240 research outputs found
Stochastic Simulations Of Calcium Contents In Sugarcane Area
The aim of this study was to quantify and to map the spatial distribution and uncertainty of soil calcium (Ca) content in a sugarcane area by sequential Gaussian and simulated-annealing simulation methods. The study was conducted in the municipality of Guariba, northeast of the Sao Paulo state. A sampling grid with 206 points separated by a distance of 50 m was established, totaling approximately 42 ha. The calcium contents were evaluated in layer of 0-0.20 m. Techniques of geostatistical estimation, ordinary kriging and stochastic simulations were used. The technique of ordinary kriging does not reproduce satisfactorily the global statistics of the Ca contents. The use of simulation techniques allows reproducing the spatial variability pattern of Ca contents. The techniques of sequential Gaussian simulation and simulated annealing showed significant variations in the contents of Ca in the small scale.19876777
Mutations in the DNA methyltransferase gene DNMT3A cause an overgrowth syndrome with intellectual disability
Overgrowth disorders are a heterogeneous group of conditions characterized by increased growth parameters and other variable clinical features such as intellectual disability and facial dysmorphism. 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 leukemia. Thus, DNMT3A joins an emerging group of epigenetic DNA- and histone-modifying genes associated with both developmental growth disorders and hematological malignancies
The Tatton-Brown-Rahman Syndrome: A clinical study of 55 individuals with de novo constitutive DNMT3A variants.
Tatton-Brown-Rahman syndrome (TBRS; OMIM 615879), also known as the DNMT3A-overgrowth syndrome, is an overgrowth intellectual disability syndrome first described in 2014 with a report of 13 individuals with constitutive heterozygous DNMT3A variants. Here we have undertaken a detailed clinical study of 55 individuals with de novoDNMT3A variants, including the 13 previously reported individuals. An intellectual disability and overgrowth were reported in >80% of individuals with TBRS and were designated major clinical associations. Additional frequent clinical associations (reported in 20-80% individuals) included an evolving facial appearance with low-set, heavy, horizontal eyebrows and prominent upper central incisors; joint hypermobility (74%); obesity (weight ³2SD, 67%); hypotonia (54%); behavioural/psychiatric issues (most frequently autistic spectrum disorder, 51%); kyphoscoliosis (33%) and afebrile seizures (22%). One individual was diagnosed with acute myeloid leukaemia in teenage years. Based upon the results from this study, we present our current management for individuals with TBRS
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
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
Suscetibilidade magnética na identificação de compartimentos da paisagem em uma vertente
The use of new techniques that assist in identifying areas with different agricultural potentials promotes greater efficiency in soil management. With the increasing concern about environmental issues related to agricultural practices, new researches have been developed to minimize the environmental impacts of traditional agriculture. In this context, the objective of this work was to study the efficiency of the magnetic susceptibility in the identification of different landscape compartments in a hillslope in the city of Gilbués, Piauí, Brazil. In a 140 hectares area, three compartments of the hillslope were identified. A sampling grid of one hectare was assembled in each compartment. Samples were collected in 121 points spaced regularly at 10 meters. The magnetic susceptibility was efficient in identifying landscape. Thus, the magnetic susceptibility can be used to locate areas with higher or lower standard of variability, assisting in the identification of specific management areas more quickly and economically.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Universidade Federal do Piauí Centro de Ciências Agrárias Campus Agrícola da Socopo (Sala), Ininga, CEP 64014-510, Teresina-PIUniversidade Estadual Paulista Júlio de Mesquita Filho Faculdade de Ciências Agrárias e Veterinárias de Jaboticabal, Via de Acesso Prof. Paulo Donato Castelanne, s/n, CEP 14884900, Jaboticabal-SPUniversidade Estadual do Piauí, Prof Joaquina Nogueira Oliveira, s/n, Aeroporto, CEP 64980-000, Corrente-PIBolsista de Produtividade em Pesquisa do CNPqUniversidade Estadual Paulista Júlio de Mesquita Filho Faculdade de Ciências Agrárias e Veterinárias de Jaboticabal, Via de Acesso Prof. Paulo Donato Castelanne, s/n, CEP 14884900, Jaboticabal-S
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
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
Primrose syndrome: Characterization of the phenotype in 42 patients
Primrose syndrome (PS; MIM# 259050) is characterized by intellectual disability (ID), macrocephaly, unusual facial features (frontal bossing, deeply set eyes, down-slanting palpebral fissures), calcified external ears, sparse body hair and distal muscle wasting. The syndrome is caused by de novo heterozygous missense variants in ZBTB20. Most of the 29 published patients are adults as characteristics appear more recognizable with age. We present 13 hitherto unpublished individuals and summarize the clinical and molecular findings in all 42 patients. Several signs and symptoms of PS develop during childhood, but the cardinal features, such as calcification of the external ears, cystic bone lesions, muscle wasting, and contractures typically develop between 10 and 16 years of age. Biochemically, anemia and increased alpha-fetoprotein levels are often present. Two adult males with PS developed a testicular tumor. Although PS should be regarded as a progressive entity, there are no indications that cognition becomes more impaired with age. No obvious genotype-phenotype correlation is present. A subgroup of patients with ZBTB20 variants may be associated with mild, nonspecific ID. Metabolic investigations suggest a disturbed mitochondrial fatty acid oxidation. We suggest a regular surveillance in all adult males with PS until it is clear whether or not there is a truly elevated risk of testicular cancer.This article is freely available via Open Access. Click on the Publisher URL to access it via the publisher's site.published version, accepted version (12 month embargo) submitted versio
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
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