Evaluation of Different Recruitment Methods: Longitudinal, Web-Based, Pan-European Physical Activity Through Sustainable Transport Approaches (PASTA) Project

ABSTRACT Background: Sufficient sample size and minimal sample bias are core requirements for empirical data analyses. Combining opportunistic recruitment with a Web-based survey and data-collection platform yields new benefits over traditional recruitment approaches. Objective: This paper aims to report the success of different recruitment methods and obtain data on participants’ characteristics, participation behavior, recruitment rates, and representativeness of the sample. Methods: A longitudinal, Web-based survey was implemented as part of the European PASTA (Physical Activity through Sustainable Transport Approaches) project, between November 2014 and December 2016. During this period, participants were recruited from 7 European cities on a rolling basis. A standardized guide on recruitment strategy was developed for all cities, to reach a sufficient number of adult participants. To make use of the strengths and minimize weakness, a combination of different opportunistic recruitment methods was applied. In addition, the random sampling approach was applied in the city of Örebro. To reduce the attrition rate and improve real-time monitoring, the Web-based platform featured a participant’s and a researchers’ user interface and dashboard. Results: Overall, 10,691 participants were recruited; most people found out about the survey through their workplace or employer (2300/10691, 21.51%), outreach promotion (2219/10691, 20.76%), and social media (1859/10691, 17.39%). The average number of questionnaires filled in per participant varied significantly between the cities (P<.001), with the highest number in Zurich (11.0, SE 0.33) and the lowest in Örebro (4.8, SE 0.17). Collaboration with local organizations, the use of Facebook and mailing lists, and direct street recruitment were the most effective approaches in reaching a high share of participants (P<.001). Considering the invested working hours, Facebook was one of the most time-efficient methods. Compared with the cities’ census data, the composition of study participants was broadly representative in terms of gender distribution; however, the study included younger and better-educated participants. Conclusions: We observed that offering a mixed recruitment approach was highly effective in achieving a high participation rate. The highest attrition rate and the lowest average number of questionnaires filled in per participant were observed in Örebro, which also recruited participants through random sampling. These findings suggest that people who are more interested in the topic are more willing to participate and stay in a survey than those who are selected randomly and may not have a strong connection to the research topic. Although direct face-to-face contacts were very effective with respect to the number of recruited participants, recruiting people through social media was not only effective but also very time efficient. The collected data are based on one of the largest recruited longitudinal samples with a common recruitment strategy in different European cities

Personal exposure to equivalent black carbon in children in Milan, Italy : Time-activity patterns and predictors by season

Air pollution is a global threat to public health, especially when considering susceptible populations, such as children. A better understanding of determinants of exposure could help epidemiologists in refining exposure assessment methods, and policy makers in identifying effective mitigation interventions. Through a participatory approach, 73 and 89 schoolchildren were involved in a two-season personal exposure monitoring campaign of equivalent black carbon (EBC) in Milan, Italy. GPS devices, time-activity diaries and a questionnaire were used to collect personal information. Exposure to EBC was 1.3 ± 1.5 μg/m3 and 3.9 ± 3.3 μg/m3 (mean ± sd) during the warm and the cold season, respectively. The highest peaks of exposure were detected during the home-to-school commute. Children received most of their daily dose at school and home (82%), but the highest dose/time intensity was related to transportation and outdoor environments. Linear mixed-effect models showed that meteorological variables were the most influencing predictors of personal exposure and inhaled dose, especially in the cold season. The total time spent in a car, duration of the home-to-school commute, and smoking habits of parents were important predictors as well. Our findings suggest that seasonality, time-activity and mobility patterns play an important role in explaining exposure patterns. Furthermore, by highlighting the contribution of traffic rush hours, transport-related microenvironments and traffic-related predictors, our study suggests that acting on a local scale could be an effective way of lowering personal exposure to EBC and inhaled dose of children in the city of Milan

Is a land use regression model capable of predicting the cleanest route to school?

Land Use Regression (LUR) modeling is a widely used technique to model the spatial variability of air pollutants in epidemiology. In this study, we explore whether a LUR model can predict home-to-school commuting exposure to black carbon (BC). During January and February 2019, 43 children walking to school were involved in a personal monitoring campaign measuring exposure to BC and tracking their home-to-school routes. At the same time, a previously developed LUR model for the study area was applied to estimate BC exposure on points along the route. Personal BC exposure varied widely with mean \ub1 SD of 9003 \ub1 4864 ng/m3. The comparison between the two methods showed good agreement (Pearson\u2019s r = 0.74, Lin\u2019s Concordance Correlation Coefficient = 0.6), suggesting that LUR estimates are capable of catching differences among routes and predicting the cleanest route. However, the model tends to underestimate absolute concentrations by 29% on average. A LUR model can be useful in predicting personal exposure and can help urban planners in Milan to build a healthier city for schoolchildren by promoting less polluted home-to-school routes

A Simple Nonviral Method to Generate Human Induced Pluripotent Stem Cells Using SMAR DNA Vectors

Induced pluripotent stem cells (iPSCs) are a powerful tool for biomedical research, but their production presents challenges and safety concerns. Yamanaka and Takahashi revolutionised the field by demonstrating that somatic cells could be reprogrammed into pluripotent cells by overexpressing four key factors for a sufficient time. iPSCs are typically generated using viruses or virus-based methods, which have drawbacks such as vector persistence, risk of insertional mutagenesis, and oncogenesis. The application of less harmful nonviral vectors is limited as conventional plasmids cannot deliver the levels or duration of the factors necessary from a single transfection. Hence, plasmids that are most often used for reprogramming employ the potentially oncogenic Epstein–Barr nuclear antigen 1 (EBNA-1) system to ensure adequate levels and persistence of expression. In this study, we explored the use of nonviral SMAR DNA vectors to reprogram human fibroblasts into iPSCs. We show for the first time that iPSCs can be generated using nonviral plasmids without the use of EBNA-1 and that these DNA vectors can provide sufficient expression to induce pluripotency. We describe an optimised reprogramming protocol using these vectors that can produce high-quality iPSCs with comparable pluripotency and cellular function to those generated with viruses or EBNA-1 vectors.</p

A Simple Nonviral Method to Generate Human Induced Pluripotent Stem Cells Using SMAR DNA Vectors

Induced pluripotent stem cells (iPSCs) are a powerful tool for biomedical research, but their production presents challenges and safety concerns. Yamanaka and Takahashi revolutionised the field by demonstrating that somatic cells could be reprogrammed into pluripotent cells by overexpressing four key factors for a sufficient time. iPSCs are typically generated using viruses or virus-based methods, which have drawbacks such as vector persistence, risk of insertional mutagenesis, and oncogenesis. The application of less harmful nonviral vectors is limited as conventional plasmids cannot deliver the levels or duration of the factors necessary from a single transfection. Hence, plasmids that are most often used for reprogramming employ the potentially oncogenic Epstein–Barr nuclear antigen 1 (EBNA-1) system to ensure adequate levels and persistence of expression. In this study, we explored the use of nonviral SMAR DNA vectors to reprogram human fibroblasts into iPSCs. We show for the first time that iPSCs can be generated using nonviral plasmids without the use of EBNA-1 and that these DNA vectors can provide sufficient expression to induce pluripotency. We describe an optimised reprogramming protocol using these vectors that can produce high-quality iPSCs with comparable pluripotency and cellular function to those generated with viruses or EBNA-1 vectors.</p

The Use of Flagella and Motility for Plant Colonization and Fitness by Different Strains of the Foodborne Pathogen Listeria monocytogenes

The role of flagella and motility in the attachment of the foodborne pathogen Listeria monocytogenes to various surfaces is mixed with some systems requiring flagella for an interaction and others needing only motility for cells to get to the surface. In nature this bacterium is a saprophyte and contaminated produce is an avenue for infection. Previous studies have documented the ability of this organism to attach to and colonize plant tissue. Motility mutants were generated in three wild type strains of L. monocytogenes by deleting either flaA, the gene encoding flagellin, or motAB, genes encoding part of the flagellar motor, and tested for both the ability to colonize sprouts and for the fitness of that colonization. The motAB mutants were not affected in the colonization of alfalfa, radish, and broccoli sprouts; however, some of the flaA mutants showed reduced colonization ability. The best colonizing wild type strain was reduced in colonization on all three sprout types as a result of a flaA deletion. A mutant in another background was only affected on alfalfa. The third, a poor alfalfa colonizer was not affected in colonization ability by any of the deletions. Fitness of colonization was measured in experiments of competition between mixtures of mutant and parent strains on sprouts. Here the flaA and motAB mutants of the three strain backgrounds were impaired in fitness of colonization of alfalfa and radish sprouts, and one strain background showed reduced fitness of both mutant types on broccoli sprouts. Together these data indicate a role for flagella for some strains to physically colonize some plants, while the fitness of that colonization is positively affected by motility in almost all cases

High-dose vs. standard-dose inactivated influenza vaccine and cardiovascular outcomes in persons with or without pre-existing atherosclerotic cardiovascular disease: the DANFLU-2 trial

Background and Aims: The aim was to evaluate and compare the relative vaccine effectiveness (rVE) of high-dose (HD-IIV) vs. standard-dose inactivated influenza vaccination (SD-IIV) on respiratory and cardiovascular outcomes in persons with or without pre-existing atherosclerotic cardiovascular disease (ASCVD). Methods: A prespecified exploratory analysis of a pragmatic, open-label, individually randomized trial conducted in Denmark during three influenza seasons. Adults ≥65 years were randomized 1:1 to HD-IIV or SD-IIV. Baseline and outcome data were collected through nationwide registries. The primary outcome was hospitalization for influenza or pneumonia. Major adverse cardiovascular events (MACE) was defined as a composite of cardiovascular death, hospitalization for myocardial infarction, or hospitalization for stroke. Heterogeneity in rVE among participants with vs. without ASCVD was assessed. Results: The incidence of all outcomes was higher in participants with pre-existing ASCVD (n = 46 825) vs. those without (n = 285 613). rVE was consistent among participants with and without ASCVD (all Pinteraction ≥ .05). The rVE for the primary outcome was 6.87% [95% confidence interval (CI), −2.52 to 15.42] among individuals without ASCVD and 4.71% (95% CI, −11.58 to 18.63) in those with (Pinteraction = .80). For influenza hospitalizations, the rVE was 42.88% (95% CI, 22.07–58.44) vs. 45.73% (95% CI, 16.68–65.16) in those without vs. with ASCVD (Pinteraction = .84). For MACE, the rVE was 4.29% (95% CI, −6.50 to 14.00) in participants without, and 0.30% (95% CI, −17.56 to 15.44) in participants with, pre-existing ASCVD (Pinteraction = .68). Conclusions: Among individuals ≥65 years, the rVE of HD-IIV vs. SD-IIV against respiratory and cardiovascular outcomes was similar among those with vs. without pre-existing ASCVD

High-dose vs. standard-dose influenza vaccine in heart failure: a prespecified analysis of the DANFLU-2 trial

Background: Influenza contributes substantially to disease burden in individuals with heart failure (HF) and is an established trigger of cardiovascular (CV) and HF events. Standard-dose inactivated influenza vaccine (SD-IIV) is recommended for HF, though immune responses may be attenuated. High-dose IIV (HD-IIV) was developed to enhance immunogenicity, but its effectiveness compared with SD-IIV against hospitalization for influenza and CV disease by HF status remains uncertain. Methods: This was a prespecified analysis of a pragmatic, prospective, individually randomized, open-label trial with registry-based endpoint-evaluation conducted in Denmark across the 2022/2023 to 2024/2025 influenza seasons. Citizens ≥65 years were randomized 1:1 to HD-IIV or SD-IIV. Outcomes included hospitalization for influenza-related illness, laboratory-confirmed influenza (LCI), any CV disease, cardio-respiratory disease, and HF, assessed by HF status. Effect of HD-IIV vs. SD-IIV in reducing risk of outcomes assessed was expressed as risk ratios (RR). Results: The trial randomized 332,438 participants (48.6% female, mean age 73.7±5.8 years), including 10,410 with HF at baseline (27.4% female, mean age 76.0±6.3 years). Overall, HD-IIV was associated with a statistically significant lower incidence of hospitalization for influenza-related illness, LCI, cardio-respiratory disease, CV disease, and HF compared with SD-IIV. In participants with HF, effect estimates were similar: RR for influenza-related hospitalization was 0.48 (95%CI, 0.20-1.06; pinteraction=0.64), for LCI hospitalization 0.55 (95%CI, 0.29-1.02; pinteraction=0.59), for cardio-respiratory hospitalization 0.89 (95%CI, 0.77-1.02; pinteraction=0.34), for CV hospitalization 0.86 (95%CI, 0.72-1.02; pinteraction=0.34), and for HF hospitalization 0.82 (95%CI, 0.61-1.11; pinteraction=0.83). Findings were consistent across HF subgroups by disease duration, recency of hospitalization, most recent N-terminal pro-B-type natriuretic peptide, and presence of device therapy. Conclusions: In this prespecified exploratory analysis of the largest individually randomized influenza vaccine trial ever conducted, HD-IIV was associated with lower rates of influenza and CV hospitalizations compared with SD-IIV, with effect estimates similar across HF status at baseline and HF subgroups

Epidural Analgesia with Ropivacaine during Labour in a Patient with a SCN5A Gene Mutation

SCN5A gene mutations can lead to ion channel defects which can cause cardiac conduction disturbances. In the presence of specific ECG characteristics, this mutation is called Brugada syndrome. Many drugs are associated with adverse events, making anesthesia in patients with SCN5A gene mutations or Brugada syndrome challenging. In this case report, we describe a pregnant patient with this mutation who received epidural analgesia using low dose ropivacaine and sufentanil during labour

Risk of Myocarditis or Pericarditis With High-Dose vs Standard-Dose Influenza Vaccine:A Prespecified Secondary Analysis of the Randomized DANFLU-2 Trial

IntroductionInfluenza infection is associated with an increased risk of myocarditis and pericarditis.1 Although such cardiac complications are rare and usually mild, they may lead to cardiogenic shock or cardiac tamponade. The high-dose inactivated influenza vaccine (HD-IIV) significantly reduces the incidence of laboratory-confirmed influenza infection compared with standard-dose IIVs (SD-IIVs) among older adults.2 However, it is unknown whether HD-IIV reduces the risk of myocarditis or pericarditis, and it has not previously been possible to explore this hypothesis given the large sample size needed. This prespecified analysis of the trial A Pragmatic Randomized Trial to Evaluate the Effectiveness of High-Dose Influenza Vaccine vs Standard-Dose Influenza Vaccine in Older Adults (DANFLU-2)3 examined the risk of myocarditis or pericarditis with HD-IIV vs SD-IIV.MethodsThis prespecified secondary analysis of a randomized clinical trial used data from the DANFLU-2 trial,3 as did another secondary analysis.4 The trial is registered (NCT05517174), and the protocol indicating prespecification of this analysis is included in Supplement 1. In brief, DANFLU-2 was a pragmatic (ie, with broadened generalizability via more representative populations studied in routine settings), registry-based, open-label, randomized clinical trial of adults aged 65 years or older conducted in Denmark during the 2022-2023, 2023-2024, and 2024-2025 influenza seasons. Participants were randomized 1:1 to HD-IIV or SD-IIV. The trial was approved by the Danish Medical Research Ethics Committees and Danish Medicines Agency. All participants provided informed consent, granting access to registry data and medical records. Approval and consent extend to this study, which is reported according to the CONSORT reporting guideline.Baseline and outcome data were collected through linkage to nationwide health registries. During each study season, participants were followed up from day 14 after vaccination through May 31 the following year. The primary outcome was hospitalization for influenza or pneumonia. As an exploratory outcome, this study examined the risk of hospitalization for myocarditis (defined as International Statistical Classification of Diseases and Related Health Problems, Tenth Revision [ICD-10] codes I40-I41) or pericarditis (defined as ICD-10 codes I30-I31) in the 2 randomization groups. Relative vaccine effectiveness ( [1 − relative risk] × 100%) based on first events was reported, with 95% CIs constructed using the exact Clopper-Pearson method for binomial proportions. Events occurring before 14 days after vaccination were included in a sensitivity analysis. Consistency of the treatment effect was assessed across baseline characteristics and conditions, with no adjustment for multiplicity. Interactions were assessed using the Cochran-Mantel-Haenszel test for homogeneity. We considered 2-sided P values &lt; .05 statistically significant. Statistical analysis was performed using SAS version 9.4 (SAS Institute), Stata MP version 19.5 (StataCorp), and R version 4.3.3 (R Project for Statistical Computing).ResultsOf 332 438 participants randomized, 1295 (mean [SD] age, 74.2 [5.7] years; 884 men [68.3%]) had a prior history of myocarditis or pericarditis, including 97 with prior myocarditis and 1218 with prior pericarditis, and 331 143 did not (mean [SD] age, 73.7 [5.8] years; 170 016 men [51.3%]) (Table). Baseline characteristics were balanced across HD-IIV and SD-IIV groups. Individuals with prior myocarditis or pericarditis were older, more often men, and had a higher prevalence of comorbidities. The incidence of myocarditis or pericarditis was lower among participants randomized to HD-IIV vs SD-IIV (19 vs 35 events; relative vaccine effectiveness, 45.71%; 95% CI, 2.46%-70.67%; P = .04) (Figure). Results were consistent when events occurring before 14 days were included. No interactions were detected