The light stop window

We show that a right-handed stop in the 200-400 GeV mass range, together with a nearly degenerate neutralino and, possibly, a gluino below 1.5 TeV, follows from reasonable assumptions, is consistent with present data, and offers interesting discovery prospects at the LHC. Triggering on an extra jet produced in association with stops allows the experimental search for stops even when their mass difference with neutralinos is very small and the decay products are too soft for direct observation. Using a razor analysis, we are able to set stop bounds that are stronger than those published by ATLAS and CMS.Comment: 21 pages, 9 figures. v2: fig. 9b has been updated and revised at large values of the stop/neutralino mass splitting. The discussion of stop co-annihilations has been upgraded including Sommerfeld enhancement

A APROVAÇÃO DE LOTEAMENTOS NO MUNICÍPIO DE ARARAQUARA ENTRE 2005 E 2016: A produção de segregação socioespacial

O objetivo é identificar a segregação socioespacial no perímetro urbano de Araraquara-SP. A hipótese é que empreendimentos aprovados no período entre 2005 e 2016 possam ter sido desviados do PD/2005, que procurava estabelecer compacidade e justiça. A pesquisa é exploratória-descritiva, de abordagem qualitativa-quantitativa, com estratégias de estudo de caso, levantamento de dados e referências bibliográficas sobre segregação socioespacial e compacidade. Observou-se que dos 24 loteamentos a menos de 5 km do Centro, 83,3% foram precificados por valores superiores a R$450,00/m2 e 75$ 367,00/m2 ou pertencem ao programa Minha Casa Minha Vida; do total de 15.511 lotes aprovados no período, 9.091 destes estão acima de 5 km do Centro e precificados abaixo dos R$ 367,00/m2

A EVOLUÇÃO URBANA DO MUNICÍPIO DE ARARAQUARA (SP): UMA CRÍTICA AO ESPRAIAMENTO

Trata-se de uma pesquisa exploratória, de caráter qualitativo-quantitativo, com técnicas de pesquisa bibliográfica, de levantamento de dados e de mapeamento geoprocessado. O objeto de estudo é a área urbana do município de Araraquara (SP), sua ocupação e uso do solo, desde o final do século XIX até a década de 2010. Foi objetivo analisar, por mapeamento geoprocessado, a evolução da área urbana identificando localização, limites e dimensões de cada loteamento aprovado, destacando-se períodos e loteamentos específicos que impactaram na forma e no total de área ocupada. Como resultado, a pesquisa pode contribuir identificando três anos (1977, 1979 e 1994) que apresentaram grande concentração na quantidade de novos loteamentos e no total da área loteada, trazendo consequências negativas no que se refere à compacidade e ao provável aumento no custo dos serviços públicos

MOBILIDADE URBANA NÃO-SUSTENTÁVEL: a forma urbana e a priorização dos modais motorizados movidos à combustíveis fósseis em Araraquara (SP)

A priorização de modais motorizados movidos a combustíveis fósseis, especialmente os individuais, são prioridade dos governos brasileiros desde a década de 1950. Sua importância chega a, essencialmente, compor uma política pública de Estado, tamanha participação nos principais setores econômicos e produtivos no Brasil. Tal importância, independentemente de vieses ideológicos, foi observada tanto em períodos de auge do desenvolvimentismo no regime militar iniciado em 1964, assim como nas reduções de IPI (Imposto sobre Produtos Industrializados) em governos de centro-esquerda em um movimento denominado de neodesenvolvimentismo. De toda forma, as principais decisões baseadas neste modelo macroeconômico trouxeram – e ainda trazem – consequências cada vez mais insustentáveis no quesito políticas públicas, demografia e planejamento urbano colocando, constantemente, os principais estudos em busca de soluções que permitam apontar/resolver decisões anteriores equivocadas. Por isso, neste artigo, objetiva-se colocar em discussão decisões que poderiam ter sido evitadas ao esmiuçar o caso do município de Araraquara (SP) que presenciou sua área urbana passar de 3.352,61 hectares no ano de 1971 para 15.504,13 hectares em 2013, impactando na quantidade de vazios urbanos e resultando em necessidades cada vez maiores de aumento da infraestrutura aos transportes coletivos para cobrir o território cada vez mais espraiado, sendo este cenário impulsionado em grande parte pela flexibilidade dos modais individuais e coletivos movidos a combustíveis fósseis, que possibilitaram a abertura de loteamentos mais distante da centralidade da área urbana e que encaminharam o encerramento do transporte coletivo movido à energia elétrica

Treg/Tcon Immunotherapy and High Dose Marrow Irradiation Ensure Full Control of Leukemia Relapse in Haploidentical Transplantation

Allogeneic hematopoietic stem cell transplantation (HSCT) is the most powerful therapy for patients with high risk of relapse. In spite of that, no matter the donor source or conditioning regimen used, leukemia relapse is still the leading cause of HSCT failure. In HLA-haploidentical HSCT, we recently applied a clinical protocol consisting of total body irradiation (TBI)-based conditioning regimen and a peripheral blood CD34+ cell graft combined with the adoptive transfer of naturally occurring regulatory T cells (Tregs) and conventional T cells (Tcons). No post-transplant pharmacologic GvHD prophylaxis was given. Such protocol was associated with low GvHD and relapse rate (Martelli et al., Blood 2014). To further reduce leukemia relapse in Treg/Tcon-based haploidentical HSCT (Treg/Tcon haplo-HSCT) we used high dose hyper-fractionated TBI (HF-TBI) in the conditioning regimen. We also extended Treg/Tcon haplo-HSCT to patients that are unfit (because of previous comorbidities) and/or too old to withstand high intensity regimens. In these patients the extra-hematologic toxicity of irradiation was reduced with the use of targeted total marrow and lymph node irradiation (TMLI). 40 patients with high risk acute leukemia (36 AML, 4 ALL) received Treg/Tcon haplo-HSCT. All but 3 patients were transplanted in complete remission. 12 younger patients (median age: 28, range: 20-43) received HF-TBI, while 28 older or unfit patients (59, 40-70) received TMLI in the conditioning regimen. HF-TBI (14.4 Gy) was administered in 12 fractions, 3 times a day for 4 days. TMLI was administered by means of Helical Tomotherapy HI-ART (9 fractions, 2 times a day for 4.5 days). Irradiation was followed by chemotherapy with Thiotepa, Fludarabine, and Cyclophosphamide. 2 × 106/kg freshly isolated CD4+CD25+FOXP3+ Tregs were transferred 4 days before the infusion of 1 × 106/kg Tcons and a mega-dose of CD34+ hematopoietic stem cells. No post-transplant pharmacologic GvHD prophylaxis was given. 38/40 patients engrafted. 12 (31%) developed aGvHD grade ³2 (10 are alive and off-therapy). 6 (16%) died because of transplant related complications (2 because of aGvHD, 2 infections, 1 veno-occlusive disease, 1 intracranial hemorrhage). Strikingly, despite the high risk diseases, no patient relapsed after a median follow up of 13 months (range 1-36, Fig. A). Further, only 1 patient developed cGvHD. Thus, cGvHD/Leukemia-free survival was 82% (Fig. B). Treg adoptive transfer allows for the safe infusion of an otherwise lethal dose of donor alloreactive Tcons in the absence of any other form of immune suppression. Our results demonstrate that the potent graft versus leukemia effect of Treg/Tcon adoptive transfer was boosted by high dose marrow irradiation. Thus, this study proves that the right combination of haploidentical Treg/Tcon immunotherapy plus a powerful conditioning regimen can fully eradicate leukemia

Efficacy of Non-Pharmacological Interventions to Prevent and Treat Delirium in Older Patients : A Systematic Overview. The SENATOR project ONTOP Series

The research leading to these results has received funding from the European Union Seventh Framework program (FP7/2007-2013) under grant agreement n° 305930 (SENATOR). The funders had no role in the study design, data collection and analysis, the decision to publish, or the preparation of the manuscript.Peer reviewedPublisher PD

Indirect Impact of PD-1/PD-L1 Blockade on a Murine Model of NK Cell Exhaustion

The induction of exhaustion on effector immune cells is an important limiting factor for cancer immunotherapy efficacy as these cells undergo a hierarchical loss of proliferation and cytolytic activity due to chronic stimulation. Targeting PD-1 has shown unprecedented clinical benefits for many cancers, which have been attributed to the prevention of immune suppression and exhaustion with enhanced anti-tumor responses. In this study, we sought to evaluate the role of the PD-1/PD-L1 pathway in murine natural killer (NK) cell activation, function, and exhaustion. In an in vivo IL-2-dependent exhaustion mouse model, neutralization of the PD-1/PD-L1 pathway improved NK cell activation after chronic stimulation when compared to control-treated mice. These cells displayed higher proliferative capabilities and enhanced granzyme B production. However, the blockade of these molecules during long-term in vitro IL-2 stimulation did not alter the progression of NK cell exhaustion (NCE), suggesting an indirect involvement of PD-1/PD-L1 on NCE. Given the expansion of CD8 T cells and regulatory T cells (Tregs) observed upon acute and chronic stimulation with IL-2, either of these two populations could influence NK cell homeostasis after PD-L1/PD-1 therapy. Importantly, CD8 T cell activation and functional phenotype were indeed enhanced by PD-1/PD-L1 therapy, particularly with anti-PD-1 treatment that resulted in the highest upregulation of CD25 during chronic stimulation and granted an advantage for IL-2 over NK cells. These results indicate a competition for resources between NK and CD8 T cells that arguably delays the onset of NCE rather than improving its activation during chronic stimulation. Supporting this notion, the depletion of CD8 T cells reversed the benefits of PD-1 therapy on chronically stimulated NK cells. These data suggest a bystander effect of anti-PD1 on NK cells, resulting from the global competition that exists between NK and CD8 T cells for IL-2 as a key regulator of these cells’ activation. Thus, achieving an equilibrium between these immune cells might be important to accomplish long-term efficacy during anti-PD-1/IL-2 therapy