Managing the risks associated with technological disruption in the road transport system: a control structure modelling approach.

Road transport is experiencing disruptive change from new first-of-a-kind technologies. While such technologies offer safety and operational benefits, they also pose new risks. It is critical to proactively identify risks during the design, development and testing of new technologies. The Systems Theoretic Accident Model and Processes (STAMP) method analyses the dynamic structure in place to manage safety risks. This study applied STAMP to develop a control structure model for emerging technologies in the Australian road transport system and identified control gaps. The control structure shows the actors responsible for managing risks associated with first-of-a-kind technologies and the existing control and feedback mechanisms. Gaps identified related to controls (e.g. legislation) and feedback mechanisms (e.g. monitoring for behavioural adaptation). The study provides an example of how STAMP can be used to identify control structure gaps requiring attention to support the safe introduction of new technologies.

This paper considers emerging risks associated with new technologies in the road transport system. It demonstrates a novel approach using STAMP to identify gaps in control and feedback mechanisms within the existing control structure which should be addressed to mitigate risk.

Prior differences in previous trauma exposure primarily drive the observed racial/ethnic differences in posttrauma depression and anxiety following a recent trauma.

BACKGROUND: Racial and ethnic groups in the USA differ in the prevalence of posttraumatic stress disorder (PTSD). Recent research however has not observed consistent racial/ethnic differences in posttraumatic stress in the early aftermath of trauma, suggesting that such differences in chronic PTSD rates may be related to differences in recovery over time. METHODS: As part of the multisite, longitudinal AURORA study, we investigated racial/ethnic differences in PTSD and related outcomes within 3 months after trauma. Participants (n = 930) were recruited from emergency departments across the USA and provided periodic (2 weeks, 8 weeks, and 3 months after trauma) self-report assessments of PTSD, depression, dissociation, anxiety, and resilience. Linear models were completed to investigate racial/ethnic differences in posttraumatic dysfunction with subsequent follow-up models assessing potential effects of prior life stressors. RESULTS: Racial/ethnic groups did not differ in symptoms over time; however, Black participants showed reduced posttraumatic depression and anxiety symptoms overall compared to Hispanic participants and White participants. Racial/ethnic differences were not attenuated after accounting for differences in sociodemographic factors. However, racial/ethnic differences in depression and anxiety were no longer significant after accounting for greater prior trauma exposure and childhood emotional abuse in White participants. CONCLUSIONS: The present findings suggest prior differences in previous trauma exposure partially mediate the observed racial/ethnic differences in posttraumatic depression and anxiety symptoms following a recent trauma. Our findings further demonstrate that racial/ethnic groups show similar rates of symptom recovery over time. Future work utilizing longer time-scale data is needed to elucidate potential racial/ethnic differences in long-term symptom trajectories.

Forecasting emergent risks in advanced AI systems: an analysis of a future road transport management system.

Artificial Intelligence (AI) is being increasingly implemented within road transport systems worldwide. Next generation of AI, Artificial General Intelligence (AGI) is imminent, and is anticipated to be more powerful than current AI. AGI systems will have a broad range of abilities and be able to perform multiple cognitive tasks akin to humans that will likely produce many expected benefits, but also potential risks. This study applied the EAST Broken Links approach to forecast the functioning of an AGI system tasked with managing a road transport system and identify potential risks. In total, 363 risks were identified that could have adverse impacts on the stated goals of safety, efficiency, environmental sustainability, and economic performance of the road system. Further, risks beyond the stated goals were identified; removal from human control, mismanaging public relations, and self-preservation. A diverse set of systemic controls will be required when designing, implementing, and operating future advanced technologies.Practitioner summary: This study demonstrated the utility of HFE methods for formally considering risks associated with the design, implementation, and operation of future technologies. This study has implications for AGI research, design, and development to ensure safe and ethical AGI implementation.

Exploring utilisation of the allied health assistant workforce in the Victorian health, aged care and disability sectors.

BACKGROUND: Allied health assistants (AHAs) support allied health professionals (AHPs) to meet workforce demands in modern healthcare systems. Previous studies have indicated that AHAs may be underutilised in some contexts. This study aims to identify factors contributing to the effective utilisation of AHAs across health, aged care and disability sectors and possible pathway elements that may optimise AHA careers in Victoria. METHODS: Using an interpretive description approach data collection included a workforce survey and semi structured interviews (individual and group). Data analysis included descriptive statistics, independent t-tests and thematic analysis. Participants included allied health assistants, allied health professionals and allied health leaders in the health, aged care or disability sectors; educators, managers or student of allied health assistance training; and consumers of Victorian health, disability or aged care services. RESULTS: The literature scan identified numerous potential barriers to and enablers of AHA workforce utilisation. A total of 727 participants completed the survey consisting of AHAs (n = 284), AHPs & allied health leaders (n = 443). Thirteen group and 25 individual interviews were conducted with a total of 119 participants. Thematic analysis of the interview data identified four interrelated factors (system, training, individual and workplace) in pre-employment training and workplace environments. These factors were reported to contribute to effective utilisation of the AHA workforce across health, aged care and disability sectors. Study findings were also used to create a conceptual diagram of potential AHA career pathway elements. CONCLUSION: This study identified pre-employment and workplace factors which may contribute to the optimal utilisation of the AHA workforce across Victorian health, aged care and disability sectors. Further study is needed to investigate the transferability of these findings to national and global contexts, and testing of the conceptual model.

(3S)-3-(2,3-difluorophenyl)-3-methoxypyrrolidine (IRL752) -a Novel Cortical-Preferring Catecholamine Transmission- and Cognition-Promoting Agent.

Here we describe for the first time the distinctive pharmacological profile for (3S)-3-(2,3-difluorophenyl)-3-methoxypyrrolidine (IRL752), a new phenyl-pyrrolidine derivative with regioselective central nervous system transmission-enhancing properties. IRL752 (3.7-150 µmol/kg, s.c.) was characterized through extensive in vivo studies using behavioral, tissue neurochemical, and gene expression as well as microdialysis methods. Behaviorally, the compound normalized tetrabenazine-induced hypoactivity, whereas it was unable to stimulate basal locomotion in normal animals or either accentuate or reverse hyperactivity induced by amphetamine or MK-801. IRL752 induced but minor changes in monoaminergic tissue neurochemistry across noradrenaline (NA)- and dopamine (DA)-dominated brain regions. The expression of neuronal activity-, plasticity-, and cognition-related immediate early genes (IEGs), however, increased by 1.5-fold to 2-fold. Furthermore, IRL752 dose-dependently enhanced cortical catecholamine dialysate output to 600%-750% above baseline, whereas striatal DA remained unaltered, and NA rose to ∼250%; cortical and hippocampal dialysate acetylcholine (ACh) increased to ∼250% and 190% above corresponding baseline, respectively. In line with this cortically preferential transmission-promoting action, the drug was also procognitive in the novel object recognition and reversal learning tests. In vitro neurotarget affinity and functional data coupled to drug exposure support the hypothesis that 5-hydroxytryptamine 7 receptor and α2(C)-adrenoceptor antagonism are key contributors to the in vivo efficacy and original profile of IRL752. The cortical-preferring facilitatory impact on catecholamine (and ACh) neurotransmission, along with effects on IEG expression and cognition-enhancing features, are in line with the potential clinical usefulness of IRL752 in conditions wherein these aspects may be dysregulated, such as in axial motor and cognitive deficits in Parkinson disease. SIGNIFICANCE STATEMENT: This report describes the distinctive preclinical profile of (3S)-3-(2,3-difluorophenyl)-3-methoxypyrrolidine (IRL752). Its in vivo neurochemical, behavioral, microdialysis, and gene expression properties are consistent with a cortically regioselective facilitatory impact on catecholaminergic and cholinergic neurotransmission accompanied by cognitive impairment-reversing features. The pharmacological characteristics of IRL752 are in line with the clinical usefulness of IRL752 in conditions wherein these aspects may be dysregulated, such as in axial motor and cognitive deficits in Parkinson disease.

Predictors and Prevalence of Nodal Disease in Salvage Oropharyngectomy.

BACKGROUND: Patients with recurrent oropharyngeal cancer often require extensive salvage surgery. For patients with clinically N0 necks, the indication for concurrent neck dissection remains unclear. This study aimed to determine predictors, prevalence, and distribution of nodal disease in patients treated with salvage oropharyngectomy. METHODS: In a case series with data collection at a single tertiary academic National Cancer Institute (NCI)-designated comprehensive cancer center, this study analyzed patients treated with prior radiation or chemoradiation who had persistent, recurrent, or second primary squamous cell carcinoma of the oropharynx requiring oropharyngeal resection between 1998 and 2017 (n = 95). Clinical and oncologic characteristics and treatment outcomes were collected, and statistical analyses were performed. RESULTS: The overall rate of nodal positivity was 21% (24/95), and the rate of occult nodal disease was 6% (4/65). Ipsilateral and contralateral level 2 were the most common areas harboring positive nodes. Bivariate analysis showed female sex (p = 0.01), initial overall stage (p = 0.02), and N status (p = 0.03), as well as recurrent overall and T stage (p = 0.05) to be predictors of nodal disease. In the multivariate analysis, recurrent T stage continued to be significantly predictive of pathologic nodal disease. Both computed tomography (CT) and positron emission tomography-CT were moderately accurate in predicting nodal disease in the salvage setting (area under the curve, 0.79 and 0.80, respectively). CONCLUSION: Occult nodal disease is observed in few patients undergoing salvage oropharyngeal resection. This study identified factors predictive of nodal disease in patients undergoing salvage oropharyngectomy and appropriate diagnostic tests in this setting.

Social Network Organization, Structure, and Patterns of Influence Within a Community of Transgender Women in Lima, Peru: Implications for Biomedical HIV Prevention.

Understanding social network structures can contribute to the introduction of new HIV prevention strategies with socially marginalized populations like transgender women (TW). We conducted 20 semi-structured interviews and four focus groups (n = 32) with TW from selected social networks in Lima, Peru between May and July, 2015. Participants described layers of social influence from diverse actors in their social networks. The majority identified a close relative as their primary social support, with whom they confided secrets but avoided issues of transgender identity, sexuality, and sex work. Participants described close circles of TW friends with whom they shared information about gender identity, body modification, and sexual partners, but avoided issues like HIV. Community leadership included political leaders (who advocated for transgender rights) as well as social leaders (who introduced TW to hormone therapy, body modification, and commercial sex). Detailed analysis of TW social networks can contribute to implementation and acceptability of new HIV prevention technologies.

Using middle finger length to determine the internal diameter of uncuffed tracheal tubes in paediatrics.

The selection of an appropriately-sized tracheal tube is of critical importance in paediatric patients to reduce both the risk of subglottic stenosis from a tracheal tube that is too large, and inadequate ventilation or poor end-tidal gas monitoring from a tracheal tube that is too small. Age formulae are widely used, but known to be unreliable, often resulting in a need to change the tracheal tube. Previous work has shown that the length of the middle finger and the internal diameter can both be used to guide depth of tracheal tube insertion. Therefore, we hypothesised that middle finger length may also be related to tube internal diameter. We enrolled children aged up to 12 years presenting to our institution for elective anaesthesia and measured the length of the middle finger on the palmar aspect of the hand. Anaesthetists chose the airway device they felt most appropriate for the procedure, and were unaware of the middle finger measurement. Of 160 patients who were enrolled, 108 were included in the final analysis. We found a linear relationship between uncuffed tracheal tube internal diameter and median middle finger length for each size of tracheal tube. Relationship between middle finger length and cuffed tracheal tube internal diameter was less clear. We propose that the formula: 'middle finger length (cm) (round up to nearest 0.5) = internal diameter of uncuffed tracheal tube (mm)' may be an improvement compared with age formulae for selecting uncuffed tracheal tubes in children, although this requires formal testing.

Efficacy of ACL injury risk screening methods in identifying high-risk landing patterns during a sport-specific task.

Screening methods sensitive to movement strategies that increase anterior cruciate ligament (ACL) loads are likely to be effective in identifying athletes at-risk of ACL injury. Current ACL injury risk screening methods are yet to be evaluated for their ability to identify athletes' who exhibit high-risk lower limb mechanics during sport-specific maneuvers associated with ACL injury occurrences. The purpose of this study was to examine the efficacy of two ACL injury risk screening methods in identifying high-risk lower limb mechanics during a sport-specific landing task. Thirty-two female athletes were screened using the Landing Error Scoring System (LESS) and Tuck Jump Assessment. Participants' also completed a sport-specific landing task, during which three-dimensional kinematic and kinetic data were collected. One-dimensional statistical parametric mapping was used to examine the relationships between screening method scores, and the three-dimensional hip and knee joint rotation and moment data from the sport-specific landing. Higher LESS scores were associated with reduced knee flexion from 30 to 57 ms after initial contact (P = 0.003) during the sport-specific landing; however, no additional relationships were found. These findings suggest the LESS and Tuck Jump Assessment may have minimal applicability in identifying athletes' who exhibit high-risk landing postures in the sport-specific task examined.

Prevention Across the Spectrum: a randomized controlled trial of three programs to reduce risk factors for both eating disorders and obesity.

BACKGROUND: A randomized controlled trial of three school-based programs and a no-intervention control group was conducted to evaluate their efficacy in reducing eating disorder and obesity risk factors. METHOD: A total of 1316 grade 7 and 8 girls and boys (mean age = 13.21 years) across three Australian states were randomly allocated to: Media Smart; Life Smart; the Helping, Encouraging, Listening and Protecting Peers (HELPP) initiative; or control (usual school class). Risk factors were measured at baseline, post-program (5 weeks later), and at the 6- and 12-month follow-ups. RESULTS: Media Smart girls had half the rate of onset of clinically significant concerns about shape and weight than control girls at the 12-month follow-up. Media Smart and HELPP girls reported significantly lower weight and shape concern than Life Smart girls at the 12-month follow-up. Media Smart and control girls scored significantly lower than HELPP girls on eating concerns and perceived pressure at the 6-month follow-up. Media Smart and HELPP boys experienced significant benefit on media internalization compared with control boys and these were sustained at the 12-month follow-up in Media Smart boys. A group × time effect found that Media Smart participants reported more physical activity than control and HELPP participants at the 6-month follow-up, while a main effect for group found Media Smart participants reported less screen time than controls. CONCLUSIONS: Media Smart was the only program to show benefit on both disordered eating and obesity risk factors. Whilst further investigations are indicated, this study suggests that this program is a promising approach to reducing risk factors for both problems.

Six-minute walk test in healthy British service personnel.

INTRODUCTION: The 6 min walk test (6MWT) is a widely used, safe and effective submaximal exercise test. The primary outcome is the distance walked, but additional physiological and patient-reported metrics can be recorded. It is used to assess function and is commonly used within UK Defence Rehabilitation. However, there are no published British military 6MWT data in a non-injured population. This study reports the 6MWT procedure and results from healthy British service personnel. METHODS: A convenience sample of 46 individuals (male n=40) undertook 95 6MWTs over three study visits throughout a year. They were performed on a 20 m straight-line route, administered by an exercise rehabilitation instructor and preceded by anthropometric measurements (height, weight). Physiological measures (HR, oxygen saturations (SpO2)) and patient-reported measures (Borg shortness of breath (SoB), rate of perceived exertion (RPE) and fatigue) were taken before and after the assessment. Statistical tests were performed between pre-test and post-test measures, and sex and body mass, and concurrent cardiopulmonary exercise tests (CPET) with 6MWT distance. RESULTS: The mean 6MWT distance was 705.5±86 m; males 709.4±86.9 m and females 685.9±81.9 m (p=0.32), with a median Borg SoB of 1 (IQR: 0-2) and RPE 9 (IQR: 7-11), and a negative correlation between body mass index and 6MWT distance, p=0.007. There were no significant differences between pre-test and post-test measures. Peak workload and VO2 Max correlated weakly with 6MWT distance (0.336, p=0.01 and 0.375, p=0.09, respectively), but submaximal CPET measures did not. CONCLUSION: These results provide a benchmark for British military 6MWT data to guide clinical and research use. However, a larger dataset is required for validation and normative values.

A Holistic Focus of Attention Enhances Vertical Jump Performance Among Inexperienced Individuals.

A holistic focus (HF) has been found to significantly improve performance over an internal focus (IF), in a similar way to an external focus (EF). There is a need to understand the effectiveness of a HF by investigating kinematic and kinetic outcome measures. 19 college-aged adults performed 12 vertical jumps under four conditions in a counterbalanced design. The conditions were, IF, EF, HF, and control, or no focus condition. All participants performed the vertical jumps on a force plate with 16 reflective markers placed on the lower extremities. Separate repeated measures ANOVAs with Sidak post-hoc were used to analyze jump height, flight height, peak force, takeoff velocity, and knee and hip flexion. A significant main effect for jump height was observed (p < 0.001). HF and EF jumped significantly higher than IF (p < 0.001; p < 0.001). EF also jumped significantly higher than control (p<.05). No significant main effects were observed for any kinematic or kinetic dependent variables. The results of this experiment support previous research by observing performance benefits of HF and EF over an IF. However, the benefits of HF and EF cannot be attributed to the kinetic or kinematic changes.

UW Supplementation with AP39 Improves Liver Viability Following Static Cold Storage.

Static cold storage of donor livers at 4°C incompletely arrests metabolism, ultimately leading to decreases in ATP levels, oxidative stress, cell death, and organ failure. Hydrogen Sulfide (H2S) is an endogenously produced gas, previously demonstrated to reduce oxidative stress, reduce ATP depletion, and protect from ischemia and reperfusion injury. H2S is difficult to administer due to its rapid release curve, resulting in cellular death at high concentrations. AP39, a mitochondrially targeted, slow-release H2S donor, has been shown to reduce ischemia-reperfusion injury in hearts and kidneys. Thus, we investigated whether the addition of AP39 during 3-day static cold storage can improve liver graft viability. At the end of storage, livers underwent six hours of acellular normothermic machine perfusion, a model of transplantation. During simulated transplantation, livers stored with AP39 showed reduced resistance, reduced cellular damage (ALT and AST), and reduced apoptosis. Additionally, bile production and glucose, as well as energy charge were improved by the addition of AP39. These results indicate that AP39 supplementation improves liver viability during static cold storage.

Optimized Partial Freezing Protocol Enables 10-Day Storage of Rat Livers.

Preserving organs at subzero temperatures with halted metabolic activity holds the potential to prolong preservation and expand the donor organ pool for transplant. Our group recently introduced partial freezing, a novel approach in high-subzero storage at -15°C, enabling 5 days storage of rodent livers through precise control over ice nucleation and unfrozen fraction. However, increased vascular resistance and tissue edema suggested a need for improvements to extend viable preservation. Here, we describe an optimized partial freezing protocol with key optimizations including increased concentration of propylene glycol to reduce ice recrystallization and maintained osmotic balance through an increase in bovine serum albumin, all while minimizing sheer stress during cryoprotectant unloading with an acclimation period. These approaches ensured the viability during preservation and recovery processes, promoting liver function and ensuring optimal preservation. This was evidenced by increased oxygen consumption, decreased vascular resistance and edema. Ultimately, we show that using the optimized protocol, livers can be stored for 10 days with comparable vascular resistance and lactate levels to 5 days, outperforming the viability of time-matched cold stored livers as the current gold standard. This study represents a significant advancement in expanding organ availability through prolonged preservation and thereby revolutionizing transplant medicine.

Anti-apoptotic treatment of warm ischemic male rat livers in machine perfusion improves symptoms of ischemia-reperfusion injury.

Background: Liver donation after cardiac death (DCD) makes up a small percentage of the organs used in transplantation and poses a higher risk of graft loss compared to donation after brain death (DBD); this is a result of ischemia reperfusion for which the exact injury mechanisms are currently not fully understood. However, reperfusion injury has been shown to lead to necrosis as well as apoptosis through oxidative stress and mitochondrial dysfunction. In this work, we propose that use of the pro-survival, anti-apoptotic CEPT cocktail in post-ischemia normothermic machine perfusion (NMP) may improve recovery in rat livers subjected to extended durations of warm ischemia. Materials and Methods: Livers procured from male Lewis rats were subjected to 90 min of warm ischemia, followed by 6 h of NMP where they were treated either with the survival-enhancing anti-apoptotic cocktail (CEPT), the vehicle (DMSO) or the base media with no additives. Results: The CEPT-treated group exhibited lower expression of hepatic injury biomarkers, and improvement in a range of hepatocellular symptoms associated with the hepatic parenchyma, biliary epithelium and the sinusoidal endothelium, including recovery of bile secretion and lowered vascular resistance. Conclusions: This study's findings suggest apoptosis plays a more significant role in ischemia-reperfusion injury than previously understood, and provide useful insight for further investigation of the specific underlying mechanisms and development of novel treatment methods.

High uptake of HPV immunisation in Scotland--perspectives on maximising uptake.

In September 2008, Scotland introduced a national human papillomavirus (HPV) immunisation programme with bivalent HPV vaccine, to prevent cervical cancer. This school-based programme routinely vaccinates girls aged between 12 and 13 years. A catch-up campaign, running over three years, also began at this time, offering vaccination to all girls aged 13 years to under 18 years old. The HPV immunisation campaign presented challenges due to this vaccine being targeted to girls in school and older girls who had left school. Following a long and comprehensive planning process, this campaign was successfully implemented across Scotland, delivering high vaccine uptake of 91.4% for three doses of vaccine in the first year (September 2008 to August 2009) for the routine cohort and 90.1% in the second year (September 2009 to August 2010) for the routine cohort. We describe the planning process, challenges and implementation strategies employed to achieve this high uptake.

Anti-apoptotic treatment of warm ischemic male rat livers in machine perfusion improves symptoms of ischemia-reperfusion injury.

Liver donation after cardiac death (DCD) makes up a small percentage of the donor pool and poses a higher risk of graft loss compared to donation after brain death (DBD); this is a result of ischemia reperfusion for which the exact injury mechanisms are currently not fully understood. However, reperfusion injury has been shown to lead to necrosis as well as apoptosis at the cellular level. In this work, we propose that use of the pro-survival, anti-apoptotic CEPT cocktail in post-ischemia normothermic machine perfusion (NMP) may improve recovery in rat livers subjected to extended durations of warm ischemia. Livers procured from male lewis rats were subjected to 90 minutes of warm ischemia, followed by 6 hours of NMP where they were treated with the survival-enhancing anti-apoptotic cocktail (CEPT), the vehicle (DMSO) or the base media with no additives. The CEPT-treated group exhibited lower expression of hepatic injury biomarkers, and improvement in a range of hepatocellular functions associated with the hepatic parenchyma, biliary epithelium and especially the sinusoidal endothelium. This study's findings provide useful insight for further investigation of the extent of apoptotic contribution to ischemia reperfusion injury (IRI).

Childhood adversities and risk of posttraumatic stress disorder and major depression following a motor vehicle collision in adulthood.

AIMS: Childhood adversities (CAs) predict heightened risks of posttraumatic stress disorder (PTSD) and major depressive episode (MDE) among people exposed to adult traumatic events. Identifying which CAs put individuals at greatest risk for these adverse posttraumatic neuropsychiatric sequelae (APNS) is important for targeting prevention interventions. METHODS: Data came from n = 999 patients ages 18-75 presenting to 29 U.S. emergency departments after a motor vehicle collision (MVC) and followed for 3 months, the amount of time traditionally used to define chronic PTSD, in the Advancing Understanding of Recovery After Trauma (AURORA) study. Six CA types were self-reported at baseline: physical abuse, sexual abuse, emotional abuse, physical neglect, emotional neglect and bullying. Both dichotomous measures of ever experiencing each CA type and numeric measures of exposure frequency were included in the analysis. Risk ratios (RRs) of these CA measures as well as complex interactions among these measures were examined as predictors of APNS 3 months post-MVC. APNS was defined as meeting self-reported criteria for either PTSD based on the PTSD Checklist for DSM-5 and/or MDE based on the PROMIS Depression Short-Form 8b. We controlled for pre-MVC lifetime histories of PTSD and MDE. We also examined mediating effects through peritraumatic symptoms assessed in the emergency department and PTSD and MDE assessed in 2-week and 8-week follow-up surveys. Analyses were carried out with robust Poisson regression models. RESULTS: Most participants (90.9%) reported at least rarely having experienced some CA. Ever experiencing each CA other than emotional neglect was univariably associated with 3-month APNS (RRs = 1.31-1.60). Each CA frequency was also univariably associated with 3-month APNS (RRs = 1.65-2.45). In multivariable models, joint associations of CAs with 3-month APNS were additive, with frequency of emotional abuse (RR = 2.03; 95% CI = 1.43-2.87) and bullying (RR = 1.44; 95% CI = 0.99-2.10) being the strongest predictors. Control variable analyses found that these associations were largely explained by pre-MVC histories of PTSD and MDE. CONCLUSIONS: Although individuals who experience frequent emotional abuse and bullying in childhood have a heightened risk of experiencing APNS after an adult MVC, these associations are largely mediated by prior histories of PTSD and MDE.