Introduction to Modified Gravity and Gravitational Alternative for Dark Energy

We review various modified gravities considered as gravitational alternative for dark energy. Specifically, we consider the versions of $f(R)$, $f(G)$ or $f(R,G)$ gravity, model with non-linear gravitational coupling or string-inspired model with Gauss-Bonnet-dilaton coupling in the late universe where they lead to cosmic speed-up. It is shown that some of such theories may pass the Solar System tests. On the same time, it is demonstrated that they have quite rich cosmological structure: they may naturally describe the effective (cosmological constant, quintessence or phantom) late-time era with a possible transition from decceleration to acceleration thanks to gravitational terms which increase with scalar curvature decrease. The possibility to explain the coincidence problem as the manifestation of the universe expansion in such models is mentioned. The late (phantom or quintessence) universe filled with dark fluid with inhomogeneous equation of state (where inhomogeneous terms are originated from the modified gravity) is also described.Comment: LaTeX file, 21 pages, references are added, lectures for 42 Karpacz Winter School on Theor Physic

Molecular imaging of inflammation - Current and emerging technologies for diagnosis and treatment

Inflammation is a key factor in multiple diseases including primary immune-mediated inflammatory diseases e.g. rheumatoid arthritis but also, less obviously, in many other common conditions, e.g. cardiovascular disease and diabetes. Together, chronic inflammatory diseases contribute to the majority of global morbidity and mortality. However, our understanding of the underlying processes by which the immune response is activated and sustained is limited by a lack of cellular and molecular information obtained in situ. Molecular imaging is the visualization, detection and quantification of molecules in the body. The ability to reveal information on inflammatory biomarkers, pathways and cells can improve disease diagnosis, guide and monitor therapeutic intervention and identify new targets for research. The optimum molecular imaging modality will possess high sensitivity and high resolution and be capable of non-invasive quantitative imaging of multiple disease biomarkers while maintaining an acceptable safety profile. The mainstays of current clinical imaging are computed tomography (CT), magnetic resonance imaging (MRI), ultrasound (US) and nuclear imaging such as positron emission tomography (PET). However, none of these have yet progressed to routine clinical use in the molecular imaging of inflammation, therefore new approaches are required to meet this goal. This review sets out the respective merits and limitations of both established and emerging imaging modalities as clinically useful molecular imaging tools in addition to potential theranostic applications

Stringy Stability of Charged Dilaton Black Holes with Flat Event Horizon

Electrically charged black holes with flat event horizon in anti-de Sitter space have received much attention due to various applications in Anti-de Sitter/Conformal Field Theory (AdS/CFT) correspondence, from modeling the behavior of quark-gluon plasma to superconductor. Crucial to the physics on the dual field theory is the fact that when embedded in string theory, black holes in the bulk may become vulnerable to instability caused by brane pair-production. Since dilaton arises naturally in the context of string theory, we study the effect of coupling dilaton to Maxwell field on the stability of flat charged AdS black holes. In particular, we study the stability of Gao-Zhang black holes, which are locally asymptotically anti-de Sitter. We find that for dilaton coupling parameter $\alpha$ > 1, flat black holes are stable against brane pair production, however for 0 < $\alpha$ < 1, the black holes eventually become unstable as the amount of electrical charges is increased. Such instability however, behaves somewhat differently from that of flat Reissner-Nordstr\"om black holes. In addition, we prove that the Seiberg-Witten action of charged dilaton AdS black hole of Gao-Zhang type with flat event horizon (at least in 5-dimension) is always logarithmically divergent at infinity for finite values of $\alpha$, and is finite and positive in the case $\alpha$ tends to infinity . We also comment on the robustness of our result for other charged dilaton black holes that are not of Gao-Zhang type.Comment: Fixed some confusions regarding whether part of the discussions concern electrically charged hole or magnetically charged one. No changes to the result

Metatarsophalangeal joint pain in psoriatic arthritis: a cross-sectional study

Methods. Thirty-four consecutive patients with PsA (mean age 45.3 years, 65% female, mean disease duration 9.9 years) and 22 control participants (mean age 37.9 years, 64% female) underwent clinical and US examination to determine the presence of pain, swelling, synovitis, erosions, effusions and submetatarsal bursae at the MTP joints. Mean barefoot peak plantar pressures were determined at each MTP joint. Levels of pain, US-determined pathology and peak pressures were compared between groups. Binary logistic regression was used to identify demographic, clinical examination-derived, US-derived and plantar pressure predictors of pain at the MTP joints in the PsA group. Results. The presence of pain, deformity, synovitis, erosions (P &amp;lt; 0.001) and submetatarsal bursae and peak plantar pressure at MTP 3 (P &amp;lt; 0.05) were significantly higher in the PsA group. MTP joint pain in PsA was independently predicted by high BMI, female gender and the presence of joint subluxation, synovitis and erosion. Conclusion. These results suggest local inflammatory and structural factors, together with systemic factors (gender, BMI), are predominantly responsible for painful MTP joints in PsA, with no clear role for plantar pressure characteristics

Localized Nasopharyngeal Amyloidosis

A mass in the nasopharynx often implies a malignancy in adults, particularly in the endemic areas of Epstein-Barr virus-associated undifferentiated carcinoma. We report an 86-year-old male patient who presented to our rhinologic outpatient department with postnasal drip for several years, with no other associated nasal symptoms. Physical examination with nasal endoscopy found a prominent bulge in the nasopharynx. Pathological examination of the biopsied specimens identified features consistent with amyloidosis. Magnetic resonance imaging demonstrated an enhanced soft-tissue mass localized to the nasopharyngeal region. We excluded the possibility of a partial representation of a potential systemic amyloidosis. Regular follow-up including nasal endoscopy was undertaken. Over 3 years of observation, the disease process remained silent. Here, the clinical presentation, diagnosis and treatment options of this rare entity are discussed

Crossing of the w=-1 Barrier in Two-Fluid Viscous Modified Gravity

Singularities in the dark energy late universe are discussed, under the assumption that the Lagrangian contains the Einstein term R plus a modified gravity term of the form R^\alpha, where \alpha is a constant. It is found, similarly as in the case of pure Einstein gravity [I. Brevik and O. Gorbunova, Gen. Rel. Grav. 37 (2005), 2039], that the fluid can pass from the quintessence region (w>-1) into the phantom region (w<-1) as a consequence of a bulk viscosity varying with time. It becomes necessary now, however, to allow for a two-fluid model, since the viscosities for the two components vary differently with time. No scalar fields are needed for the description of the passage through the phantom barrier.Comment: 16 pages latex, no figure

Survey of highly non-Keplerian orbits with low-thrust propulsion

Celestial mechanics has traditionally been concerned with orbital motion under the action of a conservative gravitational potential. In particular, the inverse square gravitational force due to the potential of a uniform, spherical mass leads to a family of conic section orbits, as determined by Isaac Newton, who showed that Kepler‟s laws were derivable from his theory of gravitation. While orbital motion under the action of a conservative gravitational potential leads to an array of problems with often complex and interesting solutions, the addition of non-conservative forces offers new avenues of investigation. In particular, non-conservative forces lead to a rich diversity of problems associated with the existence, stability and control of families of highly non-Keplerian orbits generated by a gravitational potential and a non-conservative force. Highly non-Keplerian orbits can potentially have a broad range of practical applications across a number of different disciplines. This review aims to summarize the combined wealth of literature concerned with the dynamics, stability and control of highly non-Keplerian orbits for various low thrust propulsion devices, and to demonstrate some of these potential applications

Deletion of the Androgen Receptor in Adipose Tissue in Male Mice Elevates Retinol Binding Protein 4 and Reveals Independent Effects on Visceral Fat Mass and on Glucose Homeostasis

Testosterone deficiency is epidemic in obese ageing males with type 2 diabetes, but the direction of causality remains unclear. Testosterone-deficient males and global androgen receptor (AR) knockout mice are insulin resistant with increased fat, but it is unclear whether AR signaling in adipose tissue mediates body fat redistribution and alters glucose homoeostasis. To investigate this, mice with selective knockdown of AR in adipocytes (fARKO) were generated. Male fARKO mice on normal diet had reduced perigonadal fat but were hyperinsulinemic and by age 12 months, were insulin deficient in the absence of obesity. On high-fat diet, fARKO mice had impaired compensatory insulin secretion and hyperglycemia, with increased susceptibility to visceral obesity. Adipokine screening in fARKO mice revealed a selective increase in plasma and intra-adipose retinol binding protein 4 (RBP4) that preceded obesity. AR activation in murine 3T3 adipocytes downregulated RBP4 mRNA. We conclude that AR signaling in adipocytes not only protects against high-fat diet–induced visceral obesity but also regulates insulin action and glucose homeostasis, independently of adiposity. Androgen deficiency in adipocytes in mice resembles human type 2 diabetes, with early insulin resistance and evolving insulin deficiency

Effective growth of matter density fluctuations in the running LCDM and LXCDM models

We investigate the matter density fluctuations \delta\rho/\rho for two dark energy (DE) models in the literature in which the cosmological term \Lambda is a running parameter. In the first model, the running LCDM model, matter and DE exchange energy, whereas in the second model, the LXCDM model, the total DE and matter components are conserved separately. The LXCDM model was proposed as an interesting solution to the cosmic coincidence problem. It includes an extra dynamical component, the "cosmon" X, which interacts with the running \Lambda, but not with matter. In our analysis we make use of the current value of the linear bias parameter, b^2(0)= P_{GG}/P_{MM}, where P_{MM} ~ (\delta\rho/\rho)^2 is the present matter power spectrum and P_{GG} is the galaxy fluctuation power spectrum. The former can be computed within a given model, and the latter is found from the observed LSS data (at small z) obtained by the 2dF galaxy redshift survey. It is found that b^2(0)=1 within a 10% accuracy for the standard LCDM model. Adopting this limit for any DE model and using a method based on the effective equation of state for the DE, we can set a limit on the growth of matter density perturbations for the running LCDM model, the solution of which is known. This provides a good test of the procedure, which we then apply to the LXCDM model in order to determine the physical region of parameter space, compatible with the LSS data. In this region, the LXCDM model is consistent with known observations and provides at the same time a viable solution to the cosmic coincidence problem.Comment: LaTeX, 38 pages, 8 figures. Version accepted in JCA

Long-term safety of secukinumab in patients with moderate-to-severe plaque psoriasis, psoriatic arthritis, and ankylosing spondylitis: integrated pooled clinical trial and post-marketing surveillance data.

BACKGROUND: Secukinumab, a fully human immunoglobulin G1-kappa monoclonal antibody that directly inhibits interleukin (IL)-17A, has been shown to have robust efficacy in the treatment of moderate-to-severe psoriasis (PsO), psoriatic arthritis (PsA), and ankylosing spondylitis (AS) demonstrating a rapid onset of action and sustained long-term clinical responses with a consistently favorable safety profile in multiple Phase 2 and 3 trials. Here, we report longer-term pooled safety and tolerability data for secukinumab across three indications (up to 5 years of treatment in PsO and PsA; up to 4 years in AS). METHODS: The integrated clinical trial safety dataset included data pooled from 21 randomized controlled clinical trials of secukinumab 300 or 150 or 75 mg in PsO (14 Phase 3 trials and 1 Phase 4 trial), PsA (3 Phase 3 trials), and AS (3 Phase 3 trials), along with post-marketing safety surveillance data with a cut-off date of June 25, 2017. Adverse events (AEs) were reported as exposure-adjusted incident rates (EAIRs) per 100 patient-years. Analyses included all patients who received ≥ 1 dose of secukinumab. RESULTS: A total of 5181, 1380, and 794 patients from PsO, PsA, and AS clinical trials representing secukinumab exposures of 10,416.9, 3866.9, and 1943.1 patient-years, respectively, and post-marketing data from patients with a cumulative exposure to secukinumab of ~ 96,054 patient-years were included in the analysis. The most frequent AE was upper respiratory tract infection. EAIRs across PsO, PsA, and AS indications were generally low for serious infections (1.4, 1.9, and 1.2, respectively), Candida infections (2.2, 1.5, and 0.7, respectively), inflammatory bowel disease (0.01, 0.05, and 0.1, respectively), and major adverse cardiac events (0.3, 0.4, and 0.6, respectively). No cases of tuberculosis reactivation were reported. The incidence of treatment-emergent anti-drug antibodies was low with secukinumab across all studies, with no discernible loss of efficacy, unexpected alterations in pharmacokinetics, or association with immunogenicity-related AEs. CONCLUSIONS: Secukinumab demonstrated a favorable safety profile over long-term treatment in patients with PsO, PsA, and AS. This comprehensive assessment demonstrated that the safety profile of secukinumab was consistent with previous reports in patients with PsO, PsA, and AS, supporting its long-term use in these chronic conditions