Polyhydroxybutyrate and polyhydroxydodecanoate produced by Burkholderia contaminans IPT553.

AIMS: In this paper, we introduce a new Burkholderia contaminans capable of producing a newly characterized polymer. METHODS AND RESULTS: CG-MS and magnetic nuclear resonance 1 H and 13 C were used to determine the constitution of polymers produced in glucose, glucose with casein, sucrose and sucrose with casein. Three pairs of primers were used to find the polyhydroxyalkanoates (PHA) synthase class and sequence. The synthesized polymers were composed by short-chain length PHA (scl-PHA), especially polyhydroxybutyrate (PHB), and medium chain length PHA (mcl-PHA), especially polyhydroxydodecanoate (PHDd), and their concentration, constitution and molecular weight depend on carbon source used. The bacterium showed only class I synthase which could not explain the mcl-PHA production. CONCLUSIONS: Burkholderia contaminans has a class I PHA synthase and produces PHB combined to PHDd when cultivated in sucrose or glucose, and PHDd concentration is affected when casein is used. SIGNIFICANCE AND IMPACT OF THE STUDY: PHA are natural polymers produced by a wide range of bacteria. The presence of PHDd monomers confers to the polymer elastomeric properties. Previously, PHDd was only obtained when bacteria were cultivated in related carbon source. In this work, B. contaminansIPT553 produced PHB with PHDd using simple and low-cost carbon sources that can make possible the cheaper production of a more flexible biopolymer with crystallinity and elasticity different from the more common PHAs.

Validating a natural language processing tool to exclude psychogenic nonepileptic seizures in electronic medical record-based epilepsy research.

RATIONALE: As electronic health record (EHR) systems become more available, they will serve as an important resource for collecting epidemiologic data in epilepsy research. However, since clinicians do not have a systematic method for coding psychogenic nonepileptic seizures (PNES), patients with PNES are often misclassified as having epilepsy, leading to sampling error. This study validates a natural language processing (NLP) tool that uses linguistic information to help identify patients with PNES. METHODS: Using the VA national clinical database, 2200 notes of Iraq and Afghanistan veterans who completed video electroencephalograph (VEEG) monitoring were reviewed manually, and the veterans were identified as having documented PNES or not. Reviewers identified PNES-related vocabulary to inform a NLP tool called Yale cTakes Extension (YTEX). Using NLP techniques, YTEX annotates syntactic constructs, named entities, and their negation context in the EHR. These annotations are passed to a classifier to detect patients without PNES. The classifier was evaluated by calculating positive predictive values (PPVs), sensitivity, and F-score. RESULTS: Of the 742 Iraq and Afghanistan veterans who received a diagnosis of epilepsy or seizure disorder by VEEG, 44 had documented events on VEEG: 22 veterans (3.0%) had definite PNES only, 20 (2.7%) had probable PNES, and 2 (0.3%) had both PNES and epilepsy documented. The remaining 698 veterans did not have events captured during the VEEG admission and/or did not have a definitive diagnosis. Our classifier achieved a PPV of 93%, a sensitivity of 99%, and a F-score of 96%. CONCLUSION: Our study demonstrates that the YTEX NLP tool and classifier is highly accurate in excluding PNES, diagnosed with VEEG, in EHR systems. The tool may be very valuable in preventing false positive identification of patients with epilepsy in EHR-based epidemiologic research.

The Common Data Elements for cancer research: remarks on functions and structure.

OBJECTIVES: The National Cancer Institute (NCI) has developed the Common Data Elements (CDE) to serve as a controlled vocabulary of data descriptors for cancer research, to facilitate data interchange and inter-operability between cancer research centers. We evaluated CDE's structure to see whether it could represent the elements necessary to support its intended purpose, and whether it could prevent errors and inconsistencies from being accidentally introduced. We also performed automated checks for certain types of content errors that provided a rough measure of curation quality. METHODS: Evaluation was performed on CDE content downloaded via the NCI's CDE Browser, and transformed into relational database form. Evaluation was performed under three categories: 1) compatibility with the ISO/IEC 11179 metadata model, on which CDE structure is based, 2) features necessary for controlled vocabulary support, and 3) support for a stated NCI goal, set up of data collection forms for cancer research. RESULTS: Various limitations were identified both with respect to content (inconsistency, insufficient definition of elements, redundancy) as well as structure--particularly the need for term and relationship support, as well as the need for metadata supporting the explicit representation of electronic forms that utilize sets of common data elements. CONCLUSIONS: While there are numerous positive aspects to the CDE effort, there is considerable opportunity for improvement. Our recommendations include review of existing content by diverse experts in the cancer community; integration with the NCI thesaurus to take advantage of the latter's links to nationally used controlled vocabularies, and various schema enhancements required for electronic form support.

Limitations of conventional methods of self-monitoring of blood glucose: lessons learned from 3 days of continuous glucose sensing in pediatric patients with type 1 diabetes.

OBJECTIVE: Children with type 1 diabetes are usually asked to perform self-monitoring of blood glucose (SMBG) before meals and at bedtime, and it is assumed that if results are in target range, along with HbA(1c) measurements, then overall glycemic control is adequate. However, the brief glimpses in the 24-h glucose profile provided by SMBG may miss marked glycemic excursions. The MiniMed Continuous Glucose Monitoring System (CGMS) has provided a new method to obtain continuous glucose profiles and opportunities to examine limitations of conventional monitoring. RESEARCH DESIGN AND METHODS: A total of 56 children with type 1 diabetes (age 2-18 years) wore the CGMS for 3 days. Patients entered four fingerstick blood samples into the monitor for calibration and kept records of food intake, exercise, and hypoglycemic symptoms. Data were downloaded, and glycemic patterns were identified. RESULTS: Despite satisfactory HbA(1c) levels (7.7 +/- 1.4%) and premeal glucose levels near the target range, the CGMS revealed profound postprandial hyperglycemia. Almost 90% of the peak postprandial glucose levels after every meal were >180 mg/dl (above target), and almost 50% were >300 mg/dl. Additionally, the CGMS revealed frequent and prolonged asymptomatic hypoglycemia (glucose <60 mg/dl) in almost 70% of the children. CONCLUSIONS: Despite excellent HbA(1c) levels and target preprandial glucose levels, children often experience nocturnal hypoglycemia and postprandial hyperglycemia that are not evident with routine monitoring. Repeated use of the CGMS may provide a means to optimize basal and bolus insulin replacement in patients with type 1 diabetes.

A guideline implementation system using handheld computers for office management of asthma: effects on adherence and patient outcomes.

OBJECTIVE: To evaluate effects on the process and outcomes of care brought about by use of a handheld, computer-based system that implements the American Academy of Pediatrics guideline on office management of asthma exacerbations. DESIGN: A before-after trial with randomly selected, office-based Connecticut pediatricians. In both the control and intervention phases, physicians collected data from 10 patient encounters for acute asthma exacerbations. During the intervention phase, the computer provided for structured encounter documentation and offered recommendations based on the guideline of the American Academy of Pediatrics. Patients were contacted by telephone 7 to 14 days after the visit to assess outcomes. RESULTS: Nine study-physicians enrolled 91 patients in the control phase and 74 in the intervention phase. Follow-up information was available for 93% of encounters. Use of the intervention was associated with increased mean frequency/visit of: 1) measurements of peak expiratory flow rate (2.18 vs 1.57) and oxygen saturation (1.12 vs.42), and 2) administration of nebulized beta2-agonists (1.25 vs.71). Visits in the intervention phase lasted longer and fees were higher ($145.61 vs $103.11). There were no significant differences in immediate disposition or subsequent emergency department visits, hospitalizations, missed school, or caretaker's missed work during the 7 days post visit. CONCLUSION: Use of handheld computers that provide guideline-based decision support was associated with increased physician adherence to guideline recommendations; however, visits were prolonged, fees were higher, and no improvement could be demonstrated with regard to the observed intermediate-term patient outcomes. Guideline implementers (and users) should be cautious about putting unvalidated recommendations into practice.

Computer-based guideline implementation systems: a systematic review of functionality and effectiveness.

In this systematic review, the authors analyze the functionality provided by recent computer-based guideline implementation systems and characterize the effectiveness of the systems. Twenty-five studies published between 1992 and January 1998 were identified. Articles were included if the authors indicated an intent to implement guideline recommendations for clinicians and if the effectiveness of the system was evaluated. Provision of eight information management services and effects on guideline adherence, documentation, user satisfaction, and patient outcome were noted. All systems provided patient-specific recommendations. In 19, recommendations were available concurrently with care. Explanation services were described for nine systems. Nine systems allowed interactive documentation, and 17 produced paper-based output. Communication services were present most often in systems integrated with electronic medical records. Registration, calculation, and aggregation services were infrequently reported. There were 10 controlled trials (9 randomized) and 10 time-series correlational studies. Guideline adherence improved in 14 of 18 systems in which it was measured. Documentation improved in 4 of 4 studies.

A design model for computer-based guideline implementation based on information management services.

Clinical practice guidelines must be implemented effectively if they are to influence the behavior of clinicians. The authors describe a model for computer-based guideline implementation that identifies eight information management services needed to integrate guideline-based decision support with clinical workflow. Recommendation services determine appropriate activities in specific clinical circumstances. Documentation services involve data capture. Registration services integrate demographic and administrative data. Explanation services enhance the credibility of automated recommendations by providing supportive evidence and rating the quality of evidence. Calculation services measure time intervals, suggest medication dosages, and perform other computational tasks. Communication services employ standards for information transfer and provide data security. Effective presentation services facilitate understanding of complex data, clarify trends, and format written materials (including prescriptions) for patients. Aggregation services associate outcomes with specific guideline interventions. The authors provide examples of the eight services that make up the model from five evidence-based practice parameters developed by the American Academy of Pediatrics.

Transition to a computer-based record using scannable, structured encounter forms.

OBJECTIVE: To evaluate the quality of documentation and user satisfaction with a structured documentation system for pediatric health maintenance encounters, using scanned paper-based forms to generate an electronic medical record. DESIGN: (1) A retrospective medical record review comparing 16 structured (ST) records with 16 contemporaneously created unstructured records, (2) a questionnaire evaluation of user satisfaction, and (3) an electronic records review of patients seen 1 year following the full implementation of the system to evaluate persistence of the effect. SETTING: The Yale-New Haven Hospital Pediatric Primary Care Center, New Haven, Conn, an inner-city clinic in an academic center. PARTICIPANTS: (1) A random sample of 16 health maintenance records completed by first- and second-year residents in February 1996 matched for patient's age and provider training level with 16 contemporaneously documented visits, (2) 16 of 18 pediatric level 1 residents and 14 of 16 pediatric level 2 residents who completed questionnaires, and (3) all electronic records of health maintenance visits during February 1997. MAIN OUTCOME MEASURES: The number of data elements documented and the percentage of records that record specific components of the health maintenance encounter. User satisfaction was specified on a Likert scale. RESULTS: Overall, residents in the ST records group documented more data elements per visit than did those in the unstructured records group. The number of developmental items documented was 11.5 per visit in the ST records group and 4.8 per visit in the unstructured records group (P = .004). Likewise, anticipatory guidance was more thoroughly documented in the ST records group--8.3 items per visit vs 2.5 items per visit (P < .001). Ninety percent of the users preferred the ST records. One year after the adoption of the ST recording system, high levels of thoroughness persisted. CONCLUSIONS: Structured, scannable encounter forms can facilitate documentation of patient care and are well accepted by users. They can provide an effective mechanism to ease the transition to a computer-based patient record.

Aneuploid malignant T cells from a patient with Sézary syndrome can be visualized by in situ hybridization.

BACKGROUND AND DESIGN: Enumeration of malignant cells in Sézary syndrome often relies on the identification of the Sézary cell nucleus. This morphologic method is, however, nonspecific and unreliable in the enumeration of the proportion of malignant lymphocytes in peripheral blood of patients with Sézary syndrome. Malignant lymphocytes of patients with mycosis fungoides and Sézary syndrome are often characterized by multiple chromosome aberrations. Herein, we demonstrate that fluorescent in situ hybridization can visualize and accurately enumerate malignant aneuploid mononuclear cells in a patient with Sézary syndrome. RESULTS: Fluorescent in situ hybridization demonstrated that 90% of the mononuclear cells in the patient with Sézary syndrome showed numerical aberrations for both chromosome 7 and X, a figure confirmed by flow cytometry. CONCLUSION: Fluorescent in situ hybridization may be a valuable tool to visualize and enumerate aneuploid tumor cells in patients with cutaneous T-cell lymphoma.

Behavioural problems associated with dementia: the role of newer antipsychotics.

Behavioural disorders are a common feature in dementia, especially in the later stages of the disease. The most frequent disorders are agitation, aggression, paranoid delusions, hallucinations, sleep disorders, including nocturnal wandering, incontinence and (stereotyped) vocalisations or screaming. Behavioural disorders, rather than cognitive disorders, are the main reason why caregivers place patients with dementia in a nursing home. However, although behavioural disorders are important, there is still no international agreement with respect to the description and definition of symptoms and syndromes. This also holds true for the wide variety of scales for quantification and measurement of behavioural disorders. Drug therapy should be considered after possible underlying causes such as physical illness, drug adverse effects and environmental stressors have been ruled out, or specifically addressed, and a behavioural approach has also failed. This article briefly reviews the evidence for non-antipsychotic drug therapies, which include a variety of substances. However, antipsychotics are the group of drugs which have been most frequently studied for the treatment of behavioural syndromes in dementia. Drug responsive symptoms include anxiety, verbal and physical agitation, hallucinations, delusions, uncooperativeness and hostility, whereas wandering, hoarding, unsociability, poor self-care, screaming and other stereotyped behaviour seem to be unresponsive to all drugs. Although the use of classical antipsychotics is limited by extrapyramidal symptoms, anticholinergic adverse effects, sedation and postural hypotension, the newer antipsychotics offer the chance of a better risk:benefit ratio. This article reviews the small amount of data published on the use of the newer antipsychotics, and concludes that risperidone at low dosages (0.5 to 2 mg/day) seems to be especially useful for the treatment of behavioural symptoms in dementia because of its negligible anticholinergic adverse effects. The use of clozapine is limited by its anticholinergic activity, at least in dementia of the Alzheimer and Lewy body types. However, in patients with psychosis arising from Parkinson's disease it seems to be the drug of choice, and similar activity is likely for olanzapine. There are no published data on other newer drugs, such as sertindole, quetiapine or ziprasidone. Future studies should also address questions of dementia heterogeneity and should compare different drug treatments and treatment combinations.

Age and hunting success in the brown pelican: influences of skill and patch choice on foraging efficiency.

Age-related differences in the foraging efficiency of piscivorous birds may be the results of differences in foraging skill, patch usage, or both. Brown pelicans were observed while foraging around a small Caribbean island. Areas where the birds fed were subdivided into small, homogeneous subunits (patches), and the bird's foraging success and patch use were noted and analyzed using multivariate techniques. Adult birds were found to be better at capturing prey under all conditions than were juveniles, but the differences were small in some patches. The density of prey and the birds' foraging success influenced the foraging efforts of adult and juvenile pelicans to similar degrees. Both age groups utilized local enhancement in their foraging, but such behavior augmented the foraging success only of juvenile birds. Both age groups often fed in patches where their foraging success was quite low. Such behaviour was much more costly for juvenile than for adult pelicans.

Chorioangioma placentae and feto-maternal transfusion; a report of two cases.

Chorioangioma (CA) is found in about 1% of all placentas. Here we report cases of CA: one associated with intra-uterine fetal death, and the other with feto-maternal transfusion resulting in severe anaemia of the child. Feto-maternal transfusion through a CA could, in suspected cases, be diagnosed by s-AFP, one-minute alkali-denaturation test and perhaps ultrasound of the placenta. Intra-uterine death of the child could then be prevented by Caesarean section.

Molecular cytogenetics: applications in clinical genetics.

To illustrate the advantage of fluorescence in situ hybridization (FISH) in clinical genetics, we have chosen six clinical cases from our routine laboratory where we have used molecular cytogenic techniques to optimise the cytogenetic analysis. Using centromere-specific DNA probes and whole chromosome DNA libraries either obtained from somatic cell hybrids or generated from flow-sorted chromosomes, we have been able to identify small marker chromosomes, chromosomal duplications and inversions, to determine the ploidy in interphase nuclei, and to characterize subtle chromosomal translocations. We conclude that molecular cytogenetics is a valuable technique that should be used as a supplement to conventional cytogenetics to reduce the number of unresolved karyotypes in clinical genetics.

Integration of Web-based and PC-based clinical research databases.

UNLABELLED: We have created a Web-based repository or data library of information about measurement instruments used in studies of multi-factorial geriatric health conditions (the Geriatrics Research Instrument Library - GRIL) based upon existing features of two separate clinical study data management systems. GRIL allows browsing, searching, and selecting measurement instruments based upon criteria such as keywords and areas of applicability. Measurement instruments selected can be printed and/or included in an automatically generated standalone microcomputer database application, which can be downloaded by investigators for use in data collection and data management. METHODS: Integration of database applications requires the creation of a common semantic model, and mapping from each system to this model. Various database schema conflicts at the table and attribute level must be identified and resolved prior to integration. Using a conflict taxonomy and a mapping schema facilitates this process. RESULTS: Critical conflicts at the table level that required resolution included name and relationship differences. CONCLUSIONS: A major benefit of integration efforts is the sharing of features and cross-fertilization of applications created for similar purposes in different operating environments. Integration of applications mandates some degree of metadata model unification.

An object-oriented framework for the development of computer-based guideline implementations.

Clinical practice guidelines provide a means of directing medical care towards clinically appropriate and cost-effective interventions. A direct relationship exists between the integration of a guideline into clinical workflow and the effectiveness of the guideline in influencing clinicians' behavior. Computer-based guideline implementations, used at the point-of-care, accomplish this integration. Employing object-oriented technologies, we propose a framework of reusable components for the development of guideline implementation systems. We have identified eight information management services that are common to such systems. Our framework integrates these services and their respective reusable components into clinical workflow to promote the development of comprehensive guideline implementation systems, which should ultimately enhance guideline compliance and the overall quality of care.

Visualizing the logic of a clinical guideline: a case study in childhood immunization.

IMM/Graph is a visual model designed to help knowledge-base developers understand and refine the guideline logic for childhood immunization. The IMM/Graph model is domain-specific and was developed to help build a knowledge-based system that makes patient-specific immunization recommendations. A "visual vocabulary" models issues specific to the immunization domain, such as (1) the age a child is first eligible for each vaccination dose, (2) recommended, "past due" and maximum ages, (3) minimum waiting periods between doses, (4) the vaccine brand or preparation to be given, and (5) the various factors affecting the time course of vaccination. Several lessons learned in the course of developing IMM/Graph include the following: (1) The intended use of the model may influence the choice of visual presentation; (2) There is a potentially interesting interplay between the use of visual and textual information in creating the visual model; (3) Visualization may help a development team better understand a complex clinical guideline and may also help highlight areas of incompleteness.

Approaches and informatics tools to assist in the integration of similar clinical research questionnaires.

OBJECTIVE: The integration of similar clinical research questionnaires is a complex process that can benefit from informatics approaches and tools that provide a systematic structure for performing mapping and integration. This systematic approach is necessary to address complex issues in integration such as data heterogeneity, differing levels of granularity of questions and responses, and other issues involving semantic differences. Informatics tools and approaches have been successfully applied to various standard clinical vocabulary integration processes but not for questionnaire integration or mapping. METHODS: A systematic approach to questionnaire integration was developed in the context of a collaboration of researchers using Trial/DB, a database designed to support clinical research. This approach was applied to the integration of questionnaires involving breast cancer risk factors from each of three research sites. RESULTS: From 375 questions on the three original questionnaires, we identified 65 concepts that were measured by two or three of the sites. An algorithm was developed and used to formalize the process of mapping questions and answers across the questionnaires. The approach was applied to previously collected data and prospective data in disparate data-base systems to import and merge the data from these three sites into Trial/DB. CONCLUSION: Informatics tools that support a systematic approach to mapping questionnaires can be used throughout the research process from questionnaire integration and creation, legacy data integration to data library maintenance and curation.

An outbreak of hepatitis A during a military field training exercise.

Hepatitis A continues to pose a preventable threat to modern day military forces. We describe a food-borne outbreak of hepatitis A during a field training exercise resulting in 22 ill soldiers and over 300 lost work days. Among the population at risk, the secondary attack rate was 19.6%. Faced with epidemic disease occurrence, epidemiologic investigation of potential cases and aggressive use of post-exposure prophylaxis is recommended in a field setting. Although immune serum globulin is likely to reduce transmission, not all cases of acute hepatitis A will be prevented by this action.

[Sex chromosome abnormalities and sex determination genes. Review of the literature]. / Kønskromosomabnormiteter og kønsbestemmende gener. En litteraturundersøgelse.

Molecular analysis of structural chromosomal abnormalities, involving the sex chromosomes, has provided us new knowledge concerning sex determination in humans. This has raised three hypotheses of sexual differentiation, which will be discussed even though none of these can explain all abnormalities involved. Meiotic recombination which normally takes place during the male meiotic cell division, can give rise to sex reversal syndromes such as XX male and XY female, if crossing over is abnormal. Analysis of these abnormalities has made it possible to map sex determining regions on chromosome Y, and to construct a deletion map. Methods using DNA probes, are capable of identifying Y-specific sequences in persons with sex reversal. This means a more optimal counselling, possibilities of prenatal diagnosis, and opportunities for selecting patients with risk of gonad cancers, for extirpation.

[Prenatal diagnosis in the county of Viborg before and after decentralization of sample taking]. / Praenatal diagnostik i Viborg Amt før og efter decentralisering af prøvetagning.

On account of an increase in the frequency of amniotic fluid samples (AFS), the need for further decentralisation of sampling developed. Viborg Amt (Viborg County) was able to offer this service to all pregnant women in the county after 01.VIII.1985 who fulfil the indication for prenatal diagnosis (PD). Among 902 registered AFS divided over a period of two years before and two years after the decentralisation there was no significant deterioration of the service measured by the number of spontaneous abortions and unsuccessful AFS. The indications for prenatal diagnosis altered in such a way that the unofficial indication of anxiety rose significantly while the indication of maternal age greater than or equal to 35 years decreased. Furthermore, a positive correlation was registered between a reduction of distance from the pregnant woman to the centre of sampling and the percentage of referrals made by the local practitioner. The paper also shows that more pregnant women, referred for AFS on account of advanced age, accepted PD than was registered in an earlier research, but this pattern declined in the research period.