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The (mis)estimation of neighborhood effects: causal inference for a practicable social epidemiology.

The resurgence of interest in the effect of neighborhood contexts on health outcomes, motivated by advances in social epidemiology, multilevel theories and sophisticated statistical models, too often fails to confront the enormous methodological problems associated with causal inference. This paper employs the counterfactual causal framework to illuminate fundamental obstacles in the identification, explanation, and usefulness of multilevel neighborhood effect studies. We show that identifying useful independent neighborhood effect parameters, as currently conceptualized with observational data, to be impossible. Along with the development of a dependency-based methodology and theories of social interaction, randomized community trials are advocated as a superior research strategy, one that may help social epidemiology answer the causal questions necessary for remediating disparities and otherwise improving the public's health.

Bias↗

Identifying the components of a postsynaptic potential and their amplitude, latency and shape fluctuations: analysis by means of autocovariance functions and a stochastic infinite cable model.

In addition to amplitude fluctuations, physiological mechanisms may introduce latency and shape fluctuations in the components of a postsynaptic potential (PSP). Latency fluctuations may be originated mainly by presynaptic factors. Shape fluctuations may be produced by changes in the background synaptic activity received by the postsynaptic neuron, which affect the cell membrane resistance. This article aims to develop a unified approach for the analysis of amplitude, latency and shape fluctuations in the components of a PSP. The analysis is based on: (i) the Autocovariance Functions of the PSP (ACOVs); (ii) a mathematical model able to predict the average and ACOVs of a PSP with specified components and fluctuations (the 'Stochastic Infinite Cable Model' (SICM)); and (iii) a procedure to estimate the SICM parameters that best reproduce the average and ACOVs of a given PSP (the 'SICM-based PSP identification procedure' (SICM-IP)). The SICM-IP is tested with simulated PSPs. The results obtained support the feasibility of the approach.

Algorithms↗

Supine bicycle stress echocardiography: peak exercise imaging is superior to postexercise imaging.

The abilities of peak exercise (PEAK) stress echocardiography versus postexercise (POST) stress echocardiography to detect coronary artery disease were evaluated in 136 consecutive patients undergoing supine bicycle stress echocardiography and coronary arteriography: 42 (31%) had normal coronary vessels, 38 (28%) had single-vessel disease, 34 (25%) had double-vessel disease, and 22 (16%) had triple-vessel disease. The results were as follows: (1) For detection of disease in the group of patients, sensitivity of PEAK versus POST was 94% versus 83% (p < 0.01) and specificity was 88% versus 90%. (2) For detection of disease in specific vessels, sensitivity of PEAK versus POST was 90% versus 72% (p < 0.0001) and specificity was 89% versus 92%. (3) For evaluation of the three major coronary arteries, sensitivity of PEAK versus POST was 96% versus 85% (p < 0.05) for the left anterior descending artery, 90% versus 65% (p < 0.01) for the right coronary artery, and 79% versus 60% (p < 0.05) for the left circumflex coronary artery. There were no differences in specificity. (4) The percent diameter stenosis of vessels normalizing from PEAK to POST versus vessels abnormal at PEAK and POST was 80.6% +/- 16% versus 85.9% +/- 14%, p = 0.07. There were no differences in exercise parameters between patients with and without resolution from PEAK to POST. (5) PEAK versus POST accuracy for identification of patients with multivessel disease was 93% versus 68% (p < 0.001). We conclude that stress echocardiography performed during peak exercise is superior to postexercise stress echocardiography.

Coronary Angiography↗

A multivariate time-variant AR method for the analysis of heart rate and arterial blood pressure.

This paper approaches the problem of short-term mechanisms that regulate heart rate and blood pressure variability signals, by focusing the evident changes of their frequency content during transients (dynamic situations in which the behaviour of these control mechanisms may vary on a beat-to-beat basis). In this study, we suggest an autoregressive time-variant spectral estimation method, which is able to follow such dynamic changes in the signals. This method has also been extended to a multivariate approach in order to take into account more than one process at a time, and to assess the mutual influences between the different controlling systems. The algorithms successfully tested on simulated series have also been used to analyse series recorded during a vaso-vagal syncope episode in a tilt manoeuvre and a physical exercise stress test protocol. The results show how this method is able to follow the changing dynamics of the signals on the basis of a closed-loop model of their interaction on a beat-to-beat basis. After a proper identification procedure of the blocks forming the model, it is possible, therefore, to obtain the classical spectral parameters and the gain of the transfer function between the signals. Such parameters constitute new time series that describe the physiopathology of the cardiovascular control systems, even during non-stationary epochs.

Algorithms↗

Characterization of Fasciola hepatica redial generations by morphometry and chaetotaxy under experimental conditions.

Morphometric and chaetotactic studies were carried out on the body and cephalic regions of the rediae of Fasciola hepatica (Trematoda: Fasciolidae) in order to precisely identify the different redial generations of this trematode in Lymnaea truncatula under experimental infection. At day 49 post-exposure at 20 degreesC, the length of the redia was significantly higher in the first group of the first generation (R1a) compared with successive generations, R1b, R2a and R2b/R3a. The width of the body was similar in the R1a, R1b, and R2a rediae, but was significantly lower in the R2b/R3a groups. The intrapharyngeal cavity of R1a rediae was significantly wider compared with the R1b, R2a, and R2b/R3a groups, whereas the pharyngeal wall was significantly thicker in the R2b/R3a rediae compared with the R1b and R2a groups. Four other measurements, namely the maximum length and width of the pharynx, diameter of the mouth, and width of intestine, also showed significant variations in relation to pharyngeal morphology and age of infection. Discriminant analysis based on these measurements demonstrated that 98% of the rediae were readily categorized into the four groups identified. The number of perioral sensillae ranged from 126 to 160 but a significant difference was only noted between the mean values of the first generation and those of the group R2b/R3a. From these parameters, the maximum width of the pharyngeal lumen was found to be the best characteristic in the identification of the redial generations.

Animals↗

Determination of parts per trillion levels of organophosphorus pesticides in groundwater by automated on-line liquid-solid extraction followed by liquid chromatography/atmospheric pressure chemical ionization mass spectrometry using positive and negative ion modes of operation.

Liquid chromatography/atmospheric pressure chemical ionization mass spectrometry with positive and negative ion modes of operations was used for the trace determination of several organophosphorus pesticides, (E)- and (Z)-mevinphos, dichlorvos, azinphos-methyl, azinphosethyl, parathion-methyl, parathion-ethyl, malathion, fenitrothion, fenthion, chlorfenvinphos, and diazinon, in groundwater. This method required only 100 mL of water, and it was combined with a prior automated online liquid-solid extraction step using an OSP-2 autosampler containing C18 cartridges. The limit of quantitation (LOQ) varied between 5 and 37 ng/L in positive ion (PI) mode. Under negative ion (NI) mode of operation, only the parathion group (both parathions and fenitrothion) had a better sensitivity as compared to that in PI mode, with a LOQ of 5-15 ng/L, whereas the rest of pesticides had 2-4 times higher LOQs as compared to those in PI mode. Selected ion monitoring of the group-specific fragment of the organophosphorus pesticides, e.g., [(CH3O)2PO2]- or the [M + H]+ ions, under NI or PI mode, respectively, was used. Sample cone voltage varied from 10 to 130 V. This parameter influenced the transmission and fragmentation of quasi-molecular ions, and it was optimized to achieve identification capabilities with the highest sensitivity. At 20 V, good fragmentation was obtained for most of the studied analytes. The system was used for the certification of a groundwater sample spiked at the nanograms per liter level with organophosphorus pesticides provided by Aquachek.

Chromatography, Liquid↗

Structural and thermodynamic studies on cation-Pi interactions in lectin-ligand complexes: high-affinity galectin-3 inhibitors through fine-tuning of an arginine-arene interaction.

The high-resolution X-ray crystal structures of the carbohydrate recognition domain of human galectin-3 were solved in complex with N-acetyllactosamine (LacNAc) and the high-affinity inhibitor, methyl 2-acetamido-2-deoxy-4-O-(3-deoxy-3-[4-methoxy-2,3,5,6-tetrafluorobenzamido]-beta-D-galactopyranose)-beta-D-glucopyranoside, to gain insight into the basis for the affinity-enhancing effect of the 4-methoxy-2,3,5,6-tetrafluorobenzamido moiety. The structures show that the side chain of Arg144 stacks against the aromatic moiety of the inhibitor, an interaction made possible by a reorientation of the side chain relative to that seen in the LacNAc complex. Based on these structures, synthesis of second generation LacNAc derivatives carrying aromatic amides at 3'-C, followed by screening with a novel fluorescence polarization assay, has led to the identification of inhibitors with further enhanced affinity for galectin-3 (K(d) > or = 320 nM). The thermodynamic parameters describing the binding of the galectin-3 C-terminal to selected inhibitors were determined by isothermal titration calorimetry and showed that the affinity enhancements were due to favorable enthalpic contributions. These enhancements could be rationalized by the combined effects of the inhibitor aromatic structure on a cation-Pi interaction and of direct interactions between the aromatic substituents and the protein. The results demonstrate that protein-ligand interactions can be significantly enhanced by the fine-tuning of arginine-arene interactions.

Amino Sugars↗

Timber rattlesnakes (Crotalus horridus) use chemical cues to select ambush sites.

Chemicals left by organisms moving through the environment are used by other organisms to mediate interspecific interactions. Most studies of chemical eavesdropping focus on prey responding to chemical cues from predators, despite the fact that chemical cues are frequently used by predators as a source of information about prey. Crotalus horridus uses a foraging strategy that is widespread among sedentary predators: the snake chooses a site where it is likely to encounter prey and remains immobile for many hours. I investigated this ambush hunting behavior in captive-raised timber rattlesnakes and provide evidence that sit-and-wait predators may discriminate among prey chemical cues, even when they have no prior experience with the prey. Snakes explored chemical cues with chemosensory behaviors, and more frequently adopted a stereotyped ambush foraging posture toward chemical cues from prey sympatric with their population of origin than either allopatric prey or sympatric nonprey species that are eaten by other viperids. These results support the notion that intra- and interspecific variation in diet may be mediated proximally by innate recognition of cues from particular prey items. This system also describes a bioassay that may be used in the isolation and identification of prey-derived kairomones. Studies such as this can be used to determine more realistic parameters for models of predator-prey interaction and foraging behavior that involve secretive, less active predators.

Animals↗

Temporal-phonemic processing skills in adult stutterers and nonstutterers.

The purpose of this study was to investigate the hypothesis that stuttering is related to a dysfunction in auditory temporal processing. The performance of 20 adult male stutterers and 20 matched nonstutterers was studied using two auditory processing tasks. The subjects listened to stimuli with differential onset asynchronies during temporal order judgment (TOJ) and dichotic listening tasks. Stutterers and nonstutterers were not significantly different at judging which ear received the stimulation first (TOJ task) at varying stimulus onset asynchronies (SOAs). During the dichotic listening task, stutterers made significantly fewer double-correct responses (correct report for both stimuli in a dichotic pair) than nonstutterers. The stuttering subjects correctly classified one of the syllables in a pair (single-correct response) more frequently than normal controls on the dichotic listening task. These findings suggest that SOAs as a temporal parameter do not differentiate the performance of the two groups. The more difficult auditory processing task (dichotic identification) showed a significant difference in the performance of the stutterers versus nonstutterers.

Adolescent↗

HFE mutations and transferrin receptor polymorphism analysis in porphyria cutanea tarda: a prospective study of 36 cases from southern France.

BACKGROUND: Porphyria cutanea tarda (PCT) is associated in most cases with iron overload, which may participate in decreased activity of uroporphyrinogen decarboxylase in the liver. The aetiology of this iron overload remains unknown; however, it has been demonstrated that mutations of HFE, the genetic haemochromatosis gene, might be present in a significant proportion of Anglo-Saxon and Italian patients. Furthermore, transferrin receptor polymorphism may influence the affinity of this receptor to its ligand with a subsequent increase of cellular iron absorption and storage. OBJECTIVES: To evaluate the incidence and spectrum of HFE mutations and the relative frequency of the two main alleles of transferrin receptor in patients with PCT originating from southern France, and to evaluate the relationship of these genetic data with iron status, and with hepatitis B and C and human immunodeficiency virus (HIV) infections. METHODS: Thirty-six consecutive patients with either sporadic or familial PCT were prospectively included between 1997 and 2000. Search for the presence of the three main mutations of the HFE gene and identification of the transferrin receptor alleles were performed using polymerase chain reaction followed by enzymatic digestion. Iron parameters and viral status for hepatitis B and C viruses and HIV were determined. RESULTS: Seven patients (19%) showed heterozygous C282Y mutation, but no C282Y homozygote was present; five patients (14%) carried homozygous H63D mutation, while eight (22%) were heterozygous for this mutation. One patient was heterozygous for the S65C mutation (3%). Iron parameters demonstrated overload in all patients, without a clear difference between patients with and without deleterious mutations of the HFE gene. Infection by hepatitis C virus was documented in 20 patients (56%), and was significantly less frequent in patients with deleterious HFE mutations. The profile of transferrin receptor alleles in PCT patients did not show significant variation compared with the general population. CONCLUSIONS: This study confirms the high frequency of HFE mutations in patients with PCT and supports the hypothesis that HFE gene abnormalities might play a significant part in the PCT pathomechanism, probably through iron overload; by contrast, transferrin receptor polymorphisms do not appear to play a significant part in iron overload in PCT.

Adult↗

Statistical evaluation of red cell antibody panels.

The evaluation of a red cell antibody identification panel is a subjective and lengthy process. This study evaluated red cell panels using several statistical parameters and derived an objective, numerical tool for panel evaluation. Nineteen panels were subjectively evaluated by five immunohematologists; a composite ranking was derived from a compilation of their subjective evaluations. A rank indicative of good general utility correlated with 1) the extent to which the panel was composed of red cells with homozygous genotypes in each blood group system, and 2) the number of antibody specificity exclusions which could be made using the panel. A statistical predictor of panel rank was empirically derived based on a score dependent upon the zygosity of each cell in each antigen system and the relative clinical importance of antibodies of each of these specificities. This numerical tool could be applied to a panel in less than 5 minutes. The objective evaluation on each panel tested closely correlated with the composite subjective rank (r = 0.935; p less than 0.001). Objective numerical evaluation of red cell panels may be useful in their rapid evaluation and comparison, particularly during their construction by computers.

Antibody Specificity↗

Characteristics of transient evoked otoacoustic emissions in normal-hearing and hearing-impaired children.

OBJECTIVE: Transient evoked otoacoustic emissions (TEOAEs) were measured in children with normal hearing and in children with hearing loss to investigate the characteristics of TEOAEs as they relate to overall amplitude and amplitude spectra of evoking stimuli, and to audiometric status. DESIGN: Three parameters of response measure (signal to noise ratio, amplitude and reproducibility) were assessed to determine accuracy of identification of varying degrees of hearing loss for broadband clicks, frequency-specific click bands and tone bursts. Forty-four children (66 ears) between 4 and 13 yr of age were evaluated for participation in the study. Fifty-nine ears with intact tympanic membranes were included in the final analyses: 14 ears with normal hearing and 45 ears with hearing loss. RESULTS: Children with normal hearing had robust responses that displayed nonlinear growth functions for broadband clicks and for tone bursts. Children with hearing loss had responses that decreased rapidly with decreasing stimulus level, if emissions were present at all. Data were analyzed using clinical decision analysis and receiver operator characteristic curves. Broadband clicks presented at 80 and 86 dB peSPL identified a hearing loss > or = 30 dB HL with a high degree of accuracy. Click responses filtered into octave bands centered at 500 and 1000 Hz did not improve classification of hearing loss, in fact, the 500 Hz band was particularly inaccurate. Results for click responses filtered into half-octave bands centered at 2000 and 4000 Hz were comparable with those for the broadband click, although the 2000 Hz band was superior for identification of hearing loss > or = 20 dB HL for an 80 dB peSPL click, and > or = 30 dB HL for an 86 dB peSPL click. Results for tone bursts centered at 500, 1000, 2000 and 4000 Hz, presented at 80 dB peSPL, were similar to results of the filtered click bands. Accuracy for identifying hearing loss increased with increasing center frequency. The 2000 and 4000 Hz tone bursts provided the best separation between normal-hearing and hearing-impaired ears, with 4000 Hz being slightly better. CONCLUSIONS: Data from this study suggest that TEOAEs in children can separate ears with normal hearing from those with hearing loss using a variety of stimulus and response conditions. Moreover, by using multiple stimulus levels it may be possible to distinguish between mild and moderate hearing losses.

Acoustic Stimulation↗

Self-report evaluation of health behavior, stress vulnerability, and medical outcome of heart transplant recipients.

OBJECTIVE: The purpose of this study was to explore the value of patient self-report assessment in heart transplant candidacy evaluation, utilizing the Millon Behavioral Health Inventory (MBHI). Patient's MBHI measures were related to important pretransplant patient characteristics and posttransplant measures of health behavior, medical morbidity, and mortality. METHOD: Ninety heart patients with end-stage cardiac disease completed the MBHI during pretransplant candidacy evaluations, and also were interviewed concerning their coping effectiveness, support resources, and compliance history. Postransplant follow-up of 61 living and 29 deceased patients included measures of survival time, postsurgical medical care, rejection and infection episodes, and nurse ratings of medication compliance and problematic interpersonal health behaviors. RESULTS: The MBHI coping scales were found to significantly discriminate good and poor pretransplant compliance, and interview judgments of good and poor coping and support resources, with modest accuracy. The MBHI also was superior to these interview judgments in predicting posttransplant survival time and medical care used. Certain scales were also positively associated with physical parameters of pretransplant and posttransplant status. CONCLUSIONS: Patient self-report with the MBHI can contribute to identification of patients at risk for a problematic outcome with transplant, by providing information pertinent to clinical decision making and outcome management analysis with this special population of cardiac patients.

Adult↗

Presence of Heat Shock mRNAs in Field Crown Soybeans.

Our laboratory has extensively defined many parameters of the heat shock (HS) response in etiolated soybean (Glycine max [L.] Merr.) hypocotyls, including the identification of cDNA clones for mRNAs encoding several low molecular weight HS proteins. We have now investigated the response of mature plants to a HS in a growth chamber and to high temperature stress under field conditions. Soybean plants show induction of HS mRNAs when the temperature of the chamber is rapidly shifted from 28 degrees C to 45 degrees C. This temperature of induction is significantly higher than the optimal induction temperature for etiolated hypocotyls, probably reflecting the ability of mature plants to lower their leaf temperatures below the ambient air temperature through transpirational cooling. Samples of soybean leaves were taken from an irrigated and a nonirrigated field during a 24-h period when midday temperatures reached 40 degrees C. Several HS mRNAs were present in samples from both fields, although the levels of these mRNAs were much higher in nonirrigated leaves. This differential response of HS mRNA steady state levels was not a response to water stress, since water-stressed plants at 28 degrees C did not induce HS mRNAS. Rather, these quantitative differences are probably due to differences in actual leaf temperatures between irrigated and nonirrigated leaves. The presence of these HS mRNAS in field-grown plants suggests that HS proteins are produced as part of the normal plant response to high temperature.

Journal Article↗

Crystallization and preliminary crystallographic analysis of selenomethionine-labelled progesterone 5beta-reductase from Digitalis lanata Ehrh.

Progesterone 5beta-reductase (5beta-POR) catalyzes the reduction of progesterone to 5beta-pregnane-3,20-dione and is the first stereospecific enzyme in the putative biosynthetic pathway of Digitalis cardenolides. Selenomethionine-derivatized 5beta-POR from D. lanata was successfully overproduced and crystallized. The crystals belong to space group P4(3)2(1)2, with unit-cell parameters a = 71.73, c = 186.64 A. A MAD data set collected at 2.7 A resolution allowed the identification of six out of eight possible Se-atom positions. A first inspection of the MAD-phased electron-density map shows that 5beta-POR is a Rossmann-type reductase and the quality of the map is such that it is anticipated that a complete atomic model of 5beta-POR will readily be built.

Crystallization↗

A PC-based imaging system for automated platelet identification.

In this communication, a PC-based imaging system was developed for automatically identifying fluorescence-labeled individual platelets adherent to protein-coated surface under flow conditions. It is to eliminate the laborious and time-consuming task, and the subjective error of manual measurements. Based upon the features of adherent platelets, three passes of the image processing were developed for platelet identification. From the results, 90-95% accuracy could be routinely obtained. The platelet distribution and other related parameters could be easily extracted and investigated.

Algorithms↗

A neural network model for optimizing vowel recognition by cochlear implant listeners.

Due to the variability in performance among cochlear implant (CI) patients, it is becoming increasingly important to find ways to optimally fit patients with speech processing strategies. This paper proposes an approach based on neural networks, which can be used to automatically optimize the performance of CI patients. The neural network model is implemented in two stages. In the first stage, a neural network is trained to mimic the CI patient's performance on the vowel identification task. The trained neural network is then used in the second stage to adjust a free parameter to improve vowel recognition performance for each individual patient. The parameter examined in this study was a weighting function applied to the compressed channel amplitudes extracted from a 6-channel continuous interleaved sampling (CIS) strategy. Two types of weighting functions were examined, one which assumed channel interaction, and one which assumed no interaction between channels. Results showed that the neural network models closely matched the performance of five Med-EI/CIS-Link implant patients. The resulting weighting functions obtained after neural network training improved vowel performance, with the larger improvement (4%) attained by the weighting function which modeled channel interaction.

Algorithms↗

Inflammatory activities of synovial fluids from rheumatoid- and osteo-arthritis to guinea pig skin.

For initial study to examine the chemical pathogenesis of rheumatoid and non-rheumatoid arthritis, the nature and inflammatory activities of 12 synovial fluids from rheumatoid arthritis and 10 from osteoarthritis were studied. Both rheumatoid and non-rheumatoid synovial fluids were found to have high protein concentration, acid and neutral protease activities. When injected 0.1 ml intradermally to normal guinea pig skin, both synovial fluids induced a strong vascular permeability at 0 minutes, mild one at 60 minutes, and mild inflammation which comprised histologically moderate leukocyte infiltration around the venules, swelling of venular endothelial cells, edema, and degeneration of collagen fibrils in the deep dermis of the guinea pig skin 4 hours following the injection. However, these parameters of inflammation induced by synovial fluids from both arthritis were of same degree in intensity. The identification of chemical mediators of inflammation in the synovial fluids of both arthritis requires further study.

Adult↗