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[Neural network based detection of pulmonary nodules on chest radiographs].

PURPOSE: We investigated the capabilities of an artificial neural network-based Computer-Aided Diagnosis (CAD) system in improving early detection of pulmonary nodules on chest radiographs. MATERIAL AND METHODS: We used a data-set of 145 digitized chest films. Two different radiologists read the radiographs to detect the sites of possible nodules. The system uses two neural networks trained on a training-set of 100 radiographs selected from the data-set. The first network is used to focus attention on the sites of potential nodules while the second calculates the likeliness of nodule presence in ROIs. The clinical test was performed on 45 more radiographs from the training-set, but different from those in the data-set, which were positive for both benign and malignant nodules. These latter plain films showed 65 nodular lesions which differed by shape and acquisition technique. RESULTS: Sensitivity was 89% in all radiographs while specificity, evaluated by ROI, and accuracy, were 98%. CONCLUSIONS: There are potential limitations in nodule detection on plain radiographs. Some of them are operator-dependent, such as nonsystematic investigation, lesion underestimation, and poor reading, and some are technique-dependent, such as X-ray beam/tube, low voltage, patient positioning, focus-film distance and development process. CADs may contribute to improving detection of pulmonary nodules because the false-negative rate is decreased and sensitivity consequently increased. The high sensitivity and specificity rates of neural networks encourage further trials on wider data-sets to help the radiologist in the early detection of pulmonary nodules.

Humans↗

Genesis of the novel epidemic Vibrio cholerae O139 strain: evidence for horizontal transfer of genes involved in polysaccharide synthesis.

Only Vibrio cholerae strains of serotype O1 are known to cause epidemics, while non-O1 strains are associated with sporadic cases of cholera. It was therefore unexpected that the recent cholera epidemic in Asia was caused by a non-O1 strain with the serotype O139. We provide evidence that O139 arose from a strain closely related to the causative agent of the present cholera pandemic, V. cholerae O1 El Tor, by acquisition of novel DNA which was inserted into, and replaced part of, the O antigen gene cluster of the recipient strain. Part of the novel DNA was sequenced and two open reading frames (otnA and otnB) were observed, the products of which showed homology to proteins involved in capsule and O antigen synthesis, respectively. This suggests that the otnAB DNA determines the distinct antigenic properties of the O139 cell surface. The otnAB DNA was not detected in O1 strains, but was present in two non-O1 V. cholerae strains with serotypes O69 and O141. In the O69 and O139 strains the otnAB genes were located proximate to the putative insertion sequence (IS) element rfbQRS, which is associated with O antigen synthesis genes in O1 strains, and may have played a role in the insertion of the otnAB DNA in the recipient chromosome. Our results suggest that the O139 strain arose by horizontal gene transfer between a non-O1 and an O1 strain. The acquired DNA has altered the antigenic properties of the recipient O1 strain, providing a selective advantage in a region where a large part of the population is immune to O1 strains.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

The Env-like open reading frame of the baculovirus-integrated retrotransposon TED encodes a retrovirus-like envelope protein.

TED is a 7.5-kbp member of the gypsy family of retrotransposons that was first identified by its integration within the baculovirus DNA genome. This lepidopteran (moth) transposon contains three retrovirus-like genes, including functional gag and pol that yield reverse transcriptase-containing virus-like particles. To identify and characterize the product(s) of the third env-like open reading frame, TED ORF3 was expressed in homologous lepidopteran cells by using a baculovirus vector, vENV. Immunoblots and immunoprecipitations with antiserum raised against a bacterial ORF3-fusion protein detected two ORF3-encoded proteins, p68env and gp75env. On the basis of selective incorporation of [3H]mannose and inhibition of modification by tunicamycin which blocks N-linked glycosylation, gp75env is a glycoprotein derived from core precursor p68env. As predicted by the presence of a transmembrane domain near the carboxyl terminus, both p68env and gp75env were associated with heavy membranes of vENV-infected cells. Thus, TED ORF3 encodes a membrane glycoprotein with properties characteristic of retroviral env proteins. These data are consistent with the hypothesis that TED is an invertebrate retrovirus. Moreover, TED integration within the baculovirus genome provides an example of retroelement-mediated acquisition of host genes that may contribute to virus evolution.

Animals↗

Conditions under which lorazepam can facilitate retrieval.

Memory is composed of three stages: acquisition, consolidation, and retrieval. By impairing acquisition processes, benzodiazepines cause anterograde amnesia while leaving intact information learned before the drug was taken. In some circumstances, retrieval of this information is even improved by benzodiazepines. It has been hypothesized that this phenomenon is not a true facilitation of retrieval processes, but is the result of reduced interference from items presented after drug administration and is thus a secondary consequence of drug-induced amnesia. Experiment 1 investigated the effect of 0.5, 1, and 2.5 mg of lorazepam on explicit episodic memory in healthy young volunteers. The 1-mg dose was found to significantly improve recall of items presented before drug administration without causing amnesia for items presented after drug administration, thus excluding an interference explanation. Experiment 2 investigated the conditions necessary to obtain facilitated retrieval with 1 mg of lorazepam. The results showed that facilitation was found only when two lists of semantically related material were presented, but that both of the lists could be presented before drug administration, thus excluding an effect of lorazepam on consolidation. Facilitation could be demonstrated in both direct (free recall) and indirect (backwards reading) retrieval tasks and when all of the material was presented after lorazepam administration. This improved retrieval could therefore be of clinical relevance, but any benefits would be reduced at higher doses that at the same time impair acquisition of new information. However, because 1 mg of lorazepam is an effective anxiolytic dose, these results suggest that it is possible to combine effective anxiety reduction with some benefits to memory.

Adolescent↗

Molecular cloning and hormonal control in the ovary of connexin 31.5 mRNA and correlation with the appearance of oocyte maturational competence in red seabream.

Gap junctions are aggregates of intercellular channels, composed of the protein connexin (Cx), between adjacent cells. This study examined whether, in the ovary of the red seabream Pagrus major, the connexin gene essential for the production of RNA and protein during the acquisition of oocyte maturational competence is active. Mixed primers for this reaction were designed on the basis of the high sequence homology of selected regions of known connexin genes. Polymerase-chain-reaction-amplified cDNA fragments generated by 3' and 5' rapid amplication of cDNA ends were combined to generate full-length cDNA sequences. The resulting 2400 base pair cDNA had an open reading frame encoding a polypeptide containing 275 amino acid residues (31493 Da; Cx31.5). Hydropathicity analysis of the predicted amino acid sequence indicated that red seabream Cx31.5 has four major hydrophobic regions and four major hydrophilic regions indicative of a topology similar to that of known connexins. Typical connexin consensus sequences were also observed in the first and second extracellular loops. During the acquisition of oocyte maturational competence, red seabream Cx31.5 mRNA transcription levels increased after treatment with gonadotropin-II. It is therefore proposed that expression of Cx31.5 contributes to the acquisition of oocyte maturational competence in this species.

Amino Acid Sequence↗

What happened to the "n" of sink? Children's spellings of final consonant clusters.

Children's spellings provide a window on their representations of spoken words. These representations may not always match those assumed by the conventional orthography. We examined one specific case in which this may be true, that of CVCC (consonant-vowel-consonant-consonant) syllables. In three experiments, first graders often produced spellings such as "sach" for the nonword [symbol: see text] and "pit" for the nonword /pIlt/. We suggest that many children consider these syllables to contain three phonemes instead of four phonemes. Rather than treating the postvocalic nasal or liquid as a separate phoneme, children consider it an attribute of the vowel. This suggestion was supported by the results of a phoneme counting test in which children often used three tokens for syllables such as [symbol: see text] and /pIlt/. The results suggest that, in addition to difficulties in gaining access to phonemes, nonstandard phonemic representations may be a stumbling block in the acquisition of alphabetic literacy.

Attention↗

A mechanism of membrane neutral lipid acquisition by the microsomal triglyceride transfer protein.

The microsomal triglyceride transfer protein (MTP) and apolipoprotein B (apoB) belong to the vitellogenin (VTG) family of lipid transfer proteins. MTP is essential for the intracellular assembly and secretion of apoB-containing lipoproteins, the key intravascular lipid transport proteins in vertebrates. We report the predicted three-dimensional structure of the C-terminal lipid binding cavity of MTP, modeled on the crystal structure of the lamprey VTG gene product, lipovitellin. The cavity in MTP resembles those found in the intracellular lipid-binding proteins and bactericidal/permeability-increasing protein. Two conserved helices, designated A and B, at the entrance to the MTP cavity mediate lipid acquisition and binding. Helix A (amino acids 725-736) interacts with membranes in a manner similar to viral fusion peptides. Mutation of helix A blocks the interaction of MTP with phospholipid vesicles containing triglyceride and impairs triglyceride binding. Mutations of helix B (amino acids 781-786) and of N780Y, which causes abetalipoproteinemia, have no impact on the interaction of MTP with phospholipid vesicles but impair triglyceride binding. We propose that insertion of helix A into lipid membranes is necessary for the acquisition of neutral lipids and that helix B is required for their transfer to the lipid binding cavity of MTP.

Amino Acid Sequence↗

Helicobacter pylori ribBA-mediated riboflavin production is involved in iron acquisition.

In this study, we cloned and sequenced a DNA fragment from an ordered cosmid library of Helicobacter pylori NCTC 11638 which confers to a siderophore synthesis mutant of Escherichia coli (EB53 aroB hemA) the ability to grow on iron-restrictive media and to reduce ferric iron. Sequence analysis of the DNA fragment revealed the presence of an open reading frame with high homology to the ribA gene of Bacillus subtilis. This gene encodes a bifunctional enzyme with the activities of both 3,4-dihydroxy-2-butanone 4-phosphate (DHBP) synthase and GTP cyclohydrolase II, which catalyze two essential steps in riboflavin biosynthesis. Expression of the gene (designated ribBA) resulted in the formation of one translational product, which was able to complement both the ribA and the ribB mutation in E. coli. Expression of ribBA was iron regulated, as was suggested by the presence of a putative FUR box in its promotor region and as shown by RNA dot blot analysis. Furthermore, we showed that production of riboflavin in H. pylori cells is iron regulated. E. coli EB53 containing the plasmid with H. pylori ribBA excreted riboflavin in the culture medium, and this riboflavin excretion also appeared to be iron regulated. We postulate that the iron-regulated production of riboflavin and ferric-iron-reduction activity by E. coli EB53 transformed with the H. pylori ribBA gene is responsible for the survival of EB53 on iron-restrictive medium. Because disruption of ribBA in H. pylori eliminates its ferric-iron-reduction activity, we conclude that ribBA has an important role in ferric-iron reduction and iron acquisition by H. pylori.

Aldehyde Oxidoreductases↗

Adult age differences in the effects of goals on self-regulated sentence processing.

The authors examined age differences in adults' allocation of effort when reading text for either high levels of recall accuracy or high levels of efficiency. Participants read a series of sentences, making judgments of learning before recall. Older adults showed less sensitivity than the young to the accuracy goal in both reading time allocation and memory performance. Memory accuracy and differential allocation of effort to unlearned items were age equivalent, so age differences in goal adherence were not attributable to metacognitive factors. However, comparison with data from a control reading task without monitoring showed that learning gains among older adults across trial were reduced relative to those of the young by memory monitoring, suggesting that monitoring may be resource consuming for older learners. Age differences in the responsiveness to (information-acquisition) goals could be accounted for, in part, by independent contributions from working memory and memory self-efficacy. Our data suggest that both processing capacity ("what you have") and beliefs ("knowing you can do it") can contribute to individual differences in engaging resources ("what you do") to effectively learn novel content from text.

Adult↗

Stroop effect in Spanish-English bilinguals.

The aim of this study was to analyze the performance of Spanish-English bilinguals on the Golden Stroop Test. The effects of bilingualism, participants' age, age of acquisition of the second language, and proficiency in each language were analyzed. Participants consisted of 71 Spanish-English bilinguals, 40 English monolinguals, and 11 Spanish monolinguals from South Florida. Proficiency in Spanish and English was established using a self-report questionnaire and the English and Spanish versions of the Boston Naming Test. In bilinguals, the Golden Stroop Test was administered in English and in Spanish. Overall, performance was slower in bilinguals than in monolinguals. No significant differences were observed in color reading but bilinguals performed worse in the naming color condition. Even though bilinguals were 5% to 10% slower in the color-word condition, one-way ANOVAs revealed no statistically significant differences between groups. Within the bilingual group, the Stroop Test scores were similar in both English and Spanish. Age of acquisition of the second language did not predict the Stroop Test performance. Repeated measures ANOVA demonstrated a significant interaction between Language Proficiency x Language (in which the test was administered) in some of the ST conditions. In balanced bilinguals, the language used in the ST did not matter, but in unbalanced subjects, the best-spoken language showed better results. In addition, our results support the presence of both between- and within-language interference in Spanish-English bilinguals. Different conceptualization models of the structure of bilingual memory are disclosed.

Adult↗

Cloning, complementation, and characterization of an rfaE homolog from Neisseria gonorrhoeae.

Neisseria gonorrhoeae WS1 is a spontaneous pyocin (a bacteriocin produced by Pseudomonas aeruginosa)-resistant mutant of N. gonorrhoeae FA19 that produces a truncated lipooligosaccharide (LOS) and is non-transformable. The LOS-specific mutation in WS1 was moved into a transformable background by transforming FA19 with chromosomal DNA from WS1 (generating strain JWS-1). A clone (pJCL2) capable of restoring JWS-1 to wild-type LOS expression, as detected by its acquisition of reactivity with monoclonal antibodies and by its complemented sodium dodecyl sulfate-polyacrylamide gel electrophoresis profile, was isolated. Sequential unidirectional deletion and DNA sequence analysis of pJCL2 identified an open reading frame, designated lsi-7, that could complement the defect in JWS-1. Homology searches against various databases indicated that lsi-7 bad homology with several Escherichia coli genes involved in the phosphorylation of sugars. lsi-7 is adjacent to the lsi-6 gene, another gene involved in LOS biosynthesis. Complementation studies using Salmonella typhimurium lipopolysaccharide mutants showed lsi-6 and lsi-7 to be gonococcal homologs of S. typhimurium rfaD and rfaE, respectively. Reverse transcriptase PCR analysis demonstrated that lsi-6 and lsi-7 are part of the same transcriptional unit.

Bacterial Proteins↗

90Y-ibritumomab tiuxetan in the treatment of relapsed or refractory B-cell non-Hodgkin's lymphoma.

OBJECTIVE: Non-Hodgkin's lymphoma (NHL) is the most frequently diagnosed malignancy of the immune system, with more than 53,900 new cases diagnosed in 2002. Conventional cancer therapies cure many, but not the majority of, cases of the aggressive forms of NHL, and the more indolent and follicular forms of the disease that affect nearly half of all patients with NHL are considered incurable. In the absence of cure or survival benefits, treatments such as radioimmunotherapy that induce remission and prolong time off therapy are considered valuable. (90)Y-Ibritumomab tiuxetan recently became the first radioimmunotherapy agent to be approved for commercial use by the U.S. Food and Drug Administration. After reading this article, the nuclear medicine technologist should be able to understand the incidence and prevalence of NHL, describe the ibritumomab tiuxetan therapy protocol, explain specific infusion techniques for this protocol, list acquisition parameters after injection of (111)In-ibritumomab tiuxetan, and describe specific safety techniques to keep risk as low as reasonably achievable while performing the therapy protocol.

Antibodies, Monoclonal↗

Organization of language areas in bilingual patients: a cortical stimulation study.

OBJECT: In an attempt to gain a better understanding of how multiple languages are represented in the human brain, the authors studied bilingual patients who underwent surgery for brain tumors, during which the authors mapped cortical language sites by using electrostimulation. METHODS: Reading, counting, and word retrieval tasks were studied in 12 right-handed bilingual patients with no language deficit. All bilingual patients were native to France. One patient spoke four languages. The patients constituted a nonhomogeneous group in terms of language proficiency or age of acquisition. Languages were evaluated and classified into three major groups, depending on proficiency and date of acquisition. Strict conditions of language site validation were applied, separating typical anomia sites from speech arrest or other language sites (such as hesitation sites). A total of 30 speech arrest sites, 16 anomia sites, and three sites of language difficulties (not typically classified as speech arrest) were found throughout the 26 language studies performed. Strict overlapping of language areas (for all language tasks) was found in five patients, whereas the remaining seven had at least one area that was language-specific and sometimes task-specific. Specific areas for a particular language were found for word retrieval tasks (anomia) in eight sites (50%) but also in six (20%) of the reading or counting sites (speech arrest), either in frontal (three patients) or in temporoparietal (four patients) regions. Among the four early bilingual patients tested (languages acquired before the age of 7 years), three had language-specific cortical areas. Interestingly, six patients in this series who had a discrepancy between two languages did not have more cortical areas devoted to the less proficient language (with acknowledgment of the limit in cortical exposure available for testing by the craniotomy). CONCLUSIONS: In this series, the authors found that bilingual patients could have common but also different cortical areas for both languages in temporoparietal areas and in frontal areas. In some cases, the authors found that language tasks such as counting, reading, or word retrieval in different languages can be sustained by language- and task-specific cortical areas. In bilingual patients, cortical mapping should ideally be performed using different language tasks in all languages in which the patient is fluent.

Adult↗

Quality of phonological representations, verbal learning, and phoneme awareness in dyslexic and normal readers.

This study of dyslexia was concerned with the quality of phonological representations of lexical items. It extended the studies of verbal learning in dyslexia from learning new vocabulary items (pseudo-names) to the learning of more well-specified variants of known words. The participants were 19 dyslexic adolescents in grades 4 to 6 and 19 younger normal readers in grade 2 matched on single word decoding. The dyslexics were significantly outperformed by the reading-age controls in non-word reading and in phoneme awareness. The dyslexics also took longer time to learn to associate a set of pseudo-names with pictures of persons although the dyslexics learned to associate familiar names with pictures as quickly as the controls did. The acquisition of new phonological representations of words was studied in an imitation task with maximally distinct pronunciations of long, familiar words. The dyslexics gained less than the controls in this task. They also gained less on one measure taken from a phoneme substitution task with the same words as in the distinctness task. The results are interpreted in the light of the hypothesis that poorly specified phonological representations may be an underlying problem in dyslexia.

Awareness↗

High speed 1H spectroscopic imaging in human brain by echo planar spatial-spectral encoding.

We introduce a fast and robust spatial-spectral encoding method, which enables acquisition of high resolution short echo time (13 ms) proton spectroscopic images from human brain with acquisition times as short as 64 s when using surface coils. The encoding scheme, which was implemented on a clinical 1.5 Tesla whole body scanner, is a modification of an echo-planar spectroscopic imaging method originally proposed by Mansfield Magn. Reson. Med. 1, 370-386 (1984), and utilizes a series of read-out gradients to simultaneously encode spatial and spectral information. Superficial lipid signals are suppressed by a novel double outer volume suppression along the contours of the brain. The spectral resolution and the signal-to-noise per unit time and unit volume from resonances such as N-acetyl aspartate, choline, creatine, and inositol are comparable with those obtained with conventional methods. The short encoding time of this technique enhances the flexibility of in vivo spectroscopic imaging by reducing motion artifacts and allowing acquisition of multiple data sets with different parameter settings.

Artifacts↗

The accuracy of computed tomography in assessing cervical pedicle screw placement.

STUDY DESIGN: A blinded, prospective comparison of computed tomography scan accuracy for determining the location of cervical pedicle screw position in human cadavers. OBJECTIVES: To establish recommended computed tomography technique guidelines for assessing location of cervical pedicle screws. SUMMARY OF BACKGROUND DATA: A small number of studies have described the accuracy of roentgenography regarding the assessment of pedicle screw position. However, a few studies have investigated the accuracy of computed tomography in this respect. Ebraheim et al evaluated the relation of lateral mass screws to the nerve roots within the intervertebral foramen on oblique radiographs. No study has been undertaken, to our knowledge, to specifically define the reliability and validity of computed tomography scans in the case of cervical pedicle screw placement. METHODS: As a pilot study, 10 cadaveric cervical spines from another study with bilateral 3.5 mm titanium pedicle screws were scanned with 1.0 mm axial slices. After the scans were interpreted by three blinded readers, each panel member was "trained" with regard to individual accuracy. Ten more cadaveric cervical spines were instrumented with 3.5 mm titanium screws in each pedicle (C2-C7). The specimens were then scanned with a variety of computed tomography techniques, including spiral acquisitions at 1.0 mm, 1.0 mm + reconstruction, 2.5 mm, 5.0 mm slices, and the three-dimensional Stealth Station recipes. The specimens were dissected, and malpositioned screws were recorded and photographed by independent raters. The same three readers from the pilot study then read each new scan in random order. RESULTS: Reader accuracies in the pretraining pilot study were 74%, 68%, and 52%, with kappa coefficients of 0.49, 0.37, and 0.07, respectively, and significant intrarater variances (P = 0.014). After training, the accuracy rate improved significantly to 89%, 88%, and 85% in posttraining study, and the kappa coefficients were 0.81, 0.78, and 0.73, respectively. Kappa statistical analysis showed negligible interreader variance on the entire pivotal study except by the three-dimensional Stealth Station format. The overall mean kappa coefficients were 0.77, 0.75, and 0.73. Assessment of pedicle screw position was statistically inferior with 5.0 mm axial slices, in contrast to slices <3.0 mm. CONCLUSIONS: We demonstrated that reliance on computed tomography scan data in determining the misplacement of a pedicle screw is usually accurate given proper scan acquisition, presentation windows, and adequate reader training, but a clinically significant error rate remains. A conventional computed tomography scan should not be treated as a gold standard, particularly without regard to the readers' training.

Bone Screws↗

Modeling of longitudinal academic achievement scores after pediatric traumatic brain injury.

In a prospective longitudinal study, academic achievement scores were obtained from youth 5 to 15 years of age who sustained mild-moderate (n = 34) or severe (n = 43) traumatic brain injuries (TBI). Achievement scores were collected from baseline to 5 years following TBI and were subjected to individual growth curve analysis. The models fitted age at injury, years since injury, duration of impaired consciousness, and interaction effects to Reading Decoding, Reading Comprehension, Spelling, and Arithmetic standard scores. Although scores improved significantly over the follow-up relative to normative data from the standardization sample of the tests, children with severe TBI showed persistent deficits on all achievement scores in comparison to children with mild-moderate TBI. Interactions of the slope and age parameters for the Arithmetic and Reading Decoding scores indicated greater increases over time in achievement scores of the children injured at an older age, but deceleration in growth curves for the younger children with both mild-moderate and severe TBI. These results are compatible with the hypothesis that early brain injuries disrupt the acquisition of some academic skills. Hierarchical regression models revealed that indexes of academic achievement obtained 2 years following TBI had weak relations with the duration of impaired consciousness and socioeconomic status. In contrast, concurrent cognitive variables such as phonological processing and verbal memory accounted for more variability in academic scores. Given the significant and persistent decrement in basic academic skills in youth with severe TBI, it is clear that head-injured youth require intensive, long-term remediation and intervention not only of the academic skills themselves, but also of those cognitive abilities that support the development and maintenance of reading and math.

Achievement↗

On the application of ultra-fast RARE experiments.

The ultra-fast application of the RARE experiment is described in detail, with special emphasis on its multifarious applications with preparation experiments that produce transverse magnetization. The factors affecting the temporal evolution of the magnetization during the experiment are described, and the implications for the slice profile when using a Gaussian refocusing pulse are experimentally examined. The choice of phase-encoding scheme for use with preparation experiments is discussed, as is the use of various phase-encoding schemes to reduce line broadening in the phase-encoding direction if a number of averages are acquired. An explanation for the decomposition of the echo are into two components if the read gradient is imbalanced is given, and the experimental conditions necessary for the coherent addition of these two echo groups are described. An alternative sequence that removes one of these groups from the acquisition window is proposed. The sensitivity of the sequence to flow and motion is investigated, and the drastic loss of signal in this situation explained. The in vivo and in vitro application of preparation experiments leading to the accurate measurement of T1, T2, diffusion constant, and magnetization transfer characteristics is presented. The implementation of zoom-imaging using spin- and stimulated-echo preparation is described, and 3D in vivo spin-echo zoom images are presented. Simple phantom experiments demonstrating the feasibility of chemical-shift selective and spectroscopic imaging are also given.

Animals↗