Lattice calculation of 1/p21/p^2 corrections to αs\alpha_s and of ΛQCD\Lambda_{\rm {QCD}} in the MOM~\widetilde{MOM} scheme

We report on very strong evidence of the occurrence of power terms in \as(p), the QCD running coupling constant in the $\widetilde{MOM}$ scheme, by analyzing non-perturbative measurements from the lattice three-gluon vertex between 2.0 and 10.0 GeV at zero flavor. While putting forward the caveat that this definition of the coupling is a gauge dependent one, the general relevance of such an occurrence is discussed. We fit $\Lambda_{\bar{\rm MS}}^{(n_f=0)}= 237 \pm 3 ^{+ 0}_{-10}$ MeV in perfect agreement with the result obtained by the ALPHA group with a totally different method. The power correction to \as(p) is fitted to $(0.63\pm 0.03 ^{+ 0.0}_{- 0.13}) {\rm GeV}^2/p^2$.Comment: 21 pages, 3 figure

A combined in vitro/in silico approach to identifying off-target receptor toxicity

Many xenobiotics can bind to off-target receptors and cause toxicity via the dysregulation of downstream transcription factors. Identification of subsequent off-target toxicity in these chemicals has often required extensive chemical testing in animal models. An alternative, integrated in vitro/in silico approach for predicting toxic off-target functional responses is presented to refine in vitro receptor identification and reduce the burden on in vivo testing. As part of the methodology, mathematical modelling is used to mechanistically describe processes that regulate transcriptional activity following receptor-ligand binding informed by transcription factor signalling assays. Critical reactions in the signalling cascade are identified to highlight potential perturbation points in the biochemical network that can guide and optimise additional in vitro testing. A physiologically-based pharmacokinetic model provides information on the timing and localisation of different levels of receptor activation informing whole-body toxic potential resulting from off-target binding

Catastrophic Femoral Head-Stem Trunnion Dissociation Secondary to Corrosion.

BACKGROUND: Modular femoral heads provide procedural enhancement by allowing accurate restoration of hip offset and limb-length equalization. However, corrosion may lead to adverse local tissue reactions. Severe trunnion corrosion can also lead to femoral head dissociation and catastrophic implant failure following primary total hip arthroplasty. METHODS: We describe 5 cases, from our institution, in which the femoral head became dissociated from the femoral stem trunnion secondary to severe corrosion. Possible causes are evaluated. RESULTS: Demographic commonalities among the 5 patients included a body mass index (BMI) of ≥30 kg/m(2) and male sex. All femoral heads were made of cobalt-chromium alloy and were larger-diameter implants (≥36 mm). Four of the 5 patients had a femoral head that increased the neck length above the default on a so-called standard head and 3 of the 5 had a stem with a 127° neck-shaft angle. CONCLUSIONS: Although dissociation of the femoral head from the femoral trunnion following total hip arthroplasty is exceedingly rare, the prevalence may increase with longer follow-up. The dissociation is likely related to multiple factors, including a BMI of ≥30 kg/m(2), male sex, and corrosion resulting from the use of a larger metal head with a neck length of greater than the default and a stem with high offset. It is critical that surgeons be able to recognize this mode of implant failure and appropriately prepare to remove the femoral component during revision surgery. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence

Recurrent takotsubo cardiomyopathy in the setting of transient neurological symptoms: a case report

<p>Abstract</p> <p>Introduction</p> <p>First described in Japan, takotsubo cardiomyopathy is increasingly becoming recognized worldwide as a cause of sudden and reversible diminished left ventricular function characterized by left apical ballooning and hyperkinesis of the basal segments, often with symptoms mimicking a myocardial infarction. Associated with physical or emotional stress, its exact pathogenesis has not been established, though evidence supports a neurohumoral etiology. Additionally, recurrence of this condition is rare. In this report, we present a rare case of recurrent takotsubo cardiomyopathy in a post-menopausal woman who presented with transient neurological complaints on both occasions.</p> <p>Case presentation</p> <p>We present a rare case of a 76-year-old Caucasian woman with no history of congestive heart failure who presented to our emergency department twice with transient neurological complaints. On the first occasion, she was found to have transient aphasia which resolved within 24 hours, yet during that period she also developed symptoms of congestive heart failure and was noted to have a new, significantly depressed ejection fraction with apical akinesis and possible apical thrombus. One month after her presentation a repeat echocardiogram revealed complete resolution of all wall motion abnormalities and a return to baseline status. Seven months later she presented with ataxia, was diagnosed with vertebrobasilar insufficiency, and again developed symptoms and echocardiography findings similar to those of her first presentation. Once again, at her one-month follow-up examination, all wall motion abnormalities had completely resolved and her ejection fraction had returned to normal.</p> <p>Conclusion</p> <p>Though the exact etiology of takotsubo cardiomyopathy is unclear, a neurohumoral mechanism has been proposed. Recurrence of this disorder is rare, though it has been reported in patients with structural brain abnormalities. This report is the first to describe recurrent takotsubo cardiomyopathy in a patient with transient neurological symptoms. In our patient, as expected in patients with this condition, complete resolution of all left ventricular abnormalities occurred within a short period of time. It is important for clinicians to be aware of this increasingly recognized syndrome, including its association with recurrence, especially in the clinical setting of neurologic dysfunction.</p

Exact equations for SIR epidemics on tree graphs

We consider Markovian susceptible-infectious-removed (SIR) dynamics on time-invariant weighted contact networks where the infection and removal processes are Poisson and where network links may be directed or undirected. We prove that a particular pair-based moment closure representation generates the expected infectious time series for networks with no cycles in the underlying graph. Moreover, this “deterministic” representation of the expected behaviour of a complex heterogeneous and finite Markovian system is straightforward to evaluate numerically

Edge-Based Compartmental Modeling for Infectious Disease Spread Part III: Disease and Population Structure

We consider the edge-based compartmental models for infectious disease spread introduced in Part I. These models allow us to consider standard SIR diseases spreading in random populations. In this paper we show how to handle deviations of the disease or population from the simplistic assumptions of Part I. We allow the population to have structure due to effects such as demographic detail or multiple types of risk behavior the disease to have more complicated natural history. We introduce these modifications in the static network context, though it is straightforward to incorporate them into dynamic networks. We also consider serosorting, which requires using the dynamic network models. The basic methods we use to derive these generalizations are widely applicable, and so it is straightforward to introduce many other generalizations not considered here

Three agonist antibodies in combination with high-dose IL-2 eradicate orthotopic kidney cancer in mice

<p>Abstract</p> <p>Background</p> <p>Combination immunotherapies can be effective against subcutaneous tumors in mice but the effect against orthotopic malignant disease is less well characterized. In particular, a combination of three agonist antibodies, termed Tri-mAb, consisting of anti-DR5, anti-CD40 and anti-CD137 has previously been demonstrated to eradicate a large proportion of subcutaneous renal cell carcinoma (Renca) tumors (75% long-term survival), but the effect against orthotopic disease is not known.</p> <p>Purpose</p> <p>To determine the relative response of orthotopic tumors, we inoculated Renca into the kidney followed by treatment with Tri-mAb.</p> <p>Results</p> <p>We found that orthotopic tumors responded much less to treatment (~13% survival), but a significant improvement in survival was achieved through the addition of IL-2 to the treatment regimen (55% survival). All three agonist antibodies and high dose IL-2, 100,000 IU for up to six doses, were required. CD8⁺T cells were also required for optimal anti-tumor responses. Coadministration of IL-2 led to enhanced T cell activity as demonstrated by an increased frequency of IFN-gamma-producing T cells in tumor-draining lymph nodes, which may have contributed to the observed improvement of therapy against kidney tumors.</p> <p>Implications</p> <p>Responses of subcutaneous tumors to immunotherapy do not necessarily reflect how orthotopic tumors respond. The use of combination immunotherapy stimulating multiple facets of immunity and including cytokine support for T cells can induce effective anti-tumor responses against orthotopic and metastatic tumors.</p