An ion mobility mass spectrometer coupled with a cryogenic ion trap for recording electronic spectra of charged, isomer-selected clusters.

Infrared and electronic spectra are indispensable for understanding the structural and energetic properties of charged molecules and clusters in the gas phase. However, the presence of isomers can potentially complicate the interpretation of spectra, even if the target molecules or clusters are mass-selected beforehand. Here, we describe an instrument for spectroscopically characterizing charged molecular clusters that have been selected according to both their isomeric form and their mass-to-charge ratio. Cluster ions generated by laser ablation of a solid sample are selected according to their collision cross sections with helium buffer gas using a drift tube ion mobility spectrometer and their mass-to-charge ratio using a quadrupole mass filter. The mobility- and mass-selected target ions are introduced into a cryogenically cooled, three-dimensional quadrupole ion trap where they are thermalized through inelastic collisions with an inert buffer gas (He or He/N2 mixture). Spectra of the molecular ions are obtained by tagging them with inert atoms or molecules (Ne and N2), which are dislodged following resonant excitation of an electronic transition, or by photodissociating the cluster itself following absorption of one or more photons. An electronic spectrum is generated by monitoring the charged photofragment yield as a function of wavelength. The capacity of the instrument is illustrated with the resonance-enhanced photodissociation action spectra of carbon clusters (Cn +) and polyacetylene cations (HC2nH+) that have been selected according to the mass-to-charge ratio and collision cross section with He buffer gas and of mass-selected Au2 + and Au2Ag+ clusters.

Explaining Discrepancies Between Total and Segmental DXA and BIA Body Composition Estimates Using Bayesian Regression.

INTRODUCTION/BACKGROUND: Few investigations have sought to explain discrepancies between dual-energy X-ray absorptiometry (DXA) and bioelectrical impedance analysis (BIA) body composition estimates. The purpose of this analysis was to explore physiological and anthropometric predictors of discrepancies between DXA and BIA total and segmental body composition estimates. METHODOLOGY: Assessments via DXA (GE Lunar Prodigy) and single-frequency BIA (RJL Systems Quantum V) were performed in 179 adults (103 F, 76 M, age: 33.6 ± 15.3 yr; BMI: 24.9 ± 4.3 kg/m2). Potential predictor variables for differences between DXA and BIA total and segmental fat mass (FM) and lean soft tissue (LST) estimates were obtained from demographics and laboratory techniques, including DXA, BIA, bioimpedance spectroscopy, air displacement plethysmography, and 3-dimensional optical scanning. To determine meaningful predictors, Bayesian robust regression models were fit using a t-distribution and regularized hierarchical shrinkage "horseshoe" prior. Standardized model coefficients (ß) were generated, and leave-one-out cross validation was used to assess model predictive performance. RESULTS: LST hydration (i.e., total body water:LST) was a predictor of discrepancies in all FM and LST variables (|ß|: 0.20-0.82). Additionally, extracellular fluid percentage was a predictor for nearly all outcomes (|ß|: 0.19-0.40). Height influenced the agreement between whole-body estimates (|ß|: 0.74-0.77), while the mass, length, and composition of body segments were predictors for segmental LST estimates (|ß|: 0.23-3.04). Predictors of segmental FM errors were less consistent. Select sex-, race-, or age-based differences between methods were observed. The accuracy of whole-body models was superior to segmental models (leave-one-out cross-validation-adjusted R2 of 0.83-0.85 for FMTOTAL and LSTTOTAL vs. 0.20-0.76 for segmental estimates). For segmental models, predictive performance decreased in the order of: appendicular lean soft tissue, LSTLEGS, LSTTRUNK and FMLEGS, FMARMS, FMTRUNK, and LSTARMS. CONCLUSIONS: These findings indicate the importance of LST hydration, extracellular fluid content, and height for explaining discrepancies between DXA and BIA body composition estimates. These general findings and quantitative interpretation based on the presented data allow for a better understanding of sources of error between 2 popular segmental body composition techniques and facilitate interpretation of estimates from these technologies.

3-Dimensional optical scanning for body composition assessment: A 4-component model comparison of four commercially available scanners.

BACKGROUND & AIMS: Body composition assessment via 3-dimensional optical (3DO) scanning has emerged as a rapid and simple evaluation method. The aim of this study was to establish the precision of body composition estimates from four commercially available 3DO scanners and evaluate their validity as compared to a reference 4-component (4C) model. METHODS: The body composition of 171 participants was assessed using four commercially-available 3DO scanners (FIT3D®, Naked Labs®, Size Stream®, and Styku®) and a 4C model utilizing data from dual-energy x-ray absorptiometry, air displacement plethysmography, and bioimpedance spectroscopy. Body composition estimates were compared via equivalence testing, Deming regression, Bland-Altman analysis, concordance correlation coefficients (CCC), root mean square error (RMSE), and related metrics. Precision metrics, including the root mean square coefficient of variation (RMS-%CV), precision error, and intraclass correlation coefficient, were generated for duplicate scans in 139 participants. RESULTS: All scanners produced reasonably reliable estimates, with RMS-%CV of 2.3-4.3% for body fat percentage (BF%), 2.5-4.3% for fat mass (FM), and 0.7-1.4% for fat-free mass (FFM). ICC values ranged from 0.975 to 0.996 for BF% and 0.990 to 0.999 for FM and FFM. All scanners except Styku® demonstrated equivalence with 4C, using 5% equivalence regions, and constant errors of <1% for BF% and ≤0.5 kg for FM and FFM. However, the slopes of regression lines differed from the line of identity for most scanners and variables. CCC values ranged from 0.74 to 0.90 for BF%, 0.85 to 0.95 for FM, and 0.93 to 0.97 for FFM. RMSE values ranged from 3.7 to 6.1% for BF% and 2.8-4.6 kg for FM and FFM. Bland-Altman analysis indicated proportional bias of varying magnitudes was present for all scanners. CONCLUSIONS: Commercially available 3DO scanners produce relatively reliable body composition estimates. Three out of four scanners demonstrated equivalence with a 4C model for assessments of BF%, FM, and FFM, although other metrics of validity varied among scanners, and proportional bias was present for all scanners.

Segmental body composition evaluation by bioelectrical impedance analysis and dual-energy X-ray absorptiometry: Quantifying agreement between methods.

BACKGROUND & AIMS: Segmental estimates add specificity to body composition evaluation and could potentially have greater health and function implications than whole-body estimates alone. The aim of this study was to quantify the level of agreement between total and segmental fat mass (FM) and lean soft tissue (LST) estimates from dual-energy x-ray absorptiometry (DXA) and single-frequency bioelectrical impedance analysis (SFBIA). METHODS: Assessments via DXA (GE® Lunar Prodigy) and SFBIA (RJL Systems® Quantum V) were performed in 179 adults (103 F, 76 M; 30% racial/ethnic minorities). Total and segmental FM and LST estimates were compared in the entire sample, females, and males using null hypothesis significance testing (NHST; via paired-samples t-tests), equivalence testing with 5% equivalence regions, Bland-Altman analysis with linear regression, and additional error metrics. RESULTS: In females and the entire sample, all LST variables except LSTARMS exhibited equivalence between methods, despite statistically significant differences via NHST for most variables. In males, only estimates of LSTTOTAL and appendicular lean soft tissue (ALST) were equivalent between methods. LST variables exhibited minimal proportional bias. All FM variables failed to exhibit equivalence, and most FM variables were underestimated by SFBIA. The magnitude of relative errors for FM generally appeared larger in males than females. Proportional bias was observed for FMLEGS and FMARMS, as well as FMTOTAL in females only. ALST estimates were equivalent between DXA and SFBIA in all analyses, did not differ between methods based on NHST, exhibited relatively low errors, and displayed no proportional bias. CONCLUSIONS: In the context of the present study, DXA and SFBIA LST estimates appear to exhibit better overall agreement than FM estimates. Additionally, overall agreement between SFBIA and DXA may be superior in females as compared to males. The relatively strong agreement between ALST estimates indicates potential utility of SFBIA for clinical applications, such as evaluation of sarcopenia. Further investigation into the explanatory physiological (e.g. hydration) and anthropometric (e.g. segment lengths, circumferences, and volumes) variables predicting individual discrepancies between DXA and BIA is warranted.

Digital anthropometry via three-dimensional optical scanning: evaluation of four commercially available systems.

BACKGROUND: Digital anthropometry is increasingly accessible due to commercial availability of three-dimensional optical scanners (3DO). METHODS: One hundred and seventy-nine participants were assessed by four 3DO systems (FIT3D®, Size Stream®, Styku®, and Naked Labs®) in duplicate, air displacement plethysmography (ADP), and dual-energy x-ray absorptiometry (DXA). Test-retest precision was evaluated, and validity of total and regional volumes was established. RESULTS: All scanners produced precise estimates, with root mean square coefficient of variation (RMS-%CV) of 1.1-1.3% when averaged across circumferences and 1.9-2.3% when averaged across volumes. Precision for circumferences generally decreased in the order of: hip, waist and thigh, chest, neck, and arms. Precision for volumes generally decreased in the order of: total body volume (BV), torso, legs, and arms. Total BV was significantly underestimated by Styku® (constant error [CE]: -10.1 L; root mean square error [RMSE]: 10.5 L) and overestimated by Size Stream® (CE: 8.0 L; RMSE: 8.3 L). Total BV did not differ between ADP and FIT3D® (CE: -3.9 L; RMSE: 4.2 L) or DXA BV equations (CE: 0-1.4 L; RMSE: 0.7-1.5 L). Torso volume was overestimated and leg and arm volumes were underestimated by all 3DO. No total or regional 3DO volume estimates exhibited equivalence with reference methods using 5% equivalence regions, and proportional bias of varying magnitudes was observed. CONCLUSIONS: All 3DO produced precise anthropometric estimates, although variability in specific precision estimates was observed. 3DO BV estimates did not exhibit equivalence with reference methods. Conversely, DXA-derived total BV exhibited superior validity and equivalence with ADP.

Association of Clinician Behaviors and Weight Change in School-Aged Children.

INTRODUCTION: This study uses clinical practice data to determine whether recommended weight management clinician behaviors are associated with weight status improvement in children aged 6-12 years who are overweight or obese. METHODS: Electronic health record data (2009-2014) from 52 clinics were used. Weight status was examined from 1 visit to the next as dichotomous improvement (versus worsening or no change) and change in percentage overweight (over sex/age-specific BMI95). The primary predictor was a clinician behavior variable denoting attention to high BMI alone or with assessment of medical risk/comorbidities and was defined using combinations of diagnostic codes and electronic health record orders. Covariates included time between visits and medications associated with weight gain or loss. Adjusted multilevel regression models examined the association of the clinician behavior variable with weight status improvement. Analyses were conducted from 2015 to 2018. RESULTS: Children (n=7,205) had a mean age of 8.9 years; 45.5% were overweight, 54.5% obese, and 81.1% publicly insured. For 62% of overweight children, and 38%, 21%, and 11% of those in obesity classes 1-3, respectively, no attention to high BMI/medical risk assessment at any visit was identified. Children with evidence of clinician attention to high BMI alone and who underwent a medical risk assessment had significantly greater AOR of improvement in percentage of BMI95 and percentage of BMI95 change: BMI alone, AOR=1.2 (p<0.001) and ß= -0.3 (p>0.05); BMI/medical risk, AOR=1.2 and ß= -0.5 (both p<0.001). Other factors associated with weight status improvement included prescription medications (1 or more prescriptions associated with either weight loss or none associated with weight gain) and fewer months between visits. CONCLUSIONS: This is the first study to use electronic health record data to demonstrate that widely recommended clinician behaviors are associated with weight status improvement in children aged 6-12 years who are overweight or obese.

Evaluation of a Multifaceted Intervention to Reduce Health Disparities in Hepatitis C Screening: A Pre-Post Analysis.

Hepatitis C virus (HCV) testing in persons born from 1945 to 1965 has had limited adoption despite guidelines, particularly among racial/ethnic minorities and socioeconomically disadvantaged patients, who have a higher prevalence of disease burden. We examined the effectiveness of a multifaceted intervention to improve HCV screening in a large safety-net health system. We performed a multifaceted intervention that included provider and patient education, an electronic medical record-enabled best practice alert, and increased HCV treatment capacity. We characterized HCV screening completion before and after the intervention. To identify correlates of HCV screening, we performed logistic regression for the preintervention and postintervention groups and used a generalized linear mixed model for patients observed in both preintervention and postintervention time frames. Before the intervention, 10.1% of 48,755 eligible baby boomer patients were screened. After the intervention, 34.6% of the 34,093 eligible baby boomers were screened (P < 0.0001). Prior to the intervention, HCV screening was lower among older baby boomers and providers with large patient panels and higher in high-risk subgroups including those with signs of liver disease (e.g., elevated transaminases, thrombocytopenia), human immunodeficiency virus-positive patients, and homeless patients. Postintervention, we observed increased screening uptake in older baby boomers, providers with larger patient panel size, and patients with more than one prior primary care appointment. Conclusion: Our multifaceted intervention significantly increased HCV screening, particularly among older patients, those engaged in primary care, and providers with large patient panels.

Linkage Photoisomerization of an Isolated Ruthenium Sulfoxide Complex: Sequential versus Concerted Rearrangement.

Ruthenium sulfoxide complexes undergo thermally reversible linkage isomerization of sulfoxide ligands from S- to O-bound in response to light. Here, we report photoisomerization action spectra for a ruthenium bis-sulfoxide molecular photoswitch, [Ru(bpy)2(bpSO)]2+, providing the first direct evidence for photoisomerization of a transition metal complex in the gas phase. The linkage isomers are separated and isolated in a tandem drift tube ion mobility spectrometer and exposed to tunable laser radiation provoking photoisomerization. Direct switching of the S,S-isomer to the O,O-isomer following absorption of a single photon is the predominant isomerization pathway in the gas phase, unlike in solution, where stepwise isomerization is observed with each sulfoxide ligand switching in turn. The change in isomerization dynamics is attributed to rapid vibrational quenching that suppresses isomerization in solution. Supporting electronic structure calculations predict the wavelengths and intensities of the peaks in the photoisomerization action spectra of the S,S- and S,O-isomers, indicating that they correspond to metal-to-ligand charge transfer (MLCT) and ligand-centered ππ* transitions.

Photoisomerization of Protonated Azobenzenes in the Gas Phase.

Because of their high photoisomerization efficiencies, azobenzenes and their functionalized derivatives are used in a broad range of molecular photoswitches. Here, the photochemical properties of the trans isomers of protonated azobenzene (ABH+) and protonated 4-aminoazobenzene (NH2ABH+) cations are investigated in the gas phase using a tandem ion mobility spectrometer. Both cations display a strong photoisomerization response across their S1 ← S0 bands, with peaks in their photoisomerization yields at 435 and 525 nm, respectively, red-shifted with respect to the electronic absorption bands of the unprotonated AB and NH2AB molecules. The experimental results are interpreted with the aid of supporting electronic structure calculations considering the relative stabilities and geometries of the possible isomers and protomers and vertical electronic excitation energies.

Seleniranium Ions Undergo π-Ligand Exchange via an Associative Mechanism in the Gas Phase.

Collision-induced dissociation mass spectrometry of the ammonium ions 4a and 4b results in the formation of the seleniranium ion 5, the structure and purity of which were verified using gas-phase infrared spectroscopy coupled to mass spectrometry and gas-phase ion-mobility measurements. Ion-molecule reactions between the ion 5 (m/z = 261) and cyclopentene, cyclohexene, cycloheptene, and cyclooctene resulted in the formation of the seleniranium ions 7 (m/z = 225), 6 (m/z = 239), 8 (m/z = 253), and 9 (m/z = 267), respectively. Further reaction of seleniranium 6 with cyclopentene resulted in further π-ligand exchange giving seleniranium ion 7, confirming that direct π-ligand exchange between seleniranium ion 5 and cycloalkenes occurs in the gas phase. Pseudo-first-order kinetics established relative reaction efficiencies for π-ligand exchange for cyclopentene, cyclohexene, cycloheptene. and cyclooctene as 0.20, 0.07, 0.43, and 4.32. respectively. DFT calculations at the M06/6-31+G(d) level of theory provide the following insights into the mechanism of the π-ligand exchange reactions; the cycloalkene forms a complex with the seleniranium ion 5 with binding energies of 57 and 62 kJ/mol for cyclopentene and cyclohexene, respectively, with transition states for π-ligand exchange having barriers of 17.8 and 19.3 kJ/mol for cyclopentene and cyclohexene, respectively.

Mailed Outreach Program Increases Ultrasound Screening of Patients With Cirrhosis for Hepatocellular Carcinoma.

BACKGROUND & AIMS: Surveillance of patients with cirrhosis increases early detection of hepatocellular carcinoma (HCC) and prolongs survival. However, its effectiveness is limited by underuse, particularly among racial/ethnic minorities and individuals of low socioeconomic status. We compared the effectiveness of mailed outreach strategies, with and without patient navigation, in increasing the numbers of patients with cirrhosis undergoing surveillance for HCC in a racially diverse and socioeconomically disadvantaged cohort. METHODS: We performed a prospective study of patients with documented or suspected cirrhosis at a large safety-net health system from December 2014 through March 2016. Patients were assigned randomly (1:1:1) to groups that received mailed invitations for an ultrasound screening examination (n = 600), mailed invitations for an ultrasound screening examination and patient navigation (barrier assessment and motivational education for patients who declined screening; n = 600), or usual care (visit-based screening; n = 600). Patients who did not respond to outreach invitations within 2 weeks received up to 3 reminder telephone calls. The primary outcome was completion of abdominal imaging within 6 months of randomization. RESULTS: Baseline characteristics were similar among groups. Cirrhosis was documented, based on International Classification of Diseases, 9th revision, codes, for 79.6% of patients, and suspected, based on noninvasive markers of fibrosis, for 20.4%. In an intent-to-treat analysis, significantly greater proportions of patients who received the mailed invitation and navigation (47.2%) or the mailed invitation alone (44.5%) underwent HCC screening than patients who received usual care (24.3%) (P < .001 for both comparisons). However, screening rates did not differ significantly between outreach the outreach groups (P = .25). The effects of the outreach program were consistent in all subgroups, including Caucasian vs non-Caucasian race, documented vs suspected cirrhosis, Child-Pugh A vs B cirrhosis, and receipt of gastroenterology care. CONCLUSIONS: In a prospective study, we found outreach strategies to double the percentage of patients with cirrhosis who underwent ultrasound screening for HCC. However, adding patient navigation to telephone reminders provided no significant additional benefit. ClinicalTrials.gov no: NCT02312817.

Photoisomerization of ß-Ionone Protonated Schiff Base in the Gas Phase.

The photoisomerization of ß-ionone protonated Schiff base (BIPSB) is investigated in the gas phase by irradiating mobility-selected ions in a tandem ion mobility spectrometer with tunable radiation. Four distinguishable isomers are produced by electrospray ionization whose structures are deduced from their collision cross sections and photoisomerization behavior along with density functional theory calculations. They include two geometric isomers of BIPSB with trans or cis configurations about the polyene chain's terminal C═N double bond, a bicyclic structure formed through electrocyclization of the polyene chain, and a Z-retro-γ-ionone isomer. Although trans-BIPSB and 9-cis-BIPSB have similar photoisomerization action spectra, with a maximum response at 375 nm, they photoconvert to different isomers. The trans-BIPSB isomer transforms to the bicyclic form upon exposure to light over the 320-400 nm range, whereas the cis-BIPSB isomer is prevented by steric hindrance from forming the bicyclic BIPSB isomer following irradiation and is proposed instead to form the 7,9-di-cis isomer. Neither the bicyclic isomer nor the Z-retro-γ-ionone isomer respond strongly to near-UV light.

Photo and Collision Induced Isomerization of a Cyclic Retinal Derivative: An Ion Mobility Study.

A cationic degradation product, formed in solution from retinal Schiff base (RSB), is examined in the gas phase using ion mobility spectrometry, photoisomerization action spectroscopy, and collision induced dissociation (CID). The degradation product is found to be N-n-butyl-2-(ß-ionylidene)-4-methylpyridinium (BIP) produced through 6π electrocyclization of RSB followed by protonation and loss of dihydrogen. Ion mobility measurements show that BIP exists as trans and cis isomers that can be interconverted through buffer gas collisions and by exposure to light, with a maximum response at λ = 420 nm.Graphical Abstract.

Photoisomerization action spectroscopy: flicking the protonated merocyanine-spiropyran switch in the gas phase.

Laser spectroscopy and ion mobility spectrometry are combined to provide structural and photochemical information on photoisomerizing molecules in the gas phase. The strategy exploits the fact that an ion packet propelled through buffer gas by an electric field separates spatially and temporally into its constituent isomers because of small differences in their collision cross sections. Isomers selected by an electrostatic ion gate are exposed to wavelength tunable radiation, promoting formation of photoisomers that are separated in a second ion mobility stage. The approach is demonstrated for protonated merocyanine and spiropyran isomers formed through electrospray ionization. Four isomers are observed whose relative abundances depend on pretreatment of the electrosprayed solution with either ultraviolet or visible light, and on collisional excitation before the ions are launched into the drift tube. The observations are interpreted in the light of accurate double-hybrid density functional theory calculations for the protonated spiropyran and merocyanine isomers that are used to predict structures, relative energies, isomerization barriers, collision cross sections and electronic absorption spectra. The two most abundant isomers, are merocyanine forms, in which the proton resides on the quinone oxygen atom, with either a trans or cis central bond in the linking polymethine chain. These two mero forms can be interconverted through photoexcitation, with different wavelength dependences for the forward and reverse photoisomerization processes. Protonated spiropyran is formed from protonated merocyanine isomers through collisional activation, but in only minor amounts through their photo-excitation over the 300-700 nm range.

Photoisomerization action spectroscopy of the carbocyanine dye DTC+ in the gas phase.

Molecular photoisomerization plays a crucial role in diverse biological and technological contexts. Here, we combine ion mobility spectrometry and laser spectroscopy to characterize the photoisomerization of molecular cations in the gas phase. The target molecular ions, polymethine dye cations 3,3'-diethylthiacarbocyanine (DTC(+)), are propelled through helium buffer gas by an electric field and are photoisomerized by light from a tunable laser. Photoexcitation over the 450-570 nm range converts trans-DTC(+) to cis-DTC(+), noticeably modifying the ions' arrival time distribution. The photoisomerization action spectrum, which has a maximum at 535 nm, resembles the absorption spectrum of DTC(+) in solution but is shifted 25 nm to shorter wavelength. Comparisons between measured and calculated mobilities suggest that the photoisomer involves a twist about the second C-C bond in the methine chain (8,9-cis isomer) rather than a twist about the first methine C-C bond (2,8-cis isomer). It is postulated that the excited gas-phase ions internally convert from the S1 Franck-Condon region to the S0 manifold and explore the conformational landscape as they cool through He buffer gas collisions. Master equation simulations of the relaxation process in the S0 manifold suggest that the 8,9-cis isomer is preferred over the 2,8-cis isomer because it lies lower in energy and because it is separated from the trans isomer by a substantially higher barrier. The study demonstrates that the photoisomerization of molecular ions can be probed selectively in the gas phase, providing insights into photoisomerization mechanisms and information on the solvent-free absorption spectrum.

Spring constant calibration of atomic force microscope cantilevers of arbitrary shape.

The spring constant of an atomic force microscope cantilever is often needed for quantitative measurements. The calibration method of Sader et al. [Rev. Sci. Instrum. 70, 3967 (1999)] for a rectangular cantilever requires measurement of the resonant frequency and quality factor in fluid (typically air), and knowledge of its plan view dimensions. This intrinsically uses the hydrodynamic function for a cantilever of rectangular plan view geometry. Here, we present hydrodynamic functions for a series of irregular and non-rectangular atomic force microscope cantilevers that are commonly used in practice. Cantilever geometries of arrow shape, small aspect ratio rectangular, quasi-rectangular, irregular rectangular, non-ideal trapezoidal cross sections, and V-shape are all studied. This enables the spring constants of all these cantilevers to be accurately and routinely determined through measurement of their resonant frequency and quality factor in fluid (such as air). An approximate formulation of the hydrodynamic function for microcantilevers of arbitrary geometry is also proposed. Implementation of the method and its performance in the presence of uncertainties and non-idealities is discussed, together with conversion factors for the static and dynamic spring constants of these cantilevers. These results are expected to be of particular value to the design and application of micro- and nanomechanical systems in general.