Prognostic significance of primary-tumor extension, stage and grade of nuclear differentiation in patients with renal cell carcinoma

Surgery remains the preferred therapy for renal cell carcinoma. The various adjunctive or complementary therapies currently yield disappointing results. Identifying reliable prognostic factors could help in selecting patients most likely to benefit from postoperative adjuvant therapies. We reviewed the surgical records of 78 patients who had undergone radical nephrectomy with lymphadenectomy for renal cell carcinoma, matched for type of operation and histology. According to staging (TNM), 5.1% of the patients were classified as stage I, 51.3% as stage II, 29.5% as stage III and 14.5% as stage IV. Of the 78 patients 40 were T2N0 and 21 T3aN0. Tumor grading showed that 39.7% of the patients had well-differentiated tumors(G1), 41.1% moderately-differentiated (G2), and 19.2% poorly-differentiated tumors (G3). Overall actuarial survival at 5 and 10 years was 100% for stage 1; 91.3% at 5 years and 83.1% at 10 years for stage II; 45.5% and 34.1% for stage III; and 29.1% and nil for stage IV (stage II vs stage III p = 0.0001). Patients with tumors confined to the kidney (pT2N0) had better 5- and 10-year survival rates than patients with tumors infiltrating the perirenal fat (pT3aN0) (p = 0.000006). Survival differed according to nuclear grading (G1 vs G3 ; p = 0.000005; G2 vs G3; p = 0.0009). In conclusion our review identified tumor stage, primary-tumor extension, and the grade of nuclear differentiation as reliable prognostic factors in patients with renal cell carcinomas

Source characterization guidelines for noise mapping of port areas

Maritime transport for both passengers and freight is continuously increasing and, consequently, the global attention toward its sustainability is growing. Ships offer advantages in terms of environmental impact compared to other transportation systems but the increasing traffic volume is expected to increase pollutants. Noise produced in port areas has been neglected for too long, until the INTERREG Maritime programme Italy-France 2014\u20132020 has brought to light how citizen complaints are emerging for some of the main ports in the Mediterranean. However, port noise prevention and management is difficult as knowledge on specific sources is very limited in the literature. Furthermore, on field measurements are difficult to be performed given the complexity of the port area, where multiple types of sound emitters mix and confuse each other. Noise maps represent the first important step in order to align ports to the requirements set by the Environmental Noise Directive to the transportation infrastructures. Once computed, they are an excellent tool supporting port management towards the reduction of citizens\u2019 noise exposure while ensuring traffic growth. The present paper reports a guideline for the characterization of noise sources needed as inputs for the noise maps, as developed in the framework of the INTERREG Maritime programme Italy-France 2014\u20132020. On the basis of the current state of the art, a procedure has been elaborated for different categories of noise sources acting in port, ranging from stationary to moving ships, from mooring operations to loading/unloading operations, from industrial activities to road and railway traffic

Functional consequences of mutations in CDKL5, an X-linked gene involved in infantile spasms and mental retardation

Mutations in the X-linked cyclin-dependent kinase-like 5 (CDKL5) gene have been identified in patients with Rett syndrome, West syndrome, and X-linked infantile spasms sharing the common features of generally intractable early seizures and mental retardation. Disease-causing mutations are distributed in both the catalytic domain and in the large COOH terminus. In this report, we examine the functional consequences of some Rett mutations of CDKL5 together with some synthetically designed derivatives useful to underline the functional domains of the protein. The mutated CDKL5 derivatives have been subjected to in vitro kinase assays and analyzed for phosphorylation of the TEY (Thr-Glu-Tyr) motif within the activation loop, their subcellular localization, and the capacity of CDKL5 to interact with itself. Whereas wild-type CDKL5 autophosphorylates and mediates the phosphorylation of the methyl-CpG-binding protein 2 (MeCP2) in vitro, Rett-mutated proteins show both impaired and increased catalytic activity suggesting that a tight regulation of CDKL5 is required for correct brain functions. Furthermore, we show that CDKL5 can self-associate and mediate the phosphorylation of its own TEY (Thr-Glu-Tyr) motif. Eventually, we show that the COOH terminus regulates CDKL5 properties; in particular, it negatively influences the catalytic activity and is required for its proper sub-nuclear localization. We propose a model in which CDKL5 phosphorylation is required for its entrance into the nucleus whereas a portion of the COOH-terminal domain is responsible for a stable residency in this cellular compartment probably through protein-protein interactions

Cardiogenic Shock in Obstructive Hypertrophic Cardiomyopathy Plus Apical Ballooning: Management With VA-ECMO and Myectomy

A patient with known obstructive hypertrophic cardiomyopathy developed worsening left ventricular outflow tract obstruction, severe mitral regurgitation, and apical ballooning leading to cardiogenic shock, a combination in which treatment of each component could worsen the others. Emergency veno-arterial extracorporeal membrane oxygenation, levosimendan, and noradrenaline transiently restored adequate systemic perfusion and gas exchange. Surgical myectomy offered a more definitive solution. (Level of Difficulty: Intermediate.

Direction distributions of neutrons and reference values of the personal dose equivalent in workplace fields

Within the EC project EVIDOS, double-differential (energy and direction) fluence spectra were determined by means of novel direction spectrometers. By folding the spectra with fluence-to-dose equivalent conversion coefficients, contributions to H*(10) for 14 directions, and values of the personal dose equivalent Hp(10) and the effective dose E for 6 directions of a person's orientation in the field were determined. The results of the measurements and calculations obtained within the EVIDOS project in workplace fields in nuclear installations in Europe, i.e., at Krümmel (boiling water reactor and transport cask), at Mol (Venus research reactor and fuel facility Belgonucléaire) and at Ringhals (pressurised reactor and transport cask) are presente

Characterisation of mixed neutron-photon workplace fields at nuclear facilities by spectrometry (energy and direction) within the EVIDOS project

Within the EC project EVIDOS, 17 different mixed neutron-photon workplace fields at nuclear facilities (boiling water reactor, pressurised water reactor, research reactor, fuel processing, storage of spent fuel) were characterised using conventional Bonner sphere spectrometry and newly developed direction spectrometers. The results of the analysis, using Bayesian parameter estimation methods and different unfolding codes, some of them especially adapted to simultaneously unfold energy and direction distributions of the neutron fluence, showed that neutron spectra differed strongly at the different places, both in energy and direction distribution. The implication of the results for the determination of reference values for radiation protection quantities (ambient dose equivalent, personal dose equivalent and effective dose) and the related uncertainties are discusse

Neutron area survey instrument measurements in the EVIDOS project

Neutron survey instruments have been exposed at all the measurement locations used in the EVIDOS project. These results have an important impact in the interpretation of the results from the project, since operationally the survey instrument will be used for an initial assessment of and routine monitoring of the ambient dose equivalent dose rate. Additionally, since the response of these instruments is in some cases very well characterised, their systematic deviations from the reference quantities provide an important verification of the determination of those quantitie