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1.
Ann N Y Acad Sci ; 1535(1): 76-91, 2024 May.
Article in English | MEDLINE | ID: mdl-38598473

ABSTRACT

The detrimental effect of math anxiety on math performance is thought to be mediated by executive functions. Previous studies have primarily focused on trait-math anxiety rather than state-math anxiety and have typically examined a single executive function rather than comprehensively evaluating all of them. Here, we used a structural equation modeling approach to concurrently determine the potential mediating roles of different executive functions (i.e., inhibition, switching, and updating) in the relationships between both state- and trait-math anxiety and math performance. A battery of computer-based tasks and questionnaires were administered to 205 university students. Two relevant results emerged. First, confirmatory factor analysis suggests that math anxiety encompassed both trait and state dimensions and, although they share substantial variance, trait-math anxiety predicted math performance over and above state-math anxiety. Second, working memory updating was the only executive function that mediated the relationship between math anxiety and math performance; neither inhibition nor switching played mediating roles. This calls into question whether some general proposals about the relationship between anxiety and executive functions can be extended specifically to math anxiety. We also raise the possibility that working memory updating or general cognitive difficulties might precede individual differences in math anxiety.


Subject(s)
Anxiety , Executive Function , Mathematics , Memory, Short-Term , Humans , Executive Function/physiology , Anxiety/psychology , Anxiety/physiopathology , Male , Female , Memory, Short-Term/physiology , Young Adult , Adult , Adolescent , Inhibition, Psychological , Surveys and Questionnaires
2.
Article in English | MEDLINE | ID: mdl-37675801

ABSTRACT

BACKGROUND AND OBJECTIVE: Diagnostic criteria of chronic rhinosinusitis with nasal polyps (CRSwNP) include, among others, olfactory dysfunction (OD). We hypothesize that patients suffering with CRSwNP are good at self-assessing their sense of smell through visual analogue scale (VAS) compared to smell tests. METHODS: A controlled cross-sectional study was planned. Adults diagnosed with severe CRSwNP waiting for endoscopic sinus surgery were included. A cohort of healthy controls was also studied. All participants performed Barcelona smell test (BAST-24), sinonasal outcomes test 22 (SNOT-22), and VAS for loss of smell. CRSwNP underwent blood test (eosinophils count, total serum IgE), CT scan (Lund-Mackay Score), and nasal endoscopy. RESULTS: 138 severe CRSwNP and 40 controls subjects were included. The BAST-24 identification score was strongly correlated with the VAS score in the CRSwNP group (rho=-0.79, p<0.001) but not in the control group (rho=-0.14; p=0.39), this difference between groups being statistically significant (p<0.001). A significant correlation of SNOT-22 item 21 (loss of smell) was also found with BAST-24 identification (rho=-0.65, p<0.001), this difference being statistically significant (Z=-2.43; p=0.015). In the ROC curve, the area under the curve (AUC) was 0.85 with 72.5% sensitivity and 93.1% specificity. CONCLUSION: This study demonstrates a potential role of the VAS score for the screening of OD in severe CRSwNP in daily clinical practice.

3.
Rhinology ; 61(5): 421-431, 2023 Oct 01.
Article in English | MEDLINE | ID: mdl-37475674

ABSTRACT

BACKGROUND: Patients with septal deviation and/or turbinal hypertrophy may experience olfactory disfunction (OD). The aim of this study was to analyse the effect of septoplasty and/or turbinoplasty on both lateralized and bilateral olfactory function. METHODOLOGY: Prospective study of 47 patients with nasal obstruction secondary to septal deviation and/or turbinal hypertrophy and 20 healthy controls. The Barcelona Olfactory test (BOT-8), a new supraliminal orthonasal subjective olfactometry, was applied 3 times in a row (in each nostril separately and in both simultaneously). The 8 items were applied randomly to minimize the possible risk of learning. The test has not established the minimal clinically important difference (MCID). Anterior rhinomanometry and acoustic rhinometry were performed. All participants self-assessed smell loss and nasal obstruction using a visual analogue scale (VAS) and completed questionnaires for nasal obstruction (Nasal Obstruction Symptom Evaluation, NOSE) and for quality of life (QoL), using disease-specific (SinoNasal Outcome Test-22, SNOT-22) and generic (Short Form-12 Health Survey, SF-12) questionnaires. Nasal measurements and questionnaires were performed preoperatively and 12 months after surgery. RESULTS: Before surgery, patients reported worse VAS on smell loss and on nasal obstruction compared to controls. Patients scored lower BOT-8 than controls. Lateralized preoperative olfactory function showed that all BOT-8 characteristics were lower at the narrow side than the wider one. Smell function and QoL improved significantly one year after surgery. CONCLUSIONS: Nasal septal deviation and turbinal hypertrophy lead to an olfactory impairment on the obstructed nostril. Nasal surgery provides a positive outcome on olfactory function, as well as on subjective and objective outcomes.


Subject(s)
Nasal Obstruction , Nose Deformities, Acquired , Rhinoplasty , Humans , Smell , Quality of Life , Nasal Obstruction/surgery , Nasal Obstruction/diagnosis , Prospective Studies , Anosmia/surgery , Treatment Outcome , Nasal Septum/surgery , Nose Deformities, Acquired/surgery
4.
Rhinology ; 60(5): 347-356, 2022 Oct 01.
Article in English | MEDLINE | ID: mdl-36184882

ABSTRACT

BACKGROUND: Sinonasal mucosal melanoma is an aggressive malignancy with a 5-year survival rate ranging from 20% to 39%. Despite the evolving surgical and radiotherapy techniques, and introduction of immune-checkpoint inhibitor therapy, overall survival rates remain poor. METHODOLOGY: A retrospective cohort study was conducted at the Hospital Clinic de Barcelona and the Hospital de la Santa Creu i Sant Pau between 1984 and 2020; primary outcome measures were 3 and 5-year melanoma-specific survival (MSS). Kaplan-Meier survival analysis and Cox proportional hazards model were performed to identify predictors of survival. RESULTS: Fifty patients were included, the mean age was 70.4, MSS at 3 and 5 years was 51.2%, and 29.5%, respectively. The median follow-up was 39.6 months during which 46% presented locoregional recurrence and 36%, metastasis. The univariate and multivariate analyses found as survival predictors the N category, the treatment received, the surgical margins and the mitotic index. CONCLUSIONS: We found an overall 5-year MSS of 29.5%. Those patients with intention-to-cure (stages III and IVa) treated by surgery that were N0 at diagnosis, with < 10 mitoses per HPF showed a 5-year MSS rate of 74.1%. More studies will be needed to adequately define the patients' profiles that will benefit from a better survival outcome.


Subject(s)
Melanoma , Paranasal Sinus Neoplasms , Aged , Disease-Free Survival , Humans , Immune Checkpoint Inhibitors , Melanoma/surgery , Neoplasm Recurrence, Local/pathology , Paranasal Sinus Neoplasms/pathology , Paranasal Sinus Neoplasms/surgery , Prognosis , Retrospective Studies , Survival Rate
5.
J Investig Allergol Clin Immunol ; 32(4): 291-298, 2022 Jul 22.
Article in English | MEDLINE | ID: mdl-35532333

ABSTRACT

BACKGROUND AND OBJECTIVE: Most smell tests are difficult to implement in daily clinical practice owing to their long duration. The aim of the present study was to develop and validate a short, easy-to-perform, and reusable smell test to be implemented during the COVID-19 pandemic. METHODS: The study population comprised 120 healthy adults and 195 patients with self-reported olfactory dysfunction (OD). The 8-Odorant Barcelona Olfactory Test (BOT-8) was used for detection, memory/recognition, and forced-choice identification. In addition, a rose threshold test was performed, and a visual analog scale was applied. The Smell Diskettes Olfaction Test (SDOT) was used for correlation in healthy volunteers, and the University of Pennsylvania Smell Identification Test (UPSIT) was used for patients with OD to establish cut-offs for anosmia and hyposmia. In order to take account of the COVID-19 pandemic, disposable cotton swabs with odorants were compared with the original test. RESULTS: In healthy persons, the mean (SD) BOT-8 score was 100% for detection, 94.5% (1.07) for memory/recognition, and 89.6% (0.86) for identification. In patients with OD, the equivalent values were 86% (32.8), 73.2% (37.9), and 77.1% (34.2), respectively. BOT-8 demonstrated good test-retest reliability, with agreement of 96.7% and a quadratic k of 0.84 (P<.001). A strong correlation was observed between BOT-8 and SDOT (r=0.67, P<.001) and UPSIT (r=0.86, P<.001). Agreement was excellent for disposable cotton swabs, with a k of 0.79 compared with the original test. The cut-off point for anosmia was ≤3 (area under the curve, 0.83; sensitivity, 0.673; specificity, 0.993). CONCLUSION: BOT-8 offers an efficient and fast method for assessment of smell threshold, detection, memory, and identification in daily clinical practice. Disposable cotton swabs with odorants proved to be useful and safe during the COVID-19 pandemic.


Subject(s)
COVID-19 , Olfaction Disorders , Adult , Anosmia , COVID-19/epidemiology , Humans , Odorants , Olfaction Disorders/diagnosis , Olfaction Disorders/epidemiology , Pandemics , Reproducibility of Results , Smell
6.
J. investig. allergol. clin. immunol ; 32(4): 291-298, 2022. ilus, tab, graf
Article in English | IBECS | ID: ibc-208241

ABSTRACT

Background: Most smell tests are difficult to implement in daily clinical practice owing to their long duration. The aim of the present study was to develop and validate a short, easy-to-perform, and reusable smell test to be implemented during the COVID-19 pandemic. Methods: The study population comprised 120 healthy adults and 195 patients with self-reported olfactory dysfunction (OD). The 8-Odorant Barcelona Olfactory Test (BOT-8) was used for detection, memory/recognition, and forced-choice identification. In addition, a rose threshold test was performed, and a visual analog scale was applied. The Smell Diskettes Olfaction Test (SDOT) was used for correlation in healthy volunteers, and the University of Pennsylvania Smell Identification Test (UPSIT) was used for patients with OD to establish cut-offs for anosmia and hyposmia. In order to take account of the COVID-19 pandemic, disposable cotton swabs with odorants were compared with the original test. Results: In healthy persons, the mean (SD) BOT-8 score was 100% for detection, 94.5% (1.07) for memory/recognition, and 89.6% (0.86) for identification. In patients with OD, the equivalent values were 86% (32.8), 73.2% (37.9), and 77.1% (34.2), respectively. BOT-8 demonstrated good test-retest reliability, with agreement of 96.7% and a quadratic k of 0.84 (P<.001). A strong correlation was observed between BOT-8 and SDOT (r=0.67, P<.001) and UPSIT (r=0.86, P<.001). Agreement was excellent for disposable cotton swabs, with a k of 0.79 compared with the original test. The cut-off point for anosmia was ≤3 (area under the curve, 0.83; sensitivity, 0.673; specificity, 0.993). Conclusions: BOT-8 offers an efficient and fast method for assessment of smell threshold, detection, memory, and identification in daily clinical practice. Disposable cotton swabs with odorants proved to be useful and safe during the COVID-19 pandemic (AU)


Introducción: Las olfatometrías son difíciles de implementar en la práctica clínica diaria por su larga duración. El objetivo del presente estudio fue desarrollar y validar una prueba simple, fácil y reutilizable para ser utilizada durante la pandemia de COVID-19. Métodos: Se incluyeron 120 voluntarios sanos ≥18 años y 195 pacientes con disfunción olfatoria (DO) autoreportada. Se utilizó el Barcelona Olfactory Test (BOT-8) con 8 odorantes para la detección, memoria/reconocimiento e identificación. Además, se hizo una prueba de umbral de rosa (alcohol feniletílico) de 6 diluciones, escala visual analógica (EVA). Se compararon los resultados con una prueba validada Smell Diskettes Olfaction Test (SDOT), para definir puntos de corte de hiposmia y anosmia se comparó en pacientes con DO con UPSITTM. Considerando la pandemia de COVID-19, se compararon hisopos de algodón desechables con los odorantes respecto a la prueba original. Resultados: BOT-8 se tarda entre 3 y 7 minutos en realizar. En población sana, la media de detección fue del 100%, memoria 94,5% (DE=1,07) e identificación 89,6% (DE=0,86). En pacientes con DO fue de 86% (DE=32,8), 73,2% (DE=37,9) y 77,1% (DE=34,2), respectivamente. BOT-8 demostró buena fiabilidad test-retest con 96,7% de concordancia observada y una kappa cuadrática de 0,84 (p<0,001). Presentó una fuerte correlación con SDOT (r=0,673, p <0,001) en población sana y con UPSITTM en pacientes con DO (r=0,86, p<0,001). Los hisopos de algodón desechables mostraron una excelente concordancia (kappa de 0,79) en comparación con la prueba original. El punto de corte para anosmia fue ≤ 3 (AUC=0,83, Se= 0,673, Sp=0,993) y de hiposmia ≤ 6 (AUC=0,451, Se= 0,088, Sp= 0,814). Conclusiones: BOT-8 ofrece un método eficiente y rápido para ser utilizado en la práctica clínica diaria para evaluar el sentido del olfato mediante la detección, memoria, identificación y umbral (AU)


Subject(s)
Humans , Male , Female , Adolescent , Young Adult , Adult , Middle Aged , Aged , Aged, 80 and over , Olfaction Disorders/diagnosis , Coronavirus Infections/complications , Pneumonia, Viral/complications , Pandemics , Odorants , Reproducibility of Results , Olfaction Disorders/virology
7.
J Investig Allergol Clin Immunol ; 31(1): 17-35, 2021 Feb 17.
Article in English | MEDLINE | ID: mdl-32540791

ABSTRACT

Airway examination procedures can potentially transmit infectious diseases to patients and to the health care professionals who perform them via various mechanisms. The COVID-19 pandemic has halted most of the activity of the clinics and laboratories involved in assessment of lung and nasal function, and clear recommendations in this regard have been made. Today, we still do not know for sure what its consequences will be in the short or long term, since important gaps remain in our knowledge of aspects as fundamental as virus transmission mechanisms, pathophysiology, immune response, and diagnosis. In this review, we study the examination techniques used to assess patients with respiratory allergy, asthma, and associated diseases during this period and highlight their possible advantages and disadvantages. Therefore, we focus on exploring the entire upper and lower airways, from the perspective of the safety of both health professionals and patients and their specific characteristics. We also analyze the intrinsic value of these interventions in terms of diagnosis and patient management. The changing situation of COVID-19 may mean that some of the assertions presented in this review will have to be modified in the future. While we seek to ensure a consistently broad approach, some differences in operational details may apply owing to local regulations.


Subject(s)
COVID-19 , Occupational Health , Patient Safety , Respiratory Hypersensitivity/physiopathology , Respiratory System/physiopathology , SARS-CoV-2 , COVID-19/diagnosis , COVID-19/transmission , Health Personnel , Humans , Mass Screening , Respiratory Function Tests , Ventilation
8.
J Investig Allergol Clin Immunol ; 30(5): 346-357, 2020.
Article in English | MEDLINE | ID: mdl-32554337

ABSTRACT

BACKGROUND AND OBJECTIVE: Since the initial anecdotal reports of coronavirus disease 2019 (COVID-19) from China, a growing number of studies have reported on smell and/or taste dysfunction (STD). Objective: The aim of our study was to investigate the frequency and severity of STD in COVID-19 patients and to evaluate the association with demographic characteristics, hospital admission, symptoms, comorbidities, and blood biomarkers. METHODS: We performed a multicenter cross-sectional study on patients who were positive for SARS-CoV-2 (n=846) and controls (n=143) from 15 Spanish hospitals. Data on STD were collected prospectively using an in-person survey. The severity of STD was categorized using a visual analog scale. We analyzed time to onset, recovery rate, time to recovery, hospital admission, pneumonia, comorbidities, smoking, and symptoms. RESULTS: STD was at least 2-fold more common in COVID-19-positive patients than in controls. COVID-19-positive hospitalized patients were older, with a lower frequency of STD, and recovered earlier than outpatients. Analysis stratified by severity of STD showed that more than half of COVID-19 patients presented severe loss of smell (53.7%) or taste (52.2%); both senses were impaired in >90%. In the multivariate analysis, older age (>60 years), being hospitalized, and increased C-reactive protein were associated with a better sense of smell and/or taste. COVID-19-positive patients reported improvement in smell (45.6%) and taste (46.1%) at the time of the survey; in 90.6% this was within 2 weeks of infection. CONCLUSION: STD is a common symptom in COVID-19 and presents mainly in young and nonhospitalized patients. More studies are needed to evaluate follow-up of chemosensory impairment.


Subject(s)
Betacoronavirus , Coronavirus Infections/complications , Coronavirus Infections/epidemiology , Olfaction Disorders/epidemiology , Olfaction Disorders/etiology , Pneumonia, Viral/complications , Pneumonia, Viral/epidemiology , Taste Disorders/epidemiology , Taste Disorders/etiology , Adult , Age Factors , Aged , Aged, 80 and over , Betacoronavirus/genetics , Betacoronavirus/immunology , COVID-19 , Case-Control Studies , Coronavirus Infections/diagnosis , Coronavirus Infections/virology , Cross-Sectional Studies , Female , Hospitalization , Humans , Male , Middle Aged , Olfaction Disorders/diagnosis , Pandemics , Pneumonia, Viral/diagnosis , Pneumonia, Viral/virology , Polymerase Chain Reaction , Public Health Surveillance , SARS-CoV-2 , Severity of Illness Index , Spain/epidemiology , Symptom Assessment , Taste Disorders/diagnosis , Young Adult
9.
J Investig Allergol Clin Immunol ; 30(5): 317-326, 2020.
Article in English | MEDLINE | ID: mdl-32406374

ABSTRACT

The first cases of coronavirus 2019 disease (COVID-19) occurred in Wuhan, China, and the disease rapidly become a public health emergency of international proportions. COVID-19 can cause mild-to-severe acute respiratory syndrome (SARS) and is caused by the SARS-CoV-2 coronavirus. The clinical manifestations of COVID-19 include fever, dry cough, fatigue, sputum production, shortness of breath, sore throat, and headache. We performed this narrative review to analyze the current literature on postviral olfactory dysfunction related to the SARSCoV- 2 pandemic. Since the initial anecdotal reports from China, increasingly frequent international reports on COVID-19 indicate that 5% to 85% of affected patients lose their sense of smell, thus highlighting the very heterogeneous nature of the literature in this area. Therefore, we advise home isolation measures and/or social distancing, as well as tests to detect SARS-CoV-2 when possible, in patients with sudden and severe loss of smell who cannot be promptly evaluated.


Subject(s)
Betacoronavirus/physiology , Coronavirus Infections/complications , Coronavirus Infections/epidemiology , Coronavirus Infections/virology , Disease Outbreaks , Olfaction Disorders/epidemiology , Olfaction Disorders/etiology , Pneumonia, Viral/complications , Pneumonia, Viral/epidemiology , Pneumonia, Viral/virology , COVID-19 , Female , Humans , Male , Olfaction Disorders/diagnosis , Olfaction Disorders/therapy , Olfactory Bulb/anatomy & histology , Olfactory Bulb/physiology , Pandemics , SARS-CoV-2 , Smell
10.
Opt Lett ; 45(4): 952-955, 2020 Feb 15.
Article in English | MEDLINE | ID: mdl-32058515

ABSTRACT

To overcome the resolution limits in laser processing technologies, it is highly attractive to translate concepts used in advanced optical microscopy. In this prospect, the nonlinear nature of absorption in dielectrics with femtosecond lasers is recurrently taken as a direct advantage in an analogous way to excitation in multiphoton microscopy. However, we establish that no direct benefit in resolution can be expected when laser ablation is observed. We explore widely different nonlinear regimes using ultrashort pulses at different wavelengths (1550 and 515 nm) and target materials of various bandgaps (3.8-8.8 eV). We find in the experiments that the shapes of all ablation features correspond to a one-to-one mapping of the beam contours at a strict threshold intensity. The nonlinearity-independent response shows that the incorporation of extreme UV should provide a direct route to the nanoscale resolutions routinely achieved in lithography.

11.
Psicológica (Valencia. Internet) ; 41(1): 39-65, ene. 2020. tab
Article in English | IBECS | ID: ibc-193629

ABSTRACT

The Remote Associates Test (RAT) is a measure developed by Mednick (1962) which is used to assess the convergent thinking component of creativity. This study presents a normative database in Spanish including 102 problems based on the RAT. Three sets of problems were built according to the type of between-word associations: semantic, compound, and two-word expressions. These problems were administered to a sample of 309 elementary, high-school, and university students. The results show good internal consistency as well as good convergent validity with insight problems, and discriminant validity using Guilford's Alternative Uses Test. In addition, the results indicate age-related differences in the ability to solve the different types of problems


El Test de Asociados Remotos (RAT) es una medida desarrollada por Mednick (1962) que se utiliza para evaluar el componente de pensamiento convergente de la creatividad. Este estudio presenta una base de datos normativa en español que incluye 102 problemas basados en asociados remotos. Se construyeron tres conjuntos de problemas según el tipo de asociaciones entre palabras: asociados semánticos, palabras compuestas y expresiones de dos palabras. Estos problemas se administraron a una muestra de 309 estudiantes de primaria, secundaria y universidad. Los resultados muestran una buena consistencia interna así como una buena validez convergente con problemas tipo insight y una validez discriminante con la Prueba de Usos Alternativos de Guilford. Además, los resultados indican diferencias relacionadas con la edad en la capacidad para resolver los diferentes tipos de problemas


Subject(s)
Humans , Female , Adolescent , Young Adult , Psycholinguistics/methods , Psychological Tests , Psychometrics/methods , Problem Solving/physiology , Language
12.
J Investig Allergol Clin Immunol ; 30(6): 439-447, 2020.
Article in English | MEDLINE | ID: mdl-31530512

ABSTRACT

BACKGROUND AND OBJECTIVE: Few odor tests have been developed for children. Objectives: The aim of the present study was to develop and validate a simple and quick olfactory test to evaluate odor identification and threshold in a Spanish pediatric population. METHODS: The Pediatric Barcelona Olfactory Test-6 (pBOT-6) consisted of a set of 6 odorants for a forced choice identification test and a 6-dilution phenyl ethyl alcohol geometric series for the threshold test. The pBOT-6 was compared with the Universal Sniff test (a validated international pediatric smell test) in 131 healthy Spanish volunteers aged 6-17 years. A Bland-Altman plot was used to determine the agreement between the 2 tests. Reliability was analyzed in 15 volunteers using the intraclass correlation coefficient. Normative data were obtained, and 8 children diagnosed with subjective loss of smell were tested for validation. RESULTS: The Bland-Altman analysis demonstrated a minimal bias of -1.71% with upper and lower limits of agreement of -31.1% and 27.6%, respectively. The intraclass correlation coefficient was 0.83 (95%CI, 0.6-0.96) for the identification test and 0.73 (95%CI, 0.36-0.9) for the threshold test, with excellent and good consistency between measurements over time. Mean pBOT-6 scores were significantly higher in healthy volunteers than in patients with loss of smell. Discrimination between normosmia and loss of smell was achieved with a sensitivity of 96.9% and a specificity of 100%. CONCLUSIONS: pBOT-6 offers an effective and fast method that is useful in clinical routine to distinguish, with high sensitivity and specificity, between pediatric patients with normosmia and those with loss of smell.


Subject(s)
Diagnostic Tests, Routine/methods , Odorants , Smell , Adolescent , Age Factors , Child , Diagnostic Tests, Routine/standards , Female , Healthy Volunteers , Humans , Male , Reference Values , Reproducibility of Results , Sensitivity and Specificity , Sensory Thresholds , Spain
13.
Ann Oncol ; 29(10): 2098-2104, 2018 10 01.
Article in English | MEDLINE | ID: mdl-30412222

ABSTRACT

Background: Adjuvant sunitinib has significantly improved disease-free survival versus placebo in patients with renal cell carcinoma at high risk of recurrence post-nephrectomy (hazard ratio 0.76; 95% confidence interval, 0.59-0.98; two-sided P = 0.03). We report safety, therapy management, and patient-reported outcomes for patients receiving sunitinib and placebo in the S-TRAC trial. Patients and methods: Patients were stratified by the University of California, Los Angeles Integrated Staging System and Eastern Cooperative Oncology Group performance status score, and randomized (1 : 1) to receive sunitinib (50 mg/day) or placebo. Single dose reductions to 37.5 mg, dose delays, and dose interruptions were used to manage adverse events (AEs). Patients' health-related quality of life, including key symptoms typically associated with sunitinib, were evaluated with the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30). Results: Patients maintained treatment for 9.5 (mean, SD 4.4) and 10.3 (mean, SD 3.7) months in the sunitinib and placebo arms, respectively. In the sunitinib arm, key AEs occurred ∼1 month (median) after start of treatment and resolved within ∼3.5 weeks (median). Many (40.6%) AEs leading to permanent discontinuation were grade 1/2, and most (87.2%) resolved or were resolving by 28 days after last treatment. Patients taking sunitinib showed a significantly lower EORTC QLQ-C30 overall health status score versus placebo, although this reduction was not clinically meaningful. Patients reported symptoms typically related to sunitinib treatment with diarrhea and loss of appetite showing clinically meaningful increases. Conclusions: In S-TRAC, AEs were predictable, manageable, and reversible via dose interruptions, dose reductions, and/or standard supportive medical therapy. Patients on sunitinib did report increased symptoms and reduced HRQoL, but these changes were generally not clinically meaningful, apart from appetite loss and diarrhea, and were expected in the context of known sunitinib effects. Clinical trial registration: ClinicalTrials.gov, NCT00375674.


Subject(s)
Antineoplastic Agents/therapeutic use , Carcinoma, Renal Cell/drug therapy , Kidney Neoplasms/drug therapy , Neoplasm Recurrence, Local/drug therapy , Patient Reported Outcome Measures , Quality of Life , Sunitinib/therapeutic use , Carcinoma, Renal Cell/pathology , Chemotherapy, Adjuvant , Disease Management , Double-Blind Method , Follow-Up Studies , Humans , International Agencies , Kidney Neoplasms/pathology , Neoplasm Recurrence, Local/pathology , Prognosis , Prospective Studies , Survival Rate
14.
Ann Oncol ; 29(12): 2371-2378, 2018 12 01.
Article in English | MEDLINE | ID: mdl-30346481

ABSTRACT

Background: The ATLAS trial compared axitinib versus placebo in patients with locoregional renal cell carcinoma (RCC) at risk of recurrence after nephrectomy. Patients and methods: In a phase III, randomized, double-blind trial, patients had >50% clear-cell RCC, had undergone nephrectomy, and had no evidence of macroscopic residual or metastatic disease [independent review committee (IRC) confirmed]. The intent-to-treat population included all randomized patients [≥pT2 and/or N+, any Fuhrman grade (FG), Eastern Cooperative Oncology Group status 0/1]. Patients (stratified by risk group/country) received (1 : 1) oral twice-daily axitinib 5 mg or placebo for ≤3 years, with a 1-year minimum unless recurrence, occurrence of second primary malignancy, significant toxicity, or consent withdrawal. The primary end point was disease-free survival (DFS) per IRC. A prespecified DFS analysis in the highest-risk subpopulation (pT3, FG ≥ 3 or pT4 and/or N+, any T, any FG) was conducted. Results: A total of 724 patients (363 versus 361, axitinib versus placebo) were randomized from 8 May 2012, to 1 July 2016. The trial was stopped due to futility at a preplanned interim analysis at 203 DFS events. There was no significant difference in DFS per IRC [hazard ratio (HR) = 0.870; 95% confidence interval (CI) : 0.660-1.147; P = 0.3211). In the highest-risk subpopulation, a 36% and 27% reduction in risk of a DFS event (HR; 95% CI) was observed per investigator (0.641; 0.468-0.879; P = 0.0051), and by IRC (0.735; 0.525-1.028; P = 0.0704), respectively. Overall survival data were not mature. Similar adverse events (AEs; 99% versus 92%) and serious AEs (19% versus 14%), but more grade 3/4 AEs (61% versus 30%) were reported for axitinib versus placebo. Conclusions: ATLAS did not meet its primary end point; however, improvement in DFS per investigator was seen in the highest-risk subpopulation. No new safety signals were reported. Trial registration number: NCT01599754.


Subject(s)
Antineoplastic Agents/administration & dosage , Axitinib/administration & dosage , Carcinoma, Renal Cell/therapy , Kidney Neoplasms/therapy , Neoplasm Recurrence, Local/prevention & control , Administration, Oral , Aged , Antineoplastic Agents/adverse effects , Axitinib/adverse effects , Carcinoma, Renal Cell/mortality , Carcinoma, Renal Cell/pathology , Chemotherapy, Adjuvant/methods , Disease-Free Survival , Double-Blind Method , Drug Administration Schedule , Female , Follow-Up Studies , Humans , Intention to Treat Analysis , Kidney Neoplasms/mortality , Kidney Neoplasms/pathology , Male , Middle Aged , Neoplasm Recurrence, Local/mortality , Nephrectomy , Placebos/administration & dosage , Placebos/adverse effects
15.
Psychol Res ; 82(3): 535-548, 2018 May.
Article in English | MEDLINE | ID: mdl-28280931

ABSTRACT

Working memory updating (WMU) is a core mechanism in the human mental architecture and a good predictor of a wide range of cognitive processes. This study analyzed the benefits of two different WMU training procedures, near transfer effects on a working memory measure, and far transfer effects on nonverbal reasoning. Maintenance of any benefits a month later was also assessed. Participants were randomly assigned to: an adaptive training group that performed two numerical WMU tasks during four sessions; a non-adaptive training group that performed the same tasks but on a constant and less demanding level of difficulty; or an active control group that performed other tasks unrelated with working memory. After the training, all three groups showed improvements in most of the tasks, and these benefits were maintained a month later. The gain in one of the two WMU measures was larger for the adaptive and non-adaptive groups than for the control group. This specific gain in a task similar to the one trained would indicate the use of a better strategy for performing the task. Besides this nearest transfer effect, no other transfer effects were found. The adaptability of the training procedure did not produce greater improvements. These results are discussed in terms of the training procedure and the feasibility of training WMU.


Subject(s)
Memory, Short-Term/physiology , Transfer, Psychology/physiology , Adult , Female , Humans , Male , Young Adult
16.
Ecotoxicol Environ Saf ; 125: 1-8, 2016 Mar.
Article in English | MEDLINE | ID: mdl-26650419

ABSTRACT

The environmental risk of surfactants requires toxicity measurements. As different test organisms have different sensitivity to the toxics, it is necessary to establish the most appropriate organism to classify the surfactant as very toxic, toxic, harmful or safe, in order to establish the maximum permissible concentrations in aquatic ecosystems. We have determined the toxicity values of various anionic surfactants ether carboxylic derivatives using four test organisms: the freshwater crustacean Daphnia magna, the luminescent bacterium Vibrio fischeri, the microalgae Selenastrum capricornutum (freshwater algae) and Phaeodactylum tricornutum (seawater algae). In addition, in order to compare and classify the different families of surfactants, we have included a compilation of toxicity data of surfactants collected from literature. The results indicated that V. fischeri was more sensitive to the toxic effects of the surfactants than was D. magna or the microalgae, which was the least sensitive. This result shows that the most suitable toxicity assay for surfactants may be the one using V. fischeri. The toxicity data revealed considerable variation in toxicity responses with the structure of the surfactants regardless of the species tested. The toxicity data have been related to the structure of the surfactants, giving a mathematical relationship that helps to predict the toxic potential of a surfactant from its structure. Model-predicted toxicity agreed well with toxicity values reported in the literature for several surfactants previously studied. Predictive models of toxicity is a handy tool for providing a risk assessment that can be useful to establish the toxicity range for each surfactant and the different test organisms in order to select efficient surfactants with a lower impact on the aquatic environment.


Subject(s)
Aquatic Organisms/drug effects , Environmental Monitoring/methods , Surface-Active Agents/toxicity , Toxicity Tests, Acute/methods , Water Pollutants, Chemical/toxicity , Aliivibrio fischeri/drug effects , Animals , Anions/toxicity , Daphnia/drug effects , Diatoms/drug effects , Microalgae/drug effects
17.
Front Psychol ; 6: 1544, 2015.
Article in English | MEDLINE | ID: mdl-26500594

ABSTRACT

The n-back task is a frequently used measure of working memory (WM) in cognitive neuroscience research contexts, and it has become widely adopted in other areas over the last decade. This study aimed to obtain normative data for the n-back task from a large sample of children and adolescents. To this end, a computerized verbal n-back task with three levels of WM load (1-back, 2-back, and 3-back) was administered to 3722 Spanish school children aged 7-13 years. Results showed an overall age-related increase in performance for the different levels of difficulty. This trend was less pronounced at 1-back than at 2-back when hits were considered. Gender differences were also observed, with girls outperforming boys although taking more time to respond. The theoretical implications of these results are discussed. Normative data stratified by age and gender for the three WM load levels are provided.

18.
Br J Cancer ; 113(1): 12-9, 2015 Jun 30.
Article in English | MEDLINE | ID: mdl-26086878

ABSTRACT

BACKGROUND: We report final results with extended follow-up from a global, expanded-access trial that pre-regulatory approval provided sunitinib to metastatic renal cell carcinoma (mRCC) patients, ineligible for registration-directed trials. METHODS: Patients ⩾18 years received oral sunitinib 50 mg per day on a 4-weeks-on-2-weeks-off schedule. Safety was assessed regularly. Tumour measurements were scheduled per local practice. RESULTS: A total of 4543 patients received sunitinib. Median treatment duration and follow-up were 7.5 and 13.6 months. Objective response rate was 16% (95% confidence interval (CI): 15-17). Median progression-free survival (PFS) and overall survival (OS) were 9.4 months (95% CI: 8.8-10.0) and 18.7 months (95% CI: 17.5-19.5). Median PFS in subgroups of interest: aged ⩾65 years (33%), 10.1 months; Eastern Cooperative Oncology Group performance status ⩾2 (14%), 3.5 months; non-clear cell histology (12%), 6.0 months; and brain metastases (7%), 5.3 months. OS was strongly associated with the International Metastatic Renal-Cell Carcinoma Database Consortium prognostic model (n=4065). The most common grade 3/4 treatment-related adverse events were thrombocytopenia (10%), fatigue (9%), and asthenia, neutropenia, and hand-foot syndrome (each 7%). CONCLUSION: Final analysis of the sunitinib expanded-access trial provided a good opportunity to evaluate the long-term side effects of a tyrosine kinase inhibitor used worldwide in mRCC. Efficacy and safety findings were consistent with previous results.


Subject(s)
Antineoplastic Agents/therapeutic use , Carcinoma, Renal Cell/drug therapy , Indoles/therapeutic use , Kidney Neoplasms/drug therapy , Neoplasm Metastasis , Pyrroles/therapeutic use , Adult , Aged , Aged, 80 and over , Antineoplastic Agents/adverse effects , Carcinoma, Renal Cell/pathology , Female , Humans , Indoles/adverse effects , Kidney Neoplasms/pathology , Male , Middle Aged , Pyrroles/adverse effects , Sunitinib , Young Adult
19.
Acta Psychol (Amst) ; 157: 106-13, 2015 May.
Article in English | MEDLINE | ID: mdl-25756938

ABSTRACT

Working memory updating (WMU) tasks require different elements in working memory (WM) to be maintained simultaneously, accessing one of these elements, and substituting its content. This study examined possible developmental changes from childhood to adulthood both in focus switching and substituting information in WM. In addition, possible age-related changes in interference due to representational overlap between the different elements simultaneously held in these tasks were examined. Children (8- and 11-year-olds), adolescents (14-year-olds) and younger adults (mean age=22 years) were administered a numerical updating memory task, in which updating and focus switching were manipulated. As expected, response times decreased and recall performance increased with age. More importantly, the time needed for focus switching was longer in children than in adolescents and younger adults. On the other hand, substitution of information and interference due to representational overlap were not affected by age. These results suggest that age-related changes in focus switching might mediate developmental changes in WMU performance.


Subject(s)
Aging , Attention , Memory, Short-Term , Mental Recall , Adolescent , Adult , Age Factors , Child , Female , Humans , Male , Reaction Time
20.
Q J Exp Psychol (Hove) ; 67(1): 16-32, 2014.
Article in English | MEDLINE | ID: mdl-23679060

ABSTRACT

The present study investigates the process of updating representations in working memory (WM) and how similarity between the information involved influences this process. In WM updating tasks, the similarity in terms of numerical distance between the number to be substituted and the new one facilitates the updating process. We aimed to disentangle the possible effect of two dimensions of similarity that may contribute to this numerical effect: numerical distance itself and common digits shared between the numbers involved. Three experiments were conducted in which different ranges of distances and the coincidence between the digits of the two numbers involved in updating were manipulated. Results showed that the two dimensions of similarity had an effect on updating times. The greater the similarity between the information maintained in memory and the new information that substituted it, the faster the updating. This is consistent both with the idea of distributed representations based on features, and with a selective updating process based on a feature overwriting mechanism. Thus, updating in WM can be understood as a selective substitution process influenced by similarity in which only certain parts of the representation stored in memory are changed.


Subject(s)
Mathematics , Memory, Short-Term/physiology , Recognition, Psychology/physiology , Adolescent , Adult , Analysis of Variance , Female , Humans , Male , Neuropsychological Tests , Photic Stimulation , Reaction Time , Young Adult
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