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PubMed2000

The "hidden cystic duct" syndrome and the infundibular technique of laparoscopic cholecystectomy--the danger of the false infundibulum.

BACKGROUND: The "classical" biliary injury usually involves misidentification of the common bile duct as the cystic duct. The purpose of this study was to determine if the method of cholecystectomy, specifically the "infundibular technique," might be a contributing factor in this injury. STUDY DESIGN: Twenty-one operative notes of patients who were referred with injury to the common bile duct were examined. Notes were classified as to informativeness. Patient and operative variables potentially related to injury were searched for. RESULTS: Inflammation was the main patient variable associated with injury. The main operative variable was that in most of the injuries the cystic duct was isolated and divided as the first step in the procedure. Often the operative note contained a statement indicating that the surgeon believed that the "cystic" duct (actually the common bile duct) was emanating from the infundibulum of the gallbladder and that this was the anatomic rationale for identification of the cystic duct. In no case was the triangle of Calot completely dissected before injury. CONCLUSIONS: The cystic duct may be hidden in some patients having laparoscopic cholecystectomy, especially in the presence of inflammation. This may lead to the deceptive appearance of a false infundibulum that misleads the surgeon into identifying the common duct as the cystic duct. Biliary injury is more likely when cystic duct identification is made by relying solely on the appearance of the junction of the cystic duct with the infundibulum of the gallbladder, and this technique should be abandoned.

Adolescent↗

PubMed2004

Oxidative stress in Alzheimer's and vascular dementias: masking of the antioxidant profiles by a concomitant Type II diabetes mellitus condition.

Oxidative stress is associated with Alzheimer's (DAT) and vascular (VD) dementias, as well as Type II diabetes mellitus (DIAB) and affected by hypoglycemic therapy. The population (n = 122; males = 60; mean age = 72.57 +/- 7.06) consisted of controls (CTR), DAT and VD patients, with (DAT + DIAB, VD + DIAB) and without concomitant DIAB, resulting in six groups where the antioxidant profile was determined: copper-zinc superoxide dismutase (SOD), thiobarbituric acid reactive substances (TBARS), and total antioxidant capacity (TRAP). The results were analyzed using a two-way ANOVA design and Bonferroni statistic. The ANOVAs yielded significant differences between groups for all components of the profile: SOD, p = 0.00000006; TBARS, p = 0.0000012; TRAP, p = 0.0000003. The significance level for comparisons between groups was set at alpha = 0.05. The comparisons DIAB vs. CTR, DAT+DIAB vs. DAT, and DIAB demented vs. DIAB non-demented resulted significant for all variables. VD + DIAB vs. VD resulted significant for all variables except TRAP. The antioxidant profiles of DIAB and CTR are different. The differences cannot be directly related with what is observed in dementias. The differences in profiles of demented and non-demented are somewhat hidden when demented patients are affected by a concomitant DIAB condition and/or hypoglycemic treatment, thus conditioning the diagnostic value for dementias of the profiles.

Aged↗

PubMedDate not supplied

The "latent membrane permeability" concept: QSPR analysis of inter/intralaboratory variable Caco-2 permeability.

Caco-2 cell monolayers grown on a filter support are the most widely used systems for predicting intestinal absorption. However, inter- and intralaboratory variability in Caco-2 permeability makes it difficult to analyze any QSPR relationship for a large number of compounds. We proposed the "latent membrane permeability" concept, assuming that all Caco-2 permeability data sets share a hidden, common relationship between their membrane permeability and physicochemical properties. An iterative calculation method was developed to handle this conceptual approach and applied to the analysis of Caco-2 permeability data sets from different sources. A thorough statistical analysis revealed that the "latent membrane permeability" concept be reasonable.

Caco-2 Cells↗

PubMed2006

Interpolated variable order motifs for identification of horizontally acquired DNA: revisiting the Salmonella pathogenicity islands.

MOTIVATION: There is a growing literature on the detection of Horizontal Gene Transfer (HGT) events by means of parametric, non-comparative methods. Such approaches rely only on sequence information and utilize different low and high order indices to capture compositional deviation from the genome backbone; the superiority of the latter over the former has been shown elsewhere. However even high order k-mers may be poor estimators of HGT, when insufficient information is available, e.g. in short sliding windows. Most of the current HGT prediction methods require pre-existing annotation, which may restrict their application on newly sequenced genomes. RESULTS: We introduce a novel computational method, Interpolated Variable Order Motifs (IVOMs), which exploits compositional biases using variable order motif distributions and captures more reliably the local composition of a sequence compared with fixed-order methods. For optimal localization of the boundaries of each predicted region, a second order, two-state hidden Markov model (HMM) is implemented in a change-point detection framework. We applied the IVOM approach to the genome of Salmonella enterica serovar Typhi CT18, a well-studied prokaryote in terms of HGT events, and we show that the IVOMs outperform state-of-the-art low and high order motif methods predicting not only the already characterized Salmonella Pathogenicity Islands (SPI-1 to SPI-10) but also three novel SPIs (SPI-15, SPI-16, SPI-17) and other HGT events. AVAILABILITY: The software is available under a GPL license as a standalone application at http://www.sanger.ac.uk/Software/analysis/alien_hunter CONTACT: gsv@sanger.ac.uk SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Algorithms↗

PubMed1987

Statistical issues in the estimation of assigned shares for carcinogenesis liability.

Congress is currently considering adopting a mathematical formula to assign shares in cancer causation to specific doses of radiation, for use in establishing liability and compensation awards. The proposed formula, if it were sound, would allow difficult problems in tort law and public policy to be resolved by reference to tabulated "probabilities of causation." This article examines the statistical and conceptual bases for the proposed methodology. We find that the proposed formula is incorrect as an expression for "probability and causation," that it implies hidden, debatable policy judgments in its treatment of factor interactions and uncertainties, and that it can not in general be quantified with sufficient precision to be useful. Three generic sources of statistical uncertainty are identified--sampling variability, population heterogeneity, and error propagation--that prevent accurate quantification of "assigned shares." These uncertainties arise whenever aggregate epidemiological or risk data are used to draw causal inferences about individual cases.

Disease Susceptibility↗

PubMed2004

A dynamic, architectural plant model simulating resource-dependent growth.

BACKGROUND AND AIMS: Physiological and architectural plant models have originally been developed for different purposes and therefore have little in common, thus making combined applications difficult. There is, however, an increasing demand for crop models that simulate the genetic and resource-dependent variability of plant geometry and architecture, because man is increasingly able to transform plant production systems through combined genetic and environmental engineering. MODEL: GREENLAB is presented, a mathematical plant model that simulates interactions between plant structure and function. Dual-scale automaton is used to simulate plant organogenesis from germination to maturity on the basis of organogenetic growth cycles that have constant thermal time. Plant fresh biomass production is computed from transpiration, assuming transpiration efficiency to be constant and atmospheric demand to be the driving force, under non-limiting water supply. The fresh biomass is then distributed among expanding organs according to their relative demand. Demand for organ growth is estimated from allometric relationships (e.g. leaf surface to weight ratios) and kinetics of potential growth rate for each organ type. These are obtained through parameter optimization against empirical, morphological data sets by running the model in inverted mode. Potential growth rates are then used as estimates of relative sink strength in the model. These and other 'hidden' plant parameters are calibrated using the non-linear, least-square method. KEY RESULTS AND CONCLUSIONS: The model reproduced accurately the dynamics of plant growth, architecture and geometry of various annual and woody plants, enabling 3D visualization. It was also able to simulate the variability of leaf size on the plant and compensatory growth following pruning, as a result of internal competition for resources. The potential of the model's underlying concepts to predict the plant's phenotypic plasticity is discussed.

Algorithms↗

PubMed1995

Clinical trials of antidepressants: the hidden face: where locus of control appears to play a key role in depression outcome.

It remains difficult to determine in what measure improvements observed in clinical trials of anti-depressants may be attributable to the psychological predispositions of the subjects. The present article focuses on the effect of a psychological variable, the Health Locus of Control, which measures the extent of a subject's belief that he is in control over his own health. The hypothesis is that depressed subjects whose locus of control is internal, i.e. who perceive themselves to be in control, rather than external, i.e. control perceived as being in others or just chance, will improve more markedly and consistently on the Hamilton Depression Rating Scale, across a number of clinical trials. Forty-nine depressive patients undergoing treatment with four different compounds were included, after a week's placebo run-in period, in a classical 42-day follow-up study comprising visits on days -7, 0, 10, 21; and 42. Interactions between the type of locus of control and the clinical course were investigated by MANOVA. Results show that with a classical design of clinical trials of antidepressants, locus of control plays a significant role if it is internal (P < 0.001) in consolidating the improvement process, and that this is true irrespective of type of antidepressant. The relationship between the concept of locus of control and placebo effect is discussed.

Adult↗

PubMed2001

Discovery of hidden blazars.

Every radio-loud quasar may have blazar activities, according to a unified scheme where the differences in both optical and radio observations of radio-loud quasars are the result of different viewing angles. We have predicted that blazars may be detected using emission line ratio variations caused by variable illumination of gas clouds in the broad emission line region. In a spectroscopic search of 62 quasars at a redshift of about 2, we have discovered large (>20%) variations of the emission line ratios, CIV/CIII] or CIV/Lyalpha, when compared with data taken more than 10 years ago. This result is consistent with our prediction and supports the unification scheme for radio-loud quasars.

Journal Article↗

PubMed2001

The LEP gene and age of menarche: maternal age as a potential cause of hidden stratification in association studies.

Leptin has a powerful effect on fertility and the initiation of puberty in addition to its effect on obesity. It has been suggested that that in times of fasting, infertility induced by low leptin levels protect the female from the energy demands of pregnancy. Despite this there have been no studies of the potential role of LEP gene variants on the age of onset of menarche. We genotyped 183 non-Hispanic Caucasian adult females at the LEP D7S1875 dinucleotide repeat polymorphism. The alleles were placed into three genotypes, <208/<208 bp, heterozygotes, and > or =208/> or =208 bp. A hierarchical ANOVA was performed with age of menarche as the dependent variable and LEP(1875) genotypes and maternal age (age of the mothers at birth of the subject) as independent variables. There was a significant (P </= 0.006) interaction of LEP(1875) x maternal age but neither independent variable was significant by itself. This was due to an "association crossover effect" in which the LEP(1875) by age of menarche effects were in opposite directions for those with a maternal age of <30 years compared to those with a maternal age of > or =30 years. If maternal age effects prove to be generalized, failure to take them into consideration could provide a source of hidden stratification that could significantly alter the replication of association studies.

Adult↗

PubMed1999

Artificial neural network-aided image analysis system for cell counting.

BACKGROUND: In histological preparations containing debris and synthetic materials, it is difficult to automate cell counting using standard image analysis tools, i.e., systems that rely on boundary contours, histogram thresholding, etc. In an attempt to mimic manual cell recognition, an automated cell counter was constructed using a combination of artificial intelligence and standard image analysis methods. METHODS: Artificial neural network (ANN) methods were applied on digitized microscopy fields without pre-ANN feature extraction. A three-layer feed-forward network with extensive weight sharing in the first hidden layer was employed and trained on 1,830 examples using the error back-propagation algorithm on a Power Macintosh 7300/180 desktop computer. The optimal number of hidden neurons was determined and the trained system was validated by comparison with blinded human counts. System performance at 50x and lO0x magnification was evaluated. RESULTS: The correlation index at 100x magnification neared person-to-person variability, while 50x magnification was not useful. The system was approximately six times faster than an experienced human. CONCLUSIONS: ANN-based automated cell counting in noisy histological preparations is feasible. Consistent histology and computer power are crucial for system performance. The system provides several benefits, such as speed of analysis and consistency, and frees up personnel for other tasks.

Cell Count↗

PubMed1999

A probabilistic treatment of phylogeny and sequence alignment.

Carrying out simultaneous tree-building and alignment of sequence data is a difficult computational task, and the methods currently available are either limited to a few sequences or restricted to highly simplified models of alignment and phylogeny. A method is given here for overcoming these limitations by Bayesian sampling of trees and alignments simultaneously. The method uses a standard substitution matrix model for residues together with a hidden Markov model structure that allows affine gap penalties. It escapes the heavy computational burdens of other models by using an approximation called the "*" rule, which replaces missing data by a sum over all possible values of variables. The behavior of the model is demonstrated on test sets of globins.

Bayes Theorem↗

PubMed2000

Adult learning deficits after neonatal exposure to D-methamphetamine: selective effects on spatial navigation and memory.

The effects of neonatal d-methamphetamine (MA) treatment on cued and spatial learning and memory were investigated. MA was administered to neonatal rats on postnatal days 11-20. All groups received four subcutaneous injections per day. Group MA40-4 received 40 mg. kg(-1). d(-1) of MA in four divided doses (10 mg/kg per injection). Group MA40-2 received 40 mg. kg(-1). d(-1) of MA in two divided (20 mg/kg/injection) and saline for the other two injections per day. Controls received saline for four injections per day. As adults, both MA groups showed no differences in swimming ability in a straight swimming channel. The MA40-4 group showed no differences in cued learning, but was impaired in hidden platform learning in the Morris water maze on acquisition. They also showed reduced memory performance on probe trials. Similar trends were seen on reversal learning and reversal probe trials. Reduced platform-size learning trials caused spatial learning impairments to re-emerge in the MA40-4 group. The MA40-2 group showed no differences in straight channel swimming, but was slower at finding the visible platform during cued learning. They were also impaired during acquisition and memory trials in the Morris hidden platform maze. They showed a similar trend on reversal learning and memory trials, but were not different during reduced platform-size learning trials. When the MA40-2 group's performance on hidden platform learning and memory trials was adjusted for cued trial performance, the spatial learning deficits remained. Deficits of spatial learning and memory are a selective effect of neonatal methamphetamine treatment irrespective of other learning and performance variables.

Aging↗

PubMed1965

Pruritus, an uncommon but important symptom of systemic carcinoma.

A distinctive pruritic syndrome associated with systemic cancer is described. Prolonged, variably severe pruritus with a tendency to localization on the legs, upper trunk, and extensor surfaces of the upper extremities is the presenting symptom. Patients with unexplained persistent itching as herein described should be investigated for a hidden malignancy. The persistence or recurrence of itching, months or even years after apparent cure of a systemic carcinoma, suggests that destruction or removal of the primary tumor was incomplete, or that metastasis has supervened. A small carcinomatous focus may exist for many months and at times for years before clinical recognition is possible with diagnostic methods currently available.

Adenocarcinoma↗

PubMed2005

[Identification of official rhubarb samples based on IR spectra and neural networks].

The Fourier transform infrared (IR) spectrometry and neural networks have been used to identification of official and un-official rhubarb samples in the present work. The IR spectra were compressed by using wavelet transform and then were normalized prior to network training. Spectra with 700 data points were compressed to 44 variables, therefore, the training process of neural networks were speed up. 52 rhubarb samples in which 25 official and 27 unofficial rhubarb samples are included have been used to network modeling. The effects of neuron number in hidden layer and momentum parameter on classification have been investigated. Results showed that about 98% rhubarb samples could be identified correctly when optimized parameters were used. This method can be useful for quality control in rhubarb-contained Chinese medicine production.

Drugs, Chinese Herbal↗

PubMed2006

Molecular phylogeny and phylogeography of the Australian Diplodactylus stenodactylus (Gekkota; Reptilia) species-group based on mitochondrial and nuclear genes reveals an ancient split between Pilbara and non-Pilbara D. stenodactylus.

There is a paucity of research on intra-specific morphological and genetic diversity in Australian arid-zone reptiles, and a number of Australian reptile species have for many years been regarded as "species complexes" that classical morphological analyses could not resolve. We conducted a phylogenetic and phylogeographic study of a widespread species group of Australian geckonid lizards to address two main aims. First, based on a large mitochondrial and nuclear gene data set, we have generated the first molecular phylogeny for the Diplodactylus stenodactylus species group (D. alboguttatus, D. damaeus, D. maini, and D. squarrosus, D. stenodactylus) and multiple outgroups to examine the evolutionary relationships among these arid-zone species and phylogenetic patterns within some species. The edited alignment of 41 individuals comprises 2485 characters (1163 ND2+tRNAs; 490 16s; 832 RAG-1), and of these 717 (29%) were variable and parsimony informative (568 ND2+tRNAs; 89 16s; 60 RAG-1). This broad-scale, multi-gene phylogeny has supported previous conjectures on the higher-level phylogenetic relationships among members of the D. stenodactylus species-group based on morphology, but also has uncovered hidden diversity within the group with two new species identified. Analysis at this broad level has identified patterns associated with the distribution of the D. stenodactylus species group that appear to be influenced by environmental processes operating at large geographic scales. Two major clades within the species group were associated with broad differences in habitat types, with one group largely restricted to the temperate zone of the Southwest Province and another largely restricted to central and northern Western Australia north of Kalgoorlie, in line with the Eremaean Province of the Eremaean Zone and the Northern Province of the Tropical Zone. Second, we have assembled phylogeographic data based on a mitochondrial gene (ND2+tRNAs) for five species (Rhynchoedura ornata, Diplodactylus maini, D. pulcher, D. squarrosus, D. stenodactylus) where larger sampling is available, with particular focus on D. stenodactylus, which is distributed both in the iconic but little-known Pilbara area of endemism in north-western Australia as well as in other parts of the Australian arid zone. The edited alignment of 95 individuals comprises 1142 characters and of these 601 (53%) are variable and parsimony informative. We found significant intra-specific genetic variation in all five species, highlighting the need for large-scale screening of cryptic species, with sampling specifically targeted at determining the geographic limits of such taxa. In particular, within D. stenodactylus, a deep and ancient phylogenetic split distinguishes populations in the Pilbara region from non-Pilbara populations. This split may be the result of broad differences in underlying geological substrate, with the Pilbara clade generally preferring harder soils and the non-Pilbara clade adapted to sand.

Animals↗

PubMed2006

Non-exercise activity thermogenesis: the crouching tiger hidden dragon of societal weight gain.

Non-exercise activity thermogenesis (NEAT) is the energy expenditure of all physical activities other than volitional sporting-like exercise. NEAT includes all the activities that render us vibrant, unique, and independent beings such as working, playing, and dancing. Because people of the same weight have markedly variable activity levels, it is not surprising that NEAT varies substantially between people by up to 2000 kcal per day. Evidence suggests that low NEAT may occur in obesity but in a very specific fashion. Obese individuals appear to exhibit an innate tendency to be seated for 2.5 hours per day more than sedentary lean counterparts. If obese individuals were to adopt the lean "NEAT-o-type," they could potentially expend an additional 350 kcal per day. Obesity was rare a century ago and the human genotype has not changed over that time. Thus, the obesity epidemic may reflect the emergence of a chair-enticing environment to which those with an innate tendency to sit, did so, and became obese. To reverse obesity, we need to develop individual strategies to promote standing and ambulating time by 2.5 hours per day and also re-engineer our work, school, and home environments to render active living the option of choice.

Animals↗

PubMed2006

"Despair" induced by extinction trials in the water maze: relationship with measures of anxiety in aged and adult rats.

We have previously reported that extinction of escape behavior in the water maze due to the removal of the platform coincided with the development of behavioral "despair" in aged and adult rats, as assessed by immobility. The present study examines further predictions derived from the hypothesis that the withholding of reinforcement induces behaviors akin to depression. We tested for correlations between extinction performance and immobility, as well as between immobility and measures of anxiety in aged and adult rats. Age comparisons were also performed on these variables. Forty aged and 29 adult male Wistar rats (24 and 3 months old, respectively) were examined in the open field, black/white box and elevated-plus maze followed by 6 days of training in the water maze hidden platform task and 8 days of extinction without the platform. Indices of immobility increased over trials of extinction, with the aged showing higher levels, earlier onsets and larger slope increases of immobility than the adults. A lower resistance-to-extinction was predictive of more "despair" in both age groups. Between-group differences in the open field, black/white box and elevated-plus maze indicated that the aged showed more anxiety-like behavior than the adults and/or explored these environments less. Within the aged group, indicators of fearfulness in the three tests were predictive of higher levels of "despair". The extinction-despair model is held to provide the promise of a conceptual and empirical model of human depression that is the consequence of withdrawal of reinforcement.

Affect↗

PubMed2000

Evolution of poecilogony and the biogeography of North American populations of the polychaete Streblospio.

Invertebrate interspecific developmental patterns can be highly variable and, taxonomically, are considered only weakly constrained. Intraspecifically, some invertebrate species possess multiple developmental modes-a condition known as poecilogony. Closer examination of most putative poecilogenous species, however, has not supported poecilogony, but rather has uncovered hidden or cryptic species. The polychaete Streblospio benedicti is a well-known, poecilogenous species found along the coast of North America. We collected mitochondrial cytochrome subunit I DNA sequence data from 88 individuals taken from 11 locations along the Atlantic, Gulf, and Pacific Coasts of the United States to provide a phylogenetic framework from which to interpret intraspecific variation in larval life history and brooding structure morphology in this species. Our results are consistent with a recent revision of the species into two separate species: S. benedicti, a pouched brooding form distributed along the Atlantic and Pacific Coasts, and S. gynobranchiata, a branchiate brooding form in the Gulf of Mexico. Contrary to the redescription, S. benedicti is paraphyletic because the pouched brooding population in Vero Beach, Florida shows strong genetic affinity with Gulf of Mexico populations (S. gynobranchiata). However, S. benedicti is a true poecilogenous species, with both lecithotrophic and planktotrophic individuals possessing identical mitochondrial DNA haplotypes. Crossbreeding experiments further support the molecular phylogeny with reproductive isolation demonstrated between, but not within, the major phylogenetic clades consistent with the previously described species. The genetic break near Vero Beach, Florida, corresponds to a well-known phylogeographic boundary, but the estimated time of separation for the Streblospio spp., approximately 10 million years before present, predates all other known phylogeographic subdivisions in this area. This suggests that biogeographic sundering in this region is a recurrent event. Divergence times within the major Streblospio spp. clades are recent and indicate that changes in larval life history as well as brooding structure morphology are highly plastic and can evolve rapidly.

Animals↗