Showing papers by "University of South Florida published in 1996"

Secreted amyloid beta-protein similar to that in the senile plaques of Alzheimer's disease is increased in vivo by the presenilin 1 and 2 and APP mutations linked to familial Alzheimer's disease.

Abstract: To determine whether the presenilin 1 (PS1), presenilin 2 (PS2) and amyloid beta-protein precursor (APP) mutations linked to familial Alzheimer's disease (FAD) increase the extracellular concentration of amyloid beta-protein (A beta) ending at A beta 42(43) in vivo, we performed a blinded comparison of plasma A beta levels in carriers of these mutations and controls. A beta 1-42(43) was elevated in plasma from subjects with FAD-linked PS1 (P < 0.0001), PS2N1411 (P = 0.009), APPK670N,M671L (P < 0.0001), and APPV7171 (one subject) mutations. A beta ending at A beta 42(43) was also significantly elevated in fibroblast media from subjects with PS1 (P < 0.0001) or PS2 (P = 0.03) mutations. These findings indicate that the FAD-linked mutations may all cause Alzhelmer's disease by increasing the extracellular concentration of A beta 42(43), thereby fostering cerebral deposition of this highly amyloidogenic peptide.

Increased amyloid-β42(43) in brains of mice expressing mutant presenilin 1

Abstract: MUTATIONS in the genes encoding amyloid-β precursor protein (APP)1 presenilin 1 (PS1)2 and presenilin 2 (PS2)3,4 are known to cause early-onset, autosomal dominant Alzheimer's disease. Studies of plasma and fibroblasts from subjects with these mutations have established that they all alter amyloid β-protein (βAPP) processing, which normally leads to the secretion of amyloid-β protein (relative molecular mass 4,000; Mr 4K; ∼90% Aβ1–40, ∼10% Aβ1–42(43)), so that the extracellular concentration of Aβ42(43) is increased5. This increase in Aβ42(43) is believed to be the critical change that initiates Alzheimer's disease pathogenesis because Aβ42(43) is deposited early and selectively in the senile plaques that are observed in the brains of patients with all forms of the disease. To establish that the presenilin mutations increase the amount of Aβ42(43) in the brain and to test whether presenilin mutations act as true (gain of function) dominants, we have now constructed mice expressing wild-type and mutant presenilin genes. Analysis of these mice showed that overexpression of mutant, but not wild-type, PS1 selectively increases brain Aβ42(43). These results indicate that the presenilin mutations probably cause Alzheimer's disease through a gain of deleterious function that increases the amount of Aβ42(43) in the brain.

Lymphatic mapping and sentinel node biopsy in the patient with breast cancer

Abstract: Objective. —To identify the sentinel lymph node(s) (SLN[s]) (the first node[s] draining the primary tumor in the regional lymphatic basin) in patients with invasive breast cancer and to test the hypothesis that the histologic characteristics of the SLN predict the histologic characteristics of the remaining lymph nodes in the axilla. Design. —A prospective trial. Participants. —Sixty-two patients with newly diagnosed invasive breast cancers. Intervention. —Patients underwent intraoperative lymphatic mapping using a combination of a vital blue dye and filtered technetium-labeled sulfur colloid. The SLN was identified and removed, followed by a definitive cancer operation, including a complete axillary node dissection. Main Outcome Measure. —The metastatic distribution in the axilla was determined in patients with occult nodal disease. Results. —The SLN was successfully identified in 57 (92%) of 62 patients using the 2 lymphatic mapping procedures. After localization, 18 patients (32%) were found to have metastatic disease, and the SLN tested positive in all 18 patients. There were no "skip" metastases, defined as an SLN that tested negative with higher nodes that tested positive. In 12 (67%) of 18 patients with metastatic disease, the SLN was the only site of disease. The metastatic distribution significantly favored SLN involvement. Among subjects with discordant nodal involvement, the probability of observing the distribution of SLN involvement by chance is very small (P Conclusions. —This study confirms that lymphatic mapping is technically possible in the patient with breast cancer and that the histologic characteristics of the SLN probably reflect the histologic characteristics of the rest of the axillary lymph nodes. The procedure also allows the pathologist to focus the histologic examination on 1 or 2 nodes, potentially increasing the yield of positive dissections and the accuracy of staging.

The measurement of disability.

Abstract: The frequent occurrence of desynchrony between psychiatric symptoms and disability makes it necessary to measure disability/ functional impairment in addition to psychiatric symptoms when tracking treatment outcome. Existing disability measures in psychiatry are comprehensive but lengthy. There is a need for short, simple, cost-effective, sensitive measures of disability and functional impairment in psychiatric disorders. We developed a discretized analog disability scale (DISS) which uses visual-spatial, numeric and verbal descriptive anchors to assess disability across three domains: work, social life and family life. The DISS has proved to be very sensitive to change in drug treatment studies in psychiatry. The usefulness of the DISS in assessing disability in terms of work, social and family relationships is discussed.

Efficacy of Pamidronate in Reducing Skeletal Events in Patients with Advanced Multiple Myeloma

Abstract: Background Skeletal complications are a major clinical manifestation of multiple myeloma. These complications are caused by soluble factors that stimulate osteoclasts to resorb bone. Bisphosphonates such as pamidronate inhibit osteoclastic activity and reduce bone resorption. Methods Patients with stage III multiple myeloma and at least one lytic lesion received either placebo or pamidronate (90 mg) as a four-hour intravenous infusion given every four weeks for nine cycles in addition to antimyeloma therapy. The patients were stratified according to whether they were receiving first-line (stratum 1) or second-line (stratum 2) antimyeloma chemotherapy at entry into the study. Skeletal events (pathologic fracture, irradiation of or surgery on bone, and spinal cord compression), hypercalcemia (symptoms or a serum calcium concentration >12 mg per deciliter [3.0 mmol per liter]), bone pain, analgesic-drug use, performance status, and quality of life were assessed monthly. Results Among 392 treated patients, th...

An experimental comparison of range image segmentation algorithms

Abstract: A methodology for evaluating range image segmentation algorithms is proposed. This methodology involves (1) a common set of 40 laser range finder images and 40 structured light scanner images that have manually specified ground truth and (2) a set of defined performance metrics for instances of correctly segmented, missed, and noise regions, over- and under-segmentation, and accuracy of the recovered geometry. A tool is used to objectively compare a machine generated segmentation against the specified ground truth. Four research groups have contributed to evaluate their own algorithm for segmenting a range image into planar patches.

Nonparametric analysis of statistic images from functional mapping experiments

Abstract: The analysis of functional mapping experiments in positron emission tomography involves the formation of images displaying the values of a suitable statistic, summarising the evidence in the data for a particular effect at each voxel These statistic images must then be scrutinised to locate regions showing statistically significant effects The methods most commonly used are parametric, assuming a particular form of probability distribution for the voxel values in the statistic image Scientific hypotheses, formulated in terms of parameters describing these distributions, are then tested on the basis of the assumptions Images of statistics are usually considered as lattice representations of continuous random fields These are more amenable to statistical analysis There are various shortcomings associated with these methods of analysis The many assumptions and approximations involved may not be true The low numbers of subjects and scans, in typical experiments, lead to noisy statistic images with low degrees of freedom, which are not well approximated by continuous random fields Thus, the methods are only approximately valid at best and are most suspect in single-subject studies In contrast to the existing methods, we present a nonparametric approach to significance testing for statistic images from activation studies Formal assumptions are replaced by a computationally expensive approach In a simple rest-activation study, if there is really no activation effect, the labelling of the scans as “active” or “rest” is artificial, and a statistic image formed with some other labelling is as likely as the observed one Thus, considering all possible relabellings, a p value can be computed for any suitable statistic describing the statistic image Consideration of the maximal statistic leads to a simple nonparametric single-threshold test This randomisation test relies only on minimal assumptions about the design of the experiment, is (almost) exact, with Type I error (almost) exactly that specified, and hence is always valid The absence of distributional assumptions permits the consideration of a wide range of test statistics, for instance, “pseudo” t statistic images formed with smoothed variance images The approach presented extends easily to other paradigms, permitting nonparametric analysis of most functional mapping experiments When the assumptions of the parametric methods are true, these new nonparametric methods, at worst, provide for their validation When the assumptions of the parametric methods are dubious, the nonparametric methods provide the only analysis that can be guaranteed valid and exact

Esophagitis associated with the use of alendronate

Abstract: Background Alendronate, an aminobisphosphonate and a selective inhibitor of osteoclast-mediated bone resorption, is used to treat osteoporosis in postmenopausal women and Paget's disease of bone. Aminobisphosphonates can irritate the upper gastrointestinal mucosa. Methods We describe three patients who had severe esophagitis shortly after starting to take alendronate and also analyze adverse esophageal effects reported to Merck, the manufacturer, through postmarketing surveillance. Results As of March 5, 1996, alendronate had been prescribed for an estimated 475,000 patients worldwide, and 1213 reports of adverse effects had been received. A total of 199 patients had adverse effects related to the esophagus; in 51 of these patients (26 percent), including the 3 we describe in case reports, adverse effects were categorized as serious or severe. Thirty-two patients (16 percent) were hospitalized, and two were temporarily disabled. Endoscopic findings generally indicated chemical esophagitis, with erosions o...

β-Amyloid-mediated vasoactivity and vascular endothelial damage

Abstract: Deposits of beta-amyloid are apparent in ageing and Alzheimer's disease, but the role of this peptide in neurodegeneration is unclear. The free-radical theory of ageing may also account for Alzheimer-type degeneration and consequently links between free-radical generation and beta-amyloid have been sought. We demonstrate here that beta-amyloid interacts with endothelial cells on blood vessels to produce and excess of superoxide radicals, with attendant alterations in endothelial structure and function. The superoxide radical can scavenge endothelium-derived relaxing factor and produce potent oxidizing agents, which can cause lipid peroxidation and other degenerative changes. The alterations in vascular tone and endothelial damage are prevented by the oxygen-radical-scavenging enzyme superoxide dismutase. These observations suggest a normal vasoactive role for beta-amyloid as well as a mechanism by which beta-amyloid may play a role in vascular abnormalities and neurodegeneration mediated by free radicals.

Petrogenesis of slab-derived trondhjemite–tonalite-dacite/adakite magmas

Abstract: The prospect of partial melting of the subducted oceanic crust to produce arc magmatism has been debated for over 30 years. Debate has centred on the physical conditions of slab melting and the lack of a definitive, unambiguous geochemical signature and petrogenetic process. Experimental partial melting data for basalt over a wide range of pressures (1–32 kbar) and temperatures (700–1150°C) have shown that melt compositions are primarily trondhjemite–tonalite–dacite (TTD). High-Al (> 15% Al 2 O 3 at the 70% SiO 2 level) TTD melts are produced by high-pressure (≥ 5 kbar) partial melting of basalt, leaving a restite assemblage of garnet + clinopyroxene ± hornblende. A specific Cenozoic high-Al TTD (adakite) contains lower Y, Yb and Sc and higher Sr, Sr/Y, La/Yb and.Zr/Sm relative to other TTD types and is interpreted to represent a slab melt under garnet amphibolite to eclogite conditions. High-Al TTD with an adakite-like geochemical character is prevalent in the Archean as the result of a higher geotherm that facilitated slab melting. Cenozoic adakite localities are commonly associated with the subduction of young ( −1 ) conducive for slab dehydration melting. Viable alternative or supporting tectonic effects that may enhance slab melting include highly oblique convergence and resultant high shear stresses and incipient subduction into a pristine hot mantle wedge. The minimum P–T conditions for slab melting are interpreted to be 22–26 kbar (75–85 km depth) and 750–800°C. This P–T regime is framed by the hornblende dehydration, 10°C/km, and wet basalt melting curves and coincides with numerous potential slab dehydration reactions, such as tremolite, biotite + quartz, serpentine, talc, Mg-chloritoid, paragonite, clinohumite and talc + phengite. Involvement of overthickened (>50 km) lower continental crust either via direct partial melting or as a contaminant in typical mantle wedge-derived arc magmas has been presented as an alternative to slab melting. However, the intermediate to felsic volcanic and plutonic rocks that involve the lower crust are more highly potassic, enriched in large ion lithophile elements and elevated in Sr isotopic values relative to Cenozoic adakites. Slab-derived adakites, on the other hand, ascend into and react with the mantle wedge and become progressively enriched in MgO, Cr and Ni while retaining their slab melt geochemical signature. Our studies in northern Kamchatka, Russia provide an excellent case example for adakite-mantle interaction and a rare glimpse of trapped slab melt veinlets in Na-metasomatised mantle xenoliths.

Transcriptional repression by YY1 is mediated by interaction with a mammalian homolog of the yeast global regulator RPD3

Abstract: YY1 is a mammalian zinc-finger transcription factor with unusual structural and functional features. It has been implicated as a positive and a negative regulatory factor that binds to the CCATNTT consensus DNA element located in promoters of many cellular and viral genes. A mammalian cDNA that encodes a YY1-binding protein and possesses sequence homology with the yeast transcriptional factor RPD3 has been identified. A Gal4 DNA binding domain-mammalian RPD3 fusion protein strongly represses transcription from a promoter containing Gal4 binding sites. Association between YY1 and mammalian RPD3 requires a glycine-rich region on YY1. Mutations in this region abolish the interaction with mammalian RPD3 and eliminate transcriptional repression by YY1. These data suggest that YY1 negatively regulates transcription by tethering RPD3 to DNA as a cofactor and that this transcriptional mechanism is highly conserved from yeast to human.

Intraoperative radiolymphoscintigraphy improves sentinel lymph node identification for patients with melanoma

Abstract: BACKGROUND: The sentinel lymph node (SLN), the first node draining the primary tumor site, has been shown to reflect the histologic features of the remainder of the lymphatic basin in patients with melanoma. Intraoperative localization of the SLN, first proposed by Morton and colleagues, has been accomplished with the use of a vital blue dye mapping technique. Technical difficulties resulting in unsuccessful explorations have occurred in up to 20% of the dissections. OBJECTIVES: The authors aimed to define the SLN using gamma detection probe mapping and to determine whether intraoperative radiolymphoscintigraphy using technetium sulfur colloid and a hand-held gamma-detecting probe could be used to improve detection of all SLNs for patients with melanoma. METHODS: To ensure that all initial nodes draining the primary site were removed at the time of selective lymphadenectomy, the authors used intraoperative radiolymphoscintigraphy to confirm the location of the SLN, which was determined initially with the preoperative lymphoscintigram and the intraoperative vital blue dye injection. PATIENT POPULATION: The patient population consisted of 106 consecutive patients who presented with cutaneous melanomas larger than 0.75 mm in all primary site locations. RESULTS: The preoperative lymphoscintigram revealed that 22 patients had more than one lymphatic basin sampled. Two hundred SLNs and 142 neighboring non-SLNs were harvested from 129 basins in 106 patients. After the skin incision was made, the mean ratio of hot spot to background activity was 8.5:1. The mean ratio of ex vivo SLN-to-non-SLN activity for 72 patients who had SLNs harvested was 135.6:1. When correlated with the vital blue dye mapping, 139 of 200 (69.5%) SLNs demonstrated blue dye staining, whereas 167 of 200 (83.5%) SLNs were hot according to radioisotope localization. With the use of both intraoperative mapping techniques, identification of the SLN was possible for 124 of the 129 (96%) basins sampled. Micrometastases were identified in SLNs of 16 of the 106 (15%) patients by routine histologic analysis. CONCLUSION: The use of intraoperative radiolymphoscintigraphy can improve the identification of all SLNs during selective lymphadenectomy.

Combination of multiple classifiers using local accuracy estimates

Abstract: Combination of multiple classifiers (CMC) has recently drawn attention as a method of improving classification accuracy. This paper presents a method for combining classifiers that use estimates of each individual classifier's local accuracy in small regions of feature space surrounding an unknown test sample. Only the output of the most locally accurate classifier is considered. We address issues of (1) optimization of individual classifiers, and (2) the effect of varying the sensitivity of the individual classifiers on the CMC algorithm. Our algorithm performs better on data from a real problem in mammogram image analysis than do other recently proposed CMC techniques.

Validity-guided (re)clustering with applications to image segmentation

Abstract: When clustering algorithms are applied to image segmentation, the goal is to solve a classification problem. However, these algorithms do not directly optimize classification duality. As a result, they are susceptible to two problems: 1) the criterion they optimize may not be a good estimator of "true" classification quality, and 2) they often admit many (suboptimal) solutions. This paper introduces an algorithm that uses cluster validity to mitigate problems 1 and 2. The validity-guided (re)clustering (VGC) algorithm uses cluster-validity information to guide a fuzzy (re)clustering process toward better solutions. It starts with a partition generated by a soft or fuzzy clustering algorithm. Then it iteratively alters the partition by applying (novel) split-and-merge operations to the clusters. Partition modifications that result in improved partition validity are retained. VGC is tested on both synthetic and real-world data. For magnetic resonance image (MRI) segmentation, evaluations by radiologists show that VGC outperforms the (unsupervised) fuzzy c-means algorithm, and VGC's performance approaches that of the (supervised) k-nearest-neighbors algorithm.

Average reward reinforcement learning: foundations, algorithms, and empirical results

Abstract: This paper presents a detailed study of average reward reinforcement learning, an undiscounted optimality framework that is more appropriate for cyclical tasks than the much better studied discounted framework. A wide spectrum of average reward algorithms are described, ranging from synchronous dynamic programming methods to several (provably convergent) asynchronous algorithms from optimal control and learning automata. A general sensitive discount optimality metric called n-discount-optimality is introduced, and used to compare the various algorithms. The overview identifies a key similarity across several asynchronous algorithms that is crucial to their convergence, namely independent estimation of the average reward and the relative values. The overview also uncovers a surprising limitation shared by the different algorithms: while several algorithms can provably generate gain-optimal policies that maximize average reward, none of them can reliably filter these to produce bias-optimal (or T-optimal) policies that also maximize the finite reward to absorbing goal states. This paper also presents a detailed empirical study of R-learning, an average reward reinforcement learning method, using two empirical testbeds: a stochastic grid world domain and a simulated robot environment. A detailed sensitivity analysis of R-learning is carried out to test its dependence on learning rates and exploration levels. The results suggest that R-learning is quite sensitive to exploration strategies, and can fall into sub-optimal limit cycles. The performance of R-learning is also compared with that of Q-learning, the best studied discounted RL method. Here, the results suggest that R-learning can be fine-tuned to give better performance than Q-learning in both domains.

Use of microsatellite loci to classify individuals by relatedness.

Abstract: This study investigates the use of microsatellite loci for estimating relatedness between individuals in wild, outbred, vertebrate populations. We measured allele frequencies at 20 unlinked, dinucleotide-repeat microsatellite loci in a population of wild mice (Mus musculus), and used these observed frequencies to generate the expected distributions of pairwise relatedness among full sib, half sib, and unrelated pairs of individuals, as would be estimated from the microsatellite data. In this population one should be able to discriminate between unrelated and full-sib dyads with at least 97% accuracy, and to discriminate half-sib pairs from unrelated pairs or from full-sib pairs with better than 80% accuracy. If one uses the criterion that parent-offspring pairs must share at least one allele per locus, then only 15% of full-sib pairs, 2% of half-sib pairs, and 0% of unrelated pairs in this population would qualify as potential parent-offspring pairs. We verified that the simulation results (which assume a random mating population in Hardy-Weinberg and linkage equilibrium) accurately predict results one would obtain from this population in real life by scoring laboratory-bred full- and half-sib families whose parents were wild-caught mice from the study population. We also investigated the effects of using different numbers of loci, or loci of different average heterozygosities (He), on misclassification frequencies. Both variables have strong effects on misclassification rate. For example, it requires almost twice as many loci of He = 0.62 to achieve the same accuracy as a given number of loci He = 0.75. Finally, we tested the ability of UPGMA clustering to identify family groups in our population. Clustering of allele matching scores among the offspring of four sets of independent maternal half sibships (four females, each mated to two different males) perfectly recovered the true family relationships.

Lipid Formulations of Amphotericin B: Recent Progress and Future Directions

Abstract: Three lipid formulations of amphotericin B are now either marketed for clinical use or undergoing further study before they can be approved in various countries worldwide. Amphotericin B lipid complex (ABLC; Abelcet, Liposome Company, Princeton, NJ) is a concentration of ribbonlike structures of a bilayered membrane formed by combining a 7:3 molar ratio of dimyristoyl phosphatidylcholine and dimyristoyl phosphatidylglycerol with amphotericin B. Amphotericin B colloidal dispersion (ABCD; Amphocii, Sequus Pharmaceuticals, Menlo Park, CA) is composed of disklike structures of cholesteryl sulfate complexed with amphotericin B. AmBisome (Nexstar, San Dimas, CA), the only true liposomal amphotericin B, consists of small unilamellar vesicles made up of a bilayer membrane of hydrogenated soy phosphatidylcholine and distearoylphosphatidylglycerol stabilized with cholesterol in a 2:0.8:1 ratio combined with amphotericin B. All of the preparations appear to be preferentially accumulated in organs of the reticuloendothelial system, as opposed to the kidney. In vivo animal models as well as current clinical experience suggest that use of these formulations results in overall improvement in the therapeutic index. Patients with life-threatening mycosis for whom therapy has failed or who are intolerant to therapy with amphotericin B deoxycholate have been successfully treated with these formulations. However, further study is warranted to help clarify the usefulness of each of the lipid formulations as first-line therapy for documented or suspected invasive fungal infections.

Impact of deprenyl and tocopherol treatment on Parkinson's disease in DATATOP patients requiring levodopa

Abstract: The Deprenyl and Tocopherol Antioxidant Therapy of Parkinsonism (DATATOP) trial was designed to test outcomes from treatment with 10 mg of deprenyl and/or 2,000 mg of tocopherollday in 800 untreated patients with Parkinson's disease. The need of subjects for symptomatic treatment with levodopa and the conversion of all subjects to open‐label deprenyl made it possible to study the long‐term effect of early deprenyl and tocopherol treatment on the later development of levodopa‐associated side effects. The rate of developing these side effects did not differ among the original treatment groups (early versus late deprenyl and tocopherol versus nontocopherol). About 50% of subjects developed “wearing off,” 30% dyskinesias, and 25% “freezing” in each group. At the end of the study, the groups were similarly disabled on the Hoehn‐Yahr, Schwab‐England, and Unified Parkinsonapos;s Disease Rating scales and took similar amounts of levodopa. Young subjects were more likely to develop wearing off, women to develop dyskinesias, and older subjects with rapidly progressive disease to develop freezing. We conclude that prior treatment with deprenyl or tocopherol did not reduce the occurrence of subsequent levodopa‐associated adverse effects in this population.

Explanations of body image disturbance: a test of maturational status, negative verbal commentary, social comparison, and sociocultural hypotheses.

Abstract: Objective A number of hypotheses have been offered to explain the development and/or maintenance of body image disturbance. In this study, four factors which have been hypothesized to lead to body image problems were tested: maturational status (early physical development), negative verbal commentary (a history of being teased regarding physical appearance), behavioral social comparison, and awareness/internalization of sociocultural pressures. Methods: One hundred sixty-two college females completed measures designed to index these four influences. Predictors were regressed onto multiple measures of body image and two indices of eating disturbance. Results: Even with self-esteem and level of obesity removed as influences, social comparison and societal factors were significant predictors of body dissatisfaction and eating disturbance. Negative verbal commentary also explained a small part of the variance, however, maturational status did not contribute uniquely in any analysis. Discussion: The findings offer further support for emerging theories of body image and eating disturbance. © 1996 by John Wiley & Sons, Inc.

Chapter 158 Marine chemistry and geochemistry of the lanthanides

Abstract: Publisher Summary This chapter discusses the characteristics and properties of lanthanides in seawater and presents the rationale for studying the lanthanide composition of natural waters. The lanthanides are composed of a group of fourteen elements (La, Ce, Pf, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb, and Lu). There are anthropogenic sources of lanthanides to the atmosphere (and presumably to the ocean) in the form of particles produced during the cracking of oil and the combustion of oil and gasoline products. A major objective of chemical oceanography is to understand processes controlling the concentration, distribution, speciation, and flux of elements in the oceans. The chapter describes and discusses lanthanide distributions in the oceans and the biogeochemical and physical processes responsible for these distributions. It presents the profiles of lanthanide concentrations in the water column and their variations within and between ocean basins. The redox geochemistry of Ce as revealed by vertical and horizontal variations in the Ce anomaly is discussed. The inter-oceanic mass fractionation of the strictly trivalent lanthanides is also described.

A multicenter evaluation of total intravenous anesthesia with remifentanil and propofol for elective inpatient surgery

Abstract: Remifentanil is a mu-opioid receptor agonist with a context sensitive half-time of 3 min and an elimination half-life < or = 10 min. This study sought to evaluate the efficacy of remifentanil and propofol total intravenous anesthesia (TIVA) in 161 patients undergoing inpatient surgery. Remifentanil 1 microgram/kg was given intravenously (i.v.) followed by one of two randomized infusion rates: small dose (0.5 micrograms.kg-1.min-1) or large dose (1 microgram.kg-1.min-1). Propofol (0.5-1.0 mg/kg i.v. bolus and 75 micrograms.kg-1.min-1 infusion) and vecuronium were also given. Remifentanil infusions were decreased by 50% after tracheal intubation. End points included responses (hypertension, tachycardia, and somatic responses) to tracheal intubation and surgery. More patients in the small-dose than in the large-dose group responded to tracheal intubation with hypertension and/or tachycardia (25% vs 6%; P = 0.003) but there were no other differences between groups in intraoperative responses. Recovery from anesthesia was within 3-7 min in both groups. The most frequent adverse events were hypotension (systolic blood pressure [BP] < 80 mm Hg or mean BP < 60 mm Hg) during anesthesia induction (10% small-dose versus 15% large-dose group; P = not significant [NS]) and hypotension (27% small-dose versus 30% large-dose group; P = NS), and bradycardia (7% small-dose versus 19% large-dose group; P = NS) during maintenance. In conclusion, when combined with propofol 75 micrograms.kg-1.min-1, remifentanil 1 microgram/kg i.v. as a bolus followed by an infusion of 1.0 microgram.kg-1.min-1 effectively controls responses to tracheal intubation. After tracheal intubation, remifentanil 0.25-4.0 micrograms.kg-1.min-1 effectively controlled intraoperative responses while allowing for rapid emergence from anesthesia.

Comparison of edge detectors: a methodology and initial study

Abstract: The purpose of this paper is to describe a new (to computer vision) experimental framework which allows us to make quantitative comparisons using subjective ratings made by people. This approach avoids the issue of pixel-level ground truth. As a result, it does not allow us to make statements about the frequency of false positive and false negative errors at the pixel level. Instead, using experimental design and statistical techniques borrowed from Psychology, we make statements about whether the outputs of one edge detector are rated statistically significantly higher than the outputs of another. This approach offers itself as a nice complement to signal-based quantitative measures. Also, the evaluation paradigm in this paper is goal oriented; in particular, we consider edge detection in the context of object recognition. The human judges rate the edge, detectors based on how well the capture the salient features of real objects. So far, edge detection modules have been designed and evaluated in isolation, except for the recent work by Ramesh and Haralick (1992). The only prior work (that we are aware of) which also uses humans to rate image algorithms is that of Reeves and Higdon (1995). They use human ratings to decide on regularization parameters of image restoration. Fram and Deutch (1975) also used human subjects, however, the focus was on human versus machine performance rather than using human ratings to compare different edge detectors. The use of human judges to rate image outputs mist be approached systematically. Experiments must be designed and conducted carefully, and results interpreted with appropriate statistical tools. The use of statistical analysis in vision system performance characterization has been rare. The only prior work in the area that we are aware of is that of Nair et al. (1995), who used statistical ranking procedures to compare neural network based object recognition systems.

Inputs, losses and transformations of nitrogen and phosphorus in the pelagic North Atlantic Ocean

Abstract: The North Atlantic Ocean receives the largest allochthonous supplies of nitrogen of any ocean basin because of the close proximity of industrialized nations. In this paper, we describe the major standing stocks, fluxes and transformations of nitrogen (N) and phosphorus (P) in the pelagic regions of the North Atlantic, as one part of a larger effort to understand the entire N and P budgets in the North Atlantic Ocean, its watersheds and overlying atmosphere. The primary focus is on nitrogen, however, we consider both nitrogen and phosphorus because of the close inter-relationship between the N and P cycles in the ocean. The oceanic standing stocks of N and P are orders of magnitude larger than the annual amount transported off continents or deposited from the atmosphere. Atmospheric deposition can have an impact on oceanic nitrogen cycling at locations near the coasts where atmospheric sources are large, or in the centers of the highly stratified gyres where little nitrate is supplied to the surface by vertical mixing of the ocean. All of the reactive nitrogen transported to the coasts in rivers is denitrified or buried in the estuaries or on the continental shelves and an oceanic source of nitrate of 0.7–0.95 × 1012 moles NO 3 - y-1 is required to supply the remainder of the shelf denitrification (Nixon et al., this volume). The horizontal fluxes of nitrate caused by the ocean circulation are both large and uncertain. Even the sign of the transport across the equator is uncertain and this precludes a conclusion on whether the North Atlantic Ocean as a whole is a net source or sink of nitrate. We identify a source of nitrate of 3.7–6.4 × 1012 moles NO 3 - y-1 within the main thermocline of the Sargasso Sea that we infer is caused by nitrogen fixation. This nitrate source may explain the nitrate divergence observed by Rintoul & Wunsch (1991) in the mid-latitude gyre. The magnitude of nitrogen fixation inferred from this nitrate source would exceed previous estimates of global nitrogen fixation. Nitrogen fixation requires substantial quantities of iron as a micro-nutrient and the calculated iron requirement is comparable to the rates supplied by the deposition of iron associated with Saharan dust. Interannual variability in dust inputs is large and could cause comparable signals in the nitrogen fixation rate. The balance of the fluxes across the basin boundaries suggest that the total stocks of nitrate and phosphate in the North Atlantic may be increasing on time-scales of centuries. Some of the imbalance is related to the inferred nitrogen fixation in the gyre and the atmospheric deposition of nitrogen, both of which may be influenced by human activities. However, the fluxes of dissolved organic nutrients are almost completely unknown and they have the potential to alter our perception of the overall mass balance of the North Atlantic Ocean.

Functional fetal nigral grafts in a patient with Parkinson's disease: Chemoanatomic, ultrastructural, and metabolic studies

Abstract: A patient with Parkinson's disease received bilateral fetal human nigral implants from six donors aged 6.5 to 9 weeks post-conception. Eighteen months following a post-operative clinical course characterized by marked improvement in clinical function, this patient died from events unrelated to the grafting procedure. Post-mortem histological analyses revealed the presence of viable grafts in all 12 implant sites, each containing a heterogeneous population of neurons and glia. Approximately 210,146 implanted tyrosine hydroxylase-immunoreactive (TH-ir) neurons were found. A greater number of TH-ir grafted neurons were observed in the right (128,162) than the left (81,905) putamen. Grafted TH-ir neurons were organized in an organotypic fashion. These cells provided extensive TH-ir and dopamine transporter-ir innervation to the host striatum which occurred in a patch-matrix fashion. Quantitative evaluations revealed that fetal nigral grafts reinnervated 53% and 28% of the post-commissural putamen on the right and left side, respectively. Grafts on the left side innervated a lesser area of the striatum, but optical density measurements were similar on both sides. There was no evidence that the implants induced sprouting of host TH-ir systems. Electron microscopic analyses revealed axo-dendritic and occasional axo-axonic synapses between graft and host. In contrast, axo-somatic synapses were not observed. In situ hybridization for TH mRNA revealed intensely hybridized grafted neurons which far exceeded TH mRNA expression within residual host nigral cells. In addition, γ-amino butyric acid (GABA)-ergic neurons were observed within the graft that formed a dense local neuropil which was confined to the implant site. Serotonergic neurons were not observed within the graft. Cytochrome oxidase activity was increased bilaterally within the grafted post-commissural putamen, suggesting increased metabolic activity. In this regard, a doubling of cytochrome oxidase activity was observed within the grafted post-commissural putamen bilaterally relative to the non-grafted anterior putamen. The grafts were hypovascular relative to the surrounding striatum and host substantia nigra. Blood vessels within the graft stained intensely for GLUT-1, suggesting that this marker of blood-brain barrier function is present within human nigral allografts. Taken together, these data indicate that fetal nigral neurons can survive transplantation, functionally reinnervate the host putamen, establish synaptic contacts with host neurons, and sustain many of the morphological and functional characteristics of normal nigral neurons following grafting into a patient with PD. © 1996 Wiley-Liss, Inc.