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Background: A great majority of children with idiopathic nephrotic syndrome will relapse after successful treatment of the initial episode. The possibility that different steroid dosing regimens at onset, adjusted for risk factors, can reduce the rate of relapse represents an interesting option to investigate. Objectives: To evaluate the effect of the initial steroid regimen, adjusted for time to remission (TTR), on the frequency of relapses and steroid dependence, and to verify the influence of prognostic factors on disease course. Methods: A multicentre, prospective, cohort study. Children with nephrotic syndrome, with TTR ≤ 10 days (Group A), were given a 20-week prednisone regimen (2,828 mg/m2) and those with a TTR >10 days, a 22-week regimen (3,668 mg/m2) (Group B). Previously published retrospective data from the same centers were also evaluated. Main outcomes were: relapse rate, number of frequent relapsers + steroid dependent children and total prednisone dose after induction. Results: 143 children were enrolled. Rate of relapsed subjects (77 vs. 79%) and frequent relapsers + steroid dependent subjects (40 vs. 53%) did not differ between Groups A and B, or between the retrospective and prospective cohorts. The cumulative prednisone dose taken after the induction treatment was similar in both groups and in the retrospective and prospective cohorts. TTR was not associated with relapse risk. Age at onset and total serum protein were significantly lower in relapsing patients. At ROC analysis, the best cut-off was 5.3 years for age at onset and 4.2 g/dL for total serum protein. According to these cut-offs, older children with higher total serum protein had a higher relapse free survival rate (58%) than younger children with lower total serum protein (17%). Conclusions: TTR was not found to be a prognostic factor of relapse; because of this, different steroid regimens, adjusted for TTR, did not modify the relapse rate in any relevant measure. Conversely, younger age and low total serum protein were independent predictors of relapse risk, however this outcome was not modified by higher prednisone regimens. Clinical Trial Registration:https://www.ClinicalTrials.gov/, identifier: NCT01386957 (www.nefrokid.it).

Can artificial intelligence (AI) raise productivity? If we regard AI as a com-bination of software, hardware and database use, then it can be modelled as acombination of the deployment of intangible and tangible assets. Since some aremeasured and some are not, then conventional productivity analysis might miss thecontribution of AI. We set out whether there is any evidence to support this view.

In patients with atrial fibrillation, local activation time (LAT) maps are routinely used for characterizing patient pathophysiology. The gradient of LAT maps can be used to calculate conduction velocity (CV), which directly relates to material conductivity and may provide an important measure of atrial substrate properties. Including uncertainty in CV calculations would help with interpreting the reliability of these measurements. Here, we build upon a recent insight into reduced-rank Gaussian processes (GPs) to perform probabilistic interpolation of uncertain LAT directly on human atrial manifolds. Our Gaussian process manifold interpolation (GPMI) method accounts for the topology of the atrium, and allows for calculation of statistics for predicted CV. We demonstrate our method on two clinical cases, and perform validation against a simulated ground truth. CV uncertainty depends on data density, wave propagation direction and CV magnitude. GPMI is suitable for probabilistic interpolation of other uncertain quantities on non-Euclidean manifolds.\ud \ud This article is part of the theme issue ‘Uncertainty quantification in cardiac and cardiovascular modelling and simulation’.

Oreomunnea mexicana (Stand.) J.F. Leroy is a relict species, threatened and a key species for cloud ecosystem functionof the Sierra Juárez, Oaxaca, the most extensive and best conserved in Mexico. This study includes a diagnostic on two critical stages of the process of population regeneration of O. mexicana. To this end, it analyzed the: 1) production, dispersion, viability and germination of seeds, 2) effect of predation on the growth and survival of the seedlings, and 3) effect of environmental variables (soil, canopy structure and solar radiation) on the regeneration of the species. The study was made from 2014 to 2015 in the cloud forest of Santiago Comaltepec, Oaxaca, Mexico, in two locations (San Bernardo and El Orquidiario). Differences in seed production were found between years and between locations, as well as low seed viability and a high percentage of seed parasitism. The establishment and growth of the seedlings are subject to find suitable microhabitats, since seedlings have specific illumination and soil requirements. The high edaphic specificity faced by the species could be a key factor for its fragmented and discontinuous distribution in Sierra Juárez. Further population regeneration studies are recommended to increase knowledge of the species and thereby achieve its conservation. © 2019, Instituto de Ecologia, A.C. All rights reserved.

Has productivity growth been held back by impaired capital reallocation since the financial crisis? Have low interest rates disrupted the reallocation process? This paper calculates the effect on productivity growth of capital reallocation between industries. It uses an accounting framework, due to Jorgenson and his co-authors, that computes the contribution of capital services to productivity growth relative to a counter-factual of a well-functioning financial system. Using data from 11 countries (the major EU economies plus the US), in 1997-2013, we find: (a) the contribution of reallocation to productivity growth has generally fallen in most economies since the 2000s, notably in Mediterranean countries and fell sharply in many countries in the financial crisis years (b) reallocation is impaired in countries with more uncertainty and where banks hold less regulatory capital and (c) more reallocation is correlated with lower real interest rates, contrary to the hypothesis that low real interest rates have hurt reallocation.

Panobinostat in combination with bortezomib and dexamethasone demonstrated a significant and clinically meaningful progression-free survival benefit compared with placebo, bortezomib and dexamethasone in the phase 3 PANORAMA 1 (Panobinostat Oral in Multiple Myeloma 1) trial. Despite this benefit, patients in the panobinostat arm experienced higher rates of adverse events (AEs) and higher rates of discontinuation due to AEs. This PANORAMA 1 subanalysis examined AEs between 2 treatment phases of the study (TP1 and TP2), in which administration frequency of bortezomib and dexamethasone differed per protocol. The incidences of several key AEs were lower in both arms following the planned reduction of bortezomib dosing frequency in TP2. In the panobinostat arm, rates of thrombocytopenia (grade 3/4: TP1, 56·7%; TP2, 6·0%), diarrhoea (grade 3/4: TP1, 24·1%; TP2, 7·1%), and fatigue (grade 3/4: TP1, 16·3%; TP2, 1·8%) were lower in TP2 compared with TP1. Dose intensity analysis of panobinostat and bortezomib by cycle in the panobinostat arm showed reductions of both agent doses during cycles 1–4 due to dose adjustments for AEs. Exposure-adjusted analysis demonstrated a reduction in thrombocytopenia frequency in TP1 following dose adjustment. These results suggest that optimization of dosing with this regimen could improve tolerability, potentially leading to improved patient outcomes. © 2017 John Wiley & Sons Ltd

In this paper we describe the steps followed to build a new dataset covering the universe of active private non-financial firms in Italy between 2005 and 2014. The construction of the dataset is the outcome of a collaboration between the Bank of Italy and the Italian National Statistical Agency and made use of statistical, administrative and fiscal sources. The dataset, that contains information on firms’ location, legal form, date of incorporation, industry classification, employed persons, turnover and value added, is suitable for studying the evolution of the Italian productive sectors since the mid-2000s.

Breast cancer-related lymphedema (LE) represents an important morbidity that jeopardizes breast cancer patients' quality of life. Different attempts to prevent LE brought about improvements in the incidence of the pathology but LE still represents a frequent occurrence in breast cancer survivors. Over 4 years ago, Lymphatic Microsurgical Preventing Healing Approach (LYMPHA) was proposed and long-term results are reported in this study. From July 2008 to December 2012, 74 patients underwent axillary nodal dissection for breast cancer treatment together with LYMPHA procedure. Volumetry was performed preoperatively in all patients and after 1, 3, 6, 12 months, and once a year. Lymphoscintigraphy was performed in 45 patients preoperatively and in 30 also postoperatively after at least over 1 year. Seventy one patients had no sign of LE, and volumetry was coincident to preoperative condition. In three patients, LE occurred after 8–12 months postoperatively. Lymphoscintigraphy showed the patency of lymphatic-venous anastomoses at 1–4 years after operation. LYMPHA technique represents a successful surgical procedure for primary prevention of arm LE in breast cancer patients. © 2014 Wiley Periodicals, Inc. Microsurgery 34:421–424, 2014.

rene multi cistico;agenesia renale; ipertensione arteriosa; nefrectomia; ipertrofia compensatoria

Panobinostat is a potent pan-deacetylase inhibitor that affects the growth and survival of multiple myeloma (MM) cells through alteration of epigenetic mechanisms and protein metabolism. Panobinostat plus bortezomib and dexamethasone (PAN-BTZ-Dex) led to a significant increase in progression-free survival (PFS) vs placebo plus bortezomib and dexamethasone (Pbo-BTZ-Dex) in patients with relapsed or relapsed and refractoryMMin the phase 3PANORAMA1 trial. This subgroup analysis evaluated outcomes in patients in the PANORAMA 1 trial based on prior treatment: A prior immunomodulatory drug (IMiD; n 5 485), prior bortezomib plus an IMiD (n 5 193), and ≥2 prior regimens including bortezomib and an IMiD (n5147). Median PFS with PAN-BTZ-Dex vs Pbo-BTZ-Dex across subgroups was as follows: prior IMiD (12.3 vs 7.4 months; hazard ratio [HR], 0.54; 95% confidence interval [CI], 0.43-0.68), prior bortezomib plus IMiD (10.6 vs 5.8 months; HR, 0.52;95%CI, 0.36-0.76),and ≥2 prior regimens including bortezomib and an IMiD (12.5 vs 4.7 months; HR, 0.47; 95% CI, 0.31-0.72). Common grade 3/4 adverse events and laboratory abnormalities in patients who received PAN-BTZ-Dex across the prior treatment groups included thrombocytopenia, lymphopenia, neutropenia, diarrhea, and asthenia/ fatigue. Incidence of on-treatment deaths among patients who received prior bortezomib and an IMiD (regardless of number of prior regimens) was similar between treatment arms. This analysis demonstrated a clear PFS benefit of 7.8 months with PAN-BTZ-Dex among patients who received ‡2 prior regimens including bortezomib and an IMiD, a population with limited treatment options and poorer prognosis. This trial was registered at www.clinicaltrials.gov as #NCT01023308. © 2016 by The American Society of Hematology.

La struttura produttiva italiana, caratterizzata prevalentemente da piccole e medie imprese (PMI), č considerata come un fattore limitante della capacitŕ di crescita economica, in considerazione delle limitate possibilitŕ di effettuare investimenti, e quindi di fare progressi nel campo della ricerca e dell'innovazione. Le piccole e medie imprese vantano perň un loro punto di forza ove esse siano organizzate in distretti industriali, molti dei quali sono noti come distretti del "made in Italy". Riprendendo le definizioni teoriche di distretto industriale, introdotte da Marshall e da Becattini e gli studi che hanno affrontato il problema dell'identificazione statistica dei distretti industriali1, in questo lavoro, dopo un'analisi critica delle metodologie attualmente applicate, si propone una metodologia alternativa. Essa intende ricercare un legame piů stringente tra i concetti teorici utilizzati dagli economisti - come per esempio quelli di comunitŕ di persone, di concentrazione e di specializzazione - e i concetti statistici che li possono meglio rappresentare.

The Middle Miocene Marnoso-arenacea Formation at Deruta in the northern Apennines of Italy rests unconformably on an orogenic wedge adjacent to the Adriatic foredeep. Based on a detailed facies analysis, the succession reveals two genetically related depositional systems: a distal delta-fed sand-rich system and a more proximal fan-delta slope system. Petrographic data confirm the genetic relationship between the two depositional systems, with the fan-delta slope feeding the basinward sand-rich system. The Deruta depositional setting shows a multi-step sedimentary evolution controlled by tectonically induced relative sea-level changes. The first stage, corresponding to a sea-level rise, promoted deposition in a wedge-top basin of pebbly sand and sand lobes (delta-fed). The second stage, characterized by intense tectonic activity (uplift) and sea-level fall, promoted accumulation of a prograding fan-delta slope replacing the sand-rich lobes. This phase was dominated by mass failures and methanogenic cold seepages. During these two stages, the wedge-top basin was isolated from the adjacent foredeep. Only during the third stage was a connection established, with the development of a deep-sea fan in the foredeep, fed by a deltaic depositional system.

Cell to cell communication is essential for the coordination and proper organization of different cell types in multicellular systems. Cells exchange information through a multitude of mechanisms such as secreted growth factors and chemokines, small molecules (peptides, ions, bioactive lipids and nucleotides), cell-cell contact and the secretion of extracellular matrix components. Over the last few years, however, a considerable amount of experimental evidence has demonstrated the occurrence of a sophisticated method of cell communication based on the release of specialized membranous nano-sized vesicles termed exosomes. Exosome biogenesis involves the endosomal compartment, the multivesicular bodies (MVB), which contain internal vesicles packed with an extraordinary set of molecules including enzymes, cytokines, nucleic acids and different bioactive compounds. In response to stimuli, MVB fuse with the plasma membrane and vesicles are released in the extracellular space where they can interact with neighboring cells and directly induce a signaling pathway or affect the cellular phenotype through the transfer of new receptors or even genetic material. This review will focus on exosomes as intercellular signaling organelles involved in a number of physiological as well as pathological processes and their potential use in clinical diagnostics and therapeutics.