Testing for rational speculative bubbles in the Brazilian residential real-estate market

Speculative bubbles have been occurring periodically in local or global real estate markets and are considered a potential cause of economic crises. In this context, the detection of explosive behaviors in the financial market and the implementation of early warning diagnosis tests are of critical importance. The recent increase in Brazilian housing prices has risen concerns that the Brazilian economy may have a speculative housing bubble. In the present paper, we employ a recently proposed recursive unit root test in order to identify possible speculative bubbles in data from the Brazilian residential real-estate market. The empirical results show evidence for speculative price bubbles both in Rio de Janeiro and Sao Paulo, the two main Brazilian cities

New insights in the pathogenesis of T-cell lymphomas.

Peripheral T-cell lymphomas (PTCLs) represent diverse and aggressive malignancies, with few recent therapeutic improvements. Recent high-throughput genomic studies have revealed the complex mutational landscape of these rare diseases. These novel findings provide the grounds to a more comprehensive classification of these diseases, reflected in the 2017 WHO classification. Our review is focused on selected PTCL entities. Angioimmunoblastic T-cell lymphoma and other lymphomas derived from T follicular helper cells feature a rather homogeneous mutational landscape. These neoplasms recapitulate a multistep oncogenic process associating epigenetic deregulation, and second hit mutations affecting the T-cell receptor signaling pathway. This model inferred from comprehensive analyses of patients samples, was confirmed in mouse models. Among ALK-negative anaplastic large-cell lymphomas, translocation-associated subsets are found in both systemic and cutaneous types, and the newly described breast implant-associated type is usually indolent. Extranodal lymphomas of the innate immune system also harbor a combination of mutations affecting different classes of epigenetic modifiers, and mutation-induced activation of the Janus Kinase/signal transduction and activator of transcription pathway. Understanding of PTCL pathogenesis has substantially improved, and oncogenic events have been identified. The current challenge is to mount efficient therapeutic strategies targeting these aberrations to improve patients' outcome

The magnetic properties of 177^{\rm 177}Hf and 180^{\rm 180}Hf in the strong coupling deformed model

This paper reports NMR measurements of the magnetic dipole moments of two high-K isomers, the 37/2$^-$, 51.4 m, 2740 keV state in $^{\rm 177}$Hf and the 8$^-$, 5.5 h, 1142 keV state in $^{\rm 180}$Hf by the method of on-line nuclear orientation. Also included are results on the angular distributions of gamma transitions in the decay of the $^{\rm 177}$Hf isotope. These yield high precision E2/M1 multipole mixing ratios for transitions in bands built on the 23/2$^+$, 1.1 s, isomer at 1315 keV and on the 9/2$^+$, 0.663 ns, isomer at 321 keV. The new results are discussed in the light of the recently reported finding of systematic dependence of the behavior of the g$_{\rm R}$ parameter upon the quasi-proton and quasi-neutron make up of high-K isomeric states in this region.Comment: 9 pages, 9 figures, accepted for publication in Physical Review

Controversies in the Treatment of Peripheral T-cell Lymphoma.

Peripheral T-cell lymphomas are a heterogeneous group of rare diseases with an aggressive behavior and dismal prognosis. Their classification is complex and still evolving, and several biomolecular markers now help refine the prognosis of specific disease entities, although still have limited impact in tailoring the treatment. First-line treatment strategies can cure only a minority of patients and relapsed-refractory disease still represents the major cause of failure. Frontline autologous transplantation may have an impact in the consolidation of response; however, its role is still questioned as far as complete responses obtained after induction chemotherapy are concerned. Newer drugs are now being evaluated in clinical trials, but effective salvage strategies for those who experience treatment failures are lacking. Here we review and discuss the most controversial aspects of diagnosis and treatment of peripheral T-cell lymphomas

Clinical impact of recurrently mutated genes on lymphoma diagnostics

Similar to the inherent clinical heterogeneity of most, if not all, lymphoma entities, the genetic landscape of these tumors is markedly complex in the majority of cases, with a rapidly growing list of recurrently mutated genes discovered in recent years by next-generation sequencing technology. Whilst a few genes have been implied to have diagnostic, prognostic and even predictive impact, most gene mutations still require rigorous validation in larger, preferably prospective patient series, to scrutinize their potential role in lymphoma diagnostics and patient management. In selected entities, a predominantly mutated gene is identified in almost all cases (e.g. Waldenström's macroglobulinemia/lymphoplasmacytic lymphoma and hairy-cell leukemia), while for the vast majority of lymphomas a quite diverse mutation pattern is observed, with a limited number of frequently mutated genes followed by a seemingly endless tail of genes with mutations at a low frequency. Herein, the European Expert Group on NGS-based Diagnostics in Lymphomas (EGNL) summarizes the current status of this ever-evolving field, and, based on the present evidence level, segregates mutations into the following categories: i) immediate impact on treatment decisions, ii) diagnostic impact, iii) prognostic impact, iv) potential clinical impact in the near future, or v) should only be considered for research purposes. In the coming years, coordinated efforts aiming to apply targeted next-generation sequencing in large patient series will be needed in order to elucidate if a particular gene mutation will have an immediate impact on the lymphoma classification, and ultimately aid clinical decision making

Angioimmunoblastic T-cell lymphoma and Kaposi sarcoma: A fortuitous collision?

Follicular helper T-cell (TFH) lymphoma of the angioimmunoblastic-type (AITL), one of the most prevalent T-cell lymphomas, typically encompasses proliferation of high endothelial venules and Epstein-Barr virus-positive immunoblasts, but neither infection with HHV8 nor association with Kaposi's sarcoma (KS) have been described. The aims of this study are to characterise the association between AITL and HHV8 infection or KS. Three male patients aged 49-76 years, HIV-negative, with concurrent nodal involvement by AITL and KS, were identified from our files and carefully studied. Two patients originated from countries where endemic KS occurs, including one with cutaneous KS. The lymphomas featured abundant vessels, expanded follicular dendritic cells and neoplastic TFH cells [PD1+ (three of three), ICOS+ (three of three), CXCL13+ (three of three), CD10 <sup>+</sup> (two of three), BCL6 (two of three)] but lacked EBV+ immunoblasts. The foci of KS consisted of subcapsular proliferations of ERG+, CD31 <sup>+</sup> and/or CD34 <sup>+</sup> , HHV8+ spindle cells. High-throughput sequencing showed AITL-associated mutations in TET2 (three of three), RHOA (G17V) (three of three) and IDH2 (R172) (two of three), which were absent in the microdissected KS component in two cases. Relapses in two patients consisted of AITL, without evidence of KS. No evidence of HHV8 infection was found in a control group of 23 AITL cases. Concurrent nodal involvement by AITL and KS is rare and identification of both neoplastic components may pose diagnostic challenges. The question of whether the association between AITL and KS may be fortuitous or could reflect the underlying immune dysfunction in AITL remains open

Loss of 5-hydroxymethylcytosine is a frequent event in peripheral T-cell lymphomas.

International audienc

Targeting intratumoral B cells with rituximab in addition to CHOP in angioimmunoblastic T-cell lymphoma. A clinicobiological study of the GELA.

Background In angioimmunoblastic T-cell lymphoma, symptoms linked to B-lymphocyte activation are common, and variable numbers of CD20(+) large B-blasts, often infected by Epstein-Barr virus, are found in tumor tissues. We postulated that the disruption of putative B-T interactions and/or depletion of the Epstein-Barr virus reservoir by an anti-CD20 monoclonal antibody (rituximab) could improve the clinical outcome produced by conventional chemotherapy. DESIGN AND METHODS: Twenty-five newly diagnosed patients were treated, in a phase II study, with eight cycles of rituximab + chemotherapy (R-CHOP21). Tumor infiltration, B-blasts and Epstein-Barr virus status in tumor tissue and peripheral blood were fully characterized at diagnosis and were correlated with clinical outcome. RESULTS: A complete response rate of 44% (95% CI, 24% to 65%) was observed. With a median follow-up of 24 months, the 2-year progression-free survival rate was 42% (95% CI, 22% to 61%) and overall survival rate was 62% (95% CI, 40% to 78%). The presence of Epstein-Barr virus DNA in peripheral blood mononuclear cells (14/21 patients) correlated with Epstein-Barr virus score in lymph nodes (P<0.004) and the detection of circulating tumor cells (P=0.0019). Despite peripheral Epstein-Barr virus clearance after treatment, the viral load at diagnosis (>100 copy/μg DNA) was associated with shorter progression-free survival (P=0.06). Conclusions We report here the results of the first clinical trial targeting both the neoplastic T cells and the microenvironment-associated CD20(+) B lymphocytes in angioimmunoblastic T-cell lymphoma, showing no clear benefit of adding rituximab to conventional chemotherapy. A strong relationship, not previously described, between circulating Epstein-Barr virus and circulating tumor cells is highlighted

Type II enteropathy-associated T-cell lymphoma features a unique genomic profile with highly recurrent SETD2 alterations.

Enteropathy-associated T-cell lymphoma (EATL), a rare and aggressive intestinal malignancy of intraepithelial T lymphocytes, comprises two disease variants (EATL-I and EATL-II) differing in clinical characteristics and pathological features. Here we report findings derived from whole-exome sequencing of 15 EATL-II tumour-normal tissue pairs. The tumour suppressor gene SETD2 encoding a non-redundant H3K36-specific trimethyltransferase is altered in 14/15 cases (93%), mainly by loss-of-function mutations and/or loss of the corresponding locus (3p21.31). These alterations consistently correlate with defective H3K36 trimethylation. The JAK/STAT pathway comprises recurrent STAT5B (60%), JAK3 (46%) and SH2B3 (20%) mutations, including a STAT5B V712E activating variant. In addition, frequent mutations in TP53, BRAF and KRAS are observed. Conversely, in EATL-I, no SETD2, STAT5B or JAK3 mutations are found, and H3K36 trimethylation is preserved. This study describes SETD2 inactivation as EATL-II molecular hallmark, supports EATL-I and -II being two distinct entities, and defines potential new targets for therapeutic intervention