The Influence of Visual Provenance Representations on Strategies in a Collaborative Hand-off Data Analysis Scenario.

Conducting data analysis tasks rarely occur in isolation. Especially in intelligence analysis scenarios where different experts contribute knowledge to a shared understanding, members must communicate how insights develop to establish common ground among collaborators. The use of provenance to communicate analytic sensemaking carries promise by describing the interactions and summarizing the steps taken to reach insights. Yet, no universal guidelines exist for communicating provenance in different settings. Our work focuses on the presentation of provenance information and the resulting conclusions reached and strategies used by new analysts. In an open-ended, 30-minute, textual exploration scenario, we qualitatively compare how adding different types of provenance information (specifically data coverage and interaction history) affects analysts' confidence in conclusions developed, propensity to repeat work, filtering of data, identification of relevant information, and typical investigation strategies. We see that data coverage (i.e., what was interacted with) provides provenance information without limiting individual investigation freedom. On the other hand, while interaction history (i.e., when something was interacted with) does not significantly encourage more mimicry, it does take more time to comfortably understand, as represented by less confident conclusions and less relevant information-gathering behaviors. Our results contribute empirical data towards understanding how provenance summarizations can influence analysis behaviors.

Situ: Identifying and Explaining Suspicious Behavior in Networks.

Despite the best efforts of cyber security analysts, networked computing assets are routinely compromised, resulting in the loss of intellectual property, the disclosure of state secrets, and major financial damages. Anomaly detection methods are beneficial for detecting new types of attacks and abnormal network activity, but such algorithms can be difficult to understand and trust. Network operators and cyber analysts need fast and scalable tools to help identify suspicious behavior that bypasses automated security systems, but operators do not want another automated tool with algorithms they do not trust. Experts need tools to augment their own domain expertise and to provide a contextual understanding of suspicious behavior to help them make decisions. In this paper we present Situ, a visual analytics system for discovering suspicious behavior in streaming network data. Situ provides a scalable solution that combines anomaly detection with information visualization. The system's visualizations enable operators to identify and investigate the most anomalous events and IP addresses, and the tool provides context to help operators understand why they are anomalous. Finally, operators need tools that can be integrated into their workflow and with their existing tools. This paper describes the Situ platform and its deployment in an operational network setting. We discuss how operators are currently using the tool in a large organization's security operations center and present the results of expert reviews with professionals.

Need for improved public health protection of young people wanting body piercing: evidence from a look-back exercise at a piercing and tattooing premises with poor hygiene practices, Wales (UK) 2015.

Following a cluster of serious pseudomonas skin infections linked to a body piercing and tattooing premises, a look-back exercise was carried out to offer clients a screen for blood-borne viruses. Of those attending for screening 72% (581/809) had a piercing procedure in the premises of interest: 94 (16%) were under 16 years of age at the time of screening. The most common site of piercing was ear (34%), followed by nose (27%), nipple (21%) and navel (21%). A small number (<5) tested positive for hepatitis B and C, with no evidence this was linked to the premises. However, 36% (211/581) of clients reported a skin infection associated with their piercing. Using data from client forms, 36% provided a false age. Those aged under 16 years (OR 4.5, 95% CI 2.7-7.7) and those receiving a piercing at an intimate site (OR 2.1, 95% CI 1.3-3.6) were more likely to provide a false age. The findings from this exercise were used to support the drafting of the Public Health (Wales) Bill which proposed better regulation of piercing premises and the need to provide proof of being 18 years of age or over before having a piercing of an intimate site.

The cost-effectiveness of follow-up strategies after cancer treatment: a systematic literature review.

Introduction: The cost of treatment and follow-up of cancer patients in the UK is substantial. In a budget-constrained system such as the NHS, it is necessary to consider the cost-effectiveness of the range of management strategies at different points on cancer patients' care pathways to ensure that they provide adequate value for money. Sources of data: We conducted a systematic literature review to explore the cost-effectiveness of follow-up strategies of patients previously treated for cancer with the aim of informing UK policy. All papers that were considered to be economic evaluations in the subject areas described above were extracted. Areas of agreement: The existing literature suggests that intensive follow-up of patients with colorectal disease is likely to be cost-effective, but the opposite holds for breast cancer. Areas of controversy: Interventions and strategies for follow-up in cancer patients were variable across type of cancer and setting. Drawing general conclusions about the cost-effectiveness of these interventions/strategies is difficult. Growing points: The search identified 2036 references but applying inclusion/exclusion criteria a total of 44 articles were included in the analysis. Breast cancer was the most common (n = 11) cancer type followed by colorectal (n = 10) cancer. In general, there were relatively few studies of cost-effectiveness of follow-up that could influence UK guidance. Where there was evidence, in the most part, NICE guidance broadly reflected this evidence. Areas timely to develop research: In terms of future research around the timing, frequency and composition of follow-ups, this is dependent on the type of cancer being considered. Nevertheless, across most cancers, the possibility of remote follow-up (or testing) by health professionals other than hospital consultants in other settings appears to warrant further work.

Prediction of haematocrit in dried blood spots from the measurement of haemoglobin using commercially available sodium lauryl sulphate.

Background When preparing dried blood spots (DBSs), haematocrit (Hct) can affect the ability of the blood to spread through the filter paper, thus resulting in varying quantities of sample being measured when fixed subpunches of the DBSs are taken. It may be important to predict the sample Hct to correct volume differences. Methods Blood (10 µL) was applied to Perkin Elmer 226® paper. The samples ( n = 165) were allowed to dry for 24 h, and the entire blood spots were cut out. Subpunch analysis was also performed on blood spots prepared from 75 µL EDTA blood, taking 6 mm subpunches centrally and peripherally from the spots ( n = 59). The spots were eluted with 100 µL water, and a 10 µL aliquot of lysate was added to sulfolyser reagent (80 µL) in a microtitre plate. Hb was measured at 550 nm using an ELISA plate reader. DBS samples were compared against blood samples measured on a routine Sysmex XN-9000 analyser. Results The Passing and Bablock regression showed Hct (DBS-predicted) = 0.99 Hct (Sysmex) -0.02, R2 = 0.87. Intra-assay imprecision measured at Hct values of 0.27, 0.40 and 0.52, gave CVs of 4.1%, 2.8% and 4.2%, respectively. Inter-assay imprecision showed CVs of 6.2%, 5.2% and 4.2%, respectively. DBS samples were stable for up to two days at 60℃, one month at room temperature and six months at 4℃. Conclusion This method provides a simple and fast estimation of predicted Hct in dried blood spots.

Impact of specialist rehabilitation services on hospital length of stay and associated costs.

BACKGROUND: Provision of specialist rehabilitation services in North Yorkshire and Humberside may be suboptimal. Local commissioning bodies need to prioritise investments in health care, but previous studies provide limited evidence to inform the decision to expand existing services on the basis of cost-effectiveness. We examine the impact of specialist rehabilitation services in the subregion on hospital length of stay (LoS) and associated costs compared to routine care. METHODS: Comparison of hospital LoS and associated costs in centres with greater access (Hull) and limited access (i.e. routine care, York and Northern Lincolnshire), to specialist rehabilitation services for patients with complex disabilities following illness or injury, using Hospital Episodes Statistics data. RESULTS: Average LoS and duration costs by Healthcare Resource Group (HRG) were lower for the majority of patients with greater access to specialist rehabilitation compared to routine care. Difference in LoS between groups widened with level of complexity within each HRG. For the more frequent HRG codes, the LoS difference was as high as 34 days longer for York compared to Hull and £7900 more costly. CONCLUSION: Rehabilitation patients within York and Northern Lincolnshire areas appear to have longer LoS and higher associated costs compared to those admitted to the Hull Trust. This analysis suggests that specialist rehabilitation may be cost saving compared to routine care and supports the case for expansion of the existing services to improve coverage in the area.

Exploratory examination of the utility of demoralization as a diagnostic specifier for adjustment disorder and major depression.

OBJECTIVE: Demoralization, a state of lowered morale and poor coping, has a prevalence of 13-18% among patients with advanced cancer. We surveyed clinicians' perspectives of the utility of "with demoralization" as a diagnostic specifier for adjustment and depressive disorders. METHOD: Using comparative clinical vignettes in a field survey, clinicians from a range of disciplines were asked their perception of the utility of diagnosis and treatment options. Response frequencies were compared using Cochran's Q and McNemar's tests, with sensitivity and specificity rated against expert rankings of diagnosis. Analysis of variance and paired t-tests examined significant differences in ratings of utility. RESULTS: Vignettes were assessed by 280 clinicians; 77% supported utility of the category 'adjustment disorder with demoralization' compared to 33% supporting 'adjustment disorder with anxiety' (McNemar test, p<0.001), while 83% supported the utility of 'with demoralization' for major depressive episode, matching 83% perceiving utility for 'with melancholia.' Sensitivity and specificity ratings were 77% and 94% for adjustment disorder with demoralization and 83% and 91% for major depression with demoralization. CONCLUSION: Clinicians perceived the specifier 'with demoralization' to deepen diagnostic understanding, treatment choice, and ability to communicate with clinicians and patients, particularly for the category of adjustment disorder with demoralization.

Elemental concentrations and in vitro bioaccessibility in Canadian background soils.

Elemental concentrations and bioaccessibility were determined in background soils collected in Canada as part of the North American Geochemical Landscapes Project. The concentrations of As, Cr, Cu, Co, Ni and Zn were higher in the C-horizon (parent material) compared to 0-5 cm (surface soil), and this observation along with the regional distribution suggested that most of the variability in concentrations of these elements were governed by the bedrock characteristics. Unlike the above-stated elements, Pb and Cd concentrations were higher in the surface layer reflecting the potential effects of anthropogenic deposition. Elemental bioaccessibility was variable decreasing in the order Cd > Pb > Cu > Zn > Ni > Co > As > Cr for the surface soils. With the exception of As, bioaccessibility was generally higher in the C-horizon soils compared to the 0-5 cm soils. The differences in metal bioaccessibility between the 0-5 cm and the C-horizon and among the provinces may reflect geological processes and speciation. The mean, median or 95th percentile bioaccessibility for As, Cr, Cu, Co, Ni and Pb were all below 100 %, suggesting that the use of site-specific bioaccessibility results for these elements will yield more accurate estimation of the risk associated with oral bioavailability for sites where soil ingestion is the major contributor of human health risk.

Gestational weight gain, prepregnancy body mass index and offspring attention-deficit hyperactivity disorder symptoms and behaviour at age 10.

OBJECTIVE: To assess offspring attention-deficit hyperactivity disorder (ADHD) symptoms and emotional/behavioural impairments at age 10 years in relation to maternal gestational weight gain (GWG) and prepregnancy body mass index (BMI). DESIGN AND SETTING: Longitudinal birth cohort from Magee-Womens Hospital, Pittsburgh, Pennsylvania (enrolled 1983-86). POPULATION: Mother-infant dyads (n = 511) were followed through pregnancy to 10 years. METHODS: Self-reported total GWG was converted to gestational-age-standardised z-scores. Multivariable linear and negative binomial regressions were used to estimate effects of GWG and BMI on outcomes. MAIN OUTCOME MEASURES: Child ADHD symptoms were assessed with the Conners' Continuous Performance Test. Child behaviour was assessed by parent and teacher ratings on the Child Behaviour Checklist (CBCL) and Teacher Report Form, respectively. RESULTS: The mean (SD) total GWG (kg) was 14.5 (5.9), and 10% of women had a pregravid BMI ≥30 kg/m2 . Prepregnancy obesity (BMI of 30 kg/m2 ) was associated with increased offspring problem behaviours including internalising behaviours (adjusted ß 3.3 points, 95% CI 1.7-4.9), externalising behaviours (adjusted ß 2.9 points, 95% CI 1.4-4.6), and attention problems (adjusted ß 2.3 points, 95% CI 1.1-3.4) on the CBCL, compared with normal weight mothers (BMI of 22 kg/m2 ). There were nonsignificant trends towards increased offspring impulsivity with low GWG among lean mothers (adjusted incidence rate ratio 1.2, 95% CI 0.9-1.5) and high GWG among overweight mothers (adjusted incidence rate ratio 1.7, 95% CI 0.9-2.8), but additional outcomes did not differ by GWG z-score. Results were not meaningfully different after excluding high-substance users. CONCLUSIONS: In a low-income and high-risk sample, we observed a small increase in child behaviour problems among children of obese mothers, which could have an impact on child behaviour in the population. TWEETABLE ABSTRACT: Maternal obesity is associated with a small increase in child behaviour problems.

Assessment of exposures and potential risks to the US adult population from the leaching of elements from gold and ceramic dental restorations.

Using data from the 2001 to 2004 US National Health and Nutrition Examination Survey (NHANES) on the number and placement of tooth restorations in adults, we quantified daily doses due to leaching of elements from gold (Au) alloy and ceramic restorative materials. The elements with the greatest leaching rates from these materials are often the elements of lowest proportional composition. As a result, exposure due to wear will predominate for those elements of relatively high proportional composition, while exposure due leaching may predominate for elements of relatively low proportional composition. The exposure due to leaching of silver (Ag) and palladium (Pd) from Au alloys exceeded published reference exposure levels (RELs) for these elements when multiple full surface crowns were present. Six or more molar crowns would result in exceeding the REL for Ag, whereas three or more crowns would be necessary to exceed the REL for Pd. For platinum (Pt), the majority of tooth surfaces, beyond just molar crowns, would be necessary to exceed the REL for Pd. Exposures due to leaching of elements from ceramic dental materials were less than published RELs for all components examined here, including having all restorations composed of ceramic.

Assessment of exposures and potential risks to the US adult population from wear (attrition and abrasion) of gold and ceramic dental restorations.

Little has been published on the chemical exposures and risks of dental restorative materials other than from dental amalgam and composite resins. Here we provide the first exposure and risk assessment for gold (Au) alloy and ceramic restorative materials. Based on the 2001-2004 US National Health and Nutrition Examination Survey (NHANES), we assessed the exposure of US adults to the components of Au alloy and ceramic dental restorations owing to dental material wear. Silver (Ag) is the most problematic component of Au alloy restorations, owing to a combination of toxicity and proportional composition. It was estimated that adults could possess an average of four tooth surfaces restored with Au alloy before exceeding, on average, the reference exposure level (REL) for Ag. Lithium (Li) is the most problematic component of dental ceramics. It was estimated that adults could possess an average of 15 tooth surfaces restored with ceramics before exceeding the REL for Li. Relative risks of chemical exposures from dental materials decrease in the following order: Amalgam>Au alloys>ceramics>composite resins.

Effect of denosumab versus zoledronic acid in preventing skeletal-related events in patients with bone metastases by baseline characteristics.

BACKGROUND: Analyses of phase III trials showed that denosumab was superior to zoledronic acid (ZA) in preventing skeletal-related events (SREs) irrespective of age, history of SREs, or baseline pain status. This analysis assessed the risk of SREs across additional baseline characteristics. PATIENTS AND METHODS: Patients (N = 5543) from three phase III trials who had breast cancer, prostate cancer, or other solid tumours and one or more bone metastasis were included. Superiority of denosumab versus ZA in reducing risk of first SRE and first and subsequent SREs was assessed in subgroups defined by the Eastern Cooperative Oncology Group performance status (ECOG PS), bone metastasis location, bone metastasis number, visceral metastasis presence/absence, and urinary N-telopeptide (uNTx) level using Cox proportional hazards and Anderson-Gill models. Subgroups except bone metastasis location were also assessed for each solid tumour type. RESULTS: Compared with ZA, denosumab significantly reduced the risk of first SRE across all subgroups (hazard ratio [HR] ranges: ECOG PS, 0.79-0.84; bone metastasis location, 0.78-0.83; bone metastasis number, 0.78-0.84; visceral metastasis presence/absence, 0.80-0.82; uNTx level, 0.73-0.86) and reduced the risk of first and subsequent SREs in all subgroups (HR ranges: ECOG PS, 0.76-0.83; bone metastasis location, 0.78-0.84; bone metastasis number, 0.79-0.81; visceral metastasis presence/absence, 0.79-0.81; uNTx level, 0.74-0.83). Similar results were observed in subgroups across tumour types. CONCLUSION: Denosumab was superior to ZA in preventing SREs in patients with bone metastases from advanced cancer, regardless of ECOG PS, bone metastasis number, baseline visceral metastasis presence/absence, and uNTx level.

Cost-effectiveness of integrated collaborative care for comorbid major depression in patients with cancer.

OBJECTIVES: Comorbid major depression is associated with reduced quality of life and greater use of healthcare resources. A recent randomised trial (SMaRT, Symptom Management Research Trials, Oncology-2) found that a collaborative care treatment programme (Depression Care for People with Cancer, DCPC) was highly effective in treating depression in patients with cancer. This study aims to estimate the cost-effectiveness of DCPC compared with usual care from a health service perspective. METHODS: Costs were estimated using UK national unit cost estimates and health outcomes measured using quality-adjusted life-years (QALYs). Incremental cost-effectiveness of DCPC compared with usual care was calculated and scenario analyses performed to test alternative assumptions on costs and missing data. Uncertainty was characterised using cost-effectiveness acceptability curves. The probability of DCPC being cost-effective was determined using the UK National Institute for Health and Care Excellence's (NICE) cost-effectiveness threshold range of £ 20,000 to £ 30,000 per QALY gained. RESULTS: DCPC cost on average £ 631 more than usual care per patient, and resulted in a mean gain of 0.066 QALYs, yielding an incremental cost-effectiveness ratio of £ 9549 per QALY. The probability of DCPC being cost-effective was 0.9 or greater at cost-effectiveness thresholds above £ 20,000 per QALY for the base case and scenario analyses. CONCLUSIONS: Compared with usual care, DCPC is likely to be cost-effective at the current thresholds used by NICE. This study adds to the weight of evidence that collaborative care treatment models are cost-effective for depression, and provides new evidence regarding their use in specialist medical settings.

Reduced aggression and foraging efficiency of invasive signal crayfish (Pacifastacus leniusculus) infested with non-native branchiobdellidans (Annelida: Clitellata).

BACKGROUND: Biological invasions are a principal threat to global biodiversity and identifying the determinants of non-native species' success is a conservation priority. Through their ability to regulate host populations, parasites are increasingly considered as important in determining the outcome of species' invasions. Here, we present novel evidence that the common crayfish ecto-symbiont, Xironogiton victoriensis (Annelida: Clitellata) can affect the behaviour of a widespread and ecologically important invader, the signal crayfish (Pacifastacus leniusculus). METHODS: To assess the signal crayfish-X. victoriensis relationship naïve crayfish were infested with an intensity of worms typically observed under natural conditions. Over a 10-week period the growth rate and survivorship of these animals was monitored and compared to those of uninfested counterparts. Complementary dyadic competition and foraging experiments were run to assess the behaviour of infested compared to uninfested animals. These data were analysed using General Linear Models and Generalized Linear Mixed Models. RESULTS: Whilst X. victoriensis did not affect the growth rate or survivorship of signal crayfish under laboratory conditions, infested animals were significantly less aggressive and poorer foragers than uninfested individuals. CONCLUSIONS: Through reducing aggression and foraging efficiency, infestation with X. victoriensis may disrupt the social structure, and potentially growth rate and/or dispersal of afflicted crayfish populations, with potential effects on their invasion dynamics. This is important given the widespread invasive range of crayfish and their functional roles as ecosystem engineers and keystone species.

Genome-wide copy-number variation study of psychosis in Alzheimer's disease.

About 40-60% of patients with late-onset Alzheimer's disease (AD) develop psychosis, which represents a distinct phenotype of more severe cognitive and functional deficits. The estimated heritability of AD+P is ~61%, which makes it a good target for genetic mapping. We performed a genome-wide copy-number variation (CNV) study on 496 AD cases with psychosis (AD+P), 639 AD subjects with intermediate psychosis (AD intermediate P) and 156 AD subjects without psychosis (AD-P) who were recruited at the University of Pittsburgh Alzheimer's Disease Research Center using over 1 million single-nucleotide polymorphisms (SNPs) and CNV markers. CNV load analysis found no significant difference in total and average CNV length and CNV number in the AD+P or AD intermediate P groups compared with the AD-P group. Our analysis revealed a marginally significant lower number of duplication events in AD+P cases compared with AD-P controls (P=0.059) using multivariable regression model. The most interesting finding was the presence of a genome-wide significant duplication in the APC2 gene on chromosome 19, which was protective against developing AD+P (odds ratio=0.42; P=7.2E-10). We also observed suggestive associations of duplications with AD+P in the SET (P=1.95E-06), JAG2 (P=5.01E-07) and ZFPM1 (P=2.13E-07) genes and marginal association of a deletion in CNTLN (P=8.87E-04). We have identified potential novel loci for psychosis in Alzheimer's disease that warrant follow-up in large-scale independent studies.

DIAGNOSIS AND MEDICAL AND SURGICAL MANAGEMENT OF CHRONIC INFECTIOUS FIBRINOUS PLEURITIS IN AN OKAPI (OKAPIA JOHNSTONI).

A 10-yr-old female okapi (Okapia johnstoni) at the San Diego Zoo Safari Park was evaluated for intermittent malaise, inappetence, occasional cough, abdominal splinting, and licking at both flanks. Physical examination revealed tachypnea, tachycardia, and fluid sounds on thoracic auscultation. Transthoracic ultrasound showed multiple uniform, anechoic filled structures in the right and left pleural space. Surgical exploration of the thoracic cavity revealed bilateral, mature, fibrous, compartmentalizing adhesions between the visceral and parietal pleura, confirming a diagnosis of chronic, infectious, fibrinous pleuritis. The suspected etiology was occult aspiration pneumonia secondary to historical episodes of regurgitation associated with general anesthesia. Culture of the pleural fluid and fibrous adhesions grew Trueperella (Arcanobacterium) pyogenes, Arcanobacterium haemolyticum, and few Fusobacterium species. Treatment consisted of chest-tube placement to establish drainage, thoracic lavage, unilateral surgical debridement, and long-term antibiotics. The animal made a complete clinical recovery over 7 mo.

Treatment and outcomes of metastatic colorectal cancer in Australia: defining differences between public and private practice.

BACKGROUND: Prior studies have suggested improved outcomes for cancer patients managed in private centres, despite universal healthcare within Australia. AIMS: To compare patient, disease, treatment and survival data for metastatic colorectal cancer (mCRC) managed in private versus public centres. METHODS: Analysis of prospectively collected registry data for consecutive patients with mCRC managed at 16 participating centres from July 2009. RESULTS: Data for 1065 patients were examined. Age, gender and Charlson comorbidity score were similar for public and private patients. Private patients were more commonly Eastern Cooperative Oncology Group performance score 0-1 (85% vs 78%, P = 0.008), in the highest Index of Relative Socioeconomic Advantage and Disadvantage quintile (57% vs 18%, P < 0.001) or had a single metastatic site (62% vs 54%, P = 0.009). Patients treated in private were more likely to receive chemotherapy (84% vs 70%, P < 0.001), bevacizumab (59% vs 50%, P = 0.008), be treated with curative intent (37% vs 26%, P < 0.001) and undergo metastasectomy (30% vs 22%, P = 0.001). These management differences remained statistically significant after adjusting for baseline characteristics. Management in the private setting was associated with superior overall survival (median 27.9 vs 20 months, hazard ratio 0.7, 95% confidence interval: 0.57 to 0.86, P = 0.001), significant in multivariate analysis adjusting for all baseline covariates. CONCLUSIONS: Significant differences in baseline characteristics were noted for private versus public patients. However, these do not explain the higher rates of treatment delivery in the private setting, which likely contributed towards the observed survival difference. Further studies are required to determine if the increased likelihood of intervention in the private setting is driven by patient, clinician and/or institutional factors.

Prenatal marijuana exposure, age of marijuana initiation, and the development of psychotic symptoms in young adults.

BACKGROUND: Studies have demonstrated that an early age of onset of marijuana use (EAOM) is associated with a higher risk of developing psychotic symptoms (PS) compared to initiating marijuana use at a later age or not at all. Research has also found that prenatal marijuana exposure (PME) predicts EAOM. This report evaluates the relationships among PME, EAOM, and PS. METHOD: Subjects were initially interviewed in their fourth prenatal month. Women and offspring who completed the birth assessment (n = 763) were selected for follow-up. Women and their offspring were followed until the offspring were 22 years of age: 596 offspring were evaluated. At age 22, PS were assessed in the offspring with the Diagnostic Interview Schedule using DSM-IV criteria. Analyses controlled for significant covariates including other prenatal substance exposures, race, gender, and offspring substance use at 22 years. RESULTS: PME and EAOM significantly predicted increased rates of PS at 22 years controlling for other significant covariates. The direct effect of PME on PS was marginally significant (p = 0.06) when EAOM was entered into the model and other covariates were fixed. In the mediation analysis, EAOM did not significantly mediate the association between PME and PS, controlling for significant covariates, nor was the indirect pathway significant when structural equation modeling was used. The total effect of the direct and indirect pathways was significant. CONCLUSIONS: In addition to EAOM, PME may also play a role in the association between marijuana use and the development of PS. This could highlight a new area for prevention.