Risk of Cancer among Commercially Insured HIV-Infected Adults on Antiretroviral Therapy.

The objective of this study was to explore the cancer incidence rates among HIV-infected persons with commercial insurance who were on antiretroviral therapy and compare them with those rates in the general population. Paid health insurance claims for 63,221 individuals 18 years or older, with at least one claim with a diagnostic code for HIV and at least one filled prescription for an antiretroviral medication between January 1, 2006, and September 30, 2012, were obtained from the LifeLink® Health Plan Claims Database. The expected number of cancer cases in the general population for each gender-age group (<30, 30-39, 40-49, 50-59, and >60 years) was estimated using incidence rates from the Surveillance Epidemiology and End Results (SEER) program. Standardized incidence ratios (SIRs) were estimated using their 95% confidence intervals (CIs). Compared to the general population, incidence rates for HIV-infected adults were elevated (SIR, 95% CI) for Kaposi sarcoma (46.08; 38.74-48.94), non-Hodgkin lymphoma (4.22; 3.63-4.45), Hodgkin lymphoma (9.83; 7.45-10.84), and anal cancer (30.54; 25.62-32.46) and lower for colorectal cancer (0.69; 0.52-0.76), lung cancer (0.70; 0.54, 0.77), and prostate cancer (0.54; 0.45-0.58). Commercially insured, treated HIV-infected adults had elevated rates for infection-related cancers, but not for common non-AIDS defining cancers

Cooperative action in eukaryotic gene regulation: physical properties of a viral example

The Epstein-Barr virus (EBV) infects more than 90% of the human population, and is the cause of several both serious and mild diseases. It is a tumorivirus, and has been widely studied as a model system for gene (de)regulation in human. A central feature of the EBV life cycle is its ability to persist in human B cells in states denoted latency I, II and III. In latency III the host cell is driven to cell proliferation and hence expansion of the viral population, but does not enter the lytic pathway, and no new virions are produced, while the latency I state is almost completely dormant. In this paper we study a physico-chemical model of the switch between latency I and latency III in EBV. We show that the unusually large number of binding sites of two competing transcription factors, one viral and one from the host, serves to make the switch sharper (higher Hill coefficient), either by cooperative binding between molecules of the same species when they bind, or by competition between the two species if there is sufficient steric hindrance.Comment: 7 pages, 6 figures, 1 tabl

Safety and preliminary efficacy of vorinostat with R-EPOCH in high-risk HIV-associated non-Hodgkin\u27s lymphoma (AMC-075)

We performed a phase I trial of vorinostat (VOR) given on days 1 to 5 with R-EPOCH (rituximab plus etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin hydrochloride) in patients with aggressive HIV-associated non-Hodgkin lymphoma. VOR was tolerable at 300 mg and seemingly efficacious with chemotherapy with complete response rate of 83% and 1-year event-free survival of 83%. VOR did not significantly alter chemotherapy steady-state concentrations, CD4+ cell counts, or HIV viral loads. Vorinostat (VOR), a histone deacetylase inhibitor, enhances the anti-tumor effects of rituximab (R) and cytotoxic chemotherapy, induces viral lytic expression and cell killing in Epstein-Barr virus-positive (EBV+) or human herpesvirus-8-positive (HHV-8+) tumors, and reactivates latent human immunodeficiency virus (HIV) for possible eradication by combination antiretroviral therapy (cART). We performed a phase I trial of VOR given with R-based infusional EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin hydrochloride) (n = 12) and cART in aggressive HIV-associated B-cell non-Hodgkin lymphoma (NHL) in order to identify safe dosing and schedule. VOR (300 or 400 mg) was given orally on days 1 to 5 with each cycle of R-EPOCH for 10 high-risk patients with diffuse large B-cell lymphoma (1 EBV+), 1 EBV+/HHV-8+ primary effusion lymphoma, and 1 unclassifiable NHL. VOR was escalated from 300 to 400 mg using a standard 3 + 3 design based on dose-limiting toxicity observed in cycle 1 of R-EPOCH. The recommended phase II dose of VOR was 300 mg, with dose-limiting toxicity in 2 of 6 patients at 400 mg (grade 4 thrombocytopenia, grade 4 neutropenia), and 1 of 6 treated at 300 mg (grade 4 sepsis from tooth abscess). Neither VOR, nor cART regimen, significantly altered chemotherapy steady-state concentrations. VOR chemotherapy did not negatively impact CD4+ cell counts or HIV viral loads, which decreased or remained undetectable in most patients during treatment. The response rate in high-risk patients with NHL treated with VOR(R)-EPOCH was 100% (complete 83% and partial 17%) with a 1-year event-free survival of 83% (95% confidence interval, 51.6%-97.9%). VOR combined with R-EPOCH was tolerable and seemingly efficacious in patients with aggressive HIV-NHL

Mapeamento da Cooperação Internacional da Marinha do Brasil (1999 - 2018)

As Marinhas são as forças armadas com maior vocação às relações internacionais, especialmente em um país de extenso território marítimo, tradição pacifista e potencial global, como o Brasil. No entanto, seus registros desse tipo de atuação da instituição encontravam-se dispersos, tendo sido o objetivo dessa pesquisa a criação de uma base de dados da Cooperação Internacional da Marinha do Brasil (MB) entre 1999, ano de criação do Ministério da Defesa (MD), e 2018, completando o período de duas décadas. O presente trabalho corresponde, portanto, a um relatório técnico-científico acerca da teoria, metodologia e resultados desse produto, o que está inserido no contexto da Diplomacia de Defesa. Inicialmente, a base de dados encontra-se em uma tabela de Excel, mas será transposta ainda esse ano (2019) para a Keyhole Markup Language (KML), ferramenta da Google para dados geoespaciais. Com isso, ter-se-á um mapa mundi digital, permitindo uma melhor visualização do conteúdo. Para a coleta de dados, foram utilizadas como fontes primárias as Organizações Militares (OMs) da MB e suas publicações internas. Do mesmo modo, foi consultado o acervo de outros importantes órgãos de Estado, como o MD e o Ministério das Relações Exteriores (MRE), esse último via Agência Brasileira de Cooperação (ABC) e Plataforma Concórdia. Para a organização dos dados, foram estabelecidas as categorias de classificação: ?Institucionalidade?, ?Natureza da Cooperação?, ?Eixo Hemisférico?, ?Lateralidade? e ?Tipo?. Acredita-se que, com essa base de dados, a MB terá um melhor panorama de suas relações internacionais, aumentando a robustez do processo decisório para a continuidade ou recondicionamento da sua política externa, que deve estar cada vez mais integrada com o MRE. Finalmente, destaca-se que esse projeto está de acordo com a crescente criação de produtos nas Ciências Sociais Aplicadas, o uso de ferramentas digitais na Era da Informação e a transparência esperada do meio acadêmico e instituições públicasNavies are the armed forces with the greatest vocation to international relations, specially in a country with an extensive maritime territory, peaceful behavour and global potential, like Brazil. However, this type of register in that institution was spread, which defines the goal of this research: the creation of a data basis with the international cooperation of the Brazilian Navy (MB) between 1999, the Ministry of Defense?s year of the creation, and 2018, completing two decades. The present work is, then, a technical-scientific report about the theory, the metodology and the results concerning the product created, which is inserted in the context of Defense Diplomacy. Initially, the data basis is in the format of an Excel spreadsheet, but it is going to be transferred to the Keyhole Markup Language (KML), a tool from Google to manage geospatial data. In this sense, it is going to be formed a digital world map, allowing a better view of the content. To the data mining, it was used as primary sources the military organizations (OM) of the Brazilian Navy and her internal publications. In the same way, it was consulted the collection of other important State bodies, such as the Ministry of Defense and the Ministry of International Relations (MRE), this last one through the Brazilian Cooperation Agency (ABC) and the Concórdia Platform. To the data organization, it was established the following categories of classification: ?Institutionalization?, ?Nature of Cooperation?, ?Hemisphere Axis?, ?Laterality? and ?Type?. It is believed that, with this data basis, the Brazilian Navy will have a better understanting of her international relations, improving the robustness of the decision-making process to remain or change the direction of the institution?s foreign policy, which should be each time more integrated with the Ministry of International Relations. Finally, it is highlighted that this project is going along with the growing of products creation in the Applied Social Sciences, the use of digital tools in the Age of Information and the transparency expected from public institution

Detection of the Epstein-Barr virus in blood and bone marrow mononuclear cells of patients with aggressive B-cell non Hodgkin's lymphoma is not associated with prognosis

The Epstein-Barr virus (EBV) is associated with a large spectrum of lymphoproliferative diseases. Traditional methods of EBV detection include the immunohistochemical identification of viral proteins and DNA probes to the viral genome in tumoral tissue. The present study explored the detection of the EBV genome, using the BALF5 gene, in the bone marrow or blood mononuclear cells of patients with diffuse large B-cell lymphomas (DLBCL) and related its presence to the clinical variables and risk factors. The results show that EBV detection in 21.5% of patients is not associated with age, gender, staging, B symptoms, international prog¬nostic index scores or any analytical parameters, including lactate dehydrogenase (LDH) or β-2 microglobulin (B2M). The majority of patients were treated with R-CHOP like (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone or an equivalent combination) and some with CHOP-like chemotherapy. Response rates [complete response (CR) + partial response (PR)] were not significantly different between EBV-negative and -positive cases, with 93.2 and 88.9%, respectively. The survival rate was also similar in the two groups, with 5-year overall survival (OS) rates of 64.3 and 76.7%, respectively. However, when analyzing the treatment groups separately there was a trend in EBV-positive patients for a worse prognosis in patients treated with CHOP-like regimens that was not identified in patients treated with R-CHOP-like regimens. We conclude that EBV detection in the bone marrow and blood mononuclear cells of DLBC patients has the same frequency of EBV detection on tumoral lymphoma tissue but is not associated with the risk factors, response rate and survival in patients treated mainly with immunochemotherapy plus rituximab. These results also suggest that the addition of rituximab to chemotherapy improves the prognosis associated with EBV detection in DLBCL