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Variation within serovars of Neisseria gonorrhoeae detected by structural analysis of outer-membrane protein PIB and by pulsed-field gel electrophoresis.

Outer-membrane protein PI is the antigen responsible for serovar specificity of Neisseria gonorrhoeae and is a potential vaccine target. In order to investigate possible hidden variation within a serovar, the sequence of the por genes encoding protein PIB have been obtained from a series of strains, including isolates known to be epidemiologically linked. The inferred amino acid sequences of the PIB molecules of isolates from known sexual contacts were identical, but non-related isolates showed significant heterogeneity in PIB sequence. These differences were not confined to the two variable regions (Var1 and Var2) which have previously been identified, but were largely, although not exclusively, located in regions predicted to form one of eight surface-exposed loops. The isolates were subjected to pulsed-field gel electrophoresis of restriction digests of chromosomal DNA, which also demonstrated identity between linked strains but revealed diversity within a serovar. The deduced amino acid sequences of PIB were also used to synthesize peptides for epitope-mapping experiments. These revealed that some mAbs, used to define serovar specificity, recognized linear epitopes located in loops 5 and 6, while others appeared to recognize conformational epitopes elsewhere in the molecule. The occurrence of the sequence differences within a serovar, which are not detected by the serotyping reagents, reveals that PIB represents a potential source of information which should permit considerably more detailed epidemiological studies than are currently possible and focuses attention on more conserved regions of the protein as potential targets for vaccination.

Amino Acid Sequence↗

Neural networks for the biochemical prediction of bone mass loss.

Neural networks are specialized artificial intelligence techniques that have shown high efficiency in dealing with complex problems. Paradigms such as backpropagation have been successfully applied in a number of biomedical applications, but not in attempts to identify women at risk of postmenopausal osteoporotic complications. In this paper, several neural networks were trained using different combinations of biochemical variables as inputs. Bone densitometric measurements in Ward's triangle and in the spinal column were used as separate classification criteria (outputs) between slow and fast bone mass losers. The most parsimonious model with the best performance included plasma concentrations of estrone, estradiol, osteocalcin, parathyrin and urine concentrations of calcium and hydroxyproline (expressed as ratio to creatinine excretion) as input neurons; ten neurons in a single hidden layer; and one neuron in the output layer. Diagnostic efficiency was 76% in Ward's triangle and 74% in the spinal column; sensitivity was 70 and 81%, and specificity was 77 and 65%, respectively. Linear discriminant analysis showed a diagnostic efficiency of 66% in Ward's triangle and 64% in the spinal column, sensitivity was 55 and 86%, and specificity was 75 and 13%, respectively. We conclude that performance of the stepwise discriminant analysis was not superior to the neural networks.

Adult↗

[The treatment of pulmonary tuberculosis in a special hospital. Its evolution from 1948 to 1986].

Nine hundred and sixty six patients diagnosed of pulmonary and/or pleural tuberculosis and admitted to a specialized hospital from 1948 to 1986, have been retrospectively analyzed, investigating their treatment and evolution. Sixty two percent of patients did not fulfil pharmaceutical treatment as far as number and dose of drugs, evolving through the decades (50, 60, 70, and 80s) with a 100%, 82%, 37% and 3% respectively. A 13% of patients did not receive any chemotherapy, 16% underwent surgery, and 53% received a second treatment. Real or hidden monotherapy was given to 38% of patients. Isoniazide has been the most uniformly used drug. Streptomycin has been the most frequently underdosed used drug. Sputum culture turned negative in 42% and 51% of patients during the first 3 and 6 months respectively, with a 42% of positives persisting after one year and a 30% when discharged. A statistically significant difference is observed when comparing all the variables between admitted patients up to 1969 and from 69 to 86 in favor of the second period.

Antitubercular Agents↗

Field dependence and the differentiation of affective states.

The extent to which anxiety, irritability and depression were differentiated as separate entities associated with characteristic patterns of somatic and cognitive symptoms by field dependent (FD) and field independent (FI) normal female subjects was studied with the Hidden Figures Test and Unpleasant Emotions Questionnaire. In the FI group the correlations between the three emotions were low and non-significant, reflecting a clear-cut differentiation in symptom configuration, as shown by psychiatrists. In the FD group the inter-correlations were significant and positive, corresponding to relatively poor symptom differentiation, comparable to that of a psychiatric patient group. This suggests that the cognitive style variable of field dependence may underly differences in symptom differentiation associated with psychiatrist/patient differences and, more generally, with social class and sex differences.

Adult↗

Usefulness of (18)F-fluorodeoxyglucose PET for radiosurgery planning and response monitoring in patients with recurrent spinal metastasis.

INTRODUCTION: With the advancement and successful treatment of metastatic spinal cord disease, newer treatments are needed for the long-term survivors of recurrent disease. The lack of a standardized re-treatment regimen and the difficulty in delineating the tumor margins among patients who have received the treatment with metallic spinal fixation and conventional radiation are two of the challenges to be faced in recurrent metastatic spinal cord disease. In these patients, we applied hypofractionated stereotactic radiosurgery by defining the tumor margin with (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET). PATIENTS AND METHODS: Three consecutive recurrent spinal metastasis patients underwent the CyberKnife treatment (Accuray, Inc., Sunnyvale, CA) from March 2004 to July 2004. A three-fraction schedule was applied at approximately 24 hour intervals. One patient had sarcoma and the other two patients had breast cancer. All patients had received previous conventional radiotherapy after operation ranging from 30 Gy to 45 Gy. CT-based planning was corrected by the FDG-PET hyperuptake area with the help of nuclear medicine. The mass responses were followed not only by MRI but also by FDG-PET, which was taken prior to treatment, and at one and six months after the treatment. The changes in standard uptake value (SUV) of serial PET were taken as a measure of response. To evaluate the relative SUV changes from different pretreatment values, we set a reduction index (RI), which represents the ratio of SUV change to pretreatment SUV. RESULTS: No significant complications were noted during treatment with a mean follow-up of 13.3 months. The tumor volume on CT-based planning was 2.2 times larger than that of the CT-PET combined planning in case 1 of paraspinal muscle invasion. But the tumor volumes showed minimal changes in the other cases, in which the metastatic tumors were confined to the vertebral bodies. The SUV one month after treatment showed variable decreases and the RI ranged from 0.07 to 0.7. However, the SUVs at 6 months were well correlated with the clinical results. One patient showed marginal failure and the other two patients showed local control of the tumor, as their RI values were 0.65 and 0.87, respectively. CONCLUSION: To our knowledge, this is the first report using FDG-PET with radiosurgery in patients with recurrent spinal metastases hidden under metallic artifacts. The mass responses measured by SUV changes in FDG-PET correlated with the clinical results.

Adult↗

Worse functional status among old people when admitted for arthroplasty--an evaluation with a new assessment system.

The aim of this study was to investigate whether there is a difference in functional status between younger and elderly people referred to an orthopaedic clinic for total joint replacement. A total of 709 patients with osteoarthritis of the hip or knee (aged 27-91 years) and 42 healthy controls (aged 42-83 years) were examined with a new Functional Assessment System (FAS) for lower extremity dysfunction. Age effects were explored by one-way analysis of variance. Older people showed higher dysfunction scores in almost all variables, with the exception of pain, where there was an inverse relationship, i.e, old people had lower disability scores. This age-related increase in disability scores was not observed in the control group. Old people seem to be referred for joint replacement on different grounds from those of younger people, despite the fact that age was not included in the criteria for arthroplasty. The results may indicate a hidden, age-related criterion in the selection of patients for arthroplasty. Different interpretations are discussed.

Activities of Daily Living↗

Unwelcome guests with master keys: how HIV enters cells and how it can be stopped.

HIV entry to host cells begins with binding of the viral envelope protein to CD4 molecules on the host cell surface. This binding initiates conformational changes in the envelope protein that result in binding to a coreceptor (CCR5 or CXCR4), exposure of a previously hidden domain in the viral protein, insertion of a viral fusion peptide into the host-cell membrane and fusing the viral and cell membranes. Each of these steps provides an opportunity for intervention to prevent viral entry, and a number of agents targeting these steps are in development. Studies of coreceptor inhibitors and fusion inhibitors have indicated the presence of host and viral factors that can result in variability of antiretroviral effect. Improved understanding of these factors will help to guide clinical use of these new agents. This article summarizes a presentation by Robert W. Doms, MD, PhD, at the International AIDS Society-USA course in Chicago in May 2004.

Anti-HIV Agents↗

Application of Bayesian regularized BP neural network model for analysis of aquatic ecological data-a case study of chlorophyll-a prediction in Nanzui water area of Dongting Lake.

Bayesian regularized BP neural network(BRBPNN) technique was applied in the chlorophyll-a prediction of Nanzui water area in Dongting Lake. Through BP network interpolation method, the input and output samples of the network were obtained. After the selection of input variables using stepwise/multiple linear regression method in SPSS 11.0 software, the BRBPNN model was established between chlorophyll-a and environmental parameters, biological parameters. The achieved optimal network structure was 3-11-1 with the correlation coefficients and the mean square errors for the training set and the test set as 0.999 and 0.00078426, 0.981 and 0.0216 respectively. The sum of square weights between each input neuron and the hidden layer of optimal BRBPNN models of different structures indicated that the effect of individual input parameter on chlorophyll-a declined in the order of alga amount > secchi disc depth (SD) > electrical conductivity (EC). Additionally, it also demonstrated that the contributions of these three factors were the maximal for the change of chlorophyll-a concentration, total phosphorus (TP) and total nitrogen (TN) were the minimal. All the results showed that BRBPNN model was capable of automated regularization parameter selection and thus it may ensure the excellent generation ability and robustness. Thus, this study laid the foundation for the application of BRBPNN model in the analysis of aquatic ecological data(chlorophyll-a prediction) and the explanation about the effective eutrophication treatment measures for Nanzui water area in Dongting Lake.

Bayes Theorem↗

Somitogenesis in amphibian embryos. III. Effects of ambient temperature and of developmental stage upon pattern abnormalities that follow short temperature shocks.

Temperature shocks of a few minutes duration at 37 degrees C to tail-bud embryos of Rana induce zones of abnormal segmentation along the somite files subsequently produced. The immediate result of a temperature shock is a temporary arrest of development as a whole, following which the schedule of somite determination and formation is resumed at the normal rate. It is during the period immediately following this that the zone of abnormal somite pattern is determined. Thus the length of the abnormal zone reflects the total time taken by the morphogenetic system to recover from the disturbance, and might depend upon variables affecting both the duration of the initial arrest and the duration of the recovery period itself. Observations are presented demonstrating how the length of abnormal zones, caused by a temperature shock of any particular severity, are affected by three variables; (1) the ambient temperature to which the embryos were adapted before shock, (2) the ambient temperature of post-shock development, (3) the stage in somitogenesis, i.e. the number of somites already formed at the time of shock. The data (in this and previous papers of the series) support models postulating that the spatial periodicity in cell behaviour, that is somite morphogenesis, reflects a normal interaction between two hidden aspects of development, one a wavefront of cellular activation passing down the body axis, and the other having the character of a temporal periodicity throughout the tissue. Temperature shock, as well as halting the wavefront (i.e. stopping development) temporarily, leads to a subsequent period during which there is only gradual recovery of normal co-ordination between the periodicity within cells of the tissue and the wavefront progress. It is the relative rate of this recovery, alone, that is responsible for variation in the length of the abnormal zone.

Animals↗

Position sense during imperceptibly slow movements.

Proprioceptive input provides the nervous system with information related to body position and movement. This study investigated how normal humans perceive information related to the position of a limb when it is either at rest or moving very slowly, below the threshold for movement perception. Each subject's left hand, hidden from view, was horizontally translated in the frontal plane such that joint rotation was largely isolated to the shoulder. The translation speed was too slow for the subjects to detect movement. Subjects indicated their perception of hand position at 1- or 2-min intervals by pointing with the right index finger to the perceived location of the tip of the left middle finger. The constant error (i.e., bias) and variable error (i.e., SD of mean constant error) of each pointing movement was quantified. Partway through the trial, the direction of hand movement was reversed. In two additional experimental conditions, the subjects pointed at 1- or 2-min intervals at the stationary left hand, either when they assumed the hand would be moved or when they knew it would not. During slow movement, errors in the frontal and sagittal planes were found to be independent, and therefore, data analysis focused on the frontal plane, as this was the plane relevant to the subjects' task. All subjects performed the task sufficiently well to demonstrate a clear perception of hand location during the slow movement. The accuracy of perception was better when the left (target) hand was in its ipsilateral hemifield and, correspondingly, when the right hand pointed to its contralateral hemifield. There was no significant difference in constant error when the hand moved slowly, although there was a slightly higher variable error during slow movement than when the hand was stationary. Based on the similarity of results in trials with very slow and no hand movement, it was concluded that position-sense percepts are more accurately distinguished by the speed of movement rather than whether movement is occurring or not.

Adult↗

Assessment of respondent driven sampling for recruiting female sex workers in two Vietnamese cities: reaching the unseen sex worker.

Respondent driven sampling (RDS) is a relatively new method to sample hard-to-reach populations. Until this study, female sex workers (FSWs) in Vietnam were sampled using a variety of methods, including time location sampling (TLS), which may not access the more hidden types of FSWs. This paper presents an analysis from an HIV biological and behavioral surveillance survey to assess the feasibility and effectiveness of RDS to sample FSWs, to determine if RDS can reach otherwise inaccessible FSWs in Vietnam and to compare RDS findings of HIV risk factors with a theoretical TLS. Through face-to-face interviews with FSWs in Ho Chi Minh City (HCMC) and Hai Phong (HP), data were collected about the venues where they most often solicit their clients. These data were used to create three variables to assess whether FSWs solicit their clients in locations that are visible, semi-visible and non-visible. For this analysis, the visible group simulates a sample captured using TLS. Survey results in HIV prevalence and related risk factors and service utilization, adjusted for sampling methodology, were compared across each of the three FSW visibility groups to assess potential bias in TLS relative to RDS. The number of self-reported visible FSWs (HCMC: n=311; HP: n=162) was much larger than those of the semi-visible (HCMC: n=65; HP: n=43) and non-visible (HCMC: n=37; HP: n=10) FSWs in HCMC and HP. Non-visible FSWs in both cities were just as likely as visible and semi-visible FSWs to be HIV positive (HCMC: visible 14.5%, semi-visible 13.8%, non-visible 13.5%, p value = 0.982; HP: visible 35.2%, semi-visible 30.2%, non-visible 30.0%, p value = 0.801), to practice behaviors that put them at risk for contracting and transmitting HIV (injecting drug use-HCMC: visible 13.8%, semi-visible 12.3%, non-visible 5.4%, p value = 0.347; HP: visible 38.9%, semi-visible 23.3%, non-visible 30.0%, p value = 0.378, to have no condom use in the past month -HCMC only: visible 52.7%, semi-visible 63.1%, non-visible 48.6%, p value = 0.249) and to have symptoms of a sexually transmitted infection (STI) in the past year (HCMC: visible 16.1%, semi-visible 12.3%, non-visible 16.2%, p value = 0.742; HP: visible 13.6%, semi-visible 18.6%, non-visible 20.0%, p value = 0.640). There was a difference found among the visible, semi-visible and non-visible groups in HP for no past month condom use (visible 53.1%, semi-visible 79.1%, non-visible 60.0%, p value = 0.009). This study found that RDS was successful at recruiting hidden types of FSWs in Vietnam. Past reports of FSWs in Vietnam have assessed the more visible FSWs as being the most vulnerable and at risk for HIV. Although the number of visible FSWs is much higher than those of the semi and non-visible groups, this study found that the non-visible FSWs are very vulnerable to HIV infection. If prevention programs are targeting and responding to those who are most likely to be assessed (e.g., more visible types of FSWs) then this analysis indicates that a significant proportion of the FSW population at risk for HIV may not be receiving optimal HIV information and services.

Data Collection↗

Studies on the attraction of Simulium damnosum s.l. (Diptera: Simuliidae) to its hosts. I. The relative importance of sight, exhaled breath, and smell.

Four traps used in capturing hunting female S. damnosum s.l. are discribed: the slat trap, the enclosure trap, the fan trap, and the sticky trap. In forest a man hidden inside a trap, but removing his exhaled breath through a long hose, attracted 4 times as many flies as did an unbaited trap. When the man exhaled normally into the trap the number of flies taken rose again by a further factor of 4. Carbon dioxide gas, emitted from inside the trap attracted some two-thirds as many flies as a man exhaling normally inside the trap. In both forest and Sudan-savanna environments the catches of a man stationed on an open stretch of land and fully exposed to view while his exhaled breath was removed through a long hose, were not substantially lower than those of a man in a similar situation who exhaled normally. In forest a motionless man, partly hidden among vegetation, attracted fewer flies than a moving man who was fully exposed to view (a) when both men removed their exhaled breath through long hoses, and (b) when they exhaled normally. In the forest a trap baited with CO2 gas (250 cc per min) caught more flies than a similar, unbaited trap, but the preformance of CO2-baited traps, as compared with that of human collectors, was highly variable. Catches in CO2-baited traps were uniformly low in the Sudan-savanna. In forest, removal of olfactory substances from the human skin, by vigorous washing and application of petroleum jelly, or by wearing impermeable clothing, greatly reduced the numbers of flies attracted. No such reduction was observed in Sudan savanna. In the forest, cloths, worn by men for several days and then used as bait, attracted about 10 times as many flies as did similar, unworn cloths. Addition of CO2 gas produced a 4-fold increase in the attractiveness of worn cloths and an 18-fold increase in that of unworn cloths. No corresponding experiments were done in the savanna. Fan traps could become contaminated by human handling during the assembly and setting-up procedures. They were thus rendered attractive to flies. In the Sudan-savanna, the catches of men positioned in front of warm rock surfaces were lower than those of men stationed on coller, sandy surfaces. This suggests that body heat may be an additional attractant factor. The results suggest that "forest" S. damnosum s.l. (presumably S. squamosum) females rely heavily on smell as an attractant and, to a lesser extent, on sight and exhaled breath. Smell appears to be the only obligatory attractant, and it can act by itself. This raises the possibility that a trap might be developed which incorporates only smell stimuli as bait. For "savanna" S. damnosum s.l. (presumably S. damnosum s.s.) neither smell nor exhaled breath appear to be important attractants, and some other factor, perhaps sight, appears to be the dominant attractant in this zone.

Air↗

Extranodal marginal zone (MALT) lymphoma in common variable immunodeficiency.

We describe two patients with common variable immunodeficiency (CVID) who developed extranodal marginal zone lymphoma (formerly described as mucosa-associated lymphoid tissue lymphoma or MALT lymphoma). One patient, with documented pernicious anaemia and chronic atrophic gastritis with metaplasia, developed a Helicobacter pylori-positive extranodal marginal zone lymphoma in the stomach. Three triple regimens of antibiotics were necessary to eliminate the H. pylori, after which the lymphoma completely regressed. Patient B had an H. pylori-negative extranodal marginal zone lymphoma of the parotid gland, which remarkably regressed after treatment with clarithromycin. Reviewing the literature, we found eight cases of extranodal marginal zone lymphoma complicating CVID, but probably many more cases labelled as non-Hodgkin's lymphoma are hidden in the literature. Until more data are available on the predictive value of noninvasive screening for pathology of the stomach, we recommend endoscopy to assess the gastric status in CVID patients in order to detect these malignancies at an early stage. Elimination of H. pylori infection is the treatment of choice in Helicobacter-positive extranodal marginal zone lymphoma. The possibility of elimination failure, most probably due to frequent and prolonged exposure to antibiotics in this patient group, should be taken into account. Treatment with antibiotics in Helicobacter-negative extranodal marginal zone lymphoma must be considered.

Adult↗

Evaluation of the ability of an artificial neural network model to assess the variation of groundwater quality in an area of blackfoot disease in Taiwan.

The back-propagation (BP) artificial neural network (ANN) is applied to forecast the variation of the quality of groundwater in the blackfoot disease area in Taiwan. Three types of BP ANN models were established to evaluate their learning performance. Model A included five concentration parameters as input variables for seawater intrusion and three concentration parameters as input variables for arsenic pollutant, respectively, whereas models B and C used only one concentration parameter for each. Furthermore, model C used seasonal data from two seasons to train the ANN, whereas models A and C used only data from one season. The results indicate that model C outperforms models A and B. Model C can describe complex variation of groundwater quality and be used to perform reliable forecasting. Moreover, the number of hidden nodes does not significantly influence the performance of the ANN model in training or testing.

Arsenic Poisoning↗

Algorithms for variable length Markov chain modeling.

UNLABELLED: We present a general purpose implementation of variable length Markov models. Contrary to fixed order Markov models, these models are not restricted to a predefined uniform depth. Rather, by examining the training data, a model is constructed that fits higher order Markov dependencies where such contexts exist, while using lower order Markov dependencies elsewhere. As both theoretical and experimental results show, these models are capable of capturing rich signals from a modest amount of training data, without the use of hidden states. AVAILABILITY: The source code is freely available at http://www.soe.ucsc.edu/~jill/src/

Algorithms↗

Numerical modeling of needle tip artifacts in MR gradient echo imaging.

Exact determination of needle tip position is obsolete for interventional procedures under control of magnetic resonance imaging (MRI). Exact needle tip navigation is complicated by the paramagnetism of microsurgical instruments: Local magnetic field inhomogeneities are induced resulting in position encoding artifacts and in signal voids in the surrounding of instruments and especially near their tips. The artifacts generated by the susceptibility of the material are not only dependent on the material properties themselves and on the applied MRI sequences and parameters, but also on the geometric shape of the instruments and on the orientation to the static magnetic field in the MR unit. A numerical model based on superposition of induced elementary dipole fields was developed for studying the field distortions near paramagnetic needle tips. The model was validated by comparison with experimental data using field mapping MRI techniques. Comparison between experimental data and numerical simulations revealed good correspondence for the induced field inhomogeneities. Further systematic numerical studies of the field distribution were performed for variable types of concentric and asymmetric tip shapes, for different ratios between tip length and needle diameter, and for different orientations of the needle axis in the external static magnetic field. Based on the computed local inhomogeneities of the magnetic field in the surroundings of the needle tips, signal voids in usual gradient echo images were simulated for a prediction of the artifacts. The practically relevant spatial relation between those artifacts and the hidden tip of the needle was calculated for the different tip shapes and orientations in the external field. As needle tip determination is crucial in interventional procedures, e.g., in taking biopsies, the present model can help to instruct the physician prior to surgical interventions in better estimating the needle tip position for different orientations and needle tip shapes as they appear in interventional procedures. As manufacturing prototypes with subsequent measurements of artifacts in MRI are a costly procedure the presented model may also help to optimize shapes of needle tips and of other parts of MR-compatible instruments and implants with low expense prior to production if some shape parameters can be chosen freely.

Artifacts↗

Accumulation of hippocampal place fields at the goal location in an annular watermaze task.

To explore the plastic representation of information in spatially selective hippocampal pyramidal neurons, we made multiple single-unit recordings in rats trained to find a hidden platform at a constant location in a hippocampal-dependent annular watermaze task. Hippocampal pyramidal cells exhibited place-related firing in the watermaze. Place fields tended to accumulate near the platform, even in probe trials without immediate escape. The percentage of cells with peak activity around the hidden platform was more than twice the percentage firing in equally large areas elsewhere in the arena. The effect was independent of the actual position of the platform in the room frame. It was dissociable from ongoing motor behavior and was not related to linear or angular speed, swim direction, or variation in hippocampal theta activity. There was no accumulation of firing in any particular region in rats that were trained with a variable platform location. These training-dependent effects suggest that regions of particular behavioral significance may be over-represented in the hippocampal spatial map, even when these regions are completely unmarked.

Action Potentials↗

A sequence alignment algorithm with an arbitrary gap penalty function.

An algorithm for aligning biological sequences is presented that is an adaptation of the sequence generating function approach used in the statistical mechanics of biopolymers. This algorithm uses recursion relationships developed from a partition function formalism of alignment probabilities. It is implemented within a dynamic programming format that closely resembles the forward algorithm used in hidden Markov models (HMM). The algorithm aligns sequences or structures according to the statistically dominant alignment path and will be referred to as the SDP algorithm. An advantage of this method over previous ones is that it allows more complicated and physically realistic gap penalty functions to be incorporated into the algorithm in a facile manner. The performance of this algorithm in a case study of aligning the heavy and light chain from the variable region of an immunoglobulin is investigated.

Algorithms↗