Chromosome 9p deletion in clear cell renal cell carcinoma predicts recurrence and survival following surgery

BACKGROUND: Wider clinical applications of 9p status in clear cell renal cell carcinoma (ccRCC) are limited owing to the lack of validation and consensus for interphase fluorescent in situ hybridisation (I-FISH) scoring technique. The aim of this study was to analytically validate the applicability of I-FISH in assessing 9p deletion in ccRCC and to clinically assess its long-term prognostic impact following surgical excision of ccRCC. METHODS: Tissue microarrays were constructed from 108 renal cell carcinoma (RCC) tumour paraffin blocks. Interphase fluorescent in situ hybridisation analysis was undertaken based on preset criteria by two independent observers to assess interobserver variability. 9p status in ccRCC tumours was determined and correlated to clinicopathological variables, recurrence-free survival and disease-specific survival. RESULTS: There were 80 ccRCCs with valid 9p scoring and a median follow-up of 95 months. Kappa statistic for interobserver variability was 0.71 (good agreement). 9p deletion was detected in 44% of ccRCCs. 9p loss was associated with higher stage, larger tumours, necrosis, microvascular and renal vein invasion, and higher SSIGN (stage, size, grade and necrosis) score. Patients with 9p-deleted ccRCC were at a higher risk of recurrence (P=0.008) and RCC-specific mortality (P=0.001). On multivariate analysis, 9p deletion was an independent predictor of recurrence (hazard ratio 4.323; P=0.021) and RCC-specific mortality (hazard ratio 4.603; P=0.007). The predictive accuracy of SSIGN score improved from 87.7% to 93.1% by integrating 9p status to the model (P=0.001). CONCLUSIONS: Loss of 9p is associated with aggressive ccRCC and worse prognosis in patients following surgery. Our findings independently confirm the findings of previous reports relying on I-FISH to detect 9p (CDKN2A) deletion

Significance of chromosome 9p status in renal cell carcinoma:a systematic review and quality of the reported studies

Defining the prognosis of renal cell carcinoma (RCC) using genetic tests is an evolving area. The prognostic significance of 9p status in RCC, although described in the literature, remains underutilised in clinical practice. The study explored the causes of this translational gap. A systematic review on the significance of 9p status in RCC was performed to assess its clinical applicability and impact on clinical decision-making. Medline, Embase, and other electronic searches were made for studies reporting on 9p status in RCC. We collected data on: genetic techniques, pathological parameters, clinical outcomes, and completeness of follow-up assessment. Eleven studies reporting on 1,431 patients using different genetic techniques were included. The most commonly used genetic technique for the assessment of 9p status in RCC was fluorescence in situ hybridization. Combined genomic hybridisation (CGH), microsatellite analysis, karyotyping, and sequencing were other reported techniques. Various thresholds and cut-off values were used for the diagnosis of 9p deletion in different studies. Standardization, interobserver agreement, and consensus on the interpretation of test remained poor. The studies lacked validation and had high risk of bias and poor clinical applicability as assessed by two independent reviewers using a modified quality assessment tool. Further protocol driven studies with standardised methodology including use of appropriate positive and negative controls, assessment of interobserver variations, and evidenced based follow-up protocols are needed to clarify the role of 9p status in predicting oncological outcomes in renal cell cancer

Variations in the management of acute illness in children with congenital adrenal hyperplasia: An audit of three paediatric hospitals

Objective: Episodes of acute adrenal insufficiency (AI)/adrenal crises (AC) are a serious consequence of congenital adrenal hyperplasia (CAH). This study aimed to assess morbidity from acute illness in CAH and identify factors associated with use of IV hydrocortisone, admission and diagnosis of an AC. Method: An audit of acute illness presentations among children with CAH to paediatric hospitals in New South Wales, Australia, between 2000 and 2015. Results: There were 321 acute presentations among 74 children with CAH. Two thirds (66.7%, n=214) of these resulted in admission and 49.2% (n=158) of the patients received intravenous (IV) hydrocortisone. An AC was diagnosed in (9.0%). Prior to presentation, 64.2% (n=206) had used oral stress dosing and 22.1% (n=71) had been given intramuscular (IM) hydrocortisone. Vomiting was recorded in 61.1% (n=196), 32.7% (n=64) of whom had used IM hydrocortisone. Admission, AC diagnosis, and use of stress dosing varied significantly between hospitals. IM use varied from 7.0% in one metropolitan hospital to 45.8% in the regional hospital. Children aged up to 12 months had the lowest levels of stress dosing and IV hydrocortisone administration. A higher number of prior hospital attendances for acute illness was associated with increased use of IM hydrocortisone. Conclusion: Pre-hospital and in-hospital management of children with CAH can vary between health services. Children under 12 months have lower levels of stress dosing prior to hospital than other age groups. Experience with acute episodes improves self-management of CAH in the context of acute illness in educated patient populations

The role of forest genetic resources in responding to biotic and abiotic factors in the context of anthropogenic climate change

The current distribution of forest genetic resources on Earth is the result of a combination of natural processes and human actions. Over time, tree populations have become adapted to their habitats including the local ecological disturbances they face. As the planet enters a phase of human-induced climate change of unprecedented speed and magnitude, however, previously locally-adapted populations are rendered less suitable for new conditions, and ‘natural’ biotic and abiotic disturbances are taken outside their historic distribution, frequency and intensity ranges. Tree populations rely on phenotypic plasticity to survive in extant locations, on genetic adaptation to modify their local phenotypic optimum or on migration to new suitable environmental conditions. The rate of required change, however, may outpace the ability to respond, and tree species and populations may become locally extinct after specific, but as yet unknown and unquantified, tipping points are reached. Here, we review the importance of forest genetic resources as a source of evolutionary potential for adaptation to changes in climate and other ecological factors. We particularly consider climate-related responses in the context of linkages to disturbances such as pests, diseases and fire, and associated feedback loops. The importance of management strategies to conserve evolutionary potential is emphasised and recommendations for policy-makers are provided

Differentiability of backward stochastic differential equations in Hilbert spaces with monotone generators

The aim of the present paper is to study the regularity properties of the solution of a backward stochastic differential equation with a monotone generator in infinite dimension. We show some applications to the nonlinear Kolmogorov equation and to stochastic optimal control

Heavy Quarkonium Physics from Effective Field Theories

I review recent progress in heavy quarkonium physics from an effective field theory perspective. In this unifying framework, I discuss advances in perturbative calculations for low-lying quarkonium observables and in lattice calculations for high-lying ones, and progress and lasting puzzles in quarkonium production.Comment: Plenary talk at the 4th International Conference on Quarks and Nuclear Physics (QNP06), 5-10 June 2006, Madrid, Spain; 6 pages, 1 figure, EPJ styl

Viscosity solutions of systems of PDEs with interconnected obstacles and Multi modes switching problems

This paper deals with existence and uniqueness, in viscosity sense, of a solution for a system of m variational partial differential inequalities with inter-connected obstacles. A particular case of this system is the deterministic version of the Verification Theorem of the Markovian optimal m-states switching problem. The switching cost functions are arbitrary. This problem is connected with the valuation of a power plant in the energy market. The main tool is the notion of systems of reflected BSDEs with oblique reflection.Comment: 36 page

An overview of Viscosity Solutions of Path-Dependent PDEs

This paper provides an overview of the recently developed notion of viscosity solutions of path-dependent partial di erential equations. We start by a quick review of the Crandall- Ishii notion of viscosity solutions, so as to motivate the relevance of our de nition in the path-dependent case. We focus on the wellposedness theory of such equations. In partic- ular, we provide a simple presentation of the current existence and uniqueness arguments in the semilinear case. We also review the stability property of this notion of solutions, in- cluding the adaptation of the Barles-Souganidis monotonic scheme approximation method. Our results rely crucially on the theory of optimal stopping under nonlinear expectation. In the dominated case, we provide a self-contained presentation of all required results. The fully nonlinear case is more involved and is addressed in [12]

The impact of current CH4 and N2O atmospheric loss process uncertainties on calculated ozone abundances and trends

The atmospheric loss processes of N2O and CH4, their estimated uncertainties, lifetimes, and impacts on ozone abundance and long-term trends are examined using atmospheric model calculations and updated kinetic and photochemical parameters and uncertainty factors from SPARC [2013]. The uncertainty ranges in calculated N2O and CH4 global lifetimes computed using the SPARC estimated uncertainties are reduced by nearly a factor of two compared with uncertainties from Sander et al. [2011]. Uncertainties in CH4 loss due to reaction with OH and O(1D) have relatively small impacts on present day global total ozone (±0.2-0.3%). Uncertainty in the Cl + CH4 reaction affects the amount of chlorine in radical vs. reservoir forms and has a modest impact on present day SH polar ozone (~±6%), and on the rate of past ozone decline and future recovery. Uncertainty in the total rate coefficient for the O(1D) + N2O reaction results in a substantial range in present day stratospheric odd nitrogen (±20-25%) and global total ozone (±1.5-2.5%). Uncertainty in the O(1D) + N2O reaction branching ratio for the O2 + N2 and 2*NO product channels results in moderate impacts on odd nitrogen (±10%) and global ozone (±1%),with uncertainty in N2O photolysis resulting in relatively small impacts (±5% in odd nitrogen, ±0.5% in global ozone). Uncertainties in the O(1D) + N2O reaction and its branching ratio also affect the rate of past global total ozone decline and future recovery, with a range in future ozone projections of ±1-1.5% by 2100, relative to present day

Second order backward stochastic differential equations and fully non-linear parabolic PDEs

We introduce a class of second order backward stochastic differential equations and show relations to fully non-linear parabolic PDEs. In particular, we provide a stochastic representation result for solutions of such PDEs and discuss Monte Carlo methods for their numerical treatment.Comment: 26 page