A Phantom Menace? Cosmological consequences of a dark energy component with super-negative equation of state

It is extraordinary that a number of observations indicate that we live in a spatially flat, low matter density Universe, which is currently undergoing a period of accelerating expansion. The effort to explain this current state has focused attention on cosmological models in which the dominant component of the cosmic energy density has negative pressure, with an equation of state $w \ge -1$. Remarking that most observations are consistent with models right up to the $w=-1$ or cosmological constant ($\Lambda$) limit, it is natural to ask what lies on the other side, at $w<-1$. In this regard, we construct a toy model of a ``phantom'' energy component which possesses an equation of state $w<-1$. Such a component is found to be compatible with most classical tests of cosmology based on current data, including the recent type 1a SNe data as well as the cosmic microwave background anisotropy and mass power spectrum. If the future observations continue to allow $w<-1$, then barring unanticipated systematic effects, the dominant component of the cosmic energy density may be stranger than anything expected.Comment: update of original version, includes new material, matches version appearing in Phys. Lett. B, (17 pages, 7 eps figures

The formation of professional identity in medical students: considerations for educators

&lt;b&gt;Context&lt;/b&gt; Medical education is about more than acquiring an appropriate level of knowledge and developing relevant skills. To practice medicine students need to develop a professional identity – ways of being and relating in professional contexts.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Objectives&lt;/b&gt; This article conceptualises the processes underlying the formation and maintenance of medical students’ professional identity drawing on concepts from social psychology.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Implications&lt;/b&gt; A multi-dimensional model of identity and identity formation, along with the concepts of identity capital and multiple identities, are presented. The implications for educators are discussed.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Conclusions&lt;/b&gt; Identity formation is mainly social and relational in nature. Educators, and the wider medical society, need to utilise and maximise the opportunities that exist in the various relational settings students experience. Education in its broadest sense is about the transformation of the self into new ways of thinking and relating. Helping students form, and successfully integrate their professional selves into their multiple identities, is a fundamental of medical education

Covariance of dark energy parameters and sound speed constraints from large HI surveys

An interesting probe of the nature of dark energy is the measure of its sound speed, $c_s$. We review the significance for constraining sound speed models of dark energy using large neutral hydrogen (HI) surveys with the Square Kilometre Array (SKA). Our analysis considers the effect on the sound speed measurement that arises from the covariance of $c_s$ with the dark energy density, \Omega_\LLambda, and a time-varying equation of state, $w(a)=w_0+(1-a)w_a$. We find that the approximate degeneracy between dark energy parameters that arises in power spectrum observations is lifted through redshift tomography of the HI-galaxy angular power spectrum, resulting in sound speed constraints that are not severely degraded. The cross-correlation of the galaxy and the integrated Sachs-Wolfe (ISW) effect spectra contributes approximately 10 percent of the information that is needed to distinguish variations in the dark energy parameters, and most of the discriminating signal comes from the galaxy auto-correlation spectrum. We also find that the sound speed constraints are weakly sensitive to the HI bias model. These constraints do not improve substantially for a significantly deeper HI survey since most of the clustering sensitivity to sound speed variations arises from z \lsim 1.5. A detection of models with sound speeds close to zero, c_s \lsim 0.01, is possible for dark energy models with w\gsim -0.9.Comment: submitted to MNRA

In vivo activity of the dual SYK/FLT3 inhibitor TAK-659 against pediatric acute lymphoblastic leukemia xenografts

Background: While children with acute lymphoblastic leukemia (ALL) experience close to a 90% likelihood of cure, the outcome for certain high-risk pediatric ALL subtypes remains dismal. Spleen tyrosine kinase (SYK) is a prominent cytosolic nonreceptor tyrosine kinase in pediatric B-lineage ALL (B-ALL). Activating mutations or overexpression of Fms-related receptor tyrosine kinase 3 (FLT3) are associated with poor outcome in hematological malignancies. TAK-659 (mivavotinib) is a dual SYK/FLT3 reversible inhibitor, which has been clinically evaluated in several other hematological malignancies. Here, we investigate the in vivo efficacy of TAK-659 against pediatric ALL patient-derived xenografts (PDXs). Methods: SYK and FLT3 mRNA expression was quantified by RNA-seq. PDX engraftment and drug responses in NSG mice were evaluated by enumerating the proportion of human CD45+ cells (%huCD45+) in the peripheral blood. TAK-659 was administered per oral at 60 mg/kg daily for 21 days. Events were defined as %huCD45+ ≥ 25%. In addition, mice were humanely killed to assess leukemia infiltration in the spleen and bone marrow (BM). Drug efficacy was assessed by event-free survival and stringent objective response measures. Results: FLT3 and SYK mRNA expression was significantly higher in B-lineage compared with T-lineage PDXs. TAK-659 was well tolerated and significantly prolonged the time to event in six out of eight PDXs tested. However, only one PDX achieved an objective response. The minimum mean %huCD45+ was significantly reduced in five out of eight PDXs in TAK-659-treated mice compared with vehicle controls. Conclusions: TAK-659 exhibited low to moderate single-agent in vivo activity against pediatric ALL PDXs representative of diverse subtypes

Hydroxymethylglutaryl-CoA reductase inhibition with simvastatin in acute lung injury to reduce pulmonary dysfunction (HARP-2) trial : study protocol for a randomized controlled trial

Acute lung injury (ALI) is a common devastating clinical syndrome characterized by life-threatening respiratory failure requiring mechanical ventilation and multiple organ failure. There are in vitro, animal studies and pre-clinical data suggesting that statins may be beneficial in ALI. The Hydroxymethylglutaryl-CoA reductase inhibition with simvastatin in Acute lung injury to Reduce Pulmonary dysfunction (HARP-2) trial is a multicenter, prospective, randomized, allocation concealed, double-blind, placebo-controlled clinical trial which aims to test the hypothesis that treatment with simvastatin will improve clinical outcomes in patients with ALI

A Wide Field Survey of Satellite Galaxies around the Spiral Galaxy M106

We present a wide field survey of satellite galaxies in M106 (NGC 4258) covering a 1.7\degr \times 2\degr field around M106 using Canada-France-Hawaii Telescope/MegaCam. We find 16 satellite galaxy candidates of M106. Eight of these galaxies are found to be dwarf galaxies that are much smaller and fainter than the remaining galaxies. Four of these galaxies are new findings. Surface brightness profiles of 15 out of 16 satellite galaxies can be represented well by an exponential disk profile with varying scale length. We derive the surface number density distribution of these satellite galaxies. The central number density profile (d $<100$ kpc) is well fitted by a power-law with a power index of $-2.1\pm0.5$, similar to the expected power index of isothermal distribution. The luminosity function of these satellites is represented well by the Schechter function with a faint end slope of $-1.19^{+0.03}_{-0.06}$. Integrated photometric properties (total luminosity, total colour, and disk scale length) and the spatial distribution of these satellite galaxies are found to be roughly similar to those of the Milky Way and M31.Comment: Accepted by MNRA

Immunomodulation by imiquimod in patients with high-risk primary melanoma.

Imiquimod is a synthetic Toll-like receptor 7 (TLR7) agonist approved for the topical treatment of actinic keratoses, superficial basal cell carcinoma, and genital warts. Imiquimod leads to an 80-100% cure rate of lentigo maligna; however, studies of invasive melanoma are lacking. We conducted a pilot study to characterize the local, regional, and systemic immune responses induced by imiquimod in patients with high-risk melanoma. After treatment of the primary melanoma biopsy site with placebo or imiquimod cream, we measured immune responses in the treated skin, sentinel lymph nodes (SLNs), and peripheral blood. Treatment of primary melanomas with 5% imiquimod cream was associated with an increase in both CD4+ and CD8+ T cells in the skin, and CD4+ T cells in the SLN. Most of the CD8+ T cells in the skin were CD25 negative. We could not detect any increases in CD8+ T cells specifically recognizing HLA-A(*)0201-restricted melanoma epitopes in the peripheral blood. The findings from this small pilot study demonstrate that topical imiquimod treatment results in enhanced local and regional T-cell numbers in both the skin and SLN. Further research into TLR7 immunomodulating pathways as a basis for effective immunotherapy against melanoma in conjunction with surgery is warranted

Correlation functions quantify super-resolution images and estimate apparent clustering due to over-counting

We present an analytical method to quantify clustering in super-resolution localization images of static surfaces in two dimensions. The method also describes how over-counting of labeled molecules contributes to apparent self-clustering and how the effective lateral resolution of an image can be determined. This treatment applies to clustering of proteins and lipids in membranes, where there is significant interest in using super-resolution localization techniques to probe membrane heterogeneity. When images are quantified using pair correlation functions, the magnitude of apparent clustering due to over-counting will vary inversely with the surface density of labeled molecules and does not depend on the number of times an average molecule is counted. Over-counting does not yield apparent co-clustering in double label experiments when pair cross-correlation functions are measured. We apply our analytical method to quantify the distribution of the IgE receptor (Fc{\epsilon}RI) on the plasma membranes of chemically fixed RBL-2H3 mast cells from images acquired using stochastic optical reconstruction microscopy (STORM) and scanning electron microscopy (SEM). We find that apparent clustering of labeled IgE bound to Fc{\epsilon}RI detected with both methods arises from over-counting of individual complexes. Thus our results indicate that these receptors are randomly distributed within the resolution and sensitivity limits of these experiments.Comment: 22 pages, 5 figure