulated for the electrolytes listed in the title and have also been incorporated into the extended aerosol inorganics model (E-AIM, http://www.aim.env.uea.ac.uk/aim/aim.php) together with densities of the solid salts and hydrates.

A Pitzer ion interaction model has been applied to the systems H(2)SO(4)-H(2)O (0-3 mol kg(-1), 0-55 °C) and H(2)SO(4)-(NH(4))(2)SO(4)-H(2)O (0-6 mol kg(-1), 25 °C) for the calculation of apparent molar volume and density. The dissociation reaction HSO(4)(-)((aq)) ↔ H(+)((aq)) + SO(4)(2-)((aq)) is treated explicitly. Apparent molar volumes of the SO(4)(2-) ion at infinite dilution were obtained from part 1 of this work, (1) and the value for the bisulfate ion was determined in this study from 0 to 55 °C. In dilute solutions of both systems, the change in the degree of dissociation of the HSO(4)(-) ion with concentration results in much larger variations of the apparent molar volumes of the solutes than for conventional strong (fully dissociated) electrolytes. Densities and apparent molar volumes are tabulated. Apparent molar volumes calculated using the model are combined with other data for the solutes NH(4)HSO(4) and (NH(4))(3)H(SO(4))(2) at 25 °C to obtain apparent molar volumes and densities over the entire concentration range (including solutions supersaturated with respect to the salts).

A semiempirical model is presented that predicts surface tensions (σ) of aqueous electrolyte solutions and their mixtures, for concentrations ranging from infinitely dilute solution to molten salt. The model requires, at most, only two temperature-dependent terms to represent surface tensions of either pure aqueous solutions, or aqueous or molten mixtures, over the entire composition range. A relationship was found for the coefficients of the equation σ = c(1) + c(2)T (where T (K) is temperature) for molten salts in terms of ion valency and radius, melting temperature, and salt molar volume. Hypothetical liquid surface tensions can thus be estimated for electrolytes for which there are no data, or which do not exist in molten form. Surface tensions of molten (single) salts, when extrapolated to normal temperatures, were found to be consistent with data for aqueous solutions. This allowed surface tensions of very concentrated, supersaturated, aqueous solutions to be estimated. The model has been applied to the following single electrolytes over the entire concentration range, using data for aqueous solutions over the temperature range 233-523 K, and extrapolated surface tensions of molten salts and pure liquid electrolytes: HCl, HNO(3), H(2)SO(4), NaCl, NaNO(3), Na(2)SO(4), NaHSO(4), Na(2)CO(3), NaHCO(3), NaOH, NH(4)Cl, NH(4)NO(3), (NH(4))(2)SO(4), NH(4)HCO(3), NH(4)OH, KCl, KNO(3), K(2)SO(4), K(2)CO(3), KHCO(3), KOH, CaCl(2), Ca(NO(3))(2), MgCl(2), Mg(NO(3))(2), and MgSO(4). The average absolute percentage error between calculated and experimental surface tensions is 0.80% (for 2389 data points). The model extrapolates smoothly to temperatures as low as 150 K. Also, the model successfully predicts surface tensions of ternary aqueous mixtures; the effect of salt-salt interactions in these calculations was explored.

The vapor pressures of two dicarboxylic acids, malonic acid and glutaric acid, are determined by the measurement of the evaporation rate of the dicarboxylic acids from single levitated particles. Two laboratory methods were used to isolate single particles, an electrodynamic balance and optical tweezers (glutaric acid only). The declining sizes of individual aerosol particles over time were followed using elastic Mie scattering or cavity enhanced Raman scattering. Experiments were conducted over the temperature range of 280-304 K and a range of relative humidities. The subcooled liquid vapor pressures of malonic and glutaric acid at 298.15 K were found to be 6.7(-1.2)(+2.6) x 10(-4) and 11.2(-4.7)(+9.6) x 10(-4) Pa, respectively, and the standard enthalpies of vaporization were respectively 141.9 ± 19.9 and 100.8 ± 23.9 kJ mol(-1). The vapor pressures of both glutaric acid and malonic acid in single particles composed of mixed inorganic/organic composition were found to be independent of salt concentration within the uncertainty of the measurements. Results are compared with previous laboratory determinations and theoretical predictions.

We describe a newly constructed electrodynamic balance with which to measure the relative mass of single aerosol particles at varying relative humidity. Measurements of changing mass with respect to the relative humidity allow mass (m) growth factors (m(aqueous)/m(dry)) and diameter (d) growth factors (d(aqueous)/d(dry)) of the aerosol to be determined. Four aerosol types were investigated: malonic acid, glutaric acid, mixtures of malonic acid and sodium chloride, and mixtures of glutaric acid and sodium chloride. The mass growth factors of the malonic acid and glutaric acid aqueous phase aerosols, at 85% relative humidity, were 2.11 +/- 0.08 and 1.73 +/- 0.19, respectively. The mass growth factors of the mixed organic/inorganic aerosols are dependent upon the molar fraction of the individual components. Results are compared with previous laboratory determinations and theoretical predictions.

An approach for examining the hygroscopicity of single aerosol particles over a broad range in relative humidity (RH) using aerosol optical tweezers is presented and compared with measurements made using an electrodynamic balance. In particular, benchmark measurements on aqueous sodium chloride aerosol are presented over the RH range 45-75% (293 K), a RH range that had not previously been explored with aerosol optical tweezers. Measurements of the variation in equilibrium wet droplet size with RH are made using cavity-enhanced Raman scattering, with an accuracy of 1 nm in the determination of the wet particle radius. The full range of optical tweezers experimental measurements (including previous dual trapping comparative studies approaching a saturation relative humidity of 100%) are compared with determinations using other experimental techniques and with a range of model treatments. An assessment of the models and all experimental data for estimating the equilibrium size of a sodium chloride droplet suggests that the size can be predicted with an accuracy of better than 0.1% over the RH range 48-100%. Discrepancies between different measurements lead to an increase in uncertainty above 1% below an RH of 48% as efflorescence is approached. The optical tweezers' measurements of equilibrium size consistently agree with model predictions to within an error of 1% (<50 nm for the size range explored here) and mostly with an error of less than +/-0.1%. These data demonstrate the highly accurate nature of measurements of thermodynamic equilibrium size by aerosol optical tweezers and suggest that this approach may be used to investigate the competition between thermodynamic and kinetic factors in governing aerosol particle size over the full RH range.

Background: Semantic dementia is a sporadic neurodegenerative disorder characterized by the progressive erosion of semantic processing and is one of the canonical subtypes of frontotemporal lobar degeneration. This study aimed to characterize the pattern of global and regional longitudinal brain atrophy in semantic dementia and to identify imaging biomarkers that could underpin therapeutic trials., Methods: Twenty-one patients with semantic dementia (including eight pathologically confirmed cases) underwent whole-brain and region-of-interest analyses on volumetric brain MRI scans at two time points. Sample size estimates for trials were subsequently calculated using these data., Results: Mean (SD) whole-brain atrophy rate was 39.6 (31.9) mL/y [3.2 (12.0) mL/y in controls], with ventricular enlargement of 8.9 (4.4) mL/y [1.0 (1.0) mL/y in controls]. All patients had a smaller left temporal lobe at baseline [left mean 31.9 (6.9) mL, right mean 49.2 (9.5) mL; p < 0.0001]; however, the mean rate of atrophy was significantly greater in the right temporal lobe [right 3.9 (1.7) mL/y, left 2.8 (1.2) mL/y; p = 0.02]. Similarly, whereas the left hippocampus was smaller at baseline, the mean atrophy rate was significantly greater in the right hippocampus. Using the atrophy rates generated, sample size requirements for clinical trials were found to be smallest for temporal lobe measurement., Conclusions: These findings show that the rate of tissue loss in the right temporal lobe overtakes the left temporal lobe as semantic dementia evolves, consistent with the later development of symptoms attributable to right temporal lobe dysfunction. Furthermore, our findings demonstrate that MRI measures of temporal lobe volume loss could provide a feasible and sensitive index of disease progression in semantic dementia.

Aerosol optical tweezers are used to simultaneously characterize and compare the hygroscopic properties of two aerosol droplets, one containing inorganic and organic solutes and the second, referred to as the control droplet, containing a single inorganic salt. The inorganic solute is either sodium chloride or ammonium sulfate and the organic component is glutaric acid. The time variation in the size of each droplet (3-7 microm in radius) is recorded with 1 s time resolution and with nanometre accuracy. The size of the control droplet is used to estimate the relative humidity with an accuracy of better than +/-0.09%. Thus, the Kohler curve of the multicomponent inorganic/organic droplet, which characterizes the variation in equilibrium droplet size with relative humidity, can be determined directly. The measurements presented here focus on high relative humidities, above 97%, in the limit of dilute solutes. The experimental data are compared with theoretical treatments that, while ignoring the interactions between the inorganic and organic components, are based upon accurate representations of the activity-concentration relationships of aqueous solutions of the individual salts. The organic component is treated by a parametrized fit to experimental data or by the UNIFAC model and the water activity of the equilibrium solution droplet is calculated using the approach suggested by Clegg, Seinfeld and Brimblecombe or the Zdanovskii-Stokes-Robinson approximation. It is shown that such an experimental strategy, comparing directly droplets of different composition, enables highly accurate measurements of the hygroscopic properties, allowing the theoretical treatments to be rigorously tested. Typical deviations of the experimental measurements from theoretical predictions are shown to be around 1% in equilibrium size, comparable to the variation between the theoretical frameworks considered.

Atmospheric aerosols contain a significant fraction of water-soluble organic compounds, including dicarboxylic acids. Pitzer activity coefficient models are developed, using a wide range of data at 298.15 K, for the following systems containing succinic acid (H(2)Succ) and/or succinate salts: [H(+), Li(+), Na(+), K(+), Rb(+), Cs(+)]Cl(-)-H(2)Succ-H(2)O, HNO(3)-H(2)Succ-H(2)O, H(+)-NH(4)(+)-HSucc(-)-Succ(2-)-NH(3)-H(2)Succ-H(2)O, NH(4)Cl-(NH(4))(2)Succ-H(2)O, H(+)-Na(+)-HSucc(-)-Succ(2-)-Cl(-)-H(2)Succ-H(2)O, NH(4)NO(3)-H(2)Succ-H(2)O, and H(2)SO(4)-H(2)Succ-H(2)O. The above compositions are given in terms of ions in the cases where acid dissociation was considered. Pitzer models were also developed for the following systems containing malonic acid (H(2)Malo): H(+)-Na(+)-HMalo(-)-Malo(2-)-Cl(-)-H(2)Malo-H(2)O, and H(2)Malo-H(2)SO(4)-H(2)O. The models are used to evaluate the extended Zdanovskii-Stokes-Robinson (ZSR) model proposed by Clegg and Seinfeld (J. Phys. Chem. A 2004, 108, 1008-1017) for calculating water and solute activities in solutions in which dissociation equilibria occur. The ZSR model yields satisfactory results only for systems that contain moderate to high concentrations of (nondissociating) supporting electrolyte. A practical modeling scheme is proposed for aqueous atmospheric aerosols containing both electrolytes and dissociating (organic) nonelectrolytes.

Atmospheric aerosols contain a significant fraction of water-soluble organic compounds, including dicarboxylic acids. Water activities at approximately 298.15 K (including data for highly supersaturated solutions) of oxalic, malonic, succinic, glutaric, maleic, malic, and methyl succinic acids are first correlated as a function of concentration, treating the acids as nondissociating components. Methods proposed by Clegg et al. (J. Aerosol. Sci. 2001, 32, 713-738), and by Clegg and Seinfeld (J. Phys. Chem. A 2004, 108, 1008-1017) for estimating water activities and solute activity coefficients in aqueous mixtures containing both electrolytes and uncharged solutes are then evaluated from comparisons with literature data. These data include water activities, solubilities, and determinations of the eutonic points of solutions containing up to five acids, and solutions containing one or more acids and the salts (NH(4))(2)SO(4), NH(4)NO(3), or NaCl. The extended Zdanovskii-Stokes-Robinson approach of Clegg and Seinfeld yields the more accurate predictions for aqueous mixtures containing dicarboxylic acids only, and for aqueous mixtures of the acids and salts (though by a lesser margin). A number of hybrid modeling approaches, which contain elements of both methods, are outlined.