We aimed to determine the prevalence and landscape of germline mutations among patients with young-onset pancreatic ductal adenocarcinoma (PDAC) as well as their influence in prognosis.
Patients from ...two cohorts were studied, the high-risk cohort (HRC), which included 584 PDAC patients who received genetic counseling at The University of Texas MD Anderson Cancer Center, and a general cohort (GC) with 233 metastatic PDAC patients. We defined germline DNA sequencing on 13 known pancreatic cancer susceptibility genes. The prevalence and landscape of mutations were determined, and clinical characteristics including survival were analyzed.
A total of 409 patients underwent genetic testing (277 from HRC and 132 from GC). As expected, the HRC had higher prevalence of germline mutations compared with the GC: 17.3% versus 6.81%. The most common mutations in both cohorts were in BRCA1/2 and mismatch-repair (MMR) genes. Patients younger than 60 years old had significantly higher prevalence of germline mutations in both the HRC odds ratios (OR), 1.93 ± 1.03-3.70,
= 0.039 and GC (4.78 ± 1.10-32.95,
= 0.036). Furthermore, PDAC patients with germline mutations in the GC had better overall survival than patients without mutations (HR, 0.44; 95% CI of HR, 0.25-0.76,
= 0.030).
Germline mutations are highly prevalent in patients with PDAC of early onset and can be predictive of better outcomes. Considering emerging screening strategies for relatives carrying susceptibility genes as well as impact on therapy choices, genetic counseling and testing should be encouraged in PDAC patients, particularly those of young onset.
.
Nickel stabilized nanoparticles produced by an organometallic approach (Chaudret's method) starting from the complex Ni(1,5-COD)
2 were used as electrode materials for hydrogen evolution in NaOH at ...two temperatures (298 and 323
K). The synthesis of the nickel nanoparticles was performed in the presence of two different stabilizers, 1,3-diaminopropane (DAP) and anthranilic acid (AA), by varying the molar ratios (1:1, 1:2 and 1:5 metal:ligand) in order to evaluate their influence on the shape, dispersion, size and electrocatalytic activity of the metallic particles. The presence of an appropriate amount of stabilizer is an effective alternative to the synthesis of small monodispersed metal nanoparticles with diameters around 5 and 8
nm for DAP and AA, respectively. The results are discussed in terms of morphology and the surface state of the nanoparticles. The importance of developing a well-controlled synthetic method which results in higher performances of the resulting nanoparticles is highlighted. Herein we found that the performance with respect to the HER of the Ni electrodes dispersed on a carbon black Vulcan substrate is active and comparable to that reported in the literature for the state-of-the-art electrocatalysts. Appreciable cathodic current densities of ∼240
mA
cm
−2 were measured with highly dispersed nickel particles (Ni-5
DAP). This work demonstrates that the aforementioned method can be extended to the preparation of highly active stabilized metal particles without inhibiting the electron transfer for the HER reaction, and it could also be applied to the synthesis of bimetallic nanoparticles.
Este artigo tem como objetivo investigar a educação infantil em Timor-Leste, em seus distintos períodos históricos, tendo em vista que Timor é um país relativamente jovem e há uma lacuna na ...construção de conhecimento e produção acadêmica em pesquisas sobre a história da educação de modo geral – em especial a infantil. Consideramos a hipótese de que voltar o olhar para a história é um caminho para entender e enfrentar mais assertivamente os desafios para construção de saberes no campo da educação em Timor e sua incessante luta em busca de superação do domínio e exclusão social. A metodologia utilizada neste trabalho é de natureza qualitativa, percorrendo os caminhos da história e da pesquisa bibliográfica. As referências foram diversas para abarcar os diferentes períodos e administrações vivenciados pela nação.
Photonic curing, an exposure of matter to intense and short (μs) light pulses, is herein demonstrated as an effective and versatile method to activate and stabilize electrocatalysts for the ...electrochemical reduction of CO2. Catalyst preparation by colloidal synthesis often makes use of surfactants (capping agents) that control the size and morphology of target nano-objects during and after their synthesis. However, this approach can severely compromise the catalytic properties of the as-synthesized nanomaterials. Photonic curing is suitable to gently remove surfactants from the catalyst surface without severely altering its overall structural properties (e.g., surface faceting), thereby increasing the abundance of these surface active sites that can participate in the desired (electro)catalytic reaction. This catalyst activation is exemplarily demonstrated on the basis of Cu nanowire (Cu-NW) catalysts synthesized by an oleylamine route and transferred to a glassy carbon (GC) support electrode. Although the 3D networks of the as-synthesized Cu-NW catalysts predominantly produce hydrogen as the product of the electrolysis reaction, photonically cured Cu-NWs, denoted hereinafter as Cu metal membrane catalysts (MMCs), show a high selectivity toward ethylene formation, reaching a Faradaic efficiency of FEC2H4 = 42.4% (J C2H4 = −7.8 mA cm–2, E = −1.1 V vs RHE). This high ethylene yield can even be maintained during prolonged electrolysis of 110 h. A further beneficial effect of the photonic curing treatment is related to the substantially increased mechanical stabilization of the Cu-NW film on the support electrode induced by a “mild” sintering of Cu-NWs, which remains locally confined to their points of contact. A loss of catalyst material or a delamination of the catalyst film from the support electrode during massive gas evolution can thus be prevented.
Cystic fibrosis (CF) affects multiple organs, the most severe consequences being observed in the lungs. Despite significant progress in developing CF transmembrane conductance regulator-specific ...treatments for CF lung disease, exploring alternative CF-targeted medications seems reasonable. We sought to evaluate the potential beneficial effects of oral benzbromarone as an adjuvant therapy in CF patients with reduced lung function.OBJECTIVECystic fibrosis (CF) affects multiple organs, the most severe consequences being observed in the lungs. Despite significant progress in developing CF transmembrane conductance regulator-specific treatments for CF lung disease, exploring alternative CF-targeted medications seems reasonable. We sought to evaluate the potential beneficial effects of oral benzbromarone as an adjuvant therapy in CF patients with reduced lung function.This was a prospective open-label pilot study of oral benzbromarone (100 mg/day) administered once daily for 90 days. Patients were followed at a tertiary referral center in southern Brazil. Safety was assessed by the number of reported adverse events. Secondary objectives included percent predicted FEV1 (FEV1%) and pulmonary exacerbations.METHODSThis was a prospective open-label pilot study of oral benzbromarone (100 mg/day) administered once daily for 90 days. Patients were followed at a tertiary referral center in southern Brazil. Safety was assessed by the number of reported adverse events. Secondary objectives included percent predicted FEV1 (FEV1%) and pulmonary exacerbations.Ten patients were enrolled. Benzbromarone was found to be safe, with no serious drug-related adverse events. Eight patients completed the study; the median relative change in FEV1% tended to increase during the treatment, showing an 8% increase from baseline at the final visit. However, a nonparametric test showed that the change was not significant (p = 0.06). Of a total of ten patients, only one experienced at least one pulmonary exacerbation during the study.RESULTSTen patients were enrolled. Benzbromarone was found to be safe, with no serious drug-related adverse events. Eight patients completed the study; the median relative change in FEV1% tended to increase during the treatment, showing an 8% increase from baseline at the final visit. However, a nonparametric test showed that the change was not significant (p = 0.06). Of a total of ten patients, only one experienced at least one pulmonary exacerbation during the study.Oral benzbromarone appears to be safe, and improved FEV1% has been observed in patients with CF. Further assessment in larger trials is warranted to elucidate whether oral benzbromarone can be a potential adjuvant therapy for CF.CONCLUSIONSOral benzbromarone appears to be safe, and improved FEV1% has been observed in patients with CF. Further assessment in larger trials is warranted to elucidate whether oral benzbromarone can be a potential adjuvant therapy for CF.
There is a global tendency to emphasize the prevention and early diagnosis of diseases that have a great impact on public health. Atrial fibrillation (AF) has a prevalence affecting 1.5-2% of the ...general population. Certain variables of the P wave allow us to identify and stratify patients at risk of developing AF.
This is an observational, descriptive, and longitudinal study to determine the applicability of the electrocardiographic (ECG) morphology, voltage, and P wave duration (MVP) risk score to predict the development of AF in consecutive patients with systemic hypertension (SH) in an initial follow-up of 12 months.
Initially, 104 patients were included, of whom 12 died during follow-up and 17 did not attend subsequent checkups during the COVID-19 pandemic; therefore, they were excluded. The study patients were 75, of whom AF was detected in 25 patients (33%). The average duration of the P wave was 120 ± 26 ms, the average voltage was 0.1 ± 0.5 Mv. The high-risk MVP ECG score had an area under the curve, 0.69; 95% confidence intervals (CI), 0.59-0.79 and demonstrated a specificity and a positive predictive value of 100%, a negative predictive value of 76%, and a sensitivity of 40% for predicting the development of AF.
The present study establishes for the first time that SH patients who possess a high-risk MVP ECG score have a significantly higher incidence of developing AF. The high-risk MVP Score has a specificity and a positive predictive value of 100% and a high negative predictive value with a moderate sensitivity for the prediction of the development of AF in SH patients.
Numerous cross-sectional studies have linked health-related quality of life (HRQoL) with peer victimization, but evidence of how this relationship may change over time is lacking. The main objectives ...of this study were to analyze the prevalence, incidence, and stability of peer victimization and to longitudinally relate peer victimization to HRQoL. A longitudinal study was designed and implemented at three separate time points over a 13-month period. The study involved 1,155 adolescents (43.5% boys;
n
= 503) aged between 11 and 18 years. The prevalence of victimization for each wave was, respectively, 32.4%, 25.9%, and 23.7%, with a period prevalence of 48.5% and a cumulative incidence of 25%. Eight percent of the victims were stable victims across the three waves. The most frequent type of victimization was direct verbal victimization. Peer victimization correlated significantly across the three waves (
r
> .40;
p
< .001), as did HRQoL (
r
> .50;
p
< .001). Stable victims showed the lowest HRQoL scores. There were no statistically significant differences in HRQoL among new victims, ceased victims, and intermittent victims, but all of them presented lower HRQoLs than non-victims (
p
< .001). In conclusion, this manuscript presents a unique approach to peer victimization through an epidemiological perspective and provides evidence that stable victims experience the greatest loss of HRQoL.
Background. The amount of nutrients required by pineapple varies depending on the cultivar and planting density. Knowing the nutrient requirement in quantity and the appropriate phenological stage ...will allow the development of an adequate fertilization program. Objective. To determine the effect of pineapple cultivar and planting density on N, P, and K content during plant development and at harvest. Methodology. The cultivars 'Smooth Cayenne', 'Champaka', and 'MD-2' were established at 30000, 45000, and 60000 plants ha-1. Eight samples were taken to determine the N, P, and K content in the organs and the total plant. Results. The highest and lowest N, P, and K contents were detected in the leaf and root, respectively. The highest N and K contents occurred at 441 - 506 days after planting. Higher P content occurred close to harvest. The highest N, P, and K contents per plant were at 30000 plants ha-1 (14.86, 1.52, and 16.29 g plant-1, respectively) and the lowest at 60000 plants ha-1 (10.16, 1.13, and 14.6 g plant-1, respectively). Higher N, P, and K contents per hectare were detected with 60000 plants ha-1 (609, 68, and 875 kg ha-1, respectively). At harvest, ‘Smooth Cayenne’ at 60000 plants ha-1 accumulated the highest amount of N, P, and K (147, 37, and 306 kg ha-1, respectively). Implications. The changes that can occur in the nutrient requirements of pineapple as a function of cultivar, planting density, and stage of plant development were identified. This information will be useful for producers, agricultural technicians, and researchers in Mexico and the world, to generate fertilization programs or establish new research. Conclusion. At the beginning of plant growth, a higher N, P, and K contents in the leaf, this amount decreases as the fruit harvest approaches. Regardless of cultivar, the highest nutrient content per plant occurs at the lowest planting density, however, the highest content per hectare occurs at the highest planting density. At harvest time, fewer nutrients are removed from the soil with 'Champaka' and 'MD-2' fruit.
Earth is changing rapidly and so are many plant species’ ranges. Here, we synthesize eco-evolutionary patterns found in plant range studies and how knowledge of species ranges can inform our ...understanding of species conservation in the face of global change. We discuss whether general biogeographic “rules” are reliable and how they can be used to develop adaptive conservation strategies of native plant species across their ranges. Rules considered include (1) factors that set species range limits and promote range shifts; (2) the impact of biotic interactions on species range limits; (3) patterns of abundance and adaptive properties across species ranges; (4) patterns of gene flow and their implications for genetic rescue, and (5) the relationship between range size and conservation risk. We conclude by summarizing and evaluating potential species range rules to inform future conservation and management decisions. We also outline areas of research to better understand the adaptive capacity of plants under environmental change and the properties that govern species ranges. We advise conservationists to extend their work to specifically consider peripheral and novel populations, with a particular emphasis on small ranges. Finally, we call for a global effort to identify, synthesize, and analyze prevailing patterns or rules in ecology to help speed conservation efforts.
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