Solitary electromechanical pulses in lobster neurons.

Investigations of nerve activity have focused predominantly on electrical phenomena. Nerves, however, are thermodynamic systems, and changes in temperature and in the dimensions of the nerve can also be observed during the action potential. Measurements of heat changes during the action potential suggest that the nerve pulse shares many characteristics with an adiabatic pulse. First experiments in the 1980s suggested small changes in nerve thickness and length during the action potential. Such findings have led to the suggestion that the action potential may be related to electromechanical solitons traveling without dissipation. However, there have been no modern attempts to study mechanical phenomena in nerves. Here, we present ultrasensitive AFM recordings of mechanical changes on the order of 2-12Å in the giant axons of the lobster. We show that the nerve thickness changes in phase with voltage changes. When stimulated at opposite ends of the same axon, colliding action potentials pass through one another and do not annihilate. These observations are consistent with a mechanical interpretation of the nervous impulse.

The stability of solitons in biomembranes and nerves.

We examine the stability of a class of solitons, obtained from a generalization of the Boussinesq equation, which have been proposed to be relevant for pulse propagation in biomembranes and nerves. These solitons are found to be stable with respect to small-amplitude fluctuations. They emerge naturally from non-solitonic initial excitations and are robust in the presence of dissipation. Solitary waves pass through each other with only minor dissipation when their amplitude is small. Large-amplitude solitons fall apart into several pulses and small-amplitude noise upon collision when the maximum density of the membrane is limited by the density of the solid phase membrane.

Characterising transmission of a tuberculosis genotype in Scotland: a qualitative approach to social network enquiry.

SETTING: Contact investigation resulting from specimens sent to the Scottish Mycobacteria Reference Laboratory. OBJECTIVE: To characterise patients and types of exposures associated with transmission of a prevalent Mycobacterium tuberculosis genotype in Scotland. DESIGN: A combined approach using molecular epidemiology and semi-structured patient interviews for social network enquiry. RESULTS: We investigated social connections between 64 patients diagnosed between 1994 and 2004. Fifty-five per cent had > or = 1 identifiable contact. One third (n = 14, 32.6%) of the 43 epidemiological links detected were discerned as a result of patient interviews and were not previously recorded on surveillance reports, nor recognised by nurse specialists (all were non-household contacts). Sixteen putative sites of exposure were identified, 11 were public houses. Rather than a single-source outbreak, eight pockets of transmission were identified, the largest involving UK-born alcohol-misusing males frequenting several public houses. CONCLUSIONS: Using a standardised approach to explore themes around which individuals may have been exposed to TB resulted in the detection of previously unrecognised epidemiological links. Epidemiological data obtained from cluster investigations, e.g., risk and social behaviours that increase the risk of infection and sites of putative exposure, can enhance the development of more appropriate questions for the contact tracing interview.

Tuberculosis outbreak associated with a mosque: challenges of large scale contact tracing.

In this report, we describe the investigation and management of an outbreak of TB associated with a mosque in Scotland, and consider the implications of large-scale TB contact tracing. The screening of casual contacts in this setting was complex and time-consuming with a low detection rate.

Knowledge of tuberculosis transmission among recently infected patients in Glasgow.

OBJECTIVES: To examine perceptions and understanding of disease causation in tuberculosis patients with few epidemiological links detected by contact tracing. STUDY DESIGN: An exploratory qualitative study using semi-structured interviews was undertaken. Patients' beliefs were explored against a background of medical thinking about tuberculosis transmission and the current approach to contact tracing. METHODS: Interviews were undertaken with patients (n=23) or suitable next of kin (n=3). Study patients were diagnosed with tuberculosis in Glasgow, an urban area of Scotland, between 1997 and 2004. All had a genetically indistinguishable 15-banded IS6110 restriction fragment length polymorphism pattern of the Beijing family of Mycobacterium tuberculosis, suggestive of recently transmitted infection, yet few had epidemiological links detectable as a result of contact tracing (30.8%). RESULTS: Interviewees had varying levels of knowledge, but most believed that tuberculosis was caused by a pathogen, spread by person-to-person contact. Modes of transmission were thought to include airborne transmission, sharing utensils with an infected individual, consumption of contaminated foods/liquids, and exchange of bodily fluids. Prolonged contact was not thought to be required for transmission to occur. Impaired immunity, social factors and environmental factors were believed to enhance the potential for transmission. CONCLUSIONS: Patients have complex beliefs about tuberculosis transmission and causation, which do not always mirror those of health professionals. Adopting and implementing an approach to contact identification that is aligned with lay beliefs may result in improved contact tracing outcomes.

Citation networks in high energy physics.

The citation network constituted by the SPIRES database is investigated empirically. The probability that a given paper in the SPIRES database has k citations is well described by simple power laws, P(k) proportional to k(-alpha), with alpha approximately 1.2 for k less than 50 citations and alpha approximately 2.3 for 50 or more citations. A consideration of citation distribution by subfield shows that the citation patterns of high energy physics form a remarkably homogeneous network. Further, we utilize the knowledge of the citation distributions to demonstrate the extreme improbability that the citation records of selected individuals and institutions have been obtained by a random draw on the resulting distribution.

Lieb mode in a quasi-one-dimensional bose-einstein condensate of atoms.

We calculate the dispersion relation associated with a solitary wave in a quasi-one-dimensional Bose-Einstein condensate of atoms confined in a harmonic, cylindrical trap in the limit of weak and strong interactions. In both cases, the dispersion relation is linear for long-wavelength excitations and terminates at the point where the group velocity vanishes. We also calculate the dispersion relation of sound waves in both limits of weak and strong coupling.

Products of random matrices.

We derive analytic expressions for infinite products of random 2 x 2 matrices. The determinant of the target matrix is log-normally distributed, whereas the remainder is a surprisingly complicated function of a parameter characterizing the norm of the matrix and a parameter characterizing its skewness. The distribution may have importance as an uncommitted prior in statistical image analysis.

Genetic survival analysis of age-at-onset of bipolar disorder: evidence for anticipation or cohort effect in families.

Age-at-onset (AAO) in a number of extended families ascertained for bipolar disorder was analysed using survival analysis techniques, fitting proportional hazards models to estimate the fixed effects of sex, year of birth, and generation, and a random polygenic genetic effect. Data comprised the AAO (for 171 affecteds) or age when last seen (ALS) for 327 unaffecteds, on 498 individuals in 27 families. ALS was treated as the censored time in the statistical analyses. The majority of individuals classified as affected were diagnosed with bipolar I and II (n = 103) or recurrent major depressive disorder (n = 68). In addition to the significant effects of sex and year of birth, a fitted 'generation' effect was highly significant, which could be interpreted as evidence for an anticipation effect. The risk of developing bipolar or unipolar disorder increased twofold with each generation descended from the oldest founder. However, although information from both affected and unaffected individuals was used to estimate the relative risk of subsequent generations, it is possible that the results are biased because of the 'Penrose effect'. Females had a twofold increased risk in developing depressive disorder relative to males. The risk of developing bipolar or unipolar disorder increased by approximately 4% per year of birth. A polygenic component of variance was estimated, resulting in a 'heritability' of AAO of approximately 0.52. In a family showing strong evidence of linkage to chromosome 4p (family 22), the 'affected haplotype' increased the relative risk of being affected by a factor of 46. In this family, there was strong evidence of a time trend in the AAO. When either year of birth or generation was fitted in the model, these effects were highly significant, but neither was significant in the presence of the other. For this family, there was no increase in trinucleotide repeats measured by the repeat expansion detection method in affected individuals compared with control subjects. Proportional hazard models appear appropriate to analyse AAO data, and the methodology will be extended to map quantitative trait loci (QTL) for AAO.

Random matrix theory and acoustic resonances in plates with an approximate symmetry.

We discuss a random matrix model of systems with an approximate symmetry and present the spectral fluctuation statistics and eigenvector characteristics for the model. An acoustic resonator like, e.g., an aluminum plate may have an approximate symmetry. We have measured the frequency spectrum and the widths for acoustic resonances in thin aluminum plates, cut in the shape of the so-called three-leaf clover. Due to the mirror symmetry through the middle plane of the plate, each resonance of the plate belongs to one of two mode classes and we show how to separate the modes into these two classes using their measured widths. We compare the spectral statistics of each mode class with results for the Gaussian orthogonal ensemble. By cutting a slit of increasing depth on one face of the plate, we gradually break the mirror symmetry and study the transition that takes place as the two classes are mixed. Presenting the spectral fluctuation statistics and the distribution of widths for the resonances, we find that this transition is well described by the random matrix model.

Weakly interacting Bose-Einstein condensates under rotation: mean-field versus exact solutions.

We consider a weakly interacting, harmonically trapped Bose-Einstein condensed gas under rotation and investigate the connection between the energies obtained from mean-field calculations and from exact diagonalizations in a subspace of degenerate states. From the latter we derive an approximation scheme valid in the thermodynamic limit of many particles. Mean-field results are shown to emerge as the correct leading-order approximation to exact calculations in the same subspace.

Airway goblet-cell mucus secretion.

A mucus hypersecretory phenotype is a dominant characteristic of chronic airways diseases such as chronic bronchitis and asthma. This phenotype develops following chronic exposure of the respiratory tract to particulate matter, allergens, irritants and/or pathogens. The associated increase in the mucus-producing potential of the respiratory epithelium represents an innate host response that can be modulated by elements of the adaptive host response. Although elevation of mucus production is designed to protect the airways, increasing evidence suggests that in excess it can be detrimental to health. Considerable progress has been made over the past five years in understanding the mechanisms involved in the development and regulation of the hypersecretory phenotype. This progress has set the stage for the development of successful dedicated mucomodulatory strategies to counter the negative impact of excess mucus production in respiratory disease.

Analytical results for the interaction energy of a trapped, weakly interacting Bose-Einstein condensate.

We examine the problem of a repulsive, weakly interacting and harmonically trapped Bose-Einstein condensate under rotation. We derive a simple analytic expression for the energy incorporating the interactions when the angular momentum per particle is between zero and one and find that the interaction energy decreases linearly as a function of the angular momentum in agreement with previous numerical and limiting analytical studies.

Effect of salmeterol on Pseudomonas aeruginosa infection of respiratory mucosa.

We have studied the effect of salmeterol on both P. aeruginosa interactions with the mucosa of nasal turbinate organ cultures and on pyocyanin-induced (20 microg/ml) and elastase-induced (100 microg/ml) damage to nasal epithelial cells. Organ cultures were exposed to salmeterol either by preincubation with 4 x 10(-7) M salmeterol for 30 min or by pipetting 20 microl of 4 x 10(-7) M salmeterol onto the organ culture surface immediately prior to bacterial inoculation. Infected organ cultures (8 h) had significantly (p < or = 0.01) increased epithelial damage, and P. aeruginosa was predominantly associated with damaged epithelium and mucus. Salmeterol significantly (p < or = 0.02) reduced epithelial damage caused by infection and the total number of adherent bacteria (p < or = 0.05), but bacterial distribution on the mucosa was unchanged. Nasal epithelial cells incubated with pyocyanin (20 microg/ml) or elastase (100 microg/ml) for 3 h had significantly (p < or = 0.05) increased cytoplasmic blebbing and mitochondrial damage versus control values. Elastase also significantly (p < or = 0.05) increased cell projection and reduced the level of ciliation. Cells preincubated with salmeterol (2 x 10(-7) M) showed a significant reduction in some features of cell damage caused by both toxins, which was inhibited by the beta2-adrenoceptor antagonist propranolol. Our results indicate that salmeterol reduces P. aeruginosa-induced damage to both organ culture and nasal epithelium.

The effect of mutations in genes required for lipopolysaccharide synthesis on Haemophilus influenzae type b colonization of human nasopharyngeal tissue.

Haemophilus influenzae type b (Hib) is an upper respiratory tract commensal that can cause invasive disease, particularly in young children. Lipopolysaccharide (LPS) has been implicated as a major virulence determinant of Hib, and changes in LPS structure may influence bacterial interactions with the respiratory mucosa. We have examined the effect of variations in LPS on the interaction of Hib with human nasal turbinate tissue maintained in an organ culture model with an air-interface, by using isogenic derivatives of strains RM153 (Eagan) and RM7004 expressing truncated LPS due to mutations in genes contained within the chromosomal loci lic1 and lic2 (lic1lic2) or in the galE and galK genes (galEK). Tissue was infected with an inoculating dose of 2.3-3.3 x 10(6) colony forming units (cfu) in 2 microliters of PBS and maintained for 24 h. By scanning electron microscopy the percentage of the organ culture surface exhibiting epithelial damage increased from 5.3 +/- 1.4 in controls to 12.5 +/- 6.4-26.3 +/- 9.1 following infection, with no significant difference between parent strains and their derivatives. There was significant bacterial tropism for mucus, and to a lesser extent damaged cells, which was not influenced by the LPS phenotype. All strains caused separation of epithelial cells, adhered to non-luminal cell surfaces, and invaded the epithelium intercellularly. We conclude that Hib associated with mucus and damaged epithelium, and infrequently with normal epithelium, but changes in the LPS phenotype did not affect the interaction between Hib and the mucosal surface of human nasal turbinate tissue.