Hospital characteristics affecting potentially avoidable emergency admissions: national ecological study.

Some emergency admissions can be avoided if acute exacerbations of health problems are managed by emergency and urgent care services without resorting to admission to a hospital bed. In England, these services include hospitals, emergency ambulance, and a range of primary and community services. The aim was to identify whether characteristics of hospitals affect potentially avoidable emergency admission rates. An age-sex adjusted rate of admission for 14 conditions rich in avoidable emergency admissions was calculated for 129 hospitals in England for 2008-2011. Twenty-two per cent (3,273,395/14,998,773) of emergency admissions were classed as potentially avoidable, with threefold variation between hospitals. Explanatory factors of this variation included those which hospital managers could not control (demand for hospital emergency departments) and those which they could control (supply in terms of numbers of acute beds in the hospital, and management of non-emergency and emergency patients within the hospital). Avoidable admission rates were higher for hospitals with higher emergency department attendance rates, higher numbers of acute beds per 1000 catchment population and higher conversion rates from emergency department attendance to admission. Hospital managers may be able to reduce avoidable emergency admissions by reducing supply of acute beds and conversion rates from emergency department attendance.

Single particle multichannel bio-aerosol fluorescence sensor.

We describe a prototype low-cost multi-channel aerosol fluorescence sensor designed for unattended deployment in medium to large area bio-aerosol detection networks. Individual airborne particles down to ~1mum in size are detected and sized by measurement of light scattered from a continuous-wave diode laser (660nm). This scatter signal is then used to trigger the sequential firing of two xenon sources which irradiate the particle with UV pulses at ~280 nm and ~370 nm, optimal for excitation of bio-fluorophores tryptophan and NADH (nicotinamide adenine dinucleotide) respectively. For each excitation wavelength, fluorescence is detected across two bands embracing the peak emissions of the same bio-fluorophores. Current measurement rates are up to ~125 particles/s, corresponding to all particles for concentrations up to 1.3 x 104 particles/l. Developments to increase this to ~500 particles/s are in hand. Device sensitivity is illustrated in preliminary data recorded from aerosols of E.coli, BG spores, and a variety of non-biological materials.

Postnatal depression across countries and cultures: a qualitative study.

BACKGROUND: Postnatal depression seems to be a universal condition with similar rates in different countries. However, anthropologists question the cross-cultural equivalence of depression, particularly at a life stage so influenced by cultural factors. AIMS: To develop a qualitative method to explore whether postnatal depression is universally recognised, attributed and described and to enquire into people's perceptions of remedies and services for morbid states of unhappiness within the context of local services. METHOD: The study took place in 15 centres in 11 countries and drew on three groups of informants: focus groups with new mothers, interviews with fathers and grandmothers, and interviews with health professionals. Textual analysis of these three groups was conducted separately in each centre and emergent themes compared across centres. RESULTS: All centres described morbid unhappiness after childbirth comparable to postnatal depression but not all saw this as an illness remediable by health interventions. CONCLUSIONS: Although the findings of this study support the universality of a morbid state of unhappiness following childbirth, they also support concerns about the cross-cultural equivalence of postnatal depression as an illness requiring the intervention of health professionals; this has implications for future research.

Xenopus Cyr61 regulates gastrulation movements and modulates Wnt signalling.

Cyr61 is a secreted, heparin-binding, extracellular matrix-associated protein whose activities include the promotion of adhesion and chemotaxis, and the stimulation of fibroblast and endothelial cell growth. Many, if not all, of these activities of Cyr61 are mediated through interactions with integrins. We explore the role of Cyr61 in the early development of Xenopus laevis. Gain- and loss-of-function experiments show that Xcyr61 is required for normal gastrulation movements. This role is mediated in part through the adhesive properties of Xcyr61 and its related ability to modulate assembly of the extracellular matrix. In addition, Xcyr61 can, in a context-dependent manner, stimulate or inhibit signalling through the Wnt pathway. These properties of Xcyr61 provide a mechanism for integrating cell signalling, cell adhesion and cell migration during gastrulation.

SufC hydrolyzes ATP and interacts with SufB from Thermotoga maritima.

Genetic experiments in bacteria have shown the suf operon is involved in iron homeostasis and the oxidative stress response. The sufB and sufC genes that always occur together in bacteria are also found in plants, and even the malaria parasite, associated with the plastid organelle. Although the suf operon is believed to encode an iron-dependent ABC-transporter there is no direct evidence. By immunolocalization we show here that SufB and SufC are associated with the membrane of Escherichia coli. We also present kinetic studies with a recombinant version of SufC from Thermotoga maritima that shows it is an ATPase and that it interacts with SufB in vitro.

Regulated endocytic routing modulates wingless signaling in Drosophila embryos.

Embryos have evolved various strategies to confine the action of secreted signals. Using an HRP-Wingless fusion protein to track the fate of endocytosed Wingless, we show that degradation by targeting to lysosomes is one such strategy. Wingless protein is specifically degraded at the posterior of each stripe of wingless transcription, even under conditions of overexpression. If lysosomal degradation is compromised genetically or chemically, excess Wingless accumulates and ectopic signaling ensues. In the wild-type, Wingless degradation is slower at the anterior than at the posterior. This follows in part from the segmental activation of signaling by the epidermal growth factor receptor, which accelerates Wingless degradation at the posterior, thus leading to asymmetrical Wingless signaling along the anterior-posterior axis.

Real-time observation of the change in light scattering from droplets with increasing deformity.

Commercial aerodynamic particle sizing instruments generally achieve the desired particle size measurement by accelerating a sample airstream in which the particles are suspended and measuring the velocity acquired by individual particles. The accelerating flow regime can cause liquid droplets to deform and this subsequently introduces errors. In this paper, we present an apparatus that enables droplet deformation to be observed by recording the spatial light scatter intensity. The paper presents experimental data in video format showing the changes that occur in the light scattering from droplets as a function of increasing flow rate/deformation.

Extracellularly truncated desmoglein 1 compromises desmosomes in MDCK cells.

The formation and stability of epithelial tissue involves cell adhesion and the connection of the intermediate filaments of contiguous cells, mediated by desmosomes. The cadherin family members Desmocollins (Dsc) and Desmogleins (Dsg) mediate desmosome extracellular adhesion. The main intracellular molecules identified linking Dscs and Dsgs with the intermediate filament network are Plakoglobin (PG), Plakophilins (PPs) and Desmoplakin (DP). Previous studies on desmosome-mediated adhesion have focused on the intracellular domains of Dsc and Dsg because of their capacity to interact with PG, PPs and DP. This study examines the role of the extracellular domain of Dsg1 upon desmosome stability in MDCK cells. Dsg1 was constructed containing an extracellular deletion (Dsg delta 1EC) and was expressed in MDCK cells. A high expressor Dsg delta 1EC/MDCK clone was obtained and analysed for its capacity to form desmosomes in cell monolayers and when growing under mechanical stress in three-dimensional collagen cultures. Phenotypic changes associated with the ectopic expression of Dsg1 delta EC in MDCK cells were: disturbance of the cytokeratin network, a change in the quality and number of desmosomes and impairment of the formation of cysts in suspension cultures. Interestingly, Dsg1 delta EC was not localized in desmosomes, but was still able to maintain its intracytoplasmic interaction with PG, suggesting that the disruptive effects were largely due to PG and/or PP sequestration.

Plasmodium chabaudi-infected erythrocytes adhere to CD36 and bind to microvascular endothelial cells in an organ-specific way.

Adherence of erythrocytes infected with Plasmodium falciparum to microvascular endothelial cells (sequestration) is considered to play an important role in parasite virulence and pathogenesis. However, the real importance of sequestration for infection and disease has never been fully assessed. The absence of an appropriate in vivo model for sequestration has been a major barrier. We have examined the rodent malaria parasite Plasmodium chabaudi chabaudi AS in mice as a potential model. Erythrocytes infected with this parasite adhere in vitro to purified CD36, a critical endothelium receptor for binding P. falciparum-infected erythrocytes. P. c. chabaudi-infected erythrocytes adhere in vitro to endothelial cells in a gamma interferon-dependent manner, suggesting the involvement of additional adhesion molecules in the binding process, as is also the case with P. falciparum-infected cells. Furthermore, plasma or sera from infected and hyperimmune mice, respectively, have the ability to block binding of infected erythrocytes to endothelial cells. In vivo, erythrocytes containing mature P. c. chabaudi parasites are sequestered from the peripheral circulation. Sequestration is organ specific, occurring primarily in the liver, although intimate contact between infected erythrocytes and endothelial cells is also observed in the spleen and brain. The results are discussed in the context of the use of this model to study (i) the relationship between endothelial cell activation and the level of sequestration and (ii) the primary function of sequestration in malaria infection.

Improved post-embedding immunocytochemistry of myelinated nervous tissue for electron microscopy.

The particularly high lipid content of normal mature adult myelin sheaths, together with the light fixation protocols usually necessary to retain antigenicity, combine to make white matter nervous tissue an especially problematical subject for post-embedding immuno-electron microscopy using modern acrylic resins. Fixation and infiltration modifications to standard processing schedules for Lowicryl were found to greatly improve the embedding and therefore the resulting morphology. This in turn improved the signal to noise ratio by reducing the high non-specific backgrounds usually found in poorly infiltrated areas. Using Lowicryl HM20, we have been able to obtain satisfactory immunostaining for myelin basic protein with good retention of structural integrity in the myelin of both normal and lesioned adult cortico spinal tract.

Mycobacterium tuberculosis-activated dendritic cells induce protective immunity in mice.

Activated dendritic cells are critically important in the priming of T-cell responses. In this report we show that the infection of a conditionally immortalized dendritic cell line (tsDC) with Mycobacterium tuberculosis resulted in the up-regulation of B7-1 and B7-2 co-stimulatory molecules and the induction of several inflammatory cytokines, including tumour necrosis factor-alpha and interleukin-6, -1beta and -12. In addition, we show that these activated dendritic cells were capable of eliciting antigen-specific T-cell responses and potent anti-mycobacterial protective immunity in a murine model of experimental tuberculosis infection.

Bacterial orthologues indicate the malarial plastid gene ycf24 is essential.

ycf24 is a well conserved gene found in all major groups of bacteria, as well as on red algal plastid genomes and the vestigal plastid genome of apicomplexan pathogens like the malaria parasite Plasmodium falciparum (ORF470). Some database annotations describe Ycf24 as an ABC transporter subunit, but we find the level of significance is low. To investigate ycf24's function we disrupted it in the cyanobacterium Synechocystis sp., strain PCC6803 which has a multi-copy genome. This showed ycf24 is essential, partial loss producing a terminal phenotype of chlorosis, reduced cell size, loss of DNA, and a striking arrest in cytokinesis. Attempts to disrupt the single copy of ycf24 in E. coli failed to give stable transformants. When Ycf24 was over-expressed in E. coli as a soluble fusion protein, it localized mostly as a band on either side of the nucleoid and nucleoid partitioning was aberrant. We propose the relict plastid organelle of apicomplexans retains its capacity for protein synthesis because Ycf24 is essential.

Simultaneous light scattering and intrinsic fluorescence measurement for the classification of airborne particles.

We describe a prototype laboratory light-scattering instrument that integrates two approaches to airborne particle characterization: spatial light-scattering analysis and intrinsic fluorescence measurement, with the aim of providing an effective means of classifying biological particles within an ambient aerosol. The system uses a single continuous-wave 266-nm ultraviolet laser to generate both the spatial elastic scatter data (from which an assessment of particle size and shape is made) and the particle intrinsic fluorescence data from particles in the approximate size range of 1-10-mum diameter carried in a sample airflow through the laser beam. Preliminary results suggest that this multiparameter measurement approach can provide an effective means of classifying different particle types and can reduce occurrences of false-positive detection of biological aerosols.

Light scattering from deformed droplets and droplets with inclusions. I. Experimental results.

We provide experimental results from the scattering of light by deformed liquid droplets and droplets with inclusions. The characterization of droplet deformation could lead to improved measurement of droplet size as measured by commercial aerodynamic particle-sizing instruments. The characterization of droplets with inclusions can be of importance in some industrial, occupational, and military aerosol monitoring situations. The nozzle assembly from a TSI Aerodynamic Particle Sizer was used to provide the accelerating flow conditions in which experimental data were recorded. A helium-neon laser was employed to generate the light-scattering data, and an externally triggered, pulsed copper vapor laser provided illumination for a droplet imaging system arranged orthogonal to the He-Ne scattering axis. The observed droplet deformation correlates well over a limited acceleration range with theoretical predictions derived from an analytical solution of the Navier-Stokes equation.

Light Scattering from Deformed Droplets and Droplets with Inclusions. II. Theoretical Treatment.

We provide theoretical results from the scattering of light by deformed liquid droplets and droplets with inclusions. With improved instrumentation and computer technologies available, researchers are able to employ two-dimensional angular optical scattering as a tool for analyzing such particle systems and which then could be applied in industrial, occupational, and military aerosol measurement. We present numerically calculated spatial light-scattering data from various droplet morphologies. We describe characteristic features of the theoretical data and compare these with the experimental results.

Ultrastructural localization of Sm15 and Sm25, two major tegumental adult worm antigens of Schistosoma mansoni.

Sm15 and Sm25 are two of the principal tegumental antigens recognized by antibodies from mice protectively vaccinated with adult worm tegumental membranes and may therefore be potential vaccine candidate antigens. Using antibodies affinity purified from anti-tegumental membrane anti-sera, and antibodies raised against the recombinant antigens, Sm15 and Sm25 were shown to be located specifically in the tegument of adult worms being distributed throughout the syncitium but not associated with the outer membrane.

Specialised service to children with specific language impairment in mainstream schools.

The following report describes a three year project to develop, implement and evaluate a specialised speech and language therapy (SLT) service to children with specific language impairment (SLI) who attend mainstream schools and nurseries. The report describes how the service was set up and the package of care offered. A range of evaluation measures was designed and implemented and the results of these are discussed. The service aimed to enable key-workers to support children with SLI effectively within the context of the school environment. The results suggest that the package of care offered provided an effective and high quality service as judged by the parents, schools and therapists.

Neural-network-based spatial light-scattering instrument for hazardous airborne fiber detection.

A laser light-scattering instrument has been designed to facilitate the real-time detection of potentially hazardous respirable fibers, such as asbestos, within an ambient environment. The instrument captures data relating to the spatial distribution of light scattered by individual particles in flow by use of a dedicated multielement photodiode detector array. These data are subsequently processed with an artificial neural network that has previously been trained to recognize those features or patterns within the light-scattering distribution that may be characteristic of the specific particle types being sought, such as, for example, crocidolite or chrysotile asbestos fibers. Each particle is thus classified into one of a limited set of classes based on its light-scattering properties, and from the accumulated data a particle concentration figure for each class may be produced and updated at regular intervals. Particle analysis rates in excess of 103 /s within a sample volume flow rate of 1 l /min are achievable, offering the possibility of detecting fiber concentrations at the recommended maximum exposure limit of 0.1 fibers /ml within a sampling period of a few seconds.

Plasmodium knowlesi: secondary processing of the malaria merozoite surface protein-1.

Secondary processing of the Plasmodium falciparum malaria merozoite surface protein-1 (MSP-1) is defined as a single proteolytic cleavage within the carboxy-terminal membrane-bound component of the MSP-1 protein complex on the free merozoite surface. The N-terminal cleavage product (MSP-1(33)) is shed from the parasite surface along with a number of other polypeptides, whereas the C-terminal processing product remains bound to the merozoite surface and is the only part of MSP-1 detectable in the newly invaded host cell. We report that secondary processing of MSP-1 takes place in a similar manner on invasive merozoites of the simian malaria parasite Plasmodium knowlesi. Processing can take place to a limited extent in pure isolated merozoites; however, within 10 min of the addition of purified invasive merozoites to rhesus erythrocytes, processing and shedding of MSP-1 has gone to completion only in those parasites which have undergone invasion; residual free merozoites remain uniformly reactive with antibodies against MSP-1(33). Successful invasion is therefore associated with complete shedding of MSP-1(33) from the merozoite surface. The nucleotide sequence of the 3' domain of the P. knowlesi MSP-1 gene is also presented.

Establishment and characterization of conditionally immortalized cells from the mouse urogenital ridge.

Cell cultures from the urogenital ridge have been established to facilitate the study of the regulation and downstream interactions of Sry in mammalian sex determination. Cells have been explanted from transgenic mice carrying a temperature sensitive SV40 large T-antigen, and established in ongoing cultures. Analysis of the cells in these cultures at the electron microscope level reveals multiple cell types that compare to the cell types found in vivo during this period of development. Primordial germ cells, that are simultaneously explanted in the course of these experiments, also survive in culture. The explants undergo a morphogenetic organization into branching cord-like structures when cells are trypsinized and plated in extracellular matrix (Matrigel). We analyzed the expression of a number of molecular markers of the fetal gonad during monolayer culture, during in vitro morphogenesis in Matrigel, and in clonal lines derived from the complex explants. This analysis included Sry which is found to be expressed in some cultures from XY urogenital ridges that have been maintained for as long as 8 months.