Hodgkin lymphoma treatment with ABVD in the US and the EU: neutropenia occurrence and impaired chemotherapy delivery.

BACKGROUND: In newly diagnosed patients with Hodgkin lymphoma (HL) the effect of doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD)-related neutropenia on chemotherapy delivery is poorly documented. The aim of this analysis was to assess the impact of chemotherapy-induced neutropenia (CIN) on ABVD chemotherapy delivery in HL patients. STUDY DESIGN: Data from two similarly designed, prospective, observational studies conducted in the US and the EU were analysed. One hundred and fifteen HL patients who started a new course of ABVD during 2002-2005 were included. The primary objective was to document the effect of neutropenic complications on delivery of ABVD chemotherapy in HL patients. Secondary objectives were to investigate the incidence of CIN and febrile neutropenia (FN) and to compare US and EU practice with ABVD therapy in HL. Pooled data were analysed to explore univariate associations with neutropenic events. RESULTS: Chemotherapy delivery was suboptimal (with a relative dose intensity < or = 85%) in 18-22% of patients. The incidence of grade 4 CIN in cycles 1-4 was lower in US patients (US 24% vs. EU 32%). Patients in both the US and the EU experienced similar rates of FN across cycles 1-4 (US 12% vs. EU 11%). Use of primary colony-stimulating factor (CSF) prophylaxis and of any CSF was more common in the US than the EU (37% vs. 4% and 78% vs. 38%, respectively). The relative risk (RR) of dose delays was 1.54 (95% confidence interval [CI] 1.08-2.23, p = 0.036) for patients with vs. without grade 4 CIN and the RR of grade 4 CIN was 0.35 (95% CI 0.12-1.06, p = 0.046) for patients with vs. without primary CSF prophylaxis. CONCLUSIONS: In this population of HL patients, CIN was frequent and FN occurrence clinically relevant. Chemotherapy delivery was suboptimal. CSF prophylaxis appeared to reduce CIN rates.

Trends in anemia management in US hemodialysis patients 2004-2010.

BACKGROUND: There have been major changes in the management of anemia in US hemodialysis patients in recent years. We sought to determine the influence of clinical trial results, safety regulations, and changes in reimbursement policy on practice. METHODS: We examined indicators of anemia management among incident and prevalent hemodialysis patients from a medium-sized dialysis provider over three time periods: (1) 2004 to 2006 (2) 2007 to 2009, and (3) 2010. Trends across the three time periods were compared using generalized estimating equations. RESULTS: Prior to 2007, the median proportion of patients with monthly hemoglobin >12 g/dL for patients on dialysis 0 to 3, 4 to 6 and 7 to 18 months, respectively, was 42%, 55% and 46% declined to 41%, 54%, and 40% after 2007, and declined more sharply in 2010 to 34%, 41%, and 30%. Median weekly Epoeitin alpha doses over the same periods were 18,000, 12,400, and 9,100 units before 2007; remained relatively unchanged from 2007 to 2009; and decreased sharply in the patients 3-6 and 6-18 months on dialysis to 10,200 and 7,800 units, respectively in 2010. Iron doses, serum ferritin, and transferrin saturation levels increased over time with more pronounced increases in 2010. CONCLUSION: Modest changes in anemia management occurred between 2007 and 2009, followed by more dramatic changes in 2010. Studies are needed to examine the effects of declining erythropoietin use and hemoglobin levels and increasing intravenous iron use on quality of life, transplantation rates, infection rates and survival.

Patterns in blood pressure medication use in US incident dialysis patients over the first 6 months.

BACKGROUND: Several observational studies have evaluated the effect of a single exposure window with blood pressure (BP) medications on outcomes in incident dialysis patients, but whether BP medication prescription patterns remain stable or a single exposure window design is adequate to evaluate effect on outcomes is unclear. METHODS: We described patterns of BP medication prescription over 6 months after dialysis initiation in hemodialysis and peritoneal dialysis patients, stratified by cardiovascular comorbidity, diabetes, and other patient characteristics. The cohort included 13,072 adult patients (12,159 hemodialysis, 913 peritoneal dialysis) who initiated dialysis in Dialysis Clinic, Inc., facilities January 1, 2003-June 30, 2008, and remained on the original modality for at least 6 months. We evaluated monthly patterns in BP medication prescription over 6 months and at 12 and 24 months after initiation. RESULTS: Prescription patterns varied by dialysis modality over the first 6 months; substantial proportions of patients with prescriptions for beta-blockers, renin angiotensin system agents, and dihydropyridine calcium channel blockers in month 6 no longer had prescriptions for these medications by month 24. Prescription of specific medication classes varied by comorbidity, race/ethnicity, and age, but little by sex. The mean number of medications was 2.5 at month 6 in hemodialysis and peritoneal dialysis cohorts. CONCLUSIONS: This study evaluates BP medication patterns in both hemodialysis and peritoneal dialysis patients over the first 6 months of dialysis. Our findings highlight the challenges of assessing comparative effectiveness of a single BP medication class in dialysis patients. Longitudinal designs should be used to account for changes in BP medication management over time, and designs that incorporate common combinations should be considered.

Assessing the homogenization of urban land management with an application to US residential lawn care.

Changes in land use, land cover, and land management present some of the greatest potential global environmental challenges of the 21st century. Urbanization, one of the principal drivers of these transformations, is commonly thought to be generating land changes that are increasingly similar. An implication of this multiscale homogenization hypothesis is that the ecosystem structure and function and human behaviors associated with urbanization should be more similar in certain kinds of urbanized locations across biogeophysical gradients than across urbanization gradients in places with similar biogeophysical characteristics. This paper introduces an analytical framework for testing this hypothesis, and applies the framework to the case of residential lawn care. This set of land management behaviors are often assumed--not demonstrated--to exhibit homogeneity. Multivariate analyses are conducted on telephone survey responses from a geographically stratified random sample of homeowners (n = 9,480), equally distributed across six US metropolitan areas. Two behaviors are examined: lawn fertilizing and irrigating. Limited support for strong homogenization is found at two scales (i.e., multi- and single-city; 2 of 36 cases), but significant support is found for homogenization at only one scale (22 cases) or at neither scale (12 cases). These results suggest that US lawn care behaviors are more differentiated in practice than in theory. Thus, even if the biophysical outcomes of urbanization are homogenizing, managing the associated sustainability implications may require a multiscale, differentiated approach because the underlying social practices appear relatively varied. The analytical approach introduced here should also be productive for other facets of urban-ecological homogenization.

Gene selection using iterative feature elimination random forests for survival outcomes.

Although many feature selection methods for classification have been developed, there is a need to identify genes in high-dimensional data with censored survival outcomes. Traditional methods for gene selection in classification problems have several drawbacks. First, the majority of the gene selection approaches for classification are single-gene based. Second, many of the gene selection procedures are not embedded within the algorithm itself. The technique of random forests has been found to perform well in high-dimensional data settings with survival outcomes. It also has an embedded feature to identify variables of importance. Therefore, it is an ideal candidate for gene selection in high-dimensional data with survival outcomes. In this paper, we develop a novel method based on the random forests to identify a set of prognostic genes. We compare our method with several machine learning methods and various node split criteria using several real data sets. Our method performed well in both simulations and real data analysis.Additionally, we have shown the advantages of our approach over single-gene-based approaches. Our method incorporates multivariate correlations in microarray data for survival outcomes. The described method allows us to better utilize the information available from microarray data with survival outcomes.

The Toronto Word Pool: Norms for imagery, concreteness, orthographic variables, and grammatical usage for 1,080 words

Imagery and concreteness norms and percentage noun usage were obtained on the 1,080 verbal items from the Toronto Word Pool. Imagery was defined as the rated ease with which a word aroused a mental image, and concreteness was defined in relation to level of abstraction. The degree to which a word was functionally a noun was estimated in a sentence generation task. The mean and standard deviation of the imagery and concreteness ratings for each item are reported together with letter and printed frequency counts for the words and indications of sex differences in the ratings. Additional data in the norms include a grammatical function code derived from dictionary definitions, a percent noun judgment, indexes of statistical approximation to English, and an orthographic neighbor ratio. Validity estimates for the imagery and concreteness ratings are derived from comparisons with scale values drawn from the Paivio, Yuille, and Madigan (1968) noun pool and the Toglia and Battig (1978) norms. © 1982 Psychonomic Society, Inc.

Early clopidogrel versus prasugrel use among contemporary STEMI and NSTEMI patients in the US: insights from the National Cardiovascular Data Registry.

BACKGROUND: P2Y12 antagonist therapy improves outcomes in acute myocardial infarction (MI) patients. Novel agents in this class are now available in the US. We studied the introduction of prasugrel into contemporary MI practice to understand the appropriateness of its use and assess for changes in antiplatelet management practices. METHODS AND RESULTS: Using ACTION Registry-GWTG (Get-with-the-Guidelines), we evaluated patterns of P2Y12 antagonist use within 24 hours of admission in 100 228 ST elevation myocardial infarction (STEMI) and 158 492 Non-ST elevation myocardial infarction (NSTEMI) patients at 548 hospitals between October 2009 and September 2012. Rates of early P2Y12 antagonist use were approximately 90% among STEMI and 57% among NSTEMI patients. From 2009 to 2012, prasugrel use increased significantly from 3% to 18% (5% to 30% in STEMI; 2% to 10% in NSTEMI; P for trend <0.001 for all). During the same period, we observed a decrease in use of early but not discharge P2Y12 antagonist among NSTEMI patients. Although contraindicated, 3.0% of patients with prior stroke received prasugrel. Prasugrel was used in 1.9% of patients ≥75 years and 4.5% of patients with weight <60 kg. In both STEMI and NSTEMI, prasugrel was most frequently used in patients at the lowest predicted risk for bleeding and mortality. Despite lack of supporting evidence, prasugrel was initiated before cardiac catheterization in 18% of NSTEMI patients. CONCLUSIONS: With prasugrel as an antiplatelet treatment option, contemporary practice shows low uptake of prasugrel and delays in P2Y12 antagonist initiation among NSTEMI patients. We also note concerning evidence of inappropriate use of prasugrel, and inadequate targeting of this more potent therapy to maximize the benefit/risk ratio.

Biogeography in deep time - What do phylogenetics, geology, and paleoclimate tell us about early platyrrhine evolution?

Molecular data have converged on a consensus about the genus-level phylogeny of extant platyrrhine monkeys, but for most extinct taxa and certainly for those older than the Pleistocene we must rely upon morphological evidence from fossils. This raises the question as to how well anatomical data mirror molecular phylogenies and how best to deal with discrepancies between the molecular and morphological data as we seek to extend our phylogenies to the placement of fossil taxa. Here I present parsimony-based phylogenetic analyses of extant and fossil platyrrhines based on an anatomical dataset of 399 dental characters and osteological features of the cranium and postcranium. I sample 16 extant taxa (one from each platyrrhine genus) and 20 extinct taxa of platyrrhines. The tree structure is constrained with a "molecular scaffold" of extant species as implemented in maximum parsimony using PAUP with the molecular-based 'backbone' approach. The data set encompasses most of the known extinct species of platyrrhines, ranging in age from latest Oligocene (∼26 Ma) to the Recent. The tree is rooted with extant catarrhines, and Late Eocene and Early Oligocene African anthropoids. Among the more interesting patterns to emerge are: (1) known early platyrrhines from the Late Oligocene through Early Miocene (26-16.5Ma) represent only stem platyrrhine taxa; (2) representatives of the three living platyrrhine families first occur between 15.7 Ma and 13.5 Ma; and (3) recently extinct primates from the Greater Antilles (Cuba, Jamaica, Hispaniola) are sister to the clade of extant platyrrhines and may have diverged in the Early Miocene. It is probable that the crown platyrrhine clade did not originate before about 20-24 Ma, a conclusion consistent with the phylogenetic analysis of fossil taxa presented here and with recent molecular clock estimates. The following biogeographic scenario is consistent with the phylogenetic findings and climatic and geologic evidence: Tropical South America has been a center for platyrrhine diversification since platyrrhines arrived on the continent in the middle Cenozoic. Platyrrhines dispersed from tropical South America to Patagonia at ∼25-24 Ma via a "Paraná Portal" through eastern South America across a retreating Paranense Sea. Phylogenetic bracketing suggests Antillean primates arrived via a sweepstakes route or island chain from northern South America in the Early Miocene, not via a proposed land bridge or island chain (GAARlandia) in the Early Oligocene (∼34 Ma). Patagonian and Antillean platyrrhines went extinct without leaving living descendants, the former at the end of the Early Miocene and the latter within the past six thousand years. Molecular evidence suggests crown platyrrhines arrived in Central America by crossing an intermittent connection through the Isthmus of Panama at or after 3.5Ma. Any more ancient Central American primates, should they be discovered, are unlikely to have given rise to the extant Central American taxa in situ.

Dust in the wind: How climate variables and volcanic dust affect rates of tooth wear in Central American howling monkeys.

OBJECTIVES: Two factors have been considered important contributors to tooth wear: dietary abrasives in plant foods themselves and mineral particles adhering to ingested food. Each factor limits the functional life of teeth. Cross-population studies of wear rates in a single species living in different habitats may point to the relative contributions of each factor. MATERIALS AND METHODS: We examine macroscopic dental wear in populations of Alouatta palliata (Gray, 1849) from Costa Rica (115 specimens), Panama (19), and Nicaragua (56). The sites differ in mean annual precipitation, with the Panamanian sites receiving more than twice the precipitation of those in Costa Rica or Nicaragua (∼3,500 mm vs. ∼1,500 mm). Additionally, many of the Nicaraguan specimens were collected downwind of active plinian volcanoes. Molar wear is expressed as the ratio of exposed dentin area to tooth area; premolar wear was scored using a ranking system. RESULTS: Despite substantial variation in environmental variables and the added presence of ash in some environments, molar wear rates do not differ significantly among the populations. Premolar wear, however, is greater in individuals collected downwind from active volcanoes compared with those living in environments that did not experience ash-fall. DISCUSSION: Volcanic ash seems to be an important contributor to anterior tooth wear but less so in molar wear. That wear is not found uniformly across the tooth row may be related to malformation in the premolars due to fluorosis. A surge of fluoride accompanying the volcanic ash may differentially affect the premolars as the molars fully mineralize early in the life of Alouatta.

What the awkward relatives tell us about planetary nebulae hosting binary systems

Relatives to Planetary Nebulae, such as barium stars or symbiotic systems, can shed light on the connection between Planetary Nebulae and binarity. Because of the observational selection effects against direct spectroscopic detection of binary PNe cores with orbital periods longer than a few dozen days, at present these "awkward relatives" are a critical source of our knowledge about the binary PNe population at longer periods. Below a few examples are discussed, posing constraints on the attempts to model nebula, ejection process in a binary. © 2006 International Astronomical Union.

Integración vertical en las empresas yerbateras y tealeras argentinas : variables que afectan el comportamiento de las firmas en sus decisiones de integración vertical

El sector de la yerba mate y el té en la Argentina tiene una larga historia en las provincias de Misiones y Corrientes. Esta historia siempre tiene como protagonista a la gran cantidad de productores, la industria y las autoridades políticas. Hace años entre estos actores se observa un fenómeno que es la integración vertical hacia la producción primaria por parte de las industrias. Dicho fenómeno genera preocupación en los eslabones inferiores y a la vez genera una interesante área para estudiar el comportamiento de la organización vertical de las empresas. El objetivo del presente trabajo es determinar las variables que explican la integración vertical de las empresas. Para esto se realizó un análisis de los aportes teóricos de los costos de transacción, costos de agencia e incertidumbre como principales fuentes que explicarían este fenómeno. En base a datos de 82 encuestas realizadas a empresas se estimaron modelos econométricos mediante el modelo Tobit, con el fin de cuantificar los efectos de las variables. Los resultados comprobaron que las empresas realizan una comparación entre costos de agencia vs. costos de transacción; costos de producción interna vs. precio pagado por comprar; incertidumbre de producción interna vs. la externa. Además, los factores de incertidumbre en las ventas y abastecimiento juegan otro rol importante en el nivel de integración. Se esperaba que la incertidumbre en las ventas disminuyera la integración de las empresas y generara una integración parcial, lográndose resultados opuestos. Esto último deja una interesante área de investigación posterior: el efecto del riesgo en la integración parcial de las empresas. Finalmente la integración actual de las empresas y la tendencia a aumentarla, deja en claro las diferencias en la eficiencia entre el sector primario y la industria en el desarrollo de la actividad agrícola en común

Logística externa de exportación de Quinua : estudio comparativo entre Perú y Bolivia

En los últimos años la quinua se ha constituido en un alimento de gran demanda por sus bondades nutritivas, con un elevado contenido proteico que fluctúa entre 13 a 20 por ciento el cual supera cualitativamente y cuantitativamente a otros cereales como el arroz, avena, cebada, etc. (7 a 11 por ciento). El ciclo de producción de la quinua se encuentra en un proceso de crecimiento exponencial en el cual, Perú viene posicionándose como principal productor y exportador mundial de quinua (50 por ciento), superando a Bolivia (49 por ciento) e ingresando a más de 45 mercados, con una demanda liderada por Estados Unidos. Cabe resaltar que el precio de comercialización de quinua viene siendo determinado por el mercado internacional por cuanto la quinua ha tendido a convertirse en un `commodity` y no varía de manera substancial, si proviene de Bolivia (US$ 6,64 por Kg.) o Perú (US$ 5,64 por Kg.), por lo cual estos costos serán variables de acuerdo a la eficiencia logística de proceso y distribución que permita generar una diferencia competitiva en el mercado. El objetivo de este trabajo es describir y comparar el sistema logístico de exportación de la Quinua peruana y boliviana, con la finalidad de identificar la diferencia competitiva en el mercado internacional utilizando indicadores logísticos emitidos por el Banco mundial, apoyado del diamante de Porter con énfasis en dos determinantes que son la condición de los factores y de la demanda. De acuerdo a los resultados obtenidos Perú en infraestructura, comercio exterior, idoneidad logística, trazabilidad y justo a tiempo; posee mejor desempeño comparado a Bolivia. Además, en los fletes internos (terrestres) y externos (marítimo) de quinua a mercados como EE.UU (Los Ángeles) y España (Puerto de Barcelona), el Perú tiene menores costos de exportación (US$/contenedor 890) que Bolivia (US$/contenedor 1.440), pero mayores al promedio de Latinoamérica. Uno de los factores que se apalancó para esta competitividad, son sus ventajas comparativas (cercanía de Puerto con zonas productoras), y competitivas (modernización del puerto de Callo). Además la iniciativa que ha tenido el estado peruano en la concesión de sus puertos para la modernización y la reducción de trámite documentario, así como el TLC con EE.UU que permitió a Perú tener mejores relaciones comerciales (52 ranking de 144 países evaluados) comparado con Bolivia (82). Y por último se concluye de manera general que el sistema logístico de quinua de Perú logísticamente es más competitivo que el sistema logístico de quinua de Bolivia, ya que obtuvo 10 por ciento más de ampliación de mercado externo, creando una ventaja diferenciada respecto a Bolivia que al 2014 disminuyo en un 15 por ciento en sus exportaciones con respecto al 2013. Asimismo, cerca del 70 por ciento del valor total exportado de la quinua de Perú representa quinua convencional y el otro 30 por ciento quinua orgánica, siendo esta última en promedio un 10 por ciento mejor pagada que el producto convencional. Y que generalmente la mercancía es despachada y puesta a disposición al importador generalmente dado por precio FOB.

Sistemas de producción de yacaré y helicícola : variables socio - económicas asociadas a su aprovechamiento sustentable

El uso comercial de fauna silvestre genera debates éticos y pragmáticos. Los debates pragmáticos discuten si ese aprovechamiento puede favorecer o dificultar la conservación de las especies y los ambientes donde habitan. Los abordajes conceptuales tradicionales analizan el eslabonamiento productivo a partir de los flujos de capital y producto enfatizando escasamente en los actores sociales intervinientes, lo que resulta insuficiente para evaluar su trayectoria en términos de sustentabilidad. El objetivo de este trabajo es desarrollar un modelo conceptual que identifique variables sociales y económicas y su influencia en el aprovechamiento sustentable desde la perspectiva de los actores sociales involucrados en el uso comercial de fauna silvestre. Con herramientas metodológicas propias de la etnografía, los sistemas blandos y las redes sociales se analizaron el: 1) el sistema argentino de producción de yacaré, y 2) el sistema argentino helicícola. Se conceptualizaron ambos sistemas definiendo estructuras, efectos umbral, estados de equilibrio y metas. La contrastación de sistemas aparentemente diferentes permitió identificar cinco categorías clave: 1) demanda internacional de los productos, 2) las relaciones sociales entre actores participantes, 3) la estructura productiva, 4) el marco regulatorio y 5) el estado de conservación de las poblaciones silvestres. El modelo conceptual desarrollado articula las condiciones objetivas y subjetivas sobre las que interactúan los actores sociales involucrados, reconociendo el carácter co-evolutivo entre los seres humanos y la naturaleza. Esta herramienta de diagnóstico y planificación es un aporte original que permite visualizar la magnitud de la intervención en la naturalez, según los intereses sociales que subyacen y evaluar el impacto de dicha intervención sobre la conservación de las especies utilizadas.

Efecto de variables ambientales sobre la productividad primaria neta aérea y la concentración de proteína bruta de gramíneas en sistemas silvopastoriles de ñire (Nothofagus antarctica) : creación de un modelo de simulación

Nothofagus antarctica (ñire) ocupa una importante superficie de los bosques de Patagonia Sur, siendo ampliamente usado como sistemas silvopastoriles con ganadería ovina y bovina. Sin embargo, en la mayoría de los casos el uso de estos bosques se realiza sin un manejo que permita optimizar la sustentabilidad del sistema. En esta tesis se estudió el efecto de distintas variables ambientales (temperatura, humedad del suelo, radiación) sobre la productividad y concentración de Proteína bruta (PB) de gramíneas en distintas situaciones de calidad forestal y coberturas de copas de bosques de ñire, así como también procesos asociados: descomposición y dinámica de nutrientes (mineralización-inmovilización) de residuos del estrato arbóreo y graminoso y mineralización de nitrógeno del suelo. La productividad de materia seca (MS) aérea de gramíneas (rango entre 135 a 1863 kg MS ha-1) estuvo positivamente asociada a la calidad forestal de los sitios, mientras que el efecto de las coberturas de copa dependió de la interacción con otras variables ambientales. Los valores de PB variaron principalmente según la cobertura de copa encontrándose los mayores valores en lugares más sombreados (transmisividades menor al 70 por ciento). La descomposición, tanto en hojas de ñire como en gramíneas, varió según el nivel de radiación, siendo mayores en los lugares con menor cobertura. Por otro lado, la dinámica de nutrientes no fue afectada por la CS o alguna variable estudiada. La mineralización de nitrógeno del suelo fue mayormente afectada por la humedad del suelo y el efecto de la cobertura de copa según la calidad del sitio forestal. Finalmente con los datos obtenidos e información de bibliografía se generó un modelo de simulación de productividad de MS y concentración de PB de gramíneas creciendo en bosques de ñire. El modelo generado después de ser sometido a diferentes pruebas se considera aceptable para ser usado como una herramienta de manejo sustentable en estos sistemas, aportando además nuevos conocimientos sobre las causales en la variación productiva y de calidad de los pastizales en bosques de ñire.