Phenomenology and Cosmology of an Electroweak Pseudo-Dilaton and Electroweak Baryons

In many strongly-interacting models of electroweak symmetry breaking the lowest-lying observable particle is a pseudo-Goldstone boson of approximate scale symmetry, the pseudo-dilaton. Its interactions with Standard Model particles can be described using a low-energy effective nonlinear chiral Lagrangian supplemented by terms that restore approximate scale symmetry, yielding couplings of the pseudo-dilaton that differ from those of a Standard Model Higgs boson by fixed factors. We review the experimental constraints on such a pseudo-dilaton in light of new data from the LHC and elsewhere. The effective nonlinear chiral Lagrangian has Skyrmion solutions that may be identified with the `electroweak baryons' of the underlying strongly-interacting theory, whose nature may be revealed by the properties of the Skyrmions. We discuss the finite-temperature electroweak phase transition in the low-energy effective theory, finding that the possibility of a first-order electroweak phase transition is resurrected. We discuss the evolution of the Universe during this transition and derive an order-of-magnitude lower limit on the abundance of electroweak baryons in the absence of a cosmological asymmetry, which suggests that such an asymmetry would be necessary if the electroweak baryons are to provide the cosmological density of dark matter. We revisit estimates of the corresponding spin-independent dark matter scattering cross section, with a view to direct detection experiments.Comment: 34 pages, 4 figures, additional references adde

A review of elliptical and disc galaxy structure, and modern scaling laws

A century ago, in 1911 and 1913, Plummer and then Reynolds introduced their models to describe the radial distribution of stars in `nebulae'. This article reviews the progress since then, providing both an historical perspective and a contemporary review of the stellar structure of bulges, discs and elliptical galaxies. The quantification of galaxy nuclei, such as central mass deficits and excess nuclear light, plus the structure of dark matter halos and cD galaxy envelopes, are discussed. Issues pertaining to spiral galaxies including dust, bulge-to-disc ratios, bulgeless galaxies, bars and the identification of pseudobulges are also reviewed. An array of modern scaling relations involving sizes, luminosities, surface brightnesses and stellar concentrations are presented, many of which are shown to be curved. These 'redshift zero' relations not only quantify the behavior and nature of galaxies in the Universe today, but are the modern benchmark for evolutionary studies of galaxies, whether based on observations, N-body-simulations or semi-analytical modelling. For example, it is shown that some of the recently discovered compact elliptical galaxies at 1.5 < z < 2.5 may be the bulges of modern disc galaxies.Comment: Condensed version (due to Contract) of an invited review article to appear in "Planets, Stars and Stellar Systems"(www.springer.com/astronomy/book/978-90-481-8818-5). 500+ references incl. many somewhat forgotten, pioneer papers. Original submission to Springer: 07-June-201

Pharmacokinetic-Pharmacodynamic Modeling in Pediatric Drug Development, and the Importance of Standardized Scaling of Clearance.

Pharmacokinetic/pharmacodynamic (PKPD) modeling is important in the design and conduct of clinical pharmacology research in children. During drug development, PKPD modeling and simulation should underpin rational trial design and facilitate extrapolation to investigate efficacy and safety. The application of PKPD modeling to optimize dosing recommendations and therapeutic drug monitoring is also increasing, and PKPD model-based dose individualization will become a core feature of personalized medicine. Following extensive progress on pediatric PK modeling, a greater emphasis now needs to be placed on PD modeling to understand age-related changes in drug effects. This paper discusses the principles of PKPD modeling in the context of pediatric drug development, summarizing how important PK parameters, such as clearance (CL), are scaled with size and age, and highlights a standardized method for CL scaling in children. One standard scaling method would facilitate comparison of PK parameters across multiple studies, thus increasing the utility of existing PK models and facilitating optimal design of new studies

Use of Intravenous Peramivir for Treatment of Severe Influenza A(H1N1)pdm09

Oral antiviral agents to treat influenza are challenging to administer in the intensive care unit (ICU). We describe 57 critically ill patients treated with the investigational intravenous neuraminidase inhibitor drug peramivir for influenza A (H1N1)pdm09 [pH1N1]. Most received late peramivir treatment following clinical deterioration in the ICU on enterically-administered oseltamivir therapy. The median age was 40 years (range 5 months-81 years). Common clinical complications included pneumonia or acute respiratory distress syndrome requiring mechanical ventilation (54; 95%), sepsis requiring vasopressor support (34/53; 64%), acute renal failure requiring hemodialysis (19/53; 36%) and secondary bacterial infection (14; 25%). Over half (29; 51%) died. When comparing the 57 peramivir-treated cases with 1627 critically ill cases who did not receive peramivir, peramivir recipients were more likely to be diagnosed with pneumonia/acute respiratory distress syndrome (p = 0.0002) or sepsis (p = <0.0001), require mechanical ventilation (p = <0.0001) or die (p = <0.0001). The high mortality could be due to the pre-existing clinical severity of cases prior to request for peramivir, but also raises questions about peramivir safety and effectiveness in hospitalized and critically ill patients. The use of peramivir merits further study in randomized controlled trials, or by use of methods such as propensity scoring and matching, to assess clinical effectiveness and safety

Impacto da técnica de expiração lenta e prolongada na mecânica respiratória de lactentes sibilantes

OBJECTIVE: To evaluate changes in respiratory mechanics and tidal volume (V T) in wheezing infants in spontaneous ventilation after performing the technique known as the prolonged, slow expiratory (PSE) maneuver. METHODS: We included infants with a history of recurrent wheezing and who had had no exacerbations in the previous 15 days. For the assessment of the pulmonary function, the infants were sedated and placed in the supine position, and a face mask was used and connected to a pneumotachograph. The variables of tidal breathing (V T and RR) as well as those of respiratory mechanics-respiratory system compliance (Crs), respiratory system resistance (Rrs), and the respiratory system time constant (prs)-were measured before and after three consecutive PSE maneuvers. RESULTS: We evaluated 18 infants. The mean age was 32 ± 11 weeks. After PSE, there was a significant increase in V T (79.3 ± 15.6 mL vs. 85.7 ± 17.2 mL; p = 0.009) and a significant decrease in RR (40.6 ± 6.9 breaths/min vs. 38.8 ± 0,9 breaths/min; p = 0.042). However, no significant differences were found in the variables of respiratory mechanics (Crs: 11.0 ± 3.1 mL/cmH2O vs. 11.3 ± 2.7 mL/cmH2O; Rrs: 29.9 ± 6.2 cmH2O mL-1 s-1 vs. 30.8 ± 7.1 cmH2O mL-1 s-1; and prs: 0.32 ± 0.11 s vs. 0.34 ±0.12 s; p > 0.05 for all). CONCLUSIONS: This respiratory therapy technique is able to induce significant changes in V T and RR in infants with recurrent wheezing, even in the absence of exacerbations. The fact that the variables related to respiratory mechanics remained unchanged indicates that the technique is safe to apply in this group of patients. Studies involving symptomatic infants are needed in order to quantify the functional effects of the technique.OBJETIVO: Avaliar as alterações da mecânica respiratória e do volume corrente (VC) em lactentes sibilantes em ventilação espontânea após a realização da técnica de expiração lenta e prolongada (ELPr). MÉTODOS: Foram incluídos no estudo lactentes com história de sibilância recorrente e sem exacerbações nos 15 dias anteriores. Para a avaliação da função pulmonar, os lactentes foram sedados e posicionados em decúbito dorsal com máscara facial acoplada a um pneumotacógrafo. As variáveis da respiração corrente - VC e FR - e da mecânica respiratória - complacência do sistema respiratório (Csr), resistência (Rsr) e constante de tempo (psr) - foram mensuradas antes e após a realização de três sequências consecutivas de ELPr. RESULTADOS: Foram avaliados 18 lactentes, com média de idade de 32 ± 11 semanas. Houve um aumento significante no VC após ELPr (79,3 ± 15,6 mL vs. 85,7 ± 17,2 mL; p = 0,009), assim como uma redução na FR (40,6 ± 6,9 ciclos/min vs. 38,8 ± 0,9 ciclos/min; p = 0,042). Entretanto, não houve alterações significantes nos valores da mecânica respiratória (Csr: 11,0 ± 3,1 mL/cmH2O vs. 11,3 ± 2,7 mL/cmH2O; Rsr: 29,9 ± 6,2 cmH2O mL-1 s-1 vs. 30,8 ± 7,1 cmH2O mL-1 s-1; e psr: 0,32 ± 0,11 s vs. 0,34 ± 0,12 s; p > 0,05 para todos). CONCLUSÕES: Essa técnica de fisioterapia respiratória é capaz de induzir alterações significativas no VC e na FR de lactentes com sibilância recorrente, mesmo na ausência de exacerbações. A manutenção das variáveis da mecânica respiratória indica que a técnica é segura para ser aplicada nesse grupo de pacientes. Estudos com lactentes sintomáticos são necessários para quantificar os efeitos funcionais da técnica.Universidade Nove de Julho Programa de Pós Graduação em Ciências da ReabilitaçãoUniversidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Departamento de PediatriaUniversidade Federal de São Paulo (UNIFESP) Escola Paulista de MedicinaHospital Israelita Albert Einstein Setor de Pediatria e NeonatologiaUNIFESP, EPM, Depto. de PediatriaUNIFESP, EPMSciEL

Oncoprotein HCCR-1 expression in breast cancer is well correlated with known breast cancer prognostic factors including the HER2 overexpression, p53 mutation, and ER/PR status

<p>Abstract</p> <p>Background</p> <p>Oncoprotein HCCR-1 functions as a negative regulator of the p53 and contributes breast tumorigenesis. The serum HCCR-1 assay is useful in diagnosing breast cancer and mice transgenic for HCCR developed breast cancers. But it is unknown how <it>HCCR-1 </it>contributes to human breast tumorigenesis.</p> <p>Methods</p> <p>Oncogene HCCR-1 expression levels were determined in normal breast tissues, breast cancer tissues and cancer cell lines. We examined whether HCCR-1 protein expression in breast cancer is related to different biological characteristics, including ER, PR, p53 genotype, and HER2 status in 104 primary breast cancer tissues using immunohistochemical analyses.</p> <p>Results</p> <p>HCCR-1 was upregulated in breast cancer cells and tissues compared with normal breast tissues. In this study, overexpression of HCCR-1 was well correlated with known breast cancer prognostic markers including the presence of steroid receptors (ER and PR), p53 mutation and high HER2 overexpression. HCCR-1 was not detected in the ER-negative, PR-negative, p53 negative and low HER2 breast cancer tissues. These data indicate that the level of HCCR-1 in breast cancer tissues is relatively well correlated with known breast cancer factors, including the HER2 overexpression, p53 mutation, and ER/PR status.</p> <p>Conclusion</p> <p>Determination of HCCR-1 levels as options for HER2 testing is promising although it needs further evaluation.</p

Establishing Human Lacrimal Gland Cultures with Secretory Function

PURPOSE: Dry eye syndrome is a multifactorial chronic disabling disease mainly caused by the functional disruptions in the lacrimal gland. The treatment involves palliation like ocular surface lubrication and rehydration. Cell therapy involving replacement of the gland is a promising alternative for providing long-term relief to patients. This study aimed to establish functionally competent lacrimal gland cultures in-vitro and explore the presence of stem cells in the native gland and the established in-vitro cultures. METHODS: Fresh human lacrimal gland from patients undergoing exenteration was harvested for cultures after IRB approval. The freshly isolated cells were evaluated by flow cytometry for expression of stem cell markers ABCG2, high ALDH1 levels and c-kit. Cultures were established on Matrigel, collagen and HAM and the cultured cells evaluated for the presence of stem cell markers and differentiating markers of epithelial (E-cadherin, EpCAM), mesenchymal (Vimentin, CD90) and myofibroblastic (α-SMA, S-100) origin by flow cytometry and immunocytochemistry. The conditioned media was tested for secretory proteins (scIgA, lactoferrin, lysozyme) post carbachol (100 µM) stimulation by ELISA. RESULTS: Native human lacrimal gland expressed ABCG2 (mean±SEM: 3.1±0.61%), high ALDH1 (3.8±1.26%) and c-kit (6.7±2.0%). Lacrimal gland cultures formed a monolayer, in order of preference on Matrigel, collagen and HAM within 15-20 days, containing a heterogeneous population of stem-like and differentiated cells. The epithelial cells formed 'spherules' with duct like connections, suggestive of ductal origin. The levels of scIgA (47.43 to 61.56 ng/ml), lysozyme (24.36 to 144.74 ng/ml) and lactoferrin (32.45 to 40.31 ng/ml) in the conditioned media were significantly higher than the negative controls (p<0.05 for all comparisons). CONCLUSION: The study reports the novel finding of establishing functionally competent human lacrimal gland cultures in-vitro. It also provides preliminary data on the presence of stem cells and duct-like cells in the fresh and in-vitro cultured human lacrimal gland. These significant findings could pave way for cell therapy in future

Flooding Greatly Affects the Diversity of Arbuscular Mycorrhizal Fungi Communities in the Roots of Wetland Plants

The communities of arbuscular mycorrhizal fungi (AMF) colonizing the roots of three mangrove species were characterized along a tidal gradient in a mangrove swamp. A fragment, designated SSU-ITS-LSU, including part of the small subunit (SSU), the entire internal transcribed spacer (ITS) and part of the large subunit (LSU) of rDNA from samples of AMF-colonized roots was amplified, cloned and sequenced using AMF-specific primers. Similar levels of AMF diversity to those observed in terrestrial ecosystems were detected in the roots, indicating that the communities of AMF in wetland ecosystems are not necessarily low in diversity. In total, 761 Glomeromycota sequences were obtained, which grouped, according to phylogenetic analysis using the SSU-ITS-LSU fragment, into 23 phylotypes, 22 of which belonged to Glomeraceae and one to Acaulosporaceae. The results indicate that flooding plays an important role in AMF diversity, and its effects appear to depend on the degree (duration) of flooding. Both host species and tide level affected community structure of AMF, indicating the presence of habitat and host species preferences

Supersymmetric mass spectra and the seesaw scale

Supersymmetric mass spectra within two variants of the seesaw mechanism, commonly known as type-II and type-III seesaw, are calculated using full 2-loop RGEs and minimal Supergravity boundary conditions. The type-II seesaw is realized using one pair of 15 and $\bar{15}$ superfields, while the type-III is realized using three copies of $24_M$ superfields. Using published, estimated errors on SUSY mass observables attainable at the LHC and in a combined LHC+ILC analysis, we calculate expected errors for the parameters of the models, most notably the seesaw scale. If SUSY particles are within the reach of the ILC, pure mSugra can be distinguished from mSugra plus type-II or type-III seesaw for nearly all relevant values of the seesaw scale. Even in the case when only the much less accurate LHC measurements are used, we find that indications for the seesaw can be found in favourable parts of the parameter space. Since our conclusions crucially depend on the reliability of the theoretically forecasted error bars, we discuss in some detail the accuracies which need to be achieved for the most important LHC and ILC observables before an analysis, such as the one presented here, can find any hints for type-II or type-III seesaw in SUSY spectra.Comment: 31 pages, 49 figure