The prognostic value of the hypoxia markers CA IX and GLUT 1 and the cytokines VEGF and IL 6 in head and neck squamous cell carcinoma treated by radiotherapy ± chemotherapy

BACKGROUND: Several parameters of the tumor microenvironment, such as hypoxia, inflammation and angiogenesis, play a critical role in tumor aggressiveness and treatment response. A major question remains if these markers can be used to stratify patients to certain treatment protocols. The purpose of this study was to investigate the inter-relationship and the prognostic significance of several biological and clinicopathological parameters in patients with head and neck squamous cell carcinoma (HNSCC) treated by radiotherapy ± chemotherapy. METHODS: We used two subgroups of a retrospective series for which CT-determined tumoral perfusion correlated with local control. In the first subgroup (n = 67), immunohistochemistry for carbonic anhydrase IX (CA IX) and glucose transporter-1 (GLUT-1) was performed on the pretreatment tumor biopsy. In the second subgroup (n = 34), enzyme linked immunosorbent assay (ELISA) was used to determine pretreatment levels of the cytokines vascular endothelial growth factor (VEGF) and interleukin-6 (IL-6) in serum. Correlation was investigated between tumoral perfusion and each of these biological markers, as well as between the markers mutually. The prognostic value of these microenvironmental parameters was also evaluated. RESULTS: For CA IX and GLUT-1, the combined assessment of patients with both markers expressed above the median showed an independent correlation with local control (p = 0.02) and disease-free survival (p = 0.04) with a trend for regional control (p = 0.06). In the second subgroup, IL-6 pretreatment serum level above the median was the only independent predictor of local control (p = 0.009), disease-free survival (p = 0.02) and overall survival (p = 0.005). CONCLUSION: To our knowledge, we are the first to report a link in HNSCC between IL-6 pretreatment serum levels and radioresistance in vivo. This link is supported by the strong prognostic association of pretreatment IL-6 with local control, known to be the most important parameter to judge radiotherapy responses. Furthermore, the combined assessment of CA IX and GLUT-1 correlated independently with prognosis. This is a valuable indication that a combined approach is important in the investigation of prognostic markers

First measurement of the helicity asymmetry for γp→pπ0\gamma p\rightarrow p\pi^0 in the resonance region

The first measurement of the helicity dependence of the photoproduction cross section of single neutral pions off protons is reported for photon energies from 600 to 2300\,MeV, covering nearly the full solid angle. The data are compared to predictions from the SAID, MAID, and BnGa partial wave analyses. Strikingly large differences between data and predictions are observed which are traced to differences in the helicity amplitudes of well known and established resonances. Precise values for the helicity amplitudes of several resonances are reported

Limits on the Majorana neutrino mass in the 0.1 eV range

The Heidelberg-Moscow experiment gives the most stringent limit on the Majorana neutrino mass. After 24 kg yr of data with pulse shape measurements, we set a lower limit on the half-life of the neutrinoless double beta decay in 76Ge of T_1/2 > 5.7 * 10^{25} yr at 90% C.L., thus excluding an effective Majorana neutrino mass greater than 0.2 eV. This allows to set strong constraints on degenerate neutrino mass models.Comment: 6 pages (latex) including 3 postscript figures and 2 table

Neuropeptide Y2 Receptor (NPY2R) Expression in Saliva Predicts Feeding Immaturity in the Premature Neonate

Background: The current practice in newborn medicine is to subjectively assess when a premature infant is ready to feed by mouth. When the assessment is inaccurate, the resulting feeding morbidities may be significant, resulting in long-term health consequences and millions of health care dollars annually. We hypothesized that the developmental maturation of hypothalamic regulation of feeding behavior is a predictor of successful oral feeding in the premature infant. To test this hypothesis, we analyzed the gene expression of neuropeptide Y2 receptor (NPY2R), a known hypothalamic regulator of feeding behavior, in neonatal saliva to determine its role as a biomarker in predicting oral feeding success in the neonate. Methodology/Principal Findings: Salivary samples (n = 116), were prospectively collected from 63 preterm and 13 term neonates (post-conceptual age (PCA) 26 4/7 to 41 4/7 weeks) from five predefined feeding stages. Expression of NPY2R in neonatal saliva was determined by multiplex RT-qPCR amplification. Expression results were retrospectively correlated with feeding status at time of sample collection. Statistical analysis revealed that expression of NPY2R had a 95 % positive predictive value for feeding immaturity. NPY2R expression statistically significantly decreased with advancing PCA (Wilcoxon test p value,0.01), and was associated with feeding status (chi square p value = 0.013). Conclusions/Significance: Developmental maturation of hypothalamic regulation of feeding behavior is an essential component of oral feeding success in the newborn. NPY2R expression in neonatal saliva is predictive of an immatur

The supply chain of violence

Every year, more people are killed defending the environment than are soldiers from the United Kingdom and Australia on overseas deployments in war zones combined. During the last 15 years, the number of both deaths of environmental defenders, and the countries where they occur, have increased. Recorded deaths have increased from two per week to four per week over this period. These deaths are primarily related to conflict over natural resources, across a range of sectors. Of 683 total deaths, >230 were related to mining and agribusiness between 2014 and 2017. We find that rule of law and corruption indices are closely linked to patterns of killings. Using spatial data, we investigate the drivers of these conflicts and violence and seek to identify who may be most at risk and why. We argue that businesses, investors and national governments at both ends of the chain of violence need to be more accountable

Travel risk, malaria importation and malaria transmission in Zanzibar

The prevalence of Plasmodium falciparum malaria in Zanzibar has reached historic lows. Improving control requires quantifying malaria importation rates, identifying high-risk travelers, and assessing onwards transmission