Overall survival with adjuvant atezolizumab after chemotherapy in resected stage II-IIIA non-small-cell lung cancer (IMpower010): a randomised, multicentre, open-label, phase III trial.

BACKGROUND: IMpower010 (NCT02486718) demonstrated significantly improved disease-free survival (DFS) with adjuvant atezolizumab versus best supportive care (BSC) following platinum-based chemotherapy in the programmed death-ligand 1 (PD-L1)-positive and all stage II-IIIA non-small-cell lung cancer (NSCLC) populations, at the DFS interim analysis. Results of the first interim analysis of overall survival (OS) are reported here. PATIENT AND METHODS: The design, participants, and primary-endpoint DFS outcomes have been reported for this phase III, open-label, 1 : 1 randomised study of atezolizumab (1200 mg q3w; 16 cycles) versus BSC after adjuvant platinum-based chemotherapy (1-4 cycles) in adults with completely resected stage IB (≥4 cm)-IIIA NSCLC (per the Union Internationale Contre le Cancer and American Joint Committee on Cancer staging system, 7th edition). Key secondary endpoints included OS in the stage IB-IIIA intent-to-treat (ITT) population and safety in randomised treated patients. The first pre-specified interim analysis of OS was conducted after 251 deaths in the ITT population. Exploratory analyses included OS by baseline PD-L1 expression level (SP263 assay). RESULTS: At a median of 45.3 months' follow-up on 18 April 2022, 127 of 507 patients (25%) in the atezolizumab arm and 124 of 498 (24.9%) in the BSC arm had died. The median OS in the ITT population was not estimable; the stratified hazard ratio (HR) was 0.995 [95% confidence interval (CI) 0.78-1.28]. The stratified OS HRs (95% CI) were 0.95 (0.74-1.24) in the stage II-IIIA (n = 882), 0.71 (0.49-1.03) in the stage II-IIIA PD-L1 tumour cell (TC) ≥1% (n = 476), and 0.43 (95% CI 0.24-0.78) in the stage II-IIIA PD-L1 TC ≥50% (n = 229) populations. Atezolizumab-related adverse event incidences remained unchanged since the previous analysis [grade 3/4 in 53 (10.7%) and grade 5 in 4 (0.8%) of 495 patients, respectively]. CONCLUSIONS: Although OS remains immature for the ITT population, these data indicate a positive trend favouring atezolizumab in PD-L1 subgroup analyses, primarily driven by the PD-L1 TC ≥50% stage II-IIIA subgroup. No new safety signals were observed after 13 months' additional follow-up. Together, these findings support the positive benefit-risk profile of adjuvant atezolizumab in this setting.

Demonstration of a GaSb/GaAs Quantum Dot Intermediate Band Solar Cell Operating at Maximum Power Point.

Intermediate band solar cells (IBSCs) promise high efficiencies while maintaining a low device structural complexity. A high efficiency can be obtained by harvesting below-band-gap photons, thus increasing the current, while at the same time preserving a high voltage. Here, we provide experimental proof that below-band-gap photons can be used to produce nonzero electrical work in an IBSC without compromising the voltage. For this, we manufacture a GaSb/GaAs quantum-dot IBSC. We use light biasing and make our cell operate at the maximum power point at 9 K. We measure the photocurrent response to absorption of photons with an energy of less than 1.15 eV while the cell is operating at 1.15 V. We also show that this result implies the existence of three quasi-Fermi levels linked to the three electronic bands in our device, as demanded by the IBSC theory to preserve the output voltage of the cell.

The role of the epilepsy monitoring unit in the investigation of patients with epilepsy and intellectual disabilities.

BACKGROUND: A significant proportion of the people with intellectual disabilities (ID) has epilepsy and lives in institutions. These patients tend to have atypical presentations of epileptic seizures with an increased risk of misdiagnoses. They often have drug-resistant epilepsy (DRE) requiring polypharmacy with increased risk of morbidity. The aim of this study was to determine the usefulness of Epilepsy Monitoring Unit (EMU) in the diagnosis and management of these patients. METHODS: This is a retrospective observational study of people with epilepsy and ID living in institutions that were admitted to the EMU at London Health Sciences Center (LHSC), from January 2014 to December 2016. RESULTS: Out of 1121 patients admitted to the EMU at the LHSC, 1.96% (N = 22) fulfilled the inclusion criteria for this study. The mean age was 34.5 years (interquartile range [IQR]: 28.8-53); 50%(N = 11) were female. Fourteen (63.6%) had generalized epilepsy. Six (27.3%) had a history of status epilepticus. The mean number of antiseizure medications (ASMs) in those patients was three (IQR: 2-4). Eight (36.4%) patients had severely impaired or no language skills and seven (31.8%) required wheelchair. Eleven (50%) had a mood disorder and seven (31.8%) of them were taking antipsychotic medications. The mean duration of admission duration was 6.6 days (IQR: 3.5-8.5). There was a clinical-electrographic correlation between the behavioral events and epileptic seizures in nineteen (86.4%) of the patients. CONCLUSIONS: Admission to the EMU provided an accurate characterization of transient events in people with ID and epilepsy with improvement in their medical management.

Immune checkpoint inhibitors for patients with advanced lung cancer and oncogenic driver alterations: results from the IMMUNOTARGET registry.

BACKGROUND: Anti-PD1/PD-L1 directed immune checkpoint inhibitors (ICI) are widely used to treat patients with advanced non-small-cell lung cancer (NSCLC). The activity of ICI across NSCLC harboring oncogenic alterations is poorly characterized. The aim of our study was to address the efficacy of ICI in the context of oncogenic addiction. PATIENTS AND METHODS: We conducted a retrospective study for patients receiving ICI monotherapy for advanced NSCLC with at least one oncogenic driver alteration. Anonymized data were evaluated for clinicopathologic characteristics and outcomes for ICI therapy: best response (RECIST 1.1), progression-free survival (PFS), and overall survival (OS) from ICI initiation. The primary end point was PFS under ICI. Secondary end points were best response (RECIST 1.1) and OS from ICI initiation. RESULTS: We studied 551 patients treated in 24 centers from 10 countries. The molecular alterations involved KRAS (n = 271), EGFR (n = 125), BRAF (n = 43), MET (n = 36), HER2 (n = 29), ALK (n = 23), RET (n = 16), ROS1 (n = 7), and multiple drivers (n = 1). Median age was 60 years, gender ratio was 1 : 1, never/former/current smokers were 28%/51%/21%, respectively, and the majority of tumors were adenocarcinoma. The objective response rate by driver alteration was: KRAS = 26%, BRAF = 24%, ROS1 = 17%, MET = 16%, EGFR = 12%, HER2 = 7%, RET = 6%, and ALK = 0%. In the entire cohort, median PFS was 2.8 months, OS 13.3 months, and the best response rate 19%. In a subgroup analysis, median PFS (in months) was 2.1 for EGFR, 3.2 for KRAS, 2.5 for ALK, 3.1 for BRAF, 2.5 for HER2, 2.1 for RET, and 3.4 for MET. In certain subgroups, PFS was positively associated with PD-L1 expression (KRAS, EGFR) and with smoking status (BRAF, HER2). CONCLUSIONS: : ICI induced regression in some tumors with actionable driver alterations, but clinical activity was lower compared with the KRAS group and the lack of response in the ALK group was notable. Patients with actionable tumor alterations should receive targeted therapies and chemotherapy before considering immunotherapy as a single agent.

Serum and gene expression levels of CT-1, IL-6, and TNF-α after a lifestyle intervention in obese children.

BACKGROUND: Inflammation related molecules such as tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), and cardiotrophin-1 (CT-1) are highly expressed in obese individuals and could partly explain some comorbidities associated to obesity. In obese children, lifestyle interventions are able to lower inflammation and reduce cardiovascular risk factors associated with obesity. The aim of the present work was to study changes in inflammation-related molecules serum and peripheral blood mononuclear cells (PBMC) transcript levels after a 10-week lifestyle intervention in obese children and asses their potential association with glucose metabolism. METHODS: Twenty-three obese children (mean age 11.5 years; 48% males) underwent a 10-week lifestyle not controlled intervention trial. Anthropometric and biochemical measurements were analyzed. Transcript analysis for CT-1, IL-6, and TNF-α in PBMC were performed by RT-PCR. Serum cytokine levels were also measured at baseline and after 10-weeks. RESULTS: Participants achieved a significant reduction in body adiposity (0.34 decrease in body mass index-standard deviation), total cholesterol, and glucose levels after 10-weeks. A Significant decrease in serum TNF-α and C reactive protein (CRP) were observed. CT-1 transcript levels were significantly reduced (P = .005) after lifestyle intervention, and these changes were significantly correlated with changes in serum CT-1 levels (r = 0.451; P = .031). In multiple regression analysis baseline CT-1 transcript levels were positively associated with final insulin (R2 = 0.506; P = .035) and HOMA-IR values (R2 = 0.473; P = .034). CONCLUSIONS: We reported that serum CRP, TNF-α, as well as PBMC CT-1 transcript levels were reduced after lifestyle intervention in obese children. More studies are needed to clarify the role of inflammation-related molecules in glucose metabolism.

Dual MET and ERBB inhibition overcomes intratumor plasticity in osimertinib-resistant-advanced non-small-cell lung cancer (NSCLC).

BACKGROUND: Third-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) such as osimertinib are the last line of targeted treatment of metastatic non-small-cell lung cancer (NSCLC) EGFR-mutant harboring T790M. Different mechanisms of acquired resistance to third-generation EGFR-TKIs have been proposed. It is therefore crucial to identify new and effective strategies to overcome successive acquired mechanisms of resistance. METHODS: For Amplicon-seq analysis, samples from the index patient (primary and metastasis lesions at different timepoints) as well as the patient-derived orthotopic xenograft tumors corresponding to the different treatment arms were used. All samples were formalin-fixed paraffin-embedded, selected and evaluated by a pathologist. For droplet digital PCR, 20 patients diagnosed with NSCLC at baseline or progression to different lines of TKI therapies were selected. Formalin-fixed paraffin-embedded blocks corresponding to either primary tumor or metastasis specimens were used for analysis. For single-cell analysis, orthotopically grown metastases were dissected from the brain of an athymic nu/nu mouse and cryopreserved at -80°C. RESULTS: In a brain metastasis lesion from a NSCLC patient presenting an EGFR T790M mutation, we detected MET gene amplification after prolonged treatment with osimertinib. Importantly, the combination of capmatinib (c-MET inhibitor) and afatinib (ErbB-1/2/4 inhibitor) completely suppressed tumor growth in mice orthotopically injected with cells derived from this brain metastasis. In those mice treated with capmatinib or afatinib as monotherapy, we observed the emergence of KRAS G12C clones. Single-cell gene expression analyses also revealed intratumor heterogeneity, indicating the presence of a KRAS-driven subclone. We also detected low-frequent KRAS G12C alleles in patients treated with various EGFR-TKIs. CONCLUSION: Acquired resistance to subsequent EGFR-TKI treatment lines in EGFR-mutant lung cancer patients may induce genetic plasticity. We assess the biological insights of tumor heterogeneity in an osimertinib-resistant tumor with acquired MET-amplification and propose new treatment strategies in this situation.

Comparison of digital scanning and polyvinyl siloxane impression techniques by dental students: instructional efficiency and attitudes towards technology.

INTRODUCTION: With increasing use of digital scanning with restorative procedures in the dental office, it becomes necessary that educational institutions adopt instructional methodology for introducing this technology together with conventional impression techniques. OBJECTIVE: To compare the time differences between instructing dental students on digital scanning (DS) (LAVA C.O.S. digital impression system) and a conventional impression technique (CI) (polyvinyl siloxane), and to compare students' attitudes and beliefs towards both techniques. MATERIALS AND METHODS: Volunteer sophomore dental students (n = 25) with no prior experience in clinical impressions were recruited and IRB consent obtained. Participants responded to a pre-and post-exposure questionnaire. Participants were instructed on the use of both DS and CI for a single tooth full coverage crown restoration using a consecutive sequence of video lecture, investigator-led demonstration and independent impression exercise. The time necessary for each step (minutes) was recorded. Statistical significance was calculated using dependent t-tests (time measurements) and 2-sample Mann-Whitney (questionnaire responses). RESULTS: The time spent teaching students was greater for DS than CI for video lecture (15.95 and 10.07 min, P = 0.0000), demonstration time (9.06 and 4.70 min, P = 0.0000) and impression time (18.17 and 8.59 min, P = 0.0000). Prior to the instruction and practice, students considered themselves more familiar with CI (3.96) than DS (1.96) (P = 0.0000). After the instruction and practice, participants reported CI technique proved significantly easier than expected (pre-instruction: 3.52 and post-instruction: 4.08, P = 0.002). However, overall participants' perception of ease of use for DS was not influenced by this instruction and practice experience (pre-instruction: 3.84 and post-instruction: 3.56, P = 0.106). Despite the results, 96% of participants expressed an expectation that DS will become their predominant impression technique during their careers. CONCLUSIONS: Dental students with no clinical experience have high expectations for digital scanning, and despite their initial difficulty, expect it to become their primary impression technique during their professional futures. The instructional time necessary for introducing DS into the curriculum is significantly greater than CI in both classroom (lecture) and clinical simulation settings (investigator-led demonstration).

Behavioral predictors of attrition in adolescents participating in a multidisciplinary obesity treatment program: EVASYON study.

The aims of this study were to identify the cognitive and behavioral predictors of dropping out and to estimate the attrition rate during different phases of an intervention program to treat overweight and obesity in adolescents. Overweight/obese adolescents (n=156, aged: 13-16 years; 71 male and 85 female subjects) were included in a multicomponent (diet, physical activity and psychological support) family-based group treatment program. At baseline and after 2 months (intensive phase) and 13 months (extensive phase) of follow-up, we measured adolescents' cognitive and behavioral dimensions, together with the parents' perception of their child's behavior. Of the 156 adolescents selected, 112 completed the full program (drop-out rate of 28.2%). The risk of dropping out during the extensive phase increased by 20% for each unit increase in the adolescent's social insecurity score (odds ratio=1.20, 95% confidence interval=1.07-1.34, P=0.002). The adolescents who had a high interoceptive awareness showed a significant decrease of 13.0% in the probability of dropping out (odds ratio=0.87, 95% confidence interval=0.77-0.99, P=0.040). Adolescents' social insecurity was the main predictor of drop-out in a multicomponent family-group-based obesity treatment program. To reduce attrition rates in these programs, the individual's social insecurity level needs to be reduced, whereas the family's awareness of eating-related behavior needs adjustment.

Thin-layer voltammetry of soluble species on screen-printed electrodes: proof of concept.

Thin-layer diffusion conditions were accomplished on screen-printed electrodes by placing a controlled-weight onto the cast solution and allowing for its natural spreading. The restricted diffusive conditions were assessed by cyclic voltammetry at low voltage scan rates and electrochemical impedance spectroscopy. The relationship between the weight exerted over the drop and the thin-layer thickness achieved was determined, in such a way that the simple experimental set-up designed for this work could be developed into a commercial device with variable control of the thin-layer conditions. The experimental results obtained resemble those reported for the voltammetric features of electroactive soluble species employing electrodes modified with carbon nanotubes or graphene layers, suggesting that the attainment of the benefits reported for these nanomaterials could be done simply by forcing the solution to spread over the screen-printed electrodic system to form a thin layer solution. The advantages of thin-layer voltammetry in the kinetic characterization of quasi-reversible and irreversible processes are highlighted.

Vaginal progesterone as maintenance treatment after an episode of preterm labour (PROMISE) study: a multicentre, double-blind, randomised, placebo-controlled trial.

OBJECTIVE: To evaluate whether maintenance treatment with vaginal progesterone after an arrested preterm labour reduces the incidence of preterm delivery. DESIGN: Multicentre, randomised, double-blind, placebo-controlled trial. SETTING: Twelve tertiary care centres in Spain. POPULATION: A total of 265 women with singleton pregnancy, preterm labour successfully arrested with tocolytic treatment, and cervical length of <25 mm. METHODS: Randomisation was stratified by gestational age (from 24.0 to <31.0 weeks of gestation and from 31.0 to <34.0 weeks of gestation) and centre. Patients were randomly assigned, in a 1 : 1 ratio, to either daily vaginal capsules of 200 mg progesterone or placebo until delivery or 36.6 weeks of gestation, whichever occurred first. MAIN OUTCOME MEASURES: Primary outcome was delivery before 34.0 and 37.0 weeks of gestation. Secondary outcomes were discharge-to-delivery time, readmissions because of preterm labour, emergency service use, and neonatal morbidity and mortality. RESULTS: From June 2008 through June 2012, 1419 women were screened: 472 met the inclusion criteria and 265 were randomised. The final analysis included 258 women: 126 in the progesterone group and 132 in the placebo group. There were no significant differences between the progesterone and placebo groups in terms of delivery at <34 weeks of gestation [9/126 (7.1%) versus 10/132 (7.6%), P = 0.91] or <37 weeks of gestation [36/126 (28.6%) versus 29/132 (22.0%), P = 0.22]. There were no differences observed between groups when considering the two strata of gestational age at inclusion. CONCLUSIONS: A maintenance treatment of 200 mg of daily vaginal progesterone capsules in women discharged home after an episode of arrested preterm labour did not significantly reduce the rate of preterm delivery. TWEETABLE ABSTRACT: Maintenance progesterone in 258 women after arrested PTL showed no benefit.

Yogurt consumption and abdominal obesity reversion in the PREDIMED study.

BACKGROUND AND AIMS: Evidence on the association yogurt consumption and obesity is not conclusive. The aim of this study was to prospectively evaluate the association between yogurt consumption, reversion of abdominal obesity status and waist circumference change in elderly. METHODS AND RESULTS: 4545 individuals at high cardiovascular risk were prospectively followed. Total, whole-fat and low-fat yogurt consumption were assessed using food frequency questionnaires. Generalized estimating equations were used to analyze the association between yogurt consumption and waist circumference change (measured at baseline and yearly during the follow-up). Logistic regression models were used to evaluate the odds ratios (ORs) and 95% CIs of the reversion rate of abdominal obesity for each quintile of yogurt consumption compared with the lowest quintile. After multivariable adjustment, the average yearly waist circumference change in the quintiles of whole-fat yogurt consumption was: Q1: 0.00, Q2: 0.00 (-0.23 to 0.23), Q3: -0.15 (-0.42 to 0.13), Q4: 0.10 (-0.21 to 0.42), and Q5: -0.23 (-0.46 to -0.00) cm; p for trend = 0.05. The ORs for the reversion of abdominal obesity for whole-fat yogurt consumption were Q1: 1.00, Q2: 1.40 (1.04-1.90), Q3: 1.33 (0.94-1.89), Q4: 1.21 (0.83-1.77), and Q5: 1.43 (1.06-1.93); p for trend = 0.26. CONCLUSION: Total yogurt consumption was not significantly associated with reversion of abdominal obesity status and a lower waist circumference. However, consumption of whole-fat yogurt was associated with changes in waist circumference and higher probability for reversion of abdominal obesity. Therefore, it seems that whole-fat yogurt has more beneficial effects in management of abdominal obesity in elderly population at high cardiovascular risk.

The association between chronological age, age at injury and employment: Is there a mediating effect of secondary health conditions?

STUDY DESIGN: Cross-sectional observational study with data from the 2012 community-based survey of the Swiss Spinal Cord Injury Cohort Study. OBJECTIVES: To examine the relationships between chronological age, age at injury, secondary health conditions (SHCs) and paid employment. SETTING: Community setting in Switzerland. METHODS: A total of 1159 individuals of working age (16-63 years for women and 64 years for men) with traumatic or non-traumatic spinal cord injury (SCI) were included in the study. Direct and indirect (via SHCs) effects of chronological age and age at injury on paid employment were tested using a decomposition method for logistic regression models. RESULTS: Both chronological age groups (age 35-49 and 50-63/64 years) and the group with age at injury beyond 40 years showed negative direct effects on employment status. A partial indirect effect (mediation) via chronic pain was found in the group with the highest chronological age (>50 years). Furthermore, pressure ulcer, pain and urinary tract infection were negatively related with employment in both models, that is, chronological age and employment and age at injury and employment. CONCLUSION: Being older and having a higher age at injury directly affects whether an individual is employed. Pain is mediating the relation between chronological age and employment. Furthermore, pressure ulcer, chronic pain and urinary tract infection directly reduce the likelihood to be employed and, therefore, represent important intervention targets in efforts to maintain or engage in employment of individuals with SCI.

Winter circulation weather types and hospital admissions for respiratory diseases in Galicia, Spain.

The link between various pathologies and atmospheric conditions has been a constant topic of study over recent decades in many places across the world; knowing more about it enables us to pre-empt the worsening of certain diseases, thereby optimizing medical resources. This study looked specifically at the connections in winter between respiratory diseases and types of atmospheric weather conditions (Circulation Weather Types, CWT) in Galicia, a region in the north-western corner of the Iberian Peninsula. To do this, the study used hospital admission data associated with these pathologies as well as an automatic classification of weather types. The main result obtained was that weather types giving rise to an increase in admissions due to these diseases are those associated with cold, dry weather, such as those in the east and south-east, or anticyclonic types. A second peak was associated with humid, hotter weather, generally linked to south-west weather types. In the future, this result may help to forecast the increase in respiratory pathologies in the region some days in advance.

Intermediate band solar cell with extreme broadband spectrum quantum efficiency.

We report, for the first time, about an intermediate band solar cell implemented with InAs/AlGaAs quantum dots whose photoresponse expands from 250 to ∼6000 nm. To our knowledge, this is the broadest quantum efficiency reported to date for a solar cell and demonstrates that the intermediate band solar cell is capable of producing photocurrent when illuminated with photons whose energy equals the energy of the lowest band gap. We show experimental evidence indicating that this result is in agreement with the theory of the intermediate band solar cell, according to which the generation recombination between the intermediate band and the valence band makes this photocurrent detectable.

The detection of neural autoantibodies in patients with antiepileptic-drug-resistant epilepsy predicts response to immunotherapy.

BACKGROUND AND PURPOSE: The detection of antibodies binding neural antigens in patients with epilepsy has led to the definition of 'autoimmune epilepsy'. Patients with neural antibodies not responding to antiepileptic drugs (AEDs) may benefit from immunotherapy. Aim of this study was to evaluate the frequency of autoantibodies specific to neural antigens in patients with epilepsy and their response to immunotherapy. METHODS: Eighty-one patients and 75 age- and sex-matched healthy subjects (HS) were enrolled in the study. Two groups of patients were included: 39 patients with epilepsy and other neurological symptoms and/or autoimmune diseases responsive to AEDs (group 1) and 42 patients with AED-resistant epilepsy (group 2). Patients' serum and cerebrospinal fluid were evaluated for the presence of autoantibodies directed to neural antigens by indirect immunofluorescence on frozen sections of mouse brain, cell-based assays and a radioimmunoassay. Patients with AED-resistant epilepsy and neural autoantibodies were treated with immunotherapy and the main outcome measure was the reduction in seizure frequency. RESULTS: Neural autoantibodies were detected in 22% of patients (18/81), mostly from the AED-resistant epilepsy group (P = 0.003), but not in HS. Indirect immunofluorescence on mouse brain revealed antibodies binding to unclassified antigens in 10 patients. Twelve patients received immunotherapy and nine (75%) achieved >50% reduction in seizure frequency. CONCLUSIONS: A significant proportion of patients with AED-resistant epilepsy harbor neural-specific autoantibodies. The detection of these antibodies, especially of those binding to synaptic antigens, may predict a favorable response to immunotherapy, thus overcoming AED resistance.

The Spanish Society of Neurology's official clinical practice guidelines for epilepsy. Special considerations in epilepsy: comorbidities, women of childbearing age, and elderly patients.

INTRODUCTION: The characteristics of some population groups (patients with comorbidities, women of childbearing age, the elderly) may limit epilepsy management. Antiepileptic treatment in these patients may require adjustments. DEVELOPMENT: We searched articles in Pubmed, clinical practice guidelines for epilepsy, and recommendations by the most relevant medical societies regarding epilepsy in special situations (patients with comorbidities, women of childbearing age, the elderly). Evidence and recommendations are classified according to the prognostic criteria of Oxford Centre of Evidence-Based Medicine (2001) and the European Federation of Neurological Societies (2004) for therapeutic interventions. CONCLUSIONS: Epilepsy treatment in special cases of comorbidities must be selected properly to improve efficacy with the fewest side effects. Adjusting antiepileptic medication and/or hormone therapy is necessary for proper seizure management in catamenial epilepsy. Exposure to antiepileptic drugs (AED) during pregnancy increases the risk of birth defects and may affect fetal growth and/or cognitive development. Postpartum breastfeeding is recommended, with monitoring for adverse effects if sedative AEDs are used. Finally, the elderly are prone to epilepsy, and diagnostic and treatment characteristics in this group differ from those of other age groups. Although therapeutic limitations may be more frequent in older patients due to comorbidities, they usually respond better to lower doses of AEDs than do other age groups.

Longitudinal association of telomere length and obesity indices in an intervention study with a Mediterranean diet: the PREDIMED-NAVARRA trial.

BACKGROUND: Telomeres are nucleoprotein structures that protect the ends of eukaryote chromosomes. Shorter telomere length (TL) is associated with some age-related human disorders, but its relationship with obesity or adiposity parameters remains unclear. OBJECTIVE: The aim of this study was to assess the relationship between TL and changes in adiposity indices after a 5-year nutritional intervention. DESIGN AND SUBJECTS: TL was measured by quantitative real-time PCR in 521 subjects (55-80 years, 55% women). Participants were randomly selected from the PREDIMED-NAVARRA centre after they completed a 5-year intervention programme. Anthropometric parameters were directly measured by trained personnel at baseline and on a yearly basis thereafter. TL at baseline and changes in TL after a 5-year intervention were assessed. RESULTS: Higher baseline TL significantly predicted a greater decrease in body weight (B=-1.09 kg, 95% confidence interval (CI): -2.01 to -0.16), body mass index (BMI) (B=-0.47 kg m(-2), 95% CI: -0.83 to -0.11), waist circumference (B=-1.15 cm, 95% CI: -2.28 to -0.01) and waist to height ratio (B=-0.008, 95% CI: -0.010 to -0.001) in multiple-adjusted models. In addition, changes in TL during the 5-year intervention were inversely associated with changes in the four anthropometric variables. The reduction in adiposity indices during the intervention, associated with increasing TL, was even higher among subjects with the longest telomeres at baseline. Logistic regression analysis showed that the risk of remaining obese after 5 years was lower in those participants who initially had the longest telomeres and increased their TL after intervention (odds ratio=0.27, 95% CI: 0.03-2.03). CONCLUSIONS: Our research suggests that TL is inversely associated with changes in obesity parameters. The assessment of TL can provide further insights for biological pathways leading to adiposity. We show for the first time an improvement of obesity indices when an increase in TL is observed after a 5-year Mediterranean diet intervention.

Total antioxidant capacity and oxidative stress after a 10-week dietary intervention program in obese children.

UNLABELLED: Dietary and serum total antioxidant capacity (TAC) are considered appropriate tools for investigating the potential health effects of dietary antioxidants consumed in mixed diets. The aim was to analyze the impact of a dietary intervention on macronutrient intakes and to evaluate the improvement on oxidative status after weight loss (WL) by measuring dietary and serum TAC, and urinary F2-isoprostane levels as markers of oxidative stress. Forty-four overweight/obese children (mean age 11.5 years) were enrolled to undergo a 10-week WL program. They were dichotomized at the median of body mass index-standard deviation score (BMI-SDS) change, as high (HR) and low responders (LR) after intervention. Subjects were prescribed with a fixed full-day meal diet, calculated according to their basal metabolic rate and physical activity levels. A validated food-frequency questionnaire was used to retrospectively calculate TAC and daily nutrient intake. The HR subjects were able to reduce anthropometric indices and to improve lipid and glucose profile. They also significantly diminished fat intake (p = 0.013). Moreover, baseline serum TAC values did significantly predict the reduction in urinary F2 isoprostane (B = -0.236 (-0.393 to -0.078); p = 0.014) in the HR group after the WL program. Notably, changes in dietary TAC after the treatment were associated with a decrease in body weight after the 10-week intervention (B = -2.815 (-5.313 to -0.318), p = 0.029) in the HR group. The -ΔSerumTAC/ΔDietaryTAC and the -ΔF2Isoprostane/ΔDietaryTAC ratios revealed that the relationships between oxidative markers and antioxidants dietary intake were more favorable in the HR than in the LR group. CONCLUSION: Our study showed that a 10-week WL program was able to reduce adiposity indices in obese children. Moreover, after the intervention changes in dietary TAC and WL were significantly associated. Our result suggests that specific food with a high TAC content (such as fruits, vegetables, and legumes) could be recommended to improve WL.

Participation in sport in persons with spinal cord injury in Switzerland.

STUDY DESIGN: Secondary data analysis of a questionnaire-based, cross-sectional survey in persons with spinal cord injury (SCI) in Switzerland. OBJECTIVE: To describe the frequency of participation in sport (PiS) and to identify correlates for PiS in persons with SCI in Switzerland. SETTING: Community sampleMethods:Frequency of PiS was assessed retrospectively for the time before the onset of SCI and the time of the survey using a single-item question. A comprehensive set of independent variables was selected from the original questionnaire. Descriptive statistics, bivariate analyses and ordinal regressions were carried out. RESULTS: Data from 505 participants were analyzed. Twenty independent variables were selected for analyses. PiS decreased significantly from the time before the onset of SCI to the time of the survey (P<0.001). Sport levels were significantly lower in women than men for the time of the survey (P<0.001), whereas no difference was observed before onset of SCI (P=0.446). Persons with tetraplegia participated significantly less often in sport than persons with paraplegia (P<0.001). Lesion level, active membership in a club, frequency of PiS before the onset of SCI and the subjective evaluation of the importance of sport correlate with PiS. When controlling for gender differences, only the subjective importance of sport for persons with SCI determines PiS, particularly among women. CONCLUSIONS: Persons with tetraplegia and women need special attention when planning interventions to improve PiS. Furthermore, the subjective importance of sport is important for PiS, particularly among women, whereas most other factors were only weakly associated with PiS.

"It's a Good Idea to Put It Into Words": Writing 'Rudders' in the Initial Stages of Visualization Design.

Written language is a useful tool for non-visual creative activities like composing essays and planning searches. This paper investigates the integration of written language into the visualization design process. We create the idea of a 'writing rudder,' which acts as a guiding force or strategy for the designer. Via an interview study of 24 working visualization designers, we first established that only a minority of participants systematically use writing to aid in design. A second study with 15 visualization designers examined four different variants of written rudders: asking questions, stating conclusions, composing a narrative, and writing titles. Overall, participants had a positive reaction; designers recognized the benefits of explicitly writing down components of the design and indicated that they would use this approach in future design work. More specifically, two approaches - writing questions and writing conclusions/takeaways - were seen as beneficial across the design process, while writing narratives showed promise mainly for the creation stage. Although concerns around potential bias during data exploration were raised, participants also discussed strategies to mitigate such concerns. This paper contributes to a deeper understanding of the interplay between language and visualization, and proposes a straightforward, lightweight addition to the visualization design process.