Vinblastine, bleomycin, and methotrexate chemotherapy plus irradiation for patients with early-stage, favorable Hodgkin lymphoma - The experience of the gruppo italiano studio linfomi

BACKGROUND. The acknowledged effectiveness of vinblastine, bleomycin, and methotrexate (VBM) chemotherapy in patients with early-stage Hodgkin lymphoma has been associated with conflicting toxicity reports. METHODS. One hundred forty-three patients were evaluated clinically and had favorable Stage IA or IIA Hodgkin lymphoma. Ninety-three patients were treated with the standard VBM schedule combined with extended-field radiotherapy (EFRT), leaving the choice of the therapeutic sequence free. Fifty subsequent patients were treated with a slightly modified VBM schedule (VbMp) combined with RT limited to involved fields (IF-RT) and delivered only after the end of chemotherapy. In the VbMp schedule, intervals between cycles were 21 days instead of 28 days, bleomycin doses were reduced, small doses of prednisone were given orally, and the interval before RT was prolonged. RESULTS. Clinical response was complete in 96% of patients who were treated with VBM plus EF-RT and in 94% of patients who were treated with VbMp plus IF-RT. Recurrence rates were nearly identical (12% and 11%, respectively) over necessarily different follow-up (91 months and 33 months, respectively). Hematologic toxicity was tolerable in both trials, and pulmonary side effects were moderate in the first trial and negligible in the second. On the whole, treatment was tolerated better when RT followed chemotherapy. CONCLUSIONS. The VBM regimen was confirmed to be effective in patients with early-stage Hodgkin lymphoma. Administration of all cycles before RT improved tolerance; pulmonary toxicity probably is mitigated further by reduced bleomycin doses, mild prednisone therapy, and a more prolonged resting interval before RT. A slightly higher recurrence rate was expectable in the VBM plus IF-RT trial despite the actual intensification of vinblastine and methotrexate

Systemic risk and macroeconomic fat tails

We propose a mechanism for shock amplification that potentially can account for fat tails in the distribution of the growth rate of national output. We argue that extreme macroeconomic events, such as the Great Depression and the Great Recession, were preceded by significant turmoil in the banking system. We have developed a model of bank network formation and presented numerical simulations that show that, for the benchmark case, aggregate credit follows a random walk. When we introduce fire sales the model does not only produce larger variations in the growth of aggregate credit but also shows that there is an asymmetry between booms and busts that is also consistent with empirical evidence

Analysis of Sustainability Propensity of Bike-Sharing Customers Using Partially Ordered Sets Methodology

The propensity for sustainability actions and awareness among population might be driven by ad hoc policies. For example, in the transportation framework, the bike is (re)gaining popularity as a mean of transportation both convenient and environmental-prone,and consequently more and more cities around the world are developing bike-sharing systems in urban areas to let their citizens be more \u2018green\u2019. Satisfaction for bike-sharing systems could be influenced in general by how the service is managed and by users\u2019 attitudes towards sustainability:if users\u2019 participation in sustainability is high, then the level of satisfaction will increase and the service will result more successful. In this paper we analyze the connection between propensity and orientation towards sustainability and satisfaction for a particular bike-sharing system via Partially Ordered Sets based methodology

A new in situ test for the assessment of the rock-burst alarm threshold during tunnelling

Rock-burst is one of the most serious risks associated with hard rock tunnelling and mining at high depths. Monitoring of acoustic emissions emitted by the rock-mass during excavation and their interpretation now permits the early assessment of failure events and makes the safe management of the construction works possible. A reliable set-up of the alarm threshold is thus fundamental for the correct implementation of the procedures planned to minimise rock-burst related risk. This paper focuses on a novel in situ test specifically developed to provide an experimental basis for a more accurate assessment of the alarm threshold during tunnelling, representative of the local geomechanical conditions. The test, thanks to the compression induced by two flat jacks at the tunnel side wall, produces an artificial failure process during which acoustic emissions are measured and correlated to the mechanical response of the rock-mass, without the typical limitations of scale that characterised the laboratory experiments. The new methodology, named the Mules method, was successfully tested during the excavation of some stretches of the Brenner Base Tunnel in the Brixner granite, affected by mild spalling episodes. The case-history is fully described in the paper to illustrate the practical application of the proposed approach

Optimal simple rules and the lower bound on the nominal interest rate in the Christiano–Eichenbaum–Evans model of the US business cycle

Schmitt-Grohé and Uribe (NBER wp 10724, 2004b) analyzes the optimal, simple and implementable monetary policy rules in a medium-scale macromodel, as the one proposed by Christiano et al. (J Polit Econ 113:1–45, 2005). In doing so, they use a sensible, but somewhat arbitrary constraint to account for the lower bound condition on the nominal interest rate. In this work, we check the robustness of their main results to such a criteria. We find that the optimal policies are actually absolutely robust to the easing of this criterion for all the diff erent cases considered.info:eu-repo/semantics/publishedVersio

Chemotype verboccidentafuran in Baccharis punctulata (Asteraceae): furanic sesquiterpenes correlation and molecular docking into the benzodiazepine receptor.

The compound verboccidentafuran (1) was identified from the essential oil of the leaves of Baccharis punctulata DC. (Asteraceae) specimens for the first time in Brazil. The variation of this compound found in male and female specimens may be associated to the existence of more than one type of chemotype, influenced by geographic variation, climatic conditions, stage of the vegetative cycle, genetic and ecological factors. The furanocadinan-type sesquiterpenes verboccidentafuran (1) and curzerene (2) have molecular descriptors with high similarities. Compound 2, found in Eugenia uniflora L. (Myrtaceae) and species of the genus Smyrnium L. (Apiaceae), is active to control seizures induced by pentylenetetrazole, what suggests a possible binding to the benzodiazepine-site of the GABAA (gamma-aminobutyric acid type A) receptor. Considering the occurrence and availability of 1 in the species B. punctulata and its structural similarity to compound 2, docking calculations were performed for the interaction of both compounds with the human α1-β2-γ2 GABAA receptor. The results suggest that both compounds 1 and 2 must have affinity for the cavity at α1-γ2 interface and support the development of pharmacological research on the compound verboccidentafuran 1 as a drug candidate for modulating the GABA/benzodiazepine complex in the central nervous system

Restricted intake and lipid inclusion in Santa Inês ewe lambs diet: age, weight and progesterone concentration at first ovulation.

Abstract: The age at first ovulation is influenced by several factors, and nutrition has an essential role on it. Lipids provide essential fatty acids that are positively associated to reproductive aspects. The aims of this study were to evaluate the effects of lipid inclusion and restricted intake on age and weight at the first ovulation and the serum progesterone (P4) concentration at the sixth day after first ovulation. Thirty-five Santa Inês ewe lambs with initial body weight (BW) of 21.5 ± 0.3 kg and age of 91.6 ± 1.4 days were used. Animals were blocked according to initial BW and distributed to one of four treatments: animals receiving diet without lipid inclusion (3.5% ether extract ? EE), ad libitum intake (WLI-ALI, control group, n = 9); diet without lipid inclusion and restricted intake (WLI-RI, n = 9); lipid inclusion diet, represented by toasted and broken soybean (9.8% EE), ad libitum intake (LIP-ALI, n = 8); and lipid inclusion diet and restricted intake (LIP-RI, n = 9). Ewe lambs subjected to restricted intake had 84% of the diet offered to those in ad libitum treatments. The individual daily dry matter intake (DMI) and EE intake (EEI) were measured and the animals were weekly weighted until 35 kg BW. For P4 analysis, blood samples were collected once a week after the animals reached 25 kg BW and twice a week after 30 kg until 35 kg BW. Ovulation was estimated to occur on the sixth day before P4 ?1 ng/mL. DMI, EEI, average daily weight gain until first ovulation (DWG), weight and age at first ovulation, serum P4 concentration and days in experiment until first ovulation were analyzed by GLM PROC of the SAS software (version 9.3). Ovulation occurred in 60% (21/35) of the ewe lambs (5; 5; 6; 5 from WLI-ALI; WLI-RI; LIP-ALI; and LIP-RI, respectively). DMI of ewe lambs from WLI-ALI group was greater (P 0.05) among WLI-ALI, WLI-RI, LIP-ALI, and LIP-RI treatments, respectively. The first ovulation in Santa Inês ewe lambs occurs at 30 kg BW. The restricted intake imposed in this study did not delay the age at fist ovulation. The greater lipid intake did not favor reproductive parameters. Serum P4 did not increase with the soybean inclusion in the diet. [Restrição alimentar e suplementação lipídica: idade, peso e concentração de progesterona até a primeira ovulação]. Resumo: A idade da primeira ovulação é influenciada por vários fatores e a nutrição tem um papel essencial. Lipídios fornecem ácidos graxos essenciais que estão associados de forma positiva aos aspectos reprodutivos. Os objetivos deste estudo foram avaliar os efeitos da inclusão lipídica e da restrição do consumo na idade e peso a primeira ovulação e na concentração sérica de progesterona (P4) no sexto dia após a primeira ovulação. Foram utilizadas trinta e cinco cordeiras Santa Inês com peso corporal (PC) inicial de 21,5±0,3 kg e idade de 91,6±1,4 dias. Os animais foram blocados de acordo com o PC inicial e distribuído a um dos quatro tratamentos: animais que receberam dieta sem inclusão de lipídeos (3,5% de extrato etéreo - EE), consumo ad libitum (SEM-ALI, grupo controle, n=9); dieta sem inclusão de lipídeos e restrição do consumo (SEMRE, n=9); dieta com inclusão lipídica, representada pela soja tostada e quebrada (9,8% EE), consumo ad libitum (LIP-ALI, n=8); e dieta com inclusão lipídica e restrição do consumo (LIP-RE, n=9). Cordeiras submetidas a restrição do consumo tiveram 84% da dieta oferecida em comparação aos tratamentos ad libitum. O consumo individual diário de matéria seca (CMS) e de EE (CEE) foram mensurados e os animais foram pesados semanalmente até 35 kg de PC. Para a análise de P4, amostras de sangue foram coletadas uma vez por semana depois que os animais atingiram 25 kg de PC e duas vezes por semana após 30 kg até 35 kg de PC. Estimou-se que a ovulação ocorreu no sexto dia que antecedeu P4?1 ng/mL. CMS, CEE, ganho de peso médio diário até a primeira ovulação (GPD), peso e idade da primeira ovulação, a concentração sérica de P4 e dias em experimento até a primeira ovulação foram analisados pelo PROC GLM do software SAS (versão 9.3). A ovulação ocorreu em 60% (21/35) das cordeiras (5; 5; 6; 5 do SEM-ALI; SEM-RE; LIP-ALI e LIP-RE, respectivamente). CMS de cordeiras do grupo SEM-ALI foi maior (P0,05) entre os tratamentos SEM-ALI, SEM-RE, LIP-ALI e LIP-RE, respectivamente. A primeira ovulação em borregas Santa Inês ocorreu com 30 kg de PC. A restrição do consumo imposta neste estudo não retardou a idade a primeira ovulação. A maior ingestão de lipídios não favoreceu os parâmetros reprodutivos. A P4 sérica não aumentou com a inclusão de soja na dieta.Proceedings of the 30th Annual Meeting of the Brazilian Embryo Technology Society (SBTE); Foz do Iguaçu, PR, Brazil, August 25th to 27th, 2016, and 32nd Meeting of the European Embryo Transfer Association (AETE); Barcelona, Spain, September 9th and 10th, 2016

Long-term survival of stage I multiple myeloma given chemotherapy just after diagnosis or at progression of the disease: a multicentre randomized study

We conducted a randomized trial to evaluate whether melphalan-prednisone (MPH-P) treatment administered just after diagnosis improves survival of stage I multiple myeloma (MM). Between January 1987 and March 1993, 145 consecutive previously untreated patients with stage I MM were randomized between treatment with MPH-P (administered for 4 days every 6 weeks) just after diagnosis and treatment only at disease progression. Survival was not influenced by MPH-P treatment either administered just after diagnosis or at disease progression (64 vs 71 months respectively). Comparing the first with the second group the odds ratio of death is 1.17 (95% confidence interval 0.57–2.42;P = 0.64). Disease progression occurred within a year in about 50% of patients who were initially untreated. Response rate was similar in both groups, but duration of response was shorter in patients who were treated at disease progression (48 vs 79 months, P = 0.044). Patients actually treated at disease progression (34/70) survived shorter than those who had neither disease progression nor treatment (56 vs > 92 months;P = 0.005). Starting MPH-P just after diagnosis does not improve survival and response rate in stage I MM, with respect to deferring therapy until disease progression. However, patients with stage I MM randomized to have treatment delayed and who actually progressed and were treated had shorter survival than those with stable disease and no treatment. Biologic or other disease features could identify these subgroups of patients. © 2000 Cancer Research Campaig