Computer-Assisted Diagnosis of Abdominal Pain using “Estimates” Provided by Clinicians

This paper reports a comparison between two modes of computer-aided diagnosis in a real-time prospective trial involving 472 patients with acute abdominal pain. In the first mode the computer-aided system analysed each of the 472 patients by referring to data previously collated from a large series of 600 real-life patients. In the second mode the system used as a basis for its analysis “estimates” of probability provided by a group of six clinicians. The accuracy and reliability of both modes were compared with the performance of unaided clinicians.Using “real-life” data the computer system was significantly more effective than the unaided clinician. By contrast, when using the clinicians'' own estimates the computer-aided system was often less effective than the unaided clinician—especially when diagnosing less common disorders. It seems, firstly, that future systems for computer-aided diagnosis should employ data from real-life and not clinicians'' estimates, and, secondly, that clinicians themselves cannot analyse cases in a probabilistic fashion, since often they have little idea of what the “true” probabilities are.     

A Community of One: Social Cognition and Auditory Verbal Hallucinations

Auditory verbal hallucinations have attracted a great deal of scientific interest, but despite the fact that they are fundamentally a social experience—in essence, a form of hallucinated communication—current theories remain firmly rooted in an individualistic account and have largely avoided engagement with social cognition. Nevertheless, there is mounting evidence for the role of social cognitive and social neurocognitive processes in auditory verbal hallucinations, and, consequently, it is proposed that problems with the internalisation of social models may be key to the experience.     

Serial Position Markers in Space: Visuospatial Priming of Serial Order Working Memory Retrieval

Most general theories on serial order working memory (WM) assume the existence of position markers that are bound to the to-be-remembered items to keep track of the serial order. So far, the exact cognitive/neural characteristics of these markers have remained largely underspecified, while direct empirical evidence for their existence is mostly lacking. In the current study we demonstrate that retrieval from verbal serial order WM can be facilitated or hindered by spatial cuing: begin elements of a verbal WM sequence are retrieved faster after cuing the left side of space, while end elements are retrieved faster after cuing the right side of space. In direct complement to our previous work—where we showed the reversed impact of WM retrieval on spatial processing—we argue that the current findings provide us with a crucial piece of evidence suggesting a direct and functional involvement of space in verbal serial order WM. We outline the idea that serial order in verbal WM is coded within a spatial coordinate system with spatial attention being involved when searching through WM, and we discuss how this account can explain several hallmark observations related to serial order WM.     

Exciton Annihilation in the Two Photosystems in Chloroplasts at 100°K

The fluorescence yield (F) of spinach chloroplasts at 100°K measured at 735 nm (photosystem I fluorescence—F 735) and at 685 nm (photosystem II fluorescence—F 685) has been determined with different modes of laser excitation. The modes of excitation included a single picosecond pulse, sequences of picosecond pulses (4, 22, and 300 pulses spaced 5 ns apart) and a single nonmode-locked 2-μs pulse (MP mode). The F 735/F 685 intensity ratios decrease from 1.62 to 0.61 when a single picosecond pulse (or low-power continuous helium-neon laser) is replaced by excitation with the 300-ps pulse train (PPT mode) or MP mode. In the PPT mode of excitation, the 735-nm fluorescence band is quenched by a factor of 45 as the intensity is increased from 10¹⁵ to 10¹⁸ photons/cm² per pulse train and the 685-nm fluorescence is quenched by a factor of 10. In the MP mode, the quenching factors are 25 and 7, respectively, in the same intensity range. Fluorescence quantum yield measurements with different picosecond pulse sequences indicate that relatively long-lived quenching species are operative, which survive from one picosecond pulse to another within the pulse train. The excitonic processes possible in the photosynthetic units are discussed in detail. The differences in the quenching factors between the MP and PPT modes of excitation are attributed to singlet-singlet annihilation, possible when picosecond pulses are utilized, but minimized in the MP mode of excitation. The long-lived quenchers are identified as triplets and/or bulk chlorophyll ions formed by singlet-singlet annihilation. The preferential quenching in photosystem I is attributed to triplet excitons. The influence of heating effects, photochemistry, bleaching, and two-photon processes is also considered and is shown to be negligible.     

Evaluation of Methods for Storage of Marine Macroorganisms with Optimal Recovery of Bacteria

Marine macroorganisms are a potential source for new bioactive substances. In many cases marine microorganisms—especially bacteria—associated with these macroorganisms are actually producing the bioactive substances. One often is not able to immediately isolate microorganisms from collected macroorganismic materials; we therefore evaluated different methods for storage of such material, e.g., on board research vessels. These methods were the following: storage of macerates in sintered glass beads and 5% trehalose at −20°C (SGT method); storage of sections in 5% dimethyl sulfoxide at −70°C (SD method); storage of macerates at −20°C using the commercial ROTI-STORE system (RS method); storage of macerates at −20°C in 50% glycerol (GC method); and storage of macerates covered by mineral oil at 4°C (MO method). The SGT and SD methods resulted in numbers of and especially diversity of recoverable bacteria that were higher than for the other methods. Data for the RS method indicated its potential usefulness, too. The MO method resulted in growth during storage, thereby enriching a few selected microorganisms; the GC method resulted in a survival and diversity of recovered bacteria that was too low.     

The Role of Percutaneous Lung Biopsy in the Workup of a Solitary Pulmonary Nodule

As the technique of percutaneous lung biopsy continues to evolve, it offers an increasingly accurate method of establishing the malignancy or benignity of a solitary pulmonary nodule. There are relatively few contraindications to the procedure, and the complications—primarily pneumothorax and hemoptysis—generally resolve without therapy. Transthoracic needle aspiration has an important role in the workup for a “coin lesion.” Other elements of the diagnostic workup—particularly the history, a chest roentgenogram, computed tomography, sputum cytology, and transbronchial brush biopsy—may either add to or substitute for a transthoracic needle aspiration biopsy. An algorithm can be used to guide the diagnostic approach to a solitary pulmonary nodule.     

The Development of Metaphor Comprehension and Its Relationship with Relational Verbal Reasoning and Executive Function

Our main objective was to analyse the different contributions of relational verbal reasoning (analogical and class inclusion) and executive functioning to metaphor comprehension across development. We postulated that both relational reasoning and executive functioning should predict individual and developmental differences. However, executive functioning would become increasingly involved when metaphor comprehension is highly demanding, either because of the metaphors’ high difficulty (relatively novel metaphors in the absence of a context) or because of the individual’s special processing difficulties, such as low levels of reading experience or low semantic knowledge. Three groups of participants, 11-year-olds, 15-year-olds and young adults, were assessed in different relational verbal reasoning tasks—analogical and class-inclusion—and in executive functioning tasks—updating information in working memory, inhibition, and shifting. The results revealed clear progress in metaphor comprehension between ages 11 and 15 and between ages 15 and 21. However, the importance of executive function in metaphor comprehension was evident by age 15 and was restricted to updating information in working memory and cognitive inhibition. Participants seemed to use two different strategies to interpret metaphors: relational verbal reasoning and executive functioning. This was clearly shown when comparing the performance of the "more efficient" participants in metaphor interpretation with that of the "less efficient” ones. Whereas in the first case none of the executive variables or those associated with relational verbal reasoning were significantly related to metaphor comprehension, in the latter case, both groups of variables had a clear predictor effect.     

Future of health care system tops agenda as CMA Board of Directors meets

The first part of the CMA''s efforts to spark a public debate on the future of Canada''s health care system is a “visioning exercise” in which the Board of Directors will attempt to spell out the association''s views on how the system should develop. The board also discussed CMA initiatives concerning two major public-health issues — smoking and blood transfusions.     

Pigeons (Columba livia) as Trainable Observers of Pathology and Radiology Breast Cancer Images

Pathologists and radiologists spend years acquiring and refining their medically essential visual skills, so it is of considerable interest to understand how this process actually unfolds and what image features and properties are critical for accurate diagnostic performance. Key insights into human behavioral tasks can often be obtained by using appropriate animal models. We report here that pigeons (Columba livia)—which share many visual system properties with humans—can serve as promising surrogate observers of medical images, a capability not previously documented. The birds proved to have a remarkable ability to distinguish benign from malignant human breast histopathology after training with differential food reinforcement; even more importantly, the pigeons were able to generalize what they had learned when confronted with novel image sets. The birds’ histological accuracy, like that of humans, was modestly affected by the presence or absence of color as well as by degrees of image compression, but these impacts could be ameliorated with further training. Turning to radiology, the birds proved to be similarly capable of detecting cancer-relevant microcalcifications on mammogram images. However, when given a different (and for humans quite difficult) task—namely, classification of suspicious mammographic densities (masses)—the pigeons proved to be capable only of image memorization and were unable to successfully generalize when shown novel examples. The birds’ successes and difficulties suggest that pigeons are well-suited to help us better understand human medical image perception, and may also prove useful in performance assessment and development of medical imaging hardware, image processing, and image analysis tools.     

A general mechanism for drug promiscuity: Studies with amiodarone and other antiarrhythmics

Amiodarone is a widely prescribed antiarrhythmic drug used to treat the most prevalent type of arrhythmia, atrial fibrillation (AF). At therapeutic concentrations, amiodarone alters the function of many diverse membrane proteins, which results in complex therapeutic and toxicity profiles. Other antiarrhythmics, such as dronedarone, similarly alter the function of multiple membrane proteins, suggesting that a multipronged mechanism may be beneficial for treating AF, but raising questions about how these antiarrhythmics regulate a diverse range of membrane proteins at similar concentrations. One possible mechanism is that these molecules regulate membrane protein function by altering the common environment provided by the host lipid bilayer. We took advantage of the gramicidin (gA) channels’ sensitivity to changes in bilayer properties to determine whether commonly used antiarrhythmics—amiodarone, dronedarone, propranolol, and pindolol, whose pharmacological modes of action range from multi-target to specific—perturb lipid bilayer properties at therapeutic concentrations. Using a gA-based fluorescence assay, we found that amiodarone and dronedarone are potent bilayer modifiers at therapeutic concentrations; propranolol alters bilayer properties only at supratherapeutic concentration, and pindolol has little effect. Using single-channel electrophysiology, we found that amiodarone and dronedarone, but not propranolol or pindolol, increase bilayer elasticity. The overlap between therapeutic and bilayer-altering concentrations, which is observed also using plasma membrane–like lipid mixtures, underscores the need to explore the role of the bilayer in therapeutic as well as toxic effects of antiarrhythmic agents.     

Chromatin Hydrodynamics

Following recent observations of large scale correlated motion of chromatin inside the nuclei of live differentiated cells, we present a hydrodynamic theory—the two-fluid model—in which the content of a nucleus is described as a chromatin solution with the nucleoplasm playing the role of the solvent and the chromatin fiber that of a solute. This system is subject to both passive thermal fluctuations and active scalar and vector events that are associated with free energy consumption, such as ATP hydrolysis. Scalar events drive the longitudinal viscoelastic modes (where the chromatin fiber moves relative to the solvent) while vector events generate the transverse modes (where the chromatin fiber moves together with the solvent). Using linear response methods, we derive explicit expressions for the response functions that connect the chromatin density and velocity correlation functions to the corresponding correlation functions of the active sources and the complex viscoelastic moduli of the chromatin solution. We then derive general expressions for the flow spectral density of the chromatin velocity field. We use the theory to analyze experimental results recently obtained by one of the present authors and her co-workers. We find that the time dependence of the experimental data for both native and ATP-depleted chromatin can be well-fitted using a simple model—the Maxwell fluid—for the complex modulus, although there is some discrepancy in terms of the wavevector dependence. Thermal fluctuations of ATP-depleted cells are predominantly longitudinal. ATP-active cells exhibit intense transverse long wavelength velocity fluctuations driven by force dipoles. Fluctuations with wavenumbers larger than a few inverse microns are dominated by concentration fluctuations with the same spectrum as thermal fluctuations but with increased intensity.     

Rapid quantitative profiling of complex microbial populations

Diverse and complex microbial ecosystems are found in virtually every environment on earth, yet we know very little about their composition and ecology. Comprehensive identification and quantification of the constituents of these microbial communities—a ‘census’—is an essential foundation for understanding their biology. To address this problem, we developed, tested and optimized a DNA oligonucleotide microarray composed of 10 462 small subunit (SSU) ribosomal DNA (rDNA) probes (7167 unique sequences) selected to provide quantitative information on the taxonomic composition of diverse microbial populations. Using our optimized experimental approach, this microarray enabled detection and quantification of individual bacterial species present at fractional abundances of <0.1% in complex synthetic mixtures. The estimates of bacterial species abundance obtained using this microarray are similar to those obtained by phylogenetic analysis of SSU rDNA sequences from the same samples—the current ‘gold standard’ method for profiling microbial communities. Furthermore, probes designed to represent higher order taxonomic groups of bacterial species reliably detected microbes for which there were no species-specific probes. This simple, rapid microarray procedure can be used to explore and systematically characterize complex microbial communities, such as those found within the human body.     

Unintentional Interpersonal Synchronization Represented as a Reciprocal Visuo-Postural Feedback System: A Multivariate Autoregressive Modeling Approach

People’s behaviors synchronize. It is difficult, however, to determine whether synchronized behaviors occur in a mutual direction—two individuals influencing one another—or in one direction—one individual leading the other, and what the underlying mechanism for synchronization is. To answer these questions, we hypothesized a non-leader-follower postural sway synchronization, caused by a reciprocal visuo-postural feedback system operating on pairs of individuals, and tested that hypothesis both experimentally and via simulation. In the behavioral experiment, 22 participant pairs stood face to face either 20 or 70 cm away from each other wearing glasses with or without vision blocking lenses. The existence and direction of visual information exchanged between pairs of participants were systematically manipulated. The time series data for the postural sway of these pairs were recorded and analyzed with cross correlation and causality. Results of cross correlation showed that postural sway of paired participants was synchronized, with a shorter time lag when participant pairs could see one another’s head motion than when one of the participants was blindfolded. In addition, there was less of a time lag in the observed synchronization when the distance between participant pairs was smaller. As for the causality analysis, noise contribution ratio (NCR), the measure of influence using a multivariate autoregressive model, was also computed to identify the degree to which one’s postural sway is explained by that of the other’s and how visual information (sighted vs. blindfolded) interacts with paired participants’ postural sway. It was found that for synchronization to take place, it is crucial that paired participants be sighted and exert equal influence on one another by simultaneously exchanging visual information. Furthermore, a simulation for the proposed system with a wider range of visual input showed a pattern of results similar to the behavioral results.     

Haemophilus Epiglottitis: Nine Recent Cases in Oxford

Recent experience of epiglottitis in Oxford confirms the need for doctors in this country—especially family doctors and casualty officers—to be aware of this disease and to be able to recognize it and to take appropriate action immediately. Some important diagnostic and therapeutic implications both of the anatomy of the supraglottic lesion and of the septicaemic component of the illness are discussed.     

Selection in plant populations of effectively infinite size. V. Biallelic models of trioecy

A one-locus two-allele model of trioecy (presence of hermaphrodites, males and females in one population) is considered, in order to study the conditions for the persistence of this system. All possible assignments of the three sex types to the three genotypes are considered. This leads to three different modes of inheritance of trioecy, namely (a) females heterozygous, (b) males heterozygous and (c) hermaphrodites heterozygous, where in each mode each of the remaining two sex types is homozygous for one of the alleles. For mode (c) trioecy is always persistent, and the dependence of the sex ratio (for the three sex types) on the ovule and pollen fertilities and on the hermaphrodite selfing rate is specified. For the other two modes, (a) and (b), trioecy is not protected, i.e., it may not persist for any fertilities, viabilities or selfing rates. Thus, in this situation it is important to study the conditions under which the "marginal" systems of sexuality of trioecy, i.e., hermaphroditism, dioecy and gynodioecy in mode (a), and hermaphroditism, dioecy and androdioecy in mode (b), may become established. The results show that each marginal system may evolve from each other via trioecy. The evolution of dioecy is easier in mode (a) than in (b), so that female heterogamety would be expected to occur more often than male heterogamety in the present model. Under some conditions the breeding system obtained in equilibrium populations may depend on the initial genotype frequencies.—The necessity of considering modes of inheritance for sexual polymorphisms is demonstrated by comparing our results with those obtained from an evolutionary stable strategy (ESS) analysis of a purely phenotypic model.     

Differing Dynamics of Intrapersonal and Interpersonal Coordination: Two-finger and Four-Finger Tapping Experiments

Finger-tapping experiments were conducted to examine whether the dynamics of intrapersonal and interpersonal coordination systems can be described equally by the Haken—Kelso—Bunz model, which describes inter-limb coordination dynamics. This article reports the results of finger-tapping experiments conducted in both systems. Two within-subject factors were investigated: the phase mode and the number of fingers. In the intrapersonal experiment (Experiment 1), the participants were asked to tap, paced by a gradually hastening auditory metronome, looking at their fingers moving, using the index finger in the two finger condition, or the index and middle finger in the four-finger condition. In the interpersonal experiment (Experiment 2), pairs of participants performed the task while each participant used the outside hand, tapping with the index finger in the two finger condition, or the index and middle finger in the four-finger condition. Some results did not agree with the HKB model predictions. First, from Experiment 1, no significant difference was observed in the movement stability between the in-phase and anti-phase modes in the two finger condition. Second, from Experiment 2, no significant difference was found in the movement stability between the in-phase and anti-phase mode in the four-finger condition. From these findings, different coordination dynamics were inferred between intrapersonal and interpersonal coordination systems against prediction from the previous studies. Results were discussed according to differences between intrapersonal and interpersonal coordination systems in the availability of perceptual information and the complexity in the interaction between limbs derived from a nested structure.     

Evacuation of Pedestrians with Two Motion Modes for Panic System

In this paper, we have captured an underlying mechanism of emergence of collective panic in pedestrian evacuations by using a modification of the lattice-gas model. We classify the motion of pedestrians into two modes according to their moods. One is gentle (mode I), the other is flustered (mode II). First, to research the cause for crowd, we fix the motion modes of pedestrians and increase the proportion of pedestrians with motion mode II (ρ_II). The simulation results show that the pedestrians with motion mode II are lack of evacuation efficiency and cause more casualties. Further, we use the SIS (susceptible-infective-susceptible) model to describe the spreading of the panic mood. The system can be in the high-mix state when the infection probability λ is greater than a fuzzy threshold. In addition, the distances S from wounded people to the exit are researched, the number of wounded people gets maximum at the internal S = 5 ∼ 10, which is independent of ρ_II and λ. This research can help us to understand and prevent the emergence of collective panic and reduce wounds in the real evacuation.     

Bristol Industrial Therapy Housing Association: A Contribution to Domestic Resettlement

A housing association for the rehabilitation of adults suffering from psychiatric illness now has six council houses, a former private hotel, and two large houses—providing a total of 100 places. The cost of full board and lodging is about £6·00 a week; the association shows a small profit; and virtually all the residents are in open or sheltered work.     

Segregational Drift Constrains the Evolutionary Rate of Prokaryotic Plasmids

Plasmids are extrachromosomal genetic elements in prokaryotes that have been recognized as important drivers of microbial ecology and evolution. Plasmids are found in multiple copies inside their host cell where independent emergence of mutations may lead to intracellular genetic heterogeneity. The intracellular plasmid diversity is thus subject to changes upon cell division. However, the effect of plasmid segregation on plasmid evolution remains understudied. Here, we show that genetic drift during cell division—segregational drift—leads to the rapid extinction of novel plasmid alleles. We established a novel experimental approach to control plasmid allele frequency at the levels of a single cell and the whole population. Following the dynamics of plasmid alleles in an evolution experiment, we find that the mode of plasmid inheritance—random or clustered—is an important determinant of plasmid allele dynamics. Phylogenetic reconstruction of our model plasmid in clinical isolates furthermore reveals a slow evolutionary rate of plasmid-encoded genes in comparison to chromosomal genes. Our study provides empirical evidence that genetic drift in plasmid evolution occurs at multiple levels: the host cell and the population of hosts. Segregational drift has implications for the evolutionary rate heterogeneity of extrachromosomal genetic elements.