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Children's Yale-Brown Obsessive Compulsive Scale: reliability and validity.

OBJECTIVE: To evaluate the reliability and validity of a semistructured measure of obsessive-compulsive symptom severity in children and adolescents with obsessive-compulsive disorder (OCD). METHOD: Sixty-five children with OCD (25 girls and 40 boys, aged 8 to 17 years) were assessed with the Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS). Interrater agreement was assessed by four raters in a subsample (n = 24). Discriminant and convergent validity were assessed by comparing CY-BOCS scores to self-ratings of depression, anxiety, and obsessive-compulsive symptoms. RESULTS: Internal consistency was high, measuring .87 for the 10 items. The intraclass correlations for the CY-BOCS Total, Obsession, and Compulsion scores were .84, .91, and .68, suggesting good to excellent interrater agreement for subscale and total scores. The CY-BOCS Total score showed a significantly higher correlation with a self-report of obsessive-compulsive symptoms (r = .62 for the Leyton survey) compared with the Children's Depression Inventory (r = .34) and the Children's Manifest Anxiety Scale (r = .37) (p = .02 and .05, respectively). CONCLUSIONS: The CY-BOCS yields reliable and valid subscale and total scores for obsessive-compulsive symptom severity in children and adolescents with OCD. Reliability and validity appear to be influenced by age of the child and the hazards associated with integrating data from parental and patient sources.

Adolescent↗

Clinical applications of the Shack-Hartmann aberrometer.

The efficacy of the Shack-Hartmann technique for measuring the optical aberrations of the eye was evaluated for four classes of clinical conditions associated with optically abnormal eyes. These categories (with specific examples) are: anomalies of the tear film (dry eye), corneal disease (keratoconus), corneal refractive surgery [laser-assisted in situ keratomileusis (LASIK)], and lenticular cataract. We show that in each of these cases, it is possible to obtain at least a partial topographic map of the refractive aberrations of the patient's eyes, but severe losses of data integrity can occur. We further show that the Shack-Hartmann aberrometer provides additional information about the eye's imperfections on a very fine spatial scale (< 0.4 mm) which scatter light and further degrade the quality of the retinal image. Taken together, spatial maps of the variation of optical aberrations and scatter across the eye's entrance pupil represents an improved description of the optical imperfections of the abnormal eye.

Cataract↗

Telemedicine in plastic surgery: E-consult the attending surgeon.

Telemedicine has evolved into a valuable but underused resource for the delivery of health care to patients at a distance, particularly where patient transport is impractical, expensive, complicated, and/or urgent. Today, over 250,000 telemedicine consults are generated annually, involving various specialties in both military and civilian health delivery systems. The ability to evaluate and triage plastic surgery patients through the use of telemedicine has not been widely explored. We have designed, developed, and tested a "store-and-forward" solution at UMass Memorial Hospital and Beth Israel Deaconess Hospital whereby the plastic surgery residents who responded to a consult request transmitted digital photographs by means of the Internet to the attending physician on call. The customary telephone call between resident and attending physician benefited from the additional photographic data, and patient management resulted in a clear, concise, and unambiguous treatment plan. The initial management suggested by the resident was modified on some occasions, particularly with complex problems. The use of digital images was especially helpful for evaluation of radiographs and complex wounds of the hand and face. The solution proved to be very valuable for both attending physicians and residents in plastic surgery. The photographs provide rich detail and resolution comparable to high-quality prints. The mechanics of obtaining images and the process of sending them electronically was readily mastered. Images reached their destination in only a few minutes over standard telephone lines. No problems were encountered while sending or viewing images on Macintosh or Windows platforms. Determining course of action with a complete clinical history now includes a level of visual detail previously not available. As this application expands into wider use, data integrity and safety will have to be more formally secured and monitored. Our model of telemedicine has broad-reaching ramifications for the improvement of health-care delivery locally, nationally, and internationally.

Adult↗

Remarks on the role of economic modeling.

BACKGROUND: Despite the growing scholarly acceptance of quantitative evaluation methods, modelers still struggle to define an appropriate role for their work at the decision-making level. GOAL: To make observations about the policy relevance of mathematical and economic policy modeling in HIV and sexually transmitted disease prevention and treatment. RESULTS: The debate is framed within the context of the inevitability of decision making. Viewed in this light, models can inform choices between competing alternatives by leveraging existing information, integrating data from multiple sources, addressing "what if" questions, evaluating future scenarios, and providing a uniform metric for evaluation. CONCLUSIONS: The goal of model-based evaluation should not be to supplant the decision maker, but rather to redefine the terms of the debate using quantitative methods that make the beliefs and values that lie at the heart of all difficult choices explicit.

HIV Infections↗

Studying the human-environment phenomenon using the science of complexity.

The principal argument of the present article is that a new theoretical paradigm capable of facilitating the understanding of complex phenomena is necessary to study nursing's claim to its science as the science of unitary human beings, or the integrality between humans and the environment. A research study of the complex human-environment phenomenon illuminating a four-phase methodology is presented. It is argued that much can be learned by the use of the science of complexity to integrate data gleaned from different approaches to knowledge generation into a comprehensive understanding of the human being in the environment as a unified whole.

Adaptation, Psychological↗

Prevention of osteoporosis and uterine effects in postmenopausal women taking raloxifene for 5 years.

OBJECTIVE: Raloxifene hydrochloride (60 mg/day) is a selective estrogen receptor modulator indicated for the prevention and treatment of postmenopausal osteoporosis. Raloxifene treatment for 3 years increases bone mineral density (BMD) and, unlike tamoxifen (a triphenylethylene selective estrogen receptor modulator), does not stimulate the endometrium in healthy postmenopausal women. The effect of longer duration of treatment with raloxifene is not known. Therefore, the main objectives of these analyses are (1) to compare the effect of 5 years of treatment with raloxifene (60 mg/day) with placebo in terms of the likelihood of developing osteoporosis and (2) to evaluate the effect of 5 years of raloxifene treatment on the endometrium and incidence of vaginal bleeding. DESIGN: The current analyses include integrated data from two identically designed, prospective, double-blinded trials including postmenopausal women (mean age, 55 years) randomly assigned to either placebo (n = 143) or raloxifene (60 mg/day; n = 185). Osteoporosis and osteopenia were diagnosed according to World Health Organization criteria, using the manufacturer's database for the lumbar spine and the National Health and Nutrition Examination Survey's 1998 reference base for the hip. Endometrial thickness was determined using transvaginal ultrasonography. Clinical diagnoses of endometrial hyperplasia or endometrial cancer were confirmed by blinded review of histopathology reports. RESULTS: Compared with the case of placebo, raloxifene treatment for 5 years reduced bone turnover markers (osteocalcin: -10.9%, P < 0.001; bone-specific alkaline phosphatase: -7.2%, P = 0.042; urinary C-telopeptide: -11.1%, P = 0.034) and was associated with increased BMD in the lumbar spine (2.8%; P < 0.001) and total hip BMD (2.6%; P < 0.001). Women taking raloxifene were less likely to develop osteoporosis (relative risk [RR] for raloxifene v placebo: 0.13; 95% CI: 0.00, 0.37; P = 0.001) or osteopenia (RR: 0.23; 95% CI: 0.00, 0.81; P = 0.038) at the lumbar spine and were more likely to convert to normal BMD status at the lumbar spine (RR: 4.01; 95% CI: 1.34, 11.23; P = 0.043) and total hip (RR: 3.92; 95% CI: 1.12,14.27; P = 0.011) at 5 years, compared with the case of placebo. Raloxifene also significantly reduced total cholesterol (-5.5%; P < 0.001) and low-density lipoprotein cholesterol (-8.7%; P < 0.001), compared with the case of placebo. No significant changes in high-density lipoprotein cholesterol (P = 0.257) or triglycerides (P = 0.620) were detected. Incidence of hot flashes was higher among women taking raloxifene compared with those taking placebo [raloxifene, 47 (28.8%); placebo, 21 (16.8%); P = 0.017]. Women taking placebo or raloxifene reported a similar incidence of vaginal bleeding (P = 0.999) or of mean endometrial thickness of more than 5 mm at baseline and at each visit, up to the 5-year endpoint (P >/= 0.349). No diagnoses of endometrial hyperplasia or endometrial cancer were made in either treatment group. CONCLUSIONS: Five years of raloxifene treatment in healthy postmenopausal women preserves BMD, significantly reduces the likelihood of development of osteoporosis, and was not associated with an increased rate of vaginal bleeding, endometrial hyperplasia, or endometrial carcinoma, compared with the case of placebo.

Bone Density↗

Multimodal monitoring in the neurological intensive care unit.

BACKGROUND: Neurocritical care is a specialty that focuses on the critical care management of patients with catastrophic neurologic diseases. Brain ischemia and hypoxia are often central causes of brain damage in these patients. Until recently, the only methods widely accepted for monitoring in the neurological intensive care unit have been intracranial pressure and cerebral perfusion pressure monitoring. Recent developments in technology have resulted in several new monitoring techniques that can provide the neurointensivist with information, at the cellular level, that can help guide management. REVIEW SUMMARY: The brain requires a continuous blood-borne supply of oxygen and glucose for normal metabolism. Ischemia occurs when supply is insufficient to meet the metabolic demand. Cerebral blood flow can now be directly monitored using laser Doppler or thermal diffusion techniques. Transcranial cerebral oximetry can estimate regional cerebral oxygen saturation, although the reliability is questionable. Jugular bulb oximetry can provide a global assessment of oxygen delivery, and consumption and brain tissue oxygen tension monitoring can provide a focal measurement of cerebral oxygenation. Intracerebral microdialysis can provide information about glucose metabolism and the overall health of the neuron. CONCLUSIONS: New monitoring techniques can provide the neurointensivist with crucial information about brain physiology and metabolism. Combining these techniques ("multimodal monitoring") can produce a more accurate overall picture. This approach, along with new computer systems for integrating data at the bedside, may change the way patients with brain injury are monitored and treated in the future.

Brain↗

Digital EEG: trouble in paradise?

Digital EEG embodies enormous technological advances, but also presents new problems that users have not previously encountered and are still learning to deal with. Digital recording and display can produce unique artifacts, data distortion, and risks to data integrity. If used incautiously, digital displays may obscure important activity.

Analog-Digital Conversion↗

DGKH-mediated phosphatidic acid oncometabolism as a driver of self-renewal and therapy resistance in HCC.

BACKGROUND AND AIMS: HCC is characterized by metabolic pathway aberrations, which enable cancer cells to meet their energy demands and accelerate malignant progression. Identifying novel metabolic players governing therapy resistance and self-renewal in HCC is crucial, as these properties are likely responsible for tumor recurrence. APPROACH AND RESULTS: Clinical traits and RNA-seq of patients with HCC in The Cancer Genome Atlas were used for weighted gene coexpression network analysis, where 1 module was significantly correlated with advanced pathological stage and stem cell population maintenance. Further analysis of this module by integrating data obtained from HCC patient nonresponders to tyrosine kinase inhibitors identified 361 commonly deregulated genes. Intriguingly, these genes are significantly enriched in the intracellular signal transduction pathway, with diacylglycerol kinase eta (DGKH) ranked as the most enriched gene in poorly differentiated HCC tumors. Clinically, DGKH was elevated in tumor tissues compared to nontumor tissues. Patients with higher DGKH expression exhibited a more undifferentiated state and were less responsive to tyrosine kinase inhibitors. Functional assays using DGKH-manipulated HCC cell lines demonstrated that DGKH augmented aggressive features, including cancer stemness, therapy resistance, and metastasis. Upstream of DGKH , we discovered that the E1A-associated protein p300 (EP300) binds to DGKH's promoter region, thereby increasing its transcriptomic expression. Mechanistically, DGKH promotes mTOR signaling by producing phosphatidic acid. In an immunocompetent mouse model, cotreatment with sorafenib and liver-directed AAV8-mediated Dgkh depletion significantly reduced tumor burden, self-renewal, phosphatidic acid production, and mTOR signaling. CONCLUSIONS: Our research demonstrated that DGKH is a crucial oncometabolic regulator of cancer stemness and therapy resistance, suggesting that inhibiting DGKH may lead to more effective HCC treatment.

Humans↗

Analysis of the molecular mechanism underlying di(2-ethylhexyl) phthalate-induced bladder carcinogenesis via network toxicology and molecular docking approaches: An observational study.

This study aims to investigate the toxicity of di(2-ethylhexyl) phthalate (DEHP) and the potential molecular mechanisms of DEHP-induced bladder cancer (BLCA) using network toxicology and molecular docking strategies. The toxicity of DEHP was assessed using Prox-II software, and potential targets for DEHP-induced BLCA were identified by integrating data from ChEMBL database, Search Tool for Interactions of Chemicals, SwissTargetPrediction, GeneCards, Therapeutic Target Database, Online Mendelian Inheritance in Man, and The Cancer Genome Atlas. STRING database and Cytoscape were employed to construct target networks and determine core targets. The expression levels of core targets were analyzed using R. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed on potential and core targets. Molecular docking was carried out using CB-Dock 2 to verify the interactions between DEHP and core targets. A total of 105 potential targets related to DEHP-induced BLCA were identified, from which 7 core targets were selected: cyclin-dependent kinase 1, interleukin 6, cyclin-dependent kinase 2, cyclin B1, Erb-B2 receptor tyrosine kinase 2, cyclin B2, and B-cell lymphoma 2. IL-6 and B-cell lymphoma 2 showed downregulated expression in tumor tissues, while cyclin-dependent kinase 1, cyclin-dependent kinase 2, cyclin B1, Erb-B2 receptor tyrosine kinase 2, and cyclin B2 were upregulated. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses indicated that these targets were enriched in cell signaling and cancer-related pathways. Molecular docking confirmed that DEHP interacts with these core targets. DEHP may promote the development of BLCA by interacting with key proteins and signaling pathways. This study provides a theoretical basis for understanding the molecular mechanisms of DEHP-induced BLCA and offers references for future prevention and treatment strategies.

Diethylhexyl Phthalate↗

Proposal of a new halobacterial genus Natrinema gen. nov., with two species Natrinema pellirubrum nom. nov. and Natrinema pallidum nom. nov.

A phylogenetic analysis of 69 halobacterial 16S rRNA gene sequences has been carried out, integrating data from new isolates, previously described halobacteria and cloned sequences from uncultivated halobacteria. Halobacterium halobium NCIMB 777, Halobacterium trapanicum NCIMB 784 and Halobacterium salinarium NCIMB 786, together with several other strains (strains T5.7, L11 and Halobacterium trapanicum NCIMB 767) constitute a distinct lineage with at least 98.2% sequence similarity. These strains have been incorrectly assigned to the genus Halobacterium. Therefore, based on a variety of taxonomic criteria, it is proposed that Halobacterium salinarium NCIMB 786 is renamed as Natrinema pellirubrum nom. nov., the type species of the new genus Natrinema gen. nov., and that Halobacterium halobium NCIMB 777 and Halobacterium trapanicum NCIMB 784 are renamed as a single species, Natrinema pallidum nom. nov. It was notable that halobacteria closely related to the proposed new genus have been isolated from relatively low-salt environments.

DNA, Archaeal↗

Integrated and sequence-ordered BAC- and YAC-based physical maps for the rat genome.

As part of the effort to sequence the genome of Rattus norvegicus, we constructed a physical map comprised of fingerprinted bacterial artificial chromosome (BAC) clones from the CHORI-230 BAC library. These BAC clones provide approximately 13-fold redundant coverage of the genome and have been assembled into 376 fingerprint contigs. A yeast artificial chromosome (YAC) map was also constructed and aligned with the BAC map via fingerprinted BAC and P1 artificial chromosome clones (PACs) sharing interspersed repetitive sequence markers with the YAC-based physical map. We have annotated 95% of the fingerprint map clones in contigs with coordinates on the version 3.1 rat genome sequence assembly, using BAC-end sequences and in silico mapping methods. These coordinates have allowed anchoring 358 of the 376 fingerprint map contigs onto the sequence assembly. Of these, 324 contigs are anchored to rat genome sequences localized to chromosomes, and 34 contigs are anchored to unlocalized portions of the rat sequence assembly. The remaining 18 contigs, containing 54 clones, still require placement. The fingerprint map is a high-resolution integrative data resource that provides genome-ordered associations among BAC, YAC, and PAC clones and the assembled sequence of the rat genome.

Animals↗

Genomic structure and evolution of the ancestral chromosome fusion site in 2q13-2q14.1 and paralogous regions on other human chromosomes.

Human chromosome 2 was formed by the head-to-head fusion of two ancestral chromosomes that remained separate in other primates. Sequences that once resided near the ends of the ancestral chromosomes are now interstitially located in 2q13-2q14.1. Portions of these sequences had duplicated to other locations prior to the fusion. Here we present analyses of the genomic structure and evolutionary history of >600 kb surrounding the fusion site and closely related sequences on other human chromosomes. Sequence blocks that closely flank the inverted arrays of degenerate telomere repeats marking the fusion site are duplicated at many, primarily subtelomeric, locations. In addition, large portions of a 168-kb centromere-proximal block are duplicated at 9pter, 9p11.2, and 9q13, with 98%-99% average sequence identity. A 67-kb block on the distal side of the fusion site is highly homologous to sequences at 22qter. A third ~100-kb segment is 96% identical to a region in 2q11.2. By integrating data on the extent and similarity of these paralogous blocks, including the presence of phylogenetically informative repetitive elements, with observations of their chromosomal distribution in nonhuman primates, we infer the order of the duplications that led to their current arrangement. Several of these duplicated blocks may be associated with breakpoints of inversions that occurred during primate evolution and of recurrent chromosome rearrangements in humans.

Animals↗

A physical map of the Leishmania major Friedlin genome.

An extensive physical map of the Leishmania major Friedlin genome has been assembled by the combination of fingerprint analysis of a shuttle vector cosmid library and probe hybridization. The integrated data obtained for 9004 fingerprinted clones and 974 probes have placed 91.2% of the 33.58-Mb genome into contigs representing each of the 36 chromosomes. This first-generation map has already provided a suitable framework for both high-throughput DNA sequencing and functional studies of the L. major parasite.

Animals↗

The comprehensive mouse radiation hybrid map densely cross-referenced to the recombination map: a tool to support the sequence assemblies.

We have developed a unique comprehensive mouse radiation hybrid (RH) map of nearly 23,000 markers integrating data from three international genome centers and over 400 independent laboratories. We have cross-referenced this map to the 0.5-cM resolution recombination-based Jackson Laboratory (TJL) backcross panel map, building a complete set of RH framework chromosome maps based on a high density of known-ordered anchor markers. We have systematically typed markers to improve coverage and resolve discrepancies, and have reanalyzed data sets as needed. The cross-linking of the RH and recombination maps has resulted in a highly accurate genome-wide map with consistent marker order. We have compared these linked framework maps to the Ensemble mouse genome sequence assembly, and show that they are a useful medium resolution tool for both validating sequence assembly and elucidating chromosome biology.

Animals↗

Time-resolved plasma spectroscopy of thin foils heated by a relativistic-intensity short-pulse laser.

Time-resolved K-shell x-ray spectra are recorded from sub-100 nm aluminum foils irradiated by 150-fs laser pulses at relativistic intensities of Ilambda(2)=2 x 10(18) W microm(2)/cm(2). The thermal penetration depth is greater than the foil thickness in these targets so that uniform heating takes place at constant density before hydrodynamic motion occurs. The high-contrast, high-intensity laser pulse, broad spectral band, and short time resolution utilized in this experiment permit a simplified interpretation of the dynamical evolution of the radiating matter. The observed spectrum displays two distinct phases. At early time, < or =500 fs after detecting target emission, a broad quasicontinuous spectral feature with strong satellite emission from multiply excited levels is seen. At a later time, the He-like resonance line emission is dominant. The time-integrated data is in accord with previous studies with time resolution greater than 1 ps. The early time satellite emission is shown to be a signature of an initial large area, high density, low-temperature plasma created in the foil by fast electrons accelerated by the intense radiation field in the laser spot. We conclude that, because of this early time phenomenon and contrary to previous predictions, a short, high-intensity laser pulse incident on a thin foil does not create a uniform hot and dense plasma. The heating mechanism has been studied as a function of foil thickness, laser pulse length, and intensity. In addition, the spectra are found to be in broad agreement with a hydrodynamic expansion code postprocessed by a collisional-radiative model based on superconfiguration average rates and on the unresolved transition array formalism.

Journal Article↗

Plant genome resources at the national center for biotechnology information.

The National Center for Biotechnology Information (NCBI) integrates data from more than 20 biological databases through a flexible search and retrieval system called Entrez. A core Entrez database, Entrez Nucleotide, includes GenBank and is tightly linked to the NCBI Taxonomy database, the Entrez Protein database, and the scientific literature in PubMed. A suite of more specialized databases for genomes, genes, gene families, gene expression, gene variation, and protein domains dovetails with the core databases to make Entrez a powerful system for genomic research. Linked to the full range of Entrez databases is the NCBI Map Viewer, which displays aligned genetic, physical, and sequence maps for eukaryotic genomes including those of many plants. A specialized plant query page allow maps from all plant genomes covered by the Map Viewer to be searched in tandem to produce a display of aligned maps from several species. PlantBLAST searches against the sequences shown in the Map Viewer allow BLAST alignments to be viewed within a genomic context. In addition, precomputed sequence similarities, such as those for proteins offered by BLAST Link, enable fluid navigation from unannotated to annotated sequences, quickening the pace of discovery. NCBI Web pages for plants, such as Plant Genome Central, complete the system by providing centralized access to NCBI's genomic resources as well as links to organism-specific Web pages beyond NCBI.

Biotechnology↗

DIABCARD CCMIS--a portable and scalable CPR for diabetes care.

The aim of this paper is to introduce the main software module of the DIABCARD Chip Card Medical Information System (DIABCARD CCMIS) that provides an online, portable diabetes medical record information system based on a high performance object-oriented rapid application development language such as Borland Delphi. A chip card based medical information system was developed as a good possibility to create a portable electronic patient record. In particular the patient data card makes the up-to-date patient's record available whenever needed. The developed DIABCARD Core System, described in this paper, includes a patient record management system that has the ability to handle topics such as administrative and medical data, medical anamnesis, and physical examination data. Issues tackled were simplicity, data security and reporting, customization, and internationalization. Especially for the two last issues (customization and internationalization) a novel approach based on using native initialization table files is presented. Proper care has been addressed during the development of the software modules for matters of security, data integrity and confidentiality.

Database Management Systems↗