Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 125
Filtrar
Mais filtros

Intervalo de ano de publicação
1.
BMC Plant Biol ; 24(1): 488, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38825683

RESUMO

BACKGROUND: The periderm is basic for land plants due to its protective role during radial growth, which is achieved by the polymers deposited in the cell walls. In most trees, like holm oak, the first periderm is frequently replaced by subsequent internal periderms yielding a heterogeneous outer bark made of a mixture of periderms and phloem tissues, known as rhytidome. Exceptionally, cork oak forms a persistent or long-lived periderm which results in a homogeneous outer bark of thick phellem cell layers known as cork. Cork oak and holm oak distribution ranges overlap to a great extent, and they often share stands, where they can hybridize and produce offspring showing a rhytidome-type bark. RESULTS: Here we use the outer bark of cork oak, holm oak, and their natural hybrids to analyse the chemical composition, the anatomy and the transcriptome, and further understand the mechanisms underlying periderm development. We also include a unique natural hybrid individual corresponding to a backcross with cork oak that, interestingly, shows a cork-type bark. The inclusion of hybrid samples showing rhytidome-type and cork-type barks is valuable to approach cork and rhytidome development, allowing an accurate identification of candidate genes and processes. The present study underscores that abiotic stress and cell death are enhanced in rhytidome-type barks whereas lipid metabolism and cell cycle are enriched in cork-type barks. Development-related DEGs showing the highest expression, highlight cell division, cell expansion, and cell differentiation as key processes leading to cork or rhytidome-type barks. CONCLUSION: Transcriptome results, in agreement with anatomical and chemical analyses, show that rhytidome and cork-type barks are active in periderm development, and suberin and lignin deposition. Development and cell wall-related DEGs suggest that cell division and expansion are upregulated in cork-type barks whereas cell differentiation is enhanced in rhytidome-type barks.


Assuntos
Casca de Planta , Quercus , Quercus/genética , Quercus/crescimento & desenvolvimento , Casca de Planta/genética , Casca de Planta/química , Casca de Planta/metabolismo , Transcriptoma , Hibridização Genética , Parede Celular/metabolismo , Regulação da Expressão Gênica de Plantas , Lipídeos
2.
BJU Int ; 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38940282

RESUMO

OBJECTIVE: To assess the association between achievement of prostate-specific antigen (PSA) levels ≤0.2 ng/mL (henceforth 'ultralow') and clinical outcomes in patients in the 'Targeted Investigational Treatment Analysis of Novel Anti-androgen' (TITAN) study (ClinicalTrials.gov Identifier NCT02489318) with metastatic castration-sensitive prostate cancer (mCSPC). PATIENTS AND METHODS: Patients in the TITAN study with mCSPC were randomised to 240 mg/day apalutamide (n = 525) or placebo (n = 527) plus androgen-deprivation therapy. This post hoc analysis assessed the achievement of a PSA level of 0.2->0.02 ng/mL ('ultralow one' [UL1]) and ≤0.02 ng/mL ('ultralow two' [UL2]) vs >0.2 ng/mL with apalutamide treatment and its association with radiographic progression-free survival (rPFS), overall survival (OS), time to castration-resistant PC (TTCRPC), and time to PSA progression (TTPP). The landmark analysis and Kaplan-Meier methods were used. RESULTS: By 3 months, more patients achieved UL1 and UL2 with apalutamide (38% and 23%) vs placebo (15% and 5%). In the apalutamide-treated patients, UL2 vs PSA >0.2 ng/mL at landmark 3 months was associated with significantly longer rPFS (hazard ratio [HR] 0.28, 95% confidence interval [CI] 0.14-0.54), OS (HR 0.24, 95% CI 0.13-0.43), TTCRPC (HR 0.2, 95% CI 0.11-0.38), and TTPP (HR 0.11, 95% CI 0.04-0.27; nominal P values all <0.001); this association was also observed but less pronounced for UL1. Similar findings were observed at 6 months. Early onset of decline to UL2 by 3 months was associated with improved survival vs PSA >0.2 ng/mL anytime (HR 0.12, 95% CI 0.06-0.22; P < 0.001) in apalutamide-treated patients. CONCLUSIONS: In this post hoc analysis of TITAN, patients with the deepest PSA decline derived the greatest benefit. These results extend our findings of apalutamide efficacy in the overall TITAN population, underscoring the clinical value of PSA kinetics as a marker for treatment efficacy. PATIENT SUMMARY: Patients with metastatic prostate cancer that is sensitive to ongoing hormonal treatment benefited significantly from the addition of apalutamide compared with placebo. Those who achieved rapid and deep PSA reduction had the greatest survival benefit.

3.
Future Oncol ; 20(10): 563-578, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38126311

RESUMO

WHAT IS THIS SUMMARY ABOUT?: This summary describes the results from an additional (or post hoc) analysis of the TITAN study. The TITAN study looked at whether the prostate cancer treatment apalutamide could be used to treat individuals with metastatic castration-sensitive prostate cancer (or mCSPC). A total of 1052 participants with mCSPC were included in the TITAN study. Treatment with apalutamide was compared with treatment with placebo. All participants received androgen deprivation therapy (or ADT), which is a type of hormone therapy that has been part of the main treatment for mCSPC for many years. The results showed that apalutamide plus ADT increased the length of time that participants remained alive compared with placebo plus ADT. Apalutamide plus ADT also controlled the growth of the cancer for a longer length of time compared with placebo plus ADT. Additionally, participants who received apalutamide plus ADT experienced a greater reduction in the blood levels of prostate-specific antigen (or PSA), called a deep PSA decline, compared with those who received placebo plus ADT. An additional (or post hoc) analysis was carried out to understand whether a decrease in blood PSA levels, in response to treatment, was associated with improved outcomes, including longer survival time. WHAT WERE THE RESULTS OF THE ADDITIONAL ANALYSIS?: In participants who received apalutamide plus ADT, a deep PSA decline in response to treatment was associated with longer survival time and improved outcomes. WHAT DO THESE RESULTS MEAN FOR INDIVIDUALS WITH MCSPC?: These results demonstrate that individuals with mCSPC can benefit from treatment with apalutamide plus ADT. The association seen between deep PSA decline and the longer survival time and improved outcomes highlights how PSA measurements can be used to help monitor cancer disease evolution in response to treatment. Monitoring PSA levels will assist doctors and other healthcare professionals to understand how effectively a treatment is working for a patient and to tailor their treatment approach to improve PSA decline.


Assuntos
Antígeno Prostático Específico , Neoplasias de Próstata Resistentes à Castração , Masculino , Humanos , Antagonistas de Androgênios/uso terapêutico , Neoplasias de Próstata Resistentes à Castração/patologia , Tioidantoínas/efeitos adversos
4.
Eur Radiol ; 33(11): 7371-7379, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37280356

RESUMO

OBJECTIVES: The standard therapy for small renal masses (SRMs) remains partial nephrectomy (PN), which is associated with relatively high morbidity and complication rate. Therefore, percutaneous radiofrequency ablation (PRFA) emerges as an alternative therapy. This study aimed to compare the efficacy, safety, and oncological outcomes of PRFA versus PN. METHODS: A multicenter non-inferiority study with retrospective analysis of 291 patients with SRMs (N0M0), who underwent PN or PRFA (2:1), recruited prospectively from two hospitals in the Andalusian Public Health System, Spain, between 2014 and 2021. Comparisons of treatment features were evaluated using the t test, Wilcoxon-Mann-Whitney U test, chi-square test, Fisher test, and Cochran-Armitage trend test. Kaplan-Meier curves depicted overall survival (OS), local recurrence-free survival (LRFS), and metastasis-free survival (MFS) rates in the overall study population. RESULTS: A total of 291 consecutive patients were identified; 111 and 180 patients underwent PRFA and PN, respectively. Median follow-up time was 38 and 48 months, and mean hospitalization days were 1.04 and 3.57 days, respectively. The variables underpinned with high surgical risk were significantly increased in PRFA compared to those in PN (mean age was 64.56 and 57.47 years, the solitary kidney presence was 12.6% and 5.6%, ASA score ≥ 3 was 36% and 14.5%, respectively). The rest of oncological outcomes were comparable amongst PRFA and PN. Patients undergoing PRFA did not improve OS, LRFS, and MFS compared to those undergoing PN. Limitations comprise retrospective design and limited statistical power. CONCLUSION: PRFA for SMRs in high-risk patients is non-inferior in terms of oncological outcomes and safety compared to PN. CLINICAL RELEVANCE STATEMENT: Our study has a direct clinical application as it proves that radiofrequency ablation is an effective and uncomplicated therapeutic option for patients with small renal masses. KEY POINTS: •There are non-inferiority results in overall survival, local recurrence-free survival, and metastasis-free survival between PRFA and PN. •Our two-center study showed that PRFA is non-inferior to PN in oncological outcomes. •Contrast-enhanced power ultrasound-guided PRFA provides an effective therapy for T1 renal tumors.


Assuntos
Carcinoma de Células Renais , Ablação por Cateter , Neoplasias Renais , Ablação por Radiofrequência , Humanos , Carcinoma de Células Renais/diagnóstico por imagem , Carcinoma de Células Renais/cirurgia , Estudos Retrospectivos , Neoplasias Renais/diagnóstico por imagem , Neoplasias Renais/cirurgia , Resultado do Tratamento , Nefrectomia/métodos , Ablação por Cateter/métodos
5.
Rev Panam Salud Publica ; 47: e127, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38024444

RESUMO

Objective: To analyze trends in mortality caused by cardiovascular diseases (CVD) in Chile during the period 2000-2020. Methods: Data on age-adjusted mortality rates (AAMR) from CVD per 100 000 population in Chile for 2000-2020 were extracted from the World Health Organization Mortality Database. Joinpoint regression was used to analyze the trends and compute the average annual percent change (AAPC) in Chile. In addition, analyses were conducted by sex and type of CVD. Results: Between 2000 and 2020, the AAMR from CVD decreased in Chile from 159.5 to 94.6 per 100 000 population, with a statistically significant decrease in the AAPC of 2.6% (95% CI [-2.8, -2.4]). No joinpoints were identified. The AAMR from CVD decreased annually by 2.6% (95% CI [-2.8, -2.4]) and 2.8% (95% CI [-3.5, -2.6]) in men and women, respectively. The AAMR from ischemic heart disease reduced annually by 3.6% (95% CI [-4.6, -2.7]) with two joinpoints in 2011 and 2015. In the case of stroke, the mortality rate decreased annually by 3.7% (95% CI [-4.5, -3.0]), with two joinpoints in 2008 and 2011. Conclusions: Cardiovascular disease mortality rates have decreased significantly in Chile, in both sexes, especially in women. This decrease could be explained mainly by a significant reduction in the case fatality in recent decades. These results could be a reference for developing primary prevention and acute management of CVD policies focused on populations with higher mortality.

6.
N Engl J Med ; 381(1): 13-24, 2019 07 04.
Artigo em Inglês | MEDLINE | ID: mdl-31150574

RESUMO

BACKGROUND: Apalutamide is an inhibitor of the ligand-binding domain of the androgen receptor. Whether the addition of apalutamide to androgen-deprivation therapy (ADT) would prolong radiographic progression-free survival and overall survival as compared with placebo plus ADT among patients with metastatic, castration-sensitive prostate cancer has not been determined. METHODS: In this double-blind, phase 3 trial, we randomly assigned patients with metastatic, castration-sensitive prostate cancer to receive apalutamide (240 mg per day) or placebo, added to ADT. Previous treatment for localized disease and previous docetaxel therapy were allowed. The primary end points were radiographic progression-free survival and overall survival. RESULTS: A total of 525 patients were assigned to receive apalutamide plus ADT and 527 to receive placebo plus ADT. The median age was 68 years. A total of 16.4% of the patients had undergone prostatectomy or received radiotherapy for localized disease, and 10.7% had received previous docetaxel therapy; 62.7% had high-volume disease, and 37.3% had low-volume disease. At the first interim analysis, with a median of 22.7 months of follow-up, the percentage of patients with radiographic progression-free survival at 24 months was 68.2% in the apalutamide group and 47.5% in the placebo group (hazard ratio for radiographic progression or death, 0.48; 95% confidence interval [CI], 0.39 to 0.60; P<0.001). Overall survival at 24 months was also greater with apalutamide than with placebo (82.4% in the apalutamide group vs. 73.5% in the placebo group; hazard ratio for death, 0.67; 95% CI, 0.51 to 0.89; P = 0.005). The frequency of grade 3 or 4 adverse events was 42.2% in the apalutamide group and 40.8% in the placebo group; rash was more common in the apalutamide group. CONCLUSIONS: In this trial involving patients with metastatic, castration-sensitive prostate cancer, overall survival and radiographic progression-free survival were significantly longer with the addition of apalutamide to ADT than with placebo plus ADT, and the side-effect profile did not differ substantially between the two groups. (Funded by Janssen Research and Development; TITAN ClinicalTrials.gov number, NCT02489318.).


Assuntos
Adenocarcinoma/tratamento farmacológico , Antagonistas de Androgênios/uso terapêutico , Antagonistas de Receptores de Andrógenos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Próstata/tratamento farmacológico , Tioidantoínas/uso terapêutico , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adenocarcinoma/secundário , Adulto , Idoso , Idoso de 80 Anos ou mais , Antagonistas de Androgênios/efeitos adversos , Antagonistas de Receptores de Andrógenos/efeitos adversos , Método Duplo-Cego , Exantema/induzido quimicamente , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Intervalo Livre de Progressão , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/patologia , Qualidade de Vida , Radiografia , Tioidantoínas/efeitos adversos
7.
Langmuir ; 38(10): 3276-3283, 2022 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-35229608

RESUMO

The adverse effects of electrochemical bubbles on the performance of gas-evolving electrodes have been extensively studied. However, the ways in which bubbles dynamically alter the electrochemically active surface area during bubble evolution are not well understood. Here, we study hydrogen evolution at industrially relevant current densities by using controlled microtexture to examine this fundamental relationship. Surprisingly, the most densely microtextured electrodes have the lowest performance on an active surface area basis. Using high-speed imaging, we show that the benefits of microtexture to release smaller bubbles more consistently are outweighed by the inactivation induced by bubbles growing within the denser microtexture, causing these performance limitations. Additionally, we show that the area beneath adhered bubbles is electrochemically active, contrary to currently held assumptions. Our study therefore has broad implications for electrode design to avoid ineffective use of precious catalyst materials, which is especially critical for porous electrodes and three-dimensional structures with high specific surface areas.

8.
Langmuir ; 38(3): 1020-1033, 2022 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-35014259

RESUMO

The novel use of carbon dioxide (CO2) electroreduction to generate carbon-based products which do not contribute to the greenhouse effect has promoted the vision of carbon dioxide as a renewable feedstock for future clean fuel production. Depending on the material choice for the electrocatalysis, a certain variety of products is expected from the carbon dioxide reduction reaction (CO2RR). However, as the CO2 concentration in areas close to the working electrode (relative to the diffusive boundary layer) decreases as it is being consumed and transformed into other products, the generation of H2 is favored to the detriment of CO2 electroreduction. Therefore, the extent to which H2 is produced can be used as a metric to evaluate the efficiency of CO2RR. This article proposes a model that accounts for the modes in which aqueous gas depletion evolves over time and affects the long-term CO2 electroreduction and the corresponding pH evolution near the electrode's surface. For the latter, two main contributions are distinguished: gas depletion due to CO2 consumption and ion generation in areas close to the electrocatalyst surface. pH is then suggested as an accurate and indirect means to measure CO2 concentration in a liquid electrolyte. We conclude that CO2 depletion causes a strong decay in the electrochemical reaction efficiency. In the end, we discuss several methods which may delay the onset of the adverse effects caused by gas depletion, such as the utilization of pulsed electroreduction, cycling the applied current to electrodes on and off periodically.

9.
Salud Publica Mex ; 64: S40-S45, 2022 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-36130397

RESUMO

OBJECTIVE: A narrative overview of regional academic research collaborations to address the increasing burden and gaps in care for patients at risk of, and who suffer from, stroke in Latin America (LA). MATERIALS AND METHODS: A summary of experiences and knowledge of the local situation is presented. No systematic literature review was performed. RESULTS: The rapidly increasing burden of stroke poses immense challenges in LA, where prevention and manage-ment strategies are highly uneven and inadequate. Clinical research is increasing through various academic consortia and networks formed to overcome structural, funding and skill barriers. However, strengthening the ability to generate, analyze and interpret randomized evidence is central to further develop effective therapies and healthcare systems in LA. CONCLUSIONS: Regional networks foster the conduct of multicenter studies -particularly randomized controlled trials-, even in resource-poor regions. They also contribute to the external validity of international studies and strengthen systems of care, clinical skills, critical thinking, and international knowledge exchange.


Assuntos
Atenção à Saúde , Acidente Vascular Cerebral , Competência Clínica , Humanos , América Latina , Organizações , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/terapia
10.
J Urol ; 206(4): 914-923, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34039013

RESUMO

PURPOSE: We performed an exploratory analysis of prostate cancer-related pain and fatigue on health-related quality of life in patients with metastatic castration-sensitive prostate cancer receiving apalutamide (240 mg/day) or placebo, with continuous androgen deprivation therapy (ADT), in the phase 3, randomized, double-blind, placebo controlled TITAN trial (NCT02489318). MATERIALS AND METHODS: Patient-reported outcomes for pain and fatigue were evaluated using the Brief Pain Inventory-Short Form and Brief Fatigue Inventory. Time to deterioration (TTD) was estimated by Kaplan-Meier method; hazard ratios and 95% confidence intervals were calculated using Cox proportional hazards model. General estimating equations for logistic regression estimated treatment-related differences in the likelihood of worsening pain or fatigue. RESULTS: Compliance for completing the Brief Pain Inventory-Short Form and Brief Fatigue Inventory was high (96% to 97%) in the first year. Median followup times were similar between treatments (19 to 22 months). Median pain TTD was longer with apalutamide than placebo for "pain at its least in the last 24 hours" (28.7 vs 21.8 months, respectively; p=0.0146), "pain interfered with mood" (not estimable vs 22.4 months; p=0.0017), "pain interfered with walking ability" (28.7 vs 20.2 months; p=0.0027), "pain interfered with relations" (not estimable vs 23.0 months; p=0.0139) and "pain interfered with sleep" (28.7 vs 20.9 months; p=0.0167). Likelihood for fatigue and worsening fatigue were similar between groups. CONCLUSIONS: Patients with metastatic castration-sensitive prostate cancer receiving apalutamide plus ADT vs placebo plus ADT reported consistently favorable TTD of pain. No difference for change in fatigue was observed with apalutamide vs placebo.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Dor do Câncer/tratamento farmacológico , Fadiga/tratamento farmacológico , Neoplasias da Próstata/tratamento farmacológico , Qualidade de Vida , Adulto , Idoso , Idoso de 80 Anos ou mais , Antagonistas de Androgênios/administração & dosagem , Dor do Câncer/diagnóstico , Dor do Câncer/etiologia , Dor do Câncer/psicologia , Deterioração Clínica , Fadiga/diagnóstico , Fadiga/etiologia , Fadiga/psicologia , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor/estatística & dados numéricos , Medidas de Resultados Relatados pelo Paciente , Intervalo Livre de Progressão , Neoplasias da Próstata/complicações , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/patologia , Índice de Gravidade de Doença , Tioidantoínas/administração & dosagem
11.
Int Braz J Urol ; 46(suppl.1): 86-92, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32568497

RESUMO

PURPOSE: The aim of this work is to review and synthesize the existing evidence and recommendations regarding to the therapeutic and surgical indications as well as monitoring of patients with Penile Cancer in COVID-19 era and to propose an action protocol to facilitate decision-making. MATERIAL AND METHODS: A non-systematic review of the literature regarding the management of penile cancer during the COVID-19 pandemic was performed until April 30, 2020. We propose our recommendations based on this evidence. RESULTS: Penile cancer is an uncommon but aggressive disease. Prognosis is determined by several characteristics, being the most important the presence of lymph nodes, in which case, treatment should not be delayed. For these reasons, an initial evaluation is mandatory. Priority classifications, based on the oncological outcomes when treatment is delayed, have been made in order to separate deferrable disease from the one that needs high priority treatment. In penile cancer with low risk of progression, surgical treatment can be delayed, but other options must be considered, like topical treatment or laser therapy. In cases with intermediate risk of progression, surgical treatment may be delayed up to three months, but we must consider radiation therapy and brachytherapy as effective options. When feasible, follow-up should by telemonitoring. CONCLUSIONS: In the COVID-19 era, initial evaluation of the patient is mandatory. Histological diagnosis with local staging is necessary before offering any therapeutic option. In case of superficial non-invasive disease, topical treatment is effective in absence of lymph node involvement. In selected patients, radiotherapy is an organ-preserving approach with good results. Non-deferrable surgical treatment must be performed by an experienced surgeon and as an outpatient procedure when possible. When indicated, iLND should not be delayed since it is decisive for patient survival. Follow-up should be by telemonitoring.


Assuntos
Infecções por Coronavirus/epidemiologia , Neoplasias Penianas/cirurgia , Neoplasias Penianas/terapia , Pneumonia Viral/epidemiologia , Betacoronavirus , COVID-19 , Humanos , Linfonodos/patologia , Masculino , Estadiamento de Neoplasias , Pandemias , SARS-CoV-2
12.
Lancet Oncol ; 20(11): 1518-1530, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31578173

RESUMO

BACKGROUND: In the phase 3 TITAN study, the addition of apalutamide to androgen deprivation therapy (ADT) significantly improved the primary endpoints of overall survival and radiographic progression-free survival in patients with metastatic castration-sensitive prostate cancer. We aimed to assess health-related quality of life (HRQOL) in TITAN, including pain and fatigue. METHODS: In this randomised, placebo-controlled, double-blind, phase 3 study, patients with metastatic castration-sensitive prostate cancer (defined as not receiving ADT at the time of metastatic disease progression) aged 18 years and older, receiving continuous ADT (selected at the investigator's discretion), and with an Eastern Cooperative Oncology Group performance status score of 0 or 1 were randomly assigned (1:1), using an interactive web response system, to receive oral apalutamide (four 60 mg tablets, once daily) or matching placebo. Previous localised disease treatment or previous docetaxel for metastatic castration-sensitive prostate cancer were allowed. Randomisation was stratified by Gleason score at diagnosis, region, and previous docetaxel treatment. Randomisation was done using randomly permuted blocks (block size of four). Investigators, research staff, sponsor study team, and patients were masked to the identities of test and control treatments. Patient-reported outcomes were prespecified exploratory endpoints and were the Brief Pain Inventory-Short Form (BPI-SF), Brief Fatigue Inventory (BFI), Functional Assessment of Cancer Therapy-Prostate (FACT-P), and EuroQoL 5D questionnaire 5 level (EQ-5D-5L). BPI and BFI were completed for 7 consecutive days (days -6 to 1 inclusive of each cycle visit), then at months 4, 8, and 12 in follow-up. FACT-P and EQ-5D-5L were completed during cycles 1-7, then every other cycle until the end of treatment, and at months 4, 8, and 12 in follow-up. Analyses were based on the intention-to-treat population. Missing patient-reported outcome assessments were calculated as the expected number of assessments for a visit minus the actual number of assessments received for that visit. For time-to-event endpoints, when median values could not be calculated because less than 50% of patients had degradation, 25th percentiles were compared. This study is registered with ClinicalTrials.gov, number NCT02489318, and is ongoing. FINDINGS: Between Dec 9, 2015, and July 25, 2017, 1052 eligible patients were enrolled randomly assigned to apalutamide (n=525) or placebo (n=527). Data cutoff for this analysis of patient-reported outcomes was Nov 23, 2018. Median follow-up for time to pain-related endpoints ranged from 19·4 to 22·1 months. Patients were mostly asymptomatic at baseline: on the BPI-SF pain severity scale of 0-10, median pain scores (indicating worst pain in the past 24 h) were 1·14 (IQR 0-3·17) in the apalutamide group and 1·00 (0-2·86) in the placebo group, and median worst fatigue scores on the BFI were 1·29 (IQR 0-3·29) in the apalutamide group and 1·43 (0·14-3·14) in the placebo group. Patient experience of pain and fatigue (intensity and interference) did not differ between the groups for the duration of treatment. Median time to worst pain intensity progression was 19·09 months (95% CI 11·04-not reached) in the apalutamide group versus 11·99 months (8·28-18·46) in the placebo group (HR 0·89 [95% CI 0·75-1·06]; p=0·20). Median time to pain interference progression was not reached in either group (95% CI 28·58-not reached in the apalutamide group; not reached-not reached in the placebo group). 25th percentiles for time to pain interference progression were 9·17 months (5·55-11·96) in the apalutamide group and 6·24 months (4·63-7·43) in the placebo group (HR 0·90 [95% CI 0·73-1·10]; p=0·29). FACT-P total scores and EQ-5D-5L data showed preservation of HRQOL in both groups. The median time to deterioration as determined by FACT-P total score was 8·87 months (95% CI 4·70-11·10) in the apalutamide group and 9·23 months (7·39-12·91) in the placebo group (HR 1·02 [95% CI 0·85-1·22]; p=0·85). INTERPRETATION: Apalutamide with ADT is a well-tolerated and effective option for men with metastatic castration-sensitive prostate cancer. The combination significantly improves survival outcomes compared with ADT alone while maintaining HRQOL despite additive androgen blockade. FUNDING: Janssen Research & Development.


Assuntos
Antagonistas de Androgênios/administração & dosagem , Antagonistas de Receptores de Andrógenos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Orquiectomia , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Qualidade de Vida , Tioidantoínas/administração & dosagem , Idoso , Antagonistas de Androgênios/efeitos adversos , Antagonistas de Receptores de Andrógenos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Ásia , Quimioterapia Adjuvante , Progressão da Doença , Europa (Continente) , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Metástase Neoplásica , América do Norte , Orquiectomia/efeitos adversos , Intervalo Livre de Progressão , Neoplasias de Próstata Resistentes à Castração/diagnóstico , Neoplasias de Próstata Resistentes à Castração/mortalidade , América do Sul , Tioidantoínas/efeitos adversos , Fatores de Tempo
13.
J Stroke Cerebrovasc Dis ; 28(5): 1311-1316, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30772157

RESUMO

BACKGROUND: There is evidence of a greater incidence of stroke in native populations and minorities. A total of 34% of the population in the Araucanía Region is indigenous. The association between Mapuche ethnicity and stroke is unknown. The aim of the study was to estimate the magnitude of the association between Mapuche ethnicity and stroke occurrence in patients admitted to the Dr. Hernán Henríquez Aravena Hospital (HHHA) in Temuco, Chile. METHODS: We performed an incident case-control-paired study with patients hospitalized with an acute stroke in the internal medicine service and controls from other medical services at the HHHA. One control was selected for each case, matched by gender and age (±5 years). RESULTS: A total of 104 nonconsecutive cases of stroke were included. The proportion of Mapuche individuals was similar between cases and controls (27.9% and 32.7%, respectively, P = .45). Hypertension and overweight-obesity were associated with stroke. Low socioeconomic status, rurality, diabetes, and smoking were associated with Mapuche ethnicity. In the conditional logistic regression model, Mapuche ethnicity was not associated with stroke. The odds ratio was .75 (P = .47, 95% confidence intervals: .35-1.62). CONCLUSIONS: There is no statistically significant evidence in the study to support the hypothesis of an association between Mapuche ethnicity and stroke. None of the control variables modified the effect of ethnicity on stroke.


Assuntos
Indígenas Sul-Americanos , Acidente Vascular Cerebral/etnologia , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Chile/epidemiologia , Comorbidade , Diabetes Mellitus/etnologia , Feminino , Humanos , Hipertensão/etnologia , Incidência , Masculino , Pessoa de Meia-Idade , Obesidade/etnologia , Medição de Risco , Fatores de Risco , Saúde da População Rural/etnologia , Fumar/efeitos adversos , Fumar/etnologia , Classe Social , Determinantes Sociais da Saúde/etnologia , Acidente Vascular Cerebral/diagnóstico , Saúde da População Urbana/etnologia
14.
Entropy (Basel) ; 21(2)2019 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-33266905

RESUMO

Today, there is growing interest in the automatic classification of a variety of tasks, such as weather forecasting, product recommendations, intrusion detection, and people recognition. "Mixture-of-experts" is a well-known classification technique; it is a probabilistic model consisting of local expert classifiers weighted by a gate network that is typically based on softmax functions, combined with learnable complex patterns in data. In this scheme, one data point is influenced by only one expert; as a result, the training process can be misguided in real datasets for which complex data need to be explained by multiple experts. In this work, we propose a variant of the regular mixture-of-experts model. In the proposed model, the cost classification is penalized by the Shannon entropy of the gating network in order to avoid a "winner-takes-all" output for the gating network. Experiments show the advantage of our approach using several real datasets, with improvements in mean accuracy of 3-6% in some datasets. In future work, we plan to embed feature selection into this model.

15.
Bioinformatics ; 33(5): 760-761, 2017 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-27993775

RESUMO

Summary: GENIUS is a user-friendly web server that uses a novel machine learning algorithm to infer functional gene networks focused on specific genes and experimental conditions that are relevant to biological functions of interest. These functions may have different levels of complexity, from specific biological processes to complex traits that involve several interacting processes. GENIUS also enriches the network with new genes related to the biological function of interest, with accuracies comparable to highly discriminative Support Vector Machine methods. Availability and Implementation: GENIUS currently supports eight model organisms and is freely available for public use at http://networks.bio.puc.cl/genius . Contact: genius.psbl@gmail.com. Supplementary information: Supplementary data are available at Bioinformatics online.


Assuntos
Redes Reguladoras de Genes , Aprendizado de Máquina , Software , Arabidopsis/genética
16.
Langmuir ; 34(25): 7309-7318, 2018 06 26.
Artigo em Inglês | MEDLINE | ID: mdl-29847948

RESUMO

Nanobubble nucleation is a problem that affects efficiency in electrocatalytic reactions since those bubbles can block the surface of the catalytic sites. In this article, we focus on the nucleation rate of O2 nanobubbles resulting from the electrooxidation of H2O2 at Pt disk nanoelectrodes. Bubbles form almost instantaneously when a critical peak current, inbp, is applied, but for lower currents, bubble nucleation is a stochastic process in which the nucleation (induction) time, tind, dramatically decreases as the applied current approaches inbp, a consequence of the local supersaturation level, ζ, increasing at high currents. Here, by applying different currents below inbp, nanobubbles take some time to nucleate and block the surface of the Pt electrode at which the reaction occurs, providing a means to measure the stochastic tind. We study in detail the different conditions in which nanobubbles appear, concluding that the electrode surface needs to be preconditioned to achieve reproducible results. We also measure the activation energy for bubble nucleation, Ea, which varies in the range from (6 to 30) kT, and assuming a spherically cap-shaped nanobubble nucleus, we determine the footprint diameter L = 8-15 nm, the contact angle to the electrode surface θ = 135-155°, and the number of O2 molecules contained in the nucleus (50 to 900 molecules).

17.
Langmuir ; 33(45): 12873-12886, 2017 11 14.
Artigo em Inglês | MEDLINE | ID: mdl-29041778

RESUMO

Control over the bubble growth rates forming on the electrodes of water-splitting cells or chemical reactors is critical with respect to the attainment of higher energy efficiencies within these devices. This study focuses on the diffusion-driven growth dynamics of a succession of H2 bubbles generated at a flat silicon electrode substrate. Controlled nucleation is achieved by means of a single nucleation site consisting of a hydrophobic micropit etched within a micrometer-sized pillar. In our experimental configuration of constant-current electrolysis, we identify gas depletion from (i) previous bubbles in the succession, (ii) unwanted bubbles forming on the sidewalls, and (iii) the mere presence of the circular cavity where the electrode is being held. The impact of these effects on bubble growth is discussed with support from numerical simulations. The time evolution of the dimensionless bubble growth coefficient, which is a measure of the overall growth rate of a particular bubble, of electrolysis-generated bubbles is compared to that of CO2 bubbles growing on a similar surface in the presence of a supersaturated solution of carbonated water. For electrolytic bubbles and under the range of current densities considered here (5-15 A/m2), it is observed that H2 bubble successions at large gas-evolving substrates first experience a stagnation regime, followed by a fast increase in the growth coefficient before a steady state is reached. This clearly contradicts the common assumption that constant current densities must yield time-invariant growth rates. Conversely, for the case of CO2 bubbles, the growth coefficient successively decreases for every subsequent bubble as a result of the persistent depletion of dissolved CO2.

18.
Rev Med Chil ; 145(3): 299-308, 2017 Mar.
Artigo em Espanhol | MEDLINE | ID: mdl-28548186

RESUMO

BACKGROUND: College students are in a critical stage in their life style due to the transition between high school and university and they may be prone to develop cardiovascular diseases. AIM: To compare the prevalence of cardiovascular risk factors (CVRF) in students from first and third year at the University of La Frontera, Temuco-Chile, according to faculty, gender and socioeconomic status (SES). MATERIAL AND METHODS: Cross-sectional study. Anthropometry, blood pressure, lipid profile, blood glucose, insulin resistance (IR), sedentary lifestyle, tobacco and alcohol consumption were evaluated during 2014 in randomly selected 163 freshmen aged 19.2 ± 1.8 years and 163 third year students aged 21.7 ± 2.5 years (49% females), stratified by faculty, career and gender. RESULTS: 32.4% of students had prehypertension, 30.6% abdominal obesity, 26.3% insulin resistance, 25.7% dyslipidemia and 8.9% metabolic syndrome. Third grade students had higher prevalence of elevated total and LDL cholesterol and higher alcohol consumption, especially among students of middle and high socioeconomic level. Compared with students from the School of Medicine, students from the Education Faculty had 3.9, 3.3 and 2.7 times greater likelihood of being obese, having elevated LDLcholesterol and being smokers, respectively. Women had the highest prevalence of sedentary lifestyles and dyslipidemia. Men had the highest prevalence of prehypertension and smoking. CONCLUSIONS: Educational programs are required to promote healthy lifestyles among these students.


Assuntos
Doenças Cardiovasculares/epidemiologia , Estudantes/estatística & dados numéricos , Chile/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Prevalência , Fatores de Risco , Classe Social , Universidades , Adulto Jovem
20.
Surg Innov ; 23(5): 474-80, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27130646

RESUMO

Background Abdominoplasty is considered an operation linked to a considerable rate of morbidity. The convenience of simultaneously performing an incisional hernia repair and an abdominoplasty remains controversial. Methods A total of 111 patients were randomized prospectively to compare isolated incisional hernia repair and hernia repair when combined with abdominoplasty. Primary end points were in-hospital stay and early morbidity. Secondary end points were late morbidity, recurrences, and quality of life. Patients were followed-up for 24 months. Results Duration of the surgical procedure differed significantly between both groups (39 vs 85 minutes, P < .001) and postoperative hospital stay (2.5 vs 3.5 days; P < .001). No statistically significant differences in early or late morbidity between both groups were detected. The perceived quality of life for patients was higher in the combined surgery group (P < .001) that in the isolated hernia repair group. Conclusions Postoperative in-hospital stay and early and late morbidity do not differ significantly between isolated incisional hernia repair and simultaneous hernia repair with abdominoplasty, but associated abdominoplasty provides a higher quality of life when indicated.


Assuntos
Abdominoplastia/métodos , Herniorrafia/métodos , Hérnia Incisional/cirurgia , Complicações Pós-Operatórias/fisiopatologia , Telas Cirúrgicas , Cicatrização/fisiologia , Adulto , Idoso , Terapia Combinada , Feminino , Seguimentos , Herniorrafia/efeitos adversos , Humanos , Hérnia Incisional/epidemiologia , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Morbidade , Medição da Dor , Dor Pós-Operatória/fisiopatologia , Seleção de Pacientes , Estudos Prospectivos , Recidiva , Valores de Referência , Medição de Risco , Método Simples-Cego , Resistência à Tração , Resultado do Tratamento
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA