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A total diet study (TDS) is a public health tool for determination of population dietary exposure to chemicals across the entire diet. TDSs have been performed in several countries but the comparability of data produced is limited. Harmonisation of the TDS methodology is therefore desirable and the development of comparable TDS food lists is considered essential to achieve the consistency between countries. The aim of this study is to develop and test the feasibility of a method for establishing harmonised TDS food and sample lists in five European countries with different consumption patterns (Czech Republic, Finland, Germany, Iceland and Portugal). The food lists were intended to be applicable for exposure assessment of wide range of chemical substances in adults (18–64 years) and the elderly (65–74 years). Food consumption data from recent dietary surveys measured on individuals served as the basis for this work. Since the national data from these five countries were not comparable, all foods were linked to the EFSA FoodEx2 classification and description system. The selection of foods for TDS was based on the weight of food consumed and was carried out separately for each FoodEx2 level 1 food group. Individual food approach was respected as much as possible when the TDS samples were defined. TDS food lists developed with this approach represented 94.7–98.7% of the national total diet weights. The overall number of TDS samples varied from 128 in Finland to 246 in Germany. The suggested method was successfully implemented in all five countries. Mapping of data to the EFSA FoodEx2 coding system was recognised as a crucial step in harmonisation of the developed TDS food lists.

According to much of the literature, partisanship in Britain exercises little independent influence on the vote but merely reflects voters’ prospective and retrospective evaluations of the parties’ performance with regard to their management of the economy, national security, and public services. In this view, partisanship comes close to Fiorina’s model of a “running tally” of political experiences. Similarly, Dalton’s notion of “cognitive mobilization” suggests that seeking out political information should undermine both the need for and the likelihood of party identification. Applying Mixed Markov Latent Class Analysis to the British Election Study Panel 1997–2000, we challenge these perceptions by demonstrating that partisanship is more stable than previously thought, and that high levels of political interest are linked to higher levels of partisanship and possible also to higher levels of stability. This is much more in line with classic ideas about party identification than with “revisionist” critiques of the Michigan model, and with current models of political cognition. Moreover, it suggests that political interest renders affective ties more powerful in stabilizing themselves.

Background: This review, which focused on faculty development initiatives designed to improve teaching effectiveness, synthesized findings related to intervention types, study characteristics, individual and organizational outcomes, key features, and community building. Methods: This review included 111 studies (between 2002 and 2012) that met the review criteria. Findings: Overall satisfaction with faculty development programs was high. Participants reported increased confidence, enthusiasm, and awareness of effective educational practices. Gains in knowledge and skills, and self-reported changes in teaching behaviors, were frequently noted. Observed behavior changes included enhanced teaching practices, new educational initiatives, new leadership positions, and increased academic output. Organizational changes were infrequently explored. Key features included evidence-informed educational design, relevant content, experiential learning, feedback and reflection, educational projects, intentional community building, longitudinal program design, and institutional support. Conclusion: This review holds implications for practice and research. Moving forward, we should build on current success, broaden the focus beyond individual teaching effectiveness, develop programs that extend over time, promote workplace learning, foster community development, and secure institutional support. We should also embed studies in a theoretical framework, conduct more qualitative and mixed methods studies, assess behavioral and organizational change, evaluate transfer to practice, analyse key features, and explore the role of faculty development within the larger organizational context.

Global threats to freshwater resources are prompting widespread concern about their management and implications for well-being. In recent decades, hydrologic ecosystem services (HES) have emerged as an innovative concept to evaluate freshwater resources, providing opportunity for researchers to engage in decision-relevant science. We conducted a systematic review of studies published within the last decade, documenting approaches for mapping and quantifying HES and classifying the decision context. To gauge the relevance of HES science, we evaluated 49 case studies using multiple criteria for credibility, legitimacy, and saliency. We found compelling evidence that much of the variability in the quantification of HES can be explained by research motivations and scoping, reflecting the decision-oriented framing of the ecosystem services concept. Our review highlights key knowledge gaps in the state of the science including the need to articulate beneficiaries and to make connections to policy and management more explicit. To strengthen the potential for impact of HES science, we provide recommendations to assist researchers, practitioners, and decision-makers in identifying goals, formulating relevant questions, and selecting informative approaches for quantifying HES. We argue that sustained progress in applying HES requires critical evaluation and careful framing to link science and practice.

Citations are to ‘citable documents’ (BioRxiv article. To facilitate direct comparison, distributions are plotted with the same range of citations (0-100) in each plot; articles with more than 100 citations are shown as a single bar at the right of each plot. Copyright held by Thomson Reuters prohibits publication of the raw data.

Introduction: It has been proposed that deluded and delusion-prone individuals gather less evidence before forming beliefs than those who are not deluded or delusion-prone. The primary source of evidence for this “jumping to conclusions” (JTC) bias is provided by research that utilises the “beads task” data-gathering paradigm. However, the cognitive mechanisms subserving data gathering in this task are poorly understood. Methods: In the largest published beads task study to date (n = 558), we examined data gathering in the context of influential dual-process theories of reasoning. Results: Analytic cognitive style (the willingness or disposition to critically evaluate outputs from intuitive processing and engage in effortful analytic processing) predicted data gathering in a non-clinical sample, but delusional ideation did not. Conclusion: The relationship between data gathering and analytic cognitive style suggests that dual-process theories of reasoning can contribute to our understanding of the beads task. It is not clear why delusional ideation was not found to be associated with data gathering or analytic cognitive style.

A set of process-related barriers negatively determines the effectiveness of Environmental Impact Assessment (EIA) in transport planning. Recent research highlights the unstructured stakeholder involvement and inefficient public participation in earlier phases of EIA as key bottlenecks. While the academic literature has produced promising theories for addressing these barriers, they have rarely been translated into solutions applicable and testable in practice. In order to bridge this theory–practice gap, we present a systematic literature review of interventions and mechanisms aimed at facilitating the integration of different sources and types of knowledge during the scoping phase of EIA. This review explores if and how interventions and mechanisms have been conducted in practice; if and why they worked or did not work and how relevant they are for EIA in transport planning. Based on this review, we distil a set of three specific interventions and trigger mechanisms applicable in the context of EIA in transport planning.

The linkage between precipitation and recharge is still poorly understood in the Central America region. This study focuses on stable isotopic composition in precipitation and groundwater in the northern mountainous region of the Central Valley of Costa Rica. During the dry season, rainfall samples corresponded to enriched events with high deuterium excess. By mid-May, the Intertropical Convergence Zone poses over Costa Rica resulting in a depletion of 18O/16O and 2H/H ratios. A parsimonious four-variable regression model (r2 = 0.52) was able to predict daily δ18O in precipitation. Air mass back trajectories indicated a combination of Caribbean Sea and Pacific Ocean sources, which is clearly depicted in groundwater isoscape. Aquifers relying on Pacific-originated recharge exhibited a more depleted pattern, whereas recharge areas relying on Caribbean parental moisture showed an enrichment trend. These results can be used to enhance modelling efforts in Central America where scarcity of long-term data limits water resources management plans.

Objective: Bariatric surgery is the most efficient treatment of severe obesity. We investigated to what extent BMI- or waist-hip ratio (WHR)-related genetic variants are associated with excess BMI loss (EBMIL) two years after Roux-en-Y gastric bypass (RYGB) surgery, and elucidated the affected biological pathways. Methods: Two-hundred fifty-one obese patients (age: 43 ± 10.7, preoperative BMI: 45.1 ± 6.1 kg/m2, 186 women) underwent RYGB surgery and were followed up after two years with regard to BMI. Patients were genotyped for 32 single-nucleotide polymorphisms (SNPs) that were investigated with regard to their impact on response to RYGB and preoperatively measured Three Factor Eating Questionnaire (TFEQ) scores. Results: Homozygous T carriers of the SNP rs4846567 in proximity to the Lysophospholipase-like 1 (LYPLAL1) gene showed a 7% higher EBMIL compared to wild-type and heterozygous carriers (p = 0.031). TT-allele carriers showed furthermore lower scores for Hunger (74%, p < 0.001), lower Disinhibition (53%, p < 0.001), and higher Cognitive restraint (21%, p = 0.017) than GG/GT carriers in the TFEQ. Patients within the lowest quartile of Hunger scores had a 32% greater EBMIL compared to patients in the highest quartile (p < 0.001). Conclusion: The LYPLAL1 genotype is associated with differences in eating behavior and loss of extensive body weight following RYGB surgery. Genotyping and the use of eating behavior-related questionnaires may help to estimate the RYGB-associated therapy success.

Articles publicats durant l'any 2013 en revistes d'accés obert que han rebut ajut de la UB

Ajuts concedits per publicar en revistes d'accés obert des del setembre de 2010 fins a desembre de 2015 per part del vicerectorat de Política Científica de la Universitat de Barcelona.

Antioxidant modification for C/C composites by in situ hydrothermal synthesise at 140 °C of a 4ZnO·B2O3·H2O crystallite coating has been successfully achieved. The influence of hydrothermal time on the phase composition, microstructure of the as-prepared Zn4B2O7·H2O (4ZnO·B2O3·H2O), and its antioxidant modification for C/C composites were investigated. Samples were characterised by XRD, SEM, isothermal oxidation test and TG-DSC. Results show that, 4ZnO·B2O3·H2O crystalline coating is achieved on the surface of C/C composites after the hydrothermal treatment at 140 °C for time in the range of 2–12 h. A smooth and crack-free 4ZnO·B2O3·H2O layer can be obtained when the hydrothermal time reaches 8 h. Isothermal oxidation test demonstrates that the oxidation resistance of C/C composites is improved. The as-modified composites exhibit only 1.52 g·cm−2 weight loss after oxidation at 600 °C for 15 h, while the non-modified one shows a 6.57 g·cm−2 weight loss after only 10 h oxidation. For the uncoated C/C composite the oxidation rate is approximately linear with time (non-protective oxidation), thus at 15 h exposure one can estimate the mass loss to be 6.57 g·cm−2 after 10 h for direct comparison with the coated samples.

Background: Manual delineation of structures in head and neck cancers is an extremely time-consuming and labor-intensive procedure. With centers worldwide moving towards the use of intensity-modulated radiotherapy and adaptive radiotherapy, there is a need to explore and analyze auto-segmentation (AS) software, in the search for a faster yet accurate method of structure delineation. Material and methods: A search for studies published after 2005 comparing AS and manual delineation in contouring organ at risks (OARs) and target volume for head and neck patients was conducted. The reviewed results were then categorized into arguments proposing and opposing the review title. Results: Ten studies were reviewed and derived results were assessed in terms of delineation time-saving ability and extent of delineation accuracy. The influence of other external factors (observer variability, AS strategies adopted and stage of disease) were also considered. Results were conflicting with some studies demonstrating great potential in replacing manual delineation whereas other studies illustrated otherwise. Six of 10 studies investigated time saving; the largest time saving reported being 59%. However, one study found that additional time of 15.7% was required for AS. Four studies reported AS contours to be between ‘reasonably good’ and ‘better quality’ than the clinically used contours. Remaining studies cited lack of contrast, AS strategy used and the need for physician intervention as limitations in the standardized use of AS. Discussion: The studies demonstrated significant potential of AS as a useful delineation tool in contouring target volumes and OARs in head and neck cancers. However, it is evident that AS cannot totally replace manual delineation in contouring some structures in the head and neck and cannot be used independently without human intervention. It is also emphasized that delineation studies should be conducted locally so a

Pathways of platelet activation that are not targeted by current antithrombotic therapy may be crucial for the development of ischemic events in patients undergoing coronary angiography. We therefore investigated whether in vivo and thrombin receptor activating peptide (TRAP)-stimulated platelet activation and monocyte-platelet aggregate (MPA) levels can serve as independent risk markers for adverse outcomes in aspirin-treated patients presenting for cardiac catheterization. In vivo and TRAP-stimulated platelet surface P-selectin, activated glycoprotein IIb/IIIa (GPIIb/IIIa) and MPA levels were determined in 682 consecutive patients undergoing cardiac catheterization and in 47 healthy controls. Two-year follow-up data were obtained from 562 patients. In vivo platelet surface P-selectin, activated GPIIb/IIIa and MPA levels were significantly higher in patients with angiographically-proven coronary artery disease than in healthy controls (all p≤0.02). Patients with an acute coronary syndrome (ACS; n=125) had significantly higher levels of in vivo MPA than patients without ACS (n=437; p=0.01). In the overall study population (n=562) the surface expression of P-selectin and activated GPIIb/IIIa, and the levels of MPA in vivo and in response to TRAP were similar in patients without and with subsequent ischemic events (all p>0.05). Similar results were obtained when only patients with angiographically-proven coronary artery disease (n=459), stent implantation (n=205) or ACS (n=125) were analyzed. Receiver-operating characteristic curve analyses did not reveal cut-off values for P-selectin, activated GPIIb/IIIa, and MPA levels for the prediction of ischemic events. In conclusion, in vivo and TRAP-stimulated platelet activation and MPA levels did not predict adverse ischemic outcomes in aspirin-treated patients presenting for cardiac catheterization.

Inhibition of prosurvival BCL2 family members can induce autophagy, but the mechanism is controversial. We have provided genetic evidence that BCL2 family members block autophagy by inhibiting BAX and BAK1, but others have proposed they instead inhibit BECN1. Here we confirm that small molecule BH3 mimetics can induce BAX- and BAK1-independent MAP1LC3B/LC3B lipidation, but this only occurred at concentrations far greater than required to induce apoptosis and dissociate canonical BH3 domain-containing proteins that bind more tightly than BECN1. Because high concentrations of a less-active enantiomer of ABT-263 also induced BAX- and BAK1-independent LC3B lipidation, induction of this marker of autophagy appears to be an off-target effect. Indeed, robust autophagic flux was not induced by BH3 mimetic compounds in the absence of BAX and BAK1. Therefore at concentrations that are on target and achievable in vivo, BH3 mimetics only induce autophagy in a BAX- and BAK1-dependent manner.

CYP1B1 mutational screening in a Portuguese cohort of primary congenital glaucoma patients

Desktop three-dimensional (3D) printers are becoming commonplace in business offices, public libraries, university labs and classrooms, and even private homes; however, these settings are generally not designed for exposure control. Prior experience with a variety of office equipment devices such as laser printers that emit ultrafine particles (UFP) suggests the need to characterize 3D printer emissions to enable reliable risk assessment. The aim of this study was to examine factors that influence particulate emissions from 3D printers and characterize their physical properties to inform risk assessment. Emissions were evaluated in a 0.5-m3 chamber and in a small room (32.7 m3) using real-time instrumentation to measure particle number, size distribution, mass, and surface area. Factors evaluated included filament composition and color, as well as the manufacturer-provided printer emissions control technologies while printing an object. Filament type significantly influenced emissions, with acrylonitrile butadiene styrene (ABS) emitting larger particles than polylactic acid (PLA), which may have been the result of agglomeration. Geometric mean particle sizes and total particle (TP) number and mass emissions differed significantly among colors of a given filament type. Use of a cover on the printer reduced TP emissions by a factor of 2. Lung deposition calculations indicated a threefold higher PLA particle deposition in alveoli compared to ABS. Desktop 3D printers emit high levels of UFP, which are released into indoor environments where adequate ventilation may not be present to control emissions. Emissions in nonindustrial settings need to be reduced through the use of a hierarchy of controls, beginning with device design, followed by engineering controls (ventilation) and administrative controls such as choice of filament composition and color.

A common problem in formulating models for the relative risk and risk difference is the variation dependence between these parameters and the baseline risk, which is a nuisance model. We address this problem by proposing the conditional log odds-product as a preferred nuisance model. This novel nuisance model facilitates maximum-likelihood estimation, but also permits doubly-robust estimation for the parameters of interest. Our approach is illustrated via simulations and a data analysis.

Pain disorders affect a large number of individuals throughout the world and are costly. Although randomized clinical trials assess the efficacy (i.e., how well treatments work in controlled settings) of pain pharmacotherapy, clinical trials do not assess effectiveness (i.e., how well treatments work in real-world settings). The number of observational studies that use real-world data to assess the effectiveness of medications is increasing rapidly in many disease areas. It is important for clinicians to understand how real-world data may be used to assess the effectiveness of medications. This paper aims to review the current body of literature assessing the effectiveness of pain pharmacotherapy using medical records. To do this, a literature search was conducted to identify papers published between January 2013 and September 2015 that examined the effectiveness of pain pharmacotherapy using electronic medical records. The search found only three papers meeting these criteria, which were described, reviewed, and critiqued in this paper. Electronic medical records are an underutilized source of data to assess pain outcomes in real-world settings. Although there are many methodological challenges in using these data, there is also great opportunity to impact clinical practice and explore the real-world effectiveness of pharmacotherapy used in pain management.

The aim of this study was to investigate the validity and measurement agreement of a smartphone pedometer application and a traditional pedometer, both compared to manual step count, in six environments. The study also examined the relative reliability of two positions of the smartphone pedometer application in the six environments. Twenty participants carried two smartphones (iPhone 4S) with the same pedometer application (Pedometer FREE GPS+) in two device positions together with a traditional pedometer (Yamax LS2000) while walking in six environments. The pedometer application in the chest position (app chest) differed significantly from the manual step count when walking uphill (p = 0.003), the application in the trouser (pants) position (app pants) differed for downhill (p = 0.001) and the traditional pedometer (trad ped) differed upstairs (p = 0.007). The measurement agreement was high for app pants uphill, app chest downhill and trad ped downstairs. The relative reliability was fair for app chest, but poor for app pants. In conclusion, the pedometer application and traditional pedometer were valid for step self-monitoring in some environments, and the measurement agreement compared to manual step count was mainly medium to high. The relative reliability for the smartphone pedometer application was partly acceptable. Smartphones could be useful in some environments for physical activity self-monitoring.

Objective: The aim of this study was to develop a theory-based questionnaire to measure road-crossing attitudes and potentially risky pedestrian behavior. Methods: A cross sectional validation study was carried out on a total sample of 380 young adults aged 18 to 25 years who live in Tehran, Iran. Data was collected during 27 Jan to 20 May 2015 using a self-administered structured pool of 76 items which was developed from research on Theory of Planned Behavior. A panel of subject matter experts evaluated the items for content validity index and content validity ratio and the questionnaire was pretested. Exploratory factor analysis (EFA) was performed to test construct validity. The Cronbach's alpha coefficient and Intraclass Correlation Coefficient (ICC) analyses were done to assess internal consistency and stability of the scale. Results: From the initial 76 items, 38 items were found to be appropriate for assessing the Pedestrian Road Crossing Behavior (PEROB) of young adults in Tehran. A nine-factor solution revealed an exploratory factor analysis that jointly accounted for 63.8% of the variance observed. Additional analyses also indicated acceptable results for the internal consistency with Cronbach's alpha value ranging from 0.67 to 0.88 and Intraclass Correlation Coefficients (ICC) values ranging from 0.64 to 0.96. Conclusions: This psychometric evaluation of a self-administered instrument resulted in a reliable and valid instrument to assess young adult pedestrians' self-reported road crossing attitudes and behaviors in Tehran. Further development of the instrument is needed to assess its applicability to other road users, particularly older pedestrians.

One of the main challenges of teaching statistics to engineering students is to convey the importance of being conscious of the presence of variability and of taking it into account when making technical and managerial decisions. Often, technical subjects are explained in an ideal and deterministic environment. This article shows the possibilities of simple electrical circuits—the Wheatstone Bridge among them—to explain to students how to characterize variability, how it is transmitted, and how it affects decisions. Additionally, they can be used to introduce the importance of robustness by showing that taking into account the variability of components allows the design of cheaper products with greater benefits than if one were to simply apply formulas that consider variables as exact values. The results are quite unexpected, and they arouse the interest and motivation of students. Supplementary materials for this article are available online.

The design, synthesis, structure, and in vitro anticancer and antimycobacterial activity of new hybrid imidazole (benzimidazole)/pyridine (quinoline) derivatives are described. The strategy adopted for synthesis is straight and efficient, involving a three-step setup procedure: N-acylation, N-alkylation, and quaternization of nitrogen heterocycle. The solubility in microbiological medium and anticancer and antimycobacterial activity of a selection of new synthesized compounds were evaluated. The hybrid derivatives have an excellent solubility in microbiological medium, which make them promising from the pharmacological properties point of view. One of the hybrid compounds, 9 (with a benzimidazole and 8-aminoquinoline skeleton), exhibits a very good and selective antitumor activity against Renal Cancer A498 and Breast Cancer MDA-MB-468. Moreover, the anticancer assay suggests that the hybrid Imz (Bimz)/2-AP (8-AQ) compounds present a specific affinity to Renal Cancer A498. Concerning the antimycobacterial activity, only the hybrid compound, 9, has a significant activity. SAR correlations have been performed.

Introduction: Several studies suggested a possible association between certain polymorphisms in the N-acetyl-transferase 2 (NAT2) gene (which encodes a very important enzyme involved in xenobiotic metabolism) and the risk for Parkinson’s disease (PD). As the results of studies on this issue are controversial, we conducted a systematic review and a meta-analysis of eligible studies on this putative association. Areas covered: The authors revised the relationship between NAT2 polymorphisms and the risk of developing PD using several databases, and performed a meta-analysis using the software Meta-Disc1.1.1. In addition heterogeneity between studies was analyzed. A description of studies regarding gene-gene interactions and gene-environmental interactions involving NAT2 polymorphisms is also made. Expert opinion: Despite several recent meta-analyses showing an association between several polymorphisms in genes related with detoxification mechanisms such as cytochrome P4502D6 (CYP2D6), and glutathione transferases M1 and T1 (GSTM1, and GSTT1), data on NAT2 gene polymorphisms obtained from the current meta-analysis do not support a major association with PD risk, except in Asian populations. However, data from many studies are incomplete and therefore insufficient data exists to draw definitive conclusions. Several studies suggesting gene-gene and gene-environmental factors involving NAT2 gene in PD risk await confirmation.

This study examined relational-uncertainty perceptions (a form of cognitive appraisal) to investigate how partners in 272 heterosexual couples responded emotionally to a relationship-challenging event. Participants rated themselves on attachment anxiety and avoidance. Then, after listing a challenging event, they rated how uncertain it made them about their own and their partner's continued involvement in the relationship. Participants also rated how angry and fearful the event made them. An Actor-Partner Interdependence Model yielded three sets of results. First, actor effects from insecure attachment orientations to episodic relational uncertainty emerged. Second, proposed mediation between attachment orientations and emotional reactions by uncertainty was partially supported (perceived partner-uncertainty partially mediated the positive association of anxious attachment and fear, and self-uncertainty partially mediated the positive relation between avoidant attachment and anger). Finally, a partner effect was found between one couple member's avoidant attachment and the other's perceived partner uncertainty. Men and women exhibited similar findings.

Hypoxia induces protective autophagy in glioblastoma cells and new therapeutic avenues that target this process may improve the outcome for glioblastoma patients. Recent studies have suggested that the autophagic process is upregulated in glioblastomas in response to extensive hypoxia. Hypoxia also induces the upregulation of a specific set of proteins and microRNAs (miRNAs) in a variety of cell types. IL6 (interleukin 6), an inflammatory autocrine and paracrine cytokine that is overexpressed in glioblastoma, has been reported to be a biomarker for poor prognosis because of its tumor-promoting effects. Here, we describe a novel tumor-promoting mechanism of IL6, whereby hypoxia-induced IL6 acts as a potent initiator of autophagy in glioblastoma via the phosphorylated (p)-STAT3-MIR155-3p pathway. IL6 and p-STAT3 levels correlated with the abundance of autophagic cells and HIF1A levels in human glioma tissues and with the grade of human glioma, whereas inhibition of exogenous or endogenous IL6 repressed autophagy in glioblastoma cells in vitro. Knockdown of endogenous MIR155-3p inhibited IL6-induced autophagy, and enforced expression of MIR155-3p restored the anti-autophagic activity of IL6 inhibitors. We show that the hypoxia-IL6-p-STAT3-MIR155-3p-CREBRF-CREB3-ATG5 pathway plays a central role in malignant glioma progression, with blockade of the IL6 receptor by tocilizumab demonstrating a certain level of therapeutic efficacy in a xenograft model in vivo, especially in combination with temozolomide. Moreover, tocilizumab inhibits autophagy by promoting tumor apoptosis. Collectively, our findings provide new insight into the molecular mechanisms underlying hypoxia-induced glioma cell autophagy and point toward a possible efficacious adjuvant therapy for glioblastoma patients.

Objective:In recent HIV intervention trials, intervention efficacies appear to decline over time. Researchers have attributed this to “waning,” or a loss of intervention efficacy. Another possible reason is heterogeneity in infection risk or “frailty.” We propose an approach to assessing the impact of frailty and waning on measures of intervention efficacy and statistical power in randomized-controlled trials. Methods:Using multiplicative risk reduction, we developed a mathematical formulation for computing disease incidence and the incidence rate ratio (IRR) as a function of frailty and waning. We designed study scenarios, which held study-related factors constant, varied waning and frailty parameters and measured the change in disease incidence, IRR, and statistical power. Results:We found that frailty alone can impact disease incidence over time. However, frailty has minimal impact on the IRR. The factor that has the greatest influence on the IRR is intervention efficacy and the degree to which it is projected to wane. We also found that even moderate waning can cause an unacceptable decrease in statistical power while the impact of frailty on statistical power is minimal. Discussion:We conclude that frailty has minimal impact on trial results relative to intervention efficacy. Study resources would, therefore, be better spent on efforts to keep the intervention efficacy constant throughout the trial (e.g., enhancing the vaccine schedule or promoting treatment adherence).