Long-term outcome after a treosulfan-based conditioning regimen for patients with acute myeloid leukemia: A report from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation

BACKGROUND: Allogeneic hematopoietic cell transplantation (HCT) is a curative therapy for patients with acute myeloid leukemia (AML). However, post-HCT relapse and regimen-related toxicity remain significant barriers to long-term survival. In recent years, new conditioning regimens have been explored to improve transplantation outcomes in patients with AML. Treosulfan combines a potent immunosuppressive and antileukemic effect with a low toxicity profile. METHODS: To investigate the role of treosulfan-based conditioning, the European Society for Blood and Marrow Transplantation Acute Leukemia Working Party performed a registry analysis of 520 adult patients with AML who received treosulfan-based conditioning and underwent HCT between 2000 and 2012, including 225 patients in first complete remission, 107 in second or later complete remission, and 188 with active/advanced disease 188 (88 with primary refractory disease). The median patient age was 57 years (range, 20-73 years). Donors were human leukocyte antigen-identical siblings (n = 187), unrelated donors (n = 235), or mismatched related donors (n = 98). Conditioning regimens included treosulfan (42 g/m2 [n = 396], 36 g/m2 [n = 109], or 30 g/ m2 [n = 15]) with fludarabine or alkylating agents followed by infusion of hematopoietic stem cells (bone marrow, n = 52; peripheral blood, n = 468). RESULTS: At a median follow-up of 61 months, the 5-year overall survival, leukemia-free survival, relapse incidence, and nonrelapse mortality rates were 38%, 33%, 42%, and 25%, respectively. The incidence of grade II-IV acute and chronic graft-versus-host disease was 24% (grade III-V, 11%) and 38%, respectively. Only 11 patients (2%) developed veno-occlusive disease, with two deaths (0.4%) from veno-occlusive disease. CONCLUSIONS: Treosulfan-based conditioning regimens provide an acceptable long-term survival with favorable nonrelapse mortality and a very low risk of veno-occlusive disease. Further studies are needed to optimize the treosulfan-based conditioning regimen for patients with AML

Vitamin D3-loaded electrospun cellulose acetate/polycaprolactone nanofibers: Characterization, in-vitro drug release and cytotoxicity studies

Vitamin D deficiency is nowa global health problem; despite several drug delivery systems for carrying vitaminD due to low bioavailability and loss bioactivity. Developing a new drug delivery system to deliver vitamin D3 is a strong incentive in the current study. Hence, an implantable drug delivery system (IDDS) was developed from the electrospun cellulose acetate (CA) and ε-polycaprolactone (PCL) nanofibrous membrane, in which the core of implants consists of vitamin D3-loaded CA nanofiber (CAVD) and enclosed in a thin layer of the PCL membrane (CAVD/PCL). CA nanofibrousmat loadedwith vitaminD3 at the concentrations of 6, 12, and 20% (w/w) of vitamin D3 were produced using electrospinning. The smooth and bead-free fibers with diameters ranged from 324 to 428 nm were obtained. The fiber diameters increased with an increase in vitamin D3 content. The controlled drug release profile was observed over 30-days, which fit with the zero-order model (R2 > 0.96) in the first stage. The mechanical properties of IDDS were improved. Young's modulus and tensile strength of CAVD/PCL (dry) were161 ± 14 and 13.07 ± 2.5 MPa, respectively. CA and PCL nanofibers are non-cytotoxic based on the results of the in-vitro cytotoxicity studies. This study can further broaden in-vivo study and provide a reference for developing a new IDDS to carry vitamin D3 in the future

Geothermal drilling technology update

Sandia National Laboratories conducts a comprehensive geothermal drilling research program for the US Department of Energy, Office of Geothermal Technologies. The program currently includes seven areas: lost circulation technology, hard-rock drill bit technology, high-temperature instrumentation, wireless data telemetry, slimhole drilling technology, Geothermal Drilling Organization (GDO) projects, and drilling systems studies. This paper describes the current status of the projects under way in each of these program areas

Criopreservação de sêmen de Jundiá, Rhamdia voulezi e r. branneri (Siluriformes: heptapteridae) utilizando diferentes crioprotetores

The species of catfish Rhamdia branneri and R. voulezi are endemic to the Iguaçu River Basin and have favorable characteristics which are interesting for fish farming. Semen cryopreservation technology has been widely used in aquaculture, especially in breeding and genetic conservation of endangered species. For these species had not yet studies on the subject. Thus, the objective was to conduct studies in order to compare different intracellular and extracellular cryoprotectants in semen cryopreservation catfish R. branneri and R. voulezi. Four cryoprotectant solution containing 10% of anhydrous glucose were tested (C6H12O6) as diluent. Solutions: 1 - DMSO (C2H6OS) and 10% egg yolk; 2 - methanol (CH3OH) 10% and 5% powdered milk; 3 - glycerol (C3H8O3) and 10% egg yolk and 4 - 10% glycerol and 5% milk powder, respectively intra and extracellular protector. Semen was collected and each species motility test performed for each sample, resulting in higher motility than 30 seconds considering just viable cryopreservation. Was performed semen pool of three males of R. voulezi and two males of R. branneri before submitting freezing, the solutions were tested ensuring the non-occurrence of activation by the extender solution. The activator solution was tested distilled water. The solution 1, containing DMSO was not effective for both species, showing no sperm motility after activation. For the motility time of R. voulezi the cryoprotectant solutions methanol + milk and glycerol + egg were similar to each other and higher glycerol + milk (P0.05) for the time variable motility. Assessing the motility intensity scale, the best result was obtained by glycerol + egg solution to R. branneri and equating to the glycerol + milk to R. voulezi. The semen R. branneri and R. voulezi can be cryopreserved with the solutions presented except the use of DMSO. The best extender solution in sperm motility for these species is glycerol + egg.As espécies de jundiá Rhamdia branneri e R. voulezi são endêmicas à Bacia do Rio Iguaçu e possuem características favoráveis que despertam interesse para a piscicultura. A tecnologia de criopreservação de sêmen vem sendo muito utilizada na aquicultura, principalmente no melhoramento genético e na conservação genética de espécies ameaçadas. Para estas espécies ainda não se tinham estudos relativos ao tema. Desta forma, objetivou-se realizar estudos a fim de comparar diferentes crioprotetores intra e extracelulares na criopreservação de sêmen de jundiá R. branneri e R. voulezi. Foram testadas quatro soluções crioprotetoras contendo 10% de glicose anidra (C6H12O6) como diluidor. Soluções: 1 - DMSO (C2H6OS) 10% e gema de ovo; 2 - metanol (CH3OH)10% e leite em pó 5%; 3 - glicerol (C3H8O3) 10% e gema de ovo e 4 - glicerol 10% e leite em pó 5%, respectivamente protetor intra e extracelular. Foi coletado sêmen de cada espécie e realizado teste de motilidade para cada amostra, obtendo-se motilidade superior a 30 segundos considerando assim, viáveis para criopreservação. Foi realizado pool do sêmen de três machos de R. voulezi e dois machos de R. branneri e antes de efetuar o congelamento, as soluções foram testadas garantindo a não ocorrência de ativação por parte da solução crioprotetora. A solução ativadora testada foi água destilada. A solução 1, contendo DMSO não foi eficaz para ambas espécies, não apresentando motilidade espermática após tentativa de ativação. Para o tempo de motilidade de R. voulezi as soluções crioprotetoras metanol+leite e glicerol+ovo foram similares entre si e superiores a glicerol+leite (P0,05) para a variável tempo de motilidade. Avaliando a escala de intensidade de motilidade, o melhor resultado foi obtido através da solução glicerol+ovo para R. branneri e igualando-se à glicerol+leite para R. voulezi. O sêmen de R. branneri e R. voulezi pode ser criopreservado com as soluções apresentadas excetuando a utilização de DMSO. A melhor solução crioprotetora na motilidade espermática para estas espécies é o conjunto glicerol+ovo

Suboptimal use of hormonal therapy among German men with localized high-risk prostate cancer during 2005 to 2015 : analysis of registry data

Background: This study assesses the use of hormonal therapy to treat high-risk localized prostate cancer (HRLPCa) cases diagnosed between 2005 and 2015. Methods: All N0-XM0 with ≥T3a, or PCa cases with poorly differentiated feature (equivalent to Gleason score ≥ 8), diagnosed between 2005 and 2015 were extracted from German population-based cancer registries. Cases treated by surgery or chemotherapy were excluded. Description of hormonal therapy use by HRLPCa cases’ profile was presented. Relative risk (RR) was computed with a log-link function to identify factors associated with hormonal therapy use among radiotherapy-treated HRLPCa cases. Results: A total of 5361 HRLPCa cases were analyzed. Only 27.6% (95% confidence interval [CI]: 26.4–28.8%) of the HRLPCa cases received hormonal therapy in combination with radiotherapy. The use of combined hormonal therapy and radiotherapy varied from 19.8% in Saxony to 47.8% in Schleswig-Holstein. Application of hormonal therapy was higher for the locally advanced cases compared to the poorly differentiated cases (relative risk [RR] = 1.28; 95%CI: 1.19, 1.37). Older patients showed a slightly increased use of hormonal therapy (RR for a 10-year age increase = 1.09; 95%CI: 1.02, 1.16). Compared to PCa cases from the most affluent residential areas, cases from the least affluent (RR = 0.71; 95%CI: 0.55, 0.92) and medium (RR = 0.75; 95%CI: 0.58, 0.96) areas had decreased use of hormonal therapy. The introduction of the German S3-guideline did not make a marked difference in the uptake of both hormonal therapy and radiotherapy (RR = 1.02; 95%CI: 0.95, 1.09). Conclusion: This study found a low use of hormonal therapy among HRLPCa patients treated without surgery. The introduction of the German S3-guideline for prostate cancer treatment does not seem to have impacted hormonal therapy use

Microstructure analysis of equiatomic multi-component ni20ti20ta20co20cu20 alloy

An equiatomic multi-component alloy Ni20Ti20Ta20Co20Cu20 (at. %) was obtained using vacuum arc melting. In order to characterize such an alloy, microstructure analysis has been performed using Scanning and Transmission Electron Microscopy, Electron Backscattered Diffraction, X-ray Diffraction and Energy Dispersive X-ray Spectroscopy techniques. Microstructure analysis revealed the presence of one rhombohedral and two cubic phases. Energy Dispersive X-ray Spectroscopy measurements revealed that both observed phases include five chemical elements in the structure. Using Rietveld refinement approach the lattice parameters were refined for the observed phases

Produ??o e Comercializa??o de pescado no munic?pio de Laranjeiras do Sul, PR

The production of aquatic organisms has been increasingly prominent due to the demand for fish and the limited natural stocks tending to exhaustion. Among the various obstacles that exist for the activity to reach the objectives and bring income to the producer is the commercialization. In the municipality of Laranjeiras do Sul-PR, this aspect is aggravated because the sources of data and information of production and commercialization are mismatched. In this sense, the objective of this work was to diagnose the production and commercialization of the fish in Laranjeiras do Sul - PR, in order to generate information to subsidize the policies of expansion of the local fish farming. It was visited initially 74 possible points of commercialization, and monthly for eight months those establishments that commercialize the fish in its different forms. Mapping marketing channels showed that, except for fish traded at the fish fair and sport fishing, all the rest marketed in supermarkets or markets, restaurants or bars, fish shops, or through intermediaries comes from other municipalities, states and even countries. Twenty five suppliers were identified. It was also observed that in all the center-south region of Paran? there are no fish slaughterhouses, making this also an obstacle to increase the production, commercialization and consumption of the fish. We identified 32 commercialized species with 30 in the markets, 16 in the restaurants and only 10 in the sport fishing. The most traded species in all types of establishments is tilapia (34 tons), representing more than 75% of all fish traded in the municipality during the analyzed period, and with average fillet price of R$33.97 kg-1. The information obtained demonstrates the need for greater dissemination, expansion of marketing channels and public policies to foster activity in the municipality and region.A cria??o de organismos aqu?ticos tem se destacado de forma crescente devido ? demanda por pescado ter aumentado e as fontes naturais possu?rem estoques limitados com tend?ncia ao esgotamento. Dentre os diversos obst?culos existentes para que a atividade atinja os objetivos e traga renda ao produtor est? a comercializa??o. No munic?pio de Laranjeiras do Sul-PR este aspecto se agrava, pois as fontes de dados e informa??es de produ??o e comercializa??o s?o desencontradas. Neste sentido, o objetivo deste trabalho foi diagnosticar a produ??o e comercializa??o do pescado em Laranjeiras do Sul ? PR, de forma a gerar informa??es para subsidiar as pol?ticas de expans?o da piscicultura local. Foram visitados inicialmente 74 poss?veis pontos de comercializa??o, e mensalmente durante oito meses aqueles estabelecimentos que comercializam o pescado sob suas diferentes formas. O mapeamento dos canais de comercializa??o mostrou que, exceto o pescado comercializado na feira do peixe vivo e nos pesque-pague, todo o restante comercializado em supermercados ou mercados, restaurantes ou lanchonetes, peixaria, ou atrav?s de intermedi?rios no munic?pio prov?m de outros munic?pios, estados e at? pa?ses. Foram identificados 25 fornecedores. Tamb?m foi constatado que em toda regi?o centro-sul do Paran? n?o existem abatedouros ou frigor?ficos de peixes, tornando este tamb?m um entrave para o aumento da produ??o, comercializa??o e consumo do pescado. Foram identificadas 32 esp?cies comercializadas sendo30 identificadas nos mercados, 16 nos restaurantes e apenas 10 nos pesque-pague. A esp?cie mais comercializada em todos os tipos de estabelecimentos ? a til?pia (34 toneladas), representando mais de 75pescado comercializado no munic?pio durante o per?odo analisado, e com pre?o m?dio do fil? em R$ 33,97 kg-1. As informa??es obtidas demonstram a necessidade de maior divulga??o, amplia??o dos canais de comercializa??o e pol?ticas p?blicas para fomentar a atividade no munic?pio e regi?o

Microstructure of multi-component ni35ti35ta10co10cu10 alloy

A new NiTi-based multi-component Ni35Ti35Ta10Co10Cu10 (at.%) alloy was obtained by vacuum arc melting. The microstructure of the alloy has been studied using scanning and transmission electron microscopy, backscatter electron diffraction and X-ray diffraction techniques. The performed measurements showed presence of two cubic and one tetragonal phases. Energy dispersive X-ray spectroscopy analysis confirmed that all the observed phases contained all five principal elements