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PubMed2003

Pulsed ultrasound measurements of depth and regression of basal cell carcinomas after photodynamic therapy: relationship to probability of 1-year local control.

BACKGROUND: The regression of clinical basal cell carcinoma (BCC) after photodynamic therapy (PDT) is poorly understood, but is potentially important when, as is increasingly the case, a second treatment is contemplated. High-frequency pulsed ultrasound provides noninvasive information on skin and lesion thickness. OBJECTIVES: To relate pulsed ultrasound measurements before and after PDT to the probability of local control of BCC by PDT. METHODS: Skin thickness and lesion thickness were measured by 20-MHz pulsed ultrasound in 181 patients diagnosed as having BCC. Maximal lesion thickness was determined by repeatedly sampling the BCCs. Measurements were made immediately prior to PDT with aminolaevulinic acid plus 630 nm visible light, and then at 1, 6 and 12 months. RESULTS: Skin thickness in individual patients did not vary with time in this study (mean +/- SD 2.3 +/- 0.6 mm; P = 0.8). In contrast, BCC mean +/- SD maximal thickness 4-6 weeks after PDT was significantly smaller than pretreatment (0.6 +/- 0.8 mm vs. 1.3 +/- 0.8 mm; P < 0.001). The overall probability of 1-year local control fell from 85% when only BCCs </= 1.5 mm thick were considered, to 75% when BCCs up to 3 mm were included. CONCLUSIONS: Ultrasound measurement of maximal pretreatment BCC thickness strongly predicts the probability of local control, defined clinically, at 1 year after a single PDT treatment. The degree of regression at 4-6 weeks is additionally predictive.

Aged↗

PubMed2006

A genetic model for determining MSH2 and MLH1 carrier probabilities based on family history and tumor microsatellite instability.

Mutation-predicting models can be useful when deciding on the genetic testing of individuals at risk and in determining the cost effectiveness of screening strategies at the population level. The aim of this study was to evaluate the performance of a newly developed genetic model that incorporates tumor microsatellite instability (MSI) information, called the AIFEG model, and in predicting the presence of mutations in MSH2 and MLH1 in probands with suspected hereditary non-polyposis colorectal cancer. The AIFEG model is based on published estimates of mutation frequencies and cancer penetrances in carriers and non-carriers and employs the program MLINK of the FASTLINK package to calculate the proband's carrier probability. Model performance is evaluated in a series of 219 families screened for mutations in both MSH2 and MLH1, in which 68 disease-causing mutations were identified. Predictions are first obtained using family history only and then converted into posterior probabilities using information on MSI. This improves predictions substantially. Using a probability threshold of 10% for mutation analysis, the AIFEG model applied to our series has 100% sensitivity and 71% specificity.

Adaptor Proteins, Signal Transducing↗

PubMed2001

Open probability of homomeric murine 5-HT3A serotonin receptors depends on subunit occupancy.

1. The time course of macroscopic current responses of homomeric murine serotonin 5-HT3A receptors was studied in whole cells and excised membrane patches under voltage clamp in response to rapid application of serotonin. 2. Serotonin activated whole cell currents with an EC(50) value for the peak response of 2 microM and a Hill slope of 3.0 (n = 12), suggesting that the binding of at least three agonist molecules is required to open the channel. 3. Homomeric 5-HT3A receptors in excised membrane patches had a slow activation time course (mean +/- S.E.M. 10-90 % rise time 12.5 +/- 1.6 ms; n = 9 patches) for 100 microM serotonin. The apparent activation rate was estimated by fitting an exponential function to the rising phase of responses to supramaximal serotonin to be 136 s(-1). 4. The 5-HT3A receptor response to 100 microM serotonin in outside-out patches (n = 19) and whole cells (n = 41) desensitized with a variable rate that accelerated throughout the experiment. The time course for desensitization was described by two exponential components (for patches tau(slow) 1006 +/- 139 ms, amplitude 31 %; tau(fast) 176 +/- 25 ms, amplitude 69 %). 5. Deactivation of the response following serotonin removal from excised membrane patches (n = 8) and whole cells (n = 29) was described by a dual exponential time course with time constants similar to those for desensitization (for patches tau(slow) 838 +/- 217 ms, 55 % amplitude; tau(fast) 213 +/- 44 ms, 45 % amplitude). 6. In most patches (6 of 8), the deactivation time course in response to a brief 1-5 ms pulse of serotonin was similar to or slower than desensitization. This suggests that the continued presence of agonist can induce desensitization with a similar or more rapid time course than agonist unbinding. The difference between the time course for deactivation and desensitization was voltage independent over the range -100 to -40 mV in patches (n = 4) and -100 to +50 mV in whole cells (n = 4), suggesting desensitization of these receptors in the presence of serotonin does not reflect a voltage-dependent block of the channel by agonist. 7. Simultaneously fitting the macroscopic 5-HT3A receptor responses in patches to submaximal (2 microM) and maximal (100 microM) concentrations of serotonin to a variety of state models suggests that homomeric 5-HT3A receptors require the binding of three agonists to open and possess a peak open probability greater than 0.8. Our modelling also suggests that channel open probability varies with the number of serotonin molecules bound to the receptor, with a reduced open probability for fully liganded receptors. Increasing the desensitization rate constants in this model can generate desensitization that is more rapid than deactivation, as observed in a subpopulation of our patches.

Animals↗

PubMed2004

Event-related brain potentials to irrelevant auditory stimuli during selective listening: effects of channel probability.

The purpose of this study was to identify the cognitive process reflected by a positive deflection to irrelevant auditory stimuli (Pdi) during selective listening. Event-related brain potentials were recorded from 9 participants in a two-channel (left/right ears) selective listening task. Relative event probabilities of the relevant/irrelevant channels were 25%/75%, 50%/50%, and 75%/25%. With increasing probability of the relevant channel, behavioral performances (the reaction time and hit rate) for the targets within the relevant channel improved, reflecting development of a more robust attentional trace. At the same time, the amplitude of the early Pdi (200-300 ms after stimulus onset) elicited by the stimuli in the irrelevant channel with a decreased probability was enhanced in the central region. This positive relation between the strength of the attentional trace and the amplitude of the early Pdi suggests that the early Pdi is elicited by a mismatching between an incoming irrelevant stimulus and an attentional trace.

Acoustic Stimulation↗

PubMed2006

Medications associated with probable medication overuse headache reported in a tertiary care headache center over a 15-year period.

OBJECTIVES: To evaluate the substances associated with medication overuse headache (MOH) in a headache center, over the course of the past 15 years. BACKGROUND: The acute treatment of migraine has substantially changed over the past 15 years, and therefore, the substances associated with MOH may have changed as well. METHODS: We randomly reviewed charts of subjects seen during the years of 2005, 2000, 1995, and 1990, to identify substances associated with MOH. Since the criteria proposed by the second edition of the International Classification of Headache Disorders require causal attribution, demonstrated by improvement after withdrawal (and this was not assessed in this study), herein we refer to probable MOH (PMOH). We contrasted the substances associated with PMOH over the studied years. RESULTS: Our sample consists of 1200 individuals, 300 per year of interest. The proportions of subjects with a diagnosis of PMOH remained stable over the years, varying from 64% of all cases seen in the center in 1990, to 59.3% in 2005. We found a significant decrease in the relative frequency of probable ergotamine overuse headache (from 18.6% to 0%, P < .0001), and in probable combination analgesic overuse headache (from 42.2% to 13.6%, P < .0001). The differences were not significant for opioid overuse headache. The relative frequency increased significantly for the triptans (from 0% to 21.6%, P < .0001), simple analgesics (from 8.8% to 31.8%, P < .05), and for combinations of acute medications (from 9.8% to 22.7%, P = .01). CONCLUSION: While overuse of acute medications remains an important problem in the tertiary care arena, the substances associated with the overuse have dramatically changed over the past 15 years. Educational initiatives should emphasize that the newer specific acute migraine medications (triptans) may also be associated with PMOH.

Adult↗

PubMed1996

Probable adverse drug reactions in a rural geriatric nursing home population: a four-year study.

OBJECTIVE: To quantitate probable adverse drug reactions (ADRs) in a geriatric nursing homes population. DESIGN: A repeated measures prospective study. SETTING: Two nursing home populations in rural Georgia. PATIENTS: All 332 residents present for 30 or more days over a 4-year period. MEASUREMENT: Admission and monthly drug regimen review for each resident, Naranjo algorithm assessment of each ADR, with monthly reports to attending physicians and follow-up within the next month. RESULTS: There were 444 probable ADRs in 217 of 332 residents (67.4%) during this period. The 217 residents had a mean 1.9 +/- 1.3 probable adverse drug reactions (range, 1-9). The ADR group differed statistically from the rest of the population only in the number of drugs per patient (7.8 +/- 2.6 vs 3.3 +/- 1.3), which was almost twice the number of active problems present in both the ADR (4.0 +/- 0.9) and non-ADR populations (3.8 +/- 1.4). The organ systems most commonly involved in the 444 ADRs observed were cardiovascular (188), central nervous system (129), gastrointestinal (82), endocrine (41), immune (17), hematologic (7), pulmonary (6), and renal (5). The drugs most commonly implicated in ADRs were, in decreasing order, diuretics, antipsychotics, anxiolytics, potassium supplements, digoxin, NSAIDs, insulin, theophylline, H2-receptor antagonists, antiinfectives, anticonvulsants, and thyroid supplements. There were 39 multiple drug ADRs in 34 patients. In decreasing order the drug classes in multiple ADRs were CNS depressants, antihypertensives, potassium-altering therapy, and NSAIDs. Numerous patients had repetitions of the same ADR, especially with antipsychotics, NSAIDs, and insulin. CONCLUSIONS: ADRs are a common occurrence in a geriatric nursing home population, and may be related to inadequate attention to the patients history as well as to unrealistic therapeutic endpoints.

Adverse Drug Reaction Reporting Systems↗

PubMedDate not supplied

Hydrogeologic unit flow characterization using transition probability geostatistics.

This paper describes a technique for applying the transition probability geostatistics method for stochastic simulation to a MODFLOW model. Transition probability geostatistics has some advantages over traditional indicator kriging methods including a simpler and more intuitive framework for interpreting geologic relationships and the ability to simulate juxtapositional tendencies such as fining upward sequences. The indicator arrays generated by the transition probability simulation are converted to layer elevation and thickness arrays for use with the new Hydrogeologic Unit Flow package in MODFLOW 2000. This makes it possible to preserve complex heterogeneity while using reasonably sized grids and/or grids with nonuniform cell thicknesses.

Forecasting↗

PubMed1976

Non-uniform probabilities of quantal release at the crayfish neuromuscular junction.

1. Transmitter release at the neuromuscular junction of the crayfish walking leg has been found to deviate from binomial predictions immediately after the onset of repetitive stimulation of the presynaptic nerve at frequencies of at least 15 Hz. 2. After several minutes of continuous stimulation, and at lower rates of stimulation, however, the number of quanta released could be described quite well by binomial or Poisson statistics. 3. Deviations from the theoretical expectations were characterized by (a) fewer release failures than predicted, (b) occasions in which the number of quanta released was more than the estimated number of quanta available for release, and (c) a tendency for the data to be underdispersed. 4. Each of these three characteristics are consistent with the hypothesis that different releasable quanta may have different probabilities of responding to a nerve impulse. 5. Using two different methods, different values of the non-uniform probabilities were estimated from the data. At each synaptic site at least one of the estimated probabilities was very high. 6. The need for caution in interpreting statistical description of quantal release is emphasized.

Animals↗

PubMed1986

The probability of quantal secretion along visualized terminal branches at amphibian (Bufo marinus) neuromuscular synapses.

The number of quanta secreted from selected sites along terminal branches at toad (Bufo marinus) neuromuscular junctions was determined. Terminal branches were visualized by prior staining with the fluorescent dye, 3-3 Diethyloxadicarbocyanine iodide (DiOC2(5)); neither impulse conduction nor quantal release were affected by DiOC2(5) at concentrations less than 10 microM. The evoked quantal release recorded with an extracellular micro-electrode (me) at different sites along the length of terminal branches was determined in an external calcium concentration, [Ca]o, of 0.35-0.45 mM. For short branches (40-80 microns), me remained approximately constant for over 60% of the branches; for the rest, me declined approximately exponentially with an average length constant of 17 +/- 2 microns (mean +/- S.E. of mean). For both medium (81-120 microns) and long branches (121-160 microns), me declined in nearly all cases approximately exponentially with length constants of 39 +/- 5 and 54 +/- 8 microns respectively. These changes in me were observed at synapses having a wide range of terminal branching patterns. Some DiOC2(5)-stained branches possessed discontinuous cholinesterase staining. In general, me declined along these branches in the same way as along DiOC2(5)-stained branches with continuous cholinesterase staining. It is suggested that because of the decline in me along most medium and long terminal branches, many release sites have a very low probability for secretion in low [Ca]o. Release sites near the point of nerve entry, which have a relatively high probability, therefore make the main contribution to secretion recorded with an intracellular micro-electrode. As a consequence, transmitter secretion from the whole terminal does not fluctuate from impulse to impulse as much as expected if there were a large number of release sites, each with a low probability of secretion. Transmitter secretion then follows binomial rather than Poisson statistics.

Action Potentials↗

PubMed2002

Probability density functions for hyperbolic and isodiachronic locations.

Animal locations are sometimes estimated with hyperbolic techniques by estimating the difference in distances of their sounds between pairs of receivers. Each pair specifies the animal's location to a hyperboloid because the speed of sound is assumed to be spatially homogeneous. Sufficient numbers of intersecting hyperboloids specify the location. A nonlinear method is developed for computing probability density functions for location. The method incorporates a priori probability density functions for the receiver locations, the speed of sound, winds, and the errors in the differences in travel time. The traditional linear approximation method overestimates bounds for probability density functions by one or two orders of magnitude compared with the more accurate nonlinear method. The nonlinear method incorporates a generalization of hyperbolic methods because the average speed of sound is allowed to vary between different receivers and the source. The resulting "isodiachronic" surface is the locus of points on which the difference in travel time is constant. Isodiachronic locations yield correct location errors in situations where hyperbolic methods yield incorrect results, particularly when the speed of propagation varies significantly between a source and different receivers.

Journal Article↗

PubMed1993

Nonuniform probability of glutamate release at a hippocampal synapse.

A change in the probability of neurotransmitter release (Pr) is an important mechanism underlying synaptic plasticity. Although Pr is often assumed to be the same for all terminals at a single synapse, this assumption is difficult to reconcile with the nonuniform size and structure of synaptic terminals in the central nervous system. Release probability was measured at excitatory synapses on cultured hippocampal neurons by analysis of the progressive block of N-methyl-D-aspartate receptor-mediated synaptic currents by the irreversible open channel blocker MK-801. Release probability was nonuniform (range of 0.09 to 0.54) for terminals arising from a single axon, the majority of which had a low Pr. However, terminals with high Pr are more likely to be affected by the activity-dependent modulation that occurs in long-term potentiation.

Animals↗

PubMed1979

14C-most-probable-number method for enumeration of active heterotrophic microorganisms in natural waters.

A most-probable-number method using 14C-labeled substrates is described for the enumeration of aquatic populations of heterotrophic microorganisms. Natural populations of microorganisms are inoculated into dilution replicates prepared from the natural water from which the organisms originated. The natural water is supplemented with a 14C-labeled compound added so as to approximate a true environmental concentration. 14CO2 evolved by individual replicates is trapped in NaOH and counted by liquid scintillation techniques for use in scoring replicates as positive or negative. Positives (14CO2 evolution) are easily distinguished from negatives (no 14CO2 evolution). The results from a variety of environments using the 14CO2 procedure agreed well with previously described methods, in most instances. The 14C-most-probable-number method described here reduces handling procedures over previously described most-probable-number procedures using 14C-labeled substrates. It also appears to have advantages over other enumeration methods in its attempt to approximate natural conditions more closely.

2,4-Dichlorophenoxyacetic Acid↗

PubMed1984

Modified agar medium for detecting environmental salmonellae by the most-probable-number method.

Salmonellae in the environment remain a potential source of disease. Low numbers of salmonellae have been detected and enumerated from environmental samples by most-probable-number methods which require careful colony selection from a plated agar medium. A modified xylose lysine brilliant green medium was prepared to control the loss of selectivity caused by heating the brilliant green component. Added agar reduced colony spreading. The medium contained 47 g of xylose lysine agar base per liter; the agar content was adjusted to 2%, autoclaved, cooled to 50 degrees C, and then amended just before pouring to include H2S indicator and 7 ppm (7 ml of 1:1,000 brilliant green per liter) of unheated brilliant green dye. H2S-positive salmonellae were easily detected from sewage sludge compost to the exclusion of most other gram-negative bacteria. As a result, fewer non-salmonellae were picked for further most-probable-number analysis, greatly reducing the work load associated with the most-probable-number method. Direct plating was possible for enumerating salmonellae in laboratory composts containing ca. 10(3) or more salmonellae.

Agar↗

PubMed2004

Modeling the rate of attachment of Listeria monocytogenes, Pantoea agglomerans, and Pseudomonas fluorescens to, and the probability of their detachment from, potato tissue at 10 degrees C.

The rate of attachment of bacteria to, and their subsequent detachment from, the cut surface of raw potato tissue was measured and modeled by using mathematical approaches that allowed detailed objective comparisons of adhesion processes under different conditions. Attachment was rapid and reached equilibrium after contact for 60 min. A new method to measure the probability of detachment was developed and modeled, revealing that the probability of detachment for Pseudomonas fluorescens remained unchanged for contact times between less than 5 s and 60 min. Listeria monocytogenes, however, was more easily removed initially, with the probability of detachment decreasing over the first 2 min of contact but remaining constant and equivalent to that for Pseudomonas fluorescens thereafter. For all of the bacteria tested, the number of bacteria attached after 2 min of contact was proportional to the inoculum concentration raised to the power of 0.79.

Bacterial Adhesion↗

PubMed2004

Profile of antibodies to the nucleocapsid protein of the severe acute respiratory syndrome (SARS)-associated coronavirus in probable SARS patients.

Profiles of antibodies to the nucleocapsid protein of the severe acute respiratory syndrome (SARS)-associated coronavirus in 445 probable SARS patients and 3,749 healthy people or non-SARS patients were analyzed by antigen-capturing enzyme-linked immunosorbent assay. Antinucleocapsid antibodies were elucidated in 17.5% of the probable SARS patients 1 to 7 days after the onset of symptoms and in 80% of the patients 8 to 14 days after the onset. About 90% of the probable SARS patients were positive 15 or more days after illness. Antibody titers increased up to 70 days, and high antibody titers were maintained at least for another 3 months. Of the healthy people and non-SARS patients, only seven (0.187%) were weakly positive.

Adult↗

PubMed2001

Prognostic value of stress echocardiography in women with high (> or = 80%) probability of coronary artery disease.

OBJECTIVE: To assess the prognostic significance of stress echocardiography in women with a high probability of coronary artery disease (CAD). SETTING: Secondary and tertiary cardiology unit at a university teaching hospital. PARTICIPANTS: A total of 135 women (mean (SD) age 63 (9) years) with pre-test probability of CAD > or = 80% were selected from a database of patients investigated by treadmill or dobutamine stress echocardiography between 1995 and 1998. MAIN OUTCOME MEASURES: Patients were followed up for occurrence of subsequent cardiac events (cardiac death, myocardial infarction, admission with unstable angina, and revascularisation) using a structured telephone interview and case note review. RESULTS: Each patient had between two and seven (mean 3.5) CAD risk factors and pre-test probability of CAD > or = 80%. Ninety three patients (68.9%) had negative stress echocardiography. Mean (SD) follow up was 20.1 (8.5) months. There were six events in the positive stress echocardiography group (two cardiac deaths, one unstable angina, three revascularisations), and one event in the negative stress echocardiography group. Cox regression analysis showed positive stress echocardiography (p = 0.02) and age (p = 0.03) to be the only univariate predictors and positive stress echocardiography to be the only independent predictor of future cardiac events (relative risk 8.9, confidence interval 1.0 to 76.5, p = 0.04). Cumulative event free survival to 38 months was 98% in the negative stress echocardiography and 50.7% in the positive stress echocardiography groups. CONCLUSION: In women with high pre-test likelihood of CAD: (1) negative stress echocardiography identifies a subgroup with low risk of cardiac events who do not require further invasive investigation and (2) positive stress echocardiography identifies a subgroup with increased risk of subsequent cardiac events.

Adult↗

PubMed2007

Men who have sex with men in Great Britain: comparison of a self-selected internet sample with a national probability sample.

OBJECTIVES: To compare the characteristics of a self-selected, convenience sample of men who have sex with men (MSM) recruited through the internet with MSM drawn from a national probability survey in Great Britain. METHODS: The internet sample (n = 2065) was recruited through two popular websites for homosexual men in Great Britain in May and June 2003. This sample was compared with MSM (n = 117) from the National Survey of Sexual Attitudes and Lifestyles (Natsal), a probability sample survey of adults resident in Great Britain conducted between May 1999 and February 2001. RESULTS: No significant differences were observed between the samples on a range of sociodemographic and behavioural variables (p>0.05). However, men from the internet sample were younger (p<0.001) and more likely to be students (p = 0.001), but less likely to live in London (p = 0.001) or report good health (p = 0.014). Although both samples were equally likely to report testing for HIV, men from the internet sample were more likely to report a sexually transmitted infection in the past year (16.9% v 4.8%, adjusted odds ratio 4.14, 95% CI 1.76 to 9.74; p = 0.001), anal intercourse (76.9% v 63.3%; p = 0.001) and unprotected anal intercourse in the past 3 months (45% v 36.6%; p = 0.064). CONCLUSIONS: The internet provides a means of recruiting a self-selected, convenience sample of MSM whose social and demographic characteristics are broadly similar to those of MSM drawn from a national probability survey. However, estimates of high-risk sexual behaviour based on internet convenience samples are likely to overestimate levels of sexual risk behaviour in the wider MSM population.

Adolescent↗

PubMed1991

Periodic mammographic follow-up of probably benign lesions: results in 3,184 consecutive cases.

The author prospectively evaluated the value of periodic mammographic surveillance among 3,184 consecutive cases of nonpalpable, probably benign breast lesions detected with mammography. Follow-up consisted of four mammographic examinations during a 3- or 3.5-year period. Clinical outcome was ascertained in each case after the study period, whether or not patients complied with the protocol. Probably benign lesions were subsequently found to be malignant in 17 cases (positive predictive value for cancer, 0.5%). Fifteen of the 17 cancers were identified by means of interval mammographic change prior to development of a palpable mass; all 17 were stage 0 or stage 1 tumors. All 17 women who had cancer currently show no evidence of tumor recurrence (median duration of follow-up, 5 years). These results should help establish the validity of managing mammographically detected, probably benign lesions with periodic mammographic surveillance. By decreasing the number of biopsies of benign lesions and thereby substantially reducing costs, this approach may help overcome a major barrier to widespread use of mammographic screening.

Adult↗