RESUMEN
Extraneous neuroscience information improves ratings of scientific explanations, and affects mock juror decisions in many studies, but others have yielded little to no effect. To establish the magnitude of this effect, we conducted a random-effects meta-analysis using 60 experiments from 28 publications. We found a mild but highly significant effect, with substantial heterogeneity. Planned subgroup analyses revealed that within-subjects studies, where people can compare the same material with and without neuroscience, and those using text, have stronger effects than between-subjects designs, and studies using brain image stimuli. We serendipitously found that effect sizes were stronger on outcomes of evaluating satisfaction or metacomprehension, compared with jury verdicts or assessments of convincingness. In conclusion, there is more than one type of neuroscience explanations effect. Irrelevant neuroscience does have a seductive allure, especially on self-appraised satisfaction and understanding, and when presented as text.
Asunto(s)
Neurociencias , Humanos , Toma de DecisionesRESUMEN
The overarching goal of this work is to investigate the size-dependent characteristics of the ionization potential of PbS and CdS quantum dots. The ionization potentials of quantum dots provide critical information about the energies of occupied states, which can then be used to quantify the electron-removal characteristics of quantum dots. The energy of the highest-occupied molecular orbital is used to understand electron-transfer processes when invesigating the energy-level alignment between quantum dots and electron-accepting ligands. Ionization potential is also important for investigating and interpreting electron-detachment processes induced by light (photoelectron spectra), external voltage (chemiresistance), and collision with other electrons (impact ionization). Accurate first-principles calculations of ionization potential continue to be challenging because of the computational cost associated with the construction of the frequency-dependent self-energy operator and the numerical solution of the associated Dyson equation. The computational cost becomes prohibitive as the system size increases because of the large number of 2particle-1hole (2p1h) and 1particle-2hole (1p2h) terms needed for the calculation. In this work, we present the Stratified Stochastic Enumeration of Molecular Orbitals (SSE-MO) method for efficient construction of the self-energy operator. The SSE-MO method is a real-space method and the central strategy of this method is to use stochastically enumerated sampling of molecular orbitals and molecular-orbital indices for the construction of the 2p1h and 1p2h terms. This is achieved by first constructing a composite MO-index Cartesian coordinate space followed by transformation of the frequency-dependent self-energy operator to this composite space. The evaluation of both the real and imaginary components of the self-energy operator is performed using a stratified Monte Carlo technique. The SSE-MO method was used to calculate the ionization potentials and the frequency-dependent spectral functions for a series of PbS and CdS quantum dots by solving the Dyson equation using both single-shot and iterative procedures. The ionization potentials for both PbS and CdS quantum dots were found to decrease with increasing dot size. Analysis of the frequency-dependent spectral functions revealed that for PbS quantum dots the intermediate dot size exhibited a longer relative lifetime whereas in CdS the smallest dot size had the longest relative lifetime. The results from these calculations demonstrate the efficacy of the SSE-MO method for calculating accurate ionization potentials and spectral functions of chemical systems.
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Divided attention may be more important than ever to comprehend, given ubiquitous distractors in modern living. In humans, concern has been expressed about the negative impact of distraction in education, the home, and the workplace. While acetylcholine supports divided attention, in part via muscarinic receptors, little is known about the specific muscarinic subtypes that may contribute. We designed a novel, high-response rate test of auditory sustained attention, in which rats complete variable-ratio runs on one of two levers, rather than emitting a single response. By doing this, we can present a secondary visual distractor task during some trials, for which a correct nosepoke response is reinforced with a more palatable food pellet. The nonspecific muscarinic antagonist scopolamine impaired performance, and slowed and reduced lever press activity. We then explored antagonists that preferentially block the M1 and M4 subtypes, because these receptors are potential therapeutic targets for cognitive enhancers. Telenzepine, an M1-preferring antagonist, impaired divided attention performance, but not performance of the attention task without distraction. Telenzepine also had fewer nonspecific effects than scopolamine. In contrast, the M4-preferring antagonist tropicamide had no effects. Analysis of overall behavior also indicated that accuracy in the main attention task decreased as a function of engagement with the distractor task. These results implicate the M1 receptor in divided attention.
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Atención/efectos de los fármacos , Antagonistas Muscarínicos/farmacología , Receptor Muscarínico M1/antagonistas & inhibidores , Receptor Muscarínico M4/antagonistas & inhibidores , Acetilcolina/farmacología , Animales , Condicionamiento Operante , Humanos , Masculino , Comportamiento Multifuncional/efectos de los fármacos , Pirenzepina/análogos & derivados , Pirenzepina/farmacología , Ratas , Ratas Sprague-Dawley , Receptor Muscarínico M1/metabolismo , Receptor Muscarínico M4/metabolismo , Escopolamina/farmacología , Tropicamida/farmacologíaRESUMEN
Fat-filled milk powders (FMP) are inexpensive milk alternatives predominantly exported to developing countries to satisfy growing demands for dairy proteins. Harsh climatic and sanitary conditions, poor border controls and relatively long periods for distribution and storage enhance the inherent vulnerability of FMP to fraud and stability. Rapid, low-cost methods are needed for extensive routine authentication of FMP products. This study investigated, for the first time, the sample integrity and the quality dynamics of 7 Nigerian FMP brands stored for 7 weeks at 40 °C. The prominent melamine and urea absorption peaks were absent, but protein contents were below the permitted limit. The peak absorbance of the OH functional group increased while the tryptophan contents decreased with storage time. Multiclass analyses differentiated the fresh FMP brands from one another, and from those that were aged. Robust interval-PLS predictions obtained for storage time may be excellent indicators of FMP freshness and stability.
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Embalaje de Alimentos/métodos , Leche/química , Animales , Cromatografía de Gases , Cromatografía Líquida de Alta Presión , Ácidos Grasos/análisis , Microbiología de Alimentos , Análisis de los Mínimos Cuadrados , Leche/microbiología , Nigeria , Polvos/química , Análisis de Componente Principal , Salmonella/aislamiento & purificación , Temperatura , Triazinas/análisis , Urea/análisisRESUMEN
R-FND (rituximab, fludarabine, mitoxantrone, and dexamethasone) can induce molecular remissions in indolent lymphoma. The addition of 90yttrium ibritumomab tiuxetan (90YIT) radioimmunotherapy following first-line induction treatment in patients with advanced follicular lymphoma (FL) may improve remission rates. We now report 10-year follow-up results from our sequential treatment approach with an abbreviated regimen of R-FND followed by 90YIT consolidation and rituximab maintenance. Forty-nine patients were enrolled; 47 received treatment. Patients had high-risk (FLIPI score ≥3) FL of grade 1-3A and stage III/IV with adequate hematologic function. Following R-FND, the complete and partial response rates were 91% and 8.5%, respectively. After 90YIT consolidation, the CR rate increased to 97%. The 10-year PFS rate was 49%. The most common non-hematologic, grade 3 or 4 adverse events were fatigue, dyspnea, and myalgia. Five developed myelodysplastic syndrome (MDS). This treatment approach is most appropriate in FLIPI-based high-risk patients whose outlook with standard therapy is inadequate.
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Linfoma Folicular , Radioinmunoterapia , Anticuerpos Monoclonales , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Humanos , Linfoma Folicular/tratamiento farmacológico , Linfoma Folicular/terapia , Rituximab/uso terapéutico , Resultado del Tratamiento , Radioisótopos de Itrio/uso terapéuticoRESUMEN
We present the frequency-dependent geminal-screened electron-hole interaction kernel (FD-GSIK) method for describing electron-hole correlation in electronically excited many-electron systems. The FD-GSIK is a parameter-free, first-principles method derived from excited-state wave function that was both frequency-dependent and r12-explicitly correlated. The FD-GSIK avoids using unoccupied orbitals for kernel construction by performing an infinite-order summation of particle-hole excitation and representing it as a compact real-space operator. It bypasses the computationally demanding steps of evaluation, storage, and transformation of atomic-orbital integrals by directly evaluating molecular orbital integrals in real space using the stratified Monte Carlo method. We demonstrate and discuss the advantages of this method by presenting excitation and electron-hole binding energies of large nanoparticles including Pb140S140, Pb140Se140, Cd144Se144, and Cd72S72.
RESUMEN
Doping through the incorporation of transition metal ions allows for the emergence of new optical, electrical, and magnetic properties in quantum dots (QDs). While dopants can be introduced into QDs through many synthetic methods, the control of dopant location and host-dopant (H-D) coupling through directional dopant movement is still largely unexplored. In this work, we have studied dopant behaviors in Mn:CdS/ZnS core/shell QDs and found that dopant transport behavior is very sensitive to the temperature and microenvironments within the QDs. The migration of Mn toward the alloyed interface of the core/shell QDs, below a temperature boundary (Tb) at â¼200 °C, weakens the H-D interactions. At temperatures higher than the Tb, however, dopant ejection and global alloying of CdS/ZnS QDs can occur, leading to stronger H-D coupling. The behavior of incorporated dopants inside QDs is fundamentally important for understanding doping mechanisms and the host-dopant interaction-dependent properties of doped nanomaterials.
RESUMEN
The serotonergic 5-HT1A receptor is known to be involved in both impulsivity and anxiety-related behavior. Although anxiety and impulsivity are different constructs, it has been shown that anxiogenesis can result in impulsiveness. It is therefore important to determine if the 5-HT1A receptor is involved in the commission of impulsive actions independent of its effects on anxiety. The 5-HT1A agonist 8-OH-DPAT (0.0125-0.1 mg/kg subcutaneous) increased impulsive action at low doses, but decreased it at higher doses, on the novel paced variable consecutive number with discriminative stimulus task (VCN). Neither the 5-HT1A antagonist WAY 100,635 (0.2-1.2 mg/kg subcutaneous), nor the noradrenergic antagonist and pharmacological stressor yohimbine (1-2 mg/kg intraperitoneal) altered measures of impulsivity. Stress induced by yohimbine was sufficient to produce anxiety-like behavior in the elevated zero maze, confirming that the VCN task is a selective assay of impulsive action that is not affected by anxiety. We hypothesize that the biphasic effect of 8-OH-DPAT is due to actions on presynaptic raphe 5-HT1A autoreceptors, and also postsynaptic 5-HT1A receptors. These results suggest that this receptor mediates impulsive action and that this is not secondary to its role in anxiety.
Asunto(s)
8-Hidroxi-2-(di-n-propilamino)tetralin/farmacología , Ansiedad/metabolismo , Conducta Animal/efectos de los fármacos , Conducta Impulsiva/efectos de los fármacos , Receptor de Serotonina 5-HT1A/metabolismo , Agonistas del Receptor de Serotonina 5-HT1/farmacología , Animales , Ansiedad/psicología , Autorreceptores/efectos de los fármacos , Autorreceptores/metabolismo , Discriminación en Psicología/efectos de los fármacos , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Masculino , Piperazinas/farmacología , Piridinas/farmacología , Núcleos del Rafe/efectos de los fármacos , Núcleos del Rafe/metabolismo , Ratas Sprague-Dawley , Yohimbina/farmacologíaRESUMEN
In a prospective phase II trial, pentostatin combined with cyclophosphamide and rituximab (PCR) induced strong responses and was well-tolerated in previously untreated patients with advanced-stage, indolent non-Hodgkin lymphoma (iNHL). After a median patient follow-up of more than 108 months, we performed an intent-to-treat analysis of our 83 participants. Progression-free survival (PFS) rates at 108 months for follicular lymphoma (FL), marginal zone lymphoma (MZL) and small lymphocytic lymphoma (SLL) were 71%, 67% and 15%, respectively, and were affected by clinicopathological characteristics. Ten-year PFS rates for those with beta-2-microglobulin levels <2·2 and ≥2·2 mg/l prior to treatment were 71% and 21%, respectively. Patients without bone marrow involvement had 10-year PFS rates of 72% vs. 29% for those with involvement. At time of analysis, the median overall survival (OS) had not been reached. The OS rate was 64% at 10 years and differed significantly based on histology: 94% for FL, 66% for MZL and 39% for SLL. Long-term toxicities included 18 (21·7%) patients with second malignancies and 2 (2·4%) who developed myelodysplastic syndrome after receiving additional lines of chemotherapy. Our 10-year follow-up analysis confirms that PCR is an effective, robust and tolerable treatment regimen for patients with iNHL.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Adulto , Anciano , Enfermedades de la Médula Ósea/mortalidad , Ciclofosfamida/administración & dosificación , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Femenino , Humanos , Leucemia Linfocítica Crónica de Células B/mortalidad , Masculino , Persona de Mediana Edad , Neoplasias Primarias Secundarias/mortalidad , Pentostatina/administración & dosificación , Rituximab/administración & dosificación , Resultado del TratamientoRESUMEN
BACKGROUND: Although the outcomes of patients with mantle cell lymphoma (MCL) have improved, there is still no cure. Bortezomib has a 33% response rate in relapsed/refractory MCL and has shown additive and/or synergistic effects in preclinical trials with known effective agents. METHODS: This is a report of a prospective phase 2 trial of bortezomib added to rituximab plus hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (BzR-hyperCVAD)/rituximab, high-dose methotrexate, and high-dose cytarabine (BzR-MA) for 95 patients with newly diagnosed MCL. RESULTS: The overall and complete response rates were 100% and 82%, respectively. Hematologic toxicity was high but expected and did not lead to an increased incidence of neutropenic fever or dose reductions in comparison with a similar reported regimen without bortezomib. After a median follow-up of 44 months, the median overall survival had not been reached, and the time to treatment failure (TTF) was 55 months, which is not different from that of historical controls. CONCLUSIONS: BzR-hyperCVAD/BzR-MA at the dose and schedule studied produced high rates of response and a TTF similar to that of historical reports without bortezomib. Cancer 2018;124:2561-9. © 2018 American Cancer Society.
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Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Neutropenia Febril Inducida por Quimioterapia/epidemiología , Linfoma de Células del Manto/tratamiento farmacológico , Recurrencia Local de Neoplasia/epidemiología , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Bortezomib/administración & dosificación , Bortezomib/efectos adversos , Neutropenia Febril Inducida por Quimioterapia/etiología , Ciclofosfamida/administración & dosificación , Ciclofosfamida/efectos adversos , Citarabina/administración & dosificación , Citarabina/efectos adversos , Dexametasona/administración & dosificación , Dexametasona/efectos adversos , Relación Dosis-Respuesta a Droga , Doxorrubicina/administración & dosificación , Doxorrubicina/efectos adversos , Esquema de Medicación , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Estimación de Kaplan-Meier , Linfoma de Células del Manto/mortalidad , Masculino , Metotrexato/administración & dosificación , Metotrexato/efectos adversos , Persona de Mediana Edad , Recurrencia Local de Neoplasia/prevención & control , Estudios Prospectivos , Rituximab/administración & dosificación , Rituximab/efectos adversos , Tasa de Supervivencia , Factores de Tiempo , Insuficiencia del Tratamiento , Vincristina/administración & dosificación , Vincristina/efectos adversosRESUMEN
Nodular lymphocyte Hodgkin lymphoma (NLPHL) is a rare disease for which the optimal therapy is unknown. We hypothesized that rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) could decrease rates of relapse and transformation. We retrospectively reviewed patients with NLPHL diagnosed between 1995 and 2015 confirmed by central pathologic review. Fifty-nine had sufficient treatment and follow-up data for analysis. We described progression-free survival (PFS), overall survival (OS), and histologic transformation according to treatment strategy and explored prognostic factors for PFS and OS. The median age at diagnosis was 41 years; 75% were male, and 61% had a typical growth pattern. Twenty-seven patients were treated with R-CHOP with an overall response rate of 100% (complete responses 89%). The median follow-up was 6.7 years, and the estimated 5- and 10-year PFS rates for patients treated with R-CHOP were 88.5% (95% confidence interval [CI], 68.4% to 96.1%) and 59.3 (95% CI, 25.3% to 89.1%), respectively. Excluding patients with histologic transformation at diagnosis, the 5-year cumulative incidence of histologic transformation was 2% (95% CI, 87% to 100%). No patient treated with R-CHOP experienced transformation. A high-risk score from the German Hodgkin Study Group was adversely prognostic for OS (P = .036), whereas male sex and splenic involvement were adversely prognostic for PFS (P = .006 and .002, respectively) but not OS. Our data support a potential role for R-CHOP in patients with NLPHL. Larger prospective trials are needed to define the optimal chemotherapy regimen.
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Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Enfermedad de Hodgkin/tratamiento farmacológico , Enfermedad de Hodgkin/mortalidad , Adolescente , Adulto , Anciano , Anticuerpos Monoclonales de Origen Murino/administración & dosificación , Ciclofosfamida/administración & dosificación , Supervivencia sin Enfermedad , Doxorrubicina/administración & dosificación , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Prednisona/administración & dosificación , Estudios Retrospectivos , Rituximab , Tasa de Supervivencia , Factores de Tiempo , Vincristina/administración & dosificaciónRESUMEN
BACKGROUND: Data on the incidence of adverse liver outcomes are limited for cancer patients with chronic (hepatitis B surface antigen [HBsAg]-positive/hepatitis B core antibody [anti-HBc]-positive) or past (HBsAg-negative/anti-HBc-positive) hepatitis B virus (HBV) after chemotherapy. This study was aimed at determining the impact of test timing and anti-HBV therapy on adverse liver outcomes in these patients. METHODS: Patients with solid or hematologic malignancies who received chemotherapy between 2004 and 2011 were retrospectively studied. HBV testing and anti-HBV therapy were defined as early at the initiation of cancer therapy and as late after initiation. Outcomes included hepatitis flares, hepatic impairment, liver failure, and death. Time-to-event analysis was used to determine incidence, and multivariate hazard models were used to determine predictors of outcomes. RESULTS: There were 18,688 study patients (80.4% with solid tumors). The prevalence of chronic HBV was 1.1% (52 of 4905), and the prevalence of past HBV was 7.1% (350 of 4905). Among patients with solid tumors, late identification of chronic HBV was associated with a higher risk of hepatitis flare (hazard ratio [HR], 4.02; 95% confidence interval [CI], 1.26-12.86), hepatic impairment (HR, 8.48; 95% CI, 1.86-38.66), liver failure (HR, 9.38; 95% CI, 1.50-58.86), and death (HR, 3.90; 95% CI, 1.19-12.83) in comparison with early identification. Among patients with hematologic malignancies and chronic HBV, the risk of death was 7.8 (95% CI, 1.73-35.27) times higher for persons with late initiation of anti-HBV therapy versus early initiation. Patients with late identification of chronic HBV had late or no anti-HBV therapy. Chronic HBV predicted liver failure in patients with solid or hematologic malignancies, whereas male sex and late identification were predictors for patients with solid tumors. CONCLUSIONS: Early identification correlates with early anti-HBV therapy and reduces the risk of liver failure and death in chronic HBV patients receiving chemotherapy. Cancer 2017;123:3367-76. © 2017 American Cancer Society.
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Antineoplásicos/uso terapéutico , Antivirales/uso terapéutico , Neoplasias Hematológicas/tratamiento farmacológico , Virus de la Hepatitis B/aislamiento & purificación , Hepatitis B Crónica/tratamiento farmacológico , Neoplasias/tratamiento farmacológico , Adulto , Distribución por Edad , Anciano , Estudios de Cohortes , Comorbilidad , Intervalos de Confianza , Progresión de la Enfermedad , Femenino , Neoplasias Hematológicas/diagnóstico , Neoplasias Hematológicas/epidemiología , Virus de la Hepatitis B/efectos de los fármacos , Hepatitis B Crónica/diagnóstico , Hepatitis B Crónica/epidemiología , Humanos , Incidencia , Fallo Hepático/mortalidad , Fallo Hepático/fisiopatología , Masculino , Persona de Mediana Edad , Neoplasias/epidemiología , Neoplasias/patología , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Medición de Riesgo , Distribución por Sexo , Análisis de Supervivencia , Factores de TiempoRESUMEN
We report a single-centre, randomized study evaluating the efficacy and safety of concurrent fludarabine, mitoxantrone, dexamethasone (FND) and rituximab versus sequential FND followed by rituximab in 158 patients with advanced stage, previously untreated indolent lymphoma, enrolled between 1997 and 2002. Patients were randomized to 6-8 cycles of FND followed by 6 monthly doses of rituximab or 6 doses of rituximab given concurrently with FND. All patients who achieved at least a partial response received 12 months of interferon (IFN) maintenance. Median ages were 54 and 55 years. The two groups were comparable with the exception of a higher percentage of females (65% vs. 43%) and baseline anaemia (23% vs. 11%) in the FND followed by rituximab group. Complete response/unconfirmed complete response rates were 89% and 93%. The most frequent grade ≥ 3 toxicity was neutropenia (86% vs. 96%). Neutropenic fever occurred in 21% and 16%. Late toxicity included myelodysplastic syndrome (n = 3) and acute myeloid leukaemia (n = 5). With 12·5 years of follow-up, no significant differences based on treatment schedule were observed. 10-year overall survival estimates were 76% and 73%. 10-year progression-free survival estimates were 52% and 51%. FND with concurrent or sequential rituximab, and IFN maintenance in indolent lymphoma demonstrated high response rates and robust survival.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Interferones/uso terapéutico , Linfoma no Hodgkin/tratamiento farmacológico , Adolescente , Adulto , Anciano , Dexametasona/administración & dosificación , Femenino , Humanos , Linfoma no Hodgkin/patología , Quimioterapia de Mantención , Masculino , Persona de Mediana Edad , Mitoxantrona/administración & dosificación , Inducción de Remisión , Rituximab/administración & dosificación , Vidarabina/administración & dosificación , Vidarabina/análogos & derivados , Adulto JovenRESUMEN
RATIONALE: Cannabinoid CB1 inverse agonists hold therapeutic promise as appetite suppressants but have produced suicidal behaviors among a small subpopulation in clinical trials. Anatomical and pharmacological evidence implicate the 5HT1A serotonin receptor in suicide in humans and impulsivity in humans and animals. OBJECTIVE: The objective of the study is to assess whether 5HT1A blockade is necessary for CB1 ligands to produce impulsivity. METHODS: Sprague Dawley rats were administered the CB1 inverse agonist AM 251, the CB1 antagonist AM 6527, or the peripherally restricted antagonist AM 6545, with or without pretreatment with the 5HT1A antagonist WAY 100,635 (WAY) on the paced fixed consecutive number (FCN) task, which measures choice to terminate a chain of responses prematurely. As FCN is sensitive to changes in time perception, which have been demonstrated with CB1 blockade, a novel variable consecutive number task with discriminative stimulus (VCN-S D ) was also performed and proposed to be less sensitive to changes in timing. RESULTS: Pretreatment with WAY enabled mild but significant reductions in FCN accuracy for AM 251 and AM 6527. No effects were found for AM 6545. On the VCN-S D task, substantial impairments were found for the combination of WAY and AM 251. CONCLUSIONS: AM 251, but not the antagonists AM 6527 or AM 6545, produced impulsivity only following systemic 5HT1A blockade. Although preliminary, the results may indicate that disrupted serotonin signaling produces a vulnerability to undesirable effects of CB1 inverse agonists, which is not evident in the general population. Furthermore, neutral CB1 antagonists do not produce this effect and therefore may have greater safety.
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Agonistas de Receptores de Cannabinoides/farmacología , Antagonistas de Receptores de Cannabinoides/farmacología , Conducta Impulsiva/efectos de los fármacos , Receptor Cannabinoide CB1/efectos de los fármacos , Antagonistas del Receptor de Serotonina 5-HT1/farmacología , Animales , Depresores del Apetito , Conducta de Elección/efectos de los fármacos , Agonismo Inverso de Drogas , Masculino , Morfolinas/farmacología , Piperazinas/farmacología , Piperidinas/farmacología , Pirazoles/farmacología , Piridinas/farmacología , Ratas , Ratas Sprague-Dawley , Receptor Cannabinoide CB1/agonistas , Receptor Cannabinoide CB1/antagonistas & inhibidores , Receptor de Serotonina 5-HT1ARESUMEN
There are limited reports that baseline peripheral absolute neutrophil count (ANC), absolute monocyte count (AMC), absolute lymphocyte count (ALC) and serum ß2-microglobulin level independently predict survival in patients with diffuse large B-cell lymphoma (DLBCL). To confirm these findings, we analysed these parameters together with components of the International Prognostic Index (IPI) in patients with newly-diagnosed DLBCL. We evaluated baseline clinical features for their ability to predict survival in 817 newly diagnosed, previously untreated patients with DLBCL who received frontline treatments between October 2001 and December 2011. The median age at diagnosis was 58 years. Multivariate analysis identified elevated baseline ANC (P = 0·036), AMC (P = 0·028) and serum ß2-microglobulin level (P < 0·001), poor performance status (P < 0·001) and high number of extranodal disease sites (P = 0·0497) as independent unfavourable predictors of OS; serum ß2-microglobulin level was the strongest predictor of survival outcomes among all the parameters. High baseline serum ß2-microglobulin, ANC and AMC levels are independent prognostic factors for short overall survival in patients with newly diagnosed DLBCL. Our new model, based on the above five parameters, better stratifies patients into various risk categories than the IPI for newly diagnosed DLBCL.
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Recuento de Leucocitos , Linfoma de Células B Grandes Difuso/sangre , Linfoma de Células B Grandes Difuso/mortalidad , Monocitos , Neutrófilos , Microglobulina beta-2/sangre , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores , Femenino , Estudios de Seguimiento , Humanos , Estimación de Kaplan-Meier , Linfoma de Células B Grandes Difuso/diagnóstico , Masculino , Persona de Mediana Edad , Monocitos/patología , Análisis Multivariante , Estadificación de Neoplasias , Neutrófilos/patología , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Adulto JovenRESUMEN
Cannabinoid CB1 antagonists are widely known to reduce motivation for food, but it is not known whether they induce satiety or reduce reward value of food. It may therefore be necessary to compare effects of altered satiety and reward food value in the same appetitive task, and determine whether CB1 antagonism produces a behavior pattern similar to either, both, or neither. A fine-grained analysis of fixed-ratio 10 (FR10) responding for palatable food initially included number and duration of, and between, all lever presses and food tray entries in order to differentiate the pattern of suppression of prefeeding from that caused by reducing the reward value of the pellets with quinine. Discriminant function analysis then determined that these manipulations were best differentiated by effects on tray entries, pellet retrieval latencies, and time of the first response. At 0.5 mg/kg, AM 6527 produced similar effects to reducing reward value, but at 1.0 and 4.0 mg/kg, effects were more similar to those when animals were satiated. We conclude that AM 6527 both reduced reward value and enhanced satiety, but as dose increased, effects on satiety became much more prominent. These findings contribute to knowledge about the behavioral processes affected by CB1 antagonism.
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Conducta Animal/efectos de los fármacos , Antagonistas de Receptores de Cannabinoides/farmacología , Conducta Alimentaria/efectos de los fármacos , Receptor Cannabinoide CB1/antagonistas & inhibidores , Animales , Masculino , Motivación/efectos de los fármacos , Pirazoles/farmacología , Quinina/farmacología , Ratas , Ratas Sprague-Dawley , RecompensaAsunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Clorhidrato de Bendamustina/efectos adversos , Enfermedades Transmisibles/etiología , Enfermedades Hematológicas/etiología , Mitoxantrona/efectos adversos , Rituximab/efectos adversos , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Clorhidrato de Bendamustina/farmacología , Clorhidrato de Bendamustina/uso terapéutico , Humanos , Linfoma Folicular/tratamiento farmacológico , Linfoma Folicular/patología , Persona de Mediana Edad , Mitoxantrona/farmacología , Mitoxantrona/uso terapéutico , Rituximab/farmacología , Rituximab/uso terapéuticoRESUMEN
Intensive chemotherapy regimens containing cytarabine have substantially improved remission durability and overall survival in younger adults with mantle cell lymphoma (MCL). However, there have been no long-term follow-up results for patients treated with these regimens. We present long-term survival outcomes from a pivotal phase II trial of rituximab, hyper-fractionated cyclophosphamide, vincristine, doxorubicin and dexamethasone alternating with methotrexate and cytarabine (R-HCVAD/MA). At 15 years of follow-up (median: 13·4 years), the median failure-free survival (FFS) and overall survival (OS) for all patients was 4·8 years and 10·7 years, respectively. The FFS seems to have plateaued after 10 years, with an estimated 15-year FFS of 30% in younger patients (≤65 years). Patients who achieved complete response (CR) after 2 cycles had a favourable median FFS of 8·8 years. Six patients developed myelodysplastic syndrome/acute myeloid leukaemia (MDS/AML) whilst in first CR. The 10-year cumulative incidence of MDS/AML of patients in first remission was 6·2% (95% confidence interval: 2·5-12·2%). In patients with newly diagnosed MCL, R-HCVAD/MA showed sustained efficacy, with a median OS exceeding 10 years in all patients and freedom from disease recurrence of nearly 15 years in almost one-third of the younger patients (≤65 years).