On strongly connected networks with excitable-refractory dynamics and delayed coupling.

We consider a directed graph model for the human brain's neural architecture that is based on small scale, directed, strongly connected sub-graphs (SCGs) of neurons, that are connected together by a sparser mesoscopic network. We assume transmission delays within neuron-to-neuron stimulation, and that individual neurons have an excitable-refractory dynamic, with single firing 'spikes' occurring on a much faster time scale than that of the transmission delays. We demonstrate numerically that the SCGs typically have attractors that are equivalent to continual winding maps over relatively low-dimensional tori, thus representing a limit on the range of distinct behaviour. For a discrete formulation, we conduct a large-scale survey of SCGs of varying size, but with the same local structure. We demonstrate that there may be benefits (increased processing capacity and efficiency) in brains having evolved to have a larger number of small irreducible sub-graphs, rather than few, large irreducible sub-graphs. The network of SCGs could be thought of as an architecture that has evolved to create decisions in the light of partial or early incoming information. Hence the applicability of the proposed paradigm to underpinning human cognition.

Comparison of social structures within cities of very different sizes.

People make a city, making each city as unique as the combination of its inhabitants. However, some cities are similar and some cities are inimitable. We examine the social structure of 10 different cities using Twitter data. Each city is decomposed to its communities. We show that in many cases one city can be thought of as an amalgamation of communities from another city. For example, we find the social network of Manchester is very similar to the social network of a virtual city of the same size, where the virtual city is composed of communities from the Bristol network. However, we cannot create Bristol from Manchester since Bristol contains communities with a social structure that are not present in Manchester. Some cities, such as Leeds, are outliers. That is, Leeds contains a particularly wide range of communities, meaning we cannot build a similar city from communities outside of Leeds. Comparing communities from different cities, and building virtual cities that are comparable to real cities, is a novel approach to understand social networks. This has implications when using social media to inform or advise residents of a city.

Effects of head elevation on intraocular pressure in healthy subjects: raising bed head vs using multiple pillows.

PURPOSE: To evaluate the effects of different methods of head elevation on intraocular pressure (IOP) in healthy young subjects. METHODS: Twenty-four healthy young Korean subjects were included in this prospective observational study. The IOP measurements were taken with the subjects in the sitting position and in the supine positions with the head flat and 30° up using two different methods: (1) raising the bed head and (2) using multiple pillows. IOP was measured using Tonopen AVIA in both eyes 10 min after assuming each position in a randomized sequence. The Wilcoxon signed-rank test was used to compare the IOP by changing the methods of head elevation. RESULTS: Mean IOP of both eyes when sitting was lower than that measured in the supine position with head flat (P=0.001). Compared with that measured in the supine position with head flat, the mean IOP was lower when measured in the supine position with the head kept 30 ° up by bed head elevation (P=0.001), whereas the mean IOP was not significantly different when measured in the supine position with the head elevated using multiple pillows (right eye, P=0.061; left eye, P=0.089). CONCLUSION: In normal subjects, IOP was lower when measured in the supine position with the head kept up by the bed head elevation compared with that measured when lying flat. However, such head-up position-induced IOP reduction was not found when the head was kept up using multiple pillows. These findings suggest that elevating the head using multiple pillows may not help to reduce IOP in the supine posture.

Species distributions and area relationships.

The well-known species-area relationship is one of many scaling laws, or allometries, in ecology and biology that have received much attention over the years. We present a new derivation of this relationship based on Yule׳s theory of evolution of species. Using definitions of mutation rates, our analysis yields species-area exponents that are in close agreement with previously observed values.

Inferring extinction risks from sighting records.

Estimating the probability that a species is extinct based on historical sighting records is important when deciding how much effort and money to invest in conservation policies. The framework we offer is more general than others in the literature to date. Our formulation allows for definite and uncertain observations, and thus better accommodates the realities of sighting record quality. Typically, the probability of observing a species given it is extant/extinct is challenging to define, especially when the possibility of a false observation is included. As such, we assume that observation probabilities derive from a representative probability density function. We incorporate this randomness in two different ways ("quenched" versus "annealed") using a framework that is equivalent to a Bayes formulation. The two methods can lead to significantly different estimates for extinction. In the case of definite sightings only, we provide an explicit deterministic calculation (in which observation probabilities are point estimates). Furthermore, our formulation replicates previous work in certain limiting cases. In the case of uncertain sightings, we allow for the possibility of several independent observational types (specimen, photographs, etc.). The method is applied to the Caribbean monk seal, Monachus tropicalis (which has only definite sightings), and synthetic data, with uncertain sightings.

The impact of multidrug resistance in healthcare-associated and nosocomial Gram-negative bacteraemia on mortality and length of stay: cohort study.

Multidrug-resistant Gram-negative bacteria (MDR-GNB) are an emerging public health threat. Accurate estimates of their clinical impact are vital for justifying interventions directed towards preventing or managing infections caused by these pathogens. A retrospective observational cohort study was conducted between 1 January 2007 and 31 July 2009, involving subjects with healthcare-associated and nosocomial Gram-negative bacteraemia at two large Singaporean hospitals. Outcomes studied were mortality and length of stay post-onset of bacteraemia in survivors (LOS). There were 675 subjects (301 with MDR-GNB) matching study inclusion criteria. On multivariate analysis, multidrug resistance was not associated with 30-day mortality, but it was independently associated with longer LOS in survivors (coefficient, 0.34; 95% CI, 0.21-0.48; p < 0.001). The excess LOS attributable to multidrug resistance after adjustment for confounders was 6.1 days. Other independent risk factors for higher mortality included male gender, higher APACHE II score, higher Charlson comorbidity index, intensive care unit stay and presence of concomitant pneumonia. Concomitant urinary tract infection and admission to a surgical discipline were associated with lower risk of mortality. Appropriate empirical antibiotic therapy was neither associated with 30-day mortality nor LOS, although the study was not powered to assess this covariate adequately. Our study adds to existing evidence that multidrug resistance per se is not associated with higher mortality when effective antibiotics are used for definitive therapy. However, its association with longer hospitalization justifies the use of control efforts.

Economic and clinical impact of nosocomial meticillin-resistant Staphylococcus aureus infections in Singapore: a matched case-control study.

We performed a prospective matched case-control study, with six-month follow-up for discharged subjects, to evaluate the direct clinical and financial impact of nosocomial meticillin-resistant Staphylococcus aureus (MRSA) infections in Singaporean hospitals. Consecutive nosocomial MRSA-infected cases at both tertiary public sector hospitals in Singapore were matched for age, specialty service, major surgical procedure (if applicable) and Charlson comorbidity index with up to two non-infected controls each. Chart reviews and subject interviews were performed during hospitalisation and also upon six months post-discharge for survivors. The outcomes analysed were: mortality, length of hospitalisation (LOS), healthcare-associated financial costs, and health-related quality of life. The last was evaluated via an interviewer-administered EuroQol-5D questionnaire on discharge, with conversion to a single health state summary index. Attributable outcomes were ascertained by conditional logistic and linear regression. There were 181 cases and 351 controls. MRSA infection was independently associated with in-hospital death [14.4% vs 1.4%; odds ratio (OR): 5.54; 95% confidence interval (CI): 1.63-18.79, P=0.006], longer LOS (median of 32 days vs 7 days; coefficient: 1.21; 95% CI: 1.02-1.40, P<0.001), higher hospitalisation costs (median of US$18,129.89 vs US$4,490.47; coefficient: 1.14; 95% CI: 0.93-1.35; P<0.001), higher post-discharge healthcare-associated financial costs (median of US$337.24 vs US$259.29; coefficient: 0.39; 95% CI: 0.06-0.72; P=0.021), and poorer health-related quality of life (coefficient: -0.14; 95% CI: -0.21 to -0.08; P<0.001). Outcomes were not significantly different between both hospitals. The attributable individual, institutional and societal impact of MRSA infections is considerable in Singapore. Preventing such infections will result in substantial improvements in patient outcomes and healthcare delivery.

Emergency medicine in Russia.

Russia has undergone sweeping political and social reforms within the past 5 years. The economic and social reforms heralded by the "new openness" of perestroika have led to a restructuring of medicine as well. Changes include the emergence of "for profit" organizations and acute care facilities, the introduction of private health insurance, modifications in the medical education system, and realignment of health priorities with a new trend toward primary care.

N-type inactivation in the mammalian Shaker K+ channel Kv1.4.

Mammalian voltage-gated K+ channels are oligomeric proteins, some of which may be composed in vivo of subunits derived from several similar genes. We have studied N-type inactivation in the rapidly inactivating Kv1.4 channel and, in specific, heteromultimers of this gene product with Kv1.5 noninactivating subunits. Heteromultimeric channels were analyzed for the stoichiometry of Kv1.4:Kv1.5 subunits by observing shifts in the midpoints of steady-state availability from that of homomultimeric channels. This analysis was employed to examine inactivation of heteromultimeric channels expressed in Xenopus oocytes using two model systems: by expression of a Kv1. 4-Kv1.5 tandem fusion construct and by coexpression of native Kv1.4 and Kv1.5 channels across a wide relative concentration range of microinjected mRNA. Additionally, inactivation was examined in coexpression experiments of N-terminal deletion mutants of Kv1.4. We found that (i) a single inactivating subunit conferred inactivation in all hetero-multimers studied; (ii) the rate of inactivation could not be distinguished in channels containing two inactivating subunits from those containing one inactivating subunit; and (iii) large deletions in the linker region between the N-terminal inactivation region and the first membrane-spanning domain had no effect on the rate of inactivation. These data confirm the importance of the proximal N-terminal region in the inactivation of mammalian Kv1.4 channels, and suggest that the inactivation particle remains in close proximity to the permeation pathway even when the channel is in the open state.

Structural determinant for assembly of mammalian K+ channels.

K+ channel function is regulated through the assembly of channel subunit isoforms into either homo- or heterotetrameric structures each characterized by distinct pharmacologic and kinetic properties. In studying the molecular basis of subunit association in mammalian Shaker-like K+ channels, we constructed deletion mutants of the inactivating K+ channel hKv1.4 alone and in tandem with hKv1.5 and examined the functional properties electrophysiologically in Xenopus oocytes. Deletion of 255 amino acids in the amino-terminal domain of hKv1.4 prevented the formation of hybrid channels within the subfamily but had no effect on homomultimerization or voltage-dependent gating. The amino-terminal deletion mutant of Kv2.1, a noninactivating K+ channel from a distantly related subfamily also forms functional homomultimeric channels. Although members of different K+ channel subfamilies do not coassemble, coexpression of the amino-terminal deletion mutants of hKv1.4 and Kv2.1 resulted in the formation of functional hybrid channels. These results demonstrate that the amino-terminal region of mammalian K+ channels subserves two functions. It provides a recognition site necessary for hetero- but not homomultimeric channel assembly within a subfamily and prevents coassembly between subfamilies.

The hemostatic effect of fibrin glue on graft donor sites.

One of the main uses of topical fibrin glue is hemostasis. Fibrin glue from pooled human plasma has been used in Europe for many years. It was used for fixation of skin grafts as early as 1944. Because of the risk of hepatitis and now of acquired immunodeficiency syndrome, this compound has not been approved by the U.S. Food and Drug Administration for use in the United States. It is now possible to make fibrin glue from a single unit of blood. Many blood banks have this capability, and burn centers in the United States are beginning to report its use in skin grafting procedures performed on patients with burns. In an effort to document a hemostatic effect, a prospective double-blind study was designed. Donor sites of patients with burns undergoing skin grafting were studied to provide a uniform wound; anatomic location varied, particularly with respect to gravity. Half of each donor site was sprayed with thrombin and fibrin glue, and the other half was sprayed with thrombin and placebo. A large absorbent pad was placed over the gauze dressing, and all dressings were collected and weighed by the investigators at 6 and 18 hours after the operation. Ten patients have been studied to date. In five patients slightly more bleeding occurred in the site treated with fibrin. One patient had no difference, and four had slightly less bleeding on the donor site treated with fibrin. No significant difference could be found in this initial study group.(ABSTRACT TRUNCATED AT 250 WORDS)

The hand of the helix of deoxyhemoglobin S fibers.

Electron micrographs of deoxyhemoglobin S fiber cross sections provide an end-on view of the fiber whose appearance is sensitive to small changes in orientation. We have developed a procedure to exploit this sensitivity in order to determine the hand of these particles. In a sickle hemoglobin fiber the hemoglobin molecules form long pitch helical strands which twist about the particle axis with a pitch of about 3000 A. Tilting a 400-A-thick cross section by a few degrees aligns one of the long pitch helices so that it is nearly parallel to the direction of view. When a strand of hemoglobin molecules in a fiber is aligned in this manner it appears as a strongly contrasted bright spot. It is this spot, rather than the fiber axis, which appears to be the apparent center of rotation of the cross section. The direction of the displacement of the spot from the particle axis depends upon the particle hand and tilt direction. We have used this property to determine that sickle hemoglobin fibers are right-handed particles. This method may be applicable to other particles with long pitch helices as well.

Psychiatric manifestation of systemic lupus erythematosus in Singapore. A cross-cultural comparison.

In a case-control, cross-cultural study of the psychiatric morbidity of systemic lupus erythematosus in an Oriental population, 30 patients suffering from SLE and 29 controls with rheumatoid arthritis were interviewed. The SLE patients in Singapore exhibited greater psychiatric morbidity than their Western counterparts. Significant correlation was observed between psychiatric morbidity and the clinical disease activity. The patient's perception of the severity of arthritis, myalgia and dermatological lesions was an important aetiological factor. Culturally determined, disease-related psychological stresses also contributed to the psychopathology.

A method for binding specificity analysis of anti-DNA autoantibodies in SLE.

A pattern of differential binding between an NZB/NZW mouse-derived monoclonal anti-ssDNA antibody, V'D2, and restriction fragments of plasmid pBR322 DNA was shown by electrophoresis of the fragments through a denaturing agarose gel followed by their transfer onto nitrocellulose membrane and subsequent reaction of the immobilized DNA with the antibody and 125I-protein A. The antibody showed preferential binding to a 328 base pair Alu I + Hinf I fragment (denoted FD) (AT content, 60%), compared with the other fragments (AT contents, 40-56%). In dot blot assays the antibody bound only to poly(dT) and poly(dA,dT), failing to bind to other synthetic deoxyribopolynucleotides even at the highest concentration tested (300 ng). In competition experiments, the ability of unlabeled DNA to inhibit binding of V'D2 to FD increased with AT content of the DNA. It is concluded that V'D2 has preference for AT-rich DNA. In addition, poly(dA,dT) inhibited binding to a greater extent than either poly(dA) or poly(dT), indicating that base sequence may be important in defining the antigenic determinant. The method, appropriately modified, may be applicable to a wide range of natural nucleic acids and monoclonal antibodies, allowing detection and isolation of specific DNA fragments for detailed studies of antigenic determinants.