Recommendations for empowering early career researchers to improve research culture and practice.

Early career researchers (ECRs) are important stakeholders leading efforts to catalyze systemic change in research culture and practice. Here, we summarize the outputs from a virtual unconventional conference (unconference), which brought together 54 invited experts from 20 countries with extensive experience in ECR initiatives designed to improve the culture and practice of science. Together, we drafted 2 sets of recommendations for (1) ECRs directly involved in initiatives or activities to change research culture and practice; and (2) stakeholders who wish to support ECRs in these efforts. Importantly, these points apply to ECRs working to promote change on a systemic level, not only those improving aspects of their own work. In both sets of recommendations, we underline the importance of incentivizing and providing time and resources for systems-level science improvement activities, including ECRs in organizational decision-making processes, and working to dismantle structural barriers to participation for marginalized groups. We further highlight obstacles that ECRs face when working to promote reform, as well as proposed solutions and examples of current best practices. The abstract and recommendations for stakeholders are available in Dutch, German, Greek (abstract only), Italian, Japanese, Polish, Portuguese, Spanish, and Serbian.

Economic Evaluation of a Mobile Stroke Unit Service in Germany.

BACKGROUND: Lower global disability and higher quality of life among ischemic stroke patients was found to be associated with the dispatch of mobile stroke units (MSUs) among patients eligible for recanalizing treatments in the Berlin_Prehospital Or Usual Delivery of stroke care (B_PROUD) study. The current study assessed the cost-utility and cost-effectiveness of additional MSU dispatch using data from this prospective, controlled, intervention study. METHODS: Outcomes considered in the economic evaluation included quality-adjusted life years (QALYs) derived from the 3-level version of EQ-5D (EQ-5D-3L) and modified Rankin Scale (mRS) scores for functional outcomes 3-months after stroke. Costs were prospectively collected during the study by the MSU provider (Berlin Fire Brigade) and the B_PROUD research team. We focus our results on the societal perspective. As we aimed to determine the economic consequences of the intervention beyond the study's follow-up period, both care costs and QALYs were extrapolated over 5 years. RESULTS: The additional MSU dispatch resulted in an incremental €40,984 per QALY. The best-case scenario and the worst-case scenario yielded additional costs of, respectively, €24,470.76 and €61,690.88 per QALY. In the cost-effectiveness analysis, MSU dispatch resulted in incremental costs of €81,491 per survival without disability. The best-case scenario and the worst-case scenario yielded additional costs of, respectively, €44,455.30 and €116,491.15 per survival without disability. INTERPRETATION: Among patients eligible for recanalizing treatments in ischemic stroke, MSU dispatch was associated with both higher QALYs and higher costs and is cost-effective when considering internationally accepted thresholds ranging from an additional €40,000 to €80,000 per QALY. ANN NEUROL 2023;93:942-951.

Effect of Mobile Stroke Unit Dispatch in all Patients with Acute Stroke or TIA.

OBJECTIVE: To determine the effect of additional mobile stroke unit (MSU) dispatch on functional outcomes among the full spectrum of stroke patients, regardless of subtype or potential contraindications to reperfusion therapies. METHODS: We used data from the nonrandomized Berlin-based B_PROUD study (02/2017 to 05/2019), in which MSUs were dispatched based solely on availability, and the linked B-SPATIAL stroke registry. All patients with final stroke or transient ischemic attack (TIA) diagnoses were eligible. The intervention under study was the additional dispatch of an MSU, an emergency physician-staffed ambulance equipped to provide prehospital imaging and thrombolytic treatment, compared to conventional ambulance alone. The primary outcome was the 3-month modified Rankin Scale (mRS) score, and the co-primary outcome was a 3-tiered disability scale. We identified confounders using directed acyclic graphs and obtained adjusted effect estimates using inverse probability of treatment weighting. RESULTS: MSUs were dispatched to 1,125 patients (mean age: 74 years, 46.5% female), while for 1,141 patients only conventional ambulances were dispatched (75 years, 49.9% female). After confounding adjustment, MSU dispatch was associated with more favorable 3-month mRS scores (common odds ratio [cOR] = 0.82; 95% confidence interval [CI]: 0.71-0.94). No statistically significant association was found with the co-primary outcome (cOR = 0.86; 9% CI: 0.72-1.01) or 7-day mortality (OR = 0.94; 95% CI: 0.59-1.48). INTERPRETATION: When considering the entire population of stroke/TIA patients, MSU dispatch improved 3-month functional outcomes without evidence of compromised safety. Our results are relevant for decision-makers since stroke subtype and treatment eligibility are unknown at time of dispatch. ANN NEUROL 2023;93:50-63.

Understanding random resampling techniques for class imbalance correction and their consequences on calibration and discrimination of clinical risk prediction models.

OBJECTIVE: Class imbalance is sometimes considered a problem when developing clinical prediction models and assessing their performance. To address it, correction strategies involving manipulations of the training dataset, such as random undersampling or oversampling, are frequently used. The aim of this article is to illustrate the consequences of these class imbalance correction strategies on clinical prediction models' internal validity in terms of calibration and discrimination performances. METHODS: We used both heuristic intuition and formal mathematical reasoning to characterize the relations between conditional probabilities of interest and probabilities targeted when using random undersampling or oversampling. We propose a plug-in estimator that represents a natural correction for predictions obtained from models that have been trained on artificially balanced datasets ("naïve" models). We conducted a Monte Carlo simulation with two different data generation processes and present a real-world example using data from the International Stroke Trial database to empirically demonstrate the consequences of applying random resampling techniques for class imbalance correction on calibration and discrimination (in terms of Area Under the ROC, AUC) for logistic regression and tree-based prediction models. RESULTS: Across our simulations and in the real-world example, calibration of the naïve models was very poor. The models using the plug-in estimator generally outperformed the models relying on class imbalance correction in terms of calibration while achieving the same discrimination performance. CONCLUSION: Random resampling techniques for class imbalance correction do not generally improve discrimination performance (i.e., AUC), and their use is hard to justify when aiming at providing calibrated predictions. Improper use of such class imbalance correction techniques can lead to suboptimal data usage and less valid risk prediction models.

Should Cognitive Screening Tests Be Corrected for Age and Education? Insights From a Causal Perspective.

Cognitive screening tests such as the Mini-Mental State Examination are widely used in clinical routine to predict cognitive impairment. The raw test scores are often corrected for age and education, although documented poorer discrimination performance of corrected scores has challenged this practice. Nonetheless, test correction persists, perhaps due to the seemingly counterintuitive nature of the underlying problem. We used a causal framework to inform the long-standing debate from a more intuitive angle. We illustrate and quantify the consequences of applying the age-education correction of cognitive tests on discrimination performance. In an effort to bridge theory and practical implementation, we computed differences in discrimination performance under plausible causal scenarios using Open Access Series of Imaging Studies (OASIS)-1 data. We show that when age and education are causal risk factors for cognitive impairment and independently also affect the test score, correcting test scores for age and education removes meaningful information, thereby diminishing discrimination performance.

Using LASSO Regression to Estimate the Population-Level Impact of Pneumococcal Conjugate Vaccines.

Pneumococcal conjugate vaccines (PCVs) protect against diseases caused by Streptococcus pneumoniae, such as meningitis, bacteremia, and pneumonia. It is challenging to estimate their population-level impact due to the lack of a perfect control population and the subtleness of signals when the endpoint-such as all-cause pneumonia-is nonspecific. Here we present a new approach for estimating the impact of PCVs: using least absolute shrinkage and selection operator (LASSO) regression to select variables in a synthetic control model to predict the counterfactual outcome for vaccine impact inference. We first used a simulation study based on hospitalization data from Mexico (2000-2013) to test the performance of LASSO and established methods, including the synthetic control model with Bayesian variable selection (SC). We found that LASSO achieved accurate and precise estimation, even in complex simulation scenarios where the association between the outcome and all control variables was noncausal. We then applied LASSO to real-world hospitalization data from Chile (2001-2012), Ecuador (2001-2012), Mexico (2000-2013), and the United States (1996-2005), and found that it yielded estimates of vaccine impact similar to SC. The LASSO method is accurate and easily implementable and can be applied to study the impact of PCVs and other vaccines.

The Effect of Mobile Stroke Unit Care on Functional Outcomes: An Application of the Front-door Formula.

BACKGROUND: The Berlin-based B_PROUD study was designed to assess the effect of mobile stroke unit (MSU) dispatch among ischemic stroke and transient ischemic attack (TIA) patients without contraindications to reperfusion treatments. However, a large proportion of patients for whom the MSU was dispatched did not ultimately receive MSU care. We estimated the causal effect of additional MSU care on 3-month functional outcomes among B_PROUD patients for whom an MSU was dispatched. METHODS: We used data from the B_PROUD study (1 February 2017-8 May 2019). Given the presence of exposure-outcome unmeasured confounding, we used the front-door formula to identify the distribution of modified Rankin scale (mRS) outcomes under two hypothetical interventions: (1) receiving additional MSU care and (2) only receiving conventional care. We considered the time from dispatch to thrombolysis as the full mediator and adjusted for exposure-mediator and mediator-outcome confounding. We used a parametric estimator to estimate the common odds ratio (cOR) and 95% bootstrapped confidence intervals (CI). RESULTS: We included in total 768 ischemic stroke/TIA patients with MSU dispatch. The MSU was canceled for 180 (23%) patients, whereas 588 (77%) received MSU care. The unadjusted association between the care group and mRS favored conventional care (cOR = 1.7; 95% CI = 1.2, 2.3); however, after applying the front-door formula, the mRS distribution favored MSU care (cOR = 0.88; 95% CI = 0.81, 0.96). CONCLUSIONS: Receiving MSU care was associated with better functional outcomes than conventional care only, compatible with the hypothesized beneficial effect of MSU care on poststroke outcomes, among stroke and TIA patients without contraindications to reperfusion treatments.

Estimation of migraine prevalence considering active and inactive states across different age groups.

BACKGROUND: Migraine is a very common headache disorder on the population level, characterized by symptomatic attacks (activity). For many people with migraine, the migraine symptoms intermittently or permanently cease during their lifetime (inactive migraine). The current diagnostic classification of migraine considers two states: active migraine (having migraine symptoms within the last year) and not having active migraine (including both individuals with inactive migraine and those who never had migraine). Defining a state of inactive migraine that has gone into remission may better capture the trajectories of migraine across the lifespan and contribute to a better understanding of its biological processes. We aimed to quantify the prevalence of never, active, and inactive migraine separately, using modern prevalence and incidence estimation methodology to better describe the complexity of migraine trajectories at the population level. METHODS: Using a multistate modeling approach, data from the Global Burden of Disease (GBD) study, and results from a population-based study, we estimated the transition rates by which individuals moved between migraine disease states and estimated prevalences of never, active and inactive migraine. We used data from the GBD project and a hypothetical cohort of 100,000 people with a starting age of 30 and 30 years of follow-up, both in Germany and globally, stratified by sex. RESULTS: In Germany, the estimated rate of transition from active to inactive migraine (remission rate) increased after the age of 22.5 in women and 27.5 in men. The pattern for men in Germany was similar to the one observed on the global level. The prevalence of inactive migraine among women reaches 25.7% in Germany and 16.5% globally at age 60. For men, the inactive migraine prevalence estimates at the same age were 10.4% in Germany and 7.1% globally. CONCLUSIONS: Considering an inactive migraine state explicitly reflects a different epidemiological picture of migraine across the lifecourse. We have demonstrated that many women of older ages may be in an inactive migraine state. Many pressing research questions can only be answered if population-based cohort studies collect information not only on active migraine but also on inactive migraine states.

Association Between Dispatch of Mobile Stroke Units and Functional Outcomes Among Patients With Acute Ischemic Stroke in Berlin.

Importance: Effects of thrombolysis in acute ischemic stroke are time-dependent. Ambulances that can administer thrombolysis (mobile stroke units [MSUs]) before arriving at the hospital have been shown to reduce time to treatment. Objective: To determine whether dispatch of MSUs is associated with better clinical outcomes for patients with acute ischemic stroke. Design, Setting, and Participants: This prospective, nonrandomized, controlled intervention study was conducted in Berlin, Germany, from February 1, 2017, to October 30, 2019. If an emergency call prompted suspicion of stroke, both a conventional ambulance and an MSU, when available, were dispatched. Functional outcomes of patients with final diagnosis of acute cerebral ischemia who were eligible for thrombolysis or thrombectomy were compared based on the initial dispatch (both MSU and conventional ambulance or conventional ambulance only). Exposure: Simultaneous dispatch of an MSU (computed tomographic scanning with or without angiography, point-of-care laboratory testing, and thrombolysis capabilities on board) and a conventional ambulance (n = 749) vs conventional ambulance alone (n = 794). Main Outcomes and Measures: The primary outcome was the distribution of modified Rankin Scale (mRS) scores (a disability score ranging from 0, no neurological deficits, to 6, death) at 3 months. The coprimary outcome was a 3-tier disability scale at 3 months (none to moderate disability; severe disability; death) with tier assignment based on mRS scores if available or place of residence if mRS scores were not available. Common odds ratios (ORs) were used to quantify the association between exposure and outcome; values less than 1.00 indicated a favorable shift in the mRS distribution and lower odds of higher levels of disability. Results: Of the 1543 patients (mean age, 74 years; 723 women [47%]) included in the adjusted primary analysis, 1337 (87%) had available mRS scores (primary outcome) and 1506 patients (98%) had available the 3-tier disability scale assessment (coprimary outcome). Patients with an MSU dispatched had lower median mRS scores at month 3 (1; interquartile range [IQR], 0-3) than did patients without an MSU dispatched (2; IQR, 0-3; common OR for worse mRS, 0.71; 95% CI, 0.58-0.86; P < .001). Similarly, patients with an MSU dispatched had lower 3-month coprimary disability scores: 586 patients (80.3%) had none to moderate disability; 92 (12.6%) had severe disability; and 52 (7.1%) had died vs patients without an MSU dispatched: 605 (78.0%) had none to moderate disability; 103 (13.3%) had severe disability; and 68 (8.8%) had died (common OR for worse functional outcome, 0.73, 95% CI, 0.54-0.99; P = .04). Conclusions and Relevance: In this prospective, nonrandomized, controlled intervention study of patients with acute ischemic stroke in Berlin, Germany, the dispatch of mobile stroke units, compared with conventional ambulances alone, was significantly associated with lower global disability at 3 months. Clinical trials in other regions are warranted.

Directed acyclic graphs and causal thinking in clinical risk prediction modeling.

BACKGROUND: In epidemiology, causal inference and prediction modeling methodologies have been historically distinct. Directed Acyclic Graphs (DAGs) are used to model a priori causal assumptions and inform variable selection strategies for causal questions. Although tools originally designed for prediction are finding applications in causal inference, the counterpart has remained largely unexplored. The aim of this theoretical and simulation-based study is to assess the potential benefit of using DAGs in clinical risk prediction modeling. METHODS: We explore how incorporating knowledge about the underlying causal structure can provide insights about the transportability of diagnostic clinical risk prediction models to different settings. We further probe whether causal knowledge can be used to improve predictor selection in clinical risk prediction models. RESULTS: A single-predictor model in the causal direction is likely to have better transportability than one in the anticausal direction in some scenarios. We empirically show that the Markov Blanket, the set of variables including the parents, children, and parents of the children of the outcome node in a DAG, is the optimal set of predictors for that outcome. CONCLUSIONS: Our findings provide a theoretical basis for the intuition that a diagnostic clinical risk prediction model including causes as predictors is likely to be more transportable. Furthermore, using DAGs to identify Markov Blanket variables may be a useful, efficient strategy to select predictors in clinical risk prediction models if strong knowledge of the underlying causal structure exists or can be learned.

Migraine, headache, and mortality in women: a cohort study.

BACKGROUND: Migraine carries a high global burden, disproportionately affects women, and has been implicated as a risk factor for cardiovascular disease. Migraine with aura has been consistently associated with increased risk of cardiovascular mortality. However, published evidence on relationships between migraine or non-migraine headache and all-cause mortality is inconclusive. Therefore, we aimed to estimate the effect of non-migraine headache and migraine as well as migraine subtypes on all-cause and cause-specific mortality in women. METHODS: In total, 27,844 Women's Health Study participants, aged 45 years or older at baseline, were followed up for a median of 22.7 years. We included participants who provided information on migraine (past history, migraine without aura, or migraine with aura) or headache status and a blood sample at study start. An endpoints committee of physicians evaluated reports of incident deaths and used medical records to confirm deaths due to cardiovascular, cancer, or female-specific cancer causes. We used multivariable Cox proportional hazards models to estimate the effect of migraine or headache status on both all-cause and cause-specific mortality. RESULTS: Compared to individuals without any headache, no differences in all-cause mortality for individuals suffering from non-migraine headache or any migraine were observed after adjustment for confounding (HR = 1.01, 95%CI, 0.93-1.10 and HR = 0.96, 95% CI: 0.89-1.04). No differences were observed for the migraine subtypes and all-cause death. Women having the migraine with aura subtype had  a higher mortality due to cardiovascular disease (adjusted HR = 1.64, 95%CI: 1.06-2.54). As an explanation for the lack of overall association with all-cause mortality, we observed slightly protective signals for any cancer and female-specific cancers in this group. CONCLUSIONS: In this large prospective study of women, we found no association between non-migraine headache or migraine and all-cause mortality. Women suffering from migraine with aura had an increased risk of cardiovascular death. Future studies should investigate the reasons for the increased risk of cardiovascular mortality and evaluate whether changes in migraine patterns across the life course have differential effects on mortality.

Serum Anti-NMDA (N-Methyl-D-Aspartate)-Receptor Antibodies and Long-Term Clinical Outcome After Stroke (PROSCIS-B).

Background and Purpose- NMDAR1-abs (anti-N-Methyl-D-Aspartate receptor GluN1 antibodies), predominantly known in the context of autoimmune encephalitis, have been observed in serum of healthy individuals. A previous study found smaller stroke magnetic resonance imaging lesion growth in seropositive patients, suggesting a neuroprotective effect of these antibodies. The impact of NMDAR1-abs seropositivity on long-term functional outcome and recurrent vascular events and death after first-ever stroke remains unclear. Methods- Data from the Prospective Cohort with Incident Stroke-Berlin were used. NMDAR1-abs (ie, IgM, IgA, and IgG) were measured in serum within 7 days after first stroke. Outcomes of interest included modified Rankin Scale at one year and the time-to-event of a combined end point (recurrent stroke, myocardial infarction, and all-cause mortality) within 3 years. We calculated odds ratios from adjusted partial proportional odds models and subsequently compared outcome of patients with low titers (1:10; 1:32; and 1:100), and high titers (1:320; 1:1000) to seronegative patients. Furthermore, we estimated hazard ratios for a secondary vascular event or death in NMDAR1-abs seropositive compared to seronegative patients in models adjusted for confounders. Results- The analyses included 583 patients with antibody measurements (39% female, median National Institutes of Health Stroke Scale:2, IQR:1-4), and NMDAR1-abs were observed in 76 (13%) patients. NMDAR1-abs seroprevalence was not associated with functional outcome (odds ratio=1.27; 95% CI, 0.77-2.09); sub-group analyses, however, showed worse outcome in patients with high titers (odds ratio=3.47; 95% CI, 1.54-7.80). Seropositive patients had an increased risk for a secondary vascular event or death (hazard ratios =1.83, 95% CI, 1.10-3.05). Conclusions- In our study, NMDAR1-abs seropositivity was not associated with functional outcome at one year after stroke, however, high titers (≥1:320) were associated with poor functional outcome. Furthermore, NMDAR1-abs seropositivity was associated with increased cardiovascular risk within 3 years after first stroke, independently from other risk factors. Clinical Trial Registration- URL: https://www.clinicaltrials.gov. Unique identifier: NCT01363856.

What are the costs of learning? Modest trade-offs and constitutive costs do not set the price of fast associative learning ability in a parasitoid wasp.

Learning ability has been associated with energetic costs that typically become apparent through trade-offs in a wide range of developmental, physiological, and life-history traits. Costs associated with learning ability can be either constitutive or induced, depending on whether they are always incurred or only when information is actively learned and memorized. Using lines of the parasitoid wasp Nasonia vitripennis that were selected for fast associative learning ability, we assessed a range of traits that have previously been identified as potential costs associated with learning. No difference in longevity, lipid reserves, tibia length, egg load, or fecundity was observed between the selected and control lines. All of these traits are considered to potentially lead to constitutive costs in the setup of this study. A gradual reversal to baseline learning after two forms of relaxed selection was indicative of a small constitutive cost of learning ability. We also tested for a trade-off with other memory types formed at later stages, but found no evidence that the mid-term memory that was selected for caused a decrease in performance of other memory types. In conclusion, we observe only one minor effect of a constitutive cost and none of the other costs and trade-offs that are reported in the literature to be of significant value in this case. We, therefore, argue for better inclusion of ecological and economic costs in studies on costs and benefits of learning ability.

Adjusted horizontal stacked bar graphs ("Grotta bars") for consistent presentation of observational stroke study results.

Background: Modified Rankin Scale (mRS) scores are used to measure functional outcomes after stroke. Researchers create horizontal stacked bar graphs (nicknamed "Grotta bars") to illustrate distributional differences in scores between groups. In well-conducted randomized controlled trials, Grotta bars have a causal interpretation. However, the common practice of exclusively presenting unadjusted Grotta bars in observational studies can be misleading in the presence of confounding. We demonstrated this problem and a possible solution using an empirical comparison of 3-month mRS scores among stroke/TIA patients discharged home versus elsewhere after hospitalization. Patients and methods: Using data from the Berlin-based B-SPATIAL registry, we estimated the probability of being discharged home conditional on prespecified measured confounding factors and generated stabilized inverse probability of treatment (IPT) weights for each patient. We visualized mRS distributions by group with Grotta bars for the IPT-weighted population in which measured confounding was removed. We then used ordinal logistic regression to quantify unadjusted and adjusted associations between being discharged home and the 3-month mRS score. Results: Of 3184 eligible patients, 2537 (79.7%) were discharged home. In the unadjusted analyses, those discharged home had considerably lower mRS compared with patients discharged elsewhere (common odds ratio, cOR = 0.13, 95% CI: 0.11-0.15). After removing measured confounding, we obtained substantially different mRS distributions, visually apparent in the adjusted Grotta bars. No statistically significant association was found after confounding adjustment (cOR = 0.82, 95% CI: 0.60-1.12). Discussion and conclusion: The practice of presenting only unadjusted stacked bar graphs for mRS scores together with adjusted effect estimates in observational studies can be misleading. IPT weighting can be implemented to create Grotta bars that account for measured confounding, which are more consistent with the presentation of adjusted results in observational studies.

Effects of Mobile Stroke Unit dispatch on blood pressure management and outcomes in patients with intracerebral haematoma: Results from the Berlin_Prehospital Or Usual Care Delivery in acute Stroke (B_PROUD) controlled intervention study.

INTRODUCTION: In patients with acute intracerebral haemorrhage (ICH) and elevated systolic blood pressure (BP), guidelines suggest that systolic BP reduction to <140 mmHg should be rapidly initiated. Compared with conventional care, Mobile Stroke Units (MSUs) allow for earlier ICH diagnosis through prehospital imaging and earlier BP lowering. PATIENTS AND METHODS: ICH patients were prospectively evaluated as a cohort of the controlled B_PROUD-study in which MSU availability alone determined MSU dispatch in addition to conventional ambulance. We used inverse probability of treatment weighting to adjust for confounding to estimate the effect of additional MSU dispatch in ICH patients. Outcomes of interest were 7-day mortality (primary), systolic BP (sBP) at hospital arrival, dispatch-to-imaging time, largest haematoma volume, anticoagulation reversal, length of in-hospital stay, 3-month functional outcome. RESULTS: Between February 2017 and May 2019, MSUs were dispatched to 95 (mean age: 72 ± 13 years, 45% female) and only conventional ambulances to 78 ICH patients (mean age: 71 ± 12 years, 44% female). After adjusting for confounding, we found shorter dispatch-to-imaging time (mean difference: -17.75 min, 95% CI: -27.16 to -8.21 min) and lower sBP at hospital arrival (mean difference = -16.31 mmHg, 95% CI: -30.64 to -6.19 mmHg) in the MSU group. We found no statistically significant difference for the other outcomes, including 7-day mortality (adjusted odds ratio: 1.43, 95% CI: 0.68 to 3.31) or favourable outcome (adjusted odds ratio = 0.67, 95% CI: 0.27 to 1.67). CONCLUSIONS: Although MSU dispatch led to sBP reduction and lower dispatch-to-imaging time compared to conventional ambulance care, we found no evidence of better outcomes in the MSU dispatch group.

Eleven strategies for making reproducible research and open science training the norm at research institutions.

Reproducible research and open science practices have the potential to accelerate scientific progress by allowing others to reuse research outputs, and by promoting rigorous research that is more likely to yield trustworthy results. However, these practices are uncommon in many fields, so there is a clear need for training that helps and encourages researchers to integrate reproducible research and open science practices into their daily work. Here, we outline eleven strategies for making training in these practices the norm at research institutions. The strategies, which emerged from a virtual brainstorming event organized in collaboration with the German Reproducibility Network, are concentrated in three areas: (i) adapting research assessment criteria and program requirements; (ii) training; (iii) building communities. We provide a brief overview of each strategy, offer tips for implementation, and provide links to resources. We also highlight the importance of allocating resources and monitoring impact. Our goal is to encourage researchers - in their roles as scientists, supervisors, mentors, instructors, and members of curriculum, hiring or evaluation committees - to think creatively about the many ways they can promote reproducible research and open science practices in their institutions.

Impact of time between thrombolysis and endovascular thrombectomy on outcomes in patients with acute ischaemic stroke.

Background: Benefits of endovascular thrombectomy (ET) after intravenous thrombolysis (IVT) for patients with acute ischaemic stroke (AIS) have been demonstrated, but analyses of the relationship between IVT-ET time delay and functional outcomes among patients receiving both treatments are lacking. Methods: We used data from the "Berlin-Specific Acute Treatment in Ischaemic and haemorrhAgic stroke with Long-term outcome" (B-SPATIAL) registry. Between January 1st, 2016 and December 31st, 2019, we included patients who received both IVT and ET. The primary outcome was the 3-month ordinal modified Rankin scale (mRS) score. The IVT-ET time delay was analyzed in categories and continuously. We used adjusted ordinal logistic regression to estimate common odds ratios (cOR) and 95% confidence intervals (CI). Secondary analyses involved flexible modeling of IVT-ET delay and dichotomous outcomes. Results: Of 11,049 patients, 714 who received IVT followed by ET were included. Compared with having an IVT-ET window >120 min (reference), for an IVT-ET window < 30 min, we obtained adjusted cORs for mRS of 0.41 (95% CI: 0.22 to 0.78); and 0.52 (95% CI: 0.33 to 0.82) for 30 to 120 min. Secondary analyses also found protective effects of shorter time delays against "poor" functional outcomes at 3 months. Conclusions: In patients with AIS, shorter IVT-ET intervals were associated with better 3-month functional outcomes. While the time-to-IVT and time-to-ET include the time until medical attention is received, the IVT-ET time delays fall entirely within the domain of medical management and thus might be easier to optimize.

The Effect of Socioeconomic Factors and Indoor Residual Spraying on Malaria in Mangaluru, India: A Case-Control Study.

India faces 0.5 million malaria cases annually, including half of all Plasmodium vivax malaria cases worldwide. This case-control study assessed socioeconomic determinants of urban malaria in coastal Mangaluru, Karnataka, southwestern India. Between June and December 2015, we recruited 859 malaria patients presenting at the governmental Wenlock Hospital and 2190 asymptomatic community controls. We assessed clinical, parasitological, and socioeconomic data. Among patients, p. vivax mono-infection (70.1%) predominated. Most patients were male (93%), adult (median, 27 years), had no or low-level education (70.3%), and 57.1% were daily labourers or construction workers. In controls (59.3% male; median age, 32 years; no/low-level education, 54.5%; daily labourers/construction workers, 41.3%), 4.1% showed asymptomatic Plasmodium infection. The odds of malaria was reduced among those who had completed 10th school grade (aOR, 0.3; 95% CI, 0.26-0.42), lived in a building with a tiled roof (aOR, 0.71; 95% CI, 0.53-0.95), and reported recent indoor residual spraying (aOR, 0.02; 95% CI, 0.01-0.04). In contrast, migrant status was a risk factor for malaria (aOR, 2.43; 95% CI, 1.60-3.67). Malaria in Mangaluru is influenced by education, housing condition, and migration. Indoor residual spraying greatly contributes to reducing malaria in this community and should be promoted, especially among its marginalised members.

Use of all cause mortality to quantify the consequences of covid-19 in Nembro, Lombardy: descriptive study.

OBJECTIVE: To quantify the impact of coronavirus disease 2019 (covid-19) on all cause mortality in Nembro, an Italian city severely affected by the covid-19 pandemic. DESIGN: Descriptive study. SETTING: Nembro, in the Bergamo province of Lombardy, northern Italy. POPULATION: Residents of Nembro. MAIN OUTCOME MEASURES: Monthly all cause mortality between January 2012 and April 2020 (data to 11 April), number of confirmed deaths from covid-19 to 11 April 2020, and weekly absolute number of deaths between 1 January and 4 April across recent years by age group and sex. RESULTS: Nembro had 11 505 residents as of 1 January 2020. Monthly all cause mortality between January 2012 and February 2020 fluctuated around 10 per 1000 person years, with a maximum of 21.5 per 1000 person years. In March 2020, monthly all cause mortality reached a peak of 154.4 per 1000 person years. For the first 11 days in April, this rate decreased to 23.0 per 1000 person years. The observed increase in mortality was driven by the number of deaths among older people (≥65 years), especially men. From the outbreak onset until 11 April 2020, only 85 confirmed deaths from covid-19 in Nembro were recorded, corresponding to about half of the 166 deaths from all causes observed in that period. CONCLUSIONS: The study findings show how covid-19 can have a considerable impact on the health of a small community. Furthermore, the results suggest that the full implications of the covid-19 pandemic can only be completely understood if, in addition to confirmed deaths related to covid-19, consideration is also given to all cause mortality in a given region and time frame.