Pilot Quality-Assurance Study of a Third-Generation Batch-Mode Clinical-Scale Automated Xenon-129 Hyperpolarizer.

We present a pilot quality assurance (QA) study of a clinical-scale, automated, third-generation (GEN-3) 129Xe hyperpolarizer employing batch-mode spin-exchange optical pumping (SEOP) with high-Xe densities (50% natural abundance Xe and 50% N2 in ~2.6 atm total pressure sourced from Nova Gas Technologies) and rapid temperature ramping enabled by an aluminum heating jacket surrounding the 0.5 L SEOP cell. 129Xe hyperpolarization was performed over the course of 700 gas loading cycles of the SEOP cell, simulating long-term hyperpolarized contrast agent production in a clinical lung imaging setting. High levels of 129Xe polarization (avg. %PXe = 51.0% with standard deviation σPXe = 3.0%) were recorded with fast 129Xe polarization build-up time constants (avg. Tb = 25.1 min with standard deviation σTb = 3.1 min) across the first 500 SEOP cell refills, using moderate temperatures of 75 °C. These results demonstrate a more than 2-fold increase in build-up rate relative to previously demonstrated results in a comparable QA study on a second-generation (GEN-2) 129Xe hyperpolarizer device, with only a minor reduction in maximum achievable %PXe and with greater consistency over a larger number of SEOP cell refill processes at a similar polarization lifetime duration (avg. T1 = 82.4 min, standard deviation σT1 = 10.8 min). Additionally, the effects of varying SEOP jacket temperatures, distribution of Rb metal, and preparation and operation of the fluid path are quantified in the context of device installation, performance optimization and maintenance to consistently produce high 129Xe polarization values, build-up rates (Tb as low as 6 min) and lifetimes over the course of a typical high-throughput 129Xe polarization SEOP cell life cycle. The results presented further demonstrate the significant potential for hyperpolarized 129Xe contrast agent in imaging and bio-sensing applications on a clinical scale.

Automated Low-Cost In Situ IR and NMR Spectroscopy Characterization of Clinical-Scale 129Xe Spin-Exchange Optical Pumping.

We present on the utility of in situ nuclear magnetic resonance (NMR) and near-infrared (NIR) spectroscopic techniques for automated advanced analysis of the 129Xe hyperpolarization process during spin-exchange optical pumping (SEOP). The developed software protocol, written in the MATLAB programming language, facilitates detailed characterization of hyperpolarized contrast agent production efficiency based on determination of key performance indicators, including the maximum achievable 129Xe polarization, steady-state Rb-129Xe spin-exchange and 129Xe polarization build-up rates, 129Xe spin-relaxation rates, and estimates of steady-state Rb electron polarization. Mapping the dynamics of 129Xe polarization and relaxation as a function of SEOP temperature enables systematic optimization of the batch-mode SEOP process. The automated analysis of a typical experimental data set, encompassing ∼300 raw NMR and NIR spectra combined across six different SEOP temperatures, can be performed in under 5 min on a laptop computer. The protocol is designed to be robust in operation on any batch-mode SEOP hyperpolarizer device. In particular, we demonstrate the implementation of a combination of low-cost NIR and low-frequency NMR spectrometers (∼$1,100 and ∼$300 respectively, ca. 2020) for use in the described protocols. The demonstrated methodology will aid in the characterization of NMR hyperpolarization hardware in the context of SEOP and other hyperpolarization techniques for more robust and less expensive clinical production of HP 129Xe and other contrast agents.

MORBID THOUGHTS AND SUICIDAL IDEATION IN IRAQ WAR VETERANS: THE ROLE OF DIRECT AND INDIRECT KILLING IN COMBAT.

BACKGROUND: Although research has identified numerous risk factors for military suicide, the contribution of combat exposure to suicide risk has not been clearly established. Previous studies finding no association of suicidality with combat exposure have employed overgeneral measures of exposure, which do not differentiate among the varieties of combat experiences. This study disaggregated the forms of combat exposure to assess the contribution of combat-related killing to morbid thoughts and suicidal ideation (MTSI) in National Guard troops deployed to Iraq. METHODS: We conducted parallel analyses of two related samples: a cross-sectional sample (n = 1,665) having postdeployment interview data only and a longitudinal subsample (n = 922) having pre- and postdeployment data. We used multiple logistic regression to examine the role of killing-related exposures, after controlling for general combat and other suicide risks, and examined interactions between killing and other suicide vulnerability factors. RESULTS: Killing-related exposure approximately doubled the risk of MTSI in the cross-sectional multivariate model (Adjusted Odds Ratio [AOR] = 1.87; CI = 1.26-2.78) and the longitudinal model (AOR = 2.02; CI = 1.06-3.85), which also controlled for predeployment risks. Killing exposures further increased the MTSI risk associated with other suicide vulnerability factors, including depression (AOR = 14.89 for depression and killing vs. AOR = 9.92 for depression alone), alcohol dependence (AOR = 5.63 for alcohol and killing vs. 1.91 for alcohol alone), and readjustment stress (AOR = 4.90 for stress and killing vs. 1.48 for stress alone). General combat exposure had no comparable effects. CONCLUSIONS: The findings underscore a need for assessment and treatment protocols that address the psychological effects of killing-related and other potentially "morally injurious" experiences among combat soldiers.

Use of the Columbia-Suicide Severity Rating Scale (C-SSRS) to Classify Suicidal Behaviors.

Efforts to better understand and prevent suicide have increasingly pointed to the prospective assessment of suicidal behaviors in clinical trials. These assessments are aided by instruments such as the Columbia-Suicide Severity Rating Scale (C-SSRS), which have sought to improve the conceptual uniformity and ease by which suicidal behaviors are classified. At the same time, assessment and classification of suicidal behaviors has been a longtime challenge in the field. To aid users of the C-SSRS, this article illustrates the use of the C-SSRS in instances where classification complexities arise. Illustrations are presented based on cases encountered during a clinical trial for a suicide prevention intervention. Key decision points are summarized and classification issues that warrant consideration for future refinement of such decisions are discussed.

Rationale and study design of a trial of mindfulness-based cognitive therapy for preventing suicidal behavior (MBCT-S) in military veterans.

BACKGROUND: Although suicide ranks 10th as a cause of death in the United States, and 1st among active military personnel, there are surprisingly few evidence-based therapies addressing suicidality, and development of new treatments is limited. This paper describes a clinical trial testing a novel therapy for reducing suicide risk in military veterans. The intervention, Mindfulness-Based Cognitive Therapy for Preventing Suicide Behavior (MBCT-S), is a 10-week group intervention adapted from an existing treatment for depression (Mindfulness-Based Cognitive Therapy - MBCT). MBCT-S incorporates the Safety Planning Intervention, which is currently implemented throughout the Veterans Health Administration (VHA) for veterans at high suicide risk. METHODS: MBCT-S is being tested in a VHA setting using an intention-to-treat, two-group randomized trial design in which 164 high suicide risk veterans are randomized to either VHA Treatment As Usual (TAU; n=82) or TAU+MBCT-S (n=82). Our primary outcome measure, suicide-related event, defined to include suicide preparatory behaviors, self-harm behavior with suicidal or indeterminate intent, suicide-related hospitalizations and Emergency Department (ED) visits, will be measured through five assessments administered by blinded assessors between baseline and 12months post-baseline. We will measure suicide attempts and suicide deaths as a secondary outcome, because of their anticipated low incidence during the study period. Secondary outcomes also include severity of suicidal ideation, hopelessness and depression. SIGNIFICANCE: This study has the potential to significantly enhance the quality and efficiency of VHA care for veterans at suicide risk and to substantially improve the quality of life for veterans and their families.