Development of an optimal interface between bone and orthopaedic and dental implants has taken place for many years. In order to determine whether a newly developed implant material conforms to the ...requirements of biocompatibility, mechanical stability and safety, it must undergo rigorous testing both in vitro and in vivo. Results from in vitro studies can be difficult to extrapolate to the in vivo situation. For this reason the use of animal models is often an essential step in the testing of orthopaedic and dental implants prior to clinical use in humans. This review discusses some of the more commonly available and frequently used animal models such as the dog, sheep, goat, pig and rabbit models for the evaluation of bone-implant interactions. Factors for consideration when choosing an animal model and implant design are discussed. Various bone specific features are discussed including the usage of the species, bone macrostructure and microstructure and bone composition and remodelling, with emphasis being placed on the similarity between the animal model and the human clinical situation. While the rabbit was the most commonly used of the species discussed in this review, it is clear that this species showed the least similarities to human bone. There were only minor differences in bone composition between the various species and humans. The pig demonstrated a good likeness with human bone however difficulties may be encountered in relation to their size and ease of handling. In this respect the dog and sheep/goat show more promise as animal models for the testing of bone implant materials. While no species fulfils all of the requirements of an ideal model, an understanding of the differences in bone architecture and remodelling between the species is likely to assist in the selection of a suitable species for a defined research question.
Atrial fibrillation is a strong independent risk factor for stroke.
To characterize the efficacy and safety of antithrombotic agents for stroke prevention in patients who have atrial fibrillation, ...adding 13 recent randomized trials to a previous meta-analysis.
Randomized trials identified by using the Cochrane Stroke Group search strategy, 1966 to March 2007, unrestricted by language.
All published randomized trials with a mean follow-up of 3 months or longer that tested antithrombotic agents in patients who have nonvalvular atrial fibrillation.
Two coauthors independently extracted information regarding interventions; participants; and occurrences of ischemic and hemorrhagic stroke, major extracranial bleeding, and death.
Twenty-nine trials included 28,044 participants (mean age, 71 years; mean follow-up, 1.5 years). Compared with the control, adjusted-dose warfarin (6 trials, 2900 participants) and antiplatelet agents (8 trials, 4876 participants) reduced stroke by 64% (95% CI, 49% to 74%) and 22% (CI, 6% to 35%), respectively. Adjusted-dose warfarin was substantially more efficacious than antiplatelet therapy (relative risk reduction, 39% CI, 22% to 52%) (12 trials, 12 963 participants). Other randomized comparisons were inconclusive. Absolute increases in major extracranial hemorrhage were small (< or =0.3% per year) on the basis of meta-analysis.
Methodological features and quality varied substantially and often were incompletely reported.
Adjusted-dose warfarin and antiplatelet agents reduce stroke by approximately 60% and by approximately 20%, respectively, in patients who have atrial fibrillation. Warfarin is substantially more efficacious (by approximately 40%) than antiplatelet therapy. Absolute increases in major extracranial hemorrhage associated with antithrombotic therapy in participants from the trials included in this meta-analysis were less than the absolute reductions in stroke. Judicious use of antithrombotic therapy importantly reduces stroke for most patients who have atrial fibrillation.
While much of economic sociology focuses on the stabilizing aspects of markets, the social movement perspective emphasizes the role that contentiousness plays in bringing institutional change and ...innovation to markets. Markets are inherently political, both because of their ties to the regulatory functions of the state and because markets are contested by actors who are dissatisfied with market outcomes and who use the market as a platform for social change. Research in this area focuses on the pathways to market change pursued by social movements, including direct challenges to corporations, the institutionalization of systems of private regulation, and the creation of new market categories through institutional entrepreneurship. Much contentiousness, while initially disruptive, works within the market system by producing innovation and restraining capitalism from destroying the resources it depends on for survival.
Many diagrams conventionally used to classify igneous rocks utilize mobile elements, which commonly renders them unreliable for classifying rocks from the geological record. The K2O–SiO2 diagram, ...used to subdivide volcanic arc rocks into rock type (basalts, basaltic andesites, andesites, dacites and rhyolites) and volcanic series (tholeiitic, calc-alkaline, high-K calc-alkaline and shoshonitic), is particularly susceptible to the effects of alteration. However, by using Th as a proxy for K2O and Co as a proxy for SiO2 it is possible to construct a topologically similar diagram that performs the same task but is more robust for weathered and metamorphosed rocks. This study uses >1000 carefully filtered Tertiary–Recent island arc samples to construct a Th–Co classification diagram. A ‘testing set’ comprising data not used in constructing the diagram indicates a classification success rate of c. 80%. When applied to some hydrothermally altered, then tropically weathered Cretaceous volcanic arc lavas from Jamaica, the diagram demonstrates the presence of a tholeiitic volcanic arc series dominated by intermediate–acid lavas overlain by a calc-alkaline series dominated by basic lavas.
The Arrhenius formulation for single-step irreversible unimolecular reactions has been used for many decades to describe the thermal damage and cell death processes. Arrhenius predictions are ...acceptably accurate for structural proteins, for some cell death assays, and for cell death at higher temperatures in most cell lines, above about 55 °C. However, in many cases--and particularly at hyperthermic temperatures, between about 43 and 55 °C--the particular intrinsic cell death or damage process under study exhibits a significant "shoulder" region that constant-rate Arrhenius models are unable to represent with acceptable accuracy. The primary limitation is that Arrhenius calculations always overestimate the cell death fraction, which leads to severely overoptimistic predictions of heating effectiveness in tumor treatment. Several more sophisticated mathematical model approaches have been suggested and show much-improved performance. But simpler models that have adequate accuracy would provide useful and practical alternatives to intricate biochemical analyses. Typical transient intrinsic cell death processes at hyperthermic temperatures consist of a slowly developing shoulder region followed by an essentially constant-rate region. The shoulder regions have been demonstrated to arise chiefly from complex functional protein signaling cascades that generate delays in the onset of the constant-rate region, but may involve heat shock protein activity as well. This paper shows that acceptably accurate and much-improved predictions in the simpler Arrhenius models can be obtained by adding a temperature-dependent time delay. Kinetic coefficients and the appropriate time delay are obtained from the constant-rate regions of the measured survival curves. The resulting predictions are seen to provide acceptably accurate results while not overestimating cell death. The method can be relatively easily incorporated into numerical models. Additionally, evidence is presented to support the application of compensation law behavior to the cell death processes--that is, the strong correlation between the kinetic coefficients, ln{A} and E(a), is confirmed.
Postoperative delirium is associated with increases in the neuronal injury biomarker, neurofilament light (NfL). Here we tested whether two other biomarkers, glial fibrillary acidic protein (GFAP) ...and tau, are associated with postoperative delirium.
A total of 114 surgical patients were recruited into two prospective biomarker cohort studies with assessment of delirium severity and incidence. Plasma samples were sent for biomarker analysis including tau, NfL, and GFAP, and a panel of 10 cytokines. We determined a priori to adjust for interleukin-8 (IL-8), a marker of inflammation, when assessing associations between biomarkers and delirium incidence and severity.
GFAP concentrations showed no relationship to delirium. The change in tau from preoperative concentrations to postoperative Day 1 was greater in patients with postoperative delirium (P<0.001) and correlated with delirium severity (ρ=0.39, P<0.001). The change in tau correlated with increases in IL-8 (P<0.001) and IL-10 (P=0.0029). Linear regression showed that the relevant clinical predictors of tau changes were age (P=0.037), prior stroke/transient ischaemic attack (P=0.001), and surgical blood loss (P<0.001). After adjusting for age, sex, preoperative cognition, and change in IL-8, tau remained significantly associated with delirium severity (P=0.026). Using linear mixed effect models, only tau (not NfL or IL-8) predicted recovery from delirium (P<0.001).
The change in plasma tau was associated with delirium incidence and severity, and resolved over time in parallel with delirium features. The impact of this putative perioperative neuronal injury biomarker on long-term cognition merits further investigation.
NCT02926417 and NCT03124303.
ABSTRACT
The long-period giant planet HR 5183 b has one of the most extreme orbits among exoplanets known to date, and represents a test for models of their dynamical evolution. In this work, we use ...Hipparcos–Gaia astrometry to measure the orbital inclination of this planet for the first time and find $i=89.9^{+13.3\circ }_{-13.5}$, fully consistent with edge-on. The long orbital period and high eccentricity of HR 5183 b are supported by our results, with $P=102^{+84}_{-34}$ yr and e = 0.87 ± 0.04. We confirm that HR 5183 forms a physically bound binary with HIP 67291 at a projected separation of 15 400 AU, and derive new constraints on the orbit of this pair. We combine these results to measure the mutual inclination between the planetary and binary orbits; we observe significant evidence for misalignment, which remains even after accounting for bias of the prior towards high mutual inclinations. However, our results are too imprecise to evaluate a recent prediction that the mutual inclination should reflect the formation history of HR 5183 b. Further observations, especially the release of the full Gaia astrometric data, will allow for improved constraints on the planet-binary mutual inclination. $52 \pm 16\ \hbox{per cent}$ of known planets with eccentricities e ≥ 0.8 are found in multiple star systems, a rate that we find to be greater than for the overall planet population to moderate significance (p = 0.0075). This supports the hypothesis that dynamical interactions with wide stellar companions plays an important role in the formation of highly eccentric exoplanets.
In the brain, highly connected and heterogeneous GABAergic cells are crucial in controling the activity of neuronal networks. They accomplish this task by communicating through remarkably diverse ...sets of inhibitory processes, the complexity of which is reflected by the variety of interneuron classification schemes proposed in recent years. It is now becoming clear that the subcellular localization and intrinsic properties of heteropentameric GABAA receptors themselves also constitute major sources of diversity in GABA-mediated signaling. This review summarizes some of the factors underlying this diversity, including GABAA receptor subunit composition, localization, activation, number and phosphorylation states, variance of GABA concentration in the synaptic cleft, and some of the presynaptic factors regulating GABA release. PUBLICATION ABSTRACT
Summary
Problems with tracheal intubation are infrequent but are the most common cause of anaesthetic death or brain damage. The clinical situation is not always managed well. The Difficult Airway ...Society (DAS) has developed guidelines for management of the unanticipated difficult tracheal intubation in the non‐obstetric adult patient without upper airway obstruction. These guidelines have been developed by consensus and are based on evidence and experience. We have produced flow‐charts for three scenarios: routine induction; rapid sequence induction; and failed intubation, increasing hypoxaemia and difficult ventilation in the paralysed, anaesthetised patient. The flow‐charts are simple, clear and definitive. They can be fully implemented only when the necessary equipment and training are available. The guidelines received overwhelming support from the membership of the DAS.
Disclaimer: It is not intended that these guidelines should constitute a minimum standard of practice, nor are they to be regarded as a substitute for good clinical judgement.
Past studies on the effects of environmental, social, and governance (ESG) scores on firm performance have found mixed support. To further unpack these findings, we focus on the effects of ...industry-level dynamism and the predictability of ESG scores on sales and investor expectations on the prospects of firm growth. Dynamism (predictability) is based on the standard error (R-squared) of industry ESG ratings regressed on industry sales. Taking an investor’s perspective, we focus on a forward-looking performance measure, specifically, the implied volatility in a firm’s 365-day at-the-money call options. Our findings show that although industry ESG-sales dynamism and predictability lower a firm’s implied volatility, a higher firm-level ESG rating mitigates the decline in the implied volatility under increasing ESG-sales dynamism. The findings show that investors expect lower short-term growth potential of industry firms with experimentation in leveraging ESG to increase sales (i.e., dynamism) and only lower their discounts in growth expectations for firms with higher ESG scores. The industry-level dynamics among ESG scores and sales and investor growth expectations in the form of implied volatility are added considerations in studying ESG and performance relationships.
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