249 research outputs found

    Chronicles of Oklahoma

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    Article details the author's journey to Okmulgee, the capitol of the Creek Nation, to see the Creek Indian Council in session

    On the Conditional and Unconditional Type I Error Rates and Power of Tests in Linear Models with Heteroscedastic Errors

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    Preliminary tests for homoscedasticity may be unnecessary in general linear models. Based on Monte Carlo simulations, results suggest that when testing for differences between independent slopes, the unconditional use of weighted least squares regression and HC4 regression performed the best across a wide range of conditions

    When is star formation episodic? A delay differential equation negative feedback model

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    We introduce a differential equation for star formation in galaxies that incorporates negative feedback with a delay. When the feedback is instantaneous, solutions approach a self-limiting equilibrium state. When there is a delay, even though the feedback is negative, the solutions can exhibit cyclic and episodic solutions. We find that periodic or episodic star formation only occurs when two conditions are satisfied. Firstly the delay timescale must exceed a cloud consumption timescale. Secondly the feedback must be strong. This statement is quantitatively equivalent to requiring that the timescale to approach equilibrium be greater than approximately twice the cloud consumption timescale. The period of oscillations predicted is approximately 4 times the delay timescale. The amplitude of the oscillations increases with both feedback strength and delay time. We discuss applications of the delay differential equation (DDE) model to star formation in galaxies using the cloud density as a variable. The DDE model is most applicable to systems that recycle gas and only slowly remove gas from the system. We propose likely delay mechanisms based on the requirement that the delay time is related to the observationally estimated time between episodic events. The proposed delay timescale accounting for episodic star formation in galaxy centers on periods similar to P 10 Myrs, irregular galaxies with P 100 Myrs, and the Milky Way disk with P~ 2Gyr, could be that for exciting turbulence following creation of massive stars, that for gas pushed into the halo to return and interact with the disk and that for spiral density wave evolution, respectively.Comment: submitted to MNRA

    Efficacy of CMX001 as a Prophylactic and Presymptomatic Antiviral Agent in New Zealand White Rabbits Infected with Rabbitpox Virus, a Model for Orthopoxvirus Infections of Humans

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    CMX001, a lipophilic nucleotide analog formed by covalently linking 3-(hexdecyloxy)propan-1-ol to cidofovir (CDV), is being developed as a treatment for smallpox. CMX001 has dramatically increased potency versus CDV against all dsDNA viruses and, in contrast to CDV, is orally available and has shown no evidence of nephrotoxicity in healthy volunteers or severely ill transplant patients to date. Although smallpox has been eliminated from the environment, treatments are urgently being sought due to the risk of smallpox being used as a bioterrorism agent and for monkeypox virus, a zoonotic disease of Africa, and adverse reactions to smallpox virus vaccinations. In the absence of human cases of smallpox, new treatments must be tested for efficacy in animal models. Here we first review and discuss the rabbitpox virus (RPV) infection of New Zealand White rabbits as a model for smallpox to test the efficacy of CMX001 as a prophylactic and early disease antiviral. Our results should also be applicable to monkeypox virus infections and for treatment of adverse reactions to smallpox vaccination

    Open source drug discovery - A limited tutorial

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    Open science is a new concept for the practice of experimental laboratory-based research, such as drug discovery. The authors have recently gained experience in how to run such projects and here describe some straightforward steps others may wish to take towards more openness in their own research programmes. Existing and inexpensive online tools can solve many challenges, while some psychological barriers to the free sharing of all data and ideas are more substantia

    Healthcare disparities for women hospitalised with myocardial infarction and angina

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    Ischaemic heart disease persists as the leading global cause of death. Myocardial infarction (MI) accounts for a large proportion of death due to cardiovascular disease. Between 2007 and 2016, age-sex standardised mortality for MI in Scotland has fallen by 42.5% from 129 to 74 per 100,000 population โ€“ a trend also apparent in other countries. Despite improvements in survival, considerable disparities exist according to sexin terms of delivery of guideline-recommended treatments and outcomes following MI suggesting women may be disadvantaged. Use of high-sensitivity troponin assays with sex-specific thresholds increases the detection of MI in women. However, women are less likely to undergo percutaneous coronary revascularisation (PCI) and are more often subject to underutilisation of evidence-based secondary preventative pharmacotherapy. Differences in adoption of invasive management may, in part, be explained by a perception held by clinicians and patients that outcomes are worse for women receiving PCI, as well as differences in symptoms and baseline risk profile which may impact clinical decision-making. Adverse events post-MI, including cardiogenic shock, heart failure and death, remain more common in women than in men, most notably in those with ST-elevation myocardial infarction (STEMI). Whether sex remains an independent predictor of adverse events despite adjustments for the higher risk-profile of women, notably age, is less clear. We hypothesised that sex-related differences in demographics and comorbidity underpin disparities in management and outcomes of women and men hospitalised with MI or angina. We investigated this hypothesis by analysis of a contemporary secondary care electronic registry (e-Registry) using electronic patient records (EPRs) for patients admitted to a complex regional healthcare network.PostprintPeer reviewe

    Shifting attention in viewer- and object-based reference frames after unilateral brain injury

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    The aims of the present study were to investigate the respective roles that object- and viewer-based reference frames play in reorienting visual attention, and to assess their influence after unilateral brain injury. To do so, we studied 16 right hemisphere injured (RHI) and 13 left hemisphere injured (LHI) patients. We used a cueing design that manipulates the location of cues and targets relative to a display comprised of two rectangles (i.e., objects). Unlike previous studies with patients, we presented all cues at midline rather than in the left or right visual fields. Thus, in the critical conditions in which targets were presented laterally, reorienting of attention was always from a midline cue. Performance was measured for lateralized target detection as a function of viewer-based (contra- and ipsilesional sides) and object-based (requiring reorienting within or between objects) reference frames. As expected, contralesional detection was slower than ipsilesional detection for the patients. More importantly, objects influenced target detection differently in the contralesional and ipsilesional fields. Contralesionally, reorienting to a target within the cued object took longer than reorienting to a target in the same location but in the uncued object. This finding is consistent with object-based neglect. Ipsilesionally, the means were in the opposite direction. Furthermore, no significant difference was found in object-based influences between the patient groups (RHI vs. LHI). These findings are discussed in the context of reference frames used in reorienting attention for target detection

    Matched sizes of activating and inhibitory receptor/ligand pairs are required for optimal signal integration by human Natural Killer cells

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    It has been suggested that receptor-ligand complexes segregate or co-localise within immune synapses according to their size, and this is important for receptor signaling. Here, we set out to test the importance of receptor-ligand complex dimensions for immune surveillance of target cells by human Natural Killer (NK) cells. NK cell activation is regulated by integrating signals from activating receptors, such as NKG2D, and inhibitory receptors, such as KIR2DL1. Elongating the NKG2D ligand MICA reduced its ability to trigger NK cell activation. Conversely, elongation of KIR2DL1 ligand HLA-C reduced its ability to inhibit NK cells. Whereas normal-sized HLA-C was most effective at inhibiting activation by normal-length MICA, only elongated HLA-C could inhibit activation by elongated MICA. Moreover, HLA-C and MICA that were matched in size co-localised, whereas HLA-C and MICA that were different in size were segregated. These results demonstrate that receptor-ligand dimensions are important in NK cell recognition, and suggest that optimal integration of activating and inhibitory receptor signals requires the receptor-ligand complexes to have similar dimensions

    Environmental heterogeneity promotes individual specialisation in habitat selection in a widely distributed seabird

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    1. Individual specialisations in behaviour are predicted to arise where divergence benefits fitness. Such specialisations are more likely in heterogeneous environments where there is both greater ecological opportunity and competition-driven frequency dependent selection. 2. Such an effect could explain observed differences in rates of individual specialisation in habitat selection, as it offers individuals an opportunity to select for habitat types that maximise resource gain while minimising competition; however, this mechanism has not been tested before. 3. Here, we use habitat selection functions to quantify individual specialisations while foraging by black-legged kittiwakes Rissa tridactyla, a marine top predator, at 15 colonies around the United Kingdom and Ireland, along a gradient of environmental heterogeneity. 4. We find support for the hypothesis that individual specialisations in habitat selection while foraging are more prevalent in heterogeneous environments. This trend was significant across multiple dynamic habitat variables that change over short time-scales and did not arise through site fidelity, which highlights the importance of environmental processes in facilitating behavioural adaptation by predators. 5. Individual differences may drive evolutionary processes, and therefore these results suggest that there is broad scope for the degree of environmental heterogeneity to determine current and future population, species and community dynamics
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