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Software for microbial fingerprinting by means of the infrared spectra.

Two computer programs were designed for helping in library handling and microbial identification by means of their infrared spectra. The program 'Transform' runs in the IR Data Manager environment and produces ASCII files containing transformed data from infrared absorbance spectra. The program 'WinSpectra' is written in Visual Basic v. 3.0. It imports the ASCII files created with 'Transform', and is able to handle, analyse and identify them by their mathematical comparison with a library of microbial spectra. Both programs run in graphical, menu-driven interface (GEM and MS Windows, for IBM-PC compatibles, with extensive on-line help.

Classification↗

How well do antidepressants work in older people? A systematic review of Number Needed to Treat.

OBJECTIVES: To make direct comparisons between studies of antidepressant treatment of older people using Number Needed to Treat (NNT) analysis. METHODS: Medline and Embase Search 1966-1999 and contact with manufacturers of antidepressant drugs asking for any relevant data on file; NNT analyses of outcome in terms of efficacy and adverse effects. RESULTS: Most antidepressant trials show efficacy; this is less clear for moclobemide and fluoxetine. Head-to-head comparisons between antidepressants showed significant superiority for paroxetine over fluoxetine and a trend in favour of SSRIs and venlafaxine over tricyclics. CONCLUSIONS: NNT analysis is one way of providing intelligible information on antidepressant efficacy and adverse effects which can inform clinical decisions. LIMITATIONS: Many studies do not present data in a form amenable to NNT analysis. Most head-to-head comparisons between antidepressants are underpowered.

Aged↗

Outcomes of workers' compensation claimants with low back pain undergoing intradiscal electrothermal therapy.

STUDY DESIGN: Case series. OBJECTIVE: To describe the outcomes of workers' compensation (WC) claimants who have had a lumbar intradiscal electrothermal therapy (IDET) procedure. SUMMARY OF BACKGROUND DATA: IDET was developed as a less invasive treatment alternative to fusion after failure of conservative treatment for discogenic low back pain (LBP). Initial IDET case series from single practices have reported improved pain, function, and return to work outcomes. Little is known about results when performed by a variety of providers or in WC populations. MATERIALS AND METHODS: LBP cases that underwent IDET between December 1, 1998 and February 29, 2000 were identified from WC records. Data sources included hardcopy claim files, administrative medical billing data, and computerized claim file narrative reports. Outcomes included narcotic use 6 months or more after IDET, additional invasive treatment after IDET (low back injections or surgery), and improved work status 24 months after IDET. RESULTS: One hundred forty-two cases from 23 states were identified, with 97 different providers performing the procedure. Mean duration of symptoms before IDET was 26 months. Mean follow-up duration after IDET was 22 months. Ninety-six (68%) of the cases did not meet one or more of the published inclusion criteria. Seventy-eight cases (55%) received at least two narcotic prescriptions 6 months or more after IDET. Fifty-three (37%) had at least one lumbar injection and 32 (23%) had lumbar surgery after IDET. A total of 55 (39%) were working at 24 months after IDET; of these, 28 (20%) were not working and 27 (19%) were working before IDET. Narcotic use after IDET was associated with narcotic use before IDET, the same provider performing discography and IDET (provider self-referral), and positive signs of radiculopathy (C = 0.80). Need for invasive lumbar procedures after IDET were associated with provider self-referral, narcotic use before IDET, and older age (C = 0.73). Continued work absence after IDET was associated with provider self-referral, male gender, litigation, narcotic use before IDET, and older age (C = 0.83). Conformance with published selection criteria for IDET was not associated with provider self-referral or outcomes, nor was duration before IDET associated with outcomes. CONCLUSION: The procedure may be less effective when performed by a variety of providers than suggested by initial case series performed by single providers or practices in work-related LBP cases. Provider self-referral and narcotic use before IDET are significant risk factors for poor outcomes. Randomized controlled trials are needed to determine whether there is a subset of patients with discogenic back pain who derive substantial and sustained benefit from this procedure.

Adult↗

Electronic signatures for long-lasting storage purposes in electronic archives.

Communication and co-operation in healthcare and welfare require a certain set of trusted third party (TTP) services describing both status and relation of communicating principals as well as their corresponding keys and attributes. Additional TTP services are needed to provide trustworthy information about dynamic issues of communication and co-operation such as time and location of processes, workflow relations, and system behaviour. Legal and ethical requirements demand securely stored patient information and well-defined access rights. Among others, electronic signatures based on asymmetric cryptography are important means for securing the integrity of a message or file as well as for accountability purposes including non-repudiation of both origin and receipt. Electronic signatures along with certified time stamps or time signatures are especially important for electronic archives in general, electronic health records (EHR) in particular, and especially for typical purposes of long-lasting storage. Apart from technical storage problems (e.g. lifetime of the storage devices, interoperability of retrieval and presentation software), this paper identifies mechanisms of e.g. re-signing and re-stamping of data items, files, messages, sets of archived items or documents, archive structures, and even whole archives.

Computer Security↗

Methods and framework for visualizing higher-order finite elements.

The finite element method is an important, widely used numerical technique for solving partial differential equations. This technique utilizes basis functions for approximating the geometry and the variation of the solution field over finite regions, or elements, of the domain. These basis functions are generally formed by combinations of polynomials. In the past, the polynomial order of the basis has been low-typically of linear and quadratic order. However, in recent years so-called p and hp methods have been developed, which may elevate the order of the basis to arbitrary levels with the aim of accelerating the convergence of the numerical solution. The increasing complexity of numerical basis functions poses a significant challenge to visualization systems. In the past, such systems have been loosely coupled to simulation packages, exchanging data via file transfer, and internally reimplementing the basis functions in order to perform interpolation and implement visualization algorithms. However, as the basis functions become more complex and, in some cases, proprietary in nature, it becomes increasingly difficult if not impossible to reimplement them within the visualization system. Further, most visualization systems typically process linear primitives, in part to take advantage of graphics hardware and, in part, due to the inherent simplicity of the resulting algorithms. Thus, visualization of higher-order finite elements requires tessellating the basis to produce data compatible with existing visualization systems. In this paper, we describe adaptive methods that automatically tessellate complex finite element basis functions using a flexible and extensible software framework. These methods employ a recursive, edge-based subdivision algorithm driven by a set of error metrics including geometric error, solution error, and error in image space. Further, we describe advanced pretessellation techniques that guarantees capture of the critical points of the polynomial basis. The framework has been designed using the adaptor design pattern, meaning that the visualization system need not reimplement basis functions, rather it communicates with the simulation package via simple programmatic queries. We demonstrate our method on several examples, and have implemented the framework in the open-source visualization system VTK.

Algorithms↗

[Informational structure of the national registry of bone marrow donor volunteers].

Successful Bone Marrow Transplantations with unrelated donors can be performed providing that donor and recipient are totally HLA-A, B, DR identical. To find such a suitable donor it is necessary to type a large pool of volunteers for HLA in histocompatibility laboratories. We have built a network of 36 micro-computers AT 286 for updating local files and for translating data to the national file of donors maintained on a main computer (VAX 8250). The main computer communicates regularly using modems with local computers in order to update data and exchange information. After one year of functioning, users are well satisfied with the computers system which locates regularly potential donors for recipients waiting for a graft.

Bone Marrow Transplantation↗

Susceptibility of beta-lactamase to core amino acid substitutions.

To determine which amino acids in TEM-1 beta-lactamase are important for its structure and function, random libraries were previously constructed which systematically randomized the 263 codons of the mature enzyme. A comprehensive screening of these libraries identified several TEM-1 beta-lactamase core positions, including F66 and L76, which are strictly required for wild-type levels of hydrolytic activity. An examination of positions 66 and 76 in the class A beta-lactamase gene family shows that a phenylalanine at position 66 is strongly conserved while position 76 varies considerably among other beta-lactamases. It is possible that position 76 varies in the gene family because beta-lactamase mutants with non-conservative substitutions at position 76 retain partial function. In contrast, position 66 may remain unchanged in the gene family because non-conservative substitutions at this location are detrimental for enzyme structure and function. By determining the beta-lactam resistance levels of the 38 possible mutants at positions 66 and 76 in the TEM-1 enzyme, it was confirmed that position 76 is indeed more tolerant of non-conservative substitutions. An analysis of the Protein Data Bank files for three class A beta-lactamases indicates that volume constraints at position 66 are at least partly responsible for the low tolerance of substitutions at this position.

Amino Acid Sequence↗

[Patients with fatigue in family practice: prevalence and treatment].

OBJECTIVE: To gain insight into the prevalence and treatment of severe fatigue in general practice. DESIGN: Secondary data analysis. METHOD: By means of an episode-oriented morbidity registration by 54 GPs throughout the Netherlands over the period 1985-1994 it was established how often in the course of one year 'fatigue' was listed as the reason for consultation, what diagnoses were then made, how long episodes of care because of 'fatigue' lasted and what interventions took place (n = 93,297). Of the patients with a care episode because of 'fatigue' lasting at least 6 months, age, sex, comorbidity and consumption of care were established; for this purpose use was also made of a file containing data on 4 years in succession (n = 9630). RESULTS: Per annum, 92 per 1000 listed patients consulted the GP because of fatigue. Somatic or psychic diagnoses were made in 27.7 per 1000 patients listed. The episode of care lasted 4 weeks at most in 86% and at least 6 months in approximately 4%. The GPs' management of patients with 'fatigue' included physical examination in 63% and blood testing in 34%, conversation in 35%, prescription of medication in 24% and referral to a specialist in 3%. Of the 97 patients with fatigue lasting longer than 6 months, 61% had a chronic disease or psychic problems. CONCLUSION: Fatigue is frequently encountered in general practice, but the estimate that one per 1000 listed patients meets the criteria of the chronic fatigue syndrome looks a little high. It appears that GPs, in accordance with recommendations, mostly adopt a policy of wait and see.

Adult↗

A multimodal data collection tool using REALbasic and Mac OS X.

This project uses REALbasic 3.5 in the Mac OS X environment for development of a configuration tool that builds a data collection procedure for investigating the effectiveness of sonified graphs. The advantage of using REALbasic with the Mac OS X system is that it provides rapid development of stimulus presentation, direct recording of data to files, and control over other procedural issues. The program can be made to run natively on the new Mac OS X system, older Mac OS systems, and Windows (98SE, ME, 2000 PRO). With modification, similar programs could be used to present any number of visual/auditory stimulus combinations, complete with questions for each stimulus.

Data Collection↗

Microarray data assembler.

SUMMARY: Large volumes of microarray data are generated and deposited in public databases. Most of this data is in the form of tab-delimited text files or Excel spreadsheets. Combining data from several of these files to reanalyze these data sets is time consuming. Microarray Data Assembler is specifically designed to simplify this task. The program can list files and data sources, convert selected text files into Excel files and assemble data across multiple Excel worksheets and workbooks. This program thus makes data assembling easy, saves time and helps avoid manual error. AVAILABILITY: The program is freely available for non-profit use, via email request from the author, after signing a Material Transfer Agreement with Johns Hopkins University.

Database Management Systems↗

The development of an automated method for analyzing communication rate in augmentative and alternative communication.

A significant barrier to evidence-based practice in Augmentative and Alternative Communication (AAC) is the lack of validated performance measures that can be used by speech-language pathologists and rehabilitation engineers to evaluate the communication and device use of AAC consumers. Recently an effort has been made to develop automated data-logging techniques to facilitate the transcription and analysis of the AAC speaker's device use. A major source of error for the automated measurement of communication rate is the presence of excessive Inter-Selection Intervals (ISIs) (i.e., pause times), for which no communicative activity is occurring. The goal of this study was to develop an automated technique to filter out extreme ISIs, while preserving true communication rate performance. AAC data log files were obtained from seven individuals participating in a 1-month field trial of an AAC technology. Two temporal filtering techniques (arbitrary and individual) were compared for their ability to eliminate excessive ISIs. Results indicated that use of an individualized temporal filter was more sensitive to performance variability than use of an arbitrary temporal filter. Further, the individualized temporal filter elevated the participants' communication rate (measured by words per minute) by a factor of 1.8 to 34.5 greater than that of the unfiltered communication rate estimate. In addition, the first AAC communication rate performance estimates taken from the field are presented. Implications for further research and the valid use of automated data logging and analysis are discussed.

Activities of Daily Living↗

[Diagnostic imaging and patient database managing systems: The integration of digital information in the experience of an intensive care center].

AIM: To present our experience with integrating digital information on Intensive Care Unit patients (clinical data, laboratory findings, imaging, etc) to create electronic patient records. MATERIAL AND METHODS: Using the hospital Intranet, a connection was established between the Local area Network (LAN) of the Intensive Care Unit (ICU) and the Digital Imaging and Communications in Medicine (DICOM(R)) network of the Radiology Department allowing to receive, process and archive digital images locally at the ICU. Using the software RADclient-RADimage, the information received was managed by an electronic patient record system (DIGISTAT by UMS-Unterberger Medical Software, Florence). All the above software runs on Microsoft WindowsNT 4.0 platforms. RESULTS: Images of various kinds and formats (CT, MRI, etc.) pertaining to the ICU patients were semi-automatically handled and filed on a local server acting as a central databank. The images were then included in the electronic patient record and made available to the end user who could view them using either web technologies (hypertexts were automatically generated that could be viewed through the widely available World Wide Web browsers) or specific viewing utilities supplied with DIGISTAT . DISCUSSION AND CONCLUSIONS: For the intensivist, the handling and filing of data on hospitalised or discharged patients for treatment or research purposes involves having to process large amounts of information. Furthermore, in the event of patients being re-admitted to the unit, it is crucial to have ready access to all the information regarding previous hospital stays, including diagnostic images, to avoid the need for time-consuming searches through the hospital s paper-based archives. The possibility to access clinical information and diagnostic images using a single computer programme proved to be useful both for evaluating the patient s conditions immediately after the imaging procedure and for monitoring the patient s progress over time by comparing the different diagnostic images and imaging procedures. This pilot experience could be seen to provide the basic know-how for applying the method in the future Emergency Department of the A. Gemelli Hospital in Rome.

Computer Communication Networks↗

Influence of medical school applicants' demographic and cognitive characteristics on interviewers' ratings of noncognitive traits.

BACKGROUND: Interviews are commonly used to measure noncognitive traits of medical school applicants. The present study investigated the influence of knowledge of applicants' cognitive abilities on interviewers' ratings of noncognitive traits. METHOD: Academic and demographic predictors of interview ratings of applicants' noncognitive traits were examined at the Medical University of South Carolina College of Medicine during two years: 1992, when applicants' Medical College Admission Test (MCAT) total scores and undergraduate grade-point averages (GPAs) were available to interviewers; and 1993, when MCAT and GPA data were not available. In 1992, 226 applicants met study criteria (i.e., they received ratings from three interviewers in addition to having MCAT and GPA data on file); in 1993, 245 applicants met the criteria. Step-wise regression analyses were conducted to measure the influences of seven independent variables on applicants' interview ratings. Two-way analyses of variances and t-tests were used to determine the effects of gender of applicants and interviewers. Cronbach's alpha coefficients were used as measures of interviewers' reliability. RESULTS: GPA was the best predictor for both years but accounted for double the amount of variance in interview ratings in 1992 (15.7%) compared with 1993 (7.4%). The reliability coefficients for the interviewers were .496 for 1992 and .473 for 1993. CONCLUSION: If the goal of the medical school admission interview is to assess noncognitive traits independently from academic skills, the authors recommend that MCAT and GPA data not be available to interviewers during interviews. The authors also found that gender and race influenced interview ratings in accordance with affirmative-action goals. Finally, the authors found that interview scores were only moderately reliable across different interviewers. They discuss ways to increase their reliability.

Analysis of Variance↗

LIGPLOT: a program to generate schematic diagrams of protein-ligand interactions.

The LIGPLOT program automatically generates schematic 2-D representations of protein-ligand complexes from standard Protein Data Bank file input. The output is a colour, or black-and-white, PostScript file giving a simple and informative representation of the intermolecular interactions and their strengths, including hydrogen bonds, hydrophobic interactions and atom accessibilities. The program is completely general for any ligand and can also be used to show other types of interaction in proteins and nucleic acids. It was designed to facilitate the rapid inspection of many enzyme complexes, but has found many other applications.

Algorithms↗

Prediction of a common beta-propeller catalytic domain for fructosyltransferases of different origin and substrate specificity.

The three-dimensional (3D) structure of fructan biosynthetic enzymes is still unknown. Here, we have explored folding similarities between reported microbial and plant enzymes that catalyze transfructosylation reactions. A sequence-structure compatibility search using TOPITS, SDP, 3D-PSSM, and SAM-T98 programs identified a beta-propeller fold with scores above the confidence threshold that indicate a structurally conserved catalytic domain in fructosyltransferases (FTFs) of diverse origin and substrate specificity. The predicted fold appeared related to that of neuraminidase and sialidase, of glycoside hydrolase families 33 and 34, respectively. The most reliable structural model was obtained using the crystal structure of neuraminidase (Protein Data Bank file: 5nn9) as template, and it is consistent with the location of previously identified functional residues of bacterial levansucrases (Batista et al., 1999; Song & Jacques, 1999). The sequence-sequence analysis presented here reinforces the recent inclusion of fungal and plant FTFs into glycoside hydrolase family 32, and suggests a modified sequence pattern H-x (2)-[PTV]-x (4)-[LIVMA]-[NSCAYG]-[DE]-P-[NDSC][GA]3 for this family.

Amino Acid Sequence↗

Comparison of two cyclosporine formulations in healthy Middle Eastern volunteers: bioequivalence of the new Sigmasporin Microoral and Sandimmun Neoral.

A study was conducted to establish bioequivalence between two oral cyclosporine 100 mg capsules, Sigmasporin Microoral (Gulf Pharmaceutical Industries - Julphar, United Arab Emirates, under technical co-operation with Sigma Pharma, Brazil) and Sandimmun Neoral (Novartis, Switzerland), in a Middle Eastern population, even though both formulations were found to be bioequivalent earlier in a Brazilian population (data on file). It was designed as a randomized, open label, two-way crossover study in which 30 fasting, healthy male volunteers received a single 100 mg cyclosporine dose with 240 ml of water on two treatment days separated by a 1 week washout period. After dosing, serial blood samples were collected for a period of 24 h. Plasma was analyzed for cyclosporine A by a sensitive, reproducible and accurate HPLC method with MS detection capable of detecting cyclosporine A in the range of 5-400 ng/ml with a limit of quantitation of 5 ng/ml. Various pharmacokinetic parameters including AUC(0-t), AUC(0- proportional, variant ), C(max), T(max), T(1/2), and lambda(Z) were determined from plasma concentrations of both formulations. AUC(0-t), AUC(0- proportional, variant ), and C(max) were tested for bioequivalence after log-transformation of data. No significant difference was found based on ANOVA; 90% confidence intervals (82.98-110.57% for AUC(0-t), 81.57-124.71% for AUC(0- proportional, variant ), 80.15-98.91% for C(max)) for these parameters were found to be within the bioequivalence acceptance range of 80-125%. Based on these statistical inferences, it was concluded that Sigmasporin Microoral is bioequivalent to Sandimmun Neoral.

Administration, Oral↗

Bridging between two standards for collecting information on race and ethnicity: an application to Census 2000 and vital rates.

OBJECTIVES: The 2000 Census, which provides denominators used in calculating vital statistics and other rates, allowed multiple-race responses. Many other data systems that provide numerators used in calculating rates collect only single-race data. Bridging is needed to make the numerators and denominators comparable. This report describes and evaluates the method used by the National Center for Health Statistics to bridge multiple-race responses obtained from Census 2000 to single-race categories, creating single-race population estimates that are available to the public. METHODS: The authors fitted logistic regression models to multiple-race data from the National Health Interview Survey (NHIS) for 1997-2000. These fitted models, and two bridging methods previously suggested by the Office of Management and Budget, were applied to the public-use Census Modified Race Data Summary file to create single-race population estimates for the U.S. The authors also compared death rates for single-race groups calculated using these three approaches. RESULTS: Parameter estimates differed between the NHIS models for the multiple-race groups. For example, as the percentage of multiple-race respondents in a county increased, the likelihood of stating black as a primary race increased among black/white respondents but decreased among American Indian or Alaska Native/black respondents. The inclusion of county-level contextual variables in the regression models as well as the underlying demographic differences across states led to variation in allocation percentages; for example, the allocation of black/white respondents to single-race white ranged from nearly zero to more than 50% across states. Death rates calculated using bridging via the NHIS models were similar to those calculated using other methods, except for the American Indian/Alaska Native group, which included a large proportion of multiple-race reporters. CONCLUSION: Many data systems do not currently allow multiple-race reporting. When such data systems are used with Census counts to produce race-specific rates, bridging methods that incorporate geographic and demographic factors may lead to better rates than methods that do not consider such factors.

Adolescent↗

Recombinant human tumor necrosis factor receptor (p75) Fc fusion protein (TNFR:Fc) in rheumatoid arthritis.

BACKGROUND: Tumor necrosis factor (TNF) is the dominant mediator of the cytokine cascade that causes inflammation and joint destruction in rheumatoid arthritis. A new class of agents under investigation, the biologic TNF inhibitors, inhibits the activity of TNF. Recombinant human TNF receptor p75 Fc fusion protein (TNFR:Fc; Enbrel) blocks the activity of the cytokine TNF. The preclinical, Phase I, and Phase II data of TNFR:Fc in rheumatoid arthritis are reviewed in this article. METHODS: All available data on TNFR:Fc in rheumatoid arthritis were reviewed. These data included published literature and data on file at the manufacturer. RESULTS: TNFR:Fc has been effective in many models of inflammation, including animal models of rheumatoid arthritis and in clinical rheumatoid arthritis trials. Conclusions from a study with TNFR "knockout" mice (genetically altered mice incapable of producing TNFR proteins) demonstrated that p75 TNFR is a natural antagonist of TNF-mediated inflammation. A placebo-controlled, dose-escalation, Phase I trial evaluated the safety and efficacy of TNFR:Fc in patients with rheumatoid arthritis. There were no serious adverse effects reported. A Phase II, randomized, double-blind, placebo-controlled trial evaluated 180 patients with active rheumatoid arthritis whose previous therapy had failed. A dose-response relationship was observed in the number of tender and swollen joints; patients who received the highest dose (16 mg/m2) of TNFR:Fc had the greatest improvement. Treatment was generally well tolerated. TNFR:Fc is nonimmunogenic; no antibodies to TNFR:Fc have been detected thus far in human studies. CONCLUSIONS: Preliminary data indicate that TNFR:Fc is an excellent candidate for future long-term studies in the treatment of rheumatoid arthritis.

Animals↗