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PubMed2004

Modeling of the sagittal cervical spine as a method to discriminate hypolordosis: results of elliptical and circular modeling in 72 asymptomatic subjects, 52 acute neck pain subjects, and 70 chronic neck pain subjects.

STUDY DESIGN: Computer analysis of digitized vertebral body corners on lateral cervical radiographs. OBJECTIVES: Using elliptical and circular modeling, the geometric shape of the path of the posterior bodies of C2-C7 was sought in normal, acute pain, and chronic pain subjects. To determine the least squares error per point for paths of geometric shapes, minor axis to major axis elliptical ratios (b/a), Cobb angles, sagittal balance of C2 above C7, and posterior tangent segmental and global angles. SUMMARY OF BACKGROUND DATA: When restricted to cervical lordotic configurations, normal, acute pain, and chronic pain subjects have not been compared for similarities or differences of these parameters. Conventional Cobb angles provide only a comparison of the endplates of the distal vertebrae, while geometric modeling provides the shape of the entire sagittal curves, the orientation of the spine, and segmental angles. METHODS: Radiographs of 72 normal subjects, 52 acute neck pain subjects, and 70 chronic neck pain subjects were digitized. For normal subjects, the inclusion criteria were no kyphotic cervical segments, no cranial-cervical symptoms, and less than +/- 10 mm horizontal displacement of C2 above C7. In pain subjects, inclusion criteria were no kyphotic cervical segments and less than 25 mm of horizontal displacement of C2 above C7. Measurements included segmental angles, global angles of lordosis (C1-C7 and C2-C7), height-to-length ratios, anterior weight bearing, and from modeling, circular center, and radius of curvature. RESULTS: In the normal group, a family of ellipses was found to closely approximate the posterior body margins of C2-C7 with a least squares error of less than 1 mm per vertebral body point. The only ellipse/circle found to include T1, with a least squares error of less than 1 mm, was a circle. Compared with the normal group, the pain group's mean radiographic angles were reduced and the radius of curvature was larger. For normal, acute, and chronic pain groups, the mean angles between posterior tangents on C2-C7 were 34.5 degrees, 28.6 degrees, and 22.0 degrees, C2-C7 Cobb angles were 26.8 degrees, 16.5 degrees, and 12.7 degrees, and radius of curvature were r = 132.8 mm, r = 179 mm, and r = 245.4 mm, respectively. CONCLUSIONS: The mean cervical lordosis for all groups could be closely modeled with a circle. Pain groups had hypolordosis and larger radiuses of curvature compared with the normal group. Circular modeling may be a valuable tool in the discrimination between normal lordosis and hypolordosis in normal and pain subjects.

Acute Disease↗
PubMed2005

Reflex muscle contraction in the unaware occupant in whiplash injury.

STUDY DESIGN: Computer modeling and parametric analysis were used to determine the effect of reflex contraction of the neck muscles in the unaware occupant in whiplash. OBJECTIVE: To delineate effects of reflex contraction on spinal segmental kinematics during the retraction phase. SUMMARY OF BACKGROUND DATA: The ability of reflex neck muscle contraction to mitigate whiplash injury in the unaware occupant remains unclear. Analyzing relative timing between electromyographic and head-neck kinematics, previous investigators theorized that muscle contraction alters spinal kinematics, decreasing injury likelihood. Other investigators suggested that injury occurs during the initial (retraction) phase of head-neck kinematics, before significant muscle force generation. METHODS: Computer modeling was used to determine reflex contraction effects on segmental angulations, implementing parametric analysis techniques to vary reflex delay and impact severity. RESULTS: Shorter reflex delays had a greater effect on segmental angulations later in the event and at lower impact severities. However, the magnitude of this effect, particularly at higher impact severities and during maximum cervical S-curvature (factors implicated in the whiplash injury mechanism) was minimal, altering segmental angulations by a maximum of 19%. CONCLUSIONS: Because reflex contraction did not substantially alter spinal kinematics, muscle contraction likely does not initiate in sufficient time to mitigate whiplash injuries that may occur during the retraction phase.

Cervical Vertebrae↗
PubMed2006

Ultrasound-guided spinal fracture repositioning, ligamentotaxis, and remodeling after thoracolumbar burst fractures.

STUDY DESIGN: Computed tomography aided evaluation of spinal decompression by ultrasound-guided spinal fracture repositioning, ligamentotaxis, and remodeling after thoracolumbar burst fractures. OBJECTIVES: To determine the necessity of spinal canal widening by ultrasound-guided fracture repositioning for fractures with and without neurologic deficit. SUMMARY OF BACKGROUND DATA: Ultrasound-guided spinal fracture repositioning is an alternative new approach. Reports have varied concerning ligamentotaxis and remodeling. METHODS: Computed tomography aided planimetry of the spinal canal (64 consecutive burst fractures) and neurologic evaluation by Frankel grades. RESULTS: Ultrasound-guided spinal fracture repositioning (n = 37) reduced the stenosis of the spinal canal area from 45% before surgery to 20% after surgery of the estimated original area. Fifteen patients had a primary neurologic deficit, which improved markedly in 11 cases after treatment. Patients with neurologic symptoms had a greater preoperative spinal stenosis than those without. No correlation was seen between the degree of pretreatment spinal stenosis, fracture type, and severity of the neurologic deficit. Ligamentotaxis (n = 27) reduced the stenosis from 30% before surgery to 18% after surgery and remodeling (n = 11) from 25% after surgery to 13% after metal removal. CONCLUSION: Ultrasound-guided fracture repositioning is an efficient method for spinal canal decompression of burst fractures with neurologic symptoms. The marked degree of widening of the spinal canal due to the effects of ligamentotaxis and remodeling may render the reposition of retropulsed fragments unnecessary in cases of fractures without a neurologic deficit.

Adolescent↗
PubMed2004

In silico experiments of existing and hypothetical cytokine-directed clinical trials using agent-based modeling.

OBJECTIVES: To introduce a form of mathematical modeling, agent-based modeling (ABM), and demonstrate its potential uses in the evaluation of the dynamics of the innate immune response (IIR) and the development of possible treatments for systemic inflammatory response syndrome (SIRS)/multiple organ failure (MOF). RATIONALE: The IIR can be categorized as a complex system that responds to interventions in a nonintuitive fashion, leading to difficulty in translating basic science knowledge into effective treatments for SIRS/MOF. It is proposed that ABM is particularly well suited to examining the complex interactions of the IIR and its disordered states of SIRS/MOF. STUDY DESIGN: Computer simulation and mathematical modeling. DATA SOURCE: Review articles on components and mechanisms involved in the IIR. Published results from phase III anticytokine/mediator trials. Published results from smaller clinical trials and animal studies. MAIN RESULTS: An abstract ABM of the IIR was created. The model reproduces the general behavior of the IIR with respect to outcome and cause of system "death." Patterns of levels of individual cytokines matched patterns of measured cytokines reported in the existing literature. Clinical trials of anticytokine therapy were simulated and produced outcomes qualitatively similar to those reported in the literature. A series of hypothetical treatment regimes (variation of dose and length of treatment [anti-tumor necrosis factor and anti-interleukin-1], anti-CD-18, and multiple-drug regimes [combination of anti-tumor necrosis factor, anti-interleukin-1, and anti-CD-18]) were formulated and implemented in the ABM. None of the simulated therapies showed a statistically significant improvement in system mortality. CONCLUSIONS: Presented herein is an abstracted ABM of the IIR. This model is intended primarily as an introduction to and demonstration of this technique. However, even this relatively simple model demonstrates counterintuitive system responses and the difficulty of effectively manipulating a complex system like the IIR. ABM may provide a synthetic, analytical platform to integrate basic science data on the IIR, thus eventually aiding in formulating and testing future mediator-directed therapies for SIRS/MOF before clinical trials, and it may provide insights into directions of future research.

Clinical Trials as Topic↗
PubMed2003

Defining neuroscience nursing practice: the 2001 role delineation study.

Studies that provided a blueprint for the Certified Neuroscience Registered Nurse (CNRN) examination were conducted in 1987, 1992, and 1997. In 2000, the American Board of Neuroscience Nursing (ABNN) formed a task force to re-examine the previous role delineation survey, obtain information to define current neuroscience nursing practice, and provide content validity for future CNRN examinations. Previous role delineation studies conducted by ABNN and a review of the literature provided the background for the study. The theoretical framework was the Nursing Intervention Classification (NIC) taxonomy and the methodology was a survey design. Computer Adaptive Technologies, Inc. (CAT), assisted the task force with survey development and data analysis. The survey, a three-part questionnaire, was mailed to 1,505 CNRNs and returned by 453 participants.

Certification↗
PubMed2005

Fault-tolerant quantum computation via exchange interactions.

Quantum computation can be performed by encoding logical qubits into the states of two or more physical qubits, and control of effective exchange interactions and possibly a global magnetic field. This "encoded universality" paradigm offers potential simplifications in quantum computer design since it does away with the need to control physical qubits individually. Here we show how encoded universality schemes can be combined with fault-tolerant quantum error correction, thus establishing the scalability of such schemes.

Journal Article↗
PubMed2003

Amyloid-forming peptides selected proteolytically from phage display library.

We demonstrated that amyloid-forming peptides could be selected from phage-displayed library via proteolysis-based selection protocol. The library of 28-residue peptides based on a sequence of the second zinc finger domain of Zif268, and computationally designed betabetaalpha peptide, FSD-1, was presented monovalently on the surface of M13 phage. The library coupled the infectivity of phage particles to proteolytic stability of a peptide introduced into the coat protein III linker. It was designed to include variants with a strong potential to fold into betabetaalpha motif of zinc finger domains, as expected from secondary structure propensities, but with no structure stabilization via zinc ion coordination. As our primary goal was to find novel monomeric betabetaalpha peptides, the library was selected for stable domains with the assumption that folded proteins are resistant to proteolysis. After less than four rounds of proteolytic selection with trypsin, chymotrypsin, or proteinase K, we obtained a number of proteolysis-resistant phage clones containing several potential sites for proteolytic attack with the proteinases. Eight peptides showing the highest proteolysis resistance were expressed and purified in a phage-free form. When characterized, the peptides possessed proteolytic resistance largely exceeding that of the second zinc finger domain of Zif268 and FSD-1. Six of the characterized peptides formed fibrils when solubilized at high concentrations. Three of them assembled into amyloids as determined through CD measurements, Congo red and thioflavin T binding, and transmission electron microscopy.

Amino Acid Sequence↗
PubMed2005

Prediction of aggregation rate and aggregation-prone segments in polypeptide sequences.

The reliable identification of beta-aggregating stretches in protein sequences is essential for the development of therapeutic agents for Alzheimer's and Parkinson's diseases, as well as other pathological conditions associated with protein deposition. Here, a model based on physicochemical properties and computational design of beta-aggregating peptide sequences is shown to be able to predict the aggregation rate over a large set of natural polypeptide sequences. Furthermore, the model identifies aggregation-prone fragments within proteins and predicts the parallel or anti-parallel beta-sheet organization in fibrils. The model recognizes different beta-aggregating segments in mammalian and nonmammalian prion proteins, providing insights into the species barrier for the transmission of the prion disease.

Alzheimer Disease↗
PubMed1993

Detection of a molecular defect in 40 of 44 patients with haemophilia B by PCR and denaturing gradient gel electrophoresis.

Oligonucleotides were computer designed to amplify by the polymerase chain reaction (PCR) the coding region, splice junctions, 112 bp of the 5' flanking region and 279 bp surrounding the polyadenylation site of the factor IX gene for analysis by denaturing gradient gel electrophoresis (DGGE). Forty-four unselected haemophilia B patients were studied of whom 24 had severe haemophilia and 20 had a mild to moderate form of the disease. Potential mutations were identified in 40 (91%) of the 44 cases. A defect could not be detected in three severe and one mild haemophiliac by DGGE analysis and direct sequencing of all the PCR fragments from these patients revealed no nucleotide alteration supporting the DGGE results. A total of 37 point mutations, two complete gene deletions and a duplication of 26 bp were found. The 37 point mutations included 35 single nucleotide substitutions, a deletion and an insertion of one nucleotide. The 35 single nucleotide substitutions included 26 missense mutations, seven nonsense mutations, a G (-6) to A transition in the promoter region and a G (30154) to A transition within the donor splice site of the last intron. Fifteen of these nucleotide substitutions involved CpG dinucleotides. Fifteen point mutations were found at codons where nucleotide substitutions had not been detected before. An insertion of a single nucleotide T at position 6370 and deletion of a G at nucleotide 30845 resulted in frameshift mutations creating stop codons at amino acid positions -2 and 250, respectively. A duplication of 26 bp (17747-17772) in exon V was found in a severe haemophilia patient resulting in a termination codon in exon VI. The detection of the mutation by the combined use of PCR, DGGE and direct sequencing was important for carrier diagnosis of 20 families with no prior history of haemophilia B.

Amino Acids↗
PubMed1993

The individualised birthweight ratio: a more logical outcome measure of pregnancy than birthweight alone.

OBJECTIVE: To provide a new outcome measure for pregnancy specifically related to the individual. DESIGN: Computer analysis of physiological factors affecting birthweight. SETTING: Two provincial teaching hospitals (University and City Hospitals, Nottingham) and an associated district general hospital (Derby City Hospital) serving a defined catchment area in the East Midlands. SUBJECTS: All women delivering in the above hospitals since the start of computerised obstetric records: 31,561 women with gestational age verified by early pregnancy ultrasound scan data. MAIN OUTCOME MEASURES: Calculation of the predicted birthweight taking into account maternal and fetal physiological factors. Derivation of the individualised birthweight ratio (actual birthweight divided by predicted birthweight expressed as a percentage) for each individual baby. RESULTS: The individualised birthweight ratio redefines as normally grown 41% of babies below the 10th centile of crude birthweight for gestation. Other babies previously regarded as normal are redefined as growth retarded. At the upper end of the distribution 46% of those above the 90th centile of birthweight for gestation are redefined as normally grown. CONCLUSIONS: The predicted birthweight can be calculated for an individual pregnancy at a given gestation. The standardised comparison between this predicted birthweight and the actual birthweight is a more logical reflection of the normality of intrauterine growth and therefore more logical as an outcome measure for pregnancy than crude birthweight for gestation.

Adolescent↗
PubMed1994

Clinical trials of treatments of premenstrual syndrome: entry criteria and scales for measuring treatment outcomes.

OBJECTIVE: To demonstrate similarities and differences between the various instruments used by clinical trialists for measurement of premenstrual syndrome to encourage development of consensus of measurement to aid future research. DESIGN: Computer and manual searches of all trials of drugs used for premenstrual syndrome supplemented by retrieval of all questionnaires and scales cited. Letters were sent to the main manufacturers to identify trials not in the public domain. MAIN OUTCOME MEASURES: Number of scales in current use for classifying premenstrual syndrome; the symptoms included within them; their organisation of symptoms into clusters; the numerical values used in the scaling; the most frequently used items; and the extent of overlap in the criteria used. RESULTS: Three hundred and fifty clinical trials of 115 different drugs were identified. The most common symptoms or signs used in the scales were (frequency in square brackets) irritability [44], headache or migraine [40], depression [37], tearfulness [34], tension [31], anxiety [31], breast tenderness [31], mood swings or lability [30], back pain [30], weight gain [29], abdominal bloating [28], lack of concentration [28], food craving [28], and increased appetite [26]. Sixty-five different questionnaires or scales were used to classify premenstrual syndrome and for assessing entry eligibility and treatment outcomes; of these 65, 47 included sufficient details for a formal analysis and 18 scales grouped the symptoms or items into clusters or subgroups. CONCLUSION: There is wide diversity in the scales used for assessing entry eligibility and treatment outcomes in premenstrual syndrome. This makes comparative evaluation of possible treatments extremely complex and difficult. It is recommended that authorities and organisations involved in conducting trials of treatments for premenstrual syndrome develop a consensus statement about the best instrument to be used. Regulatory authorities could perhaps provide guidance to which scales they would accept when clinical trials of drugs for premenstrual syndrome are submitted to them for assessment. This would ensure that industry-sponsored trials provide objective data. Consensus is required given the poor performance of most current treatments of premenstrual syndrome.

Clinical Trials as Topic↗
PubMed1988

Transvenous and subcutaneous electrode system for an implantable defibrillator, improved on large pigs.

The currently required surgical procedure for implantable defibrillator implantation is a limiting factor and several groups are therefore investigating transvenous approaches. Our electrode system consists of a nondistal right ventricular catheter electrode and two or three subcutaneously (SC) placed electrodes. An optimal location for these SC electrodes is important to obtain the lowest possible defibrillation threshold (DFT) by allowing a more homogeneous current distribution within the thorax. An empirical approach consists of placing randomly the SC electrodes to find out the lowest possible DFT. A mathematical approach is to calculate the SC electrode locations for an optimal electric field distribution by using magnetic resonance images of thorax cross-sections and a specially designed computer program. Our recent experimental results are based on a series of 15 pigs weighing between 60 and 102 Kg. DFT ranged between 10 and 26 joules. We conclude that an electrode system with a right ventricular electrode and two or three subcutaneous electrodes can be optimized to reach a DFT for pigs with human-near body weights which is compatible with the energy capabilities of our implantable device.

Animals↗
PubMed2005

Patient-derived health state utilities for gastroesophageal reflux disease.

BACKGROUND AND AIMS: Gastroesophageal reflux disease is a chronic disease that adversely affects health-related quality of life. The purpose of this study was to derive health state utilities for patients with chronic heartburn symptoms. METHODS: We used a custom-designed computer program in order to elicit utilities with the time-tradeoff and standard-gamble techniques. Patients with chronic (more than 6 months) symptoms of gastroesophageal reflux disease entered the study. Two interviews were performed in random sequence either initially on medications for heartburn that adequately controlled symptoms, or off of medications for 1 wk while the patient was symptomatic. We also collected data using visual-analog scales, quality of life in reflux and dyspepsia (QOLRAD), and Gastrointestinal Symptom Rating Scale (GSRS) scores. RESULTS: We invited 222 patients to participate; 158 (71%) patients (129 men, 29 women) completed the study. Barrett's esophagus was present in 40 (25%), erosive disease in 17 (11%), and 118 (74%) had comorbid conditions. The mean (+/-SD) utility ratings were 0.94 +/- 0.09 on medical therapy and 0.90 +/- 0.12 off medications for patients with reflux alone using time tradeoff (p= 0.004), and 0.94 +/- 8.0 both on and off of antireflux medications with standard-gamble assessment (p= 0.96). Mean time-tradeoff scores were also significantly lower off of medications for patients with other comorbid conditions (p= 0.002). There was no significant difference between mean utility scores for patients with or without Barrett's esophagus or erosive disease. CONCLUSION: Gastroesophageal reflux disease adversely affects health-related quality of life. Time-tradeoff utility for patients with reflux disease is substantially higher when patients are on medication than off medications.

Adult↗
PubMed2005

Retention of luting agents on implant abutments of different height and taper.

OBJECTIVE: The purpose of this study was to evaluate the retention of four cements used to lute metal restorations onto computer designed and manufactured titanium implant abutments of different heights and convergence angles. MATERIAL AND METHODS: Test specimens consisted of metal coping cemented on Procera titanium abutments of 5, 7, and 9 mm of height, and of 0 degrees , 4 degrees , and 8 degrees of convergence angle. The cements used were zinc-phosphate, zinc oxide-eugenole, polyurethane resin with and without vaseline. The samples were tested in a universal testing machine. The mean uniaxial load at point of separation was determined. The results were statistically evaluated with ANOVA. RESULTS: The luting agent, the height, and the taper influence the retention of metal casting on customized CAD-CAM implant abutments. CONCLUSION: The most retentive cement was zinc-phosphate, followed by polyurethane, polyurethane plus vaseline, and zinc oxide-eugenol.

Analysis of Variance↗
PubMed1999

A comprehensive care clinic in Swedish dental undergraduate education: 3-year report.

In 1993, a new undergraduate curriculum was introduced at the Faculty of Dentistry, Karolinska Institute. The expanded comprehensive care clinic described in this 3-year report, is proposed as a potential model for a CC-clinic in dental undergraduate education. Students enter clinical training at the beginning of the 3rd year and continue through to their final semester, in the 5th year. The one student is responsible for the total oral care of all his/her patients. Patients are stratified on admission into 3 levels, depending on the complexity of treatment need. Before being assigned their 1st patients (patient level I), the students must fulfil specified requirements of theoretical knowledge and clinical procedures and obtain a proficiency certificate. After qualifying for higher proficiency certificates, denoting their level of clinical responsibility, the students assume successively greater responsibility for treatment of patients, with less supervision from clinical instructors. Clinical supervision is the responsibility of integrated multidisciplinary teams of faculty members. Each group of students is assigned a clinical tutor, who is responsible for overall treatment planning of their patients. The individual student's clinical progress and achievements are monitored by a specially designed computer program. Criteria for a final pass in the course are: (1) clinical maturity in overall patient management; (2) technical competence in conjunction with theoretical knowledge. 3 years experience of the new model for comprehensive clinical training in a patient-centred, multidisciplinary clinic has shown that; (a) students seem to acquire a greater understanding of comprehensive case management; (b) patients receive more co-ordinated care; (c) there has been no significant change in the number of clinical procedures completed; (d) difficulties arise in co-ordination of staff over the traditional specialist boundaries; (e) assessment of student maturity and professional responsibility is impeded by the lack of objective criteria.

Clinical Competence↗
PubMed2004

Mechanical stress generated by orthodontic forces on apical root cementum: a finite element model.

OBJECTIVES: 1) To determine the mechanical stress generated at the root apex during different types of tooth movement using a finite element model of an ideal, human maxillary central incisor. 2) To determine the relationship of thickness of cementum and the magnitude of mechanical stress at the root apex. DESIGN: Computer simulation. SETTING AND SAMPLE POPULATION: Not applicable, computer simulation. EXPERIMENTAL VARIABLES: Tooth and investing tissue layers (enamel, dentin, cementum, pulp, periodontal ligament, and alveolar bone). OUTCOME MEASURE: Von Mises and maximum principal stresses. RESULTS: Increasing the apical thickness of cementum increases the amount of mechanical stress. CONCLUSION: A finite element model incorporating all layers of a human maxillary central incisor has been developed. This model was used to determine the location and magnitude of mechanical stress generated for all regions of the tooth, PDL, and enclosed alveolar bone, when orthodontic forces are applied to the tooth. Mechanical stresses were found to increase at the root apex with increasing thickness of apical cementum.

Computer Simulation↗
PubMed1997

Recording non-nutritive sucking in the neonate. Description of an automatized system for analysis.

A new method for automatic analysis of non-nutritive sucking in newborn infants is described, which uses a specially designed computer program that analyses an analogue signal obtained from a pressure transducer inside a pacifier. Validation is done with four independent methods: electromyogram, visual identification, control of the automatic treatment and comparison of inter-observer results. A high degree of correspondence is shown. The system was applied to 58 healthy full-term neonates. Infants less than 24 h old demonstrated a significantly different sucking pattern compared with the 3-day-old infant. The duration of their bursts was longer (3.7 vs 2.8 s), the frequency of their sucking was lower (1.7 vs 2.0 Hz) and the variability of their sucking pattern was greater. These results also testify to the validity of the method inasmuch as the values for the different sucking parameters are similar to corresponding values presented earlier.

Age Factors↗
PubMed2002

High power ultrasound standard.

A sensitive radiation force balance for laboratory measurement of ultrasonic power is presented. The principle of the system is based on measuring the ultrasonic radiation force exerted on a conical float suspended in water. Technical details of the implementation of the economically attractive system are described. The operation of the system is automated with the aid of the IEEE-488 bus and a desktop computer. Design aspects that affect measurement uncertainty are investigated. A theoretical model for the measurement of ultrasonic power with a conical reflector target is discussed. The expanded uncertainty (95% confidence level) of the above radiation force conical float system is estimated to be between 5% to 10%.

Journal Article↗