Correlates of substance use in a large naturalistic cohort of young people with early and emerging psychosis.

BACKGROUND: Substance use remains a barrier to recovery for young people accessing early intervention services for psychosis. While correlates of use have been explored in populations experiencing a first episode of psychosis (FEP), sample sizes have been small and less research assesses cohorts at ultrahigh risk of psychosis (UHR). METHODS: This study uses data from a naturalistic cohort including UHR and FEP participants (N = 1252) to elucidate clinical correlates of use in the past 3 months of any illicit substance, amphetamine-type stimulants (ATS), cannabis, and tobacco. Moreover, network analysis based on use of these substances and additionally alcohol, cocaine, hallucinogens, sedatives, inhalants, and opioids was completed. RESULTS: Young people with FEP used substances at significantly higher rates than those at UHR. High concurrence of use was seen between substances. In the FEP group, participants who had used any illicit substance, ATS, and/or tobacco had increased positive symptoms and decreased negative symptoms. Young people with FEP who used cannabis had increased positive symptoms. In the UHR group, participants who had used any illicit substance, ATS, and/or cannabis in the past 3 months showed decreased negative symptoms compared to those who had not. CONCLUSION: A distinct clinical picture of more florid positive symptoms and alleviated negative symptoms seen in those who use substances in the FEP group appears muted in the UHR cohort. Treating young people at UHR in early intervention services represents the earliest opportunity to address substance use early to improve outcomes.

Ascending palatine branch from the lingual artery with multiple other variations of the external carotid artery.

The external carotid artery (ECA) is the major blood supply for structures in the head and neck. Typically, it has 8 separate branches; but there are many anatomical variations, making it difficult to predict surgical outcomes and complications without 3-dimensional imaging. This case study focuses on a cadaver with multiple anatomical variations in the ECA, i.e., lingual, facial, occipital, ascending pharyngeal, and posterior auricular arteries, found during routine dissection of the right cadaveric neck. We also discuss the incidences of several other anatomical variations of the ECA branches and their surgical implications and potential complications.

Accessory anterior ethmoidal nerve and artery: a cadaveric case report.

The anterior ethmoidal artery (AEA) is an important surgical landmark for procedures involving the anterior cranial fossa. Many variations in the location and branching pattern of the AEA have been reported throughout the literature. These anatomical variations are important for surgeons to be familiar with as injury to the AEA can lead to massive haemorrhage, orbital haematomas, and cerebrospinal fluid rhinorrhoea. Anatomical landmarks such as the ethmoidal foramen can be used to identify the location of the AEA; however, it is also important to consider that the foramen may have variable presentations. If there is ever difficulty with identification of the AEA, surgeons should pursue a high-resolution computed tomography to minimise the risk of surgical complications. In this report, we present a rare case of a variant accessory anterior ethmoidal artery and nerve, and variations in the ethmoidal foramen found during cadaveric dissection.

The posterior cranial fossa's dura mater innervation and its clinical implication in headache: a comprehensive review.

The pathophysiology of migraines and headaches has been a point of interest in research as they affect a large subset of the population, and the exact mechanism is still unclear. There is evidence implicating the dura mater and its innervation as contributing factors, especially at the posterior cranial fossa. Many modes of innervation have been identified, including the dorsal root ganglion, superior cervical ganglion, vagus nerve, trigeminal nerve, hypoglossal nerve, and glossopharyngeal nerve. While the exact method of innervation is still under investigation, there is strong evidence suggesting that different types of headaches (migraine vs. occipital vs. cervicogenic) are due to specific nerves and inflammatory mediators that contribute to the dura mater in some way. By understanding how these innervation patterns manifest clinically, the course of treatment can be tailored based on the physiological aetiology. Here, we present a comprehensive literature review of the current research regarding the innervation of the dura mater of the posterior cranial fossa and its clinical implications.

Dual innervation of the submandibular gland by nerve to mylohyoid and chorda tympani.

The chorda tympani typically utilises the lingual nerve and submandibular ganglion to transmit parasympathetic fibres to the submandibular gland. During a routine anatomy dissection, the submandibular gland was found to be innervated by both the lingual nerve and the nerve to mylohyoid. The clinical implications of this variant dual innervation to the submandibular gland is not clear due to its rarity: however, recognising such a variation should be borne in mind during surgical intervention near the nerve to mylohyoid.

Anisotropic contrast optical microscope.

An optical microscope is described that reveals contrast in the Mueller matrix images of a thin, transparent, or semi-transparent specimen located within an anisotropic object plane (anisotropic filter). The specimen changes the anisotropy of the filter and thereby produces contrast within the Mueller matrix images. Here we use an anisotropic filter composed of a semi-transparent, nanostructured thin film with sub-wavelength thickness placed within the object plane. The sample is illuminated as in common optical microscopy but the light is modulated in its polarization using combinations of linear polarizers and phase plate (compensator) to control and analyze the state of polarization. Direct generalized ellipsometry data analysis approaches permit extraction of fundamental Mueller matrix object plane images dispensing with the need of Fourier expansion methods. Generalized ellipsometry model approaches are used for quantitative image analyses. These images are obtained from sets of multiple images obtained under various polarizer, analyzer, and compensator settings. Up to 16 independent Mueller matrix images can be obtained, while our current setup is limited to 11 images normalized by the unpolarized intensity. We demonstrate the anisotropic contrast optical microscope by measuring lithographically defined micro-patterned anisotropic filters, and we quantify the adsorption of an organic self-assembled monolayer film onto the anisotropic filter. Comparison with an isotropic glass slide demonstrates the image enhancement obtained by our method over microscopy without the use of an anisotropic filter. In our current instrument, we estimate the limit of detection for organic volumetric mass within the object plane of ≈49 fg within ≈7 × 7 µm2 object surface area. Compared to a quartz crystal microbalance with dissipation instrumentation, where contemporary limits require a total load of ≈500 pg for detection, the instrumentation demonstrated here improves sensitivity to a total mass required for detection by 4 orders of magnitude. We detail the design and operation principles of the anisotropic contrast optical microscope, and we present further applications to the detection of nanoparticles, to novel approaches for imaging chromatography and to new contrast modalities for observations on living cells.

Comparison of the effect of knee synovectomy in haemophilic patients with 153Sm- and 90Y-labelled hydroxyapatite 1 year after.

To compare the use of 740 Mbq (20 mCi) of (153) Sm and 185 Mbq (5mCi) of (90) Y, both labelling hydroxyapatite (HA), for knee synovectomy in haemophilic patients, 1 year after the intervention. Thirty three men (36 knees) were studied, divided into two groups: 1 - treatment using 740 Mbq of (153) Sm-HA: 20 knees of 18 patients, with mean age of 21.4 ± 13.3 years (ranging from 7 to 56 years) and mean Pettersson score of 5.3; 2 - treatment using 185 Mbq of (90) Y-HA: 16 knees of 15 patients, with mean age of 26.3 ± 10.3 (ranging from 7 to 51 years) and mean Pettersson score of 6.3. The following criteria were adopted for the evaluation before and 1 year after synovectomy: reduction in haemarthrosis episodes and pain using a visual analogue scale, as well as improved joint mobility. The occurrence of adverse events in the treatment was also considered. The chi-square, Wilcoxon and Mann-Whitney tests were used with P ≤ 0.05 set as significant. The occurrence of haemarthrosis declined by 65.7% with the use of (153) Sm-HA and 82.6% for (90) Y-HA, with no statistical difference between the groups (P = 0.632); pain reduction was 42.5% in group 1 and 30.7% in group 2, once again with no statistical difference (P = 0.637). Improvement in joint mobility was not significant for both groups. Two cases of mild reactive synovitis were observed in group 1 and one in group 2, which cleared up without medical intervention. Although the beta energy from (90) Y is the gold standard for knee synovectomy, higher activities of (153) Sm may be used in places which have only production of this material.

Analysis of free drug fractions by ultrafast immunoaffinity chromatography.

A chromatographic method was developed for measuring the nonbound (or free) fraction of drugs by using millisecond-scale extractions on small immunoaffinity columns. The design of this system was developed by considering the dissociation rates of (R)- and (S)-warfarin from the binding protein human serum albumin (HSA) and by performing computer simulations of the immunoaffinity extraction of these drugs. The final system was tested by using it to measure the free fractions of (R)- or (S)-warfarin in samples with known concentrations of these agents and HSA. The free warfarin fraction was extracted in 180 ms by a 2.1-mm-i.d. sandwich microcolumn that contained a 1.1-mm layer of an anti-warfarin antibody support. The nonretained peaks from this immunoaffinity column were passed through a series internal surface reversed-phase columns and a fluorescence detector for the analysis of any protein-bound warfarin that remained in the sample. The experimental results were found to have good agreement with those predicted from the known equilibrium constants for the binding of (R)- and (S)-warfarin with HSA. This approach can be modified for other analytes by changing the types of antibodies that are used in the immunoaffinity column and by using an appropriate detector for the nonretained drug fraction.

Development of sandwich HPLC microcolumns for analyte adsorption on the millisecond time scale.

A new class of columns is reported that uses only microgram quantities of active support and that provides for the retention of biological compounds and other analytes on the millisecond time scale. This was accomplished by packing standard HPLC supports into layers as small as 60 microm in length and using only 90 microg of support material. This provided columns with effective residence times in the millisecond time range when routine HPLC flow rates and pressures were used. The retention of analytes by such columns was examined under both adsorption- and diffusion-limited conditions. The RPLC adsorption of hemoglobin (a system with diffusion-limited retention) was found to give 95% binding in as little as 4 ms. The adsorption of fluorescein by an anti-fluorescein antibody column (an adsorption-limited system) gave 95% retention in 100-120 ms. One application examined for these columns was their use in a chromatographic-based competitive binding immunoassay. This used bovine serum albumin (BSA) as the model analyte, and fluorescein-labeled BSA was used for detection. The resulting approach had a contact time of 180 ms between the sample and an anti-BSA immunoaffinity microcolumn and provided a signal within 5-25 s after sample injection. The columns developed in this work should also be useful in other situations that involve a small amount of a stationary phase or that require short column residence times.

Chromatographic and electrophoretic studies of protein binding to chiral solutes.

Protein interactions are important in determining the transport, metabolism and/or activity of many chiral compounds within the body. This review examines data that have been obtained on these interactions by various chromatographic and electrophoretic methods, especially those based on either high-performance liquid chromatography or capillary electrophoresis. Zonal elution, frontal analysis and vacancy methods are each considered, as are approaches that employ either soluble or immobilized proteins. There are a variety of different items that can be learned about a solute-protein system through these techniques. This includes information on the binding constants and number of binding sites for a solute-protein system, as well as the thermodynamic parameters, rate constants, interaction forces and binding site structure for the protein and solute. Numerous examples are provided throughout this review, as taken from the literature and from work performed within the author's laboratory.

Separation of near-infrared fluorescent conjugates of dATP and related compounds by capillary electrophoresis.

Capillary electrophoresis was examined as a means for the separation and quantitation of deoxyadenosine triphosphate (dATP) and other nucleotides that were labeled with the near-infrared fluorescent dye IRD700 or related tags. Under the final optimized conditions the labeled dATP was separated from several possible impurities, including the unconjugated forms of IRD700 and dATP, as well as dADP, dAMP and their corresponding IRD700 conjugates. The assay was performed under two sets of conditions. First, the sample was injected onto a 50 cm x 75 microm I.D. fused-silica capillary at 25 kV in the presence of a pH 9.5, 140 mM borate running buffer. The resulting peaks were monitored at both 254 and 680 nm, where the latter wavelength was used to identify any species that contained the IRD700 label. A second injection was then performed under the same conditions but with a fixed concentration of dTTP now being added to the running buffer; this resulted in the formation of a complex between the dTTP and any dATP, dADP or dAMP-containing components, which changed their rates of migration and allowed them to be differentiated from unconjugated IRD700 or dye contaminants. Only 6 nl of a 1:10 diluted sample were required per analysis. The limit of detection at this injection volume was approximately 1.0 microM (or 6 x 10(-15) mol for a 6-nl injection) for each monitored component. The linear range extended up to at least 80 microM. The analysis time was 20 min per injection and the day-to-day precision was +/-2-3%. The same method was also found to be useful in examining related conjugates, such as those based on the dye IRD40.

Antibody immobilization to high-performance liquid chromatography supports. Characterization of maximum loading capacity for intact immunoglobulin G and Fab fragments.

This study examined various factors that affect the maximum amount of intact immunoglobulin G (IgG) or Fab fragments that can be covalently immobilized to silica and other HPLC-grade supports for use in immunoaffinity chromatography or immunoextractions. Factors that were considered included the amount of surface area available for immobilization, the pore size of the support, the type of immobilization method and the nature of the support matrix. The main factor in determining the extent of immobilization was found to be the relationship between the support's surface area and the ability of the IgG or Fab fragments to reach this surface. Access to the support surface was a function of the size of the protein being immobilized and the support porosity, with maximum immobilization being obtained with supports having pore sizes of approximately 300 A for intact IgG and 100 A for Fab fragments. Some differences in the maximum level of immobilization were noted between different coupling methods. Supports like Poros and Emphaze gave similar results to those seen with HPLC-grade silica when a comparison was made between materials with comparable pore sizes. Many of the trends observed in this work for IgG and Fab fragments should apply to other proteins that are to be immobilized to HPLC supports.

High-performance affinity chromatography and immobilized serum albumin as probes for drug- and hormone-protein binding.

The binding of drugs and hormones to proteins within the blood is an important process in determining the transport, excretion, metabolism and activity of such agents. This paper discusses the combined use of immobilized serum albumin and high-performance affinity chromatography (HPAC) as tools for the study of such binding processes. The general approaches that are used in such work and are illustrated by several examples taken from previous work in the author's laboratory. The type of qualitative and quantitative information that can be obtained by such work is described, including the comparison of relative binding affinities, competitive displacement by other agents or the measurement of equilibrium and rate constants based on immobilized albumin columns. A comparison is also provided between the results that are obtained by these methods and those that are provided by solution-phase albumin. Some newer advances that are highlighted include use of HPAC to examine the binding of non-polar compounds to albumin, the effects of binding site heterogeneity on HPAC measurements and the use of chemically-modified albumin as a tool to examined the site-specific interactions of solutes with albumin.

Large-scale databases of proper names.

Few tools for research in proper names have been available--specifically, there is no large-scale corpus of proper names. Two corpora of proper names were constructed, one based on U.S. phone book listings, the other derived from a database of Usenet text. Name frequencies from both corpora were compared with human subjects' reaction times (RTs) to the proper names in a naming task. Regression analysis showed that the Usenet frequencies contributed to predictions of human RT, whereas phone book frequencies did not. In addition, semantic neighborhood density measures derived from the HAL corpus were compared with the subjects' RTs and found to be a better predictor of RT than was frequency in either corpus. These new corpora are freely available on line for download. Potentials for these corpora range from using the names as stimuli in experiments to using the corpus data in software applications.

Characterization of minor site probes for human serum albumin by high-performance affinity chromatography.

This study used high-performance affinity chromatography (HPAC) and immobilized human serum albumin (HSA) columns to examine the specificity and cross-reactivity of various compounds that have been proposed as markers for the minor binding sites of HSA. These agents included acetyldigitoxin and digitoxin as probes for the digitoxin site, phenol red as a probe for the bilirubin site, and cisor trans-clomiphene as markers for the tamoxifen site. None of these probes showed any significant binding at HSA's indole-benzodiazepine site. However, phenol red did bind at the warfarin-azapropazone site of HSA, and cis/trans-clomiphene gave positive allosteric effects caused by the binding of warfarin to HSA. Digitoxin and acetyldigitoxin were found to bind to a common, unique region on HSA; cis- and trans-clomiphene also appeared to interact at a unique site, although trans-clomiphene displayed additional direct competition with phenol red. From these results it was possible to develop a model that described the general relationship between these binding regions on HSA. This information should be useful in future studies that employ HPAC for characterizing the binding of HSA to other drugs or clinical agents.

Development of a theoretical model for chromatographic-based competitive binding immunoassays with simultaneous injection of sample and label.

This study examined the theory and behavior of an HPLC-based chromatographic competitive binding immunoassay with the simultaneous injection of sample and a labeled analyte analogue. Equations based on nonlinear chromatographic theory were derived to describe the calibration curve for this assay in a system with adsorption-limited kinetics and homogeneous binding sites. These equations related the assay response (B/Bo) to the column's binding capacity, the moles of injected analyte or labeled analogue, and the flow rate/adsorption kinetics of the system. There was good agreement between the predicted theoretical response and experimental data obtained for the binding of human serum albumin (HSA) to an immobilized anti-HSA antibody column. This theory was also successful in describing the changes that occurred in the calibration curve when the flow rate or amount of labeled analogue applied to the column was varied. A comparison was made between the results of this study and previous theoretical work that examined the behavior of a related, sequential injection competitive binding method. On the basis of the results reported in this work, several general guidelines were developed for the design and optimization of simultaneous injection methods for use in such areas as clinical testing, pharmaceutical analysis, and environmental monitoring.

Affinity chromatography: a review of clinical applications.

Affinity chromatography is a type of liquid chromatography that makes use of biological-like interactions for the separation and specific analysis of sample components. This review describes the basic principles of affinity chromatography and examines its use in the testing of clinical samples, with an emphasis on HPLC-based methods. Some traditional applications of this approach include the use of boronate, lectin, protein A or protein G, and immunoaffinity supports for the direct quantification of solutes. Newer techniques that use antibody-based columns for on- or off-line sample extraction are examined in detail, as are methods that use affinity chromatography in combination with other analytical methods, such as reversed-phase liquid chromatography, gas chromatography, and capillary electrophoresis. Indirect analyte detection methods are also described in which immunoaffinity chromatography is used to perform flow-based immunoassays. Other applications that are reviewed include affinity-based chiral separations and the use of affinity chromatography for the study of drug or hormone interactions with binding proteins. Some areas of possible future developments are then considered, such as tandem affinity methods and the use of synthetic dyes, immobilized metal ions, molecular imprints, or aptamers as affinity ligands for clinical analytes.