Search

Background and aim: The chronic complications of diabetes mellitus (DM) are accompanied by inflammatory manifestations. Our study aimed to assess the association between inflammatory status, reflected by C-reactive protein (CRP) values and the evolution of type 1 and 2 DM patients, evaluated by glycated hemoglobin (HbA1c) levels, the length of disease duration, the average time until the onset of microvascular complications and their risk of occurrence. Methods: We conducted a retrospective observational study, involving 192 patients, randomly selected from the medical records of the Centre for Diabetes Mellitus, Nutrition and Metabolic Diseases, Cluj-Napoca, Romania. Results: We noted significant differences between the two patient groups concerning HbA1c levels in patients with stage I nephropathy and CRP values in those with retinopathy. A significant positive correlation between the levels of studied biomarkers and disease duration was noted for type 1, but not for type 2 patients. We found a higher risk of chronic complications in patients with type 2, compared to those with type 1 DM: the relative risk was higher by 1.87 (1.59–1.97) times for nephropathy, 2.57 (1.56–4.18) times for retinopathy and 3.66 (3.00–3.82) times for neuropathy. Conclusion: Our study indicates a direct link between systemic inflammation and the timely progression of type 1 DM. In patients with type 2 DM, no statistical significance was found between the levels of studied biomarkers and the occurrence of microvascular complications. Nephropathy appeared sooner in type 1 DM patients, while retinopathy and neuropathy had a similar pattern of occurrence in both types of patients. [ABSTRACT FROM AUTHOR]

The random walk' correlation matrix of multi-objective combinatorial optimization problems utilizes both local structure and general statistics of the objective functions. Reckoning time of correlation, or the random walk of lag 0, is quadratic in problem size L and number of objectives D. The computational complexity of the correlation coefficients of mNK is O (D 2 K 2 L) , and of mQAP is O (D 2 L 2) , where K is the number of interacting bits. To compute the random walk of a lag larger than 0, we employ a weighted graph Laplacian that associates a mutation operator with the difference in the objective function. We calculate the expected objective vector of a neighbourhood function and the eigenvalues of the corresponding transition matrix. The computational complexity of random walk's correlation coefficients is polynomial with the problem size L and the number of objectives D. The computational effort of the random walks correlation coefficients of mNK is O (2 K L D 2) , whereas of mQAP is O (L 6 D 2) . Numerical examples demonstrate the utilization of these techniques. [ABSTRACT FROM AUTHOR]

Purpose: Endometriosis has an incidence reaching up to 50% in infertile women. Cytokine-mediated immune responses seem to play an important role in endometriosis pathogenesis, but still the etiology and pathophysiology remain unclear. In the current study we tried to investigate whether there is a relationship between IL-10 genetic polymorphism, serum levels of IL-10 and the presence of advanced endometriosis.Methods: The presence of IL-10 592C/A, 819T/C, 1082G/A promoter polymorphisms and IL-10 serum levels were investigated in advanced endometriosis patients compared to healthy controls. Genomic DNA was extracted from peripheral blood leukocytes and further analyzed by PCR.Results: IL-10 serum levels were higher in endometriosis group compared to controls (1.48, 0.68, p < 0.001). We have observed an association between IL-10 592C/C and 819C/C genotypes, presence of C alleles and an increased risk of endometriosis. No difference was observed in IL-10 serum levels corresponding to different alleles or genotypes.Conclusion: Our results suggest that IL-10 592A/C and 819T/C promoter polymorphisms confer susceptibility to advanced endometriosis. No associations were found between the IL-10 1082A/G polymorphism and susceptibility to advanced endometriosis. [ABSTRACT FROM AUTHOR]

The efficiency of local search is proportional to the number and the distribution of basins of attraction. Often combinatorial optimisation problems have a large number of local optima, uncountable with available computational resources. Approximating the number of basins of attraction and the minimal number of samples for visiting all basins at least once are complex problems for which we assume specific distributions of basins of attraction. We define two types of basins of attraction of multi-objective combinatorial optimisation problems with complementary properties. Acknowledging that each local search run generates a Pareto front of solutions, either each Pareto local solution corresponds to a basin of attraction, or a Pareto basin matches an entire Pareto local front. Simulations compare parametric and non-parametric estimators on bi-objective quadratic assignment problem instances. [ABSTRACT FROM AUTHOR]

We use variational methods and a modified curvature flow to give an alternative proof of the existence of an embedded topological S1×Sn-1 self-shrinking hypersurface under mean curvature flow. As a consequence of the proof, we establish an upper bound for the weighted energy of our shrinking doughnuts. [ABSTRACT FROM AUTHOR]

The trade-off between the exploration of large size neighborhoods and the exploitation of Pareto fronts with high cardinality is a challenging task for the metaheuristics for many-objective combinatorial optimization problems. Cartesian products of scalarization functions, or simpler, Cartesian scalarization, is a novel technique that simplifies the search by reducing the number of objectives using sets of scalarization functions. Cartesian scalarization is an alternative to scalarization functions that scales up the local search for many-objective spaces. We introduce a method that automatically generates Cartesian scalarization functions; we use combinatorics to analyze the properties of Cartesian scalarization functions. Cartesian scalarization local search (CsLs) uses a set of Cartesian scalarization functions to generate a quality Pareto local front. We show that CsLs is a well-defined local search algorithm that converges to a Pareto local solution set in finite time. Cartesian scalarization outperforms other Pareto and scalarization local search methods on many-objective combinatorial optimization instances. [ABSTRACT FROM AUTHOR]

The aims of this study were to evaluate the health-related quality of life (HRQL) according to: type of surgery, adjuvant oncological treatment and postoperative complications. We performed a retrospective case-control study between October 2013 and November 2014 at the Ear Nose and Throat Clinic of Cluj-Napoca. We included patients diagnosed with laryngeal or hypopharyngeal cancer treated with total or partial laryngectomy, and a sample of healthy volunteers recruited from the hospital stuff. We used the European Organisation for Research and Treatment of Cancer (EOTRC) core questionnaires (the QLQ-C30 version 3) and the head and neck cancer module (the QLQ-H&N35). We included in the study 80 patients diagnosed and surgically treated for laryngeal/hypopharyngeal squamous cell carcinoma and 20 healthy volunteers. Median age of the patients was 59.90 years. The most common location was the larynx, in 72 (90 %) of cases and the hypopharynx in 8 (10 %) cases. Sixty-six (82, 50 %) underwent total laryngectomy and 14 (17, 50 %) a partial laryngectomy. Forty-eight patients had received external radiation therapy, with adjuvant chemotherapy in 25 patients. Postoperative complication rates were 14 (17, 50 %) cases. We found a low score in total laryngectomy group regarding functional scales: role (28.03), emotional (37.75) and social (37.88) and a high score on insomnia (35.86) and financial difficulties (45.45). Partial laryngectomy group had a high score on functional scales: role (47.62), emotional (51.19) and social (52.38). These two QOL instruments were effective for Romanian patients. The QLQ-H&N35 questionnaire discriminating better the problems between groups compared with QLQ-C30. [ABSTRACT FROM AUTHOR]

We perform a micromechanical analysis of general isotropic non-cohesive particulate materials idealized as three-dimensional random assemblies of uniform spheres with a simple linear elastic inter-particle contact force law and inter-particle Coulomb friction law. We obtain analytical relationships between the inter-particle friction coefficient $$\mu$$ (or inter-particle friction angle $$\phi _\mu = \tan ^{-1} \mu$$ ) on the microscale and the material friction angle $$\phi$$ on the macroscale. Our micromechanical analysis directly employs force and moment equilibrium (together with compatibility and the contact constitutive assumptions noted) rather than energy methods, and thus can account for the effects of particle rotation, and in particular the effects of mechanisms or zero-energy modes due to particle rotation. To explore the effects of particle rotation, we perform analyses with particle rotation either allowed or prohibited. To validate the analytical results obtained here, we compare the $$\phi$$ versus $$\phi _\mu$$ curves determined theoretically to those obtained by the discrete element method (DEM) for six randomly packed specimens of 3430-29, 660 uniform spherical elements with uniform inter-element Coulomb friction in Fleischmann et al. in Geotech Geol Eng 32(4):1081-1100, (). The $$\phi$$ versus $$\phi _\mu$$ curves derived here show remarkable agreement with those obtained via DEM simulations in Fleischmann et al. in Geotech Geol Eng 32(4):1081-1100, (), especially for the case in which particle rotation is not artificially restrained. [ABSTRACT FROM AUTHOR]

Quadratic assignment problems (QAPs) is a NP-hard combinatorial optimization problem. QAPs are often used to compare the performance of meta-heuristics. In this paper, we propose a QAP problem instance generator that can be used for benchmarking for heuristic algorithms. Our QAP generator combines small size QAPs with known optimum solution into a larger size QAP instance. We call these instances composite QAPs (cQAPs), and we show that the cost function of cQAPs is additively decomposable. We give mild conditions for which a cQAP instance has known optimum solution. We generate cQAP instances using uniform distributions with different bounds for the component QAPs and for the rest of the cQAP elements. Numerical and analytical techniques that measure the difficulty of the cQAP instances in comparison with other QAPs from the literature are introduced. These methods point out that some cQAP instances are difficult for local search with many local optimum of various values, low epistasis and non-trivial asymptotic behaviour. [ABSTRACT FROM AUTHOR]

The process of glucose transport via the placenta is not fully deciphered. Here, we apply a theoretical model to compute glucose fluxes via the terminal villi of the human placenta for various sets of parameter values and conclude on characteristics of transport across the two bordering membranes. Based on available measured data, the spatial geometry of the terminal villi is being simulated. Within this region, glucose concentrations and fluxes are computed by a numerical scheme that solves the diffusion equation with boundary conditions that account for transporter mediated diffusion at the membranes. Feasible parameter values (ones that induce physiological glucose fluxes) are determined for four optional symmetry characteristics of the membranes. Confronting computed results with clinical knowledge reveals the most plausible scenario-symmetric activity of the transporter at the microvillous membrane. Thus, sensitivity analysis of the computed results enables deduction about micro-scale mechanisms at the bordering membranes based on macro-scale knowledge. [ABSTRACT FROM AUTHOR]

We perform numerical simulations using the discrete element method (DEM) to determine yield surfaces for large samples of randomly packed uniform spheres with constant normal and tangential contact stiffnesses (linear spring model) and uniform inter-particle friction coefficient μ, for a large range of values of the inter-particle friction coefficient μ. The beauty of DEM is that the micromechanical properties of the spheres, especially the inter-particle friction coefficient μ, are known exactly. Further, simulations can be performed with particle rotation either prohibited or unrestrained, which provides an effective means for evaluating analytical models that employ these assumptions. We compare the resulting yield surfaces to the Mohr-Coulomb, Matsuoka-Nakai, Lade-Duncan, and Drucker-Prager yield surfaces, and determine the relationship between the resulting material friction angle ϕ on the macroscale and the inter-particle friction coefficient μ (or the inter-particle friction angle ϕ) on the microscale. We find the Lade-Duncan yield surface provides the best agreement, by far, with the simulations in all cases. We also monitor inter-particle friction work and particle rotation within each specimen during the DEM simulations, both globally and on a particle-by-particle basis, and we compare the results obtained from DEM simulations in which the spheres were allowed full three-dimensional translational and rotational freedom of motion and DEM simulations in which particle rotation was prohibited. [ABSTRACT FROM AUTHOR]

Pareto local search (PLS) methods are local search algorithms for multi-objective combinatorial optimization problems based on the Pareto dominance criterion. PLS explores the Pareto neighbourhood of a set of non-dominated solutions until it reaches a local optimal Pareto front. In this paper, we discuss and analyse three different Pareto neighbourhood exploration strategies: best, first, and neutral improvement. Furthermore, we introduce a deactivation mechanism that restarts PLS from an archive of solutions rather than from a single solution in order to avoid the exploration of already explored regions. To escape from a local optimal solution set we apply stochastic perturbation strategies, leading to stochastic Pareto local search algorithms (SPLS). We consider two perturbation strategies: mutation and path-guided mutation. While the former is unbiased, the latter is biased towards preserving common substructures between 2 solutions. We apply SPLS on a set of large, correlated bi-objective quadratic assignment problems (bQAPs) and observe that SPLS significantly outperforms multi-start PLS. We investigate the reason of this performance gain by studying the fitness landscape structure of the bQAPs using random walks. The best performing method uses the stochastic perturbation algorithms, the first improvement Pareto neigborhood exploration and the deactivation technique. [ABSTRACT FROM AUTHOR]

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Intermittent swim stress (ISS) produces deficits in swim escape learning and increases immobility in the forced swim test (FST). A previous attempt to reverse this immobility with the selective serotonin reuptake inhibitor (SSRI), fluoxetine (FLX), was unsuccessful, but the sensitivity of this immobility to other types of antidepressants is unknown. In experiment 1, we evaluate the ability of the norepinephrine (NE) selective reuptake inhibitor (NSRI), desipramine (DES), to reverse the ISS-induced immobility in the FST compared to confined controls (CC), while in experiment 2, we test the efficacy of either the SSRI or NSRI to reverse the immobility produced by either ISS or continuous swim (CS)/FST. Rats were exposed to their respective behavioral pretreatment (ISS, CS/FST, or CC) and were then injected with an antidepressant or saline solution 23.5, 5, and 1 h prior to the FST. In experiment 1, DES reduced immobility and increased the climbing behavior in the ISS group without altering these behaviors in the CC, while in experiment 2, the CS/FST-induced immobility was reduced by both antidepressants (i.e., FLX and DES), while the ISS-induced immobility was only affected by DES. These results suggest that the ISS-induced immobility is mediated through the NE system and may represent a model for atypical depression. [ABSTRACT FROM AUTHOR]

Markov Chain Monte Carlo (MCMC) methods are often used to sample from intractable target distributions. Some MCMC variants aim to improve the performance by running a population of MCMC chains. In this paper, we investigate the use of techniques from Evolutionary Computation (EC) to design population-based MCMC algorithms that exchange useful information between the individual chains. We investigate how one can ensure that the resulting class of algorithms, called Evolutionary MCMC (EMCMC), samples from the target distribution as expected from any MCMC algorithm. We analytically and experimentally show—using examples from discrete search spaces—that the proposed EMCMCs can outperform standard MCMCs by exploiting common partial structures between the more likely individual states. The MCMC chains in the population interact through recombination and selection. We analyze the required properties of recombination operators and acceptance (or selection) rules in EMCMCs. An important issue is how to preserve the detailed balance property which is a sufficient condition for an irreducible and aperiodic EMCMC to converge to a given target distribution. Transferring EC techniques to population-based MCMCs should be done with care. For instance, we prove that EMCMC algorithms with an elitist acceptance rule do not sample the target distribution correctly. [ABSTRACT FROM AUTHOR]

Objectives: To determine current demographic details of dental specialist registrars in the UK, to examine their current working patterns and ascertain their future career aspirations. Methods: A cross-sectional survey, using a self-administered postal questionnaire of all 418 dental specialist registrars (SpRs) in the UK. Results: The response rate was 78%. Of the SpRs who responded 59% were male, the majority were aged under 36, 54% were married and over one third had dependants. Orthodontics had the greatest number of SpRs with 141, followed by maxillofacial surgery (70) and restorative dentistry (52). On completion of training, 80% of SpRs intended to work full time. Significantly more women intended to work part-time. Only a fifth of SpRs said they would consider an academic appointment compared with 54% for specialist practice. Three quarters intended to work partly in the public sector and partly in a private capacity. London was the most popular choice of location for a post in the future. Access to a wide range of clinical work, continuing professional development, autonomy and sociability were the most important factors when considering their future choice of career. Conclusion: Changes in the demographic profile of dental specialists and increasing opportunities for providing care within primary care may lead to difficulties in recruitment to academic and hospital posts. Increasing provision of specialist services in the 'high street' might improve access but could lead to inequalities unless these services are commissioned according to the needs of the population. [ABSTRACT FROM AUTHOR]

Sandhoff disease is a severe inherited neurodegenerative disorder resulting from deficiency of the ß-subunit of hexosaminidases A and B, lysosomal hydrolases involved in the degradation of GM2 ganglioside and related metabolites. Currently, there is no viable treatment for the disease. Here, we show that adenovirus-mediated transfer of the ß-subunit of ß-hexosaminidase restored Hex A and Hex B activity after infection of Sandhoff fibroblasts. Gene transfer following intracerebral injection in a murine model of Sandhoff disease resulted in near-normal level of enzymatic activity in the entire brain at the different doses tested. The addition of hyperosmotic concentrations of mannitol to the adenoviral vector resulted in an enhancement of vector diffusion in the injected hemisphere. Adenoviral-induced lesions were found in brains injected with a high dose of the vector, but were not detected in brains injected with 100-fold lower doses, even in the presence of mannitol. Our data underline the advantage of the adjunction of mannitol to low doses of the adenoviral vector, allowing a high and diffuse transduction efficiency without viral cytotoxicity.Gene Therapy (2003) 10, 1841-1849. doi:10.1038/sj.gt.3302081 [ABSTRACT FROM AUTHOR]

Small-scale yielding around a stationary crack along a ductile single crystal–rigid material interface is analyzed. Plane strain conditions are assumed to prevail and geometry changes are neglected. The analyses are carried out using both continuum slip and discrete dislocation plasticity theory for model fcc and bcc crystal geometries having either two or three slip systems. Numerical and analytical asymptotic solutions are presented for continuum slip plasticity theory. Solutions exhibiting both slip bands and kink bands are obtained. The addition of a third slip system to ductile single crystals having two slip systems is found to have a significant effect on the interface crack-tip fields. The results illustrate the role that each of the formulations considered can play in elucidating crack tip fields in single crystals. [ABSTRACT FROM AUTHOR]

Gaucher disease (GD) is an inherited glycolipid storage disorder resulting from the deficiency of glucocerebrosidase, it is the most frequent lysosomal storage disease in Romania, accounting for 70% of all lysosomal disorders diagnosed since 1997 in this country. The prevalence of six common mutations (N370S, L444P, R463C, 84GG, recNcil and recTL) and their phenotypic impact were studied in 20 type 1 GD patients of non-Jewish origin. Mutation analysis identified 77.8% of the GD alleles. The N370S mutation had the highest prevalence (50%), followed by the L444P (22.2%) and the recNcil (5.6%) alleles. Mutations R463C, 84GG and recTL have not been found in our patients. Rare or novel mutations likely accounted for 22.2% of the disease-producing uncharacterised alleles. Our study indicates a high prevalence of type 1 among Romanian GD patients. Clinical phenotype and disease severity were evaluated according to the standardised severity score index. Genotype-phenotype correlations were similar to those reported for other Caucasian non-Jewish populations. The absence of neuronopathic disease in patients presenting at least one copy of the N370S allele was confirmed, but the relative mildness of N370S homozygotes was not a constant feature among our patients. The presence of the L444P or of uncharacterised sporadic mutations was always associated with severe clinical manifestations, even in compound heterozygotes with the N370S allele. A large degree of phenotypic variability was observed in patients displaying the same genotype. The particularities of genotype-phenotype correlations may suggest the impact of other genetic or non-genetic factors on the clinical picture. [ABSTRACT FROM AUTHOR]

Examines whether pronuclei of unequal size, observed in zygotes evaluated after in vitro fertilization, are predictive of chromosome anomalies in the developing embryo. Average diameters for large and small pronuclei; Mechanisms involved in pronuclei formation; Association between a higher number of oocytes retrieved and an increased frequency of unequal pronuclei after fertilization.

Abstract The intralaminar thalamic nuclei (ILn) have been implicated as a critical site of pathology in amnesia. Lesions of the ILn have been found to produce behavioral effects comparable to benzodiazepine (BDZ) receptor agonists. We compared the effects of chlordiazepoxide (CDP), a BDZ agonist, and FG 7142, a partial inverse agonist at the BDZ receptor, in rats with thalamic lesions and in unlesioned controls. Delayed matching-to sample (DMS) performances were studied during treatment with ascending doses of CDP, counterbalanced trials with 2.5 mg/kg CDP and saline, ascending doses of FG 7142, and (for unlesioned controls only) counterbalanced trials with saline and higher doses of CDP. CDP had effects similar to the ILn lesion, decreasing response speed and percent correct responding in a delay-independent fashion. These effects were additive with the impairments associated with the ILn lesion. The effects of FG 7142 were more complex. At lower doses, it increased response speed without affecting response accuracy. At higher doses, it diminished both the speed and the accuracy of DMS responding. These results support the hypothesis that ILn lesions and BDZ agonists have similar effects on DMS performance. The biphasic effects observed for FG 7142 are consistent with other evidence that low doses of this drug enhance while higher doses impair memory performance. Although DMS accuracy was not improved, the enhancement observed for response speed provides evidence that partial inverse BDZ agonists have potential utility as treatments for cognitive impairments associated with amnesia. [ABSTRACT FROM AUTHOR]

Constitutively activated mutants of the Ras-related protein TC21/R-Ras2 cause tumorigenic transformation of NIH3T3 cells. However, unlike Ras, TC21 fails to bind to and activate the Raf-1 serine-threonine kinase. Thus, whereas Ras transformation is critically dependent on Raf-1 TC21 activity is promoted by activation of Raf-independent signaling pathways. In the present study, we have further compared the functions of Ras and TC21. First we determined the basis for the inability of TC21 to activate Raf-1. Whereas Ras can interact with the two distinct Ras-binding sequences in NH2-terminus of Raf-1, designated RBS1 and Raf-Cys, TC21 could only bind Raf-Cys. Thus, the inability of TC21 to bind to RBS1 may prevent it from promoting the translocation of Raf-1 to the plasma membrane. Second, we found that TC21 is an activator of the JNK and p38, but not ERK, mitogen-activated protein kinase cascades and that TC21 transforming activity was dependent on Rac function. Thus, like Ras, TC21 may activate a Rac/JNK pathway. Third, we determined if TC21 could cause the same biological consequences as Ras in three distinct cell types. Like Ras, activated TC21 caused transformation of RIE-1 rat intestinal epithelial cells and terminal differentiation of PC12 pheochromocytoma cells. Finally, activated TC21 blocked serum starvation-induced differentiation of C2 myoblasts, whereas dominant negative TC21 greatly accelerated this differentiation process. Therefore, TC21 and Ras share indistinguishable biological activities in all cell types that we have evaluated. These results support the importance of Raf-independent pathways in mediating the actions of Ras and TC21. [ABSTRACT FROM AUTHOR]

Nonketotic hyperglycinemia (NKH) is caused by a mutation in the genes encoding the components of the glycine cleavage multi-enzyme system. More than 80% of the patients have defects in the gene encoding P-protein, whereas the rest of the patints have defects in the gene encoding T-protein. We have found a large Israeli-Arab kindred with NKH. At least 14 children were affected, and all the patients had seizures and respiratory failure within 2 days after birth. Enzymatic analysis revealed that T-protein activity was deficient in the liver specimen from one propositus. We screened this family for a mutation in the protein-coding region and exon/intron boundaries of T-protein gene by direct sequencing analysis. A missense mutation was found in exon 2; this resulted in an amino acid substitution from histidine to arginine at position 42 (H42R). Histidine 42 is conserved in human, bovine, chicken, pea, and Escherichia coli, suggesting that it has an important role in catalytic functions. Genotype analyses of 26 family members confirmed that the homozygous H42R mutation was completely associated with the onset of NKH. The availability of DNA testing facilitates the prenatal diagnosis of NKH and the identification of carriers, which is necessary for genetic counseling in the affected families. [ABSTRACT FROM AUTHOR]

Previous research has demonstrated that low doses of anxiogenic central benzodiazepine receptor (CBR) ligands, the beta-carbolines, improve performance in various learning and memory tests in animals if administered prior to training. The present experiments compared the effect of a beta-carboline (FG 7142) with that of a pharmacologically distinct anxiogenic compound, a peripheral benzodiazepine receptor (PBR) ligand, 4′-chlorodiazepam (Ro5-4864), in two tests of learning and memory in rats. As expected, FG 7142 significantly improved performance in a passive avoidance test. Ro5-4864 was without effect. In a shuttlebox escape test, Ro5-4864 significantly impaired performance while FG 7142 had no effect. The effect of Ro5-4864 was antagonized by the specific peripheral benzodiazepine receptor antagonist, PK 11195. These results indicate that the differential impact of CBR and PBR anxiogenic ligands on performance in aversively-motivated learning tests may be a reflection of their distinct pharmacologies. [ABSTRACT FROM AUTHOR]

Two experiments investigated the nature and etiology of the reduced activity in the presence of shock produced by prior exposure to inescapable shock. Previous experiments have demonstrated this deficit in the presence of gridshock. However, gridshock hurts less if movement across the grids is reduced. It is thus unclear whether the inescapable-shock-produced deficit represents a facilitation of learning to reduce movement across the grids in order to alleviate pain or is an 'unconditioned' reduction in movement in response to shock. The first experiment tested these possibilities by examining the effects of inescapable shock on subsequent movement during shock delivered via fixed tail electrodes to freely moving subjects. Inescapably shocked subjects still moved less in response to shock than did escapably shocked and restrained control subjects. Experiment 2 examined the possibility that this deficit occurs because unconditioned movement in response to shock during pretreatment diminishes after a few seconds, the reduction then being adventitiously reinforced by shortly ensuing shock termination. Activity during inescapable shock was closely monitored by ultrasonic motion detection. Although activity did decrease across trial blocks, the required within-trial patterns did not occur. Shock-elicited activity did not diminish after a few seconds of shock, but remained unchanged across the 5-sec shock presentations. [ABSTRACT FROM AUTHOR]

We introduce a method for sequencing peptides by mass spectrometry using a metalloendopeptidase that cleaves proteins at the amino side of lysine (Lys-N). When analyzed by electron transfer dissociation (ETD)–based mass spectrometric sequencing, Lys-N–digested peptides that contain a single lysine residue produce spectra dominated by c-type fragment ions, providing simple ladders for sequence determination. This method should be a valuable strategy for de novo sequencing and the analysis of post-translational modifications. [ABSTRACT FROM AUTHOR]

Objective:To determine if the same systematic alteration of serum values seen for alpha-fetoprotein (AFP) in diabetic patients is also seen for β-hCG and unconjugated estriol (uE3).Methods:Serum AFP, β-hCG, and uE3 results were obtained in 18,639 patients for whom complete follow-up information was obtained. Patients were divided into euglycemic (n = 18,088), insulin-requiring diabetics (n = 104), and non-insulin-requiring diabetics (n = 437), as well as by race.Results:The 20% adjustment used for AFP appropriately corrects serum values. No such systematic variation is seen for either β-hCG or uE3 by glycemic status or race.Conclusion:No adjustment for β-hCG or uE3 is necessary for diabetes for biochemical screening programs. [ABSTRACT FROM PUBLISHER]

Objective To assess recruitment and participation within seven school/pre-school-based programmes for fluoride varnish applications.Method Year-long pilots were undertaken in six primary schools (ages four to five years) and one pre-school (aged three years). Three applications of fluoride varnish were carried out coinciding with the three school terms.Results In spite of intensive recruitment efforts, only 78% of the total 589 children were enrolled in the pilot; 15% had to be excluded because no response could be obtained from their parents. At the end of 12 months, 79% of enrolled children (62% of total) had received all three applications. Children did not receive applications because they were absent on the days when the dental team were carrying out the screening or fluoride varnish applications, were ill, or because the child refused. The highest refusal rate was in the pre-school.Conclusions Younger children need to be targeted if improvement in the oral health of five-year-olds is to be achieved, the only dental measure in the Public Health Outcomes Framework, but they were less likely to cooperate. More research is needed on approaches to maximise participation in community programmes such as this, if they are to achieve significant population-level improvements in child dental health. [ABSTRACT FROM AUTHOR]

An 'opioid' form of analgesia ('long-term analgesia') was completely blocked by scopolamine. This effect of a muscarinic antagonist suggests that muscarinic cholinergic processes may play an important role in this analgesia and in other types of endogenous pain control. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented concerning the changes related to the publication of scientific articles by the journal.

Objective The purpose of this ecological study was to investigate the relationship between uptake of orthodontic services and factors that might influence receipt of care at a population level.Method The dental practice board supplied data on claims for courses of active orthodontic treatment from April 2001 to March 2002 for children from the former county of Avon. These data were analysed in relation to deprivation, living in an urban/rural setting and the proportion of the population from a black or minority ethnic group (BME).Results In Avon, children from deprived and rural areas were significantly less likely to be undergoing an active course of orthodontic treatment. Children from an area with a high proportion BME were significantly more likely to be undergoing treatment.Conclusion This research demonstrates that children from more deprived and rural communities in Avon are less likely to receive orthodontic treatment. This has important policy implications for primary care trusts that have a responsibility to ensure equal access to care for all of their children. [ABSTRACT FROM AUTHOR]