Logistic Regression With Machine Learning Sheds Light on the Problematic Sexual Behavior Phenotype.

OBJECTIVES: There has been a longstanding debate about whether the mechanisms involved in problematic sexual behavior (PSB) are similar to those observed in addictive disorders, or related to impulse control or to compulsivity. The aim of this report was to contribute to this debate by investigating the association between PSB, addictive disorders (internet addiction, compulsive buying), measures associated with the construct known as reward deficiency (RDS), and obsessive-compulsive disorder (OCD). METHODS: A Canadian university Office of the Registrar invited 68,846 eligible students and postdoctoral fellows. Of 4710 expressing interest in participating, 3359 completed online questionnaires, and 1801 completed the Mini-International Neuropsychiatric Interview. PSB was measured by combining those screening positive (score at least 6) on the Sexual Addiction Screening Test-Revised Core with those self-reporting PSB. Current mental health condition(s) and childhood trauma were measured by self-report. OCD was assessed by a combination of self-report and Mini-International Neuropsychiatric Interview data. RESULTS: Of 3341 participants, 407 (12.18%) screened positive on the Sexual Addiction Screening Test-Revised Core. On logistic regression, OCD, attention deficit, internet addiction, a family history of PSB, childhood trauma, compulsive buying, and male gender were associated with PSB. On multiple correspondence analysis, OCD appeared to cluster separately from the other measures, and the pattern of data differed by gender. CONCLUSIONS: In our sample, factors that have previously been associated with RDS and OCD are both associated with increased odds of PSB. The factors associated with RDS appear to contribute to a separate data cluster from OCD and to lie closer to PSB.

The feasibility and acceptability of mobile application-based assessment of suicidality using self-report components of a novel tool, the Suicide Ideation and Behavior Assessment Tool (SIBAT).

The aim of this study was to assess the validity of a mobile application-based self-report questionnaire in the assessment of suicidality. We developed a program for the administration of self-report components of the Suicide Ideation and Behavior Assessment Tool (SIBAT). We invited university students and trainees enrolled in a study of addictions to complete this component of the SIBAT using the program on their mobile devices or personal computer. 196 participants completed all required modules of the SIBAT, with 97 using their mobile device and 99 using their personal computer. Rates of completed questionnaires between the two groups were compared, as were the responses to the items and the total scores. There was a significant difference between proportions of scale completion in both groups, with a greater number of participants who used a personal computer to complete the scale not responding to all questions compared to participants who used a mobile device to complete the scale. Data collected via mobile device showed good concurrent validity with data collected via personal computer. A trend toward greater disclosure of suicidality was observed in the mobile device group however, replication of these findings using larger sample sizes is needed.

Internal consistency and concurrent validity of self-report components of a new instrument for the assessment of suicidality, the Suicide Ideation and Behavior Assessment Tool (SIBAT).

This study aimed to assess the internal consistency of self-report components of the Suicide Ideation and Behavior Assessment Tool (SIBAT) and validate it with relevant elements of the Mini International Neuropsychiatric Interview (MINI). The SIBAT is a newly developed instrument for the evaluation of suicidality. In this study, we invited university students and trainees participating in a study of addictions to complete the self-report component of the SIBAT as an add-on study. We evaluated the internal consistency of the self-report component of the SIBAT and validated it against the suicidality component of the MINI. Data were analysed using both complete case analysis and multiple imputation. SIBAT data were collected for 394 participants, 314 of whom had also completed the MINI. The internal consistency of modules 2, 3, and 5 of the SIBAT was high. Each item from module 5 had a statistically significant association with the corresponding item from the MINI. The sum of scores from modules 2 and 3 had a moderate correlation with the assessment of suicide risk determined by the MINI, and a strong correlation with the total score of SIBAT module 5. The completion median time of modules 2, 3 and 5 was 14.3 min.

Masculinity's association with the interpersonal theory of suicide among military personnel.

OBJECTIVE: Given that the majority of those who die by suicide are male, masculine traits have been examined as a potential link to the development of capability for suicide. However, research has not examined if such traits influence suicidal desire (i.e., thwarted belongingness, perceived burdensomeness). This study examined the influence of stereotypically masculine traits of stoicism, sensation seeking, physical aggression, verbal aggression, and self-reliance on all three components of the Interpersonal Theory of Suicide within a sample of male and female service members. METHODS: A total of 953 service members were recruited as part of a larger study. RESULTS: Sensation seeking and stoicism were positively associated with capability for suicide. With regard to suicidal desire, self-reliance and verbal aggression were positively associated with both perceived burdensomeness and thwarted belongingness. Stoicism was positively associated with thwarted belongingness. CONCLUSIONS: Findings suggest that different masculine traits are associated with the three components of the Interpersonal Theory of Suicide in various ways. Stoicism may be an especially important masculine trait that influences a component of suicidal desire and capability for suicide.

Quantifying groundwater flow variability in a poorly cemented fractured sandstone aquifer to inform in situ remediation.

This study applies innovative methods to characterize and quantify the magnitude of groundwater flow in a fractured and variably cemented sandstone aquifer to inform an in-situ remediation strategy for trichloroethene (TCE) contamination. A modified active-distributed temperature sensing (A-DTS) approach in which fiber optic cables were permanently grouted in the borehole was used to quantify groundwater flow rates. Two additional tracer tests were conducted: 1) fluorescein tracer injection followed by rock coring and sampling for visual mapping and porewater analysis, and 2) deployment of passive flux meters in conventional monitoring wells to evaluate groundwater velocity and mass flux distributions. Forced gradient injection of fluorescein tracer suggests a dual porosity flow system wherein higher rates of groundwater flow occur within discrete features including highly permeable bedding planes and fractures, with slower flow occurring within the rock matrix. Tracer was observed and detected in the unfractured matrix porewater >1.5 m away from the injection well. Beyond this distance, >6 m radially away from the injection hole, tracer was primarily detected within and adjacent to high transmissivity fractures serving as preferential flow paths. The Darcy flux calculated using active distributed temperature sensing (A-DTS) shows depth-discrete values ranging from 7 to 60 cm/day, with average and median values of 23 and 17 cm/day, respectively. Passive Flux Meters (PFMs) deployed in three conventional monitoring wells with slotted screens and sand filter packs showed groundwater flux values ranging from 2 to 11 cm/day, with an overall average of 4 cm/day and are likely biased low due to spreading in the sand pack. The study results were used to inform an in-situ remediation system design including the proposed injection well spacing and the amendment delivery approach. In addition, the results were used to build confidence in the viability of delivering an oxidant to the rock matrix via advective processes. This is important because 1) the matrix is where the majority of the TCE mass occurs, and 2) it provides insights on processes that directly affect remedial performance expectations given advective delivery to preferential pathways and the matrix overcomes diffusion only conditions.

Lasofoxifene as a potential treatment for therapy-resistant ER-positive metastatic breast cancer.

BACKGROUND: Endocrine therapy remains the mainstay of treatment for estrogen receptor-positive (ER+) breast cancer. Constitutively active mutations in the ligand binding domain of ERα render tumors resistant to endocrine agents. Breast cancers with the two most common ERα mutations, Y537S and D538G, have low sensitivity to fulvestrant inhibition, a typical second-line endocrine therapy. Lasofoxifene is a selective estrogen receptor modulator with benefits on bone health and breast cancer prevention potential. This study investigated the anti-tumor activity of lasofoxifene in breast cancer xenografts expressing Y537S and D538G ERα mutants. The combination of lasofoxifene with palbociclib, a CDK4/6 inhibitor, was also evaluated. METHODS: Luciferase-GFP tagged MCF7 cells bearing wild-type, Y537S, or D538G ERα were injected into the mammary ducts of NSG mice (MIND model), which were subsequently treated with lasofoxifene or fulvestrant as single agents or in combination with palbociclib. Tumor growth and metastasis were monitored with in vivo and ex vivo luminescence imaging, terminal tumor weight measurements, and histological analysis. RESULTS: As a monotherapy, lasofoxifene was more effective than fulvestrant at inhibiting primary tumor growth and reducing metastases. Adding palbociclib improved the effectiveness of both lasofoxifene and fulvestrant for tumor suppression and metastasis prevention at four distal sites (lung, liver, bone, and brain), with the combination of lasofoxifene/palbociclib being generally more potent than that of fulvestrant/palbociclib. X-ray crystallography of the ERα ligand binding domain (LBD) shows that lasofoxifene stabilizes an antagonist conformation of both wild-type and Y537S LBD. The ability of lasofoxifene to promote an antagonist conformation of Y537S, combined with its long half-life and bioavailability, likely contributes to the observed potent inhibition of primary tumor growth and metastasis of MCF7 Y537S cells. CONCLUSIONS: We report for the first time the anti-tumor activity of lasofoxifene in mouse models of endocrine therapy-resistant breast cancer. The results demonstrate the potential of using lasofoxifene as an effective therapy for women with advanced or metastatic ER+ breast cancers expressing the most common constitutively active ERα mutations.

A Smartphone App to Manage Cirrhotic Ascites Among Outpatients: Feasibility Study.

BACKGROUND: Ascites is a common, painful, and serious complication of cirrhosis. Body weight is a reliable proxy for ascites volume; therefore, daily weight monitoring is recommended to optimize ascites management. OBJECTIVE: This study aims to evaluate the feasibility of a smartphone app in facilitating outpatient ascites management. METHODS: In this feasibility study, patients with cirrhotic ascites requiring active management were identified in both inpatient and outpatient settings. Patients were provided with a Bluetooth-connected scale, which transmitted weight data to a smartphone app and then via the internet to an electronic medical record (EMR). Weights were monitored every weekday. In the event of a weight change of ≥5 lbs in 1 week, patients were called and administered a short symptom questionnaire, and providers received an email alert. The primary outcomes of this study were the percentage of enrolled days during which weight data were successfully transmitted to an EMR and the percentage of weight alerts that prompted responses by the provider. RESULTS: In this study, 25 patients were enrolled: 12 (48%) were male, and the mean age was 58 (SD 13; range 35-81) years. A total of 18 (72%) inpatients were enrolled. Weight data were successfully transmitted to an EMR during 71.2% (697/979) of the study enrollment days, with technology issues reported on 16.5% (162/979) of the days. Of a total of 79 weight change alerts fired, 41 (52%) were triggered by weight loss and 38 (48%) were by weight gain. Providers responded in some fashion to 66 (84%) of the weight alerts and intervened in response to 45 (57%) of the alerts, for example, by contacting the patient, scheduling clinic or paracentesis appointments, modifying the diuretic dose, or requesting a laboratory workup. Providers responded equally to weight increase and decrease alerts (P=.87). The staff called patients a mean of 3.7 (SD 3.5) times per patient, and the number of phone calls correlated with technology issues (r=0.60; P=.002). A total of 60% (15/25) of the patients chose to extend their participation beyond 30 days. A total of 17 patient readmissions occurred during the study period, with only 4 (24%) related to ascites. CONCLUSIONS: We demonstrated the feasibility of a smartphone app to facilitate the management of ascites and reported excellent rates of patient and provider engagement. This innovation could enable early therapeutic intervention, thereby decreasing the burden of morbidity and mortality among patients with cirrhosis.

Internal Battles: Examining How Anger/Hostility Moderate the Association Between Negative Urgency and Suicidal Desire Variables in Military and Civilian Samples.

OBJECTIVE: Suicide is consistently within the top ten leading causes of death in the United States. The suicide rate of National Guard personnel is elevated relative to the general population; however, research suggests that many of the suicide risk factors for military personnel are similar to the suicide risk factors for civilians. We examined whether negative urgency moderated the relationships between anger/hostility and perceived burdensomeness/thwarted belongingness in both a military and civilian samples. METHOD: There were two samples in the current study: (1) military personnel (majority national guard) and (2) community members oversampled for suicide attempt history. RESULTS: Our hypotheses were partially supported with the interaction of hostility and negative urgency predicting perceived burdensomeness in the military sample. Within civilians, anger interacted with negative urgency to predict perceived burdensomeness. There were nonsignificant findings for analyses predicting thwarted belongingness. Exploratory analyses indicated that in both samples, anger and hostility interacted with negative urgency to predict suicidal ideation. CONCLUSIONS: Results suggest that aggressive attributes may contribute to individuals feeling as though they are a burden on others when moderate to high levels of negative urgency are present. Additionally, this study provides foundational support for the differences between suicidal desire and ideation.

The Relationship between Post-Battle Experiences and Thwarted Belongingness and Perceived Burdensomeness in Three United States Military Samples.

Suicide rates within the military are elevated relative to the general population; however, research suggests that many of the suicide risk factors for military personnel are similar to the suicide risk factors for civilians. Given that many military specific experiences (e.g., number of deployments) are not considered robust predictors of either suicidal ideation or behavior, it has been posited that deployment specific experiences (e.g., post-battle experiences) may be better able to explain the increased rates of suicide among military personnel. Therefore, the current study aimed to examine the relationship between post-battle experiences and perceived burdensomeness (PB), thwarted belongingness (TB), and suicidal ideation within 3 different military samples: a non-clinical sample of Army National Guard personnel, a non-clinical sample of active duty U.S. Air Force Security Forces personnel, and a clinical sample of U.S. Army personnel receiving outpatient treatment. Post-battle experiences were found to be significantly associated with TB in both non-clinical samples; however, the association between post-battle experiences and TB was non-significant within the clinical sample. Furthermore, results indicated that post-battle experiences were not significantly associated with either PB or suicidal ideation in any of the samples. These findings suggest that in non-clinical samples, post-battle experiences impact a soldier's ability to feel connected to others. Within clinical samples, results indicate that post-battle experiences may not be a direct contributor to either PB or TB. These results indicate a need for universal intervention promoting interpersonal support of military personnel and their families prior to development of further need for psychological interventions. This upstream approach may decrease further development of TB and potentially prevent suicidal desire.

Glucocorticoid receptor modulation decreases ER-positive breast cancer cell proliferation and suppresses wild-type and mutant ER chromatin association.

BACKGROUND: Non-ER nuclear receptor activity can alter estrogen receptor (ER) chromatin association and resultant ER-mediated transcription. Consistent with GR modulation of ER activity, high tumor glucocorticoid receptor (GR) expression correlates with improved relapse-free survival in ER+ breast cancer (BC) patients. METHODS: In vitro cell proliferation assays were used to assess ER-mediated BC cell proliferation following GR modulation. ER chromatin association following ER/GR co-liganding was measured using global ChIP sequencing and directed ChIP analysis of proliferative gene enhancers. RESULTS: We found that GR liganding with either a pure agonist or a selective GR modulator (SGRM) slowed estradiol (E2)-mediated proliferation in ER+ BC models. SGRMs that antagonized transcription of GR-unique genes both promoted GR chromatin association and inhibited ER chromatin localization at common DNA enhancer sites. Gene expression analysis revealed that ER and GR co-activation decreased proliferative gene activation (compared to ER activation alone), specifically reducing CCND1, CDK2, and CDK6 gene expression. We also found that ligand-dependent GR occupancy of common ER-bound enhancer regions suppressed both wild-type and mutant ER chromatin association and decreased corresponding gene expression. In vivo, treatment with structurally diverse SGRMs also reduced MCF-7 Y537S ER-expressing BC xenograft growth. CONCLUSION: These studies demonstrate that liganded GR can suppress ER chromatin occupancy at shared ER-regulated enhancers, including CCND1 (Cyclin D1), regardless of whether the ligand is a classic GR agonist or antagonist. Resulting GR-mediated suppression of ER+ BC proliferative gene expression and cell division suggests that SGRMs could decrease ER-driven gene expression.

Psychopathic Personality Traits in the Military: An Examination of the Levenson Self-Report Psychopathy Scales in a Novel Sample.

The Levenson Self-Report Psychopathy Scale is a short, self-report measure initially developed to assess psychopathic traits in noninstitutionalized samples. The present study aimed to explore factor structure and convergent and discriminant validity of the Levenson Self-Report Psychopathy Scale in a large U.S. military sample (90.7% Army National Guard). Factor analytic data, regression, and correlational analyses point to the superiority of Brinkley, Diamond, Magaletta, and Heigel's three-factor model in this sample. Implications for theory and the study of psychopathic personality traits in a military sample are discussed.

Detecting Potential Underreporting of Suicide Ideation Among U.S. Military Personnel.

Using a military sample comprised largely of National Guard personnel, zero-inflation negative binomial regression was applied to estimate the effects of indirect, nonface valid indicators of suicide ideation [Thwarted Belongingness (TB), Perceived Burdensomeness (PB), and Hopelessness], in predicting suicide ideation. Data from a sample of 497 military personnel (82.1% male; mage  = 27.24; range = 18-59) were analyzed. TB and the interaction of TB with Hopelessness were significant predictors in the logistic regression, and in the negative binomial regression, the main effects of TB and hopelessness, and the interactions of TB with hopelessness and PB with hopelessness were significant. The findings further indicated that approximately 10% of those not reporting ideation would be predicted to be ideators. Clinically, these results indicate that, in samples reluctant to report ideation, the assessment of suicide risk may improve through the use of relevant measures that do not explicitly reference suicide thoughts.

How Distress Tolerance Mediates the Relationship Between Posttraumatic Stress Disorder and the Interpersonal Theory of Suicide Constructs in a U.S. Military Sample.

OBJECTIVES: Despite the general suicide rate within the military being comparable to the general population when comparing peers, there are certain branches of the military that have elevated risk. Specifically, the U.S. National Guard has suicide rates that are constantly higher than other military branches and civilian peers. The National Guard are a unique military population in which they frequently transition between military and civilian life. With these unique experiences and heightened risk, military suicide prevention efforts may benefit from further research within this population. Posttraumatic stress disorder (PTSD) is another concern amongst military personnel and has been linked to suicidal behavior. METHODS: The current study examined the indirect effects that distress tolerance, a protective factor against suicide, has on the relationship between PTSD and constructs within a well-validated theory for suicide (the Interpersonal-Psychological Theory for suicidal behaviors) in a sample of U.S. Army National Guard personnel. RESULTS: Results indicated that distress tolerance had a significant indirect effect on the relationship between PTSD and thwarted belongingness, perceived burdensomeness, and capability for suicide. CONCLUSIONS: These findings are consistent with previous literature examining the relationship between distress tolerance and our outcome variables. These results could have important clinical implications, mainly that intervention strategies targeting distress tolerance could have significant impacts on suicide-relate thoughts.

Military personnel compared to multiple suicide attempters: Interpersonal theory of suicide constructs.

The current study aimed to address the discrepancy between suicide rates in the military and general population by comparing facets of the interpersonal theory of suicide between civilians with multiple suicide attempts and U.S. military personnel. Military personnel exhibited higher levels of capability for suicide but lower levels of perceived burdensomeness and thwarted belongingness than civilian multiple attempters. When comparing only personnel endorsing ideation and civilian multiple attempters, the significant difference for capability remained, but the differences for perceived burdensomeness and thwarted belongingness became nonsignificant. Results suggest the emergence of ideation places personnel at a greater risk for suicide than many civilian multiple attempters.

Dark traits and suicide: Associations between psychopathy, narcissism, and components of the interpersonal-psychological theory of suicide.

Studies have identified independent relationships between psychopathy, narcissism, and suicidality. The current study expands upon the extant literature by exploring psychopathic and narcissistic personality traits and components of the interpersonal-psychological theory of suicide, utilizing a 3-factor model of psychopathy and 2-factor model of pathological narcissism in community, undergraduate, and military individuals. We hypothesized that the impulsive-antisocial facets of psychopathy would be related to suicidal desire, whereas all facets of psychopathy would relate to the capability for suicide. We anticipated an association between pathological narcissism, thwarted belongingness, and capability for suicide, but not perceived burdensomeness. We further hypothesized a relationship between physical pain tolerance and persistence and the affective (i.e., callousness) facet of psychopathy. Results partially supported these hypotheses and underscore the need for further examination of these associations utilizing contemporary models of psychopathy and narcissism. (PsycINFO Database Record

The influence of the ancillary ligand on the potential of cobalt(iii) complexes to act as chaperones for hydroxamic acid-based drugs.

Cobalt(iii) chaperones are a promising class of bioreductive prodrugs under investigation for the delivery of cytotoxic ligands to hypoxic solid tumours. Here we investigate a series of cobalt complexes as chaperones for hydroxamic acid ligands, comparing the properties of the cyclic cyclen (1,4,7,10-tetraazacyclododecane) ancillary ligand with the tripodal tpa (tris-(2-pyridylmethyl)amine) and tren (tris-(2-aminoethyl)amine). A small library of complexes containing several different hydroxamic acids, including the MMP inhibitor Marimistat and the fluorescent ligand C343haH2, were prepared and their pKa values, reduction potentials, and in some cases X-ray crystal structures, were determined. The antiproliferative actitivity of the series was evaluated against DLD-1 colon cancer cells and the cellular accumulation of the fluorescent C343haH2 complexes was monitored by ICPMS and confocal fluorescence microscopy, revealing that the nature of the ancillary ligand significantly influences the complexes' properties, cytotoxicity and cellular distribution.

The association between specific combat experiences and aspects of the Interpersonal Theory of Suicide.

BACKGROUND: Studies examining the relationship between combat exposure and suicide risk typically focus on combat exposure overall, combining numerous different combat experiences. Our study expands upon prior research by examining the association between specific combat experiences and components of both suicidal desire and the capability for suicide. METHOD: We hypothesized that most combat experiences would be associated with capability for suicide. Furthermore, we hypothesized that experiences that involved direct exposure to death and injury (e.g. personally witnessing the death or injury of other soldiers) would be associated with higher levels of thwarted belongingness, perceived burdensomeness, and suicidal ideation. Participants were 400 service members drawn largely from the Army National Guard who had been deployed at least once and endorsed having experienced combat. RESULTS: Consistent with hypotheses, combat experiences involving direct exposure to injury or death exhibited a more pronounced pattern of associations with suicide risk factors than did other experiences. However, only a minority of combat experiences were associated with the capability for suicide. DISCUSSION: These results, while preliminary, indicate that different combat experiences are associated with different outcomes and that, in this sense, not all combat experiences are created equal with respect to suicide risk.

The Associations Between Army National Guard Versus Active Duty Soldier Status and Perceived Burdensomeness, Thwarted Belongingness, and Acquired Capability.

OBJECTIVE: This study aimed to examine if levels of thwarted belongingness, perceived burdensomeness, and acquired capability significantly differed between guardsmen and active duty soldiers. METHOD: Multivariate analysis of covariance was used to test for differences between active duty Army (n = 1,393) and Army National Guard (n = 623) groups, before and after controlling for the effects of age, gender, race, marital status, level of education, and deployment history. RESULTS: Guardsmen reported significantly higher mean levels of thwarted belongingness and perceived burdensomeness than did active duty soldiers, even after adjusting for demographic differences. Guardsmen also reported slightly lower levels of acquired capability, though this effect was accounted for by demographic differences. CONCLUSION: These findings support the notion that National Guard and active duty soldiers differ on perceived burdensomeness and thwarted belongingness. Additional research investigating sources of perceived burdensomeness and thwarted belongingness among guardsmen is needed.

Isolating effects of moral injury and low post-deployment support within the U.S. military.

Suicide rates within U.S. military components, particularly the National Guard, are significantly higher than the general population suicide rate. To better understand and prevent suicide within this population, we must identify mechanisms of risk contributing to these discrepancies. One risk factor relevant to military service is moral injury, a term for experiences that violate one's moral beliefs. Using a series of hierarchical multiple regressions, the current study examined the moderating role of post-deployment social support on the association between moral injury (self-transgressions, other-transgressions, and betrayal) and thwarted belongingness among military personnel. The current sample was comprised of 552 military personnel with at least one previous deployment. Partially consistent with hypotheses, results revealed that other-transgressions and betrayal were significantly associated with thwarted belongingness at low, but not mean or high levels of post-deployment support. In contrast, the interaction of self-transgressions and post-deployment support was not significantly associated with thwarted belongingness, nor was there a significant main effect of self-transgressions on thwarted belongingness. This suggests that experiencing other-perpetrated morally injurious events (i.e., watching a fellow soldier die, being betrayed by a comrade) can be compounded by low post-deployment social support, increasing risk for thwarted belongingness. Implications for prevention and treatment are discussed.

Agitation as a Moderator of the Relationship Between Insomnia and Current Suicidal Ideation in the Military.

Research has established a link between agitation and insomnia, both of which are considered to be risk factors for suicide. The present study aimed to investigate the moderating role of agitation within the relationship between insomnia and current suicidal ideation in a sample of U.S. military personnel. Consistent with hypotheses, the relationship between insomnia and current suicidal ideation was significant only at high levels of agitation. Results support previous findings indicating that both insomnia and agitation are suicide risk factors. These findings clarify the role of known risk factors in the pathway to suicide and may contribute to the advancement of suicide detection and prevention, as these factors may be more easily identified in individuals unwilling to admit thoughts of death and suicide, such as many military personnel.