Advances in High Field Asymmetric Ion Mobility Spectrometry (FAIMS) Analyzers and FAIMS-Mass Spectrometry Interfaces

High field asymmetric ion mobility spectrometry (FAIMS) is a gas phase separation technique that separates ions by the ratio of high to low electric field mobility, which is a characteristic of the three dimensional structure of ions. FAIMS separation in front of mass spectrometric analysis has the ability to reduce chemical noise thereby increasing signal-to-noise ratios and limits of detection; it can also be used to separate isobaric and isomeric compounds. FAIMS analyzers are simple to construct and are easily integrated into the atmospheric pressure ion source of current mass spectrometers without major modifications. The motivation of developing FAIMS analyzers in the Glish lab has been for the study of three dimensional gas phase ion structure of biological molecules, as well as to improve separation of compounds which are irresolvable using low resolution mass spectrometry and liquid chromatography. This dissertation does not focus on the application of FAIMS for structural elucidation, but instead on the development of a FAIMS device that combines excellent speed, resolution, and sensitivity in a simple to use small package. Described in the following chapters are the background for selection of gas phase ions by shape to charge, the development of a high amplitude asymmetric waveform power supply, modifications made the planar FAIMS device designed by the Pacific Northwest National Lab and the development of four generations of planar FAIMS devices. For each device limitations and flaws in the design are discussed along with proposed solutions and data demonstrating the results of modifications to analyzer design, and the successful construction of a planar FAIMS device with high speed, high sensitivity, and resolving power equal to much larger and more expensive devices

Characterization and Quantification of Highly Sulfated Glycosaminoglycan Isomers by Gated-Trapped Ion Mobility Spectrometry Negative Electron Transfer Dissociation MS/MS

Glycosaminoglycans (GAGs) Play Vital Roles in Many Biological Processes and Are Naturally Present as Complex Mixtures of Polysaccharides with Tremendous Structural Heterogeneity, Including Many Structural Isomers. Mass Spectrometric Analysis of GAG Isomers, in Particular Highly Sulfated Heparin (Hep) and Heparan Sulfate (HS), is Challenging Because of their Structural Similarity and Facile Sulfo Losses during Analysis. Herein, We Show that Highly Sulfated Hep/HS Isomers May Be Resolved by Gated-Trapped Ion Mobility Spectrometry (Gated-TIMS) with Negligible Sulfo Losses. Subsequent Negative Electron Transfer Dissociation (NETD) Tandem Mass Spectrometry (MS/MS) Analysis of TIMS-Separated Hep/HS Isomers Generated Extensive Glycosidic and Cross-Ring Fragments for Confident Isomer Differentiation and Structure Elucidation. the High Mobility Resolution and Preservation of Labile Sulfo Modifications Afforded by Gated-TIMS MS Analysis Also Allowed Relative Quantification of Highly Sulfated Heparin Isomers. These Results Show that the Gated-TIMS-NETD MS/MS Approach is Useful for Both Qualitative and Quantitative Analysis of Highly Sulfated Hep/HS Compounds in a Manner Not Possible with Other Techniques

Surgical treatment of uterine prolapse in women with bladder exstrophy: report of two cases with modified Prolift™ procedure

The incidence of pelvic organ prolapse is 18% in women with bladder exstrophy. A vaginal technique to correct the prolapse may be preferable in these women with multiple abdominal operations in their histories. We have performed a modified Prolift™ procedure for the repair of severe uterine prolapse in two young women. A review of the literature is presented

Stigma and Social Power: Expecting to Interact with an Obese Person Activates Power in the Self-concept

People's sense of power is often a more crucial determinant of their behavior than their actual level of power. In this paper, we suggest that individuals may perceive themselves as more powerful when anticipating interaction with a member of a stigmatized out-group than with a member of a nonstigmatized group. Normal weight participants (N = 77) expected to have an interaction with a target randomly identified as obese or thin. Participants were quicker to endorse words describing themselves in terms of traits associated with power when the target was obese than thin. They were also likely to expect greater interpersonal power, to endorse more negative attitudes towards obese people and to form more negative impressions, if the target was obese rather than thin. These findings suggest that a perception of empowerment is spontaneously activated prior to interaction with an obese person.http://www.informaworld.com/smpp/content~db=all~content=a907123882~frm=titlelinkSCOPUS: ar.jinfo:eu-repo/semantics/publishe

Surgical management of mesh-related complications after prior pelvic floor reconstructive surgery with mesh

Contains fulltext : 96379.pdf (publisher's version ) (Closed access)INTRODUCTION AND HYPOTHESIS: The objective of this study is to evaluate the complications and anatomical and functional outcomes of the surgical treatment of mesh-related complications. METHODS: A retrospective cohort study of patients who underwent complete or partial mesh excision to treat complications after prior mesh-augmented pelvic floor reconstructive surgery was conducted. RESULTS: Seventy-three patients underwent 30 complete and 51 partial mesh excisions. Intraoperative complications occurred in 4 cases, postoperative complications in 13. Symptom relief was achieved in 92% of patients. Recurrence of pelvic organ prolapse (POP) occurred in 29% of complete and 5% of partial excisions of mesh used in POP surgery. De novo stress urinary incontinence (SUI) occurred in 36% of patients who underwent excision of a suburethral sling. CONCLUSIONS: Mesh excision relieves mesh-related complications effectively, although with a substantial risk of serious complications and recurrence of POP or SUI. More complex excisions should be performed in skilled centers

Recommendations for reporting ion mobility mass spectrometry measurements

© 2019 The Authors. Mass Spectrometry Reviews Published by Wiley Periodicals, Inc. Here we present a guide to ion mobility mass spectrometry experiments, which covers both linear and nonlinear methods: what is measured, how the measurements are done, and how to report the results, including the uncertainties of mobility and collision cross section values. The guide aims to clarify some possibly confusing concepts, and the reporting recommendations should help researchers, authors and reviewers to contribute comprehensive reports, so that the ion mobility data can be reused more confidently. Starting from the concept of the definition of the measurand, we emphasize that (i) mobility values (K0) depend intrinsically on ion structure, the nature of the bath gas, temperature, and E/N; (ii) ion mobility does not measure molecular surfaces directly, but collision cross section (CCS) values are derived from mobility values using a physical model; (iii) methods relying on calibration are empirical (and thus may provide method-dependent results) only if the gas nature, temperature or E/N cannot match those of the primary method. Our analysis highlights the urgency of a community effort toward establishing primary standards and reference materials for ion mobility, and provides recommendations to do so. © 2019 The Authors. Mass Spectrometry Reviews Published by Wiley Periodicals, Inc

Making sense of diabetes medication decisions: a mixed methods cluster randomized trial using a conversation aid intervention.

PURPOSE: To determine the effectiveness of a shared decision-making (SDM) tool versus guideline-informed usual care in translating evidence into primary care, and to explore how use of the tool changed patient perspectives about diabetes medication decision making. METHODS: In this mixed methods multicenter cluster randomized trial, we included patients with type 2 diabetes mellitus and their primary care clinicians. We compared usual care with or without a within-encounter SDM conversation aid. We assessed participant-reported decisions made and quality of SDM (knowledge, satisfaction, and decisional conflict), clinical outcomes, adherence, and observer-based patient involvement in decision-making (OPTION12-scale). We used semi-structured interviews with patients to understand their perspectives. RESULTS: We enrolled 350 patients and 99 clinicians from 20 practices and interviewed 26 patients. Use of the conversation aid increased post-encounter patient knowledge (correct answers, 52% vs. 45%, p = 0.02) and clinician involvement of patients (Mean between-arm difference in OPTION12, 7.3 (95% CI 3, 12); p = 0.003). There were no between-arm differences in treatment choice, patient or clinician satisfaction, encounter length, medication adherence, or glycemic control. Qualitative analyses highlighted differences in how clinicians involved patients in decision making, with intervention patients noting how clinicians guided them through conversations using factors important to them. CONCLUSIONS: Using an SDM conversation aid improved patient knowledge and involvement in SDM without impacting treatment choice, encounter length, medication adherence or improved diabetes control in patients with type 2 diabetes. Future interventions may need to focus specifically on patients with signs of poor treatment fit. CLINICAL TRIAL REGISTRATION: ClinicalTrial.gov: NCT01502891

Identification of Phosphatidylcholine Isomers in Imaging Mass Spectrometry Using Gas-Phase Charge Inversion Ion/Ion Reactions

Gas-phase ion/ion reactions have been enabled on a commercial dual source, hybrid QhFT-ICR mass spectrometer for use during imaging mass spectrometry experiments. These reactions allow for the transformation of the ion type most readily generated from the tissue surface to an ion type that gives improved chemical structural information upon tandem mass spectrometry (MS/MS) without manipulating the tissue sample. This process is demonstrated via the charge inversion reaction of phosphatidylcholine (PC) lipid cations generated from rat brain tissue via matrix-assisted laser desorption/ionization (MALDI) with 1,4-phenylenedipropionic acid (PDPA) reagent dianions generated via electrospray ionization (ESI). Collision induced dissociation (CID) of the resulting demethylated PC product anions allows for the determination of the lipid fatty acyl tail identities and positions, which is not possible via CID of the precursor lipid cations. The abundance of lipid isomers revealed by this workflow is found to vary significantly in different regions of the brain. As each isoform may have a unique cellular function, these results underscore the importance of accurately separating and identifying the many isobaric and isomeric lipids and metabolites that can complicate image interpretation and spectral analysis.</p