Travelers With Cutaneous Leishmaniasis Cured Without Systemic Therapy

Guidelines recommend wound care and/or local therapy as first-line treatment for cutaneous leishmaniasis. An analysis of a referral treatment program in 135 travelers showed that this approach was feasible in 62% of patients, with positive outcome in 83% of evaluable patient

Attitude and Performance in Mathematics I of Bachelor of Elementary Education Students: A Correlational Analysis

This paper determines the relationship between attitude and performance in Mathematics of 105 Bachelor of Elementary Education (BEEd) freshman students by using correlational research with the questionnaire as the main instrument. The study found that the performance in Mathematics I of the respondents was below average. Their attitudes are significantly correlated with their performance in Mathematics I. The higher their positive attitude, the higher their performance (r=.792**, p<0.01), whereas the higher their negative attitude the lower their performance (r= -.940**, p<0.01). Further, the respondents believe that working with Mathematics problems will make them better critical thinkers and they assume that they have more chance of becoming successful in life if they are good in Mathematics. However, the respondents consider Mathematics as the most difficult subject. They were scared of Mathematics problems and easily give up with answering when they cannot solve them. The overall result revealed that the respondents exhibit negative attitude towards Mathematics. The significant findings of this study provide valuable information for Mathematics teachers, administrators and curriculum planners to enhance policies and pedagogies relating to Mathematics instruction

EFSA Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids (CEF); Scientific Opinion on Flavouring Group Evaluation 96 (FGE.96): Consideration of 88 flavouring substances considered by EFSA for which EU production volumes / anticipated production volumes have been submitted on request by DG SANCO. Addendum to FGE. 51, 52, 53, 54, 56, 58, 61, 62, 63, 64, 68, 69, 70, 71, 73, 76, 77, 79, 80, 83, 84, 85 and 87

Overgrowth disorders are a heterogeneous group of conditions characterized by increased growth parameters and other variable clinical features such as intellectual disability and facial dysmorphism1. To identify new causes of human overgrowth, we performed exome sequencing in ten proband-parent trios and detected two de novo DNMT3A mutations. We identified 11 additional de novo mutations by sequencing DNMT3A in a further 142 individuals with overgrowth. The mutations alter residues in functional DNMT3A domains, and protein modeling suggests that they interfere with domain-domain interactions and histone binding. Similar mutations were not present in 1,000 UK population controls (13/152 cases versus 0/1,000 controls; P < 0.0001). Mutation carriers had a distinctive facial appearance, intellectual disability and greater height. DNMT3A encodes a DNA methyltransferase essential for establishing methylation during embryogenesis and is commonly somatically mutated in acute myeloid leukemia2, 3, 4. Thus, DNMT3A joins an emerging group of epigenetic DNA- and histone-modifying genes associated with both developmental growth disorders and hematological malignancie

A comprehensive molecular study on Coffin-Siris and Nicolaides-Baraitser syndromes identifies a broad molecular and clinical spectrum converging on altered chromatin remodeling

Chromatin remodeling complexes are known to modify chemical marks on histones or to induce conformational changes in the chromatin in order to regulate transcription. De novo dominant mutations in different members of the SWI/SNF chromatin remodeling complex have recently been described in individuals with Coffin-Siris (CSS) and Nicolaides-Baraitser (NCBRS) syndromes. Using a combination of whole-exome sequencing, NGS-based sequencing of 23 SWI/SNF complex genes, and molecular karyotyping in 46 previously undescribed individuals with CSS and NCBRS, we identified a de novo 1-bp deletion (c.677delG, p.Gly226Glufs*53) and a de novo missense mutation (c.914G>T, p.Cys305Phe) in PHF6 in two individuals diagnosed with CSS. PHF6 interacts with the nucleosome remodeling and deacetylation (NuRD) complex implicating dysfunction of a second chromatin remodeling complex in the pathogenesis of CSS-like phenotypes. Altogether, we identified mutations in 60% of the studied individuals (28/46), located in the genes ARID1A, ARID1B, SMARCB1, SMARCE1, SMARCA2, and PHF6. We show that mutations in ARID1B are the main cause of CSS, accounting for 76% of identified mutations. ARID1B and SMARCB1 mutations were also found in individuals with the initial diagnosis of NCBRS. These individuals apparently belong to a small subset who display an intermediate CSS/NCBRS phenotype. Our proposed genotype-phenotype correlations are important for molecular screening strategie

Spatial variability of texture in an Oxisol cultivated with citrus

Relief influences soil texture variability, since it contributes to the time of exposition of the materials to weathering factors. Our work was carried out in the city of Gavião Peixoto (SP), with the objective of characterizing the spatial variability of texture of a dystrophic Red Latosol cultivated with citrus. The hillside was divided into three segments: top, stocking lean and inferior lean. Soil samples were collected in a grid with regular intervals of 50 m, at the depths of 0.0-0.2 m and 0.6-0.8 m, comprising a total of 332 points in an area of 83.5 ha. The data were submitted to descriptive and geostatistics analyses (semivariogram modeling and kriging maps). The spatial behavior of the texture of oxisols is directly related to the relief forms in this study, which controls the direction of surface and subsurface water flows. The concept of homogeneity of clay distribution in the Oxisol profile is a piece of information that can be adjusted by knowing the spatial pattern of this distribution in different relief forms.O relevo influencia a variabilidade da textura, uma vez que condiciona o tempo de exposição dos materiais à ação do intemperismo. Neste trabalho, desenvolvido no município de Gavião Peixoto (SP), objetivou-se caracterizar a variabilidade espacial da textura de um Latossolo Vermelho distrófico sob cultivo de citros. A encosta foi dividida em três segmentos: topo, meia encosta e encosta inferior. O solo foi amostrado em malha, com intervalos regulares de 50 m, perfazendo o total de 332 pontos em uma área de 83,5 ha, nas profundidades de 0,0-0,2 m e 0,6-0,8 m. Os dados foram submetidos à análise estatística descritiva e geoestatística (modelagem de semivariogramas e mapas de krigagem). O comportamento espacial da textura de latossolos está diretamente relacionado com as formas do relevo neste estudo, que controla o sentido dos fluxos de água superficial e subsuperficial. O conceito de homogeneidade da distribuição de argila no perfil dos latossolos é uma informação que pode ser ajustada pelo conhecimento do padrão espacial dessa distribuição em diferentes formas do relevo.12113

Towards an improved understanding of biogeochemical processes across surface-groundwater interactions in intermittent rivers and ephemeral streams

Surface-groundwater interactions in intermittent rivers and ephemeral streams (IRES), waterways which do not flow year-round, are spatially and temporally dynamic because of alternations between flowing, non-flowing and dry hydrological states. Interactions between surface and groundwater often create mixing zones with distinct redox gradients, potentially driving high rates of carbon and nutrient cycling. Yet a complete understanding of how underlying biogeochemical processes across surface-groundwater flowpaths in IRES differ among various hydrological states remains elusive. Here, we present a conceptual framework relating spatial and temporal hydrological variability in surface water-groundwater interactions to biogeochemical processing hotspots in IRES. We combine a review of theIRES biogeochemistry literature with concepts of IRES hydrogeomorphology to: (i) outline common distinctions among hydrological states in IRES; (ii) use these distinctions, together with considerations of carbon, nitrogen, and phosphorus cycles within IRES, to predict the relative potential for biogeochemical processing across different reach-scale processing zones (flowing water, fragmented pools, hyporheic zones, groundwater, and emerged sediments); and (iii) explore the potential spatial and temporal variability of carbon and nutrient biogeochemical processing across entire IRES networks. Our approach estimates the greatest reach-scale potential for biogeochemical processing when IRES reaches are fragmented into isolated surface water pools, and highlights the potential of relatively understudied processing zones, such as emerged sediments. Furthermore, biogeochemical processing in fluvial networks dominated by IRES is likely more temporally than spatially variable. We conclude that biogeochemical research in IRES would benefit from focusing on interactions between different nutrient cycles, surface-groundwater interactions in non-flowing states, and consideration of fluvial network architecture. Our conceptual framework outlines opportunities to advance studies and expand understanding of biogeochemistry in IRES

Behind the scenes: mechanisms regulating climatic patterns of dissolved organic carbon uptake in headwater streams

Large variability in dissolved organic carbon (DOC) uptake rates has been reported for headwater streams, but the causes of this variability are still not well understood. Here we assessed acetate uptake rates across 11 European streams comprising different ecoregions by using whole-reach pulse acetate additions. We evaluated the main climatic and biogeochemical drivers of acetate uptake during two seasonal periods. Our results show a minor influence of sampling periods but a strong effect of climate and dissolved organic matter (DOM) composition on acetate uptake. In particular, mean annual precipitation explained half of the variability of the acetate uptake velocities (VfAcetate) across streams. Temperate streams presented the lowest VfAcetate, together with humic-like DOM and the highest stream respiration rates. In contrast, higher VfAcetate were found in semiarid streams, with protein-like DOM, indicating a dominance of reactive, labile compounds. This, together with lower stream respiration rates and molar ratios of DOC to nitrate, suggests a strong C limitation in semiarid streams, likely due to reduced inputs from the catchment. Overall, this study highlights the interplay of climate and DOM composition and its relevance to understand the biogeochemical mechanisms controlling DOC uptake in streams.Theauthors were supported by the following funding: N. C. by a Generalitat de Catalunya-Beatriu de Pinós grant (BP2016–00215), E. E. by a predoctoral grant from the Basque Government, A. G. B. by a Generalitat de Catalunya-Beatriu de Pinós (BP-00385-2016), A. M. G. F. by a predoctoral research grant (BES-2013-065770) from the Spanish Ministry of Economy and Competitiveness, P. R. L. by a Ramón Areces Foundation Postdoctoral Scholarship, and A. L. by a Kempe Foundation stipend. DOMIPEX project was funded by the First Call of Collaborative Projects among Young Researchers of the Iberian Association of Limnology (AIL; 2013–2015)

Controles locales y regionales del metabolismo en ríos de cabecera: aportaciones del primer proyecto colaborativo de la AIL

Streams play a key role in the global biogeochemical cycles, processing material from adjacent terrestrial systems and transporting it downstream. However, the drivers of stream metabolism, especially those acting at broad spatial scales, are still not well understood. Moreover, stream metabolism can be affected by hydrological changes associated with seasonality, and thus, assessing the temporality of metabolic rates is a key question to understand stream function. This study aims to analyse the geographical and temporal patterns in stream metabolism and to identify the main drivers regulating the wholeecosystem metabolic rates at local and regional scales. Using a coordinated distributed experiment, we studied ten headwaters streams located across five European ecoregions during summer and fall 2014.We characterized the magnitude and variability of gross primary production (GPP) and ecosystem respiration (ER) with the open-channel method. Moreover, we examined several climatic, geographical, hydrological, morphological, and physicochemical variables that can potentially control stream metabolic rates. Daily rates of stream metabolism varied considerately across streams, with GPP and ER ranging from 0.06 to 4.33 g O2 m?2 d?1 and from 0.72 to 14.20 g O2 m?2 d?1, respectively. All streams were highly heterotrophic (P/R < 1), except the southernmost one. We found that the drier climates tended to have the highest GPP, while humid regions presented the highest ER. Between the sampling periods no statistical differences were found. Partial-least squares models (PLS) explained ?80% of the variance in GPP and ER rates across headwater streams and included both local and regional variables. Rates of GPP varied primarily in response to the local variables, such as streambed substrate and stream water temperature. In contrast, regional variables, such as the mean annual temperature or the land use of the catchment, had more relevance to explain ER. Overall, our results highlight that stream metabolism depends on both local and regional drivers and show the positive experience of a young network of researchers to assess scientific challenges across large-scale geographic areas.Los ecosistemas fluviales tienen un papel relevante en los ciclos biogeoquímicos globales, ya que procesan el material de la cuenca y lo transportan río abajo. Sin embargo, los factores que afectan al metabolismo, especialmente aquellos que actúan en una escala espacial más amplia, todavía no se conocen completamente. Además, el metabolismo fluvial puede variar a causa de cambios hidrológicos relacionados con la estacionalidad; lo que también hace importante incluir la variabilidad temporal para entender el funcionamiento de los ríos. Mediante el uso de un experimento distribuido y coordinado, estudiamos diez ríos de cabecera localizados a lo largo de cinco ecoregiones europeas durante verano y otoño del 2014. Se midió la magnitud y la variabilidad de la producción primaria bruta (PPB) y la respiración ecosistémica (RE) mediante el método de canal abierto. Así mismo, se examinaron los factores climáticos, hidrológicos y físico-químicos que potencialmente pueden afectar las tasas metabólicas fluviales. Las tasas diarias de metabolismo fluvial variaron considerablemente entre ríos, con valores de PPB de entre 0.06 a 4.33 g O2 m-2 día-1, y de RE de entre 0.72 a 14.20 g O2 m-2 día-1. Todos los ríos fueron altamente heterotróficos (P/R < 1), excepto el río más meridional. Se observó que los climas secos tendían a tener mayor PPB y las regiones húmedas tendían a tener una mayor RE. No se encontraron diferencias estadísticas entre los períodos de estudio. Los modelos de regresión de mínimos cuadrados parciales (PLS) explicaron --80% de la varianza de PPB y RE para los ríos estudiados. Las tasas de PPB variaron principalmente con factores locales como el sustrato del lecho del río y la temperatura del agua. En cambio, las tasas de RE estuvieron estrechamente relacionadas con factores regionales, como la temperatura media anual y los impactos en la cuenca. En conjunto, nuestros resultados resaltan la necesidad de incluir la escala local y regional en el estudio del metabolismo fluvial y muestran la experiencia positiva de una red coordinada de jóvenes investigadores para lograr retos científicos de amplia escala geográfica.We thank the support of the AIL board throughout the development of the project and all the affiliated institutions for the accessibility of laboratory premises, especially the Limnology Department of Uppsala University and the Department d’Ecologia of the Universitat de Barcelona. We greatly thank all the extended team of participants for their valuable contribution in DOMIPEX project. The authors were supported by the following founding: NC by Wenner-Gren foundation stipend (Sweden, 2014-2016) and a Juan de la Cierva grant (FJCI-2014-23064), EE by a pre-doctoral grant from the Basque Government (2014-2017), AGB by a Swedish Research Council grant (SMAREF 2014-2016), PRL by a Ramón Areces Foundation Postdoctoral Scholarship AM by the Univ. of the Basque Country, AMGF and SP by pre-doctoral research grants from the Spanish Ministry of Economy and Competitiveness (Ref: BES-2013-065770, Ref: BES-2012-059743, respectively), and RR by the IMDEA-Water Institute. DOMIPEX project was founded by the First Call of Collaborative Projects among Young Researchers of the Iberian Association of Limnology (AIL; 2013-2015)

Efficacy of Immune Checkpoint Inhibitors for the Treatment of Advanced Melanoma in Patients With Concomitant Chronic Lymphocytic Leukemia

BACKGROUND: Immune checkpoint inhibitors (ICIs) have revolutionized the management of advanced melanoma (AM). However, data on ICI effectiveness have largely been restricted to clinical trials, thereby excluding patients with co-existing malignancies. Chronic lymphocytic leukemia (CLL) is the most prevalent adult leukemia and is associated with increased risk of melanoma. CLL alters systemic immunity and can induce T-cell exhaustion, which may limit the efficacy of ICIs in patients with CLL. We, therefore, sought to examine the efficacy of ICI in patients with these co-occurring diagnoses. PATIENTS AND METHODS: In this international multicenter study, a retrospective review of clinical databases identified patients with concomitant diagnoses of CLL and AM treated with ICI (US-MD Anderson Cancer Center, N = 24; US-Mayo Clinic, N = 15; AUS, N = 19). Objective response rates (ORRs), assessed by RECIST v1.1, and survival outcomes [overall survival (OS) and progression-free survival (PFS)] among patients with CLL and AM were assessed. Clinical factors associated with improved ORR and survival were explored. Additionally, ORR and survival outcomes were compared between the Australian CLL/AM cohort and a control cohort of 148 Australian patients with AM alone. RESULTS: Between 1997 and 2020, 58 patients with concomitant CLL and AM were treated with ICI. ORRs were comparable between AUS-CLL/AM and AM control cohorts (53% versus 48%, P = 0.81). PFS and OS from ICI initiation were also comparable between cohorts. Among CLL/AM patients, a majority were untreated for their CLL (64%) at the time of ICI. Patients with prior history of chemoimmunotherapy treatment for CLL (19%) had significantly reduced ORRs, PFS, and OS. CONCLUSIONS: Our case series of patients with concomitant CLL and melanoma demonstrate frequent, durable clinical responses to ICI. However, those with prior chemoimmunotherapy treatment for CLL had significantly worse outcomes. We found that CLL disease course is largely unchanged by treatment with ICI

Anaerobic biodigestion of pigs feces in the initial, growing and finishing stages fed with diets formulated with corn or sorghum

The objective of this study was to evaluate the quality and the production of biogas and biofertilizer obtained from biodigester supplied with pig feces in the initial, growing and finishing stages, fed with diets formulated based on corn or sorghum. Twenty bench biodigesters were used with hydraulic retention time of 30 days and daily loads that contained 4 to 6% of total solids (TS) and 3.6 to 5.2% of volatile solids (VS). In the effluent of the biodigesters, mean levels of TS were observed ranging between 1.6 and 2.0% and of VS between 1.2 and 1.6%. The mean reductions of TS were 57.7 to 64.7% and of VS from 61.7 to 69.0%, and there was only difference in the finishing phase, in which the major averages reductions were produced by the biodigesters supplied with feces from animals fed with diets based on corn. In biodigesters supplied with feces from animals in the initial and growing stages fed with diets based on corn, were observed higher average productions of biogas and the greatest average potentials of biogas production. The average potentials obtained were 0.033; 0.181; 0.685; 0.788 and 1.132 m³ per kg of affluent, manure, TS added, VS added and VS reduced, respectively. No differences were found on the average content of methane in the biogas between diets and stages. The average concentrations of nutrients N, P, K, Ca, Mg, Na, Fe, Mn, Zn and Cu in the biodigester affluent and effluent, ranged between diets and stages.Objetivou-se avaliar a produção e a qualidade do biogás e do biofertilizante obtidos em biodigestores abastecidos com dejetos de suínos, nas fases inicial, crescimento e terminação, alimentados com dietas formuladas à base de milho ou sorgo. Foram utilizados 20 biodigestores de bancada, com tempo de retenção hidráulica de 30 dias, e cargas diárias que continham 4,0 a 6,0% de sólidos totais (ST) e 3,6 a 5,2% de sólidos voláteis (SV). Nos efluentes dos biodigestores, foram verificados teores médios de ST variando de 1,6 a 2,0% e de SV entre 1,2 e 1,6%. As reduções médias de ST foram de 57,7 a 64,7% e de SV de 61,7 a 69,0%, sendo que houve diferença somente na fase de terminação, na qual as maiores reduções médias foram para biodigestores abastecidos com dejetos de animais alimentados com dietas à base de milho. Nos biodigestores abastecidos com dejetos de animais em fase inicial e de crescimento, alimentados com dietas formuladas à base de milho, foram verificadas maiores produções médias de biogás e os maiores potenciais médios de produção de biogás. Os potenciais médios obtidos foram 0,033; 0,181; 0,685; 0,788 e 1,132 m³ por kg de afluente, estrume, ST adicionados, SV adicionados e SV reduzidos, respectivamente. Não foram verificadas diferenças quanto ao teor médio de metano no biogás entre dietas e fases. As concentrações médias dos nutrientes N, P, K, Ca, Mg, Na, Fe, Mn, Zn e Cu no afluente e efluente dos biodigestores variaram entre as dietas e fases