Evidence-based rules from family practice to inform family practice; The learning healthcare system case study on urinary tract infections

Background: Analysis of encounter data relevant to the diagnostic process sourced from routine electronic medical record (EMR) databases represents a classic example of the concept of a learning healthcare system (LHS). By collecting International Classification of Primary Care (ICPC) coded EMR data as part of the Transition Project from Dutch and Maltese databases (using the EMR TransHIS), data mining algorithms can empirically quantify the relationships of all presenting reasons for encounter (RfEs) and recorded diagnostic outcomes. We have specifically looked at new episodes of care (EoC) for two urinary system infections: simple urinary tract infection (UTI, ICPC code: U71) and pyelonephritis (ICPC code: U70). Methods: Participating family doctors (FDs) recorded details of all their patient contacts in an EoC structure using the ICPC, including RfEs presented by the patient, and the FDs' diagnostic labels. The relationships between RfEs and episode titles were studied using probabilistic and data mining methods as part of the TRANSFoRm project. Results: The Dutch data indicated that the presence of RfE's "Cystitis/Urinary Tract Infection", "Dysuria", "Fear of UTI", "Urinary frequency/urgency", "Haematuria", "Urine symptom/complaint, other" are all strong, reliable, predictors for the diagnosis "Cystitis/Urinary Tract Infection". The Maltese data indicated that the presence of RfE's "Dysuria", "Urinary frequency/urgency", "Haematuria" are all strong, reliable, predictors for the diagnosis "Cystitis/Urinary Tract Infection". The Dutch data indicated that the presence of RfE's "Flank/axilla symptom/complaint", "Dysuria", "Fever", "Cystitis/Urinary Tract Infection", "Abdominal pain/cramps general" are all strong, reliable, predictors for the diagnosis "Pyelonephritis". The Maltese data set did not present any clinically and statistically significant predictors for pyelonephritis. Conclusions: We describe clinically and statistically significant diagnostic associations observed between UTIs and pyelonephritis presenting as a new problem in family practice, and all associated RfEs, and demonstrate that the significant diagnostic cues obtained are consistent with the literature. We conclude that it is possible to generate clinically meaningful diagnostic evidence from electronic sources of patient data

Image states in metal clusters

The existence of image states in small clusters is shown, using a quantum-mechanical many-body approach. We present image state energies and wave functions for spherical jellium clusters up to 186 atoms, calculated in the GW approximation, where G is the Green's function and W is the dynamically screened Coulomb interaction, which by construction contains the dynamic long-range correlation effects that give rise to image effects. In addition, we find that image states are also subject to quantum confinement. To extrapolate our investigations to clusters in the mesoscopic size range, we propose a semiclassical model potential, which we test against our full GW results

TADS--A CFD-Based Turbomachinery Analysis and Design System with GUI: User's Manual

The primary objective of this study was the development of a Computational Fluid Dynamics (CFD) based turbomachinery airfoil analysis and design system, controlled by a Graphical User Interface (GUI). The computer codes resulting from this effort are referred to as TADS (Turbomachinery Analysis and Design System). This document is intended to serve as a User's Manual for the computer programs which comprise the TADS system, developed under Task 18 of NASA Contract NAS3-27350, ADPAC System Coupling to Blade Analysis & Design System GUI and Task 10 of NASA Contract NAS3-27394, ADPAC System Coupling to Blade Analysis & Design System GUI, Phase II-Loss, Design and, Multi-stage Analysis. TADS couples a throughflow solver (ADPAC) with a quasi-3D blade-to-blade solver (RVCQ3D) in an interactive package. Throughflow analysis and design capability was developed in ADPAC through the addition of blade force and blockage terms to the governing equations. A GUI was developed to simplify user input and automate the many tasks required to perform turbomachinery analysis and design. The coupling of the various programs was done in such a way that alternative solvers or grid generators could be easily incorporated into the TADS framework. Results of aerodynamic calculations using the TADS system are presented for a highly loaded fan, a compressor stator, a low speed turbine blade and a transonic turbine vane

TADS: A CFD-Based Turbomachinery Analysis and Design System with GUI: Methods and Results

The primary objective of this study was the development of a Computational Fluid Dynamics (CFD) based turbomachinery airfoil analysis and design system, controlled by a Graphical User Interface (GUI). The computer codes resulting from this effort are referred to as TADS (Turbomachinery Analysis and Design System). This document is the Final Report describing the theoretical basis and analytical results from the TADS system developed under Task 10 of NASA Contract NAS3-27394, ADPAC System Coupling to Blade Analysis & Design System GUI, Phase II-Loss, Design and. Multi-stage Analysis. TADS couples a throughflow solver (ADPAC) with a quasi-3D blade-to-blade solver (RVCQ3D) or a 3-D solver with slip condition on the end walls (B2BADPAC) in an interactive package. Throughflow analysis and design capability was developed in ADPAC through the addition of blade force and blockage terms to the governing equations. A GUI was developed to simplify user input and automate the many tasks required to perform turbomachinery analysis and design. The coupling of the various programs was done in such a way that alternative solvers or grid generators could be easily incorporated into the TADS framework. Results of aerodynamic calculations using the TADS system are presented for a multistage compressor, a multistage turbine, two highly loaded fans, and several single stage compressor and turbine example cases

Triggering necroptosis in cisplatin and IAP antagonist-resistant ovarian carcinoma.

Ovarian cancer patients are typically treated with carboplatin and paclitaxel, but suffer a high rate of relapse with recalcitrant disease. This challenge has fostered the development of novel approaches to treatment, including antagonists of the 'inhibitor of apoptosis proteins' (IAPs), also called SMAC mimetics, as apoptosis-inducing agents whose action is opposed by caspase inhibitors. Surprisingly, IAP antagonist plus caspase inhibitor (IZ) treatment selectively induced a tumor necrosis factor-α (TNFα)-dependent death among several apoptosis-resistant cell lines and patient xenografts. The induction of necroptosis was common in ovarian cancer, with expression of catalytically active receptor-interacting protein kinase-3 (RIPK3) necessary for death, and in fact sufficient to compromise survival of RIPK3-negative, necroptosis-resistant ovarian cancer cells. The formation of a necrosome-like complex with a second critical effector, receptor-interacting serine-threonine kinase-1 (RIPK1), was observed. RIPK1, RIPK3 and TNFα were required for the induction of death, as agents that inhibit the function of any of these targets prevented cell death. Abundant RIPK3 transcript is common in serous ovarian cancers, suggesting that further evaluation and targeting of this RIPK3-dependent pathway may be of clinical benefit

Full stress tensor measurement using colour centres in diamond

Stress and strain are important factors in determining the mechanical, electronic, and optical properties of materials, relating to each other by the material's elasticity or stiffness. Both are represented by second rank field tensors with, in general, six independent components. Measurements of these quantities are usually achieved by measuring a property that depends on the translational symmetry and periodicity of the crystal lattice, such as optical phonon energies using Raman spectroscopy, the electronic band gap using cathodoluminescence, photoelasticity via the optical birefringence, or Electron Back Scattering Diffraction (EBSD). A reciprocal relationship therefore exists between the maximum sensitivity of the measurements and the spatial resolution. Furthermore, of these techniques, only EBSD and off-axis Raman spectroscopy allow measurement of all six components of the stress tensor, but neither is able to provide full 3D maps. Here we demonstrate a method for measuring the full stress tensor in diamond, using the spectral and optical polarization properties of the photoluminescence from individual nitrogen vacancy (NV) colour centres. We demonstrate a sensitivity of order 10 MPa, limited by local fluctuations in the stress in the sample, and corresponding to a strain of about 10^-5, comparable with the best sensitivity provided by other techniques. By using the colour centres as built-in local sensors, the technique overcomes the reciprocal relationship between spatial resolution and sensitivity and offers the potential for measuring strains as small as 10^-9 at spatial resolution of order 10 nm. Furthermore it provides a straightforward route to volumetric stress mapping. Aside from its value in understanding strain distributions in diamond, this new approach to stress and strain measurement could be adapted for use in micro or nanoscale sensors.Comment: 12 pages, 5 figures - supplementary informations included in appendi

Estimation of Large-Scale Multi-Rate Systems ⋆

model predictive control and estimation of large-scal

Ultrasound-triggered antibiotic release from PEEK clips to prevent spinal fusion infection: Initial evaluations.

Despite aggressive peri-operative antibiotic treatments, up to 10% of patients undergoing instrumented spinal surgery develop an infection. Like most implant-associated infections, spinal infections persist through colonization and biofilm formation on spinal instrumentation, which can include metal screws and rods for fixation and an intervertebral cage commonly comprised of polyether ether ketone (PEEK). We have designed a PEEK antibiotic reservoir that would clip to the metal fixation rod and that would achieve slow antibiotic release over several days, followed by a bolus release of antibiotics triggered by ultrasound (US) rupture of a reservoir membrane. We have found using human physiological fluid (synovial fluid), that higher levels (100–500 μg) of vancomycin are required to achieve a marked reduction in adherent bacteria vs. that seen in the common bacterial medium, trypticase soy broth. To achieve these levels of release, we applied a polylactic acid coating to a porous PEEK puck, which exhibited both slow and US-triggered release. This design was further refined to a one-hole or two-hole cylindrical PEEK reservoir that can clip onto a spinal rod for clinical use. Short-term release of high levels of antibiotic (340 ± 168 μg), followed by US-triggered release was measured (7420 ± 2992 μg at 48 h). These levels are sufficient to prevent adhesion of Staphylococcus aureus to implant materials. This study demonstrates the feasibility of an US-mediated antibiotic delivery device, which could be a potent weapon against spinal surgical site infection. Statement of Significance: Spinal surgical sites are prone to bacterial colonization, due to presence of instrumentation, long surgical times, and the surgical creation of a dead space (≥5 cm 3 ) that is filled with wound exudate. Accordingly, it is critical that new approaches are developed to prevent bacterial colonization of spinal implants, especially as neither bulk release systems nor controlled release systems are available for the spine. This new device uses non-invasive ultrasound (US) to trigger bulk release of supra-therapeutic doses of antibiotics from materials commonly used in existing surgical implants. Thus, our new delivery system satisfies this critical need to eradicate surviving bacteria, prevent resistance, and markedly lower spinal infection rates

Cassiopeia A: dust factory revealed via submillimetre polarimetry

If Type-II supernovae - the evolutionary end points of short-lived, massive stars - produce a significant quantity of dust (>0.1 M_sun) then they can explain the rest-frame far-infrared emission seen in galaxies and quasars in the first Gyr of the Universe. Submillimetre observations of the Galactic supernova remnant, Cas A, provided the first observational evidence for the formation of significant quantities of dust in Type-II supernovae. In this paper we present new data which show that the submm emission from Cas A is polarised at a level significantly higher than that of its synchrotron emission. The orientation is consistent with that of the magnetic field in Cas A, implying that the polarised submm emission is associated with the remnant. No known mechanism would vary the synchrotron polarisation in this way and so we attribute the excess polarised submm flux to cold dust within the remnant, providing fresh evidence that cosmic dust can form rapidly. This is supported by the presence of both polarised and unpolarised dust emission in the north of the remnant, where there is no contamination from foreground molecular clouds. The inferred dust polarisation fraction is unprecedented (f_pol ~ 30%) which, coupled with the brief timescale available for grain alignment (<300 yr), suggests that supernova dust differs from that seen in other Galactic sources (where f_pol=2-7%), or that a highly efficient grain alignment process must operate in the environment of a supernova remnant.Comment: In press at MNRAS, 10 pages, print in colou