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The preBötzinger complex (preBötC), located in the medulla, is the essential rhythm-generating neural network for breathing. The actions of opioids on this network impair its ability to generate robust, rhythmic output, contributing to life-threatening opioid-induced respiratory depression (OIRD). The occurrence of OIRD varies across individuals and internal and external states, increasing the risk of opioid use, yet the mechanisms of this variability are largely unknown. In this study, we utilize a computational model of the preBötC to perform several in silico experiments exploring how differences in network topology and the intrinsic properties of preBötC neurons influence the sensitivity of the network rhythm to opioids. We find that rhythms produced by preBötC networks in silico exhibit variable responses to simulated opioids, similar to the preBötC network in vitro. This variability is primarily due to random differences in network topology and can be manipulated by imposed changes in network connectivity and intrinsic neuronal properties. Our results identify features of the preBötC network that may regulate its susceptibility to opioids., Competing Interests: The authors declare no competing financial interests., (Copyright © 2024 Chou et al.)

Breathing is vital and must be concurrently robust and flexible. This rhythmic behavior is generated and maintained within a rostrocaudally aligned set of medullary nuclei called the ventral respiratory column (VRC). The rhythmic properties of individual VRC nuclei are well known, yet technical challenges have limited the interrogation of the entire VRC population simultaneously. Here we characterize over 15,000 medullary units using high-density electrophysiology, opto-tagging and histological reconstruction. Population dynamics analysis reveals consistent rotational trajectories through a low-dimensional neural manifold. These rotations are robust and maintained even during opioid-induced respiratory depression. During severe hypoxia-induced gasping, the low-dimensional dynamics of the VRC reconfigure from rotational to all-or-none, ballistic efforts. Thus, latent dynamics provide a unifying lens onto the activities of large, heterogeneous populations of neurons involved in the simple, yet vital, behavior of breathing, and well describe how these populations respond to a variety of perturbations., (© 2024. The Author(s).)

Sighs prevent the collapse of alveoli in the lungs, initiate arousal under hypoxic conditions, and are an expression of sadness and relief. Sighs are periodically superimposed on normal breaths, known as eupnea. Implicated in the generation of these rhythmic behaviors is the preBötzinger complex (preBötC). Our experimental evidence suggests that purinergic signaling is necessary to generate spontaneous and hypoxia-induced sighs in a mouse model. Our results demonstrate that driving calcium increases in astrocytes through pharmacological methods robustly increases sigh, but not eupnea, frequency. Calcium imaging of preBötC slices corroborates this finding with an increase in astrocytic calcium upon application of sigh modulators, increasing intracellular calcium through g-protein signaling. Moreover, photo-activation of preBötC astrocytes is sufficient to elicit sigh activity, and this response is blocked with purinergic antagonists. We conclude that sighs are modulated through neuron-glia coupling in the preBötC network, where the distinct modulatory responses of neurons and glia allow for both rhythms to be independently regulated., (© 2023. Springer Nature Limited.)

Caring Contacts (CC), a low-cost intervention originally designed and tested by Jerome Motto in 1976, remains one of the few strategies to demonstrate efficacy in the prevention of suicide deaths. Interest in CC has increased steadily over the last several years in tandem with rising U.S. suicide rates and the acceleration of suicide prevention initiatives. There have been several efforts to design interventions modeled after Motto's strategy, and the recent publication of additional large-scale randomized controlled trials (RCTs) in alignment with the intent of Motto's original model afford an opportunity to systematically review efficacy findings. The current systematic review provides an updated and focused analysis of the evidence supporting the efficacy of CC. A systematic literature search of MEDLINE, EMBASE, PsycINFO, Cochrane Library, and ClinicalTrials.gov was conducted, and PRISMA, Cochrane, and GRADE guidelines were followed. Of 2,746 abstracts reviewed, 13 publications, comprising six randomized controlled trials (RCTs) met inclusion criteria. The studies encompassed 6,218 participants across four countries and military, veteran, and civilian health care systems. The primary outcome was suicide mortality; secondary outcomes were suicide attempts and emergency department (ED) presentations/hospitalizations. The DerSimonian-Laird random-effects univariate meta-analysis was used to estimate summary effect sizes and evaluate statistical heterogeneity. Summary risk ratio estimates ranged from 0.57 to 1.29 across outcomes and time points; most estimates indicated a protective effect. For suicide deaths and ED presentations/hospitalization, interval estimates at 1-year postrandomization were consistent with either an increase or a decrease in risk. A protective effect was observed for suicide attempts at 1-year postrandomization. Implications and methodological recommendations for future work in this area reviewed and discussed. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Cellular and network properties must be capable of generating rhythmic activity that is both flexible and stable. This is particularly important for breathing, a rhythmic behavior that dynamically adapts to environmental, behavioral, and metabolic changes from the first to the last breath. The pre-Bötzinger complex (preBötC), located within the ventral medulla, is responsible for producing rhythmic inspiration. Its cellular properties must be tunable, flexible as well as stabilizing. Here, we explore the role of the hyperpolarization-activated, nonselective cation current ( I h ) for stabilizing PreBötC activity during opioid exposure and reduced excitatory synaptic transmission. Introducing I h into an in silico preBötC network predicts that loss of this depolarizing current should significantly slow the inspiratory rhythm. By contrast, in vitro and in vivo experiments revealed that the loss of I h minimally affected breathing frequency, but destabilized rhythmogenesis through the generation of incompletely synchronized bursts (burstlets). Associated with the loss of I h was an increased susceptibility of breathing to opioid-induced respiratory depression or weakened excitatory synaptic interactions, a paradoxical depolarization at the cellular level, and the suppression of tonic spiking. Tonic spiking activity is generated by nonrhythmic excitatory and inhibitory preBötC neurons, of which a large percentage express I h . Together, our results suggest that I h is important for maintaining tonic spiking, stabilizing inspiratory rhythmogenesis, and protecting breathing against perturbations or changes in network state. NEW & NOTEWORTHY The I h current plays multiple roles within the preBötC. This current is important for promoting intrinsic tonic spiking activity in excitatory and inhibitory neurons and for preserving rhythmic function during conditions that dampen network excitability, such as in the context of opioid-induced respiratory depression. We therefore propose that the I h current expands the dynamic range of rhythmogenesis, buffers the preBötC against network perturbations, and stabilizes rhythmogenesis by preventing the generation of unsynchronized bursts.

Adjustment disorders are among the most commonly diagnosed mental health disorders in both civilian and military clinical settings. Despite their high prevalence, adjustment disorders have received little research attention. The many gaps in our understanding of this group of disorders hinder the development of adequate, evidence-based treatment protocols. This study utilizes a systematic methodology to identify and prioritize research gaps in adjustment disorders. We used authoritative source reports to identify gaps in research domains from foundational science to services research. Subject-matter experts conducted literature searches to substantiate and refine research gaps, and stakeholders assessed the importance and impact of this work for researchers and policy-makers. We identified 254 possible research-needs statements, which were ultimately reduced to 11 final, prioritized research gaps. Two gaps addressed prevention and screening and three addressed treatment and services research. Six gaps addressed foundational science, epidemiology, and etiology research domains, highlighting the need for basic research. Until some of the basic science questions are resolved (e.g., diagnostic clarity, valid screening, and assessment measures) about adjustment disorders, we may not be able to develop adequate evidence-based interventions for the disorders, and it will be difficult to understand the trajectory of these disorders throughout treatment. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Death from opioid overdose is typically caused by opioid-induced respiratory depression (OIRD). A particularly dangerous characteristic of OIRD is its apparent unpredictability. The respiratory consequences of opioids can be surprisingly inconsistent, even within the same individual. Despite significant clinical implications, most studies have focused on average dose-r esponses rather than individual variation, and there remains little insight into the etiology of this apparent unpredictability. The preBötzinger complex (preBötC) in the ventral medulla is an important site for generating the respiratory rhythm and OIRD. Here, using male and female C57-Bl6 mice in vitro , we demonstrate that the preBötC can assume different network states depending on the excitability of the preBötC and the intrinsic membrane properties of preBötC neurons. These network states predict the functional consequences of opioids in the preBötC, and depending on network state, respiratory rhythmogenesis can be either stabilized or suppressed by opioids. We hypothesize that the dynamic nature of preBötC rhythmogenic properties, required to endow breathing with remarkable flexibility, also plays a key role in the dangerous unpredictability of OIRD. SIGNIFICANCE STATEMENT Opioids can cause unpredictable, life-threatening suppression of breathing. This apparent unpredictability makes clinical management of opioids difficult while also making it challenging to define the underlying mechanisms of OIRD. Here, we find in brainstem slices that the preBötC, an opioid-sensitive subregion of the brainstem, has an optimal configuration of cellular and network properties that results in a maximally stable breathing rhythm. These properties are dynamic, and the state of each individual preBötC network relative to the optimal configuration of the network predicts how vulnerable rhythmogenesis is to the effects of opioids. These insights establish a framework for understanding how endogenous and exogenous modulation of the rhythmogenic state of the preBötC can increase or decrease the risk of OIRD., (Copyright © 2021 the authors.)

The analgesic utility of opioid-based drugs is limited by the life-threatening risk of respiratory depression. Opioid-induced respiratory depression (OIRD), mediated by the μ-opioid receptor (MOR), is characterized by a pronounced decrease in the frequency and regularity of the inspiratory rhythm, which originates from the medullary preBötzinger Complex (preBötC). To unravel the cellular- and network-level consequences of MOR activation in the preBötC, MOR-expressing neurons were optogenetically identified and manipulated in transgenic mice in vitro and in vivo. Based on these results, a model of OIRD was developed in silico. We conclude that hyperpolarization of MOR - expressing preBötC neurons alone does not phenocopy OIRD. Instead, the effects of MOR activation are twofold: (1) pre-inspiratory spiking is reduced and (2) excitatory synaptic transmission is suppressed, thereby disrupting network-driven rhythmogenesis. These dual mechanisms of opioid action act synergistically to make the normally robust inspiratory rhythm-generating network particularly prone to collapse when challenged with exogenous opioids., Competing Interests: NB, NB, NB, JR No competing interests declared, (© 2021, Baertsch et al.)

Across all sensory modalities, first-stage sensory neurons are an information bottleneck: they must convey all information available for an animal to perceive and act in its environment. Our understanding of coding properties of primary sensory neurons in the auditory and visual systems has been aided by the use of increasingly complex, naturalistic stimulus sets. By comparison, encoding properties of primary somatosensory afferents are poorly understood. Here, we use the rodent whisker system to examine how tactile information is represented in primary sensory neurons of the trigeminal ganglion (Vg). Vg neurons have long been thought to segregate into functional classes associated with separate streams of information processing. However, this view is based on Vg responses to restricted stimulus sets which potentially underreport the coding capabilities of these neurons. In contrast, the current study records Vg responses to complex three-dimensional (3D) stimulation while quantifying the complete 3D whisker shape and mechanics, thereby beginning to reveal their full representational capabilities. The results show that individual Vg neurons simultaneously represent multiple mechanical features of a stimulus, do not preferentially encode principal components of the stimuli, and represent continuous and tiled variations of all available mechanical information. These results directly contrast with proposed codes in which subpopulations of Vg neurons encode select stimulus features. Instead, individual Vg neurons likely overcome the information bottleneck by encoding large regions of a complex sensory space. This proposed tiled and multidimensional representation at the Vg directly constrains the computations performed by more central neurons of the vibrissotrigeminal pathway., Competing Interests: The authors declare no competing interest.

High treatment dropout rates reported in recent literature have brought into question the effectiveness of trauma-focused posttraumatic stress disorder (PTSD) treatments among military populations. The aim of the current systematic review was to evaluate PTSD treatment dropout rates among military populations by treatment type and other study-level variables. We searched four databases as well as gray literature for randomized controlled trials that evaluated evidence-based PTSD treatments in samples of active duty personnel and/or veterans. In total, 26 studies were included in this review, with a total of 2,984 participants. We analyzed dropout rates across treatment types using multivariate meta-analysis. Across all forms of treatment, the aggregated dropout rate was 24.2%. Dropout percentages based on treatment type were 27.1% for trauma-focused treatments, 16.1% for non-trauma-focused treatments, and 6.8% for waitlist groups. We found substantial heterogeneity between studies that was not explained by military status or other study-level covariates. Summary risk ratios (RRs) comparing relative dropout between treatment groups indicated that trauma-focused treatment groups had a higher risk of dropout compared to non-trauma-focused treatments, RR = 1.60. The statistical heterogeneity of within-treatment dropout risk ratios was negligible. Dropout rates among military patients receiving trauma-focused therapies were only slightly higher than those reported in the literature among civilian populations and were not explained by study-level covariates., (© 2021 International Society for Traumatic Stress Studies.)

Objective: This study identified and prioritized research gaps for suicide prevention in the Department of Defense to inform future research investments., Methods: The 2019 VA/DoD Clinical Practice Guideline for the Assessment and Management of Patients at Risk for Suicide was the primary source document for research gaps, supplemented by an updated literature search. Institutional stakeholders rated the identified research gaps and ranked the gap categories. We used Q factor analysis to derive a list of the prioritized research gaps and category rankings., Results: Thirty-five research gaps were identified and prioritized. The highest rated research gap topic was lethal means safety interventions and their effectiveness in increasing safety behaviors and/or reducing suicide-related outcomes. Research on the effectiveness of crisis response planning and several other non-pharmacological interventions (e.g., implementation of cognitive-behavioral therapy, technology-based behavioral interventions, and applications of dialectical behavior therapy to non-Borderline patients) were also rated highly by stakeholders., Conclusions: This work generated a list of priorities for future suicide research as evaluated by Departments of Defense and Veterans Affairs stakeholders. Our findings can help guide the efforts of suicide researchers and inform decisions about future research funding for suicide prevention., (© 2021 American Association of Suicidology. This article has been contributed to by US Government employees and their work is in the public domain in the USA.)

As it becomes possible to simulate increasingly complex neural networks, it becomes correspondingly important to model the sensory information that animals actively acquire: the biomechanics of sensory acquisition directly determines the sensory input and therefore neural processing. Here, we exploit the tractable mechanics of the well-studied rodent vibrissal ("whisker") system to present a model that can simulate the signals acquired by a full sensor array actively sampling the environment. Rodents actively "whisk" ∼60 vibrissae (whiskers) to obtain tactile information, and this system is therefore ideal to study closed-loop sensorimotor processing. The simulation framework presented here, WHISKiT Physics , incorporates realistic morphology of the rat whisker array to predict the time-varying mechanical signals generated at each whisker base during sensory acquisition. Single-whisker dynamics were optimized based on experimental data and then validated against free tip oscillations and dynamic responses to collisions. The model is then extrapolated to include all whiskers in the array, incorporating each whisker's individual geometry. Simulation examples in laboratory and natural environments demonstrate that WHISKiT Physics can predict input signals during various behaviors, currently impossible in the biological animal. In one exemplary use of the model, the results suggest that active whisking increases in-plane whisker bending compared to passive stimulation and that principal component analysis can reveal the relative contributions of whisker identity and mechanics at each whisker base to the vibrissotactile response. These results highlight how interactions between array morphology and individual whisker geometry and dynamics shape the signals that the brain must process., Competing Interests: The authors declare no competing interest.

Rett syndrome (RTT), an X-chromosome-linked neurological disorder, is characterized by serious pathophysiology, including breathing and feeding dysfunctions, and alteration of cardiorespiratory coupling, a consequence of multiple interrelated disturbances in the genetic and homeostatic regulation of central and peripheral neuronal networks, redox state, and control of inflammation. Characteristic breath-holds, obstructive sleep apnea, and aerophagia result in intermittent hypoxia, which, combined with mitochondrial dysfunction, causes oxidative stress-an important driver of the clinical presentation of RTT.

Objective: Prior research indicates that there is an additive association between traumatic brain injury and mental health diagnoses on health-care utilization. This assumed additivity has not been formally assessed. The objective of this study was to estimate additive and multiplicative interactions associated with mild traumatic brain injury (mTBI) and pre-existing health conditions., Method: Active-duty military patient records over a nine-year period were sampled within four exposure groups ( N  = 4500 per group) defined jointly by incident mTBI and pre-existing mental health diagnoses. Outpatient and inpatient health encounters were compared between the four exposure groups using generalized linear models for count and proportion outcomes. Additive interactions were estimated using the interaction contrast ratio. Multiplicative interactions were estimated as a product term in the generalized linear models., Results: The joint association of mTBI and pre-existing mental health diagnoses with health-care utilization, overall, was less than multiplicative and greater than additive. Patients with both exposures experienced more health-care utilization than expected under the assumed additivity (independence) of the two exposures. PTSD and anxiety diagnoses were the MH diagnoses associated with the largest interaction contrast values specific to total outpatient encounters., Conclusions: Studies of the interaction of two diagnoses on subsequent health-care utilization should examine both additive and multiplicative interactions. The greater-than-additive findings in this study indicate that there may be synergy, for at least some patients, between mTBI injury and mental health that complicates the treatment course.

Compared to our understanding of the response properties of receptors in the auditory and visual systems, we have only a limited understanding of the mechanoreceptor responses that underlie tactile sensation. Here, we exploit the stereotyped morphology of the rat vibrissal (whisker) array to investigate coding and transduction properties of identified primary tactile afferents. We performed in vivo intra-axonal recording and labeling experiments to quantify response characteristics of four different types of identified mechanoreceptors in the vibrissal follicle: ring-sinus Merkel; lanceolate; clublike; and rete-ridge collar Merkel. Of these types, only ring-sinus Merkel endings exhibited slowly adapting properties. A weak inverse relationship between response magnitude and onset response latency was found across all types. All afferents exhibited strong "angular tuning," i.e., their response magnitude and latency depended on the whisker's deflection angle. Although previous studies suggested that this tuning should be aligned with the angular location of the mechanoreceptor in the follicle, such alignment was observed only for Merkel afferents; angular tuning of the other afferent types showed no clear alignment with mechanoreceptor location. Biomechanical modeling suggested that this tuning difference might be explained by mechanoreceptors' differential sensitivity to the force directed along the whisker length. Electron microscopic investigations of Merkel endings and lanceolate endings at the level of the ring sinus revealed unique anatomical features that may promote these differential sensitivities. The present study systematically integrates biomechanical principles with the anatomical and morphological characterization of primary afferent endings to describe the physical and cellular processing that shapes the neural representation of touch., Competing Interests: Declaration of Interests The authors declare no competing interests., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Rodents are the most commonly studied model system in neuroscience, but surprisingly few studies investigate the natural sensory stimuli that rodent nervous systems evolved to interpret. Even fewer studies examine neural responses to these natural stimuli. Decades of research have investigated the rat vibrissal (whisker) system in the context of direct touch and tactile stimulation, but recent work has shown that rats also use their whiskers to help detect and localize airflow. The present study investigates the neural basis for this ability as dictated by the mechanical response of whiskers to airflow. Mechanical experiments show that a whisker's vibration magnitude depends on airspeed and the intrinsic shape of the whisker. Surprisingly, the direction of the whisker's vibration changes as a function of airflow speed: vibrations transition from parallel to perpendicular with respect to the airflow as airspeed increases. Recordings from primary sensory trigeminal ganglion neurons show that these neurons exhibit responses consistent with those that would be predicted from direct touch. Trigeminal neuron firing rate increases with airspeed, is modulated by the orientation of the whisker relative to the airflow, and is influenced by the whisker's resonant frequencies. We develop a simple model to describe how a population of neurons could leverage mechanical relationships to decode both airspeed and direction. These results open new avenues for studying vibrissotactile regions of the brain in the context of evolutionarily important airflow-sensing behaviors and olfactory search. Although this study used only female rats, all results are expected to generalize to male rats. SIGNIFICANCE STATEMENT The rodent vibrissal (whisker) system has been studied for decades in the context of direct tactile sensation, but recent work has indicated that rats also use whiskers to help localize airflow. Neural circuits in somatosensory regions of the rodent brain thus likely evolved in part to process airflow information. This study investigates the whiskers' mechanical response to airflow and the associated neural response. Airspeed affects the magnitude of whisker vibration and the response magnitude of whisker-sensitive primary sensory neurons in the trigeminal ganglion. Surprisingly, the direction of vibration and the associated directionally dependent neural response changes with airspeed. These findings suggest a population code for airflow speed and direction and open new avenues for studying vibrissotactile regions of the brain., (Copyright © 2019 the authors.)

A recent Nature paper shows that activity in rodent forelimb somatosensory cortex is related to the animal's behavioral report of vibration intensity and identifies candidate mechanoreceptors responsible for the cortical response. Results highlight striking anatomical and neural differences from primates., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Importance: Suicide prediction models have the potential to improve the identification of patients at heightened suicide risk by using predictive algorithms on large-scale data sources. Suicide prediction models are being developed for use across enterprise-level health care systems including the US Department of Defense, US Department of Veterans Affairs, and Kaiser Permanente., Objectives: To evaluate the diagnostic accuracy of suicide prediction models in predicting suicide and suicide attempts and to simulate the effects of implementing suicide prediction models using population-level estimates of suicide rates., Evidence Review: A systematic literature search was conducted in MEDLINE, PsycINFO, Embase, and the Cochrane Library to identify research evaluating the predictive accuracy of suicide prediction models in identifying patients at high risk for a suicide attempt or death by suicide. Each database was searched from inception to August 21, 2018. The search strategy included search terms for suicidal behavior, risk prediction, and predictive modeling. Reference lists of included studies were also screened. Two reviewers independently screened and evaluated eligible studies., Findings: From a total of 7306 abstracts reviewed, 17 cohort studies met the inclusion criteria, representing 64 unique prediction models across 5 countries with more than 14 million participants. The research quality of the included studies was generally high. Global classification accuracy was good (≥0.80 in most models), while the predictive validity associated with a positive result for suicide mortality was extremely low (≤0.01 in most models). Simulations of the results suggest very low positive predictive values across a variety of population assessment characteristics., Conclusions and Relevance: To date, suicide prediction models produce accurate overall classification models, but their accuracy of predicting a future event is near 0. Several critical concerns remain unaddressed, precluding their readiness for clinical applications across health systems.

In this brief state of the science review, we provide a synopsis of the literature on psychological health mobile applications (apps) and discuss the impact of mobile technology on psychological health practice. We describe the variety of psychological health app uses from self-management, skills training, and supportive care to symptom tracking and data collection; and we summarize the current evidence for the efficacy and effectiveness of psychological health apps. Finally, we offer some pragmatic suggestions for evaluating psychological health apps for quality and clinical utility. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

In this study, we examined the indirect effect of the Virtual Hope Box (VHB) smartphone application on suicidal ideation, mediated through coping self-efficacy. A total of 117 veterans with suicidal ideation completed measures on coping self-efficacy and suicidal ideation at baseline and weeks 3, 6, and 12. Participants were randomly assigned to either the VHB or enhanced treatment as usual (eTAU) condition. Parallel process growth curve modeling (-0.20 [95% CI = -0.44, 0.00]) and auto-regressive modeling (-0.12 [95% CI = -0.35, -0.01]) revealed that a higher rate of change in coping self-efficacy in the VHB group was associated with a decrease in suicidal ideation severity, as compared to the eTAU group. Findings suggest that coping self-efficacy may be one mechanism by which the VHB operates to help reduce suicidal ideation. More broadly, the role of coping self-efficacy in reducing suicidal ideation is worthy of future study.

This paper presents data from the United States Department of Defense Suicide Event Report System for years 2012-2015 to detail descriptive, longitudinal rate data and risk factor profiles associated with military suicide. The annual findings were aggregated from all U.S. military suicide deaths and suicide attempts. Data elements included the most common method of suicide (firearms), most common behavioral health diagnoses (substance abuse/dependence), common life stressors (failed intimate-partner relationships), and an individual's history of operational deployment. Age- and sex-adjusted rates for the Services were compared with rates for the U.S. adult population. Results showed that the current reporting period (2015) is similar to patterns that have been observed over the preceding years and to patterns reported in the overall U.S. adult population. Suicide rates remain elevated but stable for both the Active and Reserve Components of the Military Services compared to historical levels observed prior to 2003. Finally, we discuss common errors and misinterpretations that can occur when analyzing surveillance data., (Published by Oxford University Press on behalf of Association of Military Surgeons of the United States 2019.)

Introduction Mild traumatic brain injury (mTBI) is an unfortunately common repercussion of military service in a combat zone. The CONTACT study tested an individualized telephone support intervention employing problem solving therapy (PST) for mTBI in soldiers recently returned from deployment. We sought to determine the cost effectiveness of this intervention from a military healthcare system perspective. Methods We conducted an intent-to-treat post-hoc analysis by building a decision analytic model that evaluated the choice between using PST or education only (EO). The model included cost-minimization and cost-effectiveness analyses. The incremental cost-effectiveness ratios (ICERs) were calculated as the differences in costs of PST versus EO relative to the differences in the outcomes of participants. Results The PST intervention resulted in an annual per-enrolee cost of $1027 (95% CI: $836 to $1248), while EO costs were $32 (95% CI: $25 to $39), resulting in a net incremental cost of $996 per enrolee (95% CI: $806 to $1,217). The ICERs were $68,658/QALY based on EQ-5D (95% CI: -$463,535 to $596,661) and $49,284/QALY based on SF-6D (95% CI: $26,971 to $159,309). Estimates of treatment costs in a real-world setting were accompanied by substantially lower ICERs that are within accepted thresholds for willingness-to-pay. Discussion Although the intervention had short-term benefits sufficient to yield acceptable ICERs, there was no long-term effect of PST over EO observed in the study. Consequently, we suggest that future studies examine the use of low-cost approaches, such as booster relapse-prevention calls, that may lead to a sustained treatment benefit for this population.

This pilot study examined the usability, acceptability, and effectiveness of a free Provider Resilience (PR) mobile application (app) designed by the National Center for Telehealth and Technology to reduce provider burnout. Outpatient mental health providers (N = 30) used the PR app for 1 month. Participants rated the PR app on the System Usability Scale with an overall score of 79.7, which is in the top quartile for usability. Results of paired sample t tests on the Professional Quality of Life Scale indicated significant decreases on the Burnout (t = 3.65, p < .001) and Compassion Fatigue (t = 4.54, p < .001) subscales. The Provider Resilience app shows promise in reducing burnout and compassion fatigue in mental health care providers.

Objective: The purpose of this study was to assess the impact of the Virtual Hope Box (VHB), a smartphone app to improve stress coping skills, suicidal ideation, and perceived reasons for living among patients at elevated risk of suicide and self-harm., Methods: The authors conducted a parallel-group randomized controlled trial with two groups of U.S. service veterans in active mental health treatment who had recently expressed suicidal ideation. Between March 2014 and April 2015, 118 patients were enrolled in the study. Participants were assigned to use the VHB (N=58) or to a control group that received printed materials about coping with suicidality (N=60) to supplement treatment as usual over a 12-week period. Three measures-the Coping Self-Efficacy Scale, Beck Scale for Suicidal Ideation, and Brief Reasons for Living Inventory-were collected at baseline (before randomization) and three, six, and 12 weeks. Secondary measures-the Interpersonal Needs Questionnaire, Perceived Stress Scale, and Columbia-Suicide Severity Rating Scale-were collected at baseline and 12 weeks., Results: VHB users reported significantly greater ability to cope with unpleasant emotions and thoughts (Coping Self-Efficacy Scale) at three (b=2.41, 95% confidence interval [CI]=.29-4.55) and 12 weeks (b=2.99, 95% CI=.08-5.90) compared with the control group. No significant advantage was found on other outcome measures for treatment augmented by the VHB., Conclusions: The VHB is a demonstrably useful accessory to treatment-an easily accessible tool that can increase stress coping skills. Because the app is easily disseminated across a large population, it is likely to have broad, positive utility in behavioral health care.

Curiosity, the tendency to engage in novel and challenging opportunities, may be an important source of resilience for those at risk for suicide. We hypothesized that curiosity would have a buffering effect against risk conferred by multiple sources of distress, whereby curiosity would be associated with reduced suicidal ideation and increased coping efficacy. As part of a larger intervention trial designed to improve coping skills and reduce suicidal ideation, 117 military veterans with suicidal ideation completed measures of curiosity and distress (perceived stress, depression, anxiety, and sleep disturbances) at baseline, and completed measures of suicidal ideation and coping efficacy (to stop negative thoughts, to enlist support from friends and family) at baseline and 3-, 6-, and 12-week follow up. Growth curve models showed that curiosity moderated the association between distress and suicidal ideation at baseline and that curiosity moderated the association between distress and increased coping efficacy to stop negative thoughts over time. Findings suggest that curiosity may buffer against the effect of heightened levels of distress on suicidal ideation and help facilitate stronger gains in coping efficacy over time. Additional work should further examine the role of curiosity as a protective factor for veterans with suicidal ideation., (Published by Elsevier B.V.)

Mild traumatic brain injury (mTBI) is a common injury for service members in recent military conflicts. There is insufficient evidence of how best to treat the consequences of mTBI. In a randomized, clinical trial, we evaluated the efficacy of telephone-delivered problem-solving treatment (PST) on psychological and physical symptoms in 356 post-deployment active duty service members from Joint Base Lewis McChord, Washington, and Fort Bragg, North Carolina. Members with medically confirmed mTBI sustained during deployment to Iraq and Afghanistan within the previous 24 months received PST or education-only (EO) interventions. The PST group received up to 12 biweekly telephone calls from a counselor for subject-selected problems. Both groups received 12 educational brochures describing common mTBI and post-deployment problems, with follow-up for all at 6 months (end of PST), and at 12 months. At 6 months, the PST group significantly improved on a measure of psychological distress (Brief Symptom Inventory; BSI-18) compared to the EO group (p = 0.005), but not on post-concussion symptoms (Rivermead Post-Concussion Symptoms Questionnaire [RPQ]; p = 0.19), the two primary endpoints. However, these effects did not persist at 12-month follow-up (BSI, p = 0.54; RPQ, p = 0.45). The PST group also had significant short-term improvement on secondary endpoints, including sleep (p = 0.01), depression (p = 0.03), post-traumatic stress disorder (p = 0.04), and physical functioning (p = 0.03). Participants preferred PST over EO (p < 0.001). Telephone-delivered PST appears to be a well-accepted treatment that offers promise for reducing psychological distress after combat-related mTBI and could be a useful adjunct treatment post-mTBI. Further studies are required to determine how to sustain its effects. (Trial registration: ClinicalTrials.gov Identifier: NCT01387490 https://clinicaltrials.gov ).

We describe recent advances in quantifying the three-dimensional (3D) geometry and mechanics of whisking. Careful delineation of relevant 3D reference frames reveals important geometric and mechanical distinctions between the localization problem ('where' is an object) and the feature extraction problem ('what' is an object). Head-centered and resting-whisker reference frames lend themselves to quantifying temporal and kinematic cues used for object localization. The whisking-centered reference frame lends itself to quantifying the contact mechanics likely associated with feature extraction. We offer the 'windowed sampling' hypothesis for active sensing: that rats can estimate an object's spatial features by integrating mechanical information across whiskers during brief (25-60ms) windows of 'haptic enclosure' with the whiskers, a motion that resembles a hand grasp., (Copyright © 2016. Published by Elsevier Ltd.)

A clearer understanding of risk factors for suicidal behavior among soldiers is of principal importance to military suicide prevention. It is unclear whether soldiers who attempt suicide and those who die by suicide have different patterns of risk factors. As such, preventive efforts aimed toward reducing suicide attempts and suicides, respectively, may require different strategies. We conducted a latent class analysis (LCA) to examine classes of risk factors among suicide attempters (n = 1,433) and decedents (n = 424). Both groups were represented by three classes: (1) External/Antisocial Risk Factors, (2) Mental Health Risk Factors, and (3) No Pattern. These findings support the conceptualization that military suicide attempters and decedents represent a single population., (Published 2016. This article is a U.S. Government work and is in the public domain in the USA.)

Tactile information available to the rat vibrissal system begins as external forces that cause whisker deformations, which in turn excite mechanoreceptors in the follicle. Despite the fundamental mechanical origin of tactile information, primary sensory neurons in the trigeminal ganglion (Vg) have often been described as encoding the kinematics (geometry) of object contact. Here we aimed to determine the extent to which Vg neurons encode the kinematics vs. mechanics of contact. We used models of whisker bending to quantify mechanical signals (forces and moments) at the whisker base while simultaneously monitoring whisker kinematics and recording single Vg units in both anesthetized rats and awake, body restrained rats. We employed a novel manual stimulation technique to deflect whiskers in a way that decouples kinematics from mechanics, and used Generalized Linear Models (GLMs) to show that Vg neurons more directly encode mechanical signals when the whisker is deflected in this decoupled stimulus space., Competing Interests: The authors declare that no competing interests exist.

Objective: Although personal electronic devices, such as mobile phones, computers, and tablets, increasingly are being leveraged as vehicles for health in the civilian world, almost nothing is known about personal technology use in the U.S. military. In 2012 we conducted a unique survey of personal technologies used by U.S. military service members. However, with the rapidly growing sophistication of personal technology and changes in consumer habits, that knowledge must be continuously updated to be useful. Accordingly, we recently surveyed new samples of active duty service members, National Guard and Reserve, and veterans., Materials and Methods: We collected data by online surveys in 2013 from 239 active, inactive, and former service members. Online surveys were completed in-person via laptop computers at a large military installation and remotely via Web-based surveys posted on the Army Knowledge Online Web site and on a Defense Center Facebook social media channel., Results and Conclusions: We measured high rates of personal technology use by service members at home across popular electronic media. The most dramatic change since our earlier survey was the tremendous increase in mobile phone use at home for a wide variety of purposes. Participants also reported moderate non-work uses of computers and tablets while on recent deployment to Iraq and Afghanistan, but almost no mobile phone use, ostensibly because of military restrictions in the war zone. These latest results will enable researchers and technology developers target their efforts on the most promising and popular technologies for psychological health in the military.

A "Hope Box" is a therapeutic tool employed by clinicians with patients who are having difficulty coping with negative thoughts and stress, including patients who may be at risk of suicide or nonsuicidal self-harm. We conducted a proof-of-concept test of a "Virtual" Hope Box (VHB)-a smartphone app that delivers patient-tailored coping tools. Compared with a conventional hope box integrated into VA behavioral health treatment, high-risk patients and their clinicians used the VHB more regularly and found the VHB beneficial, useful, easy to set up, and said they were likely to use the VHB in the future and recommend the VHB to peers., (© Published 2014. This article is a U.S. Government work and is in the public domain in the USA.)

Many military personnel returning from deployment experience increases in psychological symptoms, including post-traumatic stress disorder (PTSD), depression, and mood changes. Patient health diaries are commonly used for self-reporting over time away from the clinic. "T2 Mood Tracker" is an application ("app") for smartphones and other mobile devices that enables users to rate their moods, to self-monitor across time, and to report their emotional experiences to health providers. We designed T2 Mood Tracker to track symptoms associated with deployment-related behavioral health issues, including PTSD, Head Injury, Stress, Depression, Anxiety, and General Well-Being. We field-tested T2 Mood Tracker with a small sample of redeployed soldiers under treatment for behavioral health issues at a Warrior Transition Unit. Participants used the app an average of 10 different days over the 2- to 3-week test period. Consensus was that T2 Mood Tracker was easy to use, useful and beneficial. The majority said they would use the app in the future, would recommend it to other service members, and would use the app to share their mood information with a provider. Warrior Transition Unit providers were enthusiastic about the potential of T2 Mood Tracker as a tool for use with their patients., (Reprint & Copyright © 2014 Association of Military Surgeons of the U.S.)

Like the better-publicized pleasurable NDEs, distressing near-death experiences are both fascinating and frustrating as altered states of consciousness. Because of the deeply rooted concept of hell in Western culture and its Christian association with eternal physical torment, they pose serious challenges to the individuals who must shape their lives around such a profoundly durable event, and to their families, friends, and physicians. In the absence of clear-cut clinical data and universal cultural views, physicians are advised that neutrality of opinion and careful listening are likely to constitute best professional practice for addressing these difficult near-death experiences.

Purpose: The purpose of this trial was to evaluate the effect of a Web-based, self-report assessment and educational intervention on symptom distress during cancer therapy., Patients and Methods: A total of 752 ambulatory adult participants were randomly assigned to symptom/quality-of-life (SxQOL) screening at four time points (control) versus screening, targeted education, communication coaching, and the opportunity to track/graph SxQOL over time (intervention). A summary of the participant-reported data was delivered to clinicians at each time point in both groups. All participants used the assessment before a new therapeutic regimen, at 3 to 6 weeks and 6 to 8 weeks later, completing the final assessment at the end of therapy. Change in Symptom Distress Scale-15 (SDS-15) score from pretreatment to end of study was compared using analysis of covariance and regression analysis adjusting for selected variables., Results: We detected a significant difference between study groups in mean SDS-15 score change from baseline to end of study: 1.27 (standard deviation [SD], 6.7) in the control group (higher distress) versus -0.04 (SD, 5.8) in the intervention group (lower distress). SDS-15 score was reduced by an estimated 1.21 (95% CI, 0.23 to 2.20; P = .02) in the intervention group. Baseline SDS-15 score (P < .001) and clinical service (P = .01) were predictive. Multivariable analyses suggested an interaction between age and study group (P = .06); in subset analysis, the benefit of intervention was strongest in those age > 50 years (P = .002)., Conclusion: Web-based self-care support and communication coaching added to SxQOL screening reduced symptom distress in a multicenter sample of participants with various diagnoses during and after active cancer treatment. Participants age > 50 years, in particular, may have benefited from the intervention.

The smartphone is an increasingly widespread technological vehicle for general health and psychological health promotion, evaluation, education, and sometimes intervention. However, the psychometric performance of behavioral health screening measures has not been commonly evaluated for the new, small-format, touch-screen medium. Before mobile-based applications for behavioral health screening can be disseminated confidently, the reliability and the validity of measures administered by the smartphone must be evaluated. We compared psychometric properties (i.e., internal consistency and test-retest reliability) of seven behavioral health measures completed on paper, a computer, and an iPhone by 45 army soldiers. The results showed the internal consistencies of the smartphone-delivered measures to be equivalent and very high across all three modalities and the test-retest reliability of the iPhone measures also to be very high. Furthermore, completion of the behavioral screening measures by the iPhone was highly preferred over the other modalities and was reported to be easy and convenient. Our findings help corroborate the use of smartphones and other small mobile devices for behavioral health screening.

The Department of Defense Suicide Event Report Program collects extensive information on suicides and suicide attempts from the U.S. Air Force, Army, Marine Corps, and Navy. Data are compiled on demographics, suicide event details, behavioral health treatment history, military history, and information about other potential risk factors such as psychosocial stressors that were present at the time of the event. The ultimate goal of this standardized suicide surveillance program is to assist suicide prevention in the U.S. military. Descriptive data are presented on 816 suicides and 1,514 suicide attempts reported through the program between 2008 and 2010., (© 2013 This article is a U.S. Government work and is in the public domain in the USA.)

Objective: This research developed and tested the Military Stigma Scale (MSS), a 26-item scale, designed to measure public and self-stigma, two theorized core components of mental health stigma., Method: The sample comprised 1,038 active duty soldiers recruited from a large Army installation. Soldiers' mean age was 26.7 (standard deviation = 5.9) years, and 93.6% were male. The sample was randomly split into a scale development group (n = 520) and a confirmatory group (n = 518)., Results: Factor analysis conducted with the scale development group resulted in the adoption of two factors, named public and self-stigma, accounting for 52.1% of the variance. Confirmatory factor analysis conducted with the confirmatory group indicated good fit for the two-factor model. Both factors were components of a higher order stigma factor. The public and self-stigma scales for the exploratory and confirmatory groups demonstrated good internal consistency (α = .94 and .89; α = .95 and .87, respectively). Demographic differences in stigma were consistent with theory and previous empirical research: Soldiers who had seen a mental health provider scored lower in self-stigma than those who had not., Conclusions: The MSS comprises two internally consistent dimensions that appear to capture the constructs of public and self-stigma. The overall results indicate that public and self-stigma are dimensions of stigma that are relevant to active duty soldiers and suggest the need to assess these dimensions in future military stigma research., (© 2012 Wiley Periodicals, Inc.)

Objective: Personal technologies such as smartphones, computers, and gaming devices, are ubiquitous in the civilian world. Consequently they represent ideal vehicles for disseminating psychological and other health resources and interventions. However, almost nothing is known about personal technology use in the U.S. military. We conducted the most comprehensive survey to date of the use, availability, and need for personal technologies by U.S. military service members. Our survey asked detailed questions about computers and the Internet, phones and smartphones, other mobile or portable technologies, gaming devices, and TV and video media used during deployment and at permanent duty station or home., Materials and Methods: We collected data by paper-and-pencil survey in 2010 and 2011 from 331 active Army service members at a processing and registration center in a large military installation in the western United States. Two cohorts were surveyed: Soldiers who had previously been deployed to a warzone and soldiers who had never been deployed., Results and Conclusion: We measured high rates of personal technology use by service members at home across all popular electronic media. Soldiers at home essentially resembled civilian consumers in their use of popular technologies. Some technologies, including the Internet, gaming, and TV, were widespread on deployment. Others, most notably cellphones, were more restricted by availability, connectivity, opportunity, and military regulation in the warzone. Results will enable researchers and technology developers target their efforts on the most promising and popular technologies for psychological health in the military.

The US National Strategy for Suicide Prevention (National Strategy) described 11 goals across multiple areas, including suicide surveillance. Consistent with these goals, the Department of Defense (DoD) has engaged aggressively in the area of suicide surveillance. The DoD's population-based surveillance system, the DoD Suicide Event Report (DoDSER) collects information on suicides and suicide attempts for all branches of the military. Data collected includes suicide event details, treatment history, military and psychosocial history, and psychosocial stressors at the time of the event. Lessons learned from the DoDSER program are shared to assist other public health professionals working to address the National Strategy objectives.

An upward trend of suicides has emerged in the U.S. military, and record high suicide rates have been reported. There is abundant evidence of the negative consequences of trauma, especially posttraumatic stress disorder, as risk factors for suicide. However, stressful events and trauma sometimes can have positive psychological consequences, commonly labeled posttraumatic growth (PTG). Little formal research has examined the role of PTG in moderating suicide in the military. We examined the relationship between PTG and suicidal ideation in data reported by 5302 service members with war zone or combat experience completing the Army's Automated Behavioral Health Clinic electronic screening. Controlling for other known risk factors for suicide, we found that the more PTG service members reported, the less suicidal ideation they subsequently espoused. Our results suggest the need for further research to determine the potential clinical value of PTG as a therapeutic component of suicide prevention.

Pancratistatin is a potent anticancer natural product, whose clinical evaluation is hampered by the limited natural abundance and the stereochemically complex structure undermining practical chemical preparation. Fifteen aromatic analogues of conduritol F, l-chiro-inositol, and dihydroconduritol F that possess four of the six pancratistatin stereocenters have been synthesized and evaluated for anticancer activity. These compounds serve as truncated pancratistatin analogues lacking the lactam ring B, but retaining the crucial C10a-C10b bond with the correct stereochemistry. The lack of activity of these compounds provides further insight into pancratistatin's minimum structural requirements for cytotoxicity, particularly the criticality of the intact phenanthridone skeleton. Significantly, these series provide rare examples of simple aromatic conduritol and inositol analogues and, therefore, this study expands the chemistry and biology of these important classes of compounds.

Much is written about Internet access, Web access, Web site accessibility, and access to online health information. The term access has, however, a variety of meanings to authors in different contexts when applied to the Internet, the Web, and interactive health communication. We have summarized those varied uses and definitions and consolidated them into a framework that defines Internet and Web access issues for health researchers. We group issues into two categories: connectivity and human interface. Our focus is to conceptualize access as a multicomponent issue that can either reduce or enhance the public health utility of electronic communications.

Emerging literature suggests that quality of life (QOL) after bone marrow transplantation is relatively good but is accompanied in some patients by a variety of residual difficulties. The studies supporting this finding, however, have been somewhat limited in scale, scope, design, and analysis. We comprehensively measured changes in multidimensional QOL in a 4-year longitudinal follow-up of 415 adult patients who received hematopoietic stem cell transplants at Fred Hutchinson Cancer Research Center. Questionnaire packets containing 271 items were mailed annually posttransplantation to patients' homes. Standard methods of analysis yielded conditional estimates depending on compliance and survival, whereas new, likelihood-based methods generated unconditional estimates applicable to the full intent-to-treat population. Typical QOL levels generally remained high over the entire study period. Most QOL functioning significantly improved over 4 years, with the remainder showing no important decrement. Although isolated problem areas, such as sexual dissatisfaction, did emerge, the level of dysfunction for most physical and psychological scales remained below 30% of scale maxima. Broadly similar results were obtained for conditional estimation, which may contain an optimistic bias, and for unconditional estimation, which largely avoids the bias. Because concurrence was obtained between the 2 types of estimation, we conclude that most patients really do experience good levels of QOL in the 4 years after transplantation. Although some problems can be anticipated, typical patients can look forward to a QOL after transplantation that is broadly comparable to that of the normal population.

The authors randomly selected 400 physicians from a population of 1,545 practicing physicians providing follow-up care to patients who received bone marrow or blood stem cell transplants at the Fred Hutchinson Cancer Research Center to determine interest in receiving Internet-based transplant information. In a two-factor completely randomized factorial design, the 400 physicians were assigned to receive mailed surveys with either no compensation or a $5 check and either no follow-up call or a follow-up call 3 weeks after mailing. Overall, 51.5% of the physicians returned the mailed surveys. Comparison of logit models showed that inclusion of a $5 check in the mailer significantly (p = .016) increased the probability of returning the surveys (57.5% vs. 45.5%). In contrast, the telephone follow-up had no overall effect. The authors concluded a modest financial reward can significantly improve physician response rates to research surveys but a telephone follow-up may be inefficient and even ineffective.

Purpose/objectives: To explore the development of a customized Web site to assist Breast and Cervical Health Program (BCHP) outreach staff in a community screening program and to evaluate the Internet knowledge and access issues and barriers of outreach staff during a two-year period using the Web site., Design: Knowledge, access issues and barriers, and descriptive questionnaires., Settings: Comprehensive cancer center in Seattle, WA, workshops, and presentations around the state., Sample: BCHP outreach workers, screening coordinators, and almost exclusively public health nurses from regional health districts and program-contracted clinics., Method: Web site development was based on continuous input from sample. Detailed descriptions of computer and Internet resources and opinions about the use and usefulness of the BCHP Web site came from a 1996 evaluation and 1998 follow-up conducted using mailed and online Web questionnaires. "Hits" to the Web site were monitored monthly., Main Research Variables: Computer and Internet resources were used along with monthly Web site traffic and opinions about the use and usefulness of the BCHP Web site in the outreach program., Findings: Use of the BCHP Web site has risen steadily over two years to reach a stable plateau. User evaluations show a marked increase in the adoption of the Internet as a working tool. Users believe the Internet is becoming increasingly important to their work. More training and familiarization with the Web is needed., Conclusions: The Web is an efficient medium for improving communication and providing easy access to resources within the BCHP program., Implications for Nursing Practice: Public health programs with meager resources can benefit from the relatively inexpensive use of customized and versatile Web sites.

Background: Recent studies examining the medical and psychosocial sequelae of bone marrow transplantation have reported most survivors do relatively well while a smaller group continues to experience less than optimal quality of life (QOL). Many of these studies are limited by small sample sizes, limited scope, and focus on a narrow (1-4 year) window of survival., Methods: The descriptive survey examined the QOL, late medical complications, psychological distress, demands of long-term recovery, and health perceptions of 125 adults surviving 6-18 (mean 10) years after marrow transplantation. Seven wide-ranging tests covering 271 items were completed on average in 90 min. Two tests were developed by the authors specifically for assessing QOL in this population., Results: 74% of long-term survivors of bone marrow transplantation reported their current QOL was the same or better than before transplantation, 80% rated their current health status and QOL as good to excellent, and 88% said the benefits of transplantation outweighed the side effects. Ten years or more post-transplantation, long-term survivors continued to experience a moderate incidence of lingering complications and demands, including emotional and sexual dysfunction, fatigue, eye problems, sleep disturbance, general pain and cognitive dysfunction. However, the severity or degree of distress attributed to those complications was, for most survivors, consistently low. Nearly all were back to work or school. Only 5% rated both their QOL and health status as poor. Long-term survivors demonstrated good mood and low psychological distress compared to cancer and population norms, and had the same perceptions as the general population of their current health and expectation of future health. Demands attributed to long-term survival appeared to impose little hardship. The most frequently cited demand of recovery was the perceived lack of social support as time went on., Conclusions: Almost all long-term survivors were leading full and meaningful lives. Persistent complications were, on the whole, dismissed as relatively trivial and the overwhelming majority viewed themselves as cured and well.