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PubMed2005

Preliminary study of the lymphatic drainage system of the nose and paranasal sinuses and its role in detection of sentinel metastatic nodes.

CONCLUSIONS: The normal nasal lymphatic drainage runs via the facial vessels into the neck lymphatic nodes of levels I-II and this drainage pattern was found in our patients with sinonasal tumors. We found only one true-positive sentinel lymph node (SLN). Our pathological material was very limited and so further investigations are required before any valid conclusions can be drawn concerning the clinical value of SLNs in nasal tumors. Objectives. To detect the lymph collection route of the nasal fossae and paranasal sinuses and to identify the first echelon in the tumor metastatic cascade in order to prevent the risk of occult metastases in N0 necks in patients with primary head and neck squamous cell carcinoma (SCC). MATERIAL AND METHODS: Our control group comprised 30 patients (20 females; age range 19-50 years) suffering from chronic otitis media who had an anatomically normal nose and a cNO neck on palpation. The pathological group comprised 6 patients (2 females; age range 40-85 years) suffering from sinonasal tumors: 3 SCC, 1 recurrent melanoma, 1 ameloblastoma and 1 inverted papilloma. All had a clinically staged cNO neck on palpation and CT. In the control group, lymphoscintigraphy was carried out by means of unilateral injection of radioactive gold into the head of the inferior turbinate. The tracer was identified using a gamma camera 3 and 6 h after the injection. In the pathological group the chosen tracer was technetium, which was administered 1 day prior to surgery by means of injections into the heads of the inferior and middle turbinates, into the nasal septum and into the retromaxillary gingival mucosa. The tracer was identified transcutaneously using a navigator probe in the gamma camera at 15 min, 30 min and 1 h post-injection. A mark was drawn on the skin corresponding to the hot spot of the SLN. The study was repeated 30 min before surgery. The neck incision was selected according to the location of the SLN. A hand-held gamma probe was used in the operating theatre to detect in situ the radioactivity of the surgical excisional nasal area and the cervical SLN. Once the SLN was excised its radioactivity was confirmed ex situ, taking into account that the activity counts were at least three times greater than background. Postoperatively, all SLNs were histopathologically examined and cytokeratin staining was carried out immunohistochemically using the monoclonal antibody cocktail AE1/AE3. Results. In the control group, intense activity at the injection tracer site and lower activity in the submandibular area (level I) were detected in 26.6% of cases. Nasal radioactivity persisted for 6 h post-injection and submandibular radioactivity increased, also reaching the area corresponding to neck node level II (70%). In two cases (6.6%), radioactivity was observed in the retropharyngeal nodes. In the pathological group, the SLN was found in the submandibular area (level I) in three cases, and in the ameloblastoma patient three SLNs were found at levels I-II. Three cases were false positives, and no metastases were detected using any of the histopathological procedures. The only one true positive corresponded to a female with an SCC of the maxillary infrastructure with invasion of the gingival mucosa. The histopathological code was 1 and a metastasis was detected on hematoxylin-eosin examination. In the other two cases no SLNs were detected.

Adult↗
PubMed2006

Orienting attention based on long-term memory experience.

Attentional orienting and memory are intrinsically bound, but their interaction has rarely been investigated. Here we introduce an experimental paradigm using naturalistic scenes to investigate how long-term memory can guide spatial attention and thereby enhance identification of events in the perceptual domain. In the task, stable memories of objects embedded within complex scenes guide spatial orienting. We compared the behavioral effects and neural systems of memory-guided orienting with those in a more traditional attention-orienting task in which transient spatial cues guide attention. Memory-guided attention operated within surprisingly short intervals and conferred reliable and sizeable advantages for detection of objects embedded in scenes. Event-related functional magnetic resonance imaging showed that memory-guided attention involves the interaction between brain areas participating in retrieval of memories for spatial context with the parietal-frontal network for visual spatial orienting. Activity in the hippocampus was specifically engaged in memory-guided spatial attention and correlated with the ensuing behavioral advantage.

Adult↗
PubMed2002

Increased aeroallergen-specific interleukin-4-producing T cells in asthmatic adults.

BACKGROUND: Asthma, atopy and some forms of respiratory syncytial virus (RSV) disease are thought to be caused by T cells making IL-4 (Th2 cells). However, not all patients with similar patterns of clinical disease have the same underlying pathogenesis and the ability to detect immunopathogenic T cells by examination of the peripheral blood remains in doubt. With the prospect of specific immunotherapy for diseases caused by T cell subsets, it is important to determine whether peripheral blood mononuclear cell (PBMC) reactivity can be used to establish the presence of immunopathogenic responses and therefore to predict therapeutic effects. OBJECTIVE: To detect IL-4 and IFN-gamma production as markers of Th1 and Th2 responses in the peripheral blood of atopic and asthmatic adults. METHODS: PBMC from 22 adult asthmatics (18 of whom were atopic) and 21 non-asthmatic volunteers (ten of whom were atopic) were stimulated with cat, birch and house dust mite allergens, human rhinovirus, RSV and recombinant chimaeric F/G protein from RSV in vitro. ELISPOT assays were used to enumerate cells producing IL-4 and IFN-gamma. RESULTS: Asthmatics had a sixfold increase in frequencies of IL-4-producing cells to cat and birch allergen (median values: 37 vs. 7 per million PBMC, P < 0.01 and 20 vs. 3 per million PBMC, P < 0.04, respectively) compared to non-asthmatics. By contrast, non-asthmatic atopics showed no specific increase in antigen-specific IL-4 responses and there was no evident correlation between skin prick test reactivity and ELISPOT results. Atopics had significantly more IFN-gamma-producing cells specific for FG than nonatopics. while IFN-gamma and IL-4 responses to other antigens were not significantly different. CONCLUSION: Enhanced IL-4 responses to non-viral aeroallergens are seen in adults with asthma, while enhanced IFN-gamma responses to viral antigen FG were see in atopics. In practical terms, ELISPOT assays for specific cytokines may provide a method that could be used to monitor antigen-specific T cell responses in peripheral blood.

Adult↗
PubMed2001

Lead toxicosis and trace element levels in wild birds and mammals at a firearms training facility.

In May 1999, lead poisoning was diagnosed in a yellow-rumped warbler (Dendroica coronata) and a gray squirrel (Sciurus carolinensis) found at the Federal Law Enforcement Training Center (FLETC), Glynn County, GA, based on detection of 6.2 and 90.0 ppm wet weight (WW) lead in the liver of the warbler and squirrel, respectively. From October 21--26, 1999, 72 wild animals (37 mammals and 35 birds), comprised of 22 different species, were collected from a 24-ha area surrounding the FLETC outdoor firearms shooting range complex to evaluate exposure to lead and other trace elements. Ten animals were used as controls (five mammals and five birds) and were collected from areas 1.5--3 km outside the shooting range area. Kidney and liver tissues were analyzed for lead, zinc, and other trace elements. Bird gizzards and white-tailed deer abomasums were examined grossly and radiographically to detect metallic objects. Twenty-four (33.3%) animals (11 species) had kidney or liver tissue lead levels > 1.00 ppm, and 12 of these (6 species) had levels > 2.00 ppm. Carcasses of one brown-thrasher (Toxostoma rufum) and two white-tailed deer (Odocoileus virginianus) contained lead fragments. Elevated liver tissue levels of zinc (111.0 ppm) were detected in one brown thrasher that also had elevated kidney and liver tissue lead levels. In February 2000, seven yellow-rumped warblers and one solitary vireo (Vireo solitarius) found dead near the FLETC firearms shooting range also were diagnosed with lead poisoning, with liver and kidney tissue lead levels from 1.77--11.6 and 4.55--17.8 ppm WW, respectively. This frequency of elevated tissue lead levels among the animals examined, in combination with confirmed lead toxicosis in both avian and mammalian species at FLETC, indicates significant lead exposure of local wild bird and mammal communities via bullets and fragments in and on the soil surface of the four outdoor ranges. Most FLETC firearms training is being shifted to new baffled ranges (four walls with semiopen top) with bullet recovery capabilities to preclude future deposition of lead in the environment; existing outdoor ranges will be remediated to remove existing lead.

Animals↗
PubMed1995

Type-specific primer-mediated direct sequencing of consensus primer-generated PCR amplicons of human papilloma viruses: a new approach for the simultaneous detection of multiple viral type infections.

Consensus degenerate primers specific for the L1 and E1 regions were used to amplify anogenital HPV-DNA fragments. The mixture of the viral fragments was then directly sequenced with HPV-6, -11, -16, -18 and -33 type-specific computer-designed oligonucleotides as sequencing primers. The linking of a consensus primer-generated PCR amplification with type-specific primer-mediated direct sequencing and computer data bank analysis provided precise, more objective viral detection in the simultaneous presence of different HPV types. The method was successfully adapted for viral typing in clinical lesions which simultaneously contained different anogenital HPV sequences.

Anus Neoplasms↗
PubMed2005

Surgical skill is predicted by the ability to detect errors.

BACKGROUND: Objective analysis methods of surgical performance are now available so comparison between surgeons is available. One such method is by direct observation using the Objective Structured Assessment of Technical Skills (OSATS), but this is a time-consuming process; therefore, a simple screening tool for the ability to detect errors (previously validated) was analyzed and considered as a predictor of qualitative performance. METHODS: Thirty-eight volunteer surgeons were recruited to the skills laboratory to undertake 3 exercises. Two were bench-top surgical tasks that were scored using the global rating of the OSATS technique. The third task was the ability to detect simple errors in 22 synthetic models of common surgical procedures, some of which contained purposefully made errors. P<.05 was deemed to be statistically significant. RESULTS: The scores (interquartile ranges in parentheses) for the 3 sections were excision of sebaceous cyst=21 (19,24), closure of small bowel enterotomy=23 (21,27), and identification of errors=31 (27,34). Three scorers blinded to the operative models exhibited an interobserver reliability of .9 and .91 for the video tasks, respectively. Spearman's rank correlations between the error examination and performance on the 2 tasks were both statistically significant at .69 (cystectomy) and .54 (enterotomy). CONCLUSIONS: The ability to detect simple surgical errors is a predictor of technical skill and performance of bench tasks. What must be answered is whether the use of such models and principles can shorten the qualitative surgical learning curve.

Clinical Competence↗
PubMed2003

Is [18F]-2-fluoro-2-deoxy-d-glucose (FDG) scintigraphy with non-dedicated positron emission tomography useful in the diagnostic management of suspected metastatic thyroid carcinoma in patients with no detectable radioiodine uptake?

OBJECTIVE: Dedifferentiation of thyroid cancer leads to an inability of thyroid cells to concentrate iodine. In these cases, imaging methods that allow an accurate detection of recurrence and/or metastases at an early stage are essential for an adequate management of patients. Positron emission tomography using [18F]-2-fluoro-2-deoxy-d-glucose and a dedicated (dPET-FDG) or non-dedicated (nPET-FDG) camera has been suggested as a potential tool for the detection of tumour foci. DESIGN AND METHODS: This prospective study was undertaken to evaluate nPET-FDG in 51 consecutive patients (18 men, 33 women) with differentiated thyroid cancer (33 papillary, 11 follicular, four insular and three oncocytic (Hurthle-cell) thyroid carcinomas). Selection criteria were high thyroglobulin (Tg) levels (>10 ng/ml off-levothyroxine treatment) and no detectable radioiodine uptake, on a whole body scan performed with a high dose, in the absence of iodine contamination. RESULTS: Results were interpreted in terms of assumed presence of tumoral tIssue. Sensitivity of nPET-FDG was similar to that of conventional imaging modalities (67%). False negative nPET-FDG (n=16) were observed mostly in cases of micro-lesions (lymph nodes or lung metastases). Conversely, nPET-FDG identified new tumoral sites in 11 cases. Better sensitivity was found for nPET-FDG in patients with Tg levels higher than 15 microg/l (P<0.05). On a patient basis, results of nPET-FDG were equivalent to that of dPET-FDG. Finally, nPET-FDG changed treatment strategy in seven patients. CONCLUSIONS: nPET-FDG has a high sensitivity for the detection of tumour sites in patients when pathological iodine uptake cannot be demonstrated and appears to be a useful method in patients with elevated Tg levels, especially when dedicated PET is either unavailable or impractical.

Adenocarcinoma, Follicular↗
PubMed2003

Mechanical characteristics of rat vibrissae: resonant frequencies and damping in isolated whiskers and in the awake behaving animal.

We investigated the natural resonance properties and damping characteristics of rat macrovibrissae (whiskers). Isolated whiskers rigidly fixed at the base showed first-mode resonance peaks between 27 and 260 Hz, principally depending on whisker length. These experimentally measured resonant frequencies were matched using a theoretical model of the whisker as a conical cantilever beam, with Young's modulus as the only free parameter. The best estimate for Young's modulus was approximately 3-4 GPa. Results of both vibration and impulse experiments showed that the whiskers are strongly damped, with damping ratios between 0.11 and 0.17. In the behaving animal, whiskers that deflected past an object were observed to resonate but were damped significantly more than isolated whiskers. The time course of damping varied depending on the individual whisker and the phase of the whisking cycle, which suggests that the rat may modulate biomechanical parameters that affect damping. No resonances were observed for whiskers that did not contact the object or during free whisking in air. Finally, whiskers on the same side of the face were sometimes observed to move in opposite directions over the full duration of a whisk. We discuss the potential roles of resonance during natural exploratory behavior and specifically suggest that resonant oscillations may be important in the rat's tactile detection of object boundaries.

Animals↗
PubMed1996

Detection by polymerase chain reaction of wild-type measles virus genome in the cerebrospinal fluid of a patient with SSPE who had received measles vaccine.

BACKGROUND: Previous studies have reported that approximately 4-5% of patients with subacute sclerosing panencephalitis (SSPE) were given measles vaccination but had no history of natural measles. However, in the case who received measles vaccine, it has been extremely difficult to determine whether the actual cause of SSPE is the inoculated vaccine virus or not. OBJECTIVES: To detect the measles virus genome in a patient with SSPE and to analyze its nucleotide and deduced amino acid sequence. STUDY DESIGN: We applied the polymerase chain reaction (PCR) to detect the measles virus genome in specimens from a 12-year-old boy with SSPE who had received measles vaccine 10 years before and had no history of apparent natural measles. The oligonucleotide primers for PCR were prepared based on the nucleotide sequence of the F and NP genes of the measles virus Edmonston strain. RESULTS: F and NP genes were detected in both the cerebrospinal fluid and peripheral blood lymphocytes. Nucleotide and deduced amino acid sequence analysis of the F gene showed that the patient's virus was different from that of the vaccine strain. Judging from these results, it was likely that the SSPE-associated strain in this case was derived from the wild-type rather than the vaccine strain. CONCLUSIONS: PCR is a useful method to establish a definitive diagnosis of SSPE and to study the nature of the SSPE-associated virus.

Journal Article↗
PubMed2005

Multiple paths extraction in images using a constrained expanded trellis.

Single shortest path extraction algorithms have been used in a number of areas such as network flow and image analysis. In image analysis, shortest path techniques can be used for object boundary detection, crack detection, or stereo disparity estimation. Sometimes one needs to find multiple paths as opposed to a single path in a network or an image where the paths must satisfy certain constraints. In this paper, we propose a new algorithm to extract multiple paths simultaneously within an image using a constrained expanded trellis (CET) for feature extraction and object segmentation. We also give a number of application examples for our multiple paths extraction algorithm.

Algorithms↗
PubMed1995

Recognition performance of subjects with color-vision deficiencies on a polychromatic sonar screen for ship navigation.

To facilitate differentiation between objects that are approaching, stationary, and moving away, these objects are represented in different colors on the screens of sonar locating devices used in ship navigation. Yellow represents stationary objects, and represents approaching objects, and green represents those objects moving away. A total of 46 subjects with normal color vision and 184 individuals with color-vision deficiencies, among them 29 deuteranopic, 100 deuteranomalous, 21 protanopic and 34 protanomalous individuals, were investigated for their ability to identify different signals. Ten different objects were presented for a period of 64 s each. As a minimal requirement it was established that 50% of the respective experimental group be capable of recognizing the objects within half of this time. Whereas 73.3% of the subjects with normal color vision could meet this requirement, none of the subjects in the different groups with color-vision deficiencies could do so. Only 16.1% of the deuteranopic subjects, 33.1% of the deuteranomalous individuals, 16.2% of the protanopic subjects, and 37.6% of the protanomalous individuals detected all objects within 32 s. No appreciable difference in the ability to recognize signals occurred among the different groups of subjects with color-vision deficiencies.

Color Perception↗
PubMed2002

Early detection of cytomegalovirus (CMV) infection in bone marrow transplant patients by reverse transcription-PCR for CMV spliced late gene UL21.5: a two site evaluation.

BACKGROUND: Bone marrow transplant (BMT) patients at risk of developing cytomegalovirus (CMV) pneumonitis are identified routinely by the early detection of virus in blood. For early diagnosis of CMV infection, the RNA-based approach demonstrates advantages when compared with the current CMV antigen and DNA detection methods. OBJECTIVES: We have evaluated our previously developed reverse transcription-polymerase chain reaction (RT-PCR) to a spliced late CMV gene (SLG; J. Virol. Methods 56 (1996), 139) to monitor CMV infection in BMT patients at two clinical sites. The diagnostic value of the SLG RT-PCR was compared with the routine CMV antigen and DNA detection methods. STUDY DESIGN: Weekly blood samples from BMT patients were tested for CMV during the first 3 months post-transplant. The qualitative SLG RT-PCR, semiquantitative DNA PCR, and viral antigen tests were compared. The RNA and DNA PCR results were analysed in terms of their temporal relationship and consistency of CMV detection and compared with CMV infection diagnosed by viral antigen tests. RESULTS: Of the 101 BMT recipients studied, 25 developed CMV antigenemia and/or DNAemia resulting in symptomatic infection in two patients. All CMV PCR-positive patients were either CMV seropositive pretransplant or received marrow from seropositive donor. The highest incidence of CMV infection was seen in seropositive recipients (R+) irrespective of the donor's status. Detection of CMV infection by SLG RNA preceded CMV DNA detection by 0-2 weeks (median 1 week) and CMV antigen detection by 0-8 weeks (median 3 weeks). Once detected, the SLG RNA remained consistently positive before antiviral treatment was commenced. Both the SLG RNA and CMV DNA detection methods had the same clinical sensitivity, specificity, positive and negative predictive values of 100, 94, 80 and 100%, respectively. CONCLUSIONS: The RT-PCR for SLG RNA proved to be the earliest indicator of CMV infection in BMT patients demonstrating a sustained pattern of CMV detection during the 3 months post-transplant period. Although very similar in its diagnostic performance to CMV DNA PCR the SLG RNA RT-PCR does not require quantitation and provides an efficient and ongoing indication of active CMV infection.

Adolescent↗
PubMed2005

Tectal neurons signal impending collision of looming objects in the pigeon.

Although the optic tectum in non-mammals and its mammalian homolog, the superior colliculus, are involved in avoidance behaviors, whether and how tectal neurons respond to an object approaching on a collision course towards the animal remain unclear. Here we show by single unit recording that there exist three classes of looming-sensitive neurons in the pigeon tectal layer 13, which sends looming information to the nucleus rotundus or to the tectopontine system. The response onset time of tau cells is approximately constant whereas that for rho and eta cells depends on the square root of the diameter/velocity ratio of objects looming towards the animal, the cardioacceleration of which is also linearly related to the square root of this ratio. The receptive field of tectal cells is composed of an excitatory center and an inhibitory periphery, and this periphery does not inhibit responses to looming stimuli. These results suggest that three classes of tectal neurons are specified for detecting an object approaching on a collision course towards the animal, and that rho and eta cells may signal early warning of impending collision whereas tau cells initiate avoidance responses at a constant time before collision through the tectopontine system.

14-3-3 Proteins↗
PubMed1995

A self-rating to measure subjective effects of neuroleptic drugs, relationships to objective psychopathology, quality of life, compliance and other clinical variables.

The benefit of neuroleptic drugs in the treatment of schizophrenic patients is objectively beyond any doubt. However, most patients discontinue their neuroleptic drugs within some months. This low compliance might be caused by the lack of insight into the disease and the necessity of therapy. Also of major importance are adverse effects, not restricted to motor symptoms, but also affecting cognition and emotion. They are often too subtle to be detected by objective examination, but reported by patients who complain of a reduced quality of life with restrictions of emotionality, straight thinking and spontaneity. This syndrome, similar to negative symptoms of schizophrenia, has been named 'pharmacogenic depression' or 'neuroleptic-induced deficit syndrome'. To investigate this issue of major clinical relevance, a self-rating scale was developed to measure subjective well-being under neuroleptic treatment (SWN). First analyses indicate good practicability, reliability, validity and sensitivity. Data obtained from 280 remitted schizophrenic patients showed that the SWN was significantly correlated to objective psychopathology (Positive and Negative Symptom Scale, PANSS; r = -0.35), quality of life (r = 0.60) and other self-ratings of mood states [Profile of Mood Scale (POMS), Self-rating Depression Scale (SDS), Befindlichkeits Scale (BFS); r = 0.25-0.75]. A repeated application after 3 months in 53 patients did not show any change in SWN in those with constant neuroleptic medication, but there were marked alterations if the dosage or the drug was changed. The SWN in 28 patients treated with clozapine because of therapy resistance or major side effects was, despite negative selection, significantly better (t = 1.79, p = 0.03) than in 38 patients under classical neuroleptics. Moreover, even at dismissal, patients who were non-compliant 4-6 months later (n = 14) differed significantly (t = 3.21, p = 0.02) in SWN, but not in PANSS, from those who remained compliant (n = 34). These data indicate that the SWN is a useful tool for investigating a hitherto neglected psychopathological dimension. Subjective effects of neuroleptics are measurable, affect patients' quality of life and should be considered more thoroughly in clinical routine as well as in clinical trials of potential neuroleptic drugs.

Antipsychotic Agents↗
PubMed1998

Platelet angiotensin II binding sites and early detection of preeclampsia.

OBJECTIVE: To determine if platelet angiotensin II binding density during the second or third trimester of pregnancy can be used as a marker for early detection of women who will develop preeclampsia. METHODS: We collected blood samples from 412 nulliparous pregnant women during their second or third trimesters. They were classified in four groups after delivery: normotensive (n=297), transient hypertensive (n=54), preeclamptic (n=39), and chronic hypertensive (n=22). We also studied 35 nonpregnant women and 122 women in the peripartum period. The binding capacity of platelet angiotensin II receptors was analyzed in each patient. RESULTS: In normotensive pregnancies, there was a significant decrease in mean (+/-standard error of the mean [SEM]) platelet binding in the second trimester (1.6+/-0.2 fmol/10(9) cells) compared with nonpregnant women (3.3+/-0.7 fmol/10[9] cells). No statistical differences were observed in the mean (+/-SEM) number of platelet angiotensin II binding sites between the groups studied in the third trimester (normal: 1.7+/-0.1 fmol/10(9) cells; transient hypertensive: 2.3+/-0.4 fmol/10(9) cells; preeclamptic: 1.6+/-0.4 fmol/10(9) cells, and chronic hypertensive: 1.6+/-0.6 fmol/10(9) cells), nor were any significant differences found in second-trimester values. At cutoff levels providing identical sensitivities, angiotensin II binding showed significantly lower positive predictive values than mean arterial pressure (P < .05). With this study's sample size, we could have demonstrated an improvement in positive predictive values of 20% with a statistical power (1-beta) of 90%. CONCLUSION: The measurement of platelet angiotensin II receptor density cannot be recommended for the early detection of preeclampsia.

Adult↗
PubMed2005

Three distinct categories of time course of pain produced by oral capsaicin.

UNLABELLED: Humans vary in oral pain tolerance. Our earlier studies noted that the responses of subjects show 1 of 3 qualitative response patterns to a single oral capsaicin concentration, which we termed a tonic pattern (level detection response), a phasic pattern (change detection response), and an integrator pattern (cumulative irritation) response. These patterns were modeled quantitatively as the sum of 3 underlying processes. Two time-varying capsaicin stimulus profiles were designed from the quantitative model. In the ascending step paradigm, 30 ppm capsaicin was presented to 42 subjects for 15 minutes, followed immediately and without explanation by 300 ppm capsaicin for 25 minutes. In the descending step paradigm, 300 ppm capsaicin was presented to 36 other subjects for 24 minutes, followed by 10 ppm for 22 minutes. Subjective burn was rated at 1 minute and then at 3-minute intervals throughout the presentation. Fuzzy cluster analysis identified 3 distinct response phenotypes in each paradigm, corresponding to level detection, change detection, and cumulative irritation response patterns identified previously. Discriminant functions permitted classification of these phenotypes from the response patterns. Thus, these paradigms provide the first quantitative phenotypic description of distinct oral pain responses to a common irritant, capsaicin. PERSPECTIVE: This study examined the time-dependent behavior of pain produced by oral application of capsaicin. Three distinct temporal response phenotypes were identified objectively: level detection, change detection, and cumulative irritation detection. These time-dependent analyses provide a new dimension to understanding individual differences in pain sensation in clinical settings.

Administration, Oral↗
PubMed2004

Methods for the analysis of continuous biomarker assay data with increased sensitivity.

Prospective studies must be able to adapt to improved technology and adopt new assays with increased limits of detection. Our objective is to describe methods for incorporating new technologies in which the lower limits of quantification of a biomarker are enhanced. One may conduct an analysis of data with new and old sensitivity levels using a variety of methods, including retesting a sample of stored specimens from which multiple imputation may be applied, and a parametric approach that accounts for the changing limit of detection. We compare these methods in terms of their statistical bias and efficiency and identify the conditions under which the various methods perform well and then demonstrate our methods by evaluating differences in HIV RNA levels obtained from 2 prospective cohort studies.

Algorithms↗