On the upstream mobility scheme for two-phase flow in porous media

When neglecting capillarity, two-phase incompressible flow in porous media is modelled as a scalar nonlinear hyperbolic conservation law. A change in the rock type results in a change of the flux function. Discretizing in one-dimensional with a finite volume method, we investigate two numerical fluxes, an extension of the Godunov flux and the upstream mobility flux, the latter being widely used in hydrogeology and petroleum engineering. Then, in the case of a changing rock type, one can give examples when the upstream mobility flux does not give the right answer.Comment: A preprint to be published in Computational Geoscience

Handheld computers and the 21(st )century surgical team: a pilot study

BACKGROUND: The commercial development and expansion of mobile phone networks has led to the creation of devices combining mobile phones and personal digital assistants, which could prove invaluable in a clinical setting. This pilot study aimed to look at how one such device compared with the current pager system in facilitating inter-professional communication in a hospital clinical team. METHODS: The study looked at a heterogeneous team of doctors (n = 9) working in a busy surgical setting at St. Mary's Hospital in London and compared the use of a personal digital assistant with mobile phone and web-browsing facilities to the existing pager system. The primary feature of this device being compared to the conventional pager was its use as a mobile phone, but other features evaluated included the ability to access the internet, and reference data on the device. A crossover study was carried out for 6 weeks in 2004, with the team having access to the personal digital assistant every alternate week. The primary outcome measure for assessing efficiency of communication was the length of time it took for clinicians to respond to a call. We also sought to assess the ease of adoption of new technology by evaluating the perceptions of the team (n = 9) to personal digital assistants, by administering a questionnaire. RESULTS: Doctors equipped with a personal digital assistant rather than a pager, responded more quickly to a call and had a lower of failure to respond rate (RR: 0.44; 95%CI 0.20–0.93). Clinicians also found this technology easy to adopt as seen by a significant reduction in perceptions of nervousness to the technology over the six-week study period (mean (SD) week 1: 4.10 (SD 1.69) vs. mean (SD) week 6: 2.20 (1.99); p = 0.04). CONCLUSION: The results of this pilot study show the possible effects of replacing the current hospital pager with a newer, more technologically advanced device, and suggest that a combined personal digital assistant and mobile phone device may improve communication between doctors. In the light of these encouraging preliminary findings, we propose a large-scale clinical trial of the use of these devices in facilitating inter-professional communication in a hospital setting

Patients' and health care professionals' perceptions of blood transfusion: a systematic review

BACKGROUND Blood transfusions are frequently prescribed for acute and chronic conditions; however, the extent to which patients' and health care professionals' (HCPs') perceptions of transfusion have been investigated is unclear. Patients' treatment perceptions influence how patients cope with illnesses or symptoms. HCPs' perceptions may influence treatment decision making. STUDY DESIGN AND METHODS This was a systematic review of studies post‐1984 reporting adult patients' and HCPs' perceptions of blood transfusion. Seven databases were searched using a three‐domain search strategy capturing synonyms relating to: 1) blood transfusion, 2) perceptions, and 3) participant group (patients or HCPs). Study and sample characteristics were extracted and narratively summarized. Reported perceptions were extracted and synthesized using inductive qualitative methods to identify key themes. RESULTS Thirty‐two studies were included: 14 investigated patients' perceptions and 18 HCPs' perceptions. Surgical patients were the highest represented patient group. HCPs were from a wide range of professions. Transfusions were perceived by patients and HCPs as being of low‐to‐moderate risk. Risk and negative emotions were perceived to influence preference for alternatives. Five themes emerged from the synthesis, classified as Safety/risk, Negative emotions, Alternatives (e.g., autologous, monitoring), Health benefits, and Decision making. “Safety/risk” and “Negative emotions” were most frequently investigated over time, yet periods of research inactivity are apparent. CONCLUSIONS The literature has identified themes on how transfusions are perceived by patients and HCPs, which overlap with recognized discussion points for transfusion specialists. These themes may help HCPs when educating patients about transfusion or consenting patients. Theory‐based qualitative methods may add an important dimension to this work

Enabling comparative modeling of closely related genomes: Example genus Brucella

For many scientific applications, it is highly desirable to be able to compare metabolic models of closely related genomes. In this short report, we attempt to raise awareness to the fact that taking annotated genomes from public repositories and using them for metabolic model reconstructions is far from being trivial due to annotation inconsistencies. We are proposing a protocol for comparative analysis of metabolic models on closely related genomes, using fifteen strains of genus Brucella, which contains pathogens of both humans and livestock. This study lead to the identification and subsequent correction of inconsistent annotations in the SEED database, as well as the identification of 31 biochemical reactions that are common to Brucella, which are not originally identified by automated metabolic reconstructions. We are currently implementing this protocol for improving automated annotations within the SEED database and these improvements have been propagated into PATRIC, Model-SEED, KBase and RAST. This method is an enabling step for the future creation of consistent annotation systems and high-quality model reconstructions that will support in predicting accurate phenotypes such as pathogenicity, media requirements or type of respiration.We thank Jean Jacques Letesson, Maite Iriarte, Stephan Kohler and David O'Callaghan for their input on improving specific annotations. This project has been funded by the United States National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under Contract No. HHSN272200900040C, awarded to BW Sobral, and from the United States National Science Foundation under Grant MCB-1153357, awarded to CS Henry. J.P.F. acknowledges funding from [FRH/BD/70824/2010] of the FCT (Portuguese Foundation for Science and Technology) Ph.D. scholarship

Effects of pedunculopontine nucleus stimulation on human bladder function

AIMS: The pedunculopontine nucleus (PPN) is a deep brain stimulation target for Parkinson's disease (PD). Unilateral PPN stimulation has been described in a previous case report to provoke urinary frequency, urgency and detrusor overactivity, due to probable activation of the pontine micturition center. Our aim was to evaluate the effect of bilateral PPN DBS on urodynamic parameters and to investigate the likely mechanisms using probabilistic tractography. METHODS: Six male PD subjects with bilateral PPN deep brain stimulators were recruited. Urodynamic bladder filling assessments were carried out with the stimulators ON and OFF. Two subjects also had diffusion-weighted and T1-weighted MRI scans performed and probabilistic tractography was carried out to describe white matter connections with the stimulated area. RESULTS: Five subjects completed urodynamic testing. PPN DBS did not give rise to detrusor overactivity or lower sensory thresholds during bladder filling. However, there was a significant increase in maximal bladder capacity with stimulation: mean bladder volume at maximal capacity was 199 mL (range 103-440) ON stimulation compared with 131 mL (range 39-230) OFF stimulation. Tractography demonstrated extensive connectivity to cortical and subcortical regions, some of which have been implicated in bladder control. Fiber pathways also passed close to the vicinity of the pontine micturition center. CONCLUSIONS: Bilateral PPN DBS did not have a detrimental effect on urodynamic filling parameters or produce detrusor overactivity, but did slightly increase maximal capacity. Possible mechanisms include long-range connectivity or local effects at the pontine micturition center

Horizontal DNA transfer mechanisms of bacteria as weapons of intragenomic conflict

Horizontal DNA transfer (HDT) is a pervasive mechanism of diversification in many microbial species, but its primary evolutionary role remains controversial. Much recent research has emphasised the adaptive benefit of acquiring novel DNA, but here we argue instead that intragenomic conflict provides a coherent framework for understanding the evolutionary origins of HDT. To test this hypothesis, we developed a mathematical model of a clonally descended bacterial population undergoing HDT through transmission of mobile genetic elements (MGEs) and genetic transformation. Including the known bias of transformation toward the acquisition of shorter alleles into the model suggested it could be an effective means of counteracting the spread of MGEs. Both constitutive and transient competence for transformation were found to provide an effective defence against parasitic MGEs; transient competence could also be effective at permitting the selective spread of MGEs conferring a benefit on their host bacterium. The coordination of transient competence with cell-cell killing, observed in multiple species, was found to result in synergistic blocking of MGE transmission through releasing genomic DNA for homologous recombination while simultaneously reducing horizontal MGE spread by lowering the local cell density. To evaluate the feasibility of the functions suggested by the modelling analysis, we analysed genomic data from longitudinal sampling of individuals carrying Streptococcus pneumoniae. This revealed the frequent within-host coexistence of clonally descended cells that differed in their MGE infection status, a necessary condition for the proposed mechanism to operate. Additionally, we found multiple examples of MGEs inhibiting transformation through integrative disruption of genes encoding the competence machinery across many species, providing evidence of an ongoing "arms race." Reduced rates of transformation have also been observed in cells infected by MGEs that reduce the concentration of extracellular DNA through secretion of DNases. Simulations predicted that either mechanism of limiting transformation would benefit individual MGEs, but also that this tactic's effectiveness was limited by competition with other MGEs coinfecting the same cell. A further observed behaviour we hypothesised to reduce elimination by transformation was MGE activation when cells become competent. Our model predicted that this response was effective at counteracting transformation independently of competing MGEs. Therefore, this framework is able to explain both common properties of MGEs, and the seemingly paradoxical bacterial behaviours of transformation and cell-cell killing within clonally related populations, as the consequences of intragenomic conflict between self-replicating chromosomes and parasitic MGEs. The antagonistic nature of the different mechanisms of HDT over short timescales means their contribution to bacterial evolution is likely to be substantially greater than previously appreciated

An empirical approach to the nucleation of sulfuric acid droplets in the atmosphere

We use quantum mechanical evaluations of the Gibbs free energy of the hydrates of sulfuric acid, H2SO4. nH2O and (H2SO4)2 . nH2O to evaluate an empirical surface tension for sulfuric acid-water clusters containing few molecules. We use this surface tension to evaluate nucleation rates using classical heteromolecular theory. At low temperatures (T 213 K) the nucleation rates obtained with the empirical surface tensions are signifi cantly greater than those using bulk values of the surface tension. At higher temperatures the difference disappears

Clinical practice: Swallowing problems in cerebral palsy

Cerebral palsy (CP) is the most common physical disability in early childhood. The worldwide prevalence of CP is approximately 2–2.5 per 1,000 live births. It has been clinically defined as a group of motor, cognitive, and perceptive impairments secondary to a non-progressive defect or lesion of the developing brain. Children with CP can have swallowing problems with severe drooling as one of the consequences. Malnutrition and recurrent aspiration pneumonia can increase the risk of morbidity and mortality. Early attention should be given to dysphagia and excessive drooling and their substantial contribution to the burden of a child with CP and his/her family. This review displays the important functional and anatomical issues related to swallowing problems in children with CP based on relevant literature and expert opinion. Furthermore, based on our experience, we describe a plan for approach of investigation and treatment of swallowing problems in cerebral palsy

Effect of Soluble ICAM-1 on a Sjögren's Syndrome-like Phenotype in NOD Mice Is Disease Stage Dependent

Intercellular adhesion molecule-1 (ICAM-1) is involved in migration and co-stimulation of T and B cells. Membrane bound ICAM-1 is over expressed in the salivary glands (SG) of Sjögren's syndrome (SS) patients and has therefore been proposed as a potential therapeutic target. To test the utility of ICAM-1 as a therapeutic target, we used local gene therapy in Non Obese Diabetic (NOD) mice to express soluble (s)ICAM-1 to compete with membrane bound ICAM-1 for binding with its receptor. Therapy was given prior to and just after the influx of immune cells into the SG.A recombinant serotype 2 adeno associated virus (rAAV2) encoding ICAM-1/Fc was constructed and its efficacy tested in the female NOD mice after retrograde instillation in SG at eight (early treatment) and ten (late treatment) weeks of age. SG inflammation was evaluated by focus score and immunohistochemical quantification of infiltrating cell types. Serum and SG tissue were analyzed for immunoglobulins (Ig).Early treatment with ICAM-1/Fc resulted in decreased average number of inflammatory foci without changes in T and B cell composition. In contrast, late treated mice did not show any change in focus scores, but immunohistochemical staining showed an increase in the overall number of CD4+ and CD8+ T cells. Moreover, early treated mice showed decreased IgM within the SGs, whereas late treated mice had increased IgM levels, and on average higher IgG and IgA.Blocking the ICAM-1/LFA-1 interaction with sICAM-1/Fc may result in worsening of a SS like phenotype when infiltrates have already formed within the SG. As a treatment for human SS, caution should be taken targeting the ICAM-1 axis since most patients are diagnosed when inflammation is clearly present within the SG