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Developing and implementing an ongoing competency evaluation program for rehabilitation nurses.

Ongoing competency evaluation of all nursing staff in rehabilitation settings is mandated by regulatory bodies. Rehabilitation nurse educators are challenged to design competency evaluation programs that meet regulatory standards, promote the professional development of rehabilitation nurses, and are cost-effective. The competence of rehabilitation nurses is maintained through a combination of ongoing assessment and education activities. Key components of program development include identifying critical nursing and rehabilitation nursing skills; developing an efficient documentation system; designing the evaluation, program promotion, and implementation activities; and evaluating the program. The strategies described meet administrative and educational needs.

Clinical Competence↗

Some relationships among assessments of depression.

The Directions program provides an administratively efficient method to screen for psychological disorders in a primary-care setting (FOCUS), confirm the need for treatment, and monitor progress (COMPASS-PC). The instruments are psychometrically sound and grounded in an established theory of mental-health treatment. The present study reports the relationships between FOCUS, COMPASS-PC, and the Hamilton Depression scale for a sample of patients who have been diagnosed as major depressive disorder, dysthymia, or depressive syndrome by standardized criteria (i.e., SCID-IV and DSM-IV). Moreover, Focus and COMPASS-PC are evaluated for their ability to detect depression as defined by SCID-IV and DSM IV. Furthermore, we examine the relationship between the different instruments in their ability to measure response to treatment over time.

Adult↗

Development and optimization of an adenovirus production process.

Adenoviral vectors have a number of advantages such as their ability to infect post-mitotic tissues. They are produced at high titers and are currently used in 28% of clinical protocols targeting mainly cancer diseases through different strategies. The major disadvantages of the first generation of recombinant adenoviruses are addressed by developing new recombinant adenovirus vectors with improved capacity and safety and reduced inflammatory response. To meet increasing needs of adenovirus vectors for gene therapy programs, parallel development of efficient, scalable and reproducible production processes is required. HEK-293 complementing cell line physiology, metabolism and viral infection kinetics were studied at small scale to identify optimal culture conditions. Batch, fed-batch and perfusion culture modes were evaluated. Development of new monitoring tools (in situ GFP probe) and quantification techniques (HPLC determination of total viral particles) contributed to acceleration of process development. On-line monitoring of physiological parameters such as respiration and biovolume of the culture allowed real-time supervision and control of critical phases of the process. Use of column chromatographic steps instead of CsCl gradient purification greatly eased process scale-up. The implementation of the findings at large scale led to the development of an optimized and robust integrated process for adenovirus production using HEK-293 cells cultured in suspension and serum-free medium. The two-step column-chromatography purification was optimized targeting compliance with clinical material specifications. The complete process is routinely operated at a 20-L scale and has been scaled-up to 100 L. Scale-up of adenoviral vector production in suspension and serum-free medium, and purification according to regulatory requirements, are achievable. To overcome metabolic limitations at high cell densities, use of perfusion mode with low-shear cell retention devices is now a common trend in adenovirus manufacturing. Further process improvements will rely on better understanding of the mechanisms of virus replication and maturation in complementing host cells.

Adenoviridae↗

LODVIEW: a computer program for the graphical evaluation of lod score results in exclusion mapping of human disease genes.

For linkage analysis projects aimed at mapping hereditary disease genes in humans, hundreds of highly polymorphic microsatellite markers which can be typed by PCR (PCR markers) have become available. With this technical improvement, the availability of a technique allowing for transparency in the handling of rapidly generated lod score data is becoming important. We present a computer program LODVIEW for the graphical representation of lod score data. It is designed for the input of lod score data generated with the LINKAGE package or similar programs. LODVIEW consists of 24 preformatted files, one for each chromosome. Each file contains a table for the input of lod score data and a file for the graphical representation of the data, which will show automatically any entry that is made in the respective input table. The program provides the user with published PCR marker information pre-entered into a table and graph at the correct positions corresponding to the genetic distances between markers. The graphical display of LODVIEW allows for the rapid evaluation of lod score results calculated from PCR markers on each chromosome. The following information can be obtained from the graphical display at one glance: (i) Regions of exclusion (Z(theta) < -2) and nonexclusion, (ii) markers with positive lod scores, (iii) the distribution of positive and negative lod scores among the families examined (indication of genetic heterogeneity), (iv) multipoint lod scores, and (v) the availability of PCR markers in regions of interest. The program is continually updated for novel PCR marker information from the literature. The program will help to efficiently monitor and direct the progress of exclusion mapping projects.

Chromosome Mapping↗

Implementation of three-dimensional EEG brain mapping.

The electroencephalogram (EEG) visualization software was developed containing two-dimensional (2D) and three-dimensional (3D) brain mapping modules. The input to the program is standard clinical individual patient data recorded using digital EEG and magnetic resonance imaging (MRI). The software utilizes several techniques, such as heuristic triangulation, ray casting, Gouraud shading, and image fusion to form multimodal 3D images. The program has been applied to the 3D visualization of various EEG signals, "cortical" EEG signals, and potential fields generated by a computer model. The developed program appears to operate efficiently and intuitively in PC/Windows environment.

Algorithms↗

Sequence analysis of an 800-kb genomic DNA region on chromosome 8q21 that contains the Nijmegen breakage syndrome gene, NBS1.

An 800-kb region on chromosome 8q21, which complements the phenotype of cells from Nijmegen breakage syndrome patients, is a candidate for the locus of the underlying gene, termed NBS1. The sequence of this 800-kb region of DNA indicated that the size of this segment is 755,832 bp with an additional 36-kb gap. From this region, we identified four genes including NBS1, a gene coding for a 27-kDa vitamin D-dependent calcium-binding protein (27-kDa calbindin), the mitochondrial 2,4-dienoyl-CoA reductase gene, and a novel gene, C8orf1/hT41. All four genes were aligned in a 250-kb centromeric portion of the region, and no gene was found in the remaining telomeric portion containing 500 kb. The genomic organization of the C8orf1/hT41 and NBS1 genes has been analyzed using the computer programs GRAIL 2 and GENSCAN. They predicted and successfully found more than 93% of the exons, even a small 54-bp exon, indicating that one or more exons in any gene can be identified by these programs. GENSCAN was more efficient at locating the four genes than GRAIL 2 and identified 15 of the 16 exons of the NBS1 gene. This 800-kb region contained repetitive sequences, including 179 copies of the Alu sequence (1 copy/4.2 kb), 123 copies of the L1 sequence (1 copy/6.1 kb), 107 copies of the LTR sequence (1 copy/7.1 kb), and 63 copies of the MER sequence (1 copy/12 kb). There was a slight but not significant difference in the repetitive content of the gene-rich region and the remaining noncoding region. Our results indicate that computer-assisted methods are useful and powerful for identifying exons of both known and novel genes.

Abnormalities, Multiple↗

Protein folding in the ER.

The endoplasmic reticulum (ER) is a major protein folding compartment for secreted, plasma membrane and organelle proteins. Each of these newly-synthesized polypeptides folds in a deterministic process, affected by the unique conditions that exist in the ER. An understanding of protein folding in the ER is a fundamental biomolecular challenge at two levels. The first level addresses how the amino acid sequence programs that polypeptide to efficiently arrive at a particular fold out of a multitude of alternatives, and how different sequences obtain similar folds. At the second level are the issues introduced by folding not in the cytosol, but in the ER, including the risk of aggregation in a molecularly crowded environment, accommodation of post-translational modifications and the compatibility with subsequent intracellular trafficking. This review discusses both the physicochemical and cell biological constraints of folding, which are the challenges that the ER molecular chaperones help overcome.

Calcium↗

Breast cancer screening, with particular reference to the concept of 'high risk' groups.

An overview is presented of the salient aspects of the DOM-project of breast cancer screening carried out in the city of Utrecht, the Netherlands. Results on stage at diagnosis, case-fatality, and mortality rates suggest that the program has been effective. Attention is devoted to the issue whether knowledge about risk factors for breast cancer is helpful in making a screening program more effective or efficient. It is concluded that such knowledge is of limited importance.

Breast Neoplasms↗

Improved efficiency of protein structure calculations from NMR data using the program DIANA with redundant dihedral angle constraints.

A new strategy for NMR structure calculations of proteins with the variable target function method (Braun, W. and Go, N. (1985) J. Mol. Biol., 186, 611) is described, which makes use of redundant dihedral angle constraints (REDAC) derived from preliminary calculations of the complete structure. The REDAC approach reduces the computation time for obtaining a group of acceptable conformers with the program DIANA 5-100-fold, depending on the complexity of the protein structure, and retains good sampling of conformation space.

Amino Acid Sequence↗

Women at risk for developing osteoporosis: determination by total body neutron activation analysis and photon absorptiometry.

With stepwise multiple logistic regression (MLR), probabilistic classification equations were developed to identify asymptomatic women who are at risk for development of fracture of the spine. Clinically normal women with low TBCa/square root H ratios can be classified as at risk for osteoporosis prior to their developing spinal compression fractures. With receiver operating characteristic (ROC) analysis, it was possible to verify the accuracy of the MLR model to discriminate "normal" women at risk, with high sensitivity and specificity. With the MLR model, discrimination of osteoporotic women (50-59 years) was made correctly for 86.2% of the total osteoporotic subjects with the TBCa data. Similar models were derived from the photon absorptiometry data. From the spinal density (BDs) data, correct classification in the 50-59 year group was 55.6% of the total osteoporosis subjects; from the radius density (BMCr) data, the corresponding value was 31%. The highest probability of identifying osteoporosis in all age categories was, therefore, on the basis of TBCa data. Similar, but less accurate discrimination was achieved with the BDs and BMCr data. These conclusions were confirmed by the application of receiver operating characteristic (ROC) analysis. Correct identification of the population at risk permits the timely and efficient application of therapeutic programs prior to onset of fracture. In a serial study of 104 peri-menopausal women, for example, it was possible to determine the P value for individuals measured annually over a 3-10 year period and thus to predict normal individuals at risk for developing osteoporosis each year.

Age Factors↗

[Current patient perceptions of the physician].

BACKGROUND: The structure and organisation of German hospitals currently are undergoing radical change forced by reforms in the German public health system. Operating procedures, efficiency assays, and management programs compete with the traditional philanthropic relationship between physician and patient. To analyse this problem by scientific means, inpatients were interviewed in standardised fashion on current expectations, ideals, and experience with that relationship. PATIENTS AND METHODS: During 4 weeks, 507 inpatients were interviewed. The structured questionnaire used consisted of nine closed multiple-choice questions. The proband sex ratio was balanced, and their age pattern represented the typical patient collective in our clinic. RESULTS AND CONCLUSION: The patient perception of physicians' roles described clear priorities. Besides a skilled expert, the patients were looking for a friend and guide through their disease, diagnosis, and therapy. The paternalistic relationship between physician and patient thus is not very antiquated. In contrast, material institutional criteria, provision of services, and hotel-like atmosphere played secondary roles.

Aged↗

Population development by phenotypic selection with subsequent marker-assisted selection for line extraction in cucumber (Cucumis sativus L.).

Cucumber (Cucumis sativus L.; 2n = 2x = 14) has a narrow genetic base, and commercial yield of US processing cucumber has plateaued in the last 15 years. Yield may be increased by altering plant architecture to produce unique early flowering (days to flower, DTF), female (gynoecious, GYN), highly branched (multiple lateral branching, MLB), long-fruited (length:diameter ratio, L:D) cultivars with diverse plant statures. The genetic map position of QTL conditioning these quantitatively inherited yield component traits is known, and linked molecular markers may have utility in marker-assisted selection (MAS) programs to increase selection efficiency, and effectiveness. Therefore, a base population (C0), created by intermating four unique but complementary lines, was subjected to three cycles (C1-C3) of phenotypic (PHE) mass selection for DTF, GYN, MLB, and L:D. In tandem, two cycles of marker-assisted backcrossing for these traits began with selected C2 progeny (C2S) to produce families (F1[i.e., C2S x C2S], and BC(1) [i.e., F1 x C2S]) for line extraction, and for comparative analysis of gain from selection by PHE selection, and MAS. Frequencies of marker loci were used to monitor selection-dependent changes during PHE selection, and MAS. Similar gain from selection was detected as a result of PHE selection, and MAS for MLB (approximately 0.3 branches/cycle), and L:D (approximately 0.1 unit increase/cycle) with concomitant changes in frequency at linked marker loci. Although genetic gain was not realized for GYN during PHE selection, the percentage of female flowers of plants subjected to MAS was increased (5.6-9.8% per cycle) depending upon the BC1 population examined. Selection-dependent changes in frequency were also detected at marker loci linked to female sex expression during MAS. MAS operated to fix favorable alleles that were not exploited by PHE selection in this population, indicating that MAS could be applied for altering plant architecture in cucumber to improve its yield potential.

Biomarkers↗

Experience with a questionnaire administered by emergency medical service for pre-hospital identification of patients with acute stroke.

We prospectively verified whether an ad-hoc questionnaire administered by phone supports pre-hospital suspicion of stroke in order to reduce the time before care is given. From June 1996 to May 1997, physicians of the Emergency Medical Service in the area of Bergamo, Italy asked all people calling for a patient with symptoms and signs suggesting a cerebral vascular injury to immediately answer some questions on common symptoms and signs of stroke. The medical records of the patients hospitalized at Ospedali Riuniti of Bergamo were reviewed at the end of the study by a single neurologist, skilled in stroke management and blinded to the questionnaires. Sensitivity and specificity, in addition to positive and negative predictive values, of single questions versus final diagnosis were assessed. Logistic regression analysis was also performed to identify those questions useful to suspect strokes. We collected 143 valid questionnaires, related to 63 men and 80 women, aged 34-99 years (mean, 71.8 years). The question concerning headache had the lowest sensitivity and specificity, respectively 57.1% and 36.5%, and the question concerning leg palsy had the highest sensitivity and specificity, respectively 82.0% and 52.4%. Multivariate analysis identified questions on facial and leg palsy as independent predictors of a final diagnosis of stroke. A few questions on motor deficits proposed by emergency medical service operators may be useful in the pre-hospital identification of stroke patients. Concordance of any questions versus final diagnosis of stroke was, however, far to be satisfying. Thus, our experience supports the need for an educational program to improve the efficiency of a pre-hospital diagnosis of stroke.

Adult↗

The Mental Health Needs Council of Harris County: a case report on community collaboration and adult mental illness prevalence assessment and service need analysis.

Accurate mental illness prevalence and service needs assessment are critical to the development and delivery of effective mental health programs. Assessment precision and efficient service development and delivery are best facilitated by a close collaboration of all relevant major stakeholders. This report examines the history, mission, and composition of the Mental Health Needs Council of Harris County, Texas. This Council, located in Houston, has for the past 25 years investigated mental health service problems and recommended strategies for their solution. This Council consists of all of Harris County's major public service providers, professional groups and advocacy organizations. This report traces the evolution of the Council's prevalence and needs assessment methodologies. Its current methodologies are examined. These assessment strategies are applicable to other metropolitan areas. The Mental Health Needs Council is a model for effective community collaboration on the needs and problems of persons with mental illness.

Adult↗

Temporal changes in the inequality of early growth of Cunninghamia lanceolata (Lamb.) Hook.: a novel application of the Gini coefficient and Lorenz asymmetry.

Growth within tree populations varies among individuals due to changes in biotic and abiotic factors. The degree of such variation, defined as growth inequality, serves as a useful indicator of the uniformity of growth within a population in response to the prevalent environmental conditions. By application of the Gini coefficient (G), an index for inequality, we characterized the early growth inequality of ninety crosses of Chinese fir (Cunninghamia lanceolata (Lamb.) Hook.) and their open-pollinated parental lines. Tree cumulative height was measured annually for 8 consecutive years. Both the crosses and parental lines exhibited temporal changes in growth inequality. The inequality of total height among the crosses decreased logarithmically with age by nearly 3-fold after 13 growing seasons, suggesting that tree height became less variable among the crosses as trees grew larger. Interestingly, the Lorenz asymmetry, an index reflecting the shape of the Lorenze curve from which G is derived, revealed that the inequality of annual height increment among the crosses resulted from an alternate contribution of the fast-growing and slow-growing trees. Among parental lines, two provenances with the smallest and the largest overall inequality in total height showed a similar pattern of changes in annual growth inequality, and the provenance differences were consistent over time. Compared to the other provinces, a local provenance exhibited less variation in total height among individual trees as reflected by a smaller value of inequality, and was better adapted to the field conditions. Our results demonstrated the sensitivity and usefulness of the Gini coefficient and Lorenz asymmetry for the analysis of growth inequality in non-natural populations. Growth inequality is a potentially useful evaluation criterion for early selection. Given comparable initial growth, provenances/families with lower growth inequality values would likely outperform those with higher growth inequality, and eventually tree size of the latter would be more variable due to greater variations among individual trees. Assessment of growth inequality at early ages will advance our understanding of variability of tree growth within a population, facilitate forest genetics improvement programs, and enhance the efficiency of tree breeding.

China↗

Computer analysis of rapid eye movements.

Simulation of the saccadic eye movement mechanism and, more recently, diagnosis of neuromuscular disorders associated with saccades rely on accurate recording and analysis of saccade characteristics. Traditionally, eye movements are monitored objectively by registering a transduced voltage correlate of eye position on a pen or cathode ray oscillograph. Analysis of the record obtained is tedious and often inaccurate. The advent of small digital computers with analog-to-digital capability permits more efficient recording. However, computer programs reviewed are limited to the analysis of specific saccade parameters or partly depend on manual operations. The computer program described stores the entire saccadic event of each eye between pre-defined limits including the pre- and post-saccade intervals. Preliminary operations including artifact identification, location of onset, elimination of RC decay, DC offset and amplitude scaling prepare the data for display and subsequent analysis. The program also includes a subroutine to derive the mean and standard deviation of successive saccades.

Computers↗

Relevance of histidine-84 in the elongation factor Tu GTPase activity and in poly(Phe) synthesis: its substitution by glutamine and alanine.

Substitution of His-84 (-->Gln and -->Ala), a residue of the switch II region of E. coli elongation factor (EF) Tu, hardly affected the binding of GTP or GDP. The activity in poly(Phe) synthesis and GTP hydrolysis of EF-Tu H84Q were both reduced to about 35%, as compared to EF-Tu wt, whereas EF-Tu H84A was inactive in poly(Phe) synthesis but still showed a 10% residual GTPase activity. Phe-tRNAPhe exerted a similar inhibitory effect on the GTPase activity of EF-Tu wt and EF-Tu H84Q while abolishing that of EF-Tu H84A. Ribosomes enhanced the GTPase activity of EF-Tu H84Q, but not that of EF-Tu H84A, on which they even seemed to exert an inhibitory effect. The one-round GTP hydrolysis associated with the EF-TuH84Q-dependent binding of Phe-tRNAPhe to poly(U)-programmed ribosomes was less efficient than with EF-Tu wt. Kirromycin stimulated the GTPase activities of both mutants less than EF-Tu wt. The results of this work do not support a catalytic role of His-84 in the intrinsic GTPase of EF-Tu, but they emphasize the importance of its side-chain for polypeptide synthesis and GTP hydrolysis.

Alanine↗

Design of dosage regimens: a multiple model stochastic control approach.

This paper presents a general stochastic control framework for determining drug dosage regimens where the sample times, dosing times, desired goals, etc., occur at different times and in an asynchronous fashion. In the special case of multiple models with linear dynamics and quadratic cost (MMLQ), it is shown that the optimal open-loop stochastic control with linear control/state constraints can be solved exactly and efficiently as a quadratic program. This provides a simple and flexible method for computing open-loop feedback designs of drug dosage regimens. An implementation of the MMLQ adaptive control approach is demonstrated on a Lidocaine infusion process. For this example, the resulting MMLQ regimen is more effective than the MAP Bayesian regimen at reducing interpatient variability and keeping patients in the therapeutic range.

Drug Administration Schedule↗