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In vitro dissolution profile comparison and IVIVR. Carbamazepine case.

Dissolution data for the immediate or modified release drug products are usually collected as percent dissolved at multiple time points. Once an in-vitro/in-vivo relationship is established on a drug product, the dissolution profile becomes meaningful and important. In that context, if a firm desires to modify its formulation on which the in-vitro/in-vivo association has been established, a meaningful insight into the pharmacokinetics may be obtained by comparing the dissolution profiles of the two lots. In this presentation, we demonstrated a model dependent dissolution profile comparison approach using example of carbamazepine tablet dissolution data. Once a mathematical function was selected to describe the dissolution data coming from various standard lots, a similarity region could be constructed using the model parameter variances. To compare the test and reference lot dissolution profiles, a statistical distance was calculated between the mean parameters. A confidence region generated around the normalized mean statistical distance could then be compared with the similarity region to assess the similarity or dissimilarity of the dissolution profiles.

Biological Availability↗

FT-IR photoacoustic depth profiling spectroscopy of enamel.

Photoacoustic Fourier transform infrared (PA-FT-IR) depth profiling spectra of the enamel of an intact human tooth are obtained in a completely nondestructive fashion. The compositional and structural changes in the tissue are probed from the enamel surface to a depth of about 200 microns. These changes reflect the state of tissue development. The subsurface carbonate gradient in the enamel could be observed over the range of about 10-100 microns. The carbonate-to-phosphate ratio increases in the depth profile. The depth profile also reveals changes in the substitutional distribution of carbonate ions. Type A carbonates (hydroxyl substituted) increase relative to type B carbonates (phosphate substituted) with increasing thermal diffusion length. In addition to the changes in the carbonate ion distribution and content, the PA-FT-IR depth profile clearly indicates a dramatic increase in the protein content relative to the phosphate content with increased depth. The changes in the carbonate content and distribution, along with the changes in the protein content, may be responsible for the changes observed in the apatitic structure in the depth profile of the enamel.

Carbonates↗

Attenuation profiles of the petrous bone with acoustic neuroma.

Attenuation profiles across the petrous bone covering the whole internal auditory meatus (IAM) were constructed from the printouts obtained by computed tomography (CT) with narrow collimation performed on 12 patients with 13 acoustic neuromas. In healthy patients the attenuation profiles of right and left petrous bone were very similar in shape. The attenuation values of the individual pixels in the pixel columns of the printout located at the site of the porus and the IAM reflected the demineralization of the petrous bone and the widening of the porus and the IAM caused by the acoustic neuroma. A widening deep in the meatus was demonstrated in a patient with an intracanalicular tumor, and therefore it seems possible to make this diagnosis by CT scanning combined with the construction of attenuation profiles across the petrous bone. In the presence of unilateral acoustic neuroma there was a significant and characteristic difference in shape between the attenuation profiles of the two sides with generally lower attenuation values on the tumor side together with signs of widening of the porus and the IAM. In cases of bilateral acoustic neuroma comparison of the attenuation profiles can be made with mean attenuation curves obtained from scanning normal petrous bones. The prevailing physical limitations for demonstrating a narrow bony canal like the IAM with CT was experimentally analyzed using bone-simulating plastic material.

Humans↗

Nutritional and gonadal effects on the intra-acinar profiles of low-Km and high-Km aldehyde dehydrogenase activity in rat liver.

Total and low-Km aldehyde dehydrogenase (ALDH) activity was measured in 50-150 ng microdissected liver tissue samples of the entire sinusoidal length. High-Km ALDH activity was calculated by subtracting the low-Km ALDH values from the total ALDH activity. Enzyme activity was measured by a microchemical assay, using the oil-well technique with luminometric determination of NADH. The intra-acinar profiles of high-Km and low-Km ALDH activity could be demonstrated graphically for both male and female rats after 84 h of starvation, and after starvation and refeeding for 6 nights. In addition, the ALDH distribution patterns of juvenile, castrated, and castrated and testosterone-treated rats were determined. It could be demonstrated that starvation, and starvation followed by refeeding, lead to changes in enzyme activity which parallel the loss and regain of liver- and body-weight. The nutritional factors do not essentially alter the normal intra-acinar profiles. In juvenile rats, ALDH is lower by 30% in comparison with the controls, but sex-differences in the distribution profiles are not yet present. Castration has no effect on the amount of enzyme activity but the sex specific distribution profiles are less marked. The main effect of testosterone treatment is an elevation of low-Km ALDH in the perivenous zone. The characteristics of the intra-acinar profiles of high-Km and low-Km ALDH activity are discussed with respect to hepatic acetaldehyde oxidation and alcoholic liver damage.

Aldehyde Dehydrogenase↗

The relationship of Minnesota Multiphasic Personality Inventory (MMPI) profile clusters to pain behaviors.

Previous research involving cluster analysis of Minnesota Multiphasic Personality Inventory (MMPI) profiles among persons with chronic low back pain has suggested the existence of four distinct profile clusters. The present study had two goals: (1) to replicate the previous finding independently and (2) to investigate the relationship of the profiles to the subjects' self-reported pain history and response to treatment. Subjects were 92 patients in a multimodal inpatient low back-pain treatment program. A cluster analysis of the MMPI profiles was performed and the resultant clusters were compared in terms of histories and treatment outcome. The four clusters were successfully replicated for the total sample and for males and females separately. The profiles were significantly related to subjects' pain histories, but only one outcome difference was found. It was inferred that the MMPI is of value in understanding patients' pain coping behaviors but that further research is needed to explore the utility of the MMPI in understanding their response to treatment.

Back Pain↗

Reliability and concurrent relations between the teacher version of the Child Behavior Profile and the Conners Revised Teacher Rating Scale.

A total of 104 disturbed boys aged 6-11 were assessed with the teacher version of the Child Behavior Profile and the Conners Revised Teacher Rating Scale (TRS). A subsample of 55 boys were reassessed with both measures at an interval of 1 week. For the teacher Profile, test-retest correlations averaged r = .87 for eight behavior problem scales and r = .91 for four adaptive functioning scales. Reliabilities were slightly higher for Externalizing scales (average r = .91) than for Internalizing scales (r = .80). Reliabilities averaged .94 for the Revised TRS. Correlations between the two measures indicated a strong correspondence between the three Externalizing scales of the Profile and the factor-based TRS scales. Specifically, Profile scales labeled Inattentive, Nervous-Overactive, and Aggressive correlated highly (p less than .001) with TRS scales labeled Inattentive-Passive, Hyperactivity, and Conduct Problem, respectively. The Conners Hyperkinesis Index correlated highly with all three Externalizing scales of the Profile, particularly Aggressive (r = .82). Overall, these results support the reliability and concurrent validity of both measures.

Achievement↗

The distribution of Parascaris equorum eggs in the soil profile of bare paddocks in some Norwegian studs.

Fifteen bare paddocks, which consisted of soil only and were located on 12 different studs, were examined for their content of Parascaris equorum eggs in the upper 15 cm of the soil profile. The paddocks were classified into three different groups according to the type of soil: clayey soil (A), morainic soil (B) and gravel or gravel-like sand (C). Soil profiles were collected down to a depth of 15 cm and were divided into three layers: 0-5 cm (D1), 5-10 cm (D2) and 10-15 (D3). The eggs in each layer were counted and identified as infective or noninfective eggs. The paddocks in group C, which had good drainage conditions, had significantly lower numbers of eggs in the whole profile and in D1 and D2 than the paddocks in groups A or B. Furthermore, there was a significantly higher proportion of the total egg count present in D3 in the group C paddocks. This may have been due to a higher degree of passive transportation of eggs down in the profile in the gravel or gravel-like sand. Even though there was a significantly higher proportion of infective eggs in the soil from the group C paddocks, the lower total numbers of eggs resulted in a lower total number of infective eggs in those paddocks. The study showed that the soil type was an important factor in determining the content of P. equorum eggs in the upper layer of the soil profile in bare paddocks and consequently for the potential infestation of horses with P. equorum.

Animals↗

Large scale database experiments to assess the significance of matching DNA profiles.

Over 5,700 three-probe VNTR DNA profiles collected by several United Kingdom (UK) laboratories have been compared to examine the probability of randomly matching 2 samples from different individuals. In over 16 million comparisons, using a matching rule corresponding to the matching guideline employed by the UK Forensic Science Service, no profiles were found to match at the 3 loci D1S7 (MS1), D7S21(MS31) and D12S11 (MS43a). The frequency of occurrence of a set of Caucasian profiles have been estimated with 6 reference databases. The results show that there were greater differences in the frequency estimates when using a database of Afro-Caribbean or Asian profiles, rather than a different Caucasian database. The results further demonstrate the power and robustness of the VNTR DNA profiling technique for forensic casework.

Bayes Theorem↗

Plasmid profiles and klebocin types in epidemiologic studies of infections by Klebsiella pneumoniae.

The epidemiological methods of klebocin typing, antibiogram and plasmid DNA profile were evaluated using organisms isolated from a suspected epidemic of gentamicin-resistant Klebsiella pneumoniae and unrelated strains from different geographical areas as controls. The electrophoretic analysis of plasmid DNAs from Klebsiella pneumoniae showed the presence of at least one and up to as many as seven plasmids in each strain. The molecular weight of plasmid DNAs ranged from 1 to greater than 70 mega daltons. While none of the control Klebsiella pneumoniae strains showed identical plasmid profiles, 63% of the epidemic-related Klebsiella pneumoniae strains did. Klebocin typing and plasmid DNA profile gave different results for the same strains. Plasmid DNA profile was found to be a more valuable method than klebocin typing alone or klebocin typing in combination with antibiogram for differentiating epidemiologically related from unrelated isolates. Both plasmid DNA profile and klebocin typing methods were superior to antibiogram.

Anti-Bacterial Agents↗

Real-time observation of intra- and extracardiac blood flow profile in man using instantaneous B-mode and multichannel Doppler echocardiography.

We observed instantaneous blood flow velocity profiles at the right and left ventricular outflow tracts, the ascending aorta, and the lower thoracic aorta in human subjects using a newly devised method of real-time multichannel Doppler echocardiography. In 20 apparently healthy subjects, the blood flow velocity profile was successfully obtained in all cases at the right and left ventricular outflow tracts--in 13 cases at the ascending aorta, in 12 cases at the aortic arch, and in ten cases at the lower thoracic aorta. The configuration of the profile was almost flat during systole at the left ventricular outflow tract, the ascending aorta, and the descending aorta. The profile was triangular at the right ventricular outflow tract, where the velocity was faster at the ventricular septal side than at the free wall side, and it was also triangular at the aortic arch, where the velocity was faster at the inner side of the arch than at the outer side. These observations were very similar to those reported by others in previous experimental studies. Thus, the present study demonstrates that it is possible to record noninvasively the instantaneous blood flow velocity profile in humans using this new Doppler echocardiographic instrument.

Adolescent↗

The application of diagnostic specific cost profiles to cost and reimbursement control in hospitals.

A system has been developed to generate hospital budgets based on the types of patients served. Several hundred classes of patients are defined according to clinical attributes such as diagnoses and surgical procedures, and for each class a profile of resources consumed is determined. The class definitions are based both on homogeneity of patient care processes as well as resource consumption. These profiles are expressed as revenues generated by charging departments and as costs both direct and indirect for all services. A methodology has been developed to associate all indirect costs with their source for each service included in the profile. From a forecast of patient load by class, budgets can be computed from the cost profiles and revenues determined from the charging profiles. Further analysis thus can include the effect of changes in case mix as well as changes in patient care processes. The effect on revenues of different reimbursement mechanisms can also be projected as a function of the case mix. The system is currently being implemented for demonstration and evaluation of the Yale-New Haven Hospital.

Budgets↗

[The assessment of the facial profile in relation to head posture].

On the basis of Schwarz's [21] facial typology, soft tissue facial profile was evaluated in relation to 3 head positions: natural head position, head position according to the Frankfurter Horizontal, and head position according to a subjective personal appraisal of an aesthetically pleasing profile, i.e. aesthetic head position. Forty children (20 girls and 20 boys) and 40 adults (20 women and 20 men) with varying occlusal relationships constituted the study group. Facial photos oriented according to the above 3 head positions were evaluated. The results revealed that head posture had a decisive impact on the outcome of the facial profile evaluation. Significant differences existed between natural head position on the one hand and Frankfurter Horizontal and aesthetic head position on the other. Due to the relatively large methodological error in the registration of natural head position, and the resulting effect of this error on profile evaluation, natural head position can lead to misleading results. The advantage of Frankfurter Horizontal as opposed to aesthetic head position is the result of a subjective appraisal. Thus, when using Schwarz's method in evaluating facial profile, Frankfurter Horizontal still appears to be quite appropriate.

Adolescent↗

A non-local gap-penalty for profile alignment.

The length of an alignment of biological sequences is typically longer than the mean length of its component sequences. (This arises from the insertion of gaps in the alignment.) When such an alignment is used as a profile for the alignment of further sequences (or profiles), it will have a bias toward additional sequences that match the length of the profile, rather than the mean length of sequences in the profile, as the alignment of these will entail fewer (or smaller) insertions (so avoiding gap-penalties). An algorithm is described to correct this bias that entails monitoring the correspondence, for every pair of positions, of the mean separations in both profiles as they are aligned. The correction was incorporated into a standard dynamic programming algorithm through a modification of the gap-penalty, but, unlike other approaches, this modification is not local and takes into consideration the overall alignment of the sequences. This implies that the algorithm cannot guarantee to find the optimal alignment, but tests suggest that close approximations are obtained. The method was tested on protein families by measuring the area in the parameter space of the phase containing the correct multiple alignment. No improvement (increase in phase area) was found with a family that required few gaps to be aligned correctly. However, for highly gapped alignments, a 50% increase in area was obtained with one family and the correct alignment was found for another that could not be aligned with the unbiased method.

Algorithms↗

Effect of physician profiling on utilization. Meta-analysis of randomized clinical trials.

OBJECTIVES: An American Medical Association survey reported that more than half of physicians are subjects of either clinical or economic profiling. This multilevel meta-analysis was designed to assess the clinical effect of peer-comparison feedback intervention (profiles) in changing practice patterns. METHODS: Systematic computerized and manual searches were combined to retrieve articles on randomized controlled clinical trials testing profiling reports. Eligible studies were randomized, controlled clinical trials that tested peer-comparison feedback intervention and measured utilization of clinical procedures. To use all available information, data were abstracted and analyzed on three levels: (1) direction of effects, (2) p value fro the statistical comparison, and (3) odds ratio (OR). MAIN RESULTS: In the 12 eligible trials, 553 physicians were profiled. The test result was p < .05 for the vote-counting sign test of 12 studies (level 1) and p < .05 for the z-transformation test of 8 studies (level 2). There were 5 trials included in the OR analysis (level 3). The primary effect variable in two of the 5 trials had a nonsignificant OR. However, the overall OR calculated by the Mantel-Haenszel method was significant (1.091, confidence interval: 1.045 to 1.136). CONCLUSIONS: Profiling has a statistically significant, but minimal effect on the utilization of clinical procedures. The results of this study indicate a need for controlled clinical evaluations before subjecting large numbers of physicians to utilization management interventions.

Confidence Intervals↗

Basal activity profiles of NPH and [Nepsilon-palmitoyl Lys (B29)] human insulins in subjects with IDDM.

[Nepsilon-palmitoyl Lys (B29)] human insulin is a fatty acid-acylated derivative of insulin with extended action compared to unmodified insulin when infused intravenously (i.v.) secondary to its binding to circulating albumin. The duration and activity profile of the acylated (A) and NPH (B) insulins were assessed following subcutaneous (s.c.) doses of (A) 6 nmol/kg and (B) 1.2 nmol/kg (equivalent to 0.2 U/kg) in 9 subjects with IDDM. After overnight i.v. infusion of regular human insulin, morning glucose was (A) 6.9 +/- 0.1 and (B) 6.8 +/- 0.1 mmol/l. After the s.c. injection, i.v. human insulin or glucose was infused to maintain near-basal glycaemia and tracer glucose to assess hepatic glucose production (HGP). An activity profile was deduced for each study by expressing the glucose infusion rate at each time point, as a fraction (%) of the basal (measured) HGP, and the i.v. insulin infusion rate as a fraction (%) of the basal requirement. The two fractions are combined by adding the fractional glucose infusion rate and subtracting the fractional insulin infusion rate. Infusion rates of i.v. insulin in the morning were (A) 0.96 +/- 0.096 and (B) 1.22 +/- 0.09 pmol x kg(-1) x min(-1). After insulin injection, i.v. insulin requirements decreased and were below 10% of basal between 100 and 150 min. A constant activity profile of 0% represents a perfect substitution of the basal i.v. insulin infusion by the s.c. dose. The actual profile is defined by deviations from this (above) and was -17 +/- 11, 7 +/- 10, -9 +/- 6 and -18 +/- 18% for [Nepsilon-palmitoyl Lys (B29)] human insulin and 17 +/- 12, 5 +/- 6, -9 +/- 15, 22 +/- 18% for NPH insulin at 3, 6, 9 and 12 h after s.c. injection. HGP was similar for the two insulins, demonstrating similar metabolic actions and profiles both peripherally and at the liver.

Adult↗

Development of a measure profiling problems and needs of psychiatric patients in the community.

We argue the advantages of a measure profiling common problems faced by psychiatric patients in the community and indicating a likely need for service recognition, review and possible assistance. We describe the development of such a measure, the 35-item Profile of Community Psychiatry Clients (PCPC), and the identification of four relevant domains. Component scales assess coping limitations, behavioural problems, levels of social support and organic problems. High test-retest reliability was established, and a number of tests of the measure's validity were undertaken. Discriminant validity was established by demonstrating that those case managed by a community mental health service returned significantly higher scale scores than a comparison group who, while having a similar diagnostic profile, were not case managed. Additionally, scale scores were associated with a number of categorical and dimensional validators reflecting aspects of service need, and distinctly with service costs. We demonstrate that PCPC scores correspond with scores generated by the Life Skills Profile (LSP), a measure of disability, and examine the extent to which PCPC scales correspond to those contained in the Health of the Nation Outcome Scales (HoNOS). We argue for the scale's capacity to provide both a profile of central problems faced by patients and their likely need for community-based service assistance.

Adult↗

High resolution depth profile analysis by elastic recoil detection with heavy ions.

Elastic recoil detection (ERD) with energetic heavy ions (e.g. 60-120 MeV(127)I) is a suitable method to measure depth profiles of light and medium heavy elements in thin films. The advantages of this method are reliable and quantitative results and elementally and isotopically resolved depth profiles. A relative energy resolution of 0.07% has been measured in real ERD-experiments using the Q3D magnetic spectrograph at the Munich tandem accelerator and a large solid angle of detection of 5 msr. The good energy resolution allows atomic depth resolution near to the surface which has been obtained at flat and smooth carbon samples. A large solid angle of detection is necessary to measure a depth profile with the desired accuracy before the sample is significantly altered by the ion beam. As an example carbon profiles of thin carbon layers, prepared by a laser plasma ablation deposition process, have been investigated revealing the high depth resolution and its power to resolve elemental profiles at gradiated interfaces.

Journal Article↗

Haptic detection thresholds of Gaussian profiles over the whole range of spatial scales.

In the literature only a small subset of the broad range of scales of human haptic perception has been explored. In this experiment, haptic detection thresholds have been investigated over a wide range of spatial scales. Computer-controlled manufacturing techniques have made it possible to produce stimuli with sufficient accuracy to explore the gamut of haptic scales. We used stimuli with a convex or concave Gaussian-shaped profile running over the middle of a strip. The width of the Gaussian profile was varied between 150 microns and 240 mm. In this range of spatial scales a number of mechanisms, ranging from cutaneous mechanoreception to proprioception in fingers, arm and shoulder, contribute to haptic perception. The discrimination threshold between a flat surface and a Gaussian surface was investigated in a series of two alternative forced choice experiments on human subjects. The thresholds run from 1 micron for the narrowest Gaussian profiles to 8 mm for the broadest profile. The same thresholds were found for convex and concave shapes. Over the range of spatial scales, from 1 mm width on, the dependence of the detection threshold on the spatial width of the Gaussian profile was found to be a power function with an exponent of about 1.3.

Discrimination, Psychological↗