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Experience with the use of generalized data base management systems in cooperative group clinical trials (a project of the Gynecologic Oncology Group).

Roswell Park Management Information System (RPMIS) is a formatted video-based system of programs for file creation, data entry, editing, updating, retrieval, and report generation. It has been utilized in more than 800 intrainstitutional research studies at Roswell Park. The Gynecologic Oncology Group (GOG) is a multiinstitutional, multidisciplinary cooperative group. Its clinical trials encompass the planning, initiation, execution, analysis, and presentation of results of management and treatment of patients with gynecologic cancer. The GOG Statistical Office, located at Roswell Park Memorial Institute, is responsible for data management and analysis of all patients entered into GOG protocols. Present annual accrual is approximately 2000 patients per year; 38 protocols are actively accruing patients while follow-up continues on 14 studies that are closed to patient entry. A previous paper (J Med Syst 7:235-242, 1983) described a time study comparing use of RPMIS and a paper batch processing system in GOG data management. The time study results and potential advantages of RPMIS warranted a gradual total conversion to this system. Presently GOG maintains 43 separate, self-contained applications of RPMIS and routinely develops a new system in conjunction with each new study initiated. This paper documents GOG experience with RPMIS during the past 4 years.

Clinical Trials as Topic↗

Caloric and vestibular evoked myogenic potential tests in evaluating children with benign paroxysmal vertigo.

OBJECTIVE: This study applied caloric and vestibular evoked myogenic potential (VEMP) tests to evaluate whether children with benign paroxysmal vertigo (BPV) shares similar vestibular features with basilar type migraine. METHODS: Twenty subjects of each group including healthy and BPV children were enrolled in this study. Each subject underwent audiometry, caloric and VEMP tests. Diagnosis of BPV was based on the International Classification of Headache Disorder, second edition. RESULTS: All BPV children had normal hearing, bilaterally. Caloric test revealed normal responses in 13 patients and abnormal responses in 7 patients (35%). VEMP test showed 50% abnormality in BPV children, including absent and delayed responses. However, when results of caloric and VEMP testing were considered together, 70% of BPV children had abnormality, exhibiting non-significant difference compared with 75% abnormality in basilar type migraine. CONCLUSIONS: A combination of caloric and VEMP results reveals higher abnormality (70%) in BPV children, sharing similar features with basilar type migraine in adults, given the similarity of the two disorders. Thus, caloric and VEMP tests may serve as supplementary diagnostic tools in evaluating children with BPV.

Adolescent↗

Molecular diagnostics and integrated management challenges of tobacco streak virus: Current status and future perspectives.

Tobacco streak virus (TSV) is an economically important viral pathogen causing severe yield and quality losses in several agricultural, horticultural and medicinal crops worldwide. Its complex epidemiology involving sap transmission, infected pollen and pollen-feeding thrips, together with symptom similarity to other necrosis-inducing pathogens, frequently results in misdiagnosis and delayed disease management. This review critically evaluates recent advances in TSV diagnostics and integrated disease management strategies. Particular emphasis is placed on the transition from conventional biological and serological assays to advanced molecular diagnostics including reverse transcription polymerase chain reaction (RT-PCR), quantitative real-time PCR, multiplex PCR and emerging isothermal amplification technologies such as recombinase polymerase amplification (RPA) and loop-mediated isothermal amplification (LAMP). The review also highlights emerging innovations including CRISPR/Cas-based diagnostics in addition, integrated management approaches involving phytosanitation, weed reservoir management, vector ecology-based, host resistance breeding, RNA interference (RNAi) and genome editing technologies are critically analysed. Major challenges including inadequate field validation, limited multiplex capability, poor assay standardization and scarcity of resistant cultivars are discussed. Future objectives to develop quick, field-adaptable and durable TSV detection and management methods are additionally discussed.

CRISPR/Cas diagnostics↗

CRISPR/Cpf1-mediated knockout of FLG in human induced pluripotent stem cells generates a model for studying epidermal barrier dysfunction.

Loss of filaggrin (FLG) function impairs skin barrier formation and contributes to common inflammatory skin diseases. In this study, we established a FLG knockout human induced pluripotent stem cell (iPSC) line based on KOLF2.1 J using CRISPR/Cas12a (Cpf1)-mediated genome editing. A guide RNA targeting exon 2 introduced a homozygous mutation, which was confirmed by sequencing. The edited cells maintained typical pluripotent stem cell morphology, expressed key undifferentiated markers, and retained the ability to differentiate into all three germ layers. Karyotype and copy number variation (CNV) analyses confirmed genomic stability and parental origin; the cells were free of mycoplasma. This cell line enables studies of FLG-associated skin biology and pathology.

Humans↗

Separation methods for alkylating antineoplastic compounds.

The separating method for alkylating neoplastic compounds were reviewed based on the classification of the Merck Index (12th Edition). Each section, whenever available or relevant, was subdivided according to the following approach: stability studies, extraction methods, gas chromatography, high-performance liquid chromatography and capillary electrophoresis. At the end of each chapter a separate table summarizing the main characteristics of the separating method were established. In particular LODs and/or LOQs were expressed as quantity to facilitate comparison between methods. This review highlights the problems to measure trace levels of these compounds into biological fluids with respect to their instability, adsorption to glass and plastic or derivatization requirements. Over the last decades, HPLC seems to be more popular than GC for separating the alkylating agents. The development of narrow- or microbore LC coupled to MS is certainly the way to further improve both separation and sensitivity obtained in the different papers surveyed for this review.

Antineoplastic Agents, Alkylating↗

Automated lumen definition from 30 MHz intravascular ultrasound images.

One prerequisite for standard clinical use of intravascular ultrasound imaging is rapid evaluation of the data. The main quantities to be extracted from the data are the size and the shape of the lumen. Until now, no accurate, robust and reproducible method to obtain the lumen boundaries from intravascular ultrasound images has been described. In this study, 21 different (semi-)automated binary-segmentation methods for determining the lumen are compared with manual segmentation to find an alternative for the laborious and subjective procedure of manual editing. After a preprocessing step in which the catheter area is filled with lumen-like grey values, all approaches consist of two steps: (i) smoothing the images with different filtering methods and (ii) extracting the lumen by an object definition method. The combination of different filtering methods and object definition methods results in a total of 21 methods and 80 experiments. The results are compared with a reference image, obtained from manual editing, by use of four different quality parameters--two based on squared distances and two based on Mahalanobis distances. The evaluation has been carried out on 15 images, of which seven are obtained before balloon dilation and eight after balloon dilation. While for the post-dilation images no definite conclusions can be drawn, an automated contour model applied to images smoothed with a large kernel appears to be a good alternative to manual contouring. For pre-dilation images a fully automated active contour model, initialized by thresholding, preceded by filtering with a small-scale median filter is the best alternative for manual delineation. The results of this method are even better than manual segmentation, i.e. they are consistently closer to the reference image than the average distance of all individual manual segmentations.

Catheterization↗

Values for comparison of WAIS-III index scores with overall means.

The Wechsler Adult Intelligence Scale--Third Edition (WAIS-III; Wechsler, 1997b) provides factor-based index scores but allows only for pairwise comparison of these scores, producing inflated Type I error rates and reducing profile interpretability. This article provides tables for simultaneous comparison to the overall mean index score, thus reducing error rates and aiding interpretation. The Working Memory Index or Processing Speed Index can also be specifically compared when an individual is believed to have a condition, such as a learning disability or traumatic brain injury, associated with the selective depression of these indexes. Tables for the infrequency of specific differences are also provided, allowing the practitioner to note how unusual an obtained difference is in the general population.

Adult↗

An HLA-directed molecular and bioinformatics approach identifies new HLA-A11 HIV-1 subtype E cytotoxic T lymphocyte epitopes in HIV-1-infected Thais.

Only limited cytotoxic T lymphocyte (CTL) epitope mapping has been done in nonsubtype B HIV-infected persons. We used molecular immunogenetic tools to determine HIV-specific CTL responses in HIV-1 Env subtype E-infected female sex workers (FSWs) from northern Thailand, where more than 50% of the population is HLA-A11 positive. EpiMatrix, a computer-based T cell epitope prediction algorithm, and a manual editing approach were used to predict 77 possible HLA-A11 CTL epitopes in HIV-1, some of which were conserved between subtypes B and E. MHC binding of these peptides was determined in an HLA-A11 stabilization assay, and binding peptides were tested for CTL recognition in eight HLA-A11-positive FSWs. Subtype E versions of known HLA-A2 subtype B HIV epitopes were also tested in four HLA-A2 positive FSWs. CTL responses were detected in all HLA-A11-positive and in three of four HLA-A2-positive persons. Among the 12 FSWs responses to peptides were found to Pol in 9 (75%), Env in 7 (58%), Nef in 5 (42%), and Gag in 5 (42%), and to conserved epitopes in 8 (67%). To identify HLA-A11 CTL epitopes in the absence of prediction tools, it would have been necessary to test almost 3000 10-mer peptides. EpiMatrix and manual predictions reduced this number to 77, of which 26 were MHC binding and 12 were CTL epitopes. Six of these HLA-A11 CTL epitopes have not been previously reported and are located in RT, gp120, and gp41. This report of CTL responses in subtype E-infected individuals defines epitopes that may be useful in HIV pathogenesis or vaccine studies.

Algorithms↗

Alignment editing and identification of consensus secondary structures for nucleic acid sequences: interactive use of dot matrix representations.

We present a computer-aided approach for identifying and aligning consensus secondary structure within a set of functionally related oligonucleotide sequences aligned by sequence. The method relies on visualization of secondary structure using a generalization of the dot matrix representation appropriate for consensus sequence data sets. An interactive computer program implementing such a visualization of consensus structure has been developed. The program allows for alignment editing, data and display filtering and various modes of base pair representation, including co-variation. The utility of this approach is demonstrated with four sample data sets derived from in vitro selection experiments and one data set comprising tRNA sequences.

Algorithms↗

Geometry-driven photorealistic facial expression synthesis.

Expression mapping (also called performance driven animation) has been a popular method for generating facial animations. A shortcoming of this method is that it does not generate expression details such as the wrinkles due to skin deformations. In this paper, we provide a solution to this problem. We have developed a geometry-driven facial expression synthesis system. Given feature point positions (the geometry) of a facial expression, our system automatically synthesizes a corresponding expression image that includes photorealistic and natural looking expression details. Due to the difficulty of point tracking, the number of feature points required by the synthesis system is, in general, more than what is directly available from a performance sequence. We have developed a technique to infer the missing feature point motions from the tracked subset by using an example-based approach. Another application of our system is expression editing where the user drags feature points while the system interactively generates facial expressions with skin deformation details.

Algorithms↗

Interpreting course evaluation results: insights from thinkaloud interviews with medical students.

PURPOSE: To determine whether some of the fundamental assumptions that frequently underlie interpretation of course evaluation results are justified by investigating what medical students are thinking as they complete a typical basic science course evaluation. METHODS: A total of 24 students participated in thinkaloud cognitive interviews, voicing their thoughts while completing a typical evaluation instrument that included items on overall course design, educational materials and methods, and faculty teaching. Students' responses were organised to consider how they interpreted questions, formed judgements and selected response options. Major themes relevant to the meaningful interpretation of course evaluation data were identified. RESULTS: Medical students understood educational terms such as 'independent learning' in different ways from both one another and common usage. When formulating responses, students' judgements were sometimes based on unique or unexpected criteria, and they described editing their judgements by considering factors such as effort or caring on the part of teaching faculty. Students tended to avoid using the lower end of the rating scale, used the highest rating option selectively, but chose the second highest category indiscriminately. CONCLUSIONS: These results call into question fundamental assumptions that frequently underlie interpretation of course evaluation results, such as whether students understand the intended meanings of terms used in items; whether faculty members who receive the same rating are perceived similarly; whether ratings actually reflect teaching effectiveness, and whether 'positive' ratings reflect positive opinions. This study also demonstrates how thinkaloud interviews can be used in validity studies, providing information to supplement statistical and psychometric analyses.

Adult↗

The impact of migraine on patients with major depressive disorder.

BACKGROUND: The impact of migraine and other headache types among psychiatric outpatients with major depressive disorder (MDD) has not been fully described. OBJECTIVE: To investigate the impact of migraine on the severity, physical, and anxiety symptoms in patients with MDD and to examine the interaction between headache and depression. METHODS: This clinic-based study enrolled consecutive psychiatric outpatients meeting DSM-IV criteria for MDD. Headache types were diagnosed based on the International Classification of Headache Disorders, 2nd edition (2004). Three psychometric instruments were used to evaluate anxiety, depression, and physical components: the Hamilton Depression Rating Scale, the Beck Depression Inventory, and the Hospital Anxiety and Depression Scale. In addition, the interactions between headache and their depressive episode were also evaluated. RESULTS: Compared with patients without migraine, MDD patients with comorbid migraine (n = 73, 48.3%) had higher physical and anxiety scores on the three psychometric instruments. Migraine accounted for 5% to 11% of the variance of the total scores on the three psychometric scales. Approximately half (48.5%) of patients reported headache worsening during or after a depressive episode. CONCLUSIONS: Our study found that comorbidity of migraine in patients with MDD was associated with more anxiety and physical symptoms. Headache should not be considered as only a somatic symptom of depression, but should be treated as an important comorbid disorder because it might exacerbate or interact with depression during a depressive episode.

Adult↗

Identification of self through two-dimensional chemistry and synapses.

Cells in the immune and nervous systems communicate through informational synapses. The two-dimensional chemistry underlying the process of synapse formation is beginning to be explored using fluorescence imaging and mechanical techniques. Early analysis of two-dimensional kinetic rates (k(on) and k(off)) and equilibrium constants (K(d)) provides a number of biological insights. First, there are two regimes for adhesion-one disordered with slow k(on) and the other self-ordered with 10(4)-fold faster k(on). Despite huge variation in two-dimensional k(on), the two-dimensional k(off) is like k(off) in solution, and two-dimensional k(off) is more closely related to intrinsic properties of the interaction than the two-dimensional k(on). Thus difference in k(off) can be used to set signaling thresholds. Early signaling complexes are compartmentalized to generate synergistic signaling domains. Immune antigen receptor components have a role in neural synapse editing. This suggests significant parallels in informational synapse formation based on common two-dimensional chemistry and signaling strategies.

CD4 Antigens↗

Ceftazidime in the elderly: appropriateness of twice-daily dosing.

The disposition of drugs in the elderly is particularly relevant with antiinfectives, because this population has an increased risk of infections. Renal function deteriorates with age, yet dosage guidelines for antibiotics that allow for this reduction remain to be established. Ceftazidime, a cephalosporin with enhanced antipseudomonal activity that is eliminated primarily by glomerular filtration, has been evaluated in the elderly. Herein, we review ceftazidime's pharmacokinetic profile and dosing considerations in this population. Several aspects of renal function deteriorate with the normal aging process, including a decreased glomerular filtration rate (GFR). Using serum creatinine concentrations as an estimate of the GFR in the elderly is unreliable; a more reliable way of estimating GFR is the use of inulin or 51Cr-editic acid clearance or calculation from formulas or nomograms based on age, weight, sex, and serum creatinine. From pharmacokinetic studies it was found that the elderly individual without renal disease generally has an increased elimination half-life and decreased clearance of ceftazidime compared with a young person. A positive correlation (r = 0.7-0.95) was shown between ceftazidime clearance and GFR, suggesting that estimates of GFR may be used to determine the ceftazidime dose. In several studies, the trough (after 12 hours) ceftazidime serum concentration exceeded by several fold its minimum inhibitory concentration required to inhibit 90% of organisms for most commonly encountered organisms; efficacy and safety were also confirmed with an every-12-hour regimen. A twice-daily dosage regimen for ceftazidime in elderly patients with normal renal function should be considered based on age-related decreases in renal function and drug elimination.

Adult↗

WAIS-III factor index score patterns after traumatic brain injury.

Profile subtypes, based on the Wechsler Adult Intelligence Scale-Third Edition (WAIS-III) factor index scores, were examined in a sample of 166 patients with traumatic brain injury (TBI) by means of a two-stage clustering procedure. Three reliable subtypes were found that were differentiated primarily by level of performance across all factor index scores, although each of them demonstrated a relative weakness on the Processing Speed index. These subtypes were then validated on the basis of demographic variables, injury parameters, and additional psychometric measures that had not been included in the clustering procedures. The results indicated that performance on the WAIS-III after TBI was affected by both injury severity and level of education. It is concluded that there is no unique "signature" profile on the WAIS-III after TBI, except that a relative strength on the Processing Speed index is uncommon with this condition.

Adult↗

The criterion-related validity of the WISC-R performance scale and other nonverbal IQ tests for deaf children.

Despite the popularity of nonverbal IQ tests for psychoeducational assessment of deaf children, criterion-related validity is lacking. This may be because nonverbal IQ tests lack criterion-related validity, or because inappropriate scaling attenuates IQ achievement correlations. Two studies used samples of deaf children to test these hypotheses. The first study (N = 33) correlated WISC-R PIQs with Stanford Achievement Test-Hearing Impaired Edition (SAT-HI) grade equivalents and age-based percentiles (rs less than .37, NS). The second study (N = 64) correlated nonverbal IQs from many tests with SAT-HI scores (rs .05 to .42). The results implicate the hypothesis that criterion scale affects IQ-achievement correlations. The role of nonverbal IQ in the psychoeducational assessment of deaf children is discussed.

Achievement↗

[Strategy against nosocomial infections in France].

Because of their extent and due to the complexity of their management, nosocomial infections (NI) have become a public health problem in view of ethical and economical considerations. A decree, issued on 05.06.1988, organizes the supervision and the prevention of NI throughout the country and requires the setting up of a committee against nosocomial infections (CLIN) in every medical establishment. In 1992 five inter-areas coordination committees (C-CLIN) and one national technical struggle committee (CTIN) were established in France. A governmental plan was instituted in 1994. This plan, enacted in the 04.19.1995 text, focuses on the importance of reducing by 30% the frequency of NI by the year 2000. The creation of a NI cell in the Health Ministry and of operational hygiene teams in the hospitals have since then strenghtened the anti-infection system. The CLIN became a compulsory institution in the 1998 for private establishments and a new decree is to be issued at the end of 1999 and to come into force on 12.31.2001 at the latest. Finally, the decree n degrees 98-535 (07.01.1998) sets up the French Agencies for Health Safety and an Institute of Sanitary Supervision. Both structures are in charge of the surveillance system in Health establishments. The CTIN and the C-CLIN, together with groups of experts and learned societies (Superior Council for Public Hygiene in France, French Society for Hospital Hygiene, Health National Agency of Accreditation and Valuation), will edit official guide of technical recommendations. This ambitions strategy, based on education, information, supervision and prevention methods, requires a multidisciplinary mobilization and needs the compulsory support of the extire hospital community.

Cross Infection↗

Improving the quality of automatic DNA sequence assembly using fluorescent trace-data classifications.

Virtually all large-scale sequencing projects use automatic sequence-assembly programs to aid in the determination of DNA sequences. The computer-generated assemblies required substantial hand-editing to transform them into submissions for GenBank. As the size of sequencing projects increases, it becomes essential to improve the quality of the automated assemblies so that this time consuming hand-editing may be reduced. Current ABI sequencing technology uses base calls made from fluorescently-labeled DNA fragments run on gels. We present a new representation for the fluorescent trace data associated with individual base calls. This representation can be used before, during, and after fragment assembly to improve the quality of assemblies. We demonstrate one such use-end-trimming of sub-optimal data-that results in a significant improvement in the quality of subsequent assemblies.

Algorithms↗