Impact of N-myc amplification on median survival in children with neuroblastoma

Background: Neuroblastoma is the most common extracranial malignant solid tumor in children under 5 years, and it is characterized by wide clinical and biological heterogeneity. N-myc oncogene amplification is considered to be one of the most important prognostic factors used to evaluate survival in these patients. Objectives: The aim of our study was to determine amplification of the N-myc oncogene using real-time quantitative polymerase chain reaction (PCR) and to show the influence of N-myc amplified tumors on the overall survival rate. Patients and Methods: This study is an analytical historical cohort study of forty children with neuroblastoma admitted to the Shafa Hospital, Iran from 1999 to 2010. Paraffined blocks of tumoral tissue were analyzed for N-myc amplification by a PCR. The degree of N-myc amplification was derived from the ratio of the N-myc oncogene and the single copy reference gene, NAGK. In the statistical analysis, a Kaplan-Meier survival analysis was used. Results: We found a variable degree of N-myc amplification, from 3 to 2 200, in 32 of the 40 neuroblastomas (80%). NMYC amplification was seen more frequently in patients older than 2.5 years (71.9%), stage 4 (65.6%) and female (53.1%). Median survival time in the males was significantly longer than in the females (P = 0.03). The overall median survival for N-myc amplified tumor patients was 20 months, and 30 months for the non amplified tumors. Conclusions: The N-myc amplified tumors may increase the probability of more aggressive behavior and rapid tumor progression, especially in advanced stages of neuroblastoma. This study confirmed the importance of obtaining correct measurements of oncogene amplification in the early evaluation of neuroblastomas in order to target more aggressive therapies in patients with a higher risk of cancer progression

Chiral primary one-point functions in the D3-D7 defect conformal field theory

JHEP is an open-access journal funded by SCOAP3 and licensed under CC BY 4.0archiveprefix: arXiv primaryclass: hep-th reportnumber: NORDITA-2012-81 slaccitation: %%CITATION = ARXIV:1210.7015;%%archiveprefix: arXiv primaryclass: hep-th reportnumber: NORDITA-2012-81 slaccitation: %%CITATION = ARXIV:1210.7015;%%C.F.K. and D.Y. were supported in part by FNU through grant number 272-08-0329. G.W.S. is supported by NSERC of Canada and by the Villum foundation through their Velux Visiting Professor program

Adrenal Venous Sampling: Where Is the Aldosterone Disappearing to?

Adrenal venous sampling (AVS) is generally considered to be the gold standard in distinguishing unilateral and bilateral aldosterone hypersecretion in primary hyperaldosteronism. However, during AVS, we noticed a considerable variability in aldosterone concentrations among samples thought to have come from the right adrenal glands. Some aldosterone concentrations in these samples were even lower than in samples from the inferior vena cava. We hypothesized that the samples with low aldosterone levels were unintentionally taken not from the right adrenal gland, but from hepatic veins. Therefore, we sought to analyze the impact of unintentional cannulation of hepatic veins on AVS. Thirty consecutive patients referred for AVS were enrolled. Hepatic vein sampling was implemented in our standardized AVS protocol. The data were collected and analyzed prospectively. AVS was successful in 27 patients (90%), and hepatic vein cannulation was successful in all procedures performed. Cortisol concentrations were not significantly different between the hepatic vein and inferior vena cava samples, but aldosterone concentrations from hepatic venous blood (median, 17 pmol/l; range, 40–860 pmol/l) were markedly lower than in samples from the inferior vena cava (median, 860 pmol/l; range, 460–4510 pmol/l). The observed difference was statistically significant (P < 0.001). Aldosterone concentrations in the hepatic veins are significantly lower than in venous blood taken from the inferior vena cava. This finding is important for AVS because hepatic veins can easily be mistaken for adrenal veins as a result of their close anatomic proximity

Risk measures for direct real estate investments with non-normal or unknown return distributions

The volatility of returns is probably the most widely used risk measure for real estate. This is rather surprising since a number of studies have cast doubts on the view that volatility can capture the manifold risks attached to properties and corresponds to the risk attitude of investors. A central issue in this discussion is the statistical properties of real estate returns—in contrast to neoclassical capital market theory they are mostly non-normal and often unknown, which render many statistical measures useless. Based on a literature review and an analysis of data from Germany we provide evidence that volatility alone is inappropriate for measuring the risk of direct real estate. We use a unique data sample by IPD, which includes the total returns of 939 properties across different usage types (56% office, 20% retail, 8% others and 16% residential properties) from 1996 to 2009, the German IPD Index, and the German Property Index. The analysis of the distributional characteristics shows that German real estate returns in this period were not normally distributed and that a logistic distribution would have been a better fit. This is in line with most of the current literature on this subject and leads to the question which indicators are more appropriate to measure real estate risks. We suggest that a combination of quantitative and qualitative risk measures more adequately captures real estate risks and conforms better with investor attitudes to risk. Furthermore, we present criteria for the purpose of risk classification

Quantum interference and Klein tunneling in graphene heterojunctions

The observation of quantum conductance oscillations in mesoscopic systems has traditionally required the confinement of the carriers to a phase space of reduced dimensionality. While electron optics such as lensing and focusing have been demonstrated experimentally, building a collimated electron interferometer in two unconfined dimensions has remained a challenge due to the difficulty of creating electrostatic barriers that are sharp on the order of the electron wavelength. Here, we report the observation of conductance oscillations in extremely narrow graphene heterostructures where a resonant cavity is formed between two electrostatically created bipolar junctions. Analysis of the oscillations confirms that p-n junctions have a collimating effect on ballistically transmitted carriers. The phase shift observed in the conductance fringes at low magnetic fields is a signature of the perfect transmission of carriers normally incident on the junctions and thus constitutes a direct experimental observation of ``Klein Tunneling.''Comment: 13 pages and 6 figures including supplementary information. The paper has been modified in light of new theoretical results available at arXiv:0808.048

Clinical use of HIV integrase inhibitors : a systematic review and meta-analysis

Background: Optimal regimen choice of antiretroviral therapy is essential to achieve long-term clinical success. Integrase inhibitors have swiftly been adopted as part of current antiretroviral regimens. The purpose of this study was to review the evidence for integrase inhibitor use in clinical settings. Methods: MEDLINE and Web-of-Science were screened from April 2006 until November 2012, as were hand-searched scientific meeting proceedings. Multiple reviewers independently screened 1323 citations in duplicate to identify randomized controlled trials, nonrandomized controlled trials and cohort studies on integrase inhibitor use in clinical practice. Independent, duplicate data extraction and quality assessment were conducted. Results: 48 unique studies were included on the use of integrase inhibitors in antiretroviral therapy-naive patients and treatment-experienced patients with either virological failure or switching to integrase inhibitors while virologically suppressed. On the selected studies with comparable outcome measures and indication (n = 16), a meta-analysis was performed based on modified intention-to-treat (mITT), on-treatment (OT) and as-treated (AT) virological outcome data. In therapy-naive patients, favorable odds ratios (OR) for integrase inhibitor-based regimens were observed, (mITT OR 0.71, 95% CI 0.59-0.86). However, integrase inhibitors combined with protease inhibitors only did not result in a significant better virological outcome. Evidence further supported integrase inhibitor use following virological failure (mITT OR 0.27; 95% CI 0.11-0.66), but switching to integrase inhibitors from a high genetic barrier drug during successful treatment was not supported (mITT OR 1.43; 95% CI 0.89-2.31). Integrase inhibitor-based regimens result in similar immunological responses compared to other regimens. A low genetic barrier to drug-resistance development was observed for raltegravir and elvitegravir, but not for dolutegravir. Conclusion: In first-line therapy, integrase inhibitors are superior to other regimens. Integrase inhibitor use after virological failure is supported as well by the meta-analysis. Careful use is however warranted when replacing a high genetic barrier drug in treatment-experienced patients switching successful treatment

Lutzomyia adiketis sp. n. (Diptera: Phlebotomidae), a vector of Paleoleishmania neotropicum sp. n. (Kinetoplastida: Trypanosomatidae) in Dominican amber

<p>Abstract</p> <p>Background</p> <p>Amber fossils can be used to trace the history of disease-vector associations because microorganisms are preserved "in situ" inside the alimentary tract and body cavity of blood-sucking insects.</p> <p>Results</p> <p><it>Lutzomyia adiketis </it>sp. n. (Phlebotomidae: Diptera) is described from Dominican amber as a vector of <it>Paleoleishmania neotropicum </it>sp. n. (Kinetoplastida: Trypanosomatidae). The fossil sand fly differs from all previously described extinct and extant members of the genus by the following combination of characters: Sc forked with the branches meeting the costa and radius veins; wing L/W value of 4.1; a δ value of 18; a ratio β/α value of 0.86, and the shape and size of the spatulate rods on the ninth sternite. The trypanosomatid is characterized by the structure of its promastigotes, amastigotes and paramastigotes and its transmission by an extinct species of sand fly.</p> <p>Conclusion</p> <p>Morphological characters show that the fossil sand fly is a new extinct species and that it is host to a digenetic species of trypanosomatid. This study provides the first fossil evidence that Neotropical sand flies were vectors of trypanosomatids in the mid-Tertiary (20–30 mya).</p

Flavor Violating Higgs Decays

We study a class of nonstandard interactions of the newly discovered 125 GeV Higgs-like resonance that are especially interesting probes of new physics: flavor violating Higgs couplings to leptons and quarks. These interaction can arise in many frameworks of new physics at the electroweak scale such as two Higgs doublet models, extra dimensions, or models of compositeness. We rederive constraints on flavor violating Higgs couplings using data on rare decays, electric and magnetic dipole moments, and meson oscillations. We confirm that flavor violating Higgs boson decays to leptons can be sizeable with, e.g., h -> tau mu and h -> tau e branching ratios of order 10% perfectly allowed by low energy constraints. We estimate the current LHC limits on h -> tau mu and h -> tau e decays by recasting existing searches for the SM Higgs in the tau-tau channel and find that these bounds are already stronger than those from rare tau decays. We also show that these limits can be improved significantly with dedicated searches and we outline a possible search strategy. Flavor violating Higgs decays therefore present an opportunity for discovery of new physics which in some cases may be easier to access experimentally than flavor conserving deviations from the Standard Model Higgs framework.Comment: 39 pages, 12 figures, 3 tables; v2: Improved referencing, updated mu -> 3e bounds to include large loop contributions, corrected single top constraints; conclusions unchanged; matches version to be published in JHEP; v3: included 2-loop contributions in mu -> e conversion, improved discussion of tau -> 3 mu and of EDM constraints on FV top-Higgs couplings; conclusions unchange

Multiple primary tumours in women following breast cancer, 1973–2000

We investigated the predictors of the risk of developing a second primary cancer after breast cancer, this occurring in about 12% of affected women. The analysis included 335 191 females, registered in the National Cancer Institute's Surveillance Epidemiology and End Results (SEER) database, who had been diagnosed with breast cancer. Observed numbers of subsequent cancers in the SEER database with a first breast cancer diagnosed from 1973 to 2000 were compared with the expected numbers based on age-adjusted incidence rates to calculate standardised incidence ratios. Kaplan–Meier curves were conducted to determine the median time until the second primary cancer diagnosis. Average number of years until diagnosis varied by site and by age as well as median years until second cancer diagnosis. Most cancer risks decreased with age, but there was an increase in aging-related cancers such as lung cancer. The median years of follow-up were well beyond the 5-year mark. Breast cancer survivors should be advised of their increased risk for developing certain cancers in their lifetime

Survival from breast cancer among South Asian and non-South Asian women resident in South East England

Ethnic differences in breast cancer survival have been observed in the USA but have not been examined in Britain. We aimed to investigate such differences between South Asian (i.e. those with family roots in the Indian subcontinent) and non-South Asian (essentially British-native) women in England. Primary breast cancer cases incident in 1986 -1993 and resident in South East England were ascertained through the Thames Cancer and Registry and followed up to the end of 1997. Cases of South Asian ethnicity were identified on the basis of their names by using a previously validated computer algorithm. A total of 1037 South Asian and 50 201 non-South Asian breast cancer cases were included in the analysis; 30% of the South Asian (n=312) and 44% (n=22 201) of the non-South Asian cases died during follow-up. South Asian cases had a higher relative survival than non-South Asians throughout the follow-up period. The 10-year relative survival rates were 72.6% (95% confidence interval: 69.0, 75.9%) and 65.2% (64.5, 65.8%) for South Asians and non-South Asians, respectively. The excess mortality rates experienced by South Asians were 82% (72, 94%) of those experienced by non-South Asians (P=0.004). The magnitude of this effect was slightly reduced with adjustment for differences in age at diagnosis, but was strengthened with further adjustment for differences in stage at presentation and socioeconomic deprivation (excess mortality rates in South Asians relative to non-South Asians=72% (63, 82%), P&<0.001). These findings indicate that the higher survival from breast cancer in the first 10 years after diagnosis among South Asian was not due to differences in age at diagnosis, socioeconomic deprivation or disease stage at presentation