Plasma complement and coagulation proteins as prognostic factors of negative symptoms: An analysis of the NAPLS 2 and 3 studies.

INTRODUCTION: Negative symptoms impact the quality of life of individuals with psychosis and current treatment options for negative symptoms have limited effectiveness. Previous studies have demonstrated that complement and coagulation pathway protein levels are related to later psychotic experiences, psychotic disorder, and functioning. However, the prognostic relationship between complement and coagulation proteins and negative symptoms is poorly characterised. METHODS: In the North American Prodrome Longitudinal Studies 2 and 3, negative symptoms in 431 individuals at clinical high-risk for psychosis (mean age: 18.2, SD 3.6; 42.5 % female) were measured at multiple visits over 2 years using the Scale of Psychosis-Risk Symptoms. Plasma proteins were quantified at baseline using mass spectrometry. Four factors were derived to represent levels of proteins involved in the activation or regulation of the complement or coagulation systems. The relationships between standardised protein group factors and serial measurements of negative symptoms over time were modelled using generalised least squares regression. Analyses were adjusted for baseline candidate prognostic factors: negative symptoms, positive symptoms, functioning, depressive symptoms, suicidal ideation, cannabis use, tobacco use, antipsychotic use, antidepressant use, age, and sex. RESULTS: Clinical and demographic prognostic factors of follow-up negative symptoms included negative, positive, and depressive symptoms, functioning, and age. Adjusting for all candidate prognostic factors, the complement regulators group and the coagulation regulators group were identified as prognostic factors of follow-up negative symptoms (ß: 0.501, 95 % CI: 0.160, 0.842; ß: 0.430, 95 % CI: 0.080, 0.780 respectively. The relationship between complement regulator levels and negative symptoms was also observed in NAPLS2 alone (ß: 0.501, 95 % CI: -0.037, 1.039) and NAPLS3 alone, additionally adjusting for BMI (ß: 0.442, 95 % CI: 0.127, 0.757). CONCLUSION: The results indicate that plasma complement and coagulation regulator levels are prognostic factors of negative symptoms, independent of clinical and demographic prognostic factors. These results suggest complement and coagulation regulator levels could have potential utility in informing treatment decisions for negative symptoms in individuals at risk.

Benzene homologues contaminants in a former herbicide factory site: distribution, attenuation, risk, and remediation implication.

Benzene homologues often used as organic raw materials or as detergents in chemical industry are prone to accidental release into the environment which can cause serious long-term soil pollutions. In a large former herbicide factory site, we investigated 43 locations for benzene homologues contaminations in soil, soil gas, and groundwater and studied the hydrogeological conditions. An inverse distance weighted interpolation method was employed to determine the pollutants three-dimensional spatial distribution in the soils. Results showed that benzene homologues residues were mainly originated from the herbicide production workshop and that the pollution had horizontally expanded at the deeper soil layer. Contaminants had already migrated 15 m downward from ground surface. Contaminant phase distribution study showed that NAPL was the primary phase (> 99%) for the pollutants accumulated in the unsaturated zone, while it had not migrated to groundwater. The primary mechanism for contaminant transport and attenuation included dissolution of "occluded" NAPL into pore water and pollutant volatilization into soil pore space. Risk assessment revealed that the pollutants brought unacceptable high carcinogenic and non-carcinogenic risks to public health. In order to convert this former chemical processing factory site into a residential area, a remediation to the polluted production workshop sites is urgently required.

Laboratory Testing in Support of Surfactant-Alternating-Gas Foam Flood for NAPL Recovery from Shallow Subsurface.

Use of viscosifiers have been shown helpful for mobility control when displacing higher viscosity fluids, and to improve sweep in heterogeneous media. Foam can be used as a viscosifier for this purpose. Selected surfactant solutions were investigated for their ability to generate foam within porous media and foam stability through batch and column experiments using field-obtained soil. The approach used to generate foam in-situ consisted of several cycles (7) of surfactant-alternating-gas originally developed to recover crude oil; 0.25 pore volumes (PV) surfactant followed by 0.25 PV of air. The apparent viscosity ranged from 60 to 100 cP from the 3rd to 7th cycle, respectively. Foam was collected from the column exit after being shut-in for 3 days as a proof of foam generation and stability. Results showed that the selected surfactant formulation can be used to generate foam in-situ for use in the field for environmental restoration.

Effect of low-concentration rhamnolipid biosurfactant on Pseudomonas aeruginosa transport in natural porous media.

The effect of low-concentrations of monorhamnolipid biosurfactant on transport of Pseudomonas aeruginosa ATCC 9027 in natural porous media (silica sand and a sandy soil) was studied with miscible-displacement experiments using artificial groundwater as the background solution. Transport of two types of cells was investigated, glucose- and hexadecane-grown cells with lower and higher cell surface hydrophobicity (CSH), respectively. The effect of hexadecane presence as a residual non-aqueous phase liquid (NAPLs) on transport was also examined. A clean-bed colloid deposition model was used to calculate deposition rate coefficients (k) for quantitative assessment. Significant cell retention was observed in the sand (81% and 82% for glucose- and hexadecane-grown cells, respectively). Addition of a low-concentration rhamnolipid solution enhanced cell transport, with 40 mg/L of rhamnolipid reducing retention to 50% and 60% for glucose- and hexadecane-grown cells, respectively. The k values for both glucose- and hexadecane-grown cells correlate linearly with rhamnolipid-dependent CSH represented as bacterial-adhesion-to-hydrocarbon rate of cells. Retention of cells by the soil was nearly complete (>99%). Addition of 40 mg/L rhamnolipid solution reduced retention to 95%. The presence of NAPLs in the sand increased the retention of hexadecane-grown cells with higher CSH. Transport of cells in the presence of the NAPL was enhanced by rhamnolipid at all concentrations tested, and the relative enhancement was greater than in was in the absence of NAPL. This study shows the importance of hydrophobic interaction on bacterial transport in natural porous media and the potential of using low-concentration rhamnolipid for facilitating the transport in subsurface for bioaugmentation efforts.

Core Schemas in Youth at Clinical High Risk for Psychosis.

BACKGROUND: Schema Theory proposes that the development of maladaptive schemas are based on a combination of memories, emotions and cognitions regarding oneself and one's relationship to others. A cognitive model of psychosis suggests that schemas are crucial to the development and persistence of psychosis. Little is known about the impact that schemas may have on those considered to be at clinical high risk (CHR) of developing psychosis. AIMS: To investigate schemas over time in a large sample of CHR individuals and healthy controls. METHOD: Sample included 765 CHR participants and 280 healthy controls. Schemas were assessed at baseline, 6 and 12 months using the Brief Core Schema Scale (BCSS). Baseline schemas were compared to 2-year clinical outcome. RESULTS: CHR participants evidenced stable and more maladaptive schemas over time compared to controls. Schemas at initial contact did not vary amongst the different clinical outcome groups at 2 years although all CHR outcome groups evidenced significantly worse schemas than healthy controls. Although there were no differences on baseline schemas between those who later transitioned to psychosis compared to those who did not, those who transitioned to psychosis had more maladaptive negative self-schemas at the time of transition. Associations between negative schemas were positively correlated with earlier abuse and bullying. CONCLUSIONS: These findings demonstrate a need for interventions that aim to improve maladaptive schemas among the CHR population. Therapies targeting self-esteem, as well as schema therapy may be important work for future studies.

Polygenic Risk Score Contribution to Psychosis Prediction in a Target Population of Persons at Clinical High Risk.

OBJECTIVE: The 2-year risk of psychosis in persons who meet research criteria for a high-risk syndrome is about 15%-25%; improvements in risk prediction accuracy would benefit the development and implementation of preventive interventions. The authors sought to assess polygenic risk score (PRS) prediction of subsequent psychosis in persons at high risk and to determine the impact of adding the PRS to a previously validated psychosis risk calculator. METHODS: Persons meeting research criteria for psychosis high risk (N=764) and unaffected individuals (N=279) were followed for up to 2 years. The PRS was based on the latest schizophrenia and bipolar genome-wide association studies. Variables in the psychosis risk calculator included stressful life events, trauma, disordered thought content, verbal learning, information processing speed, and family history of psychosis. RESULTS: For Europeans, the PRS varied significantly by group and was higher in the psychosis converter group compared with both the nonconverter and unaffected groups, but was similar for the nonconverter group compared with the unaffected group. For non-Europeans, the PRS varied significantly by group; the difference between the converters and nonconverters was not significant, but the PRS was significantly higher in converters than in unaffected individuals, and it did not differ between nonconverters and unaffected individuals. The R2liability (R2 adjusted for the rate of disease risk in the population being studied, here assuming a 2-year psychosis risk between 10% and 30%) for Europeans varied between 9.2% and 12.3% and for non-Europeans between 3.5% and 4.8%. The amount of risk prediction information contributed by the addition of the PRS to the risk calculator was less than severity of disordered thoughts and similar to or greater than for other variables. For Europeans, the PRS was correlated with risk calculator variables of information processing speed and verbal memory. CONCLUSIONS: The PRS discriminates psychosis converters from nonconverters and modestly improves individualized psychosis risk prediction when added to a psychosis risk calculator. The schizophrenia PRS shows promise in enhancing risk prediction in persons at high risk for psychosis, although its potential utility is limited by poor performance in persons of non-European ancestry.

Mechanisms of mass transfer enhancement by phase-transfer catalysis for permanganate oxidizing dense non-aqueous phase liquid (DNAPL) TCE.

Phase transfer catalysts (PTCs) have been shown to be effective in lowering the limitation of mass transfer between aqueous oxidant MnO4- and NAPLs in in-situ chemical oxidation (ISCO) technologies for remediation of NAPLs. This work researched the effects of pentyltriphenylphosphonium bromide (PTPP, used as the representative PTC) for the enhancement of TCE oxidation, the extent of different treatment effects contributions and generalizability of phase transfer. Experimental results revealed that MnO4- exchanged with Br- in PTPP by ion exchange mechanism and then transferred to NAPL phase due to biphasic nature of PTPP-MnO4-. PTPP enhanced TCE dissolution in aqueous phase but had no significant effect on TCE solubilization. Enhanced TCE dissolution gradually weakened after 2.0 h and disappeared after 5.5 h, while the percentage of MnO4- in phase transfer was 14.8% at 7.5 h, which indicated that dissolution acceleration was only effective at initial stage of reaction (0-2.5 h). Therefore, persistent phase transfer process played the leading role in TCE remediation enhancement. Moreover, for different NAPL phase, more effective phase transfer could be achieved in NAPLs with higher solubility and weaker hydrophobicity. The best-fit polynomial relationship (R2 = 0.992) existed between the percentage amount of MnO4- transferred and the solubility of NAPL.

The Global Functioning: Social and Role Scales-Further Validation in a Large Sample of Adolescents and Young Adults at Clinical High Risk for Psychosis.

OBJECTIVE: Traditional measures for assessing functioning with adult patients with schizophrenia have been shown to be insufficient for assessing the issues that occur in adolescents and young adults at clinical high risk (CHR) for psychosis. The current study provides an expanded validation of the Global Functioning: Social (GF:Social) and Role (GF:Role) scales developed specifically for use with CHR individuals and explores the reliability and accuracy of the ratings, the validity of the scores in comparison to other established clinical measures, stability of functioning over a 2-year period, and psychosis predictive ability. METHODS: Seven hundred fifty-five CHR individuals and 277 healthy control (HC) participants completed the GF:Social and Role scales at baseline as part of the North American Prodrome Longitudinal Study (NAPLS2). RESULTS: Inter-rater reliability and accuracy were high for both scales. Correlations between the GF scores and other established clinical measures demonstrated acceptable convergent and discriminant validity. In addition, GF:Social and Role scores were unrelated to positive symptoms. CHR participants showed large impairments in social and role functioning over 2-years, relative to the HCs, even after adjusting for age, IQ, and attenuated positive symptoms. Finally, social decline prior to baseline was more pronounced in CHR converters, relative to non-converters. CONCLUSIONS: The GF scales can be administered in a large-scale multi-site study with excellent inter-rater reliability and accuracy. CHR individuals showed social and role functioning impairments over time that were not confounded by positive symptom severity levels. The results of this study demonstrate that social decline is a particularly effective predictor of conversion outcome.

Evaluation of ethoxylated nonionic surfactants for solubilization of chlorinated organic phases: Effects of partitioning loss and macroemulsion formation.

Selection of proper surfactants is critical for applying surfactant-enhanced remediation (SER) to sites contaminated with nonaqueous phase liquids (NAPLs). Here, ethoxylated nonionic surfactants (Tween 20, Tween 40, Tween 80, and Triton X-100) were evaluated for their applicability to remedy chlorinated organic phases, chloroform (CF), trichloroethylene (TCE), and tetrachloroethylene (PCE), on the basis of solubilization capacity, partitioning behavior, and macroemulsion formation. The most hydrophilic CF was not relevant for SER applications since excessive surfactant partitioning into CF rendered only few of them available for its solubilization. In contrast, the more hydrophobic TCE and PCE, having moderate surfactant partitioning, were effectively solubilized. Among Tween surfactants, a more hydrophobic surfactant showed a larger solubilization potential for both chloroethylenes, but it suffered from a greater partitioning loss. Depending on the type and extent of NAPL contaminations, thus, a prior consideration should be given to either solubilization capacity or partitioning loss when selecting the optimal Tween surfactant. Compared to Tween surfactants, the more hydrophobic Triton X-100 showed greater partitioning losses into all three NAPLs. Of particular, its partitioning into CF and TCE was nearly complete, making impractical its application to the remediation of both organic liquids. The formation of macroemulsions, characterized by a high turbidity, may significantly deteriorate SER applicability by producing undesirable flows in aquifers. Their formation became more problematic with the increasing surfactant hydrophilicity and the increasing NAPL hydrophobicity. When these combinations are applied, it is critical to keep such surfactant concentrations as to exploit the solubilization potential but not to cause the macroemulsion formation.

The Early Psychosis Screener (EPS): Item development and qualitative validation.

A panel of experts assembled and analyzed a comprehensive item bank from which a highly sensitive and specific early psychosis screener could be developed. Twenty well-established assessments relating to the prodromal stage, early psychosis, and psychosis were identified. Using DSM-5 criteria, we identified the core concepts represented by each of the items in each of the assessments. These granular core concepts were converted into a uniform set of 490 self-report items using a Likert scale and a 'past 30days' time frame. Partial redundancy was allowed to assure adequate concept coverage. A panel of experts and TeleSage staff rated these items and eliminated 189 items, resulting in 301 items. The items were subjected to five rounds of cognitive interviewing with 16 individuals at clinically high risk for psychosis and 26 community mental health center patients. After each round, the expert panel iteratively reviewed, rated, revised, added, or deleted items to maximize clarity and centrality to the concept. As a result of the interviews, 36 items were revised, 52 items were added, and 205 items were deleted. By the last round of cognitive interviewing, all of the items were clearly understood by all participants. In future work, responses to the final set of 148 items and machine learning techniques will be used to quantitatively identify the subset of items that will best predict clinical high-risk status and conversion.

A mobile, modular and rapidly-acting treatment system for optimizing and improving the removal of non-aqueous phase liquids (NAPLs) in groundwater.

Non-aqueous phase liquids (NAPLs) in pumped groundwater are highly variable, challenging the selection of above-ground treatment strategies in pump-and-treat system. Adjustable systems with multiple treatment units are urgently required. In the present study, a mobile, modular and rapidly-acting treatment system was developed to treat groundwater contaminated by NAPLs at a chemical industrial site. The system integrated four units of coagulation sedimentation, air flotation, air stripping and chemical oxidation. During a 3-month onsite operation, the composition of groundwater NAPLs had huge fluctuations and different treatment units had unique advantages in eliminating some components. For instance, air stripping exhibited satisfactory removal efficiencies (>80%) for short-chain petroleum hydrocarbons and chloroalkanes, but poor performance for others comparing to other units. A decision-making tool and a central control system were further developed to combine and adjust the four units in proper orders, achieving satisfied removal efficiency (70-90%) for multi-component NAPLs, regardless of composition fluctuation. These findings raise the state-of-the-art modular and rapidly-acting groundwater treatment system to clean up NAPLs contaminated groundwater through pump-and-treat strategy, help in better understanding on the decision and management to improve the treatment performance, and provide guidelines for its implication at other sites contaminated with multi-component NAPLs or undergoing accidental contamination.

The Early Psychosis Screener (EPS): Quantitative validation against the SIPS using machine learning.

Machine learning techniques were used to identify highly informative early psychosis self-report items and to validate an early psychosis screener (EPS) against the Structured Interview for Psychosis-risk Syndromes (SIPS). The Prodromal Questionnaire-Brief Version (PQ-B) and 148 additional items were administered to 229 individuals being screened with the SIPS at 7 North American Prodrome Longitudinal Study sites and at Columbia University. Fifty individuals were found to have SIPS scores of 0, 1, or 2, making them clinically low risk (CLR) controls; 144 were classified as clinically high risk (CHR) (SIPS 3-5) and 35 were found to have first episode psychosis (FEP) (SIPS 6). Spectral clustering analysis, performed on 124 of the items, yielded two cohesive item groups, the first mostly related to psychosis and mania, the second mostly related to depression, anxiety, and social and general work/school functioning. Items within each group were sorted according to their usefulness in distinguishing between CLR and CHR individuals using the Minimum Redundancy Maximum Relevance procedure. A receiver operating characteristic area under the curve (AUC) analysis indicated that maximal differentiation of CLR and CHR participants was achieved with a 26-item solution (AUC=0.899±0.001). The EPS-26 outperformed the PQ-B (AUC=0.834±0.001). For screening purposes, the self-report EPS-26 appeared to differentiate individuals who are either CLR or CHR approximately as well as the clinician-administered SIPS. The EPS-26 may prove useful as a self-report screener and may lead to a decrease in the duration of untreated psychosis. A validation of the EPS-26 against actual conversion is underway.

Functional Capacity Assessed by the Map Task in Individuals at Clinical High-Risk for Psychosis.

OBJECTIVES: Recent studies have recognized that signs of functional disability in schizophrenia are evident in early phases of the disorder, and, as a result, can potentially serve as vulnerability markers of future illness. However, functional measures in the psychosis prodrome have focused exclusively on real-world achievements, rather than on the skills required to carry-out a particular real-world function (ie, capacity). Despite growing evidence that diminished capacity is critical to the etiology of the established disorder, virtually no attention has been directed towards assessing functional capacity in the pre-illness stages. In the present study, we introduce the Map task, a measure to assess functional capacity in adolescent and young-adult high-risk populations. METHODS: The Map task was administered to 609 subjects at Clinical High-Risk (CHR) for psychosis and 242 Healthy Controls (HCs) participating in the North American Prodrome Longitudinal Study (NAPLS2). Subjects were required to efficiently complete a set of specified errands in a fictional town. RESULTS: CHR participants showed large impairments across major indices of the Map task, relative to the HCs. Most importantly, poor performance on the Map task significantly predicted conversion to psychosis, even after adjusting for age, IQ, clinical state, and other potential confounders. CONCLUSIONS: To the best of our knowledge, the Map task is one of the first laboratory-based measures to assess functional capacity in high-risk populations. Functional capacity deficits prior to the onset of psychosis may reflect a basic mechanism that underlies risk for psychosis. Early intervention targeting this domain may help to offset risk and independently improve long-term outcome.

Stress and neurodevelopmental processes in the emergence of psychosis.

The notion that stress plays a role in the etiology of psychotic disorders, especially schizophrenia, is longstanding. However, it is only in recent years that the potential neural mechanisms mediating this effect have come into sharper focus. The introduction of more sophisticated models of the interplay between psychosocial factors and brain function has expanded our opportunities for conceptualizing more detailed psychobiological models of stress in psychosis. Further, scientific advances in our understanding of adolescent brain development have shed light on a pivotal question that has challenged researchers; namely, why the first episode of psychosis typically occurs in late adolescence/young adulthood. In this paper, we begin by reviewing the evidence supporting associations between psychosocial stress and psychosis in diagnosed patients as well as individuals at clinical high risk for psychosis. We then discuss biological stress systems and examine changes that precede and follow psychosis onset. Next, research findings on structural and functional brain characteristics associated with psychosis are presented; these findings suggest that normal adolescent neuromaturational processes may go awry, thereby setting the stage for the emergence of psychotic syndromes. Finally, a model of neural mechanisms underlying the pathogenesis of psychosis is presented and directions for future research strategies are explored.