Biomarker case-detection and prediction with potential for functional psychosis screening: development and validation of a model related to biochemistry, sensory neural timing and end organ performance

The Mental Health Biomarker Project aimed to discover case-predictive biomarkers for functional psychosis. In a retrospective, cross-sectional study, candidate marker results from 67 highly characterized symptomatic participants were compared with results from 67 gender- and age-matched controls. Urine samples were analyzed for catecholamines, their metabolites, and hydroxylpyrolline-2-one, an oxidative stress marker. Blood samples were analyzed for vitamin and trace element cofactors of enzymes in catecholamine synthesis and metabolism pathways. Cognitive, auditory, and visual processing measures were assessed using a simple 45-min, office-based procedure. Receiver operating curve (ROC) and odds ratio analysis discovered biomarkers for deficits in folate, vitamin D and B6 and elevations in free copper to zinc ratio, catecholamines and the oxidative stress marker. Deficits were discovered in peripheral visual and auditory end-organ function, intracerebral auditory and visual processing speed and dichotic listening performance. Fifteen ROC biomarker variables were divided into five functional domains. Through a repeated ROC process, individual ROC variables, followed by domains and finally the overall 15 set model, were dichotomously scored and tallied for abnormal results upon which it was found that ≥3 out of 5 abnormal domains achieved an area under the ROC curve of 0.952 with a sensitivity of 84% and a specificity of 90%. Six additional middle ear biomarkers in a 21 biomarker set increased sensitivity to 94%. Fivefold cross-validation yielded a mean sensitivity of 85% for the 15 biomarker set. Non-parametric regression analysis confirmed that ≥3 out of 5 abnormally scored domains predicted >50% risk of caseness while 4 abnormally scored domains predicted 88% risk of caseness; 100% diagnostic certainty was reached when all 5 domains were abnormally scored. These findings require validation in prospective cohorts and other mental illness states. They have potential for case-detection, -screening, -monitoring, and -targeted personalized management. The findings unmask unmet needs within the functional psychosis condition and suggest new biological understandings of psychosis phenomenology.Stephanie Fryar-Williams and Jörg E. Strobe

Common Hazards in Karst Terrain

Karst refers to terrain largely drained by subsurface conduits and caves. Karst landscapes are characterized by surface features such as springs, sinkholes, shallow depressions, and rolling hills (Figure 1). Karst regions are also known for their subsurface or below-ground features such as conduits and caves (Figure 2). What makes a karst region unique is the way runoff drains from the land. In karst regions, some of the runoff flows into surface features such as sinkholes where it then travels underground. Some of this infiltrated water re-emerges at springs (Figure 1a), and some continues moving underground

Succession of fungi on dead and live wood in brackish water in Brunei

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Instabilities in the dissolution of a porous matrix

A reactive fluid dissolving the surrounding rock matrix can trigger an instability in the dissolution front, leading to spontaneous formation of pronounced channels or wormholes. Theoretical investigations of this instability have typically focused on a steadily propagating dissolution front that separates regions of high and low porosity. In this paper we show that this is not the only possible dissolutional instability in porous rocks; there is another instability that operates instantaneously on any initial porosity field, including an entirely uniform one. The relative importance of the two mechanisms depends on the ratio of the porosity increase to the initial porosity. We show that the "inlet" instability is likely to be important in limestone formations where the initial porosity is small and there is the possibility of a large increase in permeability. In quartz-rich sandstones, where the proportion of easily soluble material (e.g. carbonate cements) is small, the instability in the steady-state equations is dominant.Comment: to be published in Geophysical Research Letter

Biomarkers of a five-domain translational substrate for schizophrenia and schizoaffective psychosis

BACKGROUND: The Mental Health Biomarker Project (2010-2014) selected commercial biochemistry markers related to monoamine synthesis and metabolism and measures of visual and auditory processing performance. Within a case-control discovery design with exclusion criteria designed to produce a highly characterised sample, results from 67 independently DSM IV-R-diagnosed cases of schizophrenia and schizoaffective disorder were compared with those from 67 control participants selected from a local hospital, clinic and community catchment area. Participants underwent protocol-based diagnostic-checking, functional-rating, biological sample-collection for thirty candidate markers and sensory-processing assessment. RESULTS: Fifteen biomarkers were identified on ROC analysis. Using these biomarkers, odds ratios, adjusted for a case-control design, indicated that schizophrenia and schizoaffective disorder were highly associated with dichotic listening disorder, delayed visual processing, low visual span, delayed auditory speed of processing, low reverse digit span as a measure of auditory working memory and elevated levels of catecholamines. Other nutritional and biochemical biomarkers were identified as elevated hydroxyl pyrroline-2-one as a marker of oxidative stress, vitamin D, B6 and folate deficits with elevation of serum B12 and free serum copper to zinc ratio. When individual biomarkers were ranked by odds ratio and correlated with clinical severity, five functional domains of visual processing, auditory processing, oxidative stress, catecholamines and nutritional-biochemical variables were formed. When the strengths of their inter-domain relationships were predicted by Lowess (non-parametric) regression, predominant bidirectional relationships were found between visual processing and catecholamine domains. At a cellular level, the nutritional-biochemical domain exerted a pervasive influence on the auditory domain as well as on all other domains. CONCLUSIONS: The findings of this biomarker research point towards a much-required advance in Psychiatry: quantification of some theoretically-understandable, translationally-informative, treatment-relevant underpinnings of serious mental illness. This evidence reveals schizophrenia and schizoaffective disorder in a somewhat different manner, as a conglomerate of several disorders many of which are not currently being assessed-for or treated in clinical settings. Currently available remediation techniques for these underlying conditions have potential to reduce treatment-resistance, relapse-prevention, cost burden and social stigma in these conditions. If replicated and validated in prospective trials, such findings will improve progress-monitoring and treatment-response for schizophrenia and schizoaffective disorder.Stephanie Fryar-Williams, and Jörg E Strobe

Spatial and Temporal Variability in Seepage between a Contaminated Aquifer and Tributaries to the Ohio River

Because interactions between ground water and tributaries may influence contaminant loading to rivers, we delineated seepage along Little Bayou and Bayou Creeks in McCracken County, Kentucky, during a two-year period. From the Paducah Gaseous Diffusion Plant, on the divide between the creeks, trichloroethene and technetium-99 plumes extend several km toward the Ohio River. Gaining conditions occur where the creeks are incised into coarse sediments in the river\u27s flood plain. Such conditions were marked by upward hydraulic gradients within the bed; maximum specific discharge (q) \u3e 0.24 m d-1; relatively narrow ranges of stream, piezometer, and bed temperatures; relatively cool bed and bank temperatures in summer and early autumn; detections of trace solutes in stream water; and observations of springs, boils, and seeps. Evidence of losing or no-net-discharge conditions included downward or lateral hydraulic gradients; minimal q values (indicative of stream-water flow through the bed); and relatively broad annual ranges of stream and piezometer temperatures. Mixing calculations using δ18O and Cl- support inferences about gaining and losing reaches. Seepage rates and directions changed during dry periods in summer and early autumn and following Ohio River flooding in spring. Discharge of uncontaminated ground water dilutes contaminants in Little Bayou Creek

Effect of polycrystallinity on the optical properties of highly oriented ZnO grown by pulsed laser deposition

We report the results of photoluminescence and reflectance measurements on highly c-axis oriented polycrystalline ZnO grown by pulsed laser deposition. The samples measured were grown under identical conditions and were annealed in-situ at various temperatures for 10-15 min. The band-edge photoluminescence spectra of the material altered considerably with an increase in grain size, with increased free exciton emission and observable excitonic structure in the reflectance spectra. The green band emission also increased with increasing grain size. A deformation potential analysis of the effect of strain on the exciton energy positions of the A- and B-excitons demonstrated that the experimental exciton energies could not be explained solely in terms of sample strain. We propose that electric fields in the samples due to charge trapping at grain boundaries are responsible for the additional perturbation of the excitons. This interpretation is supported by theoretical estimates of the exciton energy perturbation due to electric fields. The behaviour of the green band in the samples provides additional evidence in favour of our model

Intersectionality and equity: Dynamic bureaucratic representation in higher education

Representative bureaucracy scholarship has yet to address two interrelated phenomena: intersectionality and changes in relative disadvantage over time. This manuscript addresses these gaps by assessing representation effects at the intersection of race/ethnicity and sex and in previously, but no longer, disadvantaged client groups. It also argues that if bureaucratic representation is viewed as a quest for equity, then representation will decline as disadvantaged client groups approach equity in policy outcomes. Using panel data for US higher education, this study highlights the importance of intersectional representation in bureaucratic organizations. In three of the four race/ethnic/sex combinations, students perform better in the presence of faculty who match them intersectionally (in the fourth case, race but not sex matters). The empirical results also find that as a formerly disadvantaged client group (women) becomes successful within an organization, the active representation relationship declines. These implications inform future representative bureaucracy scholarship examining intersectional groups