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PubMed2006

Application of mass spectrometry for metabolite identification.

Metabolism studies play a pivotal role in drug discovery and development. Characterization of metabolic "hot-spots" as well as reactive and pharmacologically active metabolites is critical to designing new drug candidates with improved metabolic stability, toxicological profile and efficacy. Metabolite identification in the preclinical species used for safety evaluation is required in order to determine whether human metabolites have been adequately tested during non-clinical safety assessment. From an instrumental standpoint, high performance liquid chromatography (HPLC) coupled with mass spectrometry (MS) dominates all analytical tools used for metabolite identification. The general strategies employed for metabolite identification in both drug discovery and drug development settings together with sample preparation techniques are reviewed herein. These include a discussion of the various ionization methods, mass analyzers, and tandem mass spectrometry (MS/MS) techniques that are used for structural characterization in a modern drug metabolism laboratory. Mass spectrometry-based techniques, such as stable isotope labeling, on-line H/D exchange, accurate mass measurement to enhance metabolite identification and recent improvements in data acquisition and processing for accelerating metabolite identification are also described. Rounding out this review, we offer additional thoughts about the potential of alternative and less frequently used techniques such as LC-NMR/MS, CRIMS and ICPMS.

Animals↗
PubMed1992

Reaction time for global and local identification of small-large composite letters presented in different orientations.

Eight men and eight women were timed as they made judgments about a large capital letter F composed of small versions of the same letter. The subjects were asked to indicate by manual key-pressing responses whether either the large letter (global identification task) or the small letters (local identification task) were normal or reflected letters. With both the large and small letters always in the same orientation but sometimes conflicting in their normal-reflected aspect, the letters were presented in six different angular orientation. Analysis showed that reaction time (RT) (1) increased in relation to the deviation of the letters from standard upright, (2) was slower when both small and large letters were reflected than when both were normal, and (3) was faster for the global than for the local identification task when the letters were completely inverted. The study provided only qualified evidence that global identification of the normalness-reflectedness of letters occurs more quickly than local identification of this attribute.

Female↗
PubMed2001

Perceptual interactions of facial dimensions in speeded classification and identification.

The representation underlying the identification and classification of semirealistic line drawings taken from a computer model of the face was investigated by using a speeded classification task and an identification task. These data were analyzed by using a multidimensional extension of signal detection theory, within which varieties of perceptual interactions between dimensions within and across stimuli can be characterized. The dimensions of interest here were eye separation, nose length, and mouth width. The response time and accuracy data from the speeded classification task suggest that processing of a given feature did depend on whether other features were present or absent, but given that other features were present, the results strongly support separability (a macrolevel, across-stimulus form of invariance) for all pairs of facial dimensions used. This separability was confirmed by the subsequent identification task. Owing to its greater resolution, the identification task can reveal interactions that might exist at more microlevels of processing. In fact, the identification data did indicate the presence of perceptual dependence between facial dimensions within a stimulus when the dimensions that were varied were close in spatial proximity (i.e., eye separation and nose length). Within the theoretical framework, perceptual dependence can be interpreted as correlated noise between otherwise separate channels (and hence, is logically distinct from separability). This dependence was greatly reduced for dimensions that were more distant (eyes and mouth). The relation between these results and the configural effects that have been observed with faces as stimuli in other studies is discussed.

Adult↗
PubMed2004

Serial processing in melody identification and the organization of musical semantic memory.

Unlike the visual stimuli used in most object identification experiments, melodies are organized temporally rather than spatially. Therefore, they may be particularly sensitive to manipulations of the order in which information is revealed. Two experiments examined whether the initial elements of a melody are differentially important for identification. Initial exposures to impoverished versions of a melody significantly decreased subsequent identification, especially when the early exposures did not include the initial notes of the melody. Analyses of the initial notes indicated that they are differentially important for melody identification because they help the listener detect the overall structure of the melody. Confusion errors tended to be songs that either were drawn from the same genre or shared similar phrasing. These data indicate that conceptual processing influences melody identification, that phrase-level information is used to organize melodies in semantic memory, and that phrase-level information is required to effectively search semantic memory.

Auditory Perception↗
PubMed2004

[Clinical usefulness of odor stick identification test for patients with olfactory disturbance].

The odor stick identification test for Japanese (OSITJ) is the latest in measuring olfactory identification. It consists of 13 odorants familiar to the Japanese population. We studied the relationship between the Japanese standard olfactory test (T & T olfactometer) and the OSITJ in 182 patients with olfactory disturbance. The identification ratio in 2 of OSITJ tests using 13 odorants was correlated significantly negatively with the detection and recognition threshold measured by the T & T olfactometer. A high correlation between identification ratio and olfactory thresholds was maintained even when the number of odorants in the OSITJ was reduced to 2. For each odorant used, the identification ratio correlated significantly with olfactory thresholds. Results from the OSITJ provide a measure of the degree of olfactory deficit because the ratio of correct answers obtained by the OSITJ decreased gradually with of the severity of olfactory disturbance. Compared to the T & T olfactometer, the OSITJ has several advantages for use in the clinic. These include minimal odor pollution of the test room, simplicity of use, and shorter clinical time needed to administer the test. The OSITJ may be ideal for use in screening due to the minimum number of odorants needed. In conclusion, the OSITJ is useful for detecting and evaluating olfactory disturbance in Japanese people.

Diagnostic Techniques and Procedures↗
PubMed2001

Characterization of microorganism identification in the United States in 1996.

CONTEXT: The National Inventory of Clinical Laboratory Testing Services (NICLTS) was designed to give an unbiased estimate of all patient testing performed by laboratories registered under the Clinical Laboratory Improvement Amendments in 1996. OBJECTIVE: Survey data were used to develop a profile of laboratory testing primarily intended to identify microorganisms or antibodies to these microorganisms. DESIGN: Estimates of the extent of microorganism identification were derived from the NICLTS database by identifying associated tests and methods. The volumes for tests performed at locations that primarily prepared blood components for distribution were excluded. Organisms of public health importance were identified from the National Notifiable Disease list maintained by the Centers for Disease Control and Prevention. PARTICIPANTS: Laboratories that were enrolled in the 1996 Online Certification Survey and Reporting System, maintained by the US Health Care Finance Administration, and that performed laboratory testing in 1996. OUTCOME MEASURE: Estimated volumes and associated confidence limits by test, method, specimen type, public health importance, and testing location. RESULTS: Excluding testing of the blood supply, 315 million tests (95% confidence limits, 280-354 million tests) were performed in the United States for microorganism identification. Those tests for which public health consensus requires national reporting represented 38% of this total. Although hospitals performed 46% of all microorganism identification, they only performed 33% of the testing for microorganisms of public health importance. Independent and specialty laboratories performed 38% of all testing but 65% of the testing for microorganisms of public health importance. Direct methods (methods not involving culture) were used in 77% of the tests for microorganisms of public health importance and in 42% of all identification tests. CONCLUSIONS: The distribution of microorganism identification testing found using NICLTS data is consistent with plans to modernize the public health surveillance system in the United States.

Data Collection↗
PubMed1989

Automated biochemical identification of bacterial fish pathogens using the Abbott Quantum II.

The Quantum II, originally designed by Abbott Diagnostics for automated rapid identification of members of Enterobacteriaceae, was adapted for the identification of bacterial fish pathogens. The instrument operates as a spectrophotometer at a wavelength of 492.600 nm. A sample cartridge containing 20 inoculated biochemical chambers is inserted in the path of the analyzing beam. Reactions are converted into a 7-digit octal biocode, relayed via a sensor to the memory module, and compared to biocodes preprogrammed in the memory. An identification is then printed. Presently, the Quantum II is capable of identifying human strains of Aeromonas hydrophila and Edwardsiella tarda. This study was initiated to determine the feasibility of expanding the use of the Quantum II to include identification of bacterial fish pathogens. Ten to 50 isolates of Edwardsiella ictaluri, Serratia liquefaciens, Yersinia ruckeri, Aeromonas hydrophila, typical Aeromonas salmonicida, and atypical Aeromonas salmonicida were utilized to determine optimal incubation conditions, relative stability of the biochemicals, and ability to obtain consistent biocode numbers. After sorting the octal biocodes from the 169 isolates into groupings using a cluster analysis technique, it was shown by a Chi-square goodness of fit test that isolates of a given species were sorted into the same cluster group at a frequency of at least 99%. Results of this study illustrate the usefulness of the Quantum II BID system for the identification of bacterial fish pathogens not contained within the system's memory module.

Animals↗
PubMed1999

Activity of neurons in human temporal cortex during identification and memory for names and words.

Extracellular recordings of human temporal cortical neuronal activity during identification and memory for object names or words were obtained from 31 neurons at 18 sites in 12 left language dominant patients undergoing left (10) or right (2) awake craniotomy for epilepsy under local anesthesia. Frequency of activity during identification was compared with perceptual controls, that during the encoding phase of recent memory to identification of the same material. Statistically significant changes in one or more temporal epoch (p < 0.005) of one or more comparisons were present for 27 of the 31 neurons in either hemisphere. Few neurons changed activity in the same direction for both words and names. The instruction to retain an item in recent memory changed activity in most neurons from that during identification of the same material, although the items presented were identical and overtly identified in each task. Any individual neuron usually changed activity in one direction for only one task. There are separate, widely distributed neural networks for identification or recent memory for each type of material. The majority of nearby neurons recorded through the same extracellular microelectrode were related to the networks for different tasks. The temporal characteristics of these changes were also investigated; 31% of the changes were "phasic": temporally related to presentation or response to the item. Most of the remaining neuron changes were sustained throughout a task, often for several minutes. These task-specific sustained changes may reflect effects of thalamo-cortical attentional systems. Individual neurons had both sustained and phasic changes to different tasks.

Action Potentials↗
PubMed2000

Hawaii's healthy start program of home visiting for at-risk families: evaluation of family identification, family engagement, and service delivery.

OBJECTIVE: To describe family identification, family engagement, and service delivery in a statewide home visiting program for at-risk families of newborns. SETTING: Six target communities of Hawaii's Healthy Start Program (HSP), which incorporates 1) early identification of at-risk families of newborns via population-based screening and assessment, and 2) paraprofessional home visiting to improve family functioning, promote child health and development, and prevent child maltreatment. DESIGN: Cross-sectional study: describes early identification process and family characteristics associated with initial enrollment. Longitudinal study: describes home visiting process and characteristics associated with continued participation. SUBJECTS: Cross-sectional study: civilian births in 6 communities (n = 6553). Longitudinal study: at-risk families in the intervention group of a randomized trial of the HSP (n = 373). MEASURES PROCESS: completeness and timeliness of early identification and home visiting activities; family characteristics: sociodemographics, child abuse risk factors, infant biologic risk. RESULTS: Early identification staff determined risk status for 84% of target families. Families with higher risk scores, young mothers with limited schooling, and families with infants at biologic risk were more likely to enroll in home visiting. Half of those who enrolled were active at 1 year with an average of 22 visits. Families where the father had multiple risk factors and where the mother was substance abusing were more likely to have >/=12 visits; mothers who were unilaterally violent toward the father were less likely. Most families were linked with a medical home; linkage rates for other community resources varied widely by type of service. Half of families overall, but >/=80% of those active at 1 year, received core home visiting services. Performance varied by program site. CONCLUSIONS: It is challenging to engage and retain at-risk families in home visiting. Service monitoring must be an integral part of operations.

Child↗
PubMed2001

Combinatorial peptide libraries as an alternative approach to the identification of ligands for tumor-reactive cytolytic T lymphocytes.

The recent identification of molecularly defined human tumor antigens recognized by autologous CTLs has opened new opportunities for the development of antigen-specific cancer vaccines. Despite extensive work, however, the number of CTL-defined tumor antigens that are suitable targets for generic vaccination of cancer patients is still limited, mostly because of the painstaking and lengthy nature of the procedures currently used for their identification. A novel approach is based on the combined use of combinatorial peptide libraries in positional scanning format (positional scanning synthetic combinatorial peptide libraries, PS-SCLs) and tumor-reactive CTL clones. To validate this approach, we herein analyzed in detail the recognition of PS-SCLs by Melan-A-specific CTL clones. Our results indicate that, at least for some clones, most of the amino acids composing the native antigenic peptide can be identified through the use of PS-SCLs. Interestingly, this analysis also allowed the identification of peptide analogues with increased antigenic activity as well as agonist peptides containing multiple amino-acid substitutions. In addition, biometrical analysis of the data generated by PS-SCL screening allowed the identification of the native ligand in a public database. Overall, these data demonstrate the successful use of PS-SCLs for the identification and optimization of tumor-associated CTL epitopes.

Amino Acid Sequence↗
PubMed2002

Digital imaging methods as an aid in dental identification of human remains.

The physical comparison of known (K) and questioned (Q) evidence samples is an accepted tool in numerous forensic identification disciplines (1). A subset of this process is the use of antemortem and postmortem dental radiographs to identify unidentified human remains. This method has been generally accepted for decades (2). The outcome is performed with a considerable degree of accuracy, due in part to a finite pool of possible candidates for identification derived via the NCIC database, passenger lists, and law enforcement Missing Persons reports. This paper describes a dental identification comparison protocol that incorporated digital imaging technology in this process. The computer was used to create digital exemplars of the K and Q evidence that were spatially and quantitatively compared (3). The digital mode allowed direct metric and morphologic comparison through the aid of a digital camera, desktop computer, monitor, and printer. The well-known computer program Adobe Photoshop 5.0 (4) was used to process the digital information in two forensic cases described in this paper. It is a commercially available digital imaging editing program that is operated on laptop and desktop computers possessing sufficient chip speed and RAM (Pentium II or equivalent and at least 76MB RAM) to open the large-size files generated by high-resolution digital capture devices. This program accepts raster-based image formats (e.g. .JPG, .BMP). Photoshop is noted for its diverse imaging functions, which allow the computer monitor to be used as a comparison microscope when Q and K sample images are tiled side-by-side and/or superimposed. Two and three-dimensional Q and K evidence samples can be individually digitized and then independently resized to allow two-dimensional comparison. The investigator also has the ability to create magnified images (200% to 300%) when the original digital image has been captured at near photoquality resolution (300 dpi). The visual comparison of physical features on the computer monitor permits a large field of view and robust digital control over image quality. Photographic measurement and enhancement features of Adobe Photoshop mimics and in some circumstances surpasses the historic use of conventional photographic manipulation in forensic casework. This paper presents two cases processed via routine forensic odontology identification protocols. These protocols had minimal results due to limitations described in the case histories. The additional application of digital methods proved useful in the ultimate identification of these human remains.

Adolescent↗
PubMed2002

[Clinical and histological factors associated with sentinel node identification in breast cancer].

OBJECTIVE: To study the predictive factors that are associated with intraoperative identification of the sentinel lymph node (SLN). METHODS: Lymphatic mapping using blue dye was performed in 108 patients with stage I and II operable primary breast cancer. Subsequently the patients received operations of breast cancer including axillary dissection. Clinical and histological factors were assessed to determine those that were associated with intraoperative identification of the SLN. RESULTS: The sentinel node was identified at the time of surgery in 84 patients (77.78%). Of the clinical factors assessed, age(y) < 50 (chi(2) = 7.447, P < 0.01), tumour in the upper quadrant (chi(2) = 6.330, P < 0.05), diagnosis by preoperative biopsy (chi(2) = 5.509, P < 0.05), successful mapping of the lymphatic duct (chi(2) = 13.125, P < 0.01) were significant in identifying the sentinel node at operation. No histological factor was associated with intraoperative identification of the sentinel node. CONCLUSION: There are the possibility of failure of SLN identification at sentinel lymph node biopsy. Our results suggest that the best predictor of intraoperative sentinel node identification is the visualization of the lymphatic duct on mapping by blue dye. Other factors such as age, tumour site as well as diagnostic method are also important in determining the success of the procedure.

Breast Neoplasms↗
PubMed2002

The confidence-accuracy relationship in eyewitness identification: the effects of reflection and disconfirmation on correlation and calibration.

Participants viewed a simulated crime and attempted an identification from an 8-person target-present or target-absent lineup. The authors examined identification confidence-accuracy relations, contrasting a control condition (n = 310) with 2 manipulations designed to improve confidence scaling. Before indicating confidence, participants reflected on encoding and identification test conditions (n = 316) or suggested hypotheses about why their identification decision might have been wrong (n = 318). Confidence-accuracy correlations were weak and did not differ across conditions. However, for positive identifications, confidence and accuracy were well calibrated in the experimental conditions, although not in the control condition; similar patterns were observed for lineup rejections. Explanations for calibration differences in terms of discrimination difficulty, (mis)match between encoding and test stimuli, and the availability of confidence cues were advanced.

Adolescent↗
PubMedDate not supplied

[Possible express identification of human remains in case of their intense destruction after exposure to physical factors].

The problem of identification of human remains is still one of the most difficult and pressing problems of forensic medicine. Such identification is particularly difficult in cases of intense destruction caused by exposure to physical factors (explosion, contusion, fire, compression, etc.). Approaches to identification in such cases are less available and differ essentially from traditional approaches used, for example, in cases when the remains are exposed to natural long-acting factors. This "white spot" is attempted to be liquidated by investigating aircraft accidents with grave destructive results. The potentialities of express identification of human remains in such cases are shown and a complex of characteristic signs which can serve as the landmarks are distinguished. The authors emphasize the strict adherence to certain regulations when working at the site of technogenic disasters and the hazards of disordering the process of identification in case these regulations are neglected.

Accidents, Aviation↗
PubMed2003

Identification of regulatory binding sites using minimum spanning trees.

Recognition of protein-binding sites from the upstream regions of genes is a highly important and unsolved problem. In this paper, we present a new approach for studying this challenging issue. We formulate the binding-site recognition problem as a cluster identification problem, i.e., to identify clusters in a data set that exhibit significantly different features (e.g., density) than the overall background of the data set. We have developed a general framework for solving such a cluster identification problem. The foundation of the framework is a rigorous relationship between data clusters and subtrees of a minimum spanning tree (MST) representation of a data set. We have proposed a formal and general definition of clusters, and have demonstrated that a cluster is always represented as a connected component of the MST, and further it corresponds to a substring of a linear representation of the MST. Hence a cluster identification problem is reduced to a problem of finding substrings with certain features, for which algorithms have been developed. We have applied this MST-based cluster identification algorithm to a number of binding site identification problems. The results are highly encouraging.

Algorithms↗
PubMed2003

Dentists' qualifications affect the accuracy of radiographic identification.

This study assessed the effects of forensic odontologists' training and experience upon the accuracy of their dental radiographic identifications. Forty participating odontologists with various levels of training and experience completed a Web-based survey of their qualifications and then completed nine Web-based radiographic identification cases. They made their identifications using the American Board of Forensic Odontology Categories and Terminology for Body Identification. The results indicate that odontologists with high levels of training and experience performed significantly more accurately than those with lower levels. We conclude that high levels of training and experience in forensic odontology should be developed, maintained, and required of dentists who participate in a forensic team dealing with challenging identification cases.

Analysis of Variance↗
PubMed2003

The gander disaster: dental identification in a military tragedy.

The authors record the contributions of dentistry to the identification of victims of one of the most significant disasters in aviation and U.S. military history--the December 1985 crash of a DC-8 charter airliner near Gander, Newfoundland (now known as Newfoundland and Labrador), Canada, which killed 248 Army personnel and 8 crewmembers. Most of the dental records of the military victims were destroyed in the crash, and, as a result, this loss hampered dental identification. Nevertheless, dental identification was the primary means of identification for many because a very high percentage of the bodies were severely burned and fragmented. Many phases of the U.S. identification efforts have been reported, but the dental-investigation aspects have been mentioned only in passing. Therefore, this article documents the dental team's organization, methodology, and a variety of remarkable problems that the team encountered.

Accidents, Aviation↗
PubMed2004

[Parasite identification in the surveillance of imported leishmaniasis cases in Italy].

An accurate Leishmania classification was defined since 1980s by the use of isoenzyme analysis. To date, this procedure still represents the reference identification technique, despite the increasing use of molecular approaches. Studies and surveillance methods on leishmaniases are strongly conditioned by the knowledge and mapping of all the parameters characterizing each nosogeographical entity. On this respect, the identification of parasites from all the actors of the natural life cycle plays a key role. With the increasing population movements and climate changes, novel risk factors could be identified associated to Leishmania geographical distribution and spreading: a) the introduction into Italy of new populations of L. infantum from other countries; b) the introduction of new Leishmania species that may find a suitable milieau to support their life cycle in our country. The objective of this report is to present the surveillance activity on imported leishmaniases by the Leishmania Identification Reference Centre, ISS. Two different methodologies were routinely applied: a) isoenzyme electrophoretic analysis, which requires parasite culture, and b) a number of molecular techniques, used for both diagnosis and parasite identification, differently applied according to the geographical origin of the suspected leishmaniasis case. When possible, both types of methodologies were applied. From 1986 to June 2002, 38 imported cases of leishmaniases were identified: 9 visceral (VL) and 29 cutaneous (CL) cases, of which 22 from the Old and 7 from the New World. Pathology, Leishmania species/zymodeme and geographical origin features are reported in the paper. Seven out of 9 VL patients were HIV positive, of whom 5 detected in the period 1993-1995. This high importation rate can be associated to the general increase in Mediterranean Leishmania/HIV coinfections in that period. Following HAART treatment, VL imported cases became occasional; no introduction of new L. infantum populations has been detected. On the other hand, our findings show an increase of CL imported cases from different areas of the Old and New Worlds. This phenomenon, however, is so far limited to new Leishmania species that could hardly be introduced in our country, because of their strict biological requirements (i.e. vectors and/or natural reservoir hosts). Since June 2002, 10 further suspected imported cases were recorded. For these patients--whose Leishmania identification is still in course--the origin/visited geographical areas were only slight different from the previous. However, the characteristics of the patients are changing: there are more immigrants that occasionally visited their place of origin, and Italian military staff.

AIDS-Related Opportunistic Infections↗