Safety and tolerability of an ovine-derived polyclonal anti-TNFα Fab fragment (AZD9773) in patients with severe sepsis

Sepsis remains a significant medical problem. TNFα is a central cytokine in sepsis pathophysiology. We conducted a phase IIa trial in patients with severe sepsis to assess the safety and tolerability of an intravenously infused ovine-derived polyclonal anti-TNFα Fab fragment (AZD9773)

Lessons Learned: Using the Caprini Risk Assessment Model to Provide Safe and Efficacious Thromboprophylaxis Following Hip and Knee Arthroplasty

© The Author(s) 2020. Two of the more common potential complications after arthroplasty are venous thromboembolism (VTE), which includes deep vein thrombosis (DVT) and pulmonary embolus (PE), and excess bleeding. Appropriate chemoprophylaxis choices are essential to prevent some of these adverse events and from exacerbating others. Risk stratification to prescribe safe and effective medications in the prevention of postoperative VTE has shown benefit in this regard. The Department of Orthopaedic Surgery at Syosset Hospital/Northwell Health, which performs over 1200 arthroplasties annually, has validated and is using the 2013 version of the Caprini Risk Assessment Model (RAM) to stratify each patient for risk of postoperative VTE. This tool results in a culling of information, past and present, personal and familial, that provides a truly thorough evaluation of the patient’s risk for postoperative VTE. The Caprini score then guides the medication choices for thromboprophylaxis. The Caprini score is only valuable if the data is properly collected, and we have learned numerous lessons after applying it for 18 months. Risk stratification requires practice and experience to achieve expertise in perioperative patient evaluation. Having access to pertinent patient information, while gaining proficiency in completing the Caprini RAM, is vital to its efficacy. Ongoing, real time analyses of patient outcomes, with subsequent change in process, is key to improving patient care

The comparative evaluation of ERTS-1 imagery for resource inventory in land use planning

The author has identified the following significant results. Multidiscipline team interpretation and mapping of resources for Crook County is complete on 1:250,000 scale enlargements of ERTS imagery and 1:120,000 hi-flight photography. Maps of geology, soils, vegetation-land use and land resources units were interpreted to show limitations, suitabilities, and geologic hazards for land use planning. Mapping of lineaments and structures from ERTS imagery has shown a number of features not previously mapped in Oregon. A multistage timber inventory of Ochoco National Forest was made, using ERTS images as the first stage. Inventory of forest clear-cutting practices was successfully demonstrated with color composites. Soil tonal differences in fallow fields correspond with major soil boundaries in loess-mantled terrain. A digital classification system used for discriminating natural vegetation and geologic material classes was successful in separating most major classes around Newberry Caldera, Mt. Washington, and Big Summit Prairie

Magnetic structure of Yb2Pt2Pb: Ising moments on the Shastry-Sutherland lattice.

Neutron diffraction measurements were carried out on single crystals and powders of Yb2Pt2Pb, where Yb moments form two interpenetrating planar sublattices of orthogonal dimers, a geometry known as Shastry-Sutherland lattice, and are stacked along the c axis in a ladder geometry. Yb2Pt2Pb orders antiferromagnetically at TN=2.07K, and the magnetic structure determined from these measurements features the interleaving of two orthogonal sublattices into a 5×5×1 magnetic supercell that is based on stripes with moments perpendicular to the dimer bonds, which are along (110) and (−110). Magnetic fields applied along (110) or (−110) suppress the antiferromagnetic peaks from an individual sublattice, but leave the orthogonal sublattice unaffected, evidence for the Ising character of the Yb moments in Yb2Pt2Pb that is supported by point charge calculations. Specific heat, magnetic susceptibility, and electrical resistivity measurements concur with neutron elastic scattering results that the longitudinal critical fluctuations are gapped with ΔE≃0.07meV

Free Energy Simulations of a GTPase: GTP and GDP Binding to Archaeal Initiation Factor 2

International audienceArchaeal initiation factor 2 (aIF2) is a protein involved in the initiation of protein biosynthesis. In its GTP-bound, "ON" conformation, aIF2 binds an initiator tRNA and carries it to the ribosome. In its GDP-bound, "OFF" conformation, it dissociates from tRNA. To understand the specific binding of GTP and GDP and its dependence on the ON or OFF conformational state of aIF2, molecular dynamics free energy simulations (MDFE) are a tool of choice. However, the validity of the computed free energies depends on the simulation model, including the force field and the boundary conditions, and on the extent of conformational sampling in the simulations. aIF2 and other GTPases present specific difficulties; in particular, the nucleotide ligand coordinates a divalent Mg(2+) ion, which can polarize the electronic distribution of its environment. Thus, a force field with an explicit treatment of electronic polarizability could be necessary, rather than a simpler, fixed charge force field. Here, we begin by comparing a fixed charge force field to quantum chemical calculations and experiment for Mg(2+):phosphate binding in solution, with the force field giving large errors. Next, we consider GTP and GDP bound to aIF2 and we compare two fixed charge force fields to the recent, polarizable, AMOEBA force field, extended here in a simple, approximate manner to include GTP. We focus on a quantity that approximates the free energy to change GTP into GDP. Despite the errors seen for Mg(2+):phosphate binding in solution, we observe a substantial cancellation of errors when we compare the free energy change in the protein to that in solution, or when we compare the protein ON and OFF states. Finally, we have used the fixed charge force field to perform MDFE simulations and alchemically transform GTP into GDP in the protein and in solution. With a total of about 200 ns of molecular dynamics, we obtain good convergence and a reasonable statistical uncertainty, comparable to the force field uncertainty, and somewhat lower than the predicted GTP/GDP binding free energy differences. The sign and magnitudes of the differences can thus be interpreted at a semiquantitative level, and are found to be consistent with the experimental binding preferences of ON- and OFF-aIF2

The Moral of the Tale: Stories, Trust, and Public Engagement with Clinical Ethics via Radio and Theatre.

Trust is frequently discussed with reference to the professional-patient relationship. However, trust is less explored in relation to the ways in which understanding of, and responses to, questions of ethics are discussed by both the "public" and "experts." Public engagement activity in healthcare ethics may invoke "trust" in analysing a moral question or problem but less frequently conceives of trust as integral to "public engagement" itself. This paper explores the relationship between trust and the ways in which questions of healthcare ethics are identified and negotiated by both "experts" and the public. Drawing on two examples from the author's "public engagement" work-a radio programme for the British Broadcasting Corporation and work with a playwright and theatre-the paper interrogates the ways in which "public engagement" is often characterized. The author argues that the common approach to public engagement in questions of ethics is unhelpfully constrained by a systemic disposition which continues to privilege the professional or expert voice at the expense of meaningful exchange and dialogue. By creating space for novel interactions between the "expert" and the "public," authentic engagement is achieved that enables not only the participants to flourish but also contributes to trust itself

A New Model for the Spiral Structure of the Galaxy. Superposition of 2+4-armed patterns

We investigate the possibility of describing the spiral pattern of the Milky Way in terms of a model of superposition 2- and 4-armed wave harmonics (the simplest description, besides pure modes). Two complementary methods are used: a study of stellar kinematics, and direct tracing of positions of spiral arms. In the first method, the parameters of the galactic rotation curve and the free parameters of the spiral density waves were obtained from Cepheid kinematics, under different assumptions. To turn visible the structure corresponding to these models, we computed the evolution of an ensemble of N-particles, simulating the ISM clouds, in the perturbed galactic gravitational field. In the second method, we present a new analysis of the longitude-velocity (l-v) diagram of the sample of galactic HII regions, converting positions of spiral arms in the galactic plane into locii of these arms in the l-v diagram. Both methods indicate that the ``self-sustained'' model, in which the 2-armed and 4-armed mode have different pitch angles (6 arcdeg and 12 arcdeg, respectively) is a good description of the disk structure. An important conclusion is that the Sun happens to be practically at the corotation circle. As an additional result of our study, we propose an independent test for localization of the corotation circle in a spiral galaxy: a gap in the radial distribution of interstellar gas has to be observed in the corotation region.Comment: 17 pages, 9 figures, Latex, uses aas2pp4.st

Variational Methods for Biomolecular Modeling

Structure, function and dynamics of many biomolecular systems can be characterized by the energetic variational principle and the corresponding systems of partial differential equations (PDEs). This principle allows us to focus on the identification of essential energetic components, the optimal parametrization of energies, and the efficient computational implementation of energy variation or minimization. Given the fact that complex biomolecular systems are structurally non-uniform and their interactions occur through contact interfaces, their free energies are associated with various interfaces as well, such as solute-solvent interface, molecular binding interface, lipid domain interface, and membrane surfaces. This fact motivates the inclusion of interface geometry, particular its curvatures, to the parametrization of free energies. Applications of such interface geometry based energetic variational principles are illustrated through three concrete topics: the multiscale modeling of biomolecular electrostatics and solvation that includes the curvature energy of the molecular surface, the formation of microdomains on lipid membrane due to the geometric and molecular mechanics at the lipid interface, and the mean curvature driven protein localization on membrane surfaces. By further implicitly representing the interface using a phase field function over the entire domain, one can simulate the dynamics of the interface and the corresponding energy variation by evolving the phase field function, achieving significant reduction of the number of degrees of freedom and computational complexity. Strategies for improving the efficiency of computational implementations and for extending applications to coarse-graining or multiscale molecular simulations are outlined.Comment: 36 page

Medication administration errors for older people in long-term residential care

Background Older people in long-term residential care are at increased risk of medication errors. The purpose of this study was to evaluate a computerised barcode medication management system designed to improve drug administrations in residential and nursing homes, including comparison of error rates and staff awareness in both settings. Methods All medication administrations were recorded prospectively for 345 older residents in thirteen care homes during a 3-month period using the computerised system. Staff were surveyed to identify their awareness of administration errors prior to system introduction. Overall, 188,249 attempts to administer medication were analysed to determine the prevalence of potential medication administration errors (MAEs). Error classifications included attempts to administer medication at the wrong time, to the wrong person or discontinued medication. Analysis compared data at residential and nursing home level and care and nursing staff groups. Results Typically each resident was exposed to 206 medication administration episodes every month and received nine different drugs. Administration episodes were more numerous (p < 0.01) in nursing homes (226.7 per resident) than in residential homes (198.7). Prior to technology introduction, only 12% of staff administering drugs reported they were aware of administration errors being averted in their care home. Following technology introduction, 2,289 potential MAEs were recorded over three months. The most common MAE was attempting to give medication at the wrong time. On average each resident was exposed to 6.6 potential errors. In total, 90% of residents were exposed to at least one MAE with over half (52%) exposed to serious errors such as attempts to give medication to the wrong resident. MAEs rates were significantly lower (p < 0.01) in residential homes than nursing homes. The level of non-compliance with system alerts was low in both settings (0.075% of administrations) demonstrating virtually complete error avoidance. Conclusion Potentially inappropriate administration of medication is a serious problem in long-term residential care. A computerised barcode system can accurately and automatically detect inappropriate attempts to administer drugs to residents. This tool can reliably be used by care staff as well as nurses to improve quality of care and patient safety