Extracting information on pneumonia in infants using natural language processing of radiology reports

Natural language processing (NLP) is critical for improvement of the healthcare process because it can encode clinical data in patient documents. Many clinical applications such as decision support require coded data to function appropriately. However, in order to be applicable for healthcare, performance must be adequate. A valuable automated application is the detection of infectious diseases, such as surveillance of pneumonia in newborns (e.g., neonates) because the disease produces significant rates of morbidity and mortality, and manual surveillance is challenging. Studies have demonstrated that automated surveillance using NLP is a useful adjunct to manual surveillance and an effective tool for infection control practitioners. This paper presents a study evaluating the feasibility of an NLP-based monitoring system to screen for healthcare-associated pneumonia in neonates. We estimated sensitivity, specificity, and positive predictive value by comparing results with clinicians' judgments. Sensitivity was 71% and specificity was 99%. Our results demonstrated that the automated method was feasible.     

Haplotype analysis of the BRCA2 9254delATCAT recurrent mutation in breast/ovarian cancer families from Spain

A frame-shift 9254del5 mutation was independently identified in 12 families, eleven of them with Spanish ancestors, in a BRCA2 screening performed in 841 breast and/or ovarian cancer families and in 339 women with breast cancer diagnosed before the age of 40 at different centers in France and Spain. We sought to analyze in detail the haplotype and founder effects of the 9254del5 and to estimate the time of origin of the mutation. Eight polymorphic microsatellite markers and two BRCA2 polymorphisms were used for the haplotype analyses. The markers were located flanking the BRCA2 gene spanning a region of 6.1 cM. Our results suggest that these families shared a common ancestry with BRCA2 9254del5, which is a founder mutation originating in the Northeast Spanish, with an estimated age of 92 (95% CI 56-141) generations.     

Worldwide genomic diversity of the human papillomaviruses-53, 56, and 66, a group of high-risk HPVs unrelated to HPV-16 and HPV-18

Among more than 200 human papillomavirus (HPV) types presumed to exist, 18 "high-risk" HPV types are frequently found in anogenital cancer. The best studied types are HPV-16 and 18, which are only distantly related to one another and form two separate phylogenetic branches, each including six closely related types. HPV-30, 53, 56, and 66 form a third phylogenetic branch unrelated to HPV-16 and 18. Worldwide comparison of HPV-16 and 18 isolates revealed a distribution of variant genomes that correlated with the geographic origin and the ethnicity of the infected cohort and led to the concept of unique African, European, Asian, and Native American HPV-16 and 18 variants. Here, we address the question whether similar phylogenies are found for HPV-53, 56, and 66 by determining the sequence of the long control regions (LCR) of these HPVs in samples from Europe, Asia, and Africa, and from immigrant societies in North and South America. Phylogenetic trees calculated from point mutations and a few insertions/deletions affecting 2-4.2% of the nucleotide sequences were distinct for each of the three HPVs and divergent from HPV-16 and 18. In contrast to the "star-phylogenies" formed by HPV-16 and 18 variants, 44 HPV-53 isolates represented nine variants, which formed two deep dichotomic branches reminiscent of the beginning split into two new taxa, as recently observed for subtypes of HPV-44 and 68. A total of 66 HPV-56 isolates represented 17 variants, which formed three branches preferentially containing European, Asian, and African variants. Variants of a fourth branch, deeply separated from the other three, were characterized by a 25 bp insertion and created a dichotomy rather than star-like phylogeny. As it contained isolates from cohorts in all continents, it may have evolved before the spread of humans into all continents. 18 of 31 HPV-66 isolates represented the prototype clone, which was found in all parts of the world, while the remaining 13 clones formed 11 branches without any geographic association. Our findings confirm the notion of a quantitatively limited genomic diversity of each HPV type with some correlation to the geographic origin of the sample. In addition, we observed in some variants of these three HPV types mutations that affect the amino acid sequence of the E6 oncoproteins and the L1 capsid protein, supporting the possibility of immunogenic and oncogenic diversity between variants of any HPV type.     

Recombinant cysteine proteinase from Leishmania (Leishmania) chagasi implicated in human and dog T-cell responses

High in vitro lymphoproliferative responses were induced in humans and dogs by a recombinant Leishmania (Leishmania) chagasi cysteine proteinase, with secretion of IFN-gamma in asymptomatic subjects or of IFN-gamma, interleukin 4 (IL-4), and IL-10 in oligosymptomatic subjects. In contrast, responses of symptomatic patients and dogs were lower, with production of IL-4 and IL-10.     

Cutaneous papillary squamous cell carcinoma. Report of three new cases and review of the literature

Squamous cell carcinoma is one of the most common malignant cutaneous tumors. Several histological variants have been described; the papillary subtype is one of the most infrequent, with only four cases having being reported previously. We report three new cases of this unusual variant of cutaneous squamous cell carcinoma, review the literature and consider the main differential diagnoses. Polymerase chain reaction performed in our three cases did not demonstrate human papilloma virus infection.     

Proprioception does not quickly drift during visual occlusion

Several perceptual studies have shown that the ability to estimate the location of the arm degrades quickly during visual occlusion. To account for this effect, it has been suggested that proprioception drifts when not continuously calibrated by vision. In the present study, we re-evaluated this hypothesis by isolating the proprioceptive component of position sense (i.e., the subjects were forced to rely exclusively on proprioception to locate their hand, which was not the case in earlier studies). Three experiments were conducted. In experiment 1, subjects were required to estimate the location of their unseen right hand, at rest, using a visual spot controlled by the left hand through a joystick. Results showed that the mean accuracy was identical whether the localization task was performed immediately after the positioning of the hand or after a 10-s delay. In experiments 2 and 3, subjects were required to point, without vision of their limb, to visual targets. These two experiments relied on the demonstration that biases in the perception of the initial hand location induced systematic variations of the movement characteristics (initial direction, final accuracy, end-point variability). For these motor tasks, the subjects did not pay attention to the initial hand location, which removed the possible occurrence of confounding cognitive strategies. Results indicated that movement characteristics were, on average, not affected when a 15-s or 20-s delay was introduced between the positioning of the arm at the starting point and the presentation of the target. When considered together, our results suggest that proprioception does not quickly drift in the absence of visual information. The potential origin of the discrepancy between our results and earlier studies is discussed.     

Sublingual immunotherapy for hazelnut food allergy: a randomized, double-blind, placebo-controlled study with a standardized hazelnut extract

BACKGROUND: Food allergy may be life-threatening, and patients affected need to receive accurate diagnoses and treatment. Hazelnut has often been implicated as responsible for allergic reactions, and trace quantities can induce systemic reactions. OBJECTIVE: The aim of this study was to evaluate the efficacy and tolerance of sublingual immunotherapy with a standardized hazelnut extract in patients allergic to hazelnut. METHODS: This was a randomized, double-blind, placebo-controlled study. Inclusion criteria were a history of hazelnut allergy and positive skin prick test and double-blind placebo-controlled food challenge results. Patients were then randomly assigned into 2 treatment groups (hazelnut immunotherapy or placebo). Efficacy was assessed by double-blind, placebo-controlled food challenge after 8 to 12 weeks of treatment. Blood samples were drawn for measurement of specific IgE, IgG(4), and serum cytokines before and after treatment. RESULTS: Twenty-three patients were enrolled and divided into 2 treatment groups. Twenty-two patients reached the planned maximum dose at 4 days. Systemic reactions were observed in only 0.2% of the total doses administered. Mean hazelnut quantity provoking objective symptoms increased from 2.29 g to 11.56 g (P = .02; active group) versus 3.49 g to 4.14 g (placebo; NS). Moreover, almost 50% of patients who underwent active treatment reached the highest dose (20 g), but only 9% in the placebo. Laboratory data showed an increase in IgG(4) and IL-10 levels after immunotherapy in only the active group. CONCLUSION: Our data confirm significant increases in tolerance to hazelnut after sublingual immunotherapy as assessed by double-blind, placebo-controlled food challenge, and good tolerance to this treatment.     

Histological study of the proximal and distal segments of the embryonic outflow tract and great arteries

The normal development of the ventricular outlets and proximal region of the great arteries is a controversial subject. It is known that the conus, truncus arteriosus (truncus), and aortic sac participate; however, there are some doubts as to the actual prospective fate of the truncus. Some authors propose that it gives origin to the proximal region of the great arteries and that the myocardial cells of its wall become smooth muscle. Nevertheless, others think that the truncus only forms the arterial valve apparatus and that therefore the myocardial cells transform into fibroblasts. As a first approach to beginning to elucidate which process occurs, the aim of this article was to study the histological changes in the wall of these components of the developing heart in chick embryos whose hearts had been labeled at the truncoconal boundary at stage 22HH, tracing the changes up to stage 36HH. Also, the histological constitution of the wall of the pulmonary arterial trunk and its valve apparatus were studied in the posthatching and adult hearts of chickens and rats. The conus and truncus walls were always encircled by a myocardial sleeve from the outset of their development. Between stages 26HH to 28HH, the truncal myocardial cells adjacent to the mesenchymal tissue of the ridges began to lose cell-to-cell contacts and invaded the extracellular matrix. At stage 24HH, the aortic sac began to project into the pericardial cavity and became divided into two channels by the aortic-pulmonary septum at stage 26HH. The wall of the aortic sac is mostly constituted by a compact mesenchymal tissue. Initially, it does not have smooth muscle but this starts to appear at stage 30HH. The insertion ring of the valves, a broad structure, was formed by mesenchymal tissue. Both structures were always covered by a myocardial sleeve. The leaflets developed from the truncal ridges, the segment immediately proximal to the aortic sac. Our results indicate that the proximal region of the pulmonary and aortic arteries do not originate from the truncus arteriosus; rather, we found that they take origin from the aortic sac. Thus, our findings agree with the proposal that the myocardial cells of the external sleeve of the truncus become fibroblastic and suggest that the insertion ring of the arterial valves has a dual origin: fibroblasts produced by truncal myocardial transdiferentiation and the mesenchymal tissue of the proximal region of the truncal ridges, while the leaflets have their origin from the truncal ridges. We discuss the fact that, because the truncus arteriosus does not give origin to the trunks of the aortic and pulmonary arteries, it may be necessary to modify terminology. Based on our results, together with the new findings obtained by in vivo labeling, immunostaining, a chimeric approach, and ultrastructural studies, we propose a developmental model that correlates the fate of the conus, truncus, and aortic sac with the normal morphogenesis of the ventricular outlet tracts and the trunks of the great arteries. (c) 2005 Wiley-Liss, Inc.     

Molecular peculiarities of the lytA gene isolated from clinical pneumococcal strains that are bile insoluble

The autolytic LytA amidase from 12 bile (deoxycholate)-insoluble streptococcal isolates (formerly classified as atypical Streptococcus pneumoniae) showing different antibiotic resistance patterns was studied. These atypical strains, which autolyze at the end of the stationary phase of growth, contain highly divergent lytA alleles (pairwise evolutionary distances of about 20%) compared to the lytA alleles of typical pneumococci. The atypical LytA amidases exhibit a peculiar deletion of two amino acids responsible for cell wall anchoring in the carboxy-terminal domain and have a reduced specific activity. These enzymes were inhibited by 1% deoxycholate but were activated by 1% Triton X-100, a detergent that could be used as an alternative diagnostic test for this kind of strain. Preparation of functional chimeric enzymes, PCR mutagenesis, and gene replacements demonstrated that the characteristic bile insolubility of these atypical strains was due to their peculiar carboxy-terminal domain and that the 2-amino-acid deletion was responsible for the inhibitory effect of deoxycholate. However, the deletion alone did not affect the specific activity of LytA. A detailed characterization of the genes encoding the 16S rRNA and SodA together with multilocus sequence typing indicated that the strains studied here are not a single clone and, although they cannot be strictly classified as typical pneumococci, they represent a quite diverse pool of organisms closely related to S. pneumoniae. The clinical importance of these findings is underlined by the role of the lytA gene in shaping the course of pneumococcal diseases. This study can also contribute to solving diagnostic problems and to understanding the evolution and pathogenic potential of species of the Streptococcus mitis group.