8,962 research outputs found
Homology modelling of transferrin-binding protein A from Neisseria meningitidis
Neisseria meningitidis, a causative agent of bacterial
meningitis, obtains transferrin-bound iron by expressing
two outer membrane located transferrin-binding proteins,
TbpA and TbpB. TbpA is thought to be an integral outer
membrane pore that facilitates iron uptake. Evidence suggests
that TbpA is a useful antigen for inclusion in a vaccine
effective against meningococcal disease, hence the identification
of regions involved in ligand binding is of paramount
importance to design strategies to block uptake of iron. The
protein shares sequence and functional similarities to the
Escherichia coli siderophore receptors FepA and FhuA,
whose structures have been determined. These receptors
are composed of two domains, a 22-stranded b-barrel and
an N-terminal plug region that sits within the barrel and
occludes the transmembrane pore. A three-dimensional
TbpA model was constructed using FepA and FhuA structural
templates, hydrophobicity analysis and homology
modelling. TbpA was found to possess a similar architecture
to the siderophore receptors. In addition to providing
insights into the highly immunogenic nature of TbpA and
allowing the prediction of potentially important ligandbinding
epitopes, the model also reveals a narrow channel
through its entire length. The relevance of this channel and
the spatial arrangement of external loops, to the mechanism
of iron translocation employed by TbpA is discussed
Local structure of Liquid-Vapour Interfaces
The structure of a simple liquid may be characterised in terms of ground
state clusters of small numbers of atoms of that same liquid. Here we use this
sensitive structural probe to consider the effect of a liquid-vapour interface
upon the liquid structure. At higher temperatures (above around half the
critical temperature) we find that the predominant effect of the interface is
to reduce the local density, which significantly suppresses the local cluster
populations. At lower temperatures, however, pronounced interfacial layering is
found. This appears to be connected with significant orientational ordering of
clusters based on 3- and 5-membered rings, with the rings aligning
perpendicular and parallel to the interface respectively. At all temperatures,
we find that the population of five-fold symmetric structures is suppressed,
rather than enhanced, close to the interface.Comment: 10 pages, 8 figures, accepted for publication by Molecular Physic
Studying clinical reasoning, part 2: Applying social judgement theory
Part 1 of this paper (Harries and Harries 2001) examined the reasoning studies of the 1980s and 1990s and critiqued the ethnographic and informationprocessing approaches, based on stated information use. The need for an approach that acknowledged the intuitive nature of experienced thinkers’ reasoning was identified. Part 2 describes such an approach ± social judgement theory ± and presents a pilot application in occupational therapy research. The method used is judgement analysis. The issue under study is that of prioritisation policies in community mental health work. The results present the prioritisation policies of four occupational therapists in relation to managing community mental health referrals
Human response to vibration in residential environments (NANR209), Technical report 6 : determination of exposure-response relationships
This technical report presents the development of exposure-response relationships for the human response to vibration in residential environments. The data used to formulate the relationships presented in this report are those which were collected for the Defra funded project “NANR209: Human response to vibration in residential environments”, the main aim of which was the development of exposure-response relationships. Vibration caused by railway traffic, construction work, and internal sources outside of the residents’ control were considered. Response data was collected via face to face interviews with residents in their own homes. The questionnaire was presented as a neighbourhood satisfaction survey and gathered information on, among other things, annoyance caused by vibration and noise exposure. Development and implementation of the questionnaire used for the collection of response data is discussed in Technical Report 2 and Technical Report 5. Vibration exposure was determined via measurement and prediction in such a way that, where possible, an estimation of internal vibration exposure was established for each residence in which a questionnaire was completed. The measurement procedures and methods employed to estimate vibration exposure are detailed in Technical Report 1 and Technical Report 3. Estimations of noise exposure were also derived for each residence using the methods detailed in Technical Report 4
The Universe is not a Computer
When we want to predict the future, we compute it from what we know about the
present. Specifically, we take a mathematical representation of observed
reality, plug it into some dynamical equations, and then map the time-evolved
result back to real-world predictions. But while this computational process can
tell us what we want to know, we have taken this procedure too literally,
implicitly assuming that the universe must compute itself in the same manner.
Physical theories that do not follow this computational framework are deemed
illogical, right from the start. But this anthropocentric assumption has
steered our physical models into an impossible corner, primarily because of
quantum phenomena. Meanwhile, we have not been exploring other models in which
the universe is not so limited. In fact, some of these alternate models already
have a well-established importance, but are thought to be mathematical tricks
without physical significance. This essay argues that only by dropping our
assumption that the universe is a computer can we fully develop such models,
explain quantum phenomena, and understand the workings of our universe. (This
essay was awarded third prize in the 2012 FQXi essay contest; a new afterword
compares and contrasts this essay with Robert Spekkens' first prize entry.)Comment: 10 pages with new afterword; matches published versio
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Discriminating active from latent tuberculosis in patients presenting to community clinics.
BACKGROUND: Because of the high global prevalence of latent TB infection (LTBI), a key challenge in endemic settings is distinguishing patients with active TB from patients with overlapping clinical symptoms without active TB but with co-existing LTBI. Current methods are insufficiently accurate. Plasma proteomic fingerprinting can resolve this difficulty by providing a molecular snapshot defining disease state that can be used to develop point-of-care diagnostics. METHODS: Plasma and clinical data were obtained prospectively from patients attending community TB clinics in Peru and from household contacts. Plasma was subjected to high-throughput proteomic profiling by mass spectrometry. Statistical pattern recognition methods were used to define mass spectral patterns that distinguished patients with active TB from symptomatic controls with or without LTBI. RESULTS: 156 patients with active TB and 110 symptomatic controls (patients with respiratory symptoms without active TB) were investigated. Active TB patients were distinguishable from undifferentiated symptomatic controls with accuracy of 87% (sensitivity 84%, specificity 90%), from symptomatic controls with LTBI (accuracy of 87%, sensitivity 89%, specificity 82%) and from symptomatic controls without LTBI (accuracy 90%, sensitivity 90%, specificity 92%). CONCLUSIONS: We show that active TB can be distinguished accurately from LTBI in symptomatic clinic attenders using a plasma proteomic fingerprint. Translation of biomarkers derived from this study into a robust and affordable point-of-care format will have significant implications for recognition and control of active TB in high prevalence settings
Natural ventilation for the prevention of airborne contagion.
BACKGROUND: Institutional transmission of airborne infections such as tuberculosis (TB) is an important public health problem, especially in resource-limited settings where protective measures such as negative-pressure isolation rooms are difficult to implement. Natural ventilation may offer a low-cost alternative. Our objective was to investigate the rates, determinants, and effects of natural ventilation in health care settings. METHODS AND FINDINGS: The study was carried out in eight hospitals in Lima, Peru; five were hospitals of "old-fashioned" design built pre-1950, and three of "modern" design, built 1970-1990. In these hospitals 70 naturally ventilated clinical rooms where infectious patients are likely to be encountered were studied. These included respiratory isolation rooms, TB wards, respiratory wards, general medical wards, outpatient consulting rooms, waiting rooms, and emergency departments. These rooms were compared with 12 mechanically ventilated negative-pressure respiratory isolation rooms built post-2000. Ventilation was measured using a carbon dioxide tracer gas technique in 368 experiments. Architectural and environmental variables were measured. For each experiment, infection risk was estimated for TB exposure using the Wells-Riley model of airborne infection. We found that opening windows and doors provided median ventilation of 28 air changes/hour (ACH), more than double that of mechanically ventilated negative-pressure rooms ventilated at the 12 ACH recommended for high-risk areas, and 18 times that with windows and doors closed (p < 0.001). Facilities built more than 50 years ago, characterised by large windows and high ceilings, had greater ventilation than modern naturally ventilated rooms (40 versus 17 ACH; p < 0.001). Even within the lowest quartile of wind speeds, natural ventilation exceeded mechanical (p < 0.001). The Wells-Riley airborne infection model predicted that in mechanically ventilated rooms 39% of susceptible individuals would become infected following 24 h of exposure to untreated TB patients of infectiousness characterised in a well-documented outbreak. This infection rate compared with 33% in modern and 11% in pre-1950 naturally ventilated facilities with windows and doors open. CONCLUSIONS: Opening windows and doors maximises natural ventilation so that the risk of airborne contagion is much lower than with costly, maintenance-requiring mechanical ventilation systems. Old-fashioned clinical areas with high ceilings and large windows provide greatest protection. Natural ventilation costs little and is maintenance free, and is particularly suited to limited-resource settings and tropical climates, where the burden of TB and institutional TB transmission is highest. In settings where respiratory isolation is difficult and climate permits, windows and doors should be opened to reduce the risk of airborne contagion
Hepatic retransplantation in cholestatic liver disease: Impact of the interval to retransplantation on survival and resource utilization
The aim of our study was to quantitatively assess the impact of hepatic retransplantation on patient and graft survival and resource utilization. We studied patients undergoing hepatic retransplantation among 447 transplant recipients with primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) at 3 transplantation centers. Cox proportional hazards regression analysis was used for survival analysis. Measures of resource utilization included the duration of hospitalization, length of stay in the intensive care unit, and the duration of transplantation surgery. Forty-six (10.3%) patients received 2 or more grafts during the follow-up period (median, 2.8 years). Patients who underwent retransplantation had a 3.8-fold increase in the risk of death compared with those without retransplantation (P < .01). Retransplantation after an interval of greater than 30 days from the primary graft was associated with a 6.7-fold increase in the risk of death (P < .01). The survival following retransplantations performed 30 days or earlier was similar to primary transplantations. Resource utilization was higher in patients who underwent multiple consecutive transplantations, even after adjustment for the number of grafts during the hospitalization. Among cholestatic liver disease patients, poor survival following hepatic retransplantation is attributed to late retransplantations, namely those performed more than 30 days after the initial transplantation. While efforts must be made to improve the outcome following retransplantation, a more critical evaluation may be warranted for late retransplantation candidates
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