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Acne vulgaris, a prevalent dermatological disorder, frequently affects individuals' self-perception and general psychosocial functioning. The growing demand for home-based light therapy devices prompted a systematic review to assess the efficacy of visible light in acne treatment. Overall, 35 studies were included, representing 1185 cases of acne vulgaris (mean age: 23.7 years; sex: 63% female). A total of 69% of the included studies were level 2 evidence. Overall, 92% of patients achieved partial remission of their acne lesions using visible light therapy. Among the patients who experienced a partial remission of their acne, 46% experienced a reduction of 0% to 50% in their acne lesions, while 33% and 12% experienced reductions of 51% to 74% and 75% to 99%, respectively. Notably, blue light emerged as the predominant treatment modality in this context, used in around 64% of the cases. A total of 95% of the patients who were treated with blue light experienced a partial clearance of acne lesions; 44% experienced a reduction of 0% to 50% in their acne lesions, while 42% and 9% experienced reductions of 51% to 74% and 75% to 99%, respectively. Overall, the average total lesion count improved by 43% at week 4 compared to the baseline. The average number of treatment sessions was 22 (range 1-112 sessions). On average, treated patients responded within a period of 4 weeks. Commonly reported side effects included skin irritation and erythema. This review highlights the potential of visible light therapy in acne treatment. Head-to-head studies are needed to compare the efficacy of visible light compared to existing therapies for the treatment of acne., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Volumetric additive manufacturing techniques are a promising pathway to ultra-rapid light-based 3D fabrication. Their widespread adoption, however, demands significant improvement in print fidelity. Currently, volumetric additive manufacturing prints suffer from systematic undercuring of fine features, making it impossible to print objects containing a wide range of feature sizes, precluding effective adoption in many applications. Here, we uncover the reason for this limitation: light dose spread in the resin due to chemical diffusion and optical blurring, which becomes significant for features ⪅0.5 mm. We develop a model that quantitatively predicts the variation of print time with feature size and demonstrate a deconvolution method to correct for this error. This enables prints previously beyond the capabilities of volumetric additive manufacturing, such as a complex gyroid structure with variable thickness and a fine-toothed gear. These results position volumetric additive manufacturing as a mature 3D printing method, all but eliminating the gap to industry-standard print fidelity., (© 2023. Crown.)

The coronavirus disease (COVID-19) pandemic shows the rapid pace at which vaccine development can occur which highlights the need for more fast and efficient analytical methodologies to track and characterize candidate vaccines during manufacturing and purification processes. The candidate vaccine in this work comprises plant-derived Norovirus-like particles (NVLPs) which are structures that mimic the virus but lack any infectious genetic material. Presented here is a liquid chromatography-tandem mass spectrometry (LC-MS/MS) methodology for the quantification of viral protein VP1, the main component of the NVLPs in this study. It combines isotope dilution mass spectrometry (IDMS) with multiple reaction monitoring (MRM) to quantify targeted peptides in process intermediates. Multiple MRM transitions (precursor/product ion pairs) for VP1 peptides were tested with varying MS source conditions and collision energies. Final parameter selection for quantification includes three peptides with two MRM transitions each offering maximum detection sensitivity under optimized MS conditions. For quantification, a known concentration of the isotopically labeled version of the peptides to be quantified was added into working standard solutions to serve as an internal standard (IS); calibration curves were generated for concentration of native peptide vs. the peak area ratio of native-to-isotope labeled peptide. VP1 peptides in samples were quantified with labeled versions of the peptides added at the same level as that of the standards. Peptides were quantified with limit of detection (LOD) as low as 1.0 fmol μL -1 and limit of quantitation (LOQ) as low as 2.5 fmol μL -1 . NVLP preparations spiked with known quantities of either native peptides or drug substance (DS) comprising assembled NVLPs produced recoveries indicative of minimal matrix effects. Overall, we report a fast, specific, selective, and sensitive LC-MS/MS strategy to track NVLPs through the purification steps of the DS of a Norovirus candidate vaccine. To the best of our knowledge, this is the first application of an IDMS method to track virus-like particles (VLPs) produced in plants as well as measurements performed with VP1, a Norovirus capsid protein.

Tomographic volumetric additive manufacturing (VAM) is an optical 3D printing technique where an object is formed by photopolymerizing resin via tomographic projections. Currently, these projections are calculated using the Radon transform from computed tomography but it ignores two fundamental properties of real optical projection systems: finite etendue and non-telecentricity. In this work, we introduce 3D ray tracing as a new method of computing projections in tomographic VAM and demonstrate high fidelity printing in non-telecentric and higher etendue systems, leading to a 3x increase in vertical build volume than the standard Radon method. The method introduced here expands the possible tomographic VAM printing configurations, enabling faster, cheaper, and higher fidelity printing.

Introduction: The Centre de Médecine de Plongée du Québec (CMPQ) established a bilingual 24-hour dive emergency call line and diving medicine information service in 2004. The toll-free number (888-835-7121) works throughout Canada. Calls and emails (cmpq.cisssca@ssss.gouv.qc.ca) are answered by a CMPQ coordinator or on-call hyperbaric physicians and other consultants as needed. We reviewed 15 years of activity., Methods: Details of phone calls and email enquiries to the centre were reviewed individually and compiled into a database. Data were analysed to characterise contact volume and issues addressed. Contacts were categorised into five groups: information only (INF); medical opinion required (MOP); medical issue after the critical period of urgency had passed (PUR); current urgent but not immediate life-threatening issue (NLT); and immediate life- or health-threatening issue (ILT). Data presented as mean (standard deviation) or percentage., Results: A total of 3,232 contacts were made from May 2004 through December 2018: 19 (SD 8) per month [215 (70) per year]. Primary issues of concern were: emergency planning (20%); technical (not medical/physiology) questions (16%); otorhinolaryngological (12%); and decompression sickness-related (7%). Categorisation was 52% INF, 28% MOP, 13% PUR, 7% NLT, and 0.1% ILT, with 0.2% lacking sufficient detail to categorise. The nature of the diving activity of interest was determined in 67% of cases: 48% (n = 1,039) professional; 46% (n = 1,008) recreational; and 1% (n = 11) breath-hold., Conclusions: The call centre serves as a resource to the community, providing information on health and safety for diving in addition to being available to assist with emergent needs., (Copyright: This article is the copyright of the authors who grant Diving and Hyperbaric Medicine a non-exclusive licence to publish the article in electronic and other forms.)

Light-based additive manufacturing techniques enable a rapid transition from object design to production. In these approaches, a 3D object is typically built by successive polymerization of 2D layers in a photocurable resin. A recently demonstrated technique, however, uses tomographic dose patterning to establish a 3D light dose distribution within a cylindrical glass vial of photoresin. Lensing distortion from the cylindrical vial is currently mitigated by either an index matching bath around the print volume or a cylindrical lens. In this work, we show that these hardware approaches to distortion correction are unnecessary. Instead, we demonstrate how the lensing effect can be computationally corrected by resampling the parallel-beam radon transform into an aberrated geometry. We also demonstrate a more general application of our computational approach by correcting for non-telecentricity inherent in most optical projection systems. We expect that our results will underpin a more simple and flexible class of tomographic 3D printers where deviations from the assumed parallel-beam projection geometry are rectified computationally.

Purpose: Clinical ordinal rating scales of movements, e.g., the Expanded Disability Status Scale, have poor intra- and interrater reliability, are insensitive to subtle differences and result in coarse-grained ratings compared to relative comparative rating methods. We therefore established video-based setwise comparison as a fine-grained, reliable and efficient rating method of motor dysfunction using algorithmic support. Materials and methods: Eight neurologists rated a set of 40 multiple sclerosis patient videos of the Finger-to-Nose-Test using both the newly developed setwise comparison and the established pairwise comparison techniques, which result in a continuous rating scale. Reliability was assessed by the intra-class correlation coefficient. Construct validity was estimated as Pearson's correlation between the continuous scale and severity ratings according to the Neurostatus scale for upper-extremity tremor/dysmetria and the Nine-hole-peg-test. Comparing the time needed for ratings assessed efficiency. Results: Intra-class correlation coefficient was 0.83 for setwise and 0.7 for pairwise comparison. Correlation to the tremor/dysmetria score of the Neurostatus was 0.86 for both rating procedures and correlation to the Nine-hole-peg-test was 0.64 (setwise) and 0.66 (pairwise). The time needed to rate 40 videos was 22.9 ± 6.9 minutes (setwise) and 77.8 ± 14.5 minutes (pairwise). Conclusions: Setwise comparison is an efficient, valid and reliable method for fine-grained rating of motor dysfunction that can be applied to larger datasets. It is substantially more efficient than pairwise comparison.Implications for rehabilitationDisability rating is crucial in clinical neurorehabilitation and in clinical trials.Humans are naturally inconsistent in rating items on ordinal scales leading to poor intra- and interrater reliability, insensitivity to subtle differences and coarse-grained ratings.Video-based setwise comparison is a new rating method enabling fine-grained, reliable and efficient ratings of motor dysfunction using algorithmic support.

Purpose: Effective targeted therapies are lacking for refractory and relapsed T-cell acute lymphoblastic leukemia (T-ALL). Suppression of the NOTCH pathway using gamma-secretase inhibitors (GSI) is toxic and clinically not effective. The goal of this study was to identify alternative therapeutic strategies for T-ALL., Experimental Design: We performed a comprehensive analysis of our high-throughput drug screen across hundreds of human cell lines including 15 T-ALL models. We validated and further studied the top hit, navitoclax (ABT-263). We used multiple human T-ALL cell lines as well as primary patient samples, and performed both in vitro experiments and in vivo studies on patient-derived xenograft models., Results: We found that T-ALL are hypersensitive to navitoclax, an inhibitor of BCL2 family of antiapoptotic proteins. Importantly, GSI-resistant T-ALL are also susceptible to navitoclax. Sensitivity to navitoclax is due to low levels of MCL-1 in T-ALL. We identify an unsuspected regulation of mTORC1 by the NOTCH pathway, resulting in increased MCL-1 upon GSI treatment. Finally, we show that pharmacologic inhibition of mTORC1 lowers MCL-1 levels and further sensitizes cells to navitoclax in vitro and leads to tumor regressions in vivo ., Conclusions: Our results support the development of navitoclax, as single agent and in combination with mTOR inhibitors, as a new therapeutic strategy for T-ALL, including in the setting of GSI resistance., (©2018 American Association for Cancer Research.)

Background: A reduction in the rate of death and hospitalisations in patients with heart failure (HF) with reduced ejection fraction receiving sacubitril/valsartan compared to enalapril was demonstrated in the PARADIGM-HF study. However, tolerability when initiating and optimising sacubitril/valsartan treatment in real clinical practice is unknown., Methods: We performed a prospective cohort study of clinical and biochemical parameters of the first 100 patients receiving sacubitril/valsartan in a tertiary HF clinic. Patients had titration of the molecule guided by an algorithm developed by pharmacists and cardiologists in the clinic. The objective was to evaluate the proportion of patients reaching the maximal dosage, the time to reach maximal dosage, and the rate of adverse events, as well as the required modification of other HF therapy during the sacubitril/valsartan titration., Results: Forty-six per cent of patients reached the sacubitril/valsartan maximal dose of 97/103 mg (200 mg) twice daily and 73% received at least 49/51 mg (100 mg) twice daily. Mean titration time was 30 ± 9 days. Symptomatic hypotension, renal dysfunction (increase in creatinine level > 30%) and hyperkalaemia (potassium level > 5.5 mmol/l) occurred in nine, four and 2% of patients, respectively. Background HF pharmacological treatment remained stable during the sacubitril/valsartan titration but daily dosage of furosemide was reduced by 13% ( p = 0.0005)., Conclusions: This algorithm is a safe and easy-to-use tool in daily clinical practice for the introduction and titration of sacubitril/valsartan. Almost half of the patients reached the maximal dose, with a tolerability profile in line with the original study.

A new technique for measuring the spatial and temporal structure of the poloidal field is presented, whereby the magnetic field causes the polarization of light traveling through an optical fiber to rotate via the Faraday effect by an amount proportional to the strength of the field oriented along the fiber. In fiber optic pulsed polarimetry, changes in the polarization of the backscatter light from the fiber are detected, thereby permitting measurement of the field as a function of position along the fiber. In this proof-of-principle experiment, specially prepared single-mode fibers with weak fiber Bragg gratings were installed in the poloidal direction on the outside of the thermal blanket on DIII-D. Light at 532 nm from a mode-locked Nd:YAG laser was injected into the optical fibers. The laser repetition rate was 895 kHz with a pulse length of <10 ps, resulting in ∼1 μ s temporal resolution. A photodetector system measured the Stokes polarization components necessary to determine the amount of polarization rotation. For this experiment, bandwidth limitations of the detectors resulted in a spatial resolution of ≈2 cm. The measured temporal and spatial distributions of the poloidal field are consistent with inductive probe measurements and Elastodynamic Finite Integration Technique reconstructions of the spatial distribution. This demonstrates the ability of this technique to provide real-time detection of the temporal and spatial variations of the poloidal field. Besides revealing more detailed information about the plasma, this new diagnostic capability can also help in detecting instabilities in real time, thereby enabling enhanced machine protection.

Motor dysfunction, particularly ataxia, is one of the predominant clinical manifestations in patients with multiple sclerosis (MS). Assessment of motor dysfunction suffers from a high variability. We investigated whether the clinical rating of ataxia can be improved through the use of reference videos, covering the spectrum of severity degrees as defined in the Neurostatus-Expanded Disability Status Scale. Twenty-five neurologists participated. The variability of their assessments was significantly lower when reference videos were used (SD = 0.12; range = 0.40 vs SD = 0.26; range = 0.88 without reference videos; p  = 0.013). Reference videos reduced the variability of clinical assessments and may be useful tools to improve the precision and consistency in the clinical assessment of motor functions in MS.

Statistical shape models have become essential for medical image registration or segmentation and are used in many biomedical applications. These models are often based on Gaussian distributions learned from a training set. We propose in this paper a shape model which does not rely on the estimation of a Gaussian distribution, but on similarities computed with a kernel function. Our model takes advantage of the one-class support vector machine (OCSVM) to do so. In this context, we propose in this paper a method for reconstructing the spine of scoliotic patients using OCSVM regularization. Current state-of-the-art methods use conventional statistical shape models, and the reconstruction is commonly processed by minimizing a Mahalanobis distance. Nevertheless, when a shape differs significantly from the statistical model, the associated Mahalanobis distance often overstates the need for statistical regularization. We show that OCSVM regularization is more robust and is less sensitive to weak landmarks definition and is hardly influenced by the presence of outliers in the training data. The proposed OCSVM model applied to 3-D spine reconstruction was evaluated on real patient data, and results showed that our approach allows precise reconstruction.

The presence of a single centromere on each chromosome that signals formation of a mitotic kinetochore is central to accurate chromosome segregation. The histone H3 variant centromere protein-A (CENP-A) is critical for centromere identity and function; CENP-A chromatin acts as an epigenetic mark to direct both centromere and kinetochore assembly. Interpreting the centromere epigenetic mark ensures propagation of a single centromere per chromosome to maintain ploidy. Thus, understanding the nature of CENP-A chromatin is crucial for all cell divisions. However, there are ongoing debates over the fundamental composition of centromeric chromatin. Here we show that natively assembled human CENP-A nucleosomes are octameric throughout the cell cycle. Using total internal reflection fluorescence (TIRF)-coupled photobleaching-assisted copy-number counting of single nucleosomes obtained from cultured cells, we find that the majority of CENP-A nucleosomes contain CENP-A dimers. In addition, we detect the presence of H2B and H4 in these nucleosomes. Surprisingly, CENP-A associated with the chaperone HJURP can exist as either monomer or dimer, indicating possible assembly intermediates. Thus, our findings indicate that octameric CENP-A nucleosomes mark the centromeric region to ensure proper epigenetic inheritance and kinetochore assembly., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Intraoperative management of bleeding is a critical skill all surgeons must possess. It is, however, very challenging to create a safe and realistic learning environment for its acquisition. In this paper, we propose a simple and efficient approach to integrate blood circulation to computerized surgical simulation systems and allow for real-time processing of punctures, ruptures, and cauterization of blood vessels. Blood pressures and flows are calculated using a system of ordinary differential equations, which can be simulated very efficiently. The equation system itself is constructed using a graph of the vessels' connectivity extracted from magnetic resonance angiograms (MRA) and completed with virtual vessels deduced from the principle of minimum work. Real-time performances of the method are assessed and results are demonstrated on ten patients who underwent a MRA before removal of a brain tumor.

We present a groupwise US to CT registration algorithm for guiding percutaneous spinal interventions. In addition, we introduce a comprehensive validation scheme that accounts for changes in the curvature of the spine between preoperative and intraoperative imaging. In our registration methodology, each vertebra in CT is treated as a sub-volume and transformed individually. A biomechanical model is used to constrain the displacement of the vertebrae relative to one another. The sub-volumes are then reconstructed into a single volume. During each iteration of registration, an US image is simulated from the reconstructed CT volume and an intensity-based similarity metric is calculated with the real US image. Validation studies are performed on CT and US images from a sheep cadaver, five patient-based phantoms designed to preserve realistic curvatures of the spine and a sixth patient-based phantom where the curvature of the spine is changed between preoperative and intraoperative imaging. For datasets where the spine curve between two imaging modalities was artificially perturbed, the proposed methodology was able to register initial misalignments of up to 20mm with a success rate of 95%. For the phantom with a physical change in the curvature of the spine introduced between the US and CT datasets, the registration success rate was 98.5%. Finally, the registration success rate for the sheep cadaver with soft-tissue information was 87%. The results demonstrate that our algorithm allows for robust registration of US and CT datasets, regardless of a change in the patients pose between preoperative and intraoperative image acquisitions., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Traditional Chinese Medicine (TCM) has made great contributions to human history, especially in China, as has been recorded for thousands of years. The characteristics of TCM in both theory and practice make it different from Conventional Western Medicine (CWM). The characteristics of TCM include phenomenological, philosophical, and methodological aspects. This paper briefly discusses some historical turning points and innovations in TCM development in China, explores human body enigmas such as the heart, compares different aspects of TCM and CWM, and identifies the unique characteristics of TCM treatment, as compared to other medical systems.

Severe cases of spinal deformities such as scoliosis are usually treated by a surgery where instrumentation (hooks, screws and rods) is installed to the spine to correct deformities. Even if the purpose is to obtain a normal spine curve, the result is often straighter than normal. In this paper, we propose a fast statistical reconstruction algorithm based on a general model which can deal with such instrumented spines. To this end, we present the concept of multilevel statistical model where the data are decomposed into a within-group and a between-group component. The reconstruction procedure is formulated as a second-order cone program which can be solved very fast (few tenths of a second). Reconstruction errors were evaluated on real patient data and results showed that multilevel modeling allows better 3D reconstruction than classical models.

This paper proposes a novel method for fast 3D reconstructions of the scoliotic spine from two planar radiographs. The method uses a statistical model of the shape of the spine for computing the 3D reconstruction that best matches the user input (about 7 control points per radiograph). In addition, the spine was modelled as an articulated structure to take advantage of the dependencies between adjacent vertebrae in terms of location, orientation and shape. The accuracy of the method was assessed for a total of 30 patients with mild to severe scoliosis (Cobb angle [22°, 70°]) by comparison with a previous validated method. Reconstruction time was 90 s for mild patients, and 110 s for severe. Results show an accuracy of ∼0.5mm locating vertebrae, while orientation accuracy was up to 1.5° for all except axial rotation (3.3° on moderate and 4.4° on severe cases). Clinical indices presented no significant differences to the reference method (Wilcoxon test, p ≤ 0.05) on patients with moderate scoliosis. Significant differences were found for two of the five indices (p=0.03) on the severe cases, while errors remain within the inter-observer variability of the reference method. Comparison with state-of-the-art methods shows that the method proposed here generally achieves superior accuracy while requiring less reconstruction time, making it especially appealing for clinical routine use., (Copyright © 2011 IPEM. All rights reserved.)

Three-dimensional models of the spine are commonly used to diagnose, to treat, and to study spinal deformities. Creating these models is however time-consuming and, therefore, expensive. We propose in this paper a reconstruction method that finds the most likely 3D reconstruction given a maximal error bound on a limited set of landmark locations supplied by the user. This problem can be solved using second-order cone programming, leading to a globally convergent method that is considerably faster than currently available methods. A user can, with our current implementation, interactively modify the landmark locations and receive instantaneous feedback on the effect of those changes on the 3D reconstruction instead of blindly selecting landmarks. The proposed method was validated on a set of 53 patients who had adolescent idiopathic scoliosis using real and synthetic tests. Test results showed that the proposed method is considerably faster than currents methods (about forty times faster), is extremely flexible, and offers comparable accuracy.

Motivation: Spinal needle injections are technically demanding procedures. The use of ultrasound image guidance without prior CT and MR imagery promises to improve the efficacy and safety of these procedures in an affordable manner., Methodology: We propose to create a statistical shape model of the lumbar spine and warp this atlas to patient-specific ultrasound images during the needle placement procedure. From CT image volumes of 35 patients, statistical shape model of the L3 vertebra is built, including mean shape and main modes of variation. This shape model is registered to the ultrasound data by simultaneously optimizing the parameters of the model and its relative pose. Ground-truth data was established by printing 3D anatomical models of 3 patients using a rapid prototyping. CT and ultrasound data of these models were registered using fiducial markers., Results: Pairwise registration of the statistical shape model and 3D ultrasound images led to a mean target registration error of 3.4 mm, while 81% of all cases yielded clinically acceptable accuracy below the 3.5 mm threshold.

Registration of intraoperative ultrasound (US) with preoperative computed tomography (CT) data for interventional guidance is a subject of immense interest, particularly for percutaneous spinal injections. We propose a biomechanically constrained group-wise registration of US to CT images of the lumbar spine. Each vertebra in CT is treated as a sub-volume and transformed individually. The sub-volumes are then reconstructed into a single volume. The algorithm simulates an US image from the CT data at each iteration of the registration. This simulated US image is used to calculate an intensity based similarity metric with the real US image. A biomechanical model is used to constrain the displacement of the vertebrae relative to one another. Covariance Matrix Adaption - Evolution Strategy (CMA-ES) is utilized as the optimization strategy. Validation is performed on CT and US images from a phantom designed to preserve realistic curvatures of the spine. The technique is able to register initial misalignments of up to 20 mm with a success rate of 82%, and those of up to 10 mm with a success rate of 98.6%.

Three-dimensional models of the spine are extremely important to the assessment of spinal deformities. However, it could be difficult in practical situations to obtain enough accurate information to reconstruct complete 3-D models. This paper presents a set of methods to rebuild complete models either from partial 3-D models or from 2-D landmarks. The spine was modeled as an articulated object to take advantage of its natural anatomical variability. A statistical model of the vertebrae and spine shape was first derived. Then, complete models were computed by finding the articulated spine descriptions that were consistent with the observations while optimizing the prior probability given by the statistical model. The observations used were the absolute positions, orientations, and shapes of the vertebrae when a partial 3-D model was available. The reconstruction of 3-D spine models from 2-D landmarks identified on radiograph(s) was performed by minimizing the Mahalanobis distance and the landmarks reprojection error. The vertebrae estimated from partial models were within 2 mm of the measured values (which is comparable to the accuracy of currently used methods) if at least 25% of the vertebrae were available. Experiments also suggest that the reconstruction from posterior-anterior and lateral radiographs using the proposed method is more accurate than the conventional triangulation method.

This paper introduces a method to analyze the variability of the spine shape and of the spine shape deformations using articulated shape models. The spine shape was expressed as a vector of relative poses between local coordinate systems of neighboring vertebrae. Spine shape deformations were then modeled by a vector of rigid transformations that transforms one spine shape into another. Because rigid transformations do not naturally belong to a vector space, conventional mean and covariance could not be applied. The Fréchet mean and a generalized covariance were used instead. The spine shapes of a group of 295 scoliotic patients were quantitatively analyzed as well as the spine shape deformations associated with the Cotrel-Dubousset corrective surgery (33 patients), the Boston brace (39 patients), and the scoliosis progression without treatment (26 patients). The variability of intervertebral poses was found to be inhomogeneous (lumbar vertebrae were more variable than the thoracic ones) and anisotropic (with maximal rotational variability around the coronal axis and maximal translational variability along the axial direction). Finally, brace and surgery were found to have a significant effect on the Fréchet mean and on the generalized covariance in specific spine regions where treatments modified the spine shape.

Three-dimensional classification of scoliosis is important. However, analyzing large databases of 3D spine models is a difficult and time consuming task. To facilitate this task a method that automatically extracts the most important deformation modes from a set of 3D spine models is proposed. The 3D spine models are first converted into vertebrae relative positions and orientations. Then, a variability model composed of the Fréchet mean and of a generalized covariance is computed. A principal component analysis is applied to that variability model and the extracted components are converted into deformation modes. Those modes are visualized by animating a 3D spine model where the deformation strength varies (for a given mode). The proposed method was applied to a group of 307 scoliotic patients and meaningful deformation modes were successfully extracted. For example, patients' growth, double curves, simple thoracic curves and lumbar lordosis were extracted in the first four deformation modes. Moreover, the obtained deformation modes are not disconnected from conventional surgical classifications since a logistic regression confirmed that there is a statistically significant relation between King's classification and the first four principal deformation modes. The proposed method successfully extracted important deformation modes from a set of 3D spine models and can be used to refine arbitrary classes (King's or Lenke's classes, for instance), thus helping the design of new clinically relevant 3D classifications.

Bracing is a widely used treatment of scoliosis, but there is still no consensus about its actual effect. Previous studies were based on global descriptors of the spine shape (Cobb angle, plane of maximal deformity, etc.). We present a new method to analyze braces effects at a finer scale and to find which vertebral levels are significantly affected by this treatment. The proposed method compares a group of patients treated with a brace and a control group. The 3D spine geometry of the patients from the two groups was digitized on two separate occasions: with and without brace (first group) or two times without brace (control group). The modifications of the vertebrae relative poses (combination of relative translation and rotation between consecutive vertebrae) were then extracted from 3D reconstructions. Centrality and dispersion measures of the relative poses modifications were computed using a method that take into account the non-linearity of the rotation matrix. Then, finally, multivariate hypothesis tests were used to compare the centrality and dispersion of the two groups. The method was applied to 28 untreated scoliotic patients and 41 patients treated with a Boston brace. Significant differences (p<0.01) between the centrality and dispersion measures of the relative poses modifications were respectively found from T1 to T6 and from T8 to L1. Those significant differences concords with the back flattening effect and the spatially limited correction found in other studies; however the proposed method offers a more specific evaluation of the localization of those effects.

The maintenance of tolerance is likely to rely on the ability of a T cell to polarize surface molecules providing "help" to only specific APCs. The formation of a mature immunological synapse leads to concentration of the TCR at the APC interface. In this study, we show that the CD40-CD154 receptor-ligand pair is also highly concentrated into a central region of the synapse on mouse lymphocytes only after the formation of the TCR/CD3 c-SMAC. Concentration of this ligand was strictly dependent on TCR recognition, the binding of ICAM-1 to T cell integrins and the presence of an intact cytoskeleton in the T cells. This may provide a novel explanation for the specificity of T cell help directing the help signal to the site of Ag receptor signal. It may also serve as a site for these molecular aggregates to coassociate and/or internalize alongside other signaling receptors., (Copyright 2004 The American Association of Immunologists, Inc.)

This review article aims at summarizing the data regarding fetal and neonatal hydronephrosis, at correlating controversial data with the differences in the practice of obstetrical sonography from one country to another, and finally, at presenting our own criteria for fetal renal collecting system dilatation along with our own guidelines of postnatal investigation.

The interaction of T cells with antigen-presenting cells results in the formation of a contact face, termed the immunological synapse. The prototypical dynamics of this process are well established and involve cessation of crawling, a highly fluid 'immature' synapse phase during which signaling is initiated, and ultimately the formation of a 'mature' synapse characterized by centralized and peripheral supramolecular activating complexes. Ongoing research is directed towards defining how these supramolecular assemblies are formed and, more importantly, to what end. With regard to the former, progress has been made in defining the order in which various molecules are recruited to signaling centers in prototypical settings. With regard to the latter, however, the issue now appears more complex, as both developmental changes in T cells and variations in the environment appear to modulate features of mature synapse development. Although many details of the immunological synapse have been established, emerging evidence suggests a great variability in the ultimate form of these contacts and their effects on T-cell functions.

Background: Hepatitis C virus (HCV) is a leading cause of chronic liver disease, yet little is known about the intrahepatic immune response in end-stage patients. Chemokines and their receptors are important regulators of immunity, particularly in the migration and localization of circulating leukocytes within peripheral tissues., Aims: This report provides a comprehensive comparison of the chemokine receptor and activation phenotype of the major leukocyte subsets present in end-stage HCV-infected and non-HCV infected livers., Methods: Lymphocytes were purified from homogenized explant liver tissue and analyzed by flow cytometry., Results: NK cells are the predominant cell type, followed by T cells, B cells and NK-T cells, independent of HCV status. T cells displayed a memory phenotype and low levels of activation markers. CCR5, CXCR3 and CXCR6 were expressed on a large fraction of activated cells, while moderate to low expression of CCR2, CCR6 and CX(3)CR1 was observed. Several other tissue-specific and inflammatory chemokine receptors were absent from infiltrating lymphocytes., Conclusions: These results identify the chemokine receptors present on infiltrating lymphocytes during end-stage liver disease and suggest that such infiltration is predominantly controlled by non-tissue-specific inflammatory chemokines, a situation that may be distinct from liver homing pathways under normal conditions.

Differential expression of adhesion molecules and chemokine receptors has been useful for identification of peripheral blood memory lymphocyte subsets with distinct tissue and microenvironmental tropisms. Expression of CCR4 by circulating memory CD4(+) lymphocytes is associated with cutaneous and other systemic populations while expression of CCR9 is associated with a small intestine-homing subset. CCR5 and CXCR3 are also expressed by discrete memory CD4(+) populations in blood, as well as by tissue-infiltrating lymphocytes from a number of sites. To characterize the similarities and differences among tissue-infiltrating lymphocytes, and to shed light on the specialization of lymphocyte subsets that mediate inflammation and immune surveillance in particular tissues, we have examined the expression of CCR4, CXCR3, and CCR5 on CD4(+) lymphocytes directly isolated from a wide variety of normal and inflamed tissues. Extra-lymphoid tissues contained only memory lymphocytes, many of which were activated (CD69(+)). As predicted by classical studies, skin lymphocytes were enriched in CLA expression whereas intestinal lymphocytes were enriched in alpha(4)beta(7) expression. CCR4 was expressed at high levels by skin-infiltrating lymphocytes, at lower levels by lung and synovial fluid lymphocytes, but never by intestinal lymphocytes. Only the high CCR4 levels characteristic of skin lymphocytes were associated with robust chemotactic and adhesive responses to TARC, consistent with a selective role for CCR4 in skin lymphocyte homing. In contrast, CXCR3 and CCR5 were present on the majority of lymphocytes from each non-lymphoid tissue examined, suggesting that these receptors are unlikely to determine tissue specificity, but rather, may play a wider role in tissue inflammation.

Children with single ventricle anatomy are among the most complicated and challenging patients encountered in pediatric cardiology. Current management involves staged surgical procedures, beginning with neonatal palliation and followed by a bidirectional cavopulmonary anastomosis in infancy and culminating in the Fontan procedure. The Fontan procedure, despite separating the circulation, remains a palliative procedure with many long-term concerns. This report discusses the staged surgical management of patients with single ventricle anatomy and the nursing issues relevant to each stage., (Copyright 2001 by W.B. Saunders Company)

Prior studies seeking evidence of viral replication in peripheral lymphocytes of hepatitis C virus (HCV)-infected patients have yielded conflicting results. This study sought to quantitatively determine whether a permissive HCV cell interaction could be detected in leukocytes from infected patients. Peripheral leukocytes from chronically infected patients were purified and were tested for HCV RNA. The results show that virus load is highest in B cells. Other subsets of peripheral leukocytes consistently had very low levels of viral RNA or were negative. Negative-strand HCV was found only in hepatocytes. To determine whether HCV replication could be induced by activation, B cells from HCV-infected patients were stimulated in vitro. No HCV replicating in peripheral leukocytes was detected by a highly sensitive assay. If HCV replication occurs in the leukocyte subsets analyzed here, it is at extremely low levels or occurs under alternate physiological conditions.

Purpose: To explore patients' perceptions of anesthetic care as measured by a patient-centered care survey. Specifically, the survey examined patient views of multiple diverse dimensions of care that are not typically fully addressed among patients receiving anesthesia services, namely opinions on Information Provision, Involvement in Care, Respect Shown, Physical Comfort, and Emotional Support., Method: A total of 268 patients responded to a patient-centered care survey, a self-report factor analytically derived instrument designed to measure the aforementioned dimensions of care., Results: Analyses revealed that the highest ratings of care were given to Physical Comfort and Respect. Ratings of Information Provision, Involvement, and Emotional Support were significantly lower. Ratings did not differ as a function of site of service, inpatient vs day surgery, surgical service, type of anesthetic, or anesthesiologist., Discussion: The findings generated from the study are of value in obtaining a broader understanding of anesthesia services from the patient's perspective, and also in directing quality improvement initiatives. Other departments of anesthesiology interested in quality improvement initiatives may similarly benefit from measurement of patient-centered care.

Chemokine receptor expression is finely controlled during T-cell development. We show that newly identified chemokine receptor Bonzo/CXCR6 is expressed by subsets of Th1 or T-cytotoxic 1 (Tc1) cells, but not by Th2 or Tc2 cells, establishing Bonzo as a differential marker of polarized type 1 T cells in vitro and in vivo. Priming of naive T cells by dendritic cells induces expression of Bonzo on T cells. IL-12 enhances this dendritic cell-dependent upregulation, while IL-4 inhibits it. In blood, 35-56% of Bonzo+ CD4 T cells are Th1 cells, and 60-65% of Bonzo+ CD8 T cells are Tc1 cells, while few Bonzo+ cells are type 2 T cells. Almost all Bonzo+ Tc1 cells contain preformed granzyme A and display cytotoxic effector phenotype. Most Bonzo+ T cells lack L-selectin and/or CCR7, homing receptors for lymphoid tissues. Instead, Bonzo+ T cells are dramatically enriched among T cells in tissue sites of inflammation, such as rheumatoid joints and inflamed livers. Bonzo may be important in trafficking of effector T cells that mediate type 1 inflammation, making it a potential target for therapeutic modulation of inflammatory diseases.

CCR7, along with L-selectin and LFA-1, mediates homing of T cells to secondary lymphoid organs via high endothelial venules (HEV). CCR7 has also been implicated in microenvironmental positioning of lymphocytes within secondary lymphoid organs and in return of lymphocytes and dendritic cells to the lymph after passage through nonlymphoid tissues. We have generated mAbs to human CCR7, whose specificities correlate with functional migration of lymphocyte subsets to known CCR7 ligands. We find that CCR7 is expressed on the vast majority of peripheral blood T cells, including most cells that express adhesion molecules (cutaneous lymphocyte Ag alpha(4)beta(7) integrin) required for homing to nonlymphoid tissues. A subset of CD27(neg) memory CD4 T cells from human peripheral blood is greatly enriched in the CCR7(neg) population, as well as L-selectin(neg) cells, suggesting that these cells are incapable of homing to secondary lymphoid organs. Accordingly, CD27(neg) T cells are rare within tonsil, a representative secondary lymphoid organ. All resting T cells within secondary lymphoid organs express high levels of CCR7, but many activated cells lack CCR7. CCR7 loss in activated CD4 cells accompanies CXC chemokine receptor (CXCR)5 gain, suggesting that the reciprocal expression of these two receptors may contribute to differential positioning of resting vs activated cells within the organ. Lymphocytes isolated from nonlymphoid tissues (such as skin, lung, or intestine) contain many CD27(neg) cells lacking CCR7. The ratio of CD27(neg)/CCR7(neg) cells to CD27(pos)/CCR7(pos) cells varies from tissue to tissue, and may correlate with the number of cells actively engaged in Ag recognition within a given tissue.

The functional status of virus-specific CD8+ T cells is important for the outcome and the immunopathogenesis of viral infections. We have developed an assay for the direct functional analysis of antigen-specific CD8+ T cells, which does not require prolonged in vitro cultivation and amplification of T cells. Whole blood samples were incubated with peptide antigens for <5 h, followed by staining with peptide-MHC tetramers to identify epitope-specific T cells. The cells were also stained for the activation marker CD69 or for the production of cytokines such as interferon-gamma (IFNgamma) or tumor necrosis factor-alpha (TNFalpha). With the combined staining with tetramer and antibodies to CD69 or cytokines the number of antigen-specific CD8+ T cells as well as the functional response of each individual cell to the cognate antigen can be determined in a single experiment. Virus-specific CD8+ T cells that are nonfunctional, as well as those that are functional under the same stimulating conditions can be simultaneously detected with this assay, which is not possible by using other T-cell functional assays including cytotoxicity assay, intracellular cytokine staining, and enzyme-linked immunospot (ELISPOT) assay.

The immune system has evolved specialized cellular and molecular mechanisms for targeting and regulating immune responses at epithelial surfaces. Here we show that small intestinal intraepithelial lymphocytes and lamina propria lymphocytes migrate to thymus-expressed chemokine (TECK). This attraction is mediated by CC chemokine receptor (CCR)9, a chemoattractant receptor expressed at high levels by essentially all CD4(+) and CD8(+) T lymphocytes in the small intestine. Only a small subset of lymphocytes in the colon are CCR9(+), and lymphocytes from other tissues including tonsils, lung, inflamed liver, normal or inflamed skin, inflamed synovium and synovial fluid, breast milk, and seminal fluid are universally CCR9(-). TECK expression is also restricted to the small intestine: immunohistochemistry reveals that intense anti-TECK reactivity characterizes crypt epithelium in the jejunum and ileum, but not in other epithelia of the digestive tract (including stomach and colon), skin, lung, or salivary gland. These results imply a restricted role for lymphocyte CCR9 and its ligand TECK in the small intestine, and provide the first evidence for distinctive mechanisms of lymphocyte recruitment that may permit functional specialization of immune responses in different segments of the gastrointestinal tract. Selective expression of chemokines by differentiated epithelium may represent an important mechanism for targeting and specialization of immune responses.

A laboratory study on the sublethal effects of cadmium (Cd) on the net-spinning process of the larvae of Hydropsyche slossonae was conducted in order to assess the potential of net anomalies as an indicator of chronic exposure to Cd. Two major anomalies with different frequency levels were identified after chronic exposure to 0.37, 1.2, 11.6, 21.4 and 43.3 microg l(-1) of Cd. The first was a distortion of the midline meshes where the diamond-shape structure is disrupted and the meshes are separated by extra strands (called 'midline' anomaly). The second aberration consisted of a distortion of the rectilinear structure of net opening by strands being fused or added over the meshes (called 'crossover' anomaly). The midline distortion may be linked to a physiological stress caused by Cd, which can affect the control of the net-spinning process. It was not possible to relate the crossover aberrations to a specific toxic action of Cd, but data indicated that both anomalies are independent from each other and that two modes of action could be implicated. Protein analyses of capture nets have revealed silk polypeptide modifications at the highest Cd concentration tested, indicating a possible effect of Cd interaction with silk proteins. However, neither a gradient-concentration nor a time-dependent response could be established with both aberration frequencies. Silk protein modifications would rather play a secondary role in the appearance of both net anomalies, and mostly at a high concentration level. Finally, the toxicity curves (EC(50)) show that the sensitivity threshold for both types of aberration ranged from 1 to 5 microg l(-1) which is highly sensitive compared with other sublethal effects of Cd on other macroinvertebrate species. Hence, the use of capture-net anomalies of hydropsychid larvae would represent a valuable indicator of sublethal toxicity induced by Cd and possibly by other metals in running waters.

In order to assess the potential of hydropsychid capture net anomalies as a bioindicator of chronic toxicity in streams and rivers, the effects of 2,4-dichlorophenol (2,4-DCP) exposure on the net-spinning behavior of Hydropsyche slossonae were examined for anomalies after 0, 5, 10, 15, and 20 exposure days to gradient concentration of 2,4-dichlorophenol. The net-spinning behavior was significantly affected when larvae were exposed to 1.0, 10, 25, and 50 microg small middle dotL(-1), as expressed by the occurrence of two distinct abnormalities. The first one was a distortion of the midline meshes, where the normal diamond-shape structure is disrupted and the meshes are separated by extra strands (called "midline anomaly). The second aberration observed was called "chaotic net, where the nets are highly irregular without any real structure or well-defined areas. A good correlation was found between the chaotic net frequencies and the reduction of ATP concentrations in the larvae, indicating possible uncoupling effects of 2,4-DCP on the oxidative phosphorylation process. Toxicity curves demonstrate that the sensitivity threshold of chaotic net frequencies ranged from 3.5 to 7 microg small middle dotL(-1), which is highly sensitive compared with other sublethal effects of 2,4-DCP on other aquatic species., (Copyright 2000 Academic Press.)

Background and Objectives: Because C. trachomatis serovars correlate with the clinical manifestations of cervical infection, we undertook this study to determine whether clinical, behavioral, and laboratory findings correlate with C. trachomatis serovars isolated from rectal infections., Goal of This Study: To correlate C. trachomatis serovar with signs and symptoms of rectal infection., Study Design: A cross-sectional study of 454 men with rectal C. trachomatis infection attending an urban sexually transmitted disease (STD) clinic was undertaken. Isolates were thawed, passaged to high titer, and typed using a panel of monoclonal antibodies. Compared to men infected with B complex isolates (164), men with C complex isolates (55) were less likely to report symptoms (OR: 0.4; 95% CI: 0.1-0.8), or to have erythema, bleeding, or mucopus (OR: 0.3; 95% CI: 0.1-0.8). Among men with inclusion counts of more than 100, those infected with FG group versus B complex isolates were more likely to present with mucopus (OR: 10.5; 95% CI: 1.2-95.5), more than 15 polymorphonuclear leukocytes (OR: 19.2; 95% CI: 1.7-219.8), and proctitis (OR: 4.2; 95% CI: 1.1-16.7)., Conclusion: Signs and symptoms of rectal infection correlate with the serovar of C. trachomatis isolates.

It is believed that the hepatitis C virus (HCV)-specific CD8(+) cytotoxic T lymphocytes (CTLs) play a role in the development of liver cell injury and in the clearance of the virus. To develop a direct binding assay for HCV-specific CTLs, we generated two peptide-MHC tetramers by using the recombinant HLA A2.1 molecule and A2-restricted T cell epitopes of the HCV NS3 protein. With these reagents we are able to detect specific CD8(+) cells in the blood of 15 of 20 HLA-A2(+), HCV-infected patients, at a frequency ranging from 0.01% to 1.2% of peripheral CD8(+) T cells. Phenotypic analysis of these specific cells indicated that there is a significant variation in the expression of the CD45 isoforms and CD27 in different patients. A 6-hour incubation of one patient's blood with NS3 peptides resulted in the activation of the epitope-specific CD8(+) cells, as indicated by their expression of CD69 and IFN-gamma. We also detected NS3-specific CD8(+) T cells in the intrahepatic lymphocyte population isolated from liver biopsies of two HCV-infected patients. The frequency of these specific CD8(+) cells in the liver was 1-2%, at least 30-fold higher than in the peripheral blood. All of the intrahepatic NS3-specific CD8(+) T cells were CD69(+), suggesting that they were activated CTLs. Direct quantitation and characterization of HCV-specific CTLs should extend our understanding of the immunopathogenesis and the mechanism of clearance or persistence of HCV.

Purpose: To determine if abnormal liver architecture at ultrasonography (US) is related to abnormal function in children with cystic fibrosis (CF)., Materials and Methods: For 1 year, all 195 children (112 boys, 83 girls; mean age, 8.5 years) attending a CF clinic underwent abdominal US and a standard set of liver function tests. Aspartate aminotransferase, alanine aminotransferase, and gamma-glutamyltransferase levels were analyzed. US signs were interpreted as follows: hypoechogenicity with prominent portal tracks as edema, hyperechogenicity as steatosis, and increased attenuation and nodules within or at the edge of the liver as cirrhosis. Signs of portal hypertension also were sought. US signs were compared with liver function test results., Results: Liver sonograms were abnormal in 38 children (19%); of these, 24 (63%) had abnormal test results. The 157 children with normal liver architecture had a much lower prevalence of biochemical abnormality (33 patients [21%]; P < or = .001). All eight children with signs of portal hypertension had abnormal test results. Fourteen (82%) of 17 children with signs of cirrhosis had abnormal liver function. Eight (57%) of 14 patients with signs of steatosis had abnormal function. Diffuse hypoechogenicity of the liver with prominent portal tracks in 16 patients was associated with abnormal function in only five patients., Conclusion: The relation between abnormal liver architecture at US and results of three liver function tests in children with CF was significant. The most specific US abnormalities related to abnormal function are signs suggestive of portal hypertension and cirrhosis.

This study examines worry themes among 87 anxiety disorder patients divided into three groups: (a) 24 primary generalized anxiety disorder (GAD) patients, (b) 25 secondary GAD patients, and (c) 38 other anxiety disorder patients (primarily obsessive-compulsive disorder, social phobia and panic disorder with agoraphobia). Structured and free-recall measures were used to measure five worry themes: relationships, work, finances, physical threat, and the future. Both types of measures revealed that GAD patients worry more about the future than non-GAD patients. Further, post hoc analyses testing for linear relationships indicated that primary GAD patients worry more about the future than secondary GAD patients who in turn worry more about the future than other anxiety disorder patients. The results suggest that although worry about immediate problems may not differentiate GAD patients from other anxiety disorder patients, high levels of worry about future events may be a distinguishing feature of GAD.

This study evaluated the efficacy of a cognitive-behavioral treatment package for pathological gambling. Twenty-nine men who met criteria for pathological gambling in accordance with the Diagnostic and Statistical Manual of Mental Disorders (3rd ed., revised; DSM-III-R; American Psychiatric Association, 1987) were randomly assigned to treatment or wait-list control. The treatment included 4 components: (a) cognitive correction of erroneous perceptions about gambling, (b) problem-solving training, (c) social skills training, and (d) relapse prevention. The dependent variables were the South Oaks Gambling Screen, perception of control, frequency of gambling, perceived self-efficacy, desire to gamble, and number of DSM-III-R criteria met by participants. Posttest results indicated highly significant changes in the treatment group on all outcome measures, and analysis of data from 6- and 12-month follow-ups revealed maintenance of therapeutic gains. Recommendations for clinical interventions are discussed and focus on the cognitive correction of erroneous perceptions of gambling.

An HPLC method for the quantification of ketoprofen enantiomers in human plasma is described. Following extraction with a disposable C18 solid-phase extraction column, separation of ketoprofen enantiomers and I.S. (3,4-dimethoxy benzoic acid) was achieved using a chiral column [Chirex 3005; (R)-1-naphthylglycine 3,5-dinitrobenzoic acid] with the mobile phase, 0.02 M ammonium acetate in methanol, set at a flow-rate of 1.2 ml/min. Baseline separation of ketoprofen enantiomers and I.S., free from interferences, was achieved in less than 20 min. The calibration curves (n = 14) were linear over the concentration range of 0.16 to 5.00 micrograms/ml per enantiomer [mean r2 of 0.999 for both enantiomers, root mean square error were 0.015 for R(-) and 0.013 for S(+)]. The inter-day coefficient of variation for duplicate analysis of spiked samples was less than 7% and the accuracy was more than 93% over the over the concentration range of 0.2 to 4.0 micrograms/ml for individual enantiomer using 1 ml of plasma sample. This method has been applied to a pharmacokinetic study from healthy human volunteers following the administration of a ketoprofen extended release product (200 mg). This method is simple, fast and should find wide application in monitoring pharmacokinetic studies of ketoprofen.

Cardiac arrhythmias are being depressed with increased frequency in the pediatric population. Causes of pediatric arrhythmias in the general population include severe metabolic or electrolyte disturbances, drug toxicity, and chest trauma. Repairs of complex congenital heart disease have frequently left this population with persistent or recurrent postoperative arrhythmias. The diagnosis, evaluation, and management of pediatric arrhythmias requires nurses to be skilled in hemodynamic assessment and arrhythmia detection. The registered nurse's grasp of developmental issues and family education is vital in providing quality care to families dealing with these diagnoses.

Laboratory bioassays evaluated the pathogenicity of the entomopathogenic fungus Tolypocladium cylindrosporum against Aedes triseriatus. All larval instars were found to be susceptible at temperatures from 18 to 25 degrees C. Blastoconidia were more virulent than conidia. Mortality was proportional to exposure time in assays using blastoconidia. Blastoconidia and exposure time appear to be a more adequate method for bioassay of T. cylindrosporum virulence than the standard procedure of using conidia and continuous exposure. Tolypocladium cylindrosporum was also active against Simulium vittatum black fly larvae, but the mortality recorded was much lower than with mosquito larvae.

The efficacy of a behavioral treatment for pathological gamblers, including cognitive interventions, problem solving and relapse prevention is examined. Three pathological gamblers meeting DSM-III-R criteria were studied in an experimental multiple baseline design. By the end of treatment the subjects ceased all gambling behaviors, increased their perception of self-control of gambling, and evaluated their problems as less severe. Therapeutic gains were maintained at 6- and 9-month follow-ups. The importance of problem solving and the modification of erroneous perceptions in treatment programs for pathological gambling is discussed.

Pathological gambling creates enormous problems for the afflicted individuals, their families, employers, and society, and has numerous disastrous financial consequences. The present study evaluates the financial burdens of pathological gambling by questioning pathological gamblers in treatment in Gamblers Anonymous (n=60; 56 males, 4 females; mean age = 40 years old) about personal debts, loss of productivity at work, illegal activities, medical costs and the presence of other dependencies. Results show that important debts, loss of productivity at work and legal problems are associated with pathological gambling. Discussion is formulated in terms of the social cost of adopting a liberal attitude toward the legalization of various gambling activities.

Infections by insect-pathogenic fungi of the order Entomophthorales in two adult black fly populations were studied in the Réserve Faunique du Saint-Maurice (Quebec). Entomophaga near limoniae infected Simulium verecundum/rostratum in June whereas Erynia curvispora predominantly parasitized Simulium decorum from the 2nd week of July to September and Erynia conica attacked the Simulium venustum complex, Simulium verecundum/rostratum, and the Simulium vittatum complex from May to September. The fungi did not infect the adult stage of Prosimulium species. Possible evidence of host specificity for Erynia conica is discussed.