Case Report: Neratinib Therapy Improves Glycemic Control in a Patient With Type 2 Diabetes and Breast Cancer

A critical decline of functional insulin-producing pancreatic β-cells is the central pathologic element of both type 1 and type 2 diabetes. Mammalian Sterile 20-like kinase 1 (MST1) is a key mediator of β-cell failure and the identification of neratinib as MST1 inhibitor with potent effects on β-cell survival represents a promising approach for causative diabetes therapy. Here we report a case of robust glycemia and HbA1c normalization in a patient with breast cancer-T2D comorbidity under neratinib, a potent triple kinase inhibitor of HER2/EGFR and MST1. The patient, aged 62 years, was enrolled in the plasmaMATCH clinical trial and received 240 mg neratinib once daily. Neratinib therapy correlated with great improvement in glucose and HbA1c both to physiological levels during the whole treatment period (average reduction of random glucose from 13.6 ± 0.4 to 6.3 ± 0.5 mmol/l and of HbA1c from 82.2 ± 3.9 to 45.6 ± 4.2 mmol/mol before and during neratinib). 18 months later, when neratinib was withdrawn, random glucose rapidly raised together with high blood glucose fluctuations, which reflected in elevated HbA1c levels. This clinical case reports the combination of HER2/EGFR/MST1-inhibition by neratinib for the pharmacological intervention to effectively restore normoglycemia in a patient with poorly controlled T2D and suggests neratinib as potent therapeutic regimen for the cancer-diabetes comorbidity

Unitarity Bounds for Gauged Axionic Interactions and the Green-Schwarz Mechanism

We analyze the effective actions of anomalous models in which a four-dimensional version of the Green-Schwarz mechanism is invoked for the cancellation of the anomalies, and we compare it with those models in which gauge invariance is restored by the presence of a Wess-Zumino term. Some issues concerning an apparent violation of unitarity of the mechanism, which requires Dolgov-Zakharov poles, are carefully examined, using a class of amplitudes studied in the past by Bouchiat-Iliopoulos-Meyer (BIM), and elaborating on previous studies. In the Wess-Zumino case we determine explicitly the unitarity bound using a realistic model of intersecting branes (the Madrid model) by studying the corresponding BIM amplitudes. This is shown to depend significantly on the St\"uckelberg mass and on the coupling of the extra anomalous gauge bosons and allows one to identify Standard-Model-like regions (which are anomaly-free) from regions where the growth of certain amplitudes is dominated by the anomaly, separated by an inflection point which could be studied at the LHC. The bound can even be around 5-10 TeV's for a $Z'$ mass around 1 TeV and varies sensitively with the anomalous coupling. The results for the WZ case are quite general and apply to all the models in which an axion-like interaction is introduced as a generalization of the Peccei-Quinn mechanism, with a gauged axion.Comment: 50 pages, 28 figure

A complete 3D numerical study of the effects of pseudoscalar-photon mixing on quasar polarizations

We present the results of three-dimensional simulations of quasar polarizations in the presence of pseudoscalar-photon mixing in the intergalactic medium. The intergalactic magnetic field is assumed to be uncorrelated in wave vector space but correlated in real space. Such a field may be obtained if its origin is primordial. Furthermore we assume that the quasars, located at cosmological distances, have negligible initial polarization. In the presence of pseudoscalar-photon mixing we show, through a direct comparison with observations, that this may explain the observed large scale alignments in quasar polarizations within the framework of big bang cosmology. We find that the simulation results give a reasonably good fit to the observed data.Comment: 15 pages, 8 figures, significant changes, to appear in EPJ

Electromagnetic Probes

A review is presented of dilepton and real photon measurements in relativistic heavy ion collisions over a very broad energy range from the low energies of the BEVALAC up to the highest energies available at RHIC. The dileptons cover the invariant mass range \mll = 0 - 2.5 GeV/c$^2$, i.e. the continuum at low and intermediate masses and the light vector mesons, $\rho, \omega, \phi$. The review includes also measurements of the light vector mesons in elementary reactions.Comment: To be published in Landolt-Boernstein Volume 1-23A; 40 pages, 24 figures. Final version updated with small changes to the text, updated references and updated figure

Electromagnetic probes

We introduce the seminal developments in the theory and experiments of electromagnetic probes for the study of the dynamics of relativistic heavy ion collisions and quark gluon plasma.Comment: 47 pages, 33 Figures; Lectures delivered by Dinesh K. Srivastava at QGP Winter School (QGPWS08) at Jaipur, India, February 1-3, 200

NA60 results on thermal dimuons

The NA60 experiment at the CERN SPS has measured muon pairs with unprecedented precision in 158A GeV In-In collisions. A strong excess of pairs above the known sources is observed in the whole mass region 0.2<M<2.6 GeV. The mass spectrum for M<1 GeV is consistent with a dominant contribution from pi+pi- -> rho -> mu+mu- annihilation. The associated rho spectral function shows a strong broadening, but essentially no shift in mass. For M>1 GeV, the excess is found to be prompt, not due to enhanced charm production, with pronounced differences to Drell-Yan pairs. The slope parameter Teff associated with the transverse momentum spectra rises with mass up to the rho, followed by a sudden decline above. The rise for M<1 GeV is consistent with radial flow of a hadronic emission source. The seeming absence of significant flow for M>1 GeV and its relation to parton-hadron duality is discussed in detail, suggesting a dominantly partonic emission source in this region. A comparison of the data to the present status of theoretical modeling is also contained. The accumulated empirical evidence, including also a Planck-like shape of the mass spectra at low pT and the lack of polarization, is consistent with a global interpretation of the excess dimuons as thermal radiation. We conclude with first results on omega in-medium effects.Comment: 10 pages, 12 figures, submitted to Eur. Phys. J.

Constraints on Dark Matter Annihilation in Clusters of Galaxies with the Fermi Large Area Telescope

Nearby clusters and groups of galaxies are potentially bright sources of high-energy gamma-ray emission resulting from the pair-annihilation of dark matter particles. However, no significant gamma-ray emission has been detected so far from clusters in the first 11 months of observations with the Fermi Large Area Telescope. We interpret this non-detection in terms of constraints on dark matter particle properties. In particular for leptonic annihilation final states and particle masses greater than ~200 GeV, gamma-ray emission from inverse Compton scattering of CMB photons is expected to dominate the dark matter annihilation signal from clusters, and our gamma-ray limits exclude large regions of the parameter space that would give a good fit to the recent anomalous Pamela and Fermi-LAT electron-positron measurements. We also present constraints on the annihilation of more standard dark matter candidates, such as the lightest neutralino of supersymmetric models. The constraints are particularly strong when including the fact that clusters are known to contain substructure at least on galaxy scales, increasing the expected gamma-ray flux by a factor of ~5 over a smooth-halo assumption. We also explore the effect of uncertainties in cluster dark matter density profiles, finding a systematic uncertainty in the constraints of roughly a factor of two, but similar overall conclusions. In this work, we focus on deriving limits on dark matter models; a more general consideration of the Fermi-LAT data on clusters and clusters as gamma-ray sources is forthcoming.Comment: accepted to JCAP, Corresponding authors: T.E. Jeltema and S. Profumo, minor revisions to be consistent with accepted versio

Observation of inverse Compton emission from a long γ-ray burst.

Long-duration γ-ray bursts (GRBs) originate from ultra-relativistic jets launched from the collapsing cores of dying massive stars. They are characterized by an initial phase of bright and highly variable radiation in the kiloelectronvolt-to-megaelectronvolt band, which is probably produced within the jet and lasts from milliseconds to minutes, known as the prompt emission1,2. Subsequently, the interaction of the jet with the surrounding medium generates shock waves that are responsible for the afterglow emission, which lasts from days to months and occurs over a broad energy range from the radio to the gigaelectronvolt bands1-6. The afterglow emission is generally well explained as synchrotron radiation emitted by electrons accelerated by the external shock7-9. Recently, intense long-lasting emission between 0.2 and 1 teraelectronvolts was observed from GRB 190114C10,11. Here we report multi-frequency observations of GRB 190114C, and study the evolution in time of the GRB emission across 17 orders of magnitude in energy, from 5 × 10-6 to 1012 electronvolts. We find that the broadband spectral energy distribution is double-peaked, with the teraelectronvolt emission constituting a distinct spectral component with power comparable to the synchrotron component. This component is associated with the afterglow and is satisfactorily explained by inverse Compton up-scattering of synchrotron photons by high-energy electrons. We find that the conditions required to account for the observed teraelectronvolt component are typical for GRBs, supporting the possibility that inverse Compton emission is commonly produced in GRBs

Global surveillance of cancer survival 1995-2009: analysis of individual data for 25,676,887 patients from 279 population-based registries in 67 countries (CONCORD-2)

BACKGROUND: Worldwide data for cancer survival are scarce. We aimed to initiate worldwide surveillance of cancer survival by central analysis of population-based registry data, as a metric of the effectiveness of health systems, and to inform global policy on cancer control. METHODS: Individual tumour records were submitted by 279 population-based cancer registries in 67 countries for 25·7 million adults (age 15-99 years) and 75,000 children (age 0-14 years) diagnosed with cancer during 1995-2009 and followed up to Dec 31, 2009, or later. We looked at cancers of the stomach, colon, rectum, liver, lung, breast (women), cervix, ovary, and prostate in adults, and adult and childhood leukaemia. Standardised quality control procedures were applied; errors were corrected by the registry concerned. We estimated 5-year net survival, adjusted for background mortality in every country or region by age (single year), sex, and calendar year, and by race or ethnic origin in some countries. Estimates were age-standardised with the International Cancer Survival Standard weights. FINDINGS: 5-year survival from colon, rectal, and breast cancers has increased steadily in most developed countries. For patients diagnosed during 2005-09, survival for colon and rectal cancer reached 60% or more in 22 countries around the world; for breast cancer, 5-year survival rose to 85% or higher in 17 countries worldwide. Liver and lung cancer remain lethal in all nations: for both cancers, 5-year survival is below 20% everywhere in Europe, in the range 15-19% in North America, and as low as 7-9% in Mongolia and Thailand. Striking rises in 5-year survival from prostate cancer have occurred in many countries: survival rose by 10-20% between 1995-99 and 2005-09 in 22 countries in South America, Asia, and Europe, but survival still varies widely around the world, from less than 60% in Bulgaria and Thailand to 95% or more in Brazil, Puerto Rico, and the USA. For cervical cancer, national estimates of 5-year survival range from less than 50% to more than 70%; regional variations are much wider, and improvements between 1995-99 and 2005-09 have generally been slight. For women diagnosed with ovarian cancer in 2005-09, 5-year survival was 40% or higher only in Ecuador, the USA, and 17 countries in Asia and Europe. 5-year survival for stomach cancer in 2005-09 was high (54-58%) in Japan and South Korea, compared with less than 40% in other countries. By contrast, 5-year survival from adult leukaemia in Japan and South Korea (18-23%) is lower than in most other countries. 5-year survival from childhood acute lymphoblastic leukaemia is less than 60% in several countries, but as high as 90% in Canada and four European countries, which suggests major deficiencies in the management of a largely curable disease. INTERPRETATION: International comparison of survival trends reveals very wide differences that are likely to be attributable to differences in access to early diagnosis and optimum treatment. Continuous worldwide surveillance of cancer survival should become an indispensable source of information for cancer patients and researchers and a stimulus for politicians to improve health policy and health-care systems