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Abstract Follicular lymphoma (FL) is a clinically heterogeneous disease. The need for treatment, treatment sequencing, number of treatment lines, and its association with survival have not been described in a population‐based setting. We identified all patients diagnosed with FL in the Swedish Lymphoma register from 2007 to 2014, followed until 2020, with detailed data on progression/relapse, transformation, and 2nd and further lines of therapy. During a median follow‐up of 6.8 years, 1226 patients (69%) received 1st systemic treatment, 358 patients (20%) were managed with watch‐and‐wait (WaW) only, and 188 (10%) patients were treated with radiotherapy and did not require additional therapy during the study period. Among patients starting systemic treatment, 496 (40%), 224 (18%), and 88 (7%) received 2nd‐, 3rd‐, or 4th‐line therapy, respectively. The 10‐year cause‐specific cumulative incidence of transformation was 13%. Among patients managed with 1st line R‐single, R‐CHOP, or BR, 54%, 33%, and 29% required 2nd line, respectively. The cumulative probability of starting subsequent treatment within 2 years was 26% after 1st line and 35% after 2nd line treatment. Two‐year OS following 1st, 2nd, 3rd, and 4th line systemic treatment was 84%, 70%, 52%, and 36%, respectively, and remained similar when excluding transformations. We conclude that a substantial proportion of FL patients can be managed with WaW for a long period of time, while patients who require multiple treatment lines constitute a group with a large clinical unmet need. These results constitute valuable real‐world reference data for FL.

Abstract Objective Adjuvant chemotherapy is often indicated in patients diagnosed with early breast cancer (EBC). Among others, weight gain is one of the observed side effects of both chemotherapy and other cancer treatments; however, the mechanism is not well‐described. In this study, we aimed to assess thyroid function before and shortly after the course of chemotherapy for EBC. Methods This is a prospective cohort study of women diagnosed with EBC. The main outcome was the thyroid function and body weight before and after completing chemotherapy. Secondary outcomes were the presence of thyroid autoantibodies and treatment radiation dosage. We included 72 patients treated with adjuvant chemotherapy, whereas 59 patients also received supraclavicular locoregional radiotherapy. Triple‐negative breast cancer (BC) patients receiving chemoimmunotherapy were excluded. Results After the chemotherapy, we observed an increase in thyroid‐stimulating hormone (p = 0.03) and a decrease in free‐thyroxine (p = 0.0006), with no significant weight change. The prevalence of autoimmune thyroiditis was low. On average 3 months post‐chemo, we found no statistically significant difference in the thyroid function of women treated versus not treated with supraclavicular locoregional radiotherapy. Conclusions Although statistically significant changes in thyroid hormones were observed, this study suggests no obvious clinically significant changes in thyroid function in women with early BC after the course of chemotherapy. The decrease in thyroid function was not related to autoimmunity, non‐thyroidal illness, radiotherapy, or high‐dose corticosteroids. Further studies with a longer follow‐up of thyroid function after adjuvant chemotherapy and supraclavicular locoregional radiotherapy are needed.

Background The aim of this study was to investigate temporal trends in survival and subsequent cardiovascular events in a nationwide myocardial infarction population with and without diabetes. Methods and Results Between 2006 and 2020, we identified 2527 individuals with type 1 diabetes, 48 321 individuals with type 2 diabetes and 243 170 individuals without diabetes with first myocardial infarction in national health care registries. Outcomes were trends in all‐cause death after 30 and 365 days, cardiovascular death and major adverse cardiovascular events (ie, nonfatal stroke, nonfatal myocardial infarction, cardiovascular death, and heart failure hospitalization). Pseudo‐observations were used to estimate the mortality risk, with 95% CIs, using linear regression, adjusted for age and sex. Individuals with type 1 diabetes were younger (62±12.2 years) and more often women (43.6%) compared with individuals with type 2 diabetes (75±10.8 years; women, 38.1%), and individuals without diabetes (73±13.2 years; women, 38.4%). Early death decreased in people without diabetes from 23.1% to 17.5%, (annual change −0.48% [95% CI, −0.52% to −0.44%]) and in people with type 2 diabetes from 22.6% to 19.3% (annual change, −0.33% [95% CI, −0.43% to −0.24%]), with no such significant trend in people with type 1 diabetes from 23.8% to 21.7% (annual change, −0.18% [95% CI, −0.53% to 0.17%]). Similar trends were observed with regard to 1‐year death, cardiovascular death, and major adverse cardiovascular events. Conclusions During the past 15 years, the trend in survival and major adverse cardiovascular events in people with first myocardial infarction without diabetes and with type 2 diabetes have improved significantly. In contrast, a similar improvement was not seen in people with type 1 diabetes.

Abstract Background A child's socioeconomic environment can shape central aspects of their life, including vulnerability to mental disorders. Negative environmental influences in youth may interfere with the extensive and dynamic brain development occurring at this time. Indeed, there are numerous yet diverging reports of associations between parental socioeconomic status (SES) and child cortical brain morphometry. Most of these studies have used single metric‐ or unimodal analyses of standard cortical morphometry that downplay the probable scenario where numerous biological pathways in sum account for SES‐related cortical differences in youth. Methods To comprehensively capture such variability, using data from 9758 children aged 8.9–11.1 years from the ABCD Study®, we employed linked independent component analysis (LICA) and fused vertex‐wise cortical thickness, surface area, curvature and grey‐/white‐matter contrast (GWC). LICA revealed 70 uni‐ and multimodal components. We then assessed the linear relationships between parental education, parental income and each of the cortical components, controlling for age, sex, genetic ancestry, and family relatedness. We also assessed whether cortical structure moderated the negative relationships between parental SES and child general psychopathology. Results Parental education and income were both associated with larger surface area and higher GWC globally, in addition to local increases in surface area and to a lesser extent bidirectional GWC and cortical thickness patterns. The negative relation between parental income and child psychopathology were attenuated in children with a multimodal pattern of larger frontal‐ and smaller occipital surface area, and lower medial occipital thickness and GWC. Conclusion Structural brain MRI is sensitive to SES diversity in childhood, with GWC emerging as a particularly relevant marker together with surface area. In low‐income families, having a more developed cortex across MRI metrics, appears beneficial for mental health.

Abstract A fungal biorefinery is presented to valorize food waste to fungal monofilaments with tunable properties for different textile applications. Rhizopus delemar is successfully grown on bread waste and the fibrous cell wall is isolated. A spinnable hydrogel is produced from cell wall by protonation of amino groups of chitosan followed by homogenization and concentration. Fungal hydrogel is wet spun to form fungal monofilaments which underwent post‐treatments to tune the properties. The highest tensile strength of untreated monofilaments is 65 MPa (and 4% elongation at break). The overall highest tensile strength of 140.9 MPa, is achieved by water post‐treatment. Moreover, post‐treatment with 3% glycerol resulted in the highest elongation % at break, i.e., 14%. The uniformity of the monofilaments also increased after the post‐treatments. The obtained monofilaments are compared with commercial fibers using Ashby's plots and potential applications are discussed. The wet spun monofilaments are located in the category of natural fibers in Ashby's plots. After water and glycerol treatments, the properties shifted toward metals and elastomers, respectively. The compatibility of the monofilaments with human skin cells is supported by a biocompatibility assay. These findings demonstrate fungal monofilaments with tunable properties fitting a wide range of sustainable textiles applications.

Background Patients with out‐of‐hospital cardiac arrest (OHCA) in rural areas experience longer emergency response times and have lower survival rates compared with patients in urban areas. Volunteer responders might improve care and outcomes for patients with OHCA specifically in rural areas. Therefore, we investigated volunteer responder interventions based on the degree of urbanization. Methods and Results We included 1310 OHCAs from 3 different regions in Denmark where volunteer responders had arrived at the OHCA location. The location was classified as urban, suburban, or rural according to the Eurostat Degree of Urbanization Tool. A logistic regression model was used to examine associations between the degree of urbanization and volunteer responder arrival before emergency medical services, cardiopulmonary resuscitation, or defibrillation. We found the odds for volunteer responder arrival before emergency medical services more than doubled in rural areas (odds ratio [OR], 2.60 [95% CI, 1.91–3.53]) and suburban areas (OR, 2.05 [95% CI, 1.56–2.69]) compared with urban areas. In OHCA cases where volunteer responders arrived first, odds for bystander cardiopulmonary resuscitation was tripled in rural areas (OR, 3.83 [95% CI, 1.64–8.93]) and doubled in suburban areas (OR, 2.27 [95% CI, 1.17–4.41]) compared with urban areas. Bystander defibrillation was more common in suburban areas (OR, 1.53 [95% CI, 1.02–2.31]), where almost 1 out of 4 patients received bystander defibrillation, compared with urban areas. Conclusions Volunteer responders are significantly more likely to arrive before emergency medical services in rural and suburban areas than in urban areas. Patients with OHCA received more cardiopulmonary resuscitation in rural and suburban areas and more defibrillation in suburban areas than in urban areas.

Abstract Objective Etiological classification of infantile spasms syndrome (ISS) is important, considering the influence on prognosis based on the presence or absence of a known etiology. This study was performed to describe the limitations and difficulties experienced within the South Asian region when classifying the etiology of ISS according to the current recommendation. Method Data on healthcare indices and facilities related to management of ISS for the nine countries in the South Asian region were gathered by the South Asian West Syndrome Research Group. A Google survey was performed among three hundred and thirty pediatric neurologists in the region. The capacity within each country for investigating etiology of ISS according to current described benchmarks was evaluated. The difficulties experienced in this regard and the potential solutions were investigated. Results One hundred and sixty pediatric neurologists (response rate 48%) from Bangladesh (19/25), India (94/255), Myanmar (11/11), Nepal (6/8), Pakistan (19/25), and from Sri Lanka (7/8) responded. Three countries had no pediatric neurology services. Fifty‐six percent attempted to classify ISS etiology according to classification outlined by International League Against Epilepsy in 2017. The facilities to perform metabolic, genetic, and immunological investigations were very limited. Lack of funding for investigations and poor laboratory support were the two most frequent barriers encountered. Sixty percent indicated that a separate classification is suitable for low‐income setting; 78% suggested inclusion of separate category as “incompletely investigated” as an alternative solution to mitigate the barrier of achieving a better understanding of the etiological subtypes seen more frequently in this region. Significance The resources in South Asian region are limited to meet the recommendations for investigating etiology of ISS. Including the etiological subcategory “incompletely investigated” is proposed as an alternative to understand the true proportions of children in this region, with a definite known etiology and those with an unknown etiology.

Methylation of the BRCA1 promoter is an epigenetic gene expression regulator and is frequently observed in ovarian cancer; however, conversion of methylation status is thought to drive disease recurrence. Therefore, longitudinal monitoring of methylation status by liquid biopsy in cell‐free DNA may be a predictive marker. In total, 135 plasma samples were collected from 69 ovarian cancer patients before and during systemic treatment. Our liquid biopsy assay could detect down to a single molecule of methylated DNA in a high background of normal DNA (0.03%) with perfect specificity in control samples. We found that 60% of the cancer patients exhibited BRCA1 promoter hypermethylation at one point, although 24% lost hypermethylation during treatment. Multivariate survival analyses indicate that relapses are independent events and that hypermethylation and methylation conversion are independently correlated to longer relapse‐free survival. We present a highly sensitive and specific methylation‐specific quantitative PCR‐based liquid biopsy assay. BRCA1 promoter hypermethylation is frequently found in ovarian cancer and is often reversed upon recurrence, indicating the selection of therapy‐resistant clones and unfavorable clinical outcome.

Abstract Estimating the contribution of demographic parameters to changes in population growth is essential for understanding why populations fluctuate. Integrated population models (IPMs) offer a possibility to estimate the contributions of additional demographic parameters, for which no data have been explicitly collected—typically immigration. Such parameters are often subsequently highlighted as important drivers of population growth. Yet, accuracy in estimating their temporal variation, and consequently their contribution to changes in population growth rate, has not been investigated. To quantify the magnitude and cause of potential biases when estimating the contribution of immigration using IPMs, we simulated data (using northern wheatear Oenanthe oenanthe population estimates) from controlled scenarios to examine potential biases and how they depend on IPM parameterization, formulation of priors, the level of temporal variation in immigration and sample size. We also used empirical data on populations with known rates of immigration: Soay sheep Ovis aries and Mauritius kestrel Falco punctatus with zero immigration and grey wolf Canis lupus in Scandinavia with near‐zero immigration. IPMs strongly overestimated the contribution of immigration to changes in population growth in scenarios when immigration was simulated with zero temporal variation (proportion of variance attributed to immigration = 63% for the more constrained formulation and real sample size) and in the wild populations, where the true number of immigrants was zero or near‐zero (kestrel 19.1%–98.2%, sheep 4.2%–36.1% and wolf 84.0%–99.2%). Although the estimation of the contribution of immigration in the simulation study became more accurate with increasing temporal variation and sample size, it was often not possible to distinguish between an accurate estimation from data with high temporal variation versus an overestimation from data with low temporal variation. Unrealistically, large sample sizes may be required to estimate the contribution of immigration well. To minimize the risk of overestimating the contribution of immigration (or any additional parameter) in IPMs, we recommend to: (a) look for evidence of variation in immigration before investigating its contribution to population growth, (b) simulate and model data for comparison to the real data and (c) use explicit data on immigration when possible.

Abstract Heavy metal concentrations often vary at small spatial scales not captured by air monitoring networks, with implications for environmental justice in industrial‐adjacent communities. Pollutants measured in moss tissues are commonly used as a screening tool to guide use of more expensive resources, like air monitors. Such studies, however, rarely address environmental justice issues or involve the residents and other decision makers expected to utilize results. Here, we piloted a community science approach, engaging over 55 people from nine institutions, to map heavy metals using moss in two industrial‐adjacent neighborhoods. This area, long known for disproportionately poor air quality, health outcomes, and racial inequities, has only one monitor for heavy metals. Thus, an initial understanding of spatial patterns is critical for gauging whether, where, and how to invest further resources toward investigating heavy metals. Local youth‐led sampling of the moss Orthotrichum lyellii from trees across a 250 × 250 m sampling grid (n = 79) and generated data comparable to expert‐collected samples (n = 19). We mapped 21 chemical elements measured in moss, including 6 toxic “priority” metals: arsenic, cadmium, chromium, cobalt, lead, and nickel. Compared to other urban O. lyellii studies, local moss had substantially higher priority metals, especially arsenic and chromium, encouraging community members to investigate further. Potential hotspots of priority metals varied somewhat but tended to peak near the central industrial core where many possible emission sources, including legacy contamination and converge. Informed by these findings, community members successfully advocated regulators for a second study phase—a community‐directed air monitoring campaign to evaluate residents' exposure to heavy metals—as is needed to connect moss results back to the partnership's core goal of understanding drivers of health disparities. This follow‐up campaign will measure metals in the PM10 fraction owing to clues in the current study that airborne soil and dust may be locally important carriers of priority metals. Future work will address how our approach combining bioindicators and community science ultimately affects success addressing longstanding environmental justice concerns. For now, we illustrate the potential to co‐create new knowledge, to help catalyze and strategize next steps, in a complex air quality investigation.

Background Children with congenital heart defects (CHD) have an increased risk of developmental delay. It remains sparsely investigated if these patients also have a delayed pubertal development. In this nationwide cohort study, we evaluated if CHD was associated with timing of puberty using longitudinally collected data on pubertal milestones. Methods and Results We used data from the Danish nationwide Puberty Cohort. Information on CHD was obtained from the Danish National Patient Register. Information on pubertal development was obtained from 15 780 children through questionnaires answered half‐yearly from 11 years until 18 years or full maturity. Using a multivariable regression model for censored time‐to‐event data, mean difference in age at attaining each pubertal milestone was estimated, including a combined pubertal marker. Compared with children without CHD, analyses were performed for both CHD overall and subdivided into simple and complex CHD. In a subanalysis, analyses were repeated in children born at term. In total, 137 children (62 boys and 75 girls) had a CHD diagnosis. Overall, no difference in age at pubertal timing was observed for children with CHD compared with unaffected children. The average differences were small for both boys (1.6 [95% CI, −2.6 to 5.7] months) and girls (1.0 [95% CI, −2.5 to 4.4] months). The same differences were observed when subdividing into simple or complex CHD and when restricting to children born at term. Conclusions We found no association between CHD and pubertal timing. For the group of children with complex CHD, we were unable to exclude a later pubertal timing.

Background Little is known about how COVID‐19 influenced engagement of citizen responders dispatched to out‐of‐hospital cardiac arrest (OHCA) by a smartphone application. The objective was to describe and analyze the Danish Citizen Responder Program and bystander interventions (both citizen responders and nondispatched bystanders) during the first COVID‐19 lockdown in 2020. Methods and Results All OHCAs from January 1, 2020, to June 30, 2020, with citizen responder activation in 2 regions of Denmark were included. We compared citizen responder engagement for OHCA in the nonlockdown period (January 1, 2020, to March 10, 2020, and April 21, 2020, to June 30, 2020) with the lockdown period (March 11, 2020, to April 20, 2020). Data are displayed in the order lockdown versus nonlockdown period. Bystander cardiopulmonary resuscitation rates did not differ in the 2 periods (99% versus 92%; P=0.07). Bystander defibrillation (9% versus 14%; P=0.4) or return‐of‐spontaneous circulation (23% versus 23%; P=1.0) also did not differ. A similar amount of citizen responders accepted alarms during the lockdown (6 per alarm; interquartile range, 6) compared with the nonlockdown period (5 per alarm; interquartile range, 5) (P=0.05). More citizen responders reported performing chest‐compression‐only cardiopulmonary resuscitation during lockdown compared with nonlockdown (79% versus 59%; P=0.0029), whereas fewer performed standardized cardiopulmonary resuscitation, including ventilations (19% versus 38%; P=0.0061). Finally, during lockdown, more citizen responders reported being not psychologically affected by attending an OHCA compared with nonlockdown period (68% versus 56%; P

Background We aim to examine diurnal and weekday variations in citizen responder availability and intervention at out‐of‐hospital cardiac arrest (OHCA) resuscitation. Methods and Results We included confirmed OHCAs where citizen responders were activated by a smartphone application in the Capital Region of Denmark between September 1, 2017 and August 31, 2018. OHCAs were analyzed by time of day (daytime: 07:00 am–03:59 pm, evening: 4:00–11:59 pm, and nighttime: 12:00–06:59 am) and day of week (Monday–Friday or Saturday–Sunday/public holidays). We included 438 OHCAs where 6836 citizen responders were activated. More citizen responders accepted alarms in the evening (mean 4.8 [95% CI, 4.4–5.3]) compared with daytime (3.7 [95% CI, 3.4–4.4]) and nighttime (1.8 [95% CI, 1.5–2.2]) (P

Abstract Background Cyclin‐dependent kinase (CDK) 4/6 inhibitors have recently been approved for the treatment of hormone receptor–positive and HER2‐negative metastatic breast cancer in association with endocrine therapy in postmenopausal women. Data on the interaction of CDK4/6 inhibition and radiotherapy are scarce, but some studies show unexpected toxicity. Cases We report three cases of unexpected severe or prolonged soft tissue, skin, and gastrointestinal toxicity in patients treated with a combination of radiotherapy and the CDK4/6 inhibitor palbociclib. Conclusion These cases indicate a possible interaction between radiotherapy and palbociclib. Therefore, we recommend using radiotherapy cautiously when combined with CDK4/6 inhibitors.

Abstract Objectives Considering the dearth of literature on West syndrome (WS) from South Asian countries, this study aimed to evaluate the management practices in South Asia by an online survey and meta‐analysis. Methods An online questionnaire was sent to 223 pediatric neurologists/pediatricians in India, Pakistan, Myanmar, Sri Lanka, Bhutan, Nepal, and Bangladesh. Their responses were evaluated and supplemented by a meta‐analysis. Results Of 125 responses received (response rate: 56%), around 60% of responders observed male preponderance and an approximate lead‐time‐to‐treatment (LTTT) of 4‐12 weeks. The commonest etiology observed was a static structural insult (88.6% of responders). Most commonly used first‐line drug (country‐wise) was as follows: India—adrenocorticotropin hormone (ACTH, 50%); Pakistan—oral steroids (45.5%); Myanmar, Sri Lanka, and Nepal—oral steroids (94.4%); Bangladesh—ACTH (2/2); Bhutan—vigabatrin (3/5). ACTH and vigabatrin are not available in Myanmar and Nepal. The most commonly used regime for ACTH was maximal‐dose‐at‐initiation‐regime in India, Sri Lanka, and Bangladesh and gradually escalating‐regime in Pakistan. Maximum dose of prednisolone was variable—most common response from India: 3‐4 mg/kg/d; Pakistan, Bhutan, and Bangladesh: 2 mg/kg/d; Sri Lanka, Nepal, and Myanmar: 5‐8 mg/kg/d or 60 mg/d. The total duration of hormonal therapy (including tapering) ranged from 4 to 12 weeks (67/91). Most responders considered cessation of spasms for four weeks as complete response (54/111) and advised electroencephalography (EEG; 104/123) to check for hypsarrhythmia resolution. Difficult access to pediatric EEG in Bhutan and Nepal is concerning. More than 95% of responders felt a need for more awareness. The meta‐analysis supported the preponderance of male gender (68%; confidence interval [CI]: 64%‐73%), structural etiology(80%; CI 73%‐86%), longer LTTT (2.4 months; CI 2.1‐2.6 months), and low response rate to hormonal therapy(18% and 28% for ACTH and oral steroids respectively) in WS in South Asia. Significance This study highlights the practices and challenges in the management of WS in South Asia. These include a preponderance of male gender and structural etiology, a longer LTTT, difficult access to pediatric EEG, nonavailability of ACTH and vigabatrin in some countries, and low effectiveness of hormonal therapy in this region.

Patients with recurrent glioblastoma achieving response to bevacizumab combined with chemotherapy have clinical improvement and prolonged survival. High gene expression of angiotensinogen (AGT) is associated with a poor bevacizumab response. Because AGT expression is epigenetically regulated, we aimed to investigate whether AGT promoter methylation in tumor tissue predicts response to bevacizumab combination therapy in patients with recurrent glioblastoma. The study included 159 patients with recurrent glioblastoma, treated with bevacizumab combination treatment (training cohort, n = 77; validation cohort, n = 82). All patients could be evaluated for treatment response and biomarkers. DNA methylation of 4 CpG sites in the AGT promoter was measured using pyrosequencing. A model for nonresponse was established using logistic regression analysis. In the training cohort, lower methylation of each of the four CpG sites in the AGT promoter was significantly associated with nonresponse (all P

Abstract Introduction Many consequences of cerebrovascular disease are identifiable by magnetic resonance imaging (MRI), but variation in methods limits multicenter studies and pooling of data. The European Union Joint Program on Neurodegenerative Diseases (EU JPND) funded the HARmoNizing Brain Imaging MEthodS for VaScular Contributions to Neurodegeneration (HARNESS) initiative, with a focus on cerebral small vessel disease. Methods Surveys, teleconferences, and an in‐person workshop were used to identify gaps in knowledge and to develop tools for harmonizing imaging and analysis. Results A framework for neuroimaging biomarker development was developed based on validating repeatability and reproducibility, biological principles, and feasibility of implementation. The status of current MRI biomarkers was reviewed. A website was created at www.harness‐neuroimaging.org with acquisition protocols, a software database, rating scales and case report forms, and a deidentified MRI repository. Conclusions The HARNESS initiative provides resources to reduce variability in measurement in MRI studies of cerebral small vessel disease.

Background Little is known about the psychological risks of dispatched citizen responders who have participated in resuscitation attempts. Methods and Results A cross‐sectional survey study was performed with 102 citizen responders who participated in a resuscitation attempt from July 23, 2018, to August 22, 2018, in the Capital Region of Denmark. Psychological distress, defined as symptoms of posttraumatic stress disorder, was assessed 3 weeks after the resuscitation attempt and measured with the Impact of Event Scale‐Revised. Perceived stress was measured with the Perceived Stress Scale. Individual differences were assessed as the personality traits of agreeableness, conscientiousness, extraversion, neuroticism, and openness to experience with the Big Five Inventory, general self‐efficacy, and coping mechanisms (Brief Coping Orientation to Problems Experienced Inventory). Associations between continuous variables were examined with the Pearson correlation. The associations between psychological distress levels and contextual factors and individual differences were analyzed in multivariable linear regression models to determine factors independently associated with psychological distress levels. The mean overall posttraumatic stress disorder score was 0.65 of 12; the mean perceived stress score was 7.61 of 40. The most common coping mechanisms were acceptance and emotional support. Low perceived stress was significantly associated with high general self‐efficacy, and high perceived stress was significantly associated with high scores on neuroticism and openness to experience. Non–healthcare professionals were less likely to report symptoms of posttraumatic stress disorder. Conclusions Citizen responders who participated in resuscitation reported low levels of psychological distress. Individual differences were significantly associated with levels of psychological distress and should be considered when engaging citizen responders in resuscitation.