Community introduction of practice parameters for autistic spectrum disorders: Advancing early recognition.

OBJECTIVES: Within a strong interdisciplinary framework, improvement in the quality of care for children with autistic spectrum disorders through a 2 year implementation program of Practice Parameters, aimed principally at improving early detection and intervention. METHOD: We developed Practice Parameters (PPs) for Pervasive Developmental Disorders and circulated the PPs to all child and adolescent psychiatrists practicing in the region. RESULTS: PP development and parallel information strategies resulted in a significant decrease of 1.5 years in the mean-age-at-diagnosis. However, further analysis indicated that improvement was only transient. CONCLUSION: Despite the encouraging improvement in mean-age-at-diagnosis 2 years after PP implementation, other indicators showed a failure to maintain the improvements. A systematic screening program would be the most reliable method to reinforce the PPs.

A novel method for automated classification of epileptiform activity in the human electroencephalogram-based on independent component analysis.

Diagnosis of several neurological disorders is based on the detection of typical pathological patterns in the electroencephalogram (EEG). This is a time-consuming task requiring significant training and experience. Automatic detection of these EEG patterns would greatly assist in quantitative analysis and interpretation. We present a method, which allows automatic detection of epileptiform events and discrimination of them from eye blinks, and is based on features derived using a novel application of independent component analysis. The algorithm was trained and cross validated using seven EEGs with epileptiform activity. For epileptiform events with compensation for eyeblinks, the sensitivity was 65 +/- 22% at a specificity of 86 +/- 7% (mean +/- SD). With feature extraction by PCA or classification of raw data, specificity reduced to 76 and 74%, respectively, for the same sensitivity. On exactly the same data, the commercially available software Reveal had a maximum sensitivity of 30% and concurrent specificity of 77%. Our algorithm performed well at detecting epileptiform events in this preliminary test and offers a flexible tool that is intended to be generalized to the simultaneous classification of many waveforms in the EEG.

Compact portable biosensor for arsenic detection in aqueous samples with Escherichia coli bioreporter cells.

We present a compact portable biosensor to measure arsenic As(III) concentrations in water using Escherichia coli bioreporter cells. Escherichia coli expresses green fluorescent protein in a linearly dependent manner as a function of the arsenic concentration (between 0 and 100 μg/L). The device accommodates a small polydimethylsiloxane microfluidic chip that holds the agarose-encapsulated bacteria, and a complete optical illumination/collection/detection system for automated quantitative fluorescence measurements. The device is capable of sampling water autonomously, controlling the whole measurement, storing and transmitting data over GSM networks. We demonstrate highly reproducible measurements of arsenic in drinking water at 10 and 50 μg/L within 100 and 80 min, respectively.

Early detection of idiopathic Parkinson's disease based on magnetic resonance imaging

The diagnosis of idiopathic Parkinson's disease (IPD) is entirely clinical. The fact that neuronal damage begins 5-10 years before occurrence of sub-clinical signs, underlines the importance of preclinical diagnosis. A new approach for in-vivo pathophysiological assessment of IPD-related neurodegeneration was implemented based on recently developed neuroimaging methods. It is based on non- invasive magnetic resonance data sensitive to brain tissue property changes that precede macroscopic atrophy in the early stages of IPD. This research aims to determine the brain tissue property changes induced by neurodegeneration that can be linked to clinical phenotypes which will allow us to create a predictive model for early diagnosis in IPD. We hypothesized that the degree of disease progression in IPD patients will have a differential and specific impact on brain tissue properties used to create a predictive model of motor and non-motor impairment in IPD. We studied the potential of in-vivo quantitative imaging sensitive to neurodegeneration- related brain tissue characteristics to detect changes in patients with IPD. We carried out methodological work within the well established SPM8 framework to estimate the sensitivity of tissue probability maps for automated tissue classification for detection of early IPD. We performed whole-brain multi parameter mapping at high resolution followed by voxel-based morphometric (VBM) analysis and voxel-based quantification (VBQ) comparing healthy subjects to IPD patients. We found a trend demonstrating non-significant tissue property changes in the olfactory bulb area using the MT and R1 parameter with p<0.001. Comparing to the IPD patients, the healthy group presented a bilateral higher MT and R1 intensity in this specific functional region. These results did not correlate with age, severity or duration of disease. We failed to demonstrate any changes with the R2* parameter. We interpreted our findings as demyelination of the olfactory tract, which is clinically represented as anosmia. However, the lack of correlation with duration or severity complicates its implications in the creation of a predictive model of impairment in IPD.

Endoleak and in-stent thrombus detection with CT angiography in a thoracic aortic aneurysm phantom at different tube energies using filtered back projection and iterative algorithms.

PURPOSE: To determine the lower limit of dose reduction with hybrid and fully iterative reconstruction algorithms in detection of endoleaks and in-stent thrombus of thoracic aorta with computed tomographic (CT) angiography by applying protocols with different tube energies and automated tube current modulation. MATERIALS AND METHODS: The calcification insert of an anthropomorphic cardiac phantom was replaced with an aortic aneurysm model containing a stent, simulated endoleaks, and an intraluminal thrombus. CT was performed at tube energies of 120, 100, and 80 kVp with incrementally increasing noise indexes (NIs) of 16, 25, 34, 43, 52, 61, and 70 and a 2.5-mm section thickness. NI directly controls radiation exposure; a higher NI allows for greater image noise and decreases radiation. Images were reconstructed with filtered back projection (FBP) and hybrid and fully iterative algorithms. Five radiologists independently analyzed lesion conspicuity to assess sensitivity and specificity. Mean attenuation (in Hounsfield units) and standard deviation were measured in the aorta to calculate signal-to-noise ratio (SNR). Attenuation and SNR of different protocols and algorithms were analyzed with analysis of variance or Welch test depending on data distribution. RESULTS: Both sensitivity and specificity were 100% for simulated lesions on images with 2.5-mm section thickness and an NI of 25 (3.45 mGy), 34 (1.83 mGy), or 43 (1.16 mGy) at 120 kVp; an NI of 34 (1.98 mGy), 43 (1.23 mGy), or 61 (0.61 mGy) at 100 kVp; and an NI of 43 (1.46 mGy) or 70 (0.54 mGy) at 80 kVp. SNR values showed similar results. With the fully iterative algorithm, mean attenuation of the aorta decreased significantly in reduced-dose protocols in comparison with control protocols at 100 kVp (311 HU at 16 NI vs 290 HU at 70 NI, P ≤ .0011) and 80 kVp (400 HU at 16 NI vs 369 HU at 70 NI, P ≤ .0007). CONCLUSION: Endoleaks and in-stent thrombus of thoracic aorta were detectable to 1.46 mGy (80 kVp) with FBP, 1.23 mGy (100 kVp) with the hybrid algorithm, and 0.54 mGy (80 kVp) with the fully iterative algorithm.

Prenatal detection of congenital renal malformations by fetal ultrasonographic examination: an analysis of 709,030 births in 12 European countries.

The study was performed to evaluate the prevalence of prenatal ultrasound diagnoses for renal anomalies in 20 registries of 12 European countries, and to compare the different prenatal scanning policies. Standardized data were acquired from 709,030 livebirths, stillbirths, and induced abortions during the study period of 2.5 years and transmitted for central analysis. At least one renal malformation was diagnosed in 1130 infants and fetuses. Prenatal diagnosis (PD) was given in 81.8% of all cases, 29% of these pregnancies were terminated. The highest detection rate was reported for unilateral multicystic dysplastic kidneys with 97% (102/105). An early diagnosis was documented for exstrophy of bladder at a mean gestational age of 18.5 weeks. Dilatations of the upper urinary tract were seen late in pregnancy at 28.3 weeks. Terminations of pregnancies (TOP) were performed in 67% (58/86) of the detected bilateral renal agenesis/dysgenesis, but only 4% of the unilateral multicystic dysplastic renal malformations (4/102). In about 1/3 of the cases, renal malformations are within the category of associated malformations, which include multiple non-syndromal malformations, chromosomal aberrations, and non-chromosomal syndromes. Renal malformations were detected in 2/3 of the associated category by the first prenatal ultrasound scan. Detection rates vary in the different countries of the European community due to diverse policies, ethical, and religious background. Countries with no routine ultrasound show the lowest rates in detection, and termination of pregnancy. Prenatally detected renal malformations should result in a careful examination for further anomalies. Prenatal ultrasound fulfills the needs of screening examinations and is a good tool in detecting lethal and severe renal malformations.

Integration of Bridge Damage Detection Concepts and Components (3 volumes), TR-636, 2013

This work is divided into three volumes: Volume I: Strain-Based Damage Detection; Volume II: Acceleration-Based Damage Detection; Volume III: Wireless Bridge Monitoring Hardware. Volume I: In this work, a previously-developed structural health monitoring (SHM) system was advanced toward a ready-for-implementation system. Improvements were made with respect to automated data reduction/analysis, data acquisition hardware, sensor types, and communication network architecture. The statistical damage-detection tool, control-chart-based damage-detection methodologies, were further investigated and advanced. For the validation of the damage-detection approaches, strain data were obtained from a sacrificial specimen attached to the previously-utilized US 30 Bridge over the South Skunk River (in Ames, Iowa), which had simulated damage,. To provide for an enhanced ability to detect changes in the behavior of the structural system, various control chart rules were evaluated. False indications and true indications were studied to compare the damage detection ability in regard to each methodology and each control chart rule. An autonomous software program called Bridge Engineering Center Assessment Software (BECAS) was developed to control all aspects of the damage detection processes. BECAS requires no user intervention after initial configuration and training. Volume II: In this work, a previously developed structural health monitoring (SHM) system was advanced toward a ready-for-implementation system. Improvements were made with respect to automated data reduction/analysis, data acquisition hardware, sensor types, and communication network architecture. The objective of this part of the project was to validate/integrate a vibration-based damage-detection algorithm with the strain-based methodology formulated by the Iowa State University Bridge Engineering Center. This report volume (Volume II) presents the use of vibration-based damage-detection approaches as local methods to quantify damage at critical areas in structures. Acceleration data were collected and analyzed to evaluate the relationships between sensors and with changes in environmental conditions. A sacrificial specimen was investigated to verify the damage-detection capabilities and this volume presents a transmissibility concept and damage-detection algorithm that show potential to sense local changes in the dynamic stiffness between points across a joint of a real structure. The validation and integration of the vibration-based and strain-based damage-detection methodologies will add significant value to Iowa’s current and future bridge maintenance, planning, and management Volume III: In this work, a previously developed structural health monitoring (SHM) system was advanced toward a ready-for-implementation system. Improvements were made with respect to automated data reduction/analysis, data acquisition hardware, sensor types, and communication network architecture. This report volume (Volume III) summarizes the energy harvesting techniques and prototype development for a bridge monitoring system that uses wireless sensors. The wireless sensor nodes are used to collect strain measurements at critical locations on a bridge. The bridge monitoring hardware system consists of a base station and multiple self-powered wireless sensor nodes. The base station is responsible for the synchronization of data sampling on all nodes and data aggregation. Each wireless sensor node include a sensing element, a processing and wireless communication module, and an energy harvesting module. The hardware prototype for a wireless bridge monitoring system was developed and tested on the US 30 Bridge over the South Skunk River in Ames, Iowa. The functions and performance of the developed system, including strain data, energy harvesting capacity, and wireless transmission quality, were studied and are covered in this volume.

Comparison of five commercial serological tests for the detection of anti-Chlamydia trachomatis antibodies.

Screening for Chlamydia trachomatis-specific antibodies is valuable in investigating recurrent miscarriage, tubal infertility and extrauterine pregnancy. We compared here the performance of immunofluorescence (IF) to four other commercial tests in detecting IgG antibodies directed against C. trachomatis: two enzyme-linked immunosorbent assays (ELISAs) using the major outer membrane protein (MOMP) as the antigen, commercialised respectively by Medac and R-Biopharm (RB), one ELISA using the chlamydial heat shock protein 60 (cHSP60) as the antigen (Medac), as well as a new automated epifluorescence immunoassay (InoDiag). A total of 405 patients with (n = 251) and without (n = 154) miscarriages were tested by all five tests. The prevalence of C. trachomatis-specific IgG antibodies as determined by the IF, cHSP60-Medac, MOMP-Medac, MOMP-RB and InoDiag was 14.3, 23.2, 14.3, 11.9 and 26.2%, respectively. InoDiag exhibited the highest sensitivity, whereas MOMP-RB showed the best specificity. Cross-reactivity was observed with C. pneumoniae using IF, MOMP-RB and InoDiag, and Parachlamydia acanthamoebae using the cHSP60 ELISA test. No cross-reactivity was observed between C. trachomatis and the other Chlamydiales (Neochlamydia hartmannellae, Waddlia chondrophila and Simkania negevensis). Given its high sensitivity, the new automated epifluorescence immunoassay from InoDiag represents an interesting alternative. The MOMP-based ELISA of R-Biopharm should be preferred for large serological studies, given the high throughput of ELISA and its excellent specificity.

Review of Automated Vehicle Technology: Policy and Implementation Implications; Version 1.0; RB28-015, 2016

This report provides recommendations for the state of Iowa over the next five years in regards to automated vehicle policy development. These administrative, planning, legal, and community strategy recommendations for government agencies include: • Encouraging automation by preparing government agencies, infrastructure, leveraging procurement, and advocating for safety mandates • Adjusting long range planning processes by identifying and incorporating a wide range of new automation scenarios • Beginning to analyze and, as necessary, clarify existing law as it apples to automated driving • Auditing existing law • Enforcing existing laws • Ensuring vehicle owners and operators bear the true cost of driving • Embracing flexibility by giving agencies the statutory authority to achieve regulatory goals through different means, allowing them to make small-scale exemptions to statutory regimes and clarifying their enforcement discretion • Thinking locally and preparing publicly • Sharing the steps being taken to promote (as well as to anticipate and regulate) automated driving • Instituting public education about automated vehicle technologies.

Label-free detection of tobramycin in serum by transmission-localized surface plasmon resonance.

In order to improve the efficacy and safety of treatments, drug dosage needs to be adjusted to the actual needs of each patient in a truly personalized medicine approach. Key for widespread dosage adjustment is the availability of point-of-care devices able to measure plasma drug concentration in a simple, automated, and cost-effective fashion. In the present work, we introduce and test a portable, palm-sized transmission-localized surface plasmon resonance (T-LSPR) setup, comprised of off-the-shelf components and coupled with DNA-based aptamers specific to the antibiotic tobramycin (467 Da). The core of the T-LSPR setup are aptamer-functionalized gold nanoislands (NIs) deposited on a glass slide covered with fluorine-doped tin oxide (FTO), which acts as a biosensor. The gold NIs exhibit localized plasmon resonance in the visible range matching the sensitivity of the complementary metal oxide semiconductor (CMOS) image sensor employed as a light detector. The combination of gold NIs on the FTO substrate, causing NIs size and pattern irregularity, might reduce the overall sensitivity but confers extremely high stability in high-ionic solutions, allowing it to withstand numerous regeneration cycles without sensing losses. With this rather simple T-LSPR setup, we show real-time label-free detection of tobramycin in buffer, measuring concentrations down to 0.5 μM. We determined an affinity constant of the aptamer-tobramycin pair consistent with the value obtained using a commercial propagating-wave based SPR. Moreover, our label-free system can detect tobramycin in filtered undiluted blood serum, measuring concentrations down to 10 μM with a theoretical detection limit of 3.4 μM. While the association signal of tobramycin onto the aptamer is masked by the serum injection, the quantification of the captured tobramycin is possible during the dissociation phase and leads to a linear calibration curve for the concentrations over the tested range (10-80 μM). The plasmon shift following surface binding is calculated in terms of both plasmon peak location and hue, with the latter allowing faster data elaboration and real-time display of the results. The presented T-LSPR system shows for the first time label-free direct detection and quantification of a small molecule in the complex matrix of filtered undiluted blood serum. Its uncomplicated construction and compact size, together with the remarkable performances, represent a leap forward toward effective point-of-care devices for therapeutic drug concentration monitoring.

Evaluation of a new serological test for the detection of anti-Coxiella and anti-Rickettsia antibodies.

Coxiella burnetii and members of the genus Rickettsia are obligate intracellular bacteria. Since cultivation of these organisms requires dedicated techniques, their diagnosis usually relies on serological or molecular biology methods. Immunofluorescence is considered the gold standard to detect antibody-reactivity towards these organisms. Here, we assessed the performance of a new automated epifluorescence immunoassay (InoDiag) to detect IgM and IgG against C. burnetii, Rickettsia typhi and Rickettsia conorii. Samples were tested with the InoDiag assay. A total of 213 sera were tested, of which 63 samples from Q fever, 20 from spotted fever rickettsiosis, 6 from murine typhus and 124 controls. InoDiag results were compared to micro-immunofluorescence. For acute Q fever, the sensitivity of phase 2 IgG was only of 30% with a cutoff of 1 arbitrary unit (AU). In patients with acute Q fever with positive IF IgM, sensitivity reached 83% with the same cutoff. Sensitivity for chronic Q fever was 100% whereas sensitivity for past Q fever was 65%. Sensitivity for spotted Mediterranean fever and murine typhus were 91% and 100%, respectively. Both assays exhibited a good specificity in control groups, ranging from 79% in sera from patients with unrelated diseases or EBV positivity to 100% in sera from healthy patients. In conclusion, the InoDiag assay exhibits an excellent performance for the diagnosis of chronic Q fever but a very low IgG sensitivity for acute Q fever likely due to low reactivity of phase 2 antigens present on the glass slide. This defect is partially compensated by the detection of IgM. Because it exhibits a good negative predictive value, the InoDiag assay is valuable to rule out a chronic Q fever. For the diagnosis of rickettsial diseases, the sensitivity of the InoDiag method is similar to conventional immunofluorescence.

Screening premorbid metabolic syndrome in community pharmacies: a cross-sectional descriptive study

Background: Premorbid metabolic syndrome (pre-MetS) is a cluster of cardiometabolic risk factors characterised by central obesity, elevated fasting glucose, atherogenic dyslipidaemia and hypertension without established cardiovascular disease or diabetes. Community pharmacies are in an excellent position to develop screening programmes because of their direct contact with the population. The main aim of the study was to determine the prevalence of pre-MetS in people who visited community pharmacies for measurement of any of its five risk factors to detect the presence of other risk factors. The secondary aims were to study the presence of other cardiovascular risk factors and determine patients" cardiovascular risk. Methods: Cross-sectional, descriptive, multicentre study. Patients meeting selection criteria aged between 18 and 65 years who visited participating community pharmacies to check any of five pre-MetS diagnostic factors were included. The study involved 23 community pharmacies in Catalonia (Spain). Detection criteria for pre-MetS were based on the WHO proposal following IDF and AHA/NHBI consensus. Cardiovascular risk (CVR) was calculated by Regicor and Score methods. Other variables studied were smoking habit, physical activity, body mass index (BMI), and pharmacological treatment of dyslipidemia and hypertension. The data were collected and analysed with the SPSS programme. Comparisons of variables were carried out using the Student"s T-test, Chi-Squared test or ANOVA test. Level of significance was 5% (0.05). Results: The overall prevalence of pre-MetS was 21.9% [95% CI 18.7-25.2]. It was more prevalent in men, 25.5% [95% CI 22.1-28.9], than in women, 18.6% [95% CI 15.5-21.7], and distribution increased with age. The most common risk factors were high blood pressure and abdominal obesity. About 70% of people with pre-MetS were sedentary and over 85% had a BMI ≥25 Kg/m2 . Some 22.4% had two metabolic criteria and 27.2% of patients with pre-MetS had no previous diagnosis. Conclusions: The prevalence of pre-MetS in our study (21.9%) was similar to that found in other studies carried out in Primary Care in Spain. The results of this study confirm emergent cardiometabolic risk factors such as hypertension, obesity and physical inactivity. Our study highlights the strategic role of the community pharmacy in the detection of pre-MetS in the apparently healthy population.

An automated microreactor for semi-continuous biosensor measurements.

Living bacteria or yeast cells are frequently used as bioreporters for the detection of specific chemical analytes or conditions of sample toxicity. In particular, bacteria or yeast equipped with synthetic gene circuitry that allows the production of a reliable non-cognate signal (e.g., fluorescent protein or bioluminescence) in response to a defined target make robust and flexible analytical platforms. We report here how bacterial cells expressing a fluorescence reporter ("bactosensors"), which are mostly used for batch sample analysis, can be deployed for automated semi-continuous target analysis in a single concise biochip. Escherichia coli-based bactosensor cells were continuously grown in a 13 or 50 nanoliter-volume reactor on a two-layered polydimethylsiloxane-on-glass microfluidic chip. Physiologically active cells were directed from the nl-reactor to a dedicated sample exposure area, where they were concentrated and reacted in 40 minutes with the target chemical by localized emission of the fluorescent reporter signal. We demonstrate the functioning of the bactosensor-chip by the automated detection of 50 μgarsenite-As l(-1) in water on consecutive days and after a one-week constant operation. Best induction of the bactosensors of 6-9-fold to 50 μg l(-1) was found at an apparent dilution rate of 0.12 h(-1) in the 50 nl microreactor. The bactosensor chip principle could be widely applicable to construct automated monitoring devices for a variety of targets in different environments.

Childhood community-acquired pneumonia

Background: Community-acquired pneumonia is a leading cause of morbidity and mortality in children worldwide. New, rapid methods are needed to improve the microbiologic diagnosis of pneumonia in clinical practice. The increasing incidence of parapneumonic empyema in children accentuates the importance of the identification of the causative agent and clinical predictors of empyema. Aims and methods: Two prospective studies were conducted to find feasible diagnostic methods for the detection of causative agents of pneumonia. The usefulness of pneumolysin-targeted real-time PCR in the diagnosis of pneumococcal disease was studied in children with pneumonia and empyema, and the clinical utility of induced sputum analysis in the microbiologic diagnosis of pneumonia was investigated in children with pneumonia. In addition, two retrospective clinical studies were performed to describe the frequency and clinical profile of influenza pneumonia in children and the frequency, clinical profile and clinical predictors of empyema in children. Results: Pneumolysin-PCR in pleural fluid significantly improved the microbiologic diagnosis of empyema by increasing the detection rate of pneumococcus almost tenfold to that of pleural fluid culture (75 % vs. 8 %). In whole blood samples, PCR detected pneumococcus in only one child with pneumonia and one child with pneumococcal empyema. Sputum induction provided good-quality sputum specimens with high microbiologic yield. Streptococcus pneumoniae (46 %) and rhinovirus (29 %) were the most common microbes detected. The quantification results of the paired sputum and nasopharyngeal aspirate specimens provided support that the majority of the bacteria (79 %) and viruses (55 %) found in sputum originated from the lower airways. Pneumonia was detected in 14 % of children with influenza infection. A history of prolonged duration of fever, tachypnea, and pain on abdominal palpation were found to be independently significant predictors of empyema. Conclusions: Pneumolysin-targeted real-time PCR is a useful and rapid method for the diagnosis of pneumococcal empyema in children. Induced sputum analysis with paired nasopharyngeal aspirate analysis can be of clinical value in the microbiologic diagnosis of pneumonia. Influenza pneumonia is an infrequent and generally benign disease in children with rare fatalities. Repeat chest radiograph and ultrasound imaging are recommended in children with pneumonia presenting with clinical predictors of empyema and in children with persistent fever and high CRP levels during hospitalization.

Automated flow-injection method for cadmium determination with pre-concentration and reagent preparation on-line

The spectrophotometric determination of Cd(II) using a flow injection system provided with a solid-phase reactor for cadmium preconcentration and on-line reagent preparation, is described. It is based on the formation of a dithizone-Cd complex in basic medium. The calibration curve is linear between 6 and 300 µg L-1 Cd(II), with a detection limit of 5.4 µg L-1, an RSD of 3.7% (10 replicates in duplicate) and a sample frequency of 11.4 h-1. The proposed method was satisfactorily applied to the determination of Cd(II) in surface, well and drinking waters.