一体化数字医院硬件平台设计

硬件平台是医院数字化体系中最重要、投资最大的基础设施，其方案的选择对硬件平台的经费投入、处理性能、安全性，扩展性、易管理性诸多方面产生直接影响。本文根据作者在制订方案时和两年多应用中的亲身体验，提出了数据物理集中、综合考虑性能、降低结构复杂度等建设原则。全面介绍了作者单位采用的SAN架构的集中存储方案，实现了全院业务和数据的集中处理和存储，做到了软件系统与硬件平台的完美统一，收到了满意的运行效果。结合SAN技术总结了该方案的优势和特点，这些优势和特点决定了该方案不仅适合于一体化软件系统，也适合于多厂商产品集成的系统。     

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.     

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.     

Association of interleukin 1 gene family polymorphisms with duodenal ulcer disease

Cytokine genes taking part in the immunological response to Helicobacter pylori infection are good candidates to study for genetic predisposition to duodenal ulcer disease (DU). Among cytokines, interleukin (IL)-1beta and its natural specific inhibitor, the interleukin-1 receptor antagonist, are cytokines that play a key role in regulating gastric acid secretion and modulating the immune response in the gastrointestinal mucosa. We aimed to investigate whether polymorphisms in the IL-1B and IL-1RN genes are involved in the susceptibility to duodenal ulcer. DNA from 131 unrelated Spanish Caucasian patients with DU and 105 ethnically matched healthy controls was typed for the IL-1B-511, IL-1B-31, and IL-1B + 3954 gene polymorphisms, and the VNTR polymorphism in intron 2 of the IL-1RN gene by polymerase chain reaction (PCR)-based methods and TaqMan assays. H. pylori status and non-steroidal anti-inflammatory drugs (NSAIDs) use was determined in all patients and controls. Logistic regression analysis identified H. pylori infection (OR: 9.74; 95%CI = 3.53-26.89) and NSAIDs use (OR: 8.82; 95%CI = 3.51-22.17) as independent risk factors for DU. In addition, the simultaneous carriage of IL-1RN*2, IL-1B-511*C, IL-1B-31*T and IL-1B + 3954*C alleles was a genetic risk factor for DU in patients with H. pylori infection (OR: 3.22; 95%CI = 1.09-9.47). No significant differences in IL-1RN and IL-1B genotypes were found when patients were categorized according to gender, age of onset, smoking habit, NSAIDs use, type of complication and positive family history. Our results provide further evidence that host genetic factors play a key role in the pathogenesis of duodenal ulcer.     

Heterogeneity of structural abnormalities in the 7q31.3 approximately q34 region in myeloid malignancies

Abnormalities in the long arm of chromosome 7 are a frequent chromosomal aberration in myeloid disorders. Most studies have focused on the analysis of del(7q), demonstrating the presence of several minimal deleted regions in 7q22 approximately q31. By contrast, few studies in myeloid disorders have been devoted to the analysis of translocations, either balanced or unbalanced, involving 7q. In this study, we used fluorescence in situ hybridization (FISH) to characterize the 7q31.3 approximately q34 region (markers D7S480-D7S2227) in patients with deletion or translocation of 7q. A total of 910 cases of myeloid disorders were studied by conventional cytogenetics. Fifty-eight (6%) patients had structural aberrations of 7q. FISH studies were carried out in the 27 patients with involvement of 7q31 approximately q34: 14 cases had an acute myelogenous leukemia and 13 cases had a myelodysplastic syndrome. FISH analysis revealed the existence of high complexity in the 7q31.3 approximately q34 region in patients with unbalanced translocations. No breakpoints in 7q31.3 approximately q34 were found in the cases with deletion or balanced translocation. Nevertheless, studies of unbalanced translocations showed several breakpoints in markers D7S480-D7S2227, which delineate a commonly altered region. The complexity of 7q rearrangements suggests that a synergy of different genetic factors, rather than the alteration of a single tumor suppressor gene, could be involved in the pathogenesis of del(7q) in myeloid disorders.