Changes in Brain Activity Immediately Post-Exercise Indicate a Role for Central Fatigue in the Volitional Termination of Exercise.

Electroencephalography (EEG) allows for the evaluation of real time changes in brain (electrocortical) activity during exercise. A few studies have examined changes in electrocortical activity using stationary cycling, but the findings have been mixed. Some of these studies have found increases in brain activity following exercise, while others have found decreases in brain activity following exercise. Hence, it is of importance to identify post-exercise changes in brain activity. Sixteen healthy, untrained subjects (8 males; 8 females) participated in the study. All 16 participants performed a graded exercise test (GXT) to volitional exhaustion on an upright cycle ergometer. Continuous EEG recordings were sampled before (PRE) and immediately following (IP) the GXT. Regions of interest were primarily the dorsolateral prefrontal cortex (DLPFC), ventrolateral prefrontal cortex (VLPFC), and left and right motor cortex (MC). In the DLPFC, a frontal asymmetry index was also identified. There was a statistically significant increase in theta power in the DLPFC, VLPFC, and left and right MC from PRE to IP (all p < 0.05). There was also a shift towards right hemisphere asymmetry at the IP time point in the DLPFC (p < 0.05). Finally, there was an increase in alpha power from PRE to IP in the right MC (p < 0.05). EEG could prove to be an important way to measure the effects of central fatigue on brain activity before and immediately following exercise.

Report of the European Medicines Agency Conference on RNA-Based Medicines.

RNA-based medicines have potential to treat a large variety of diseases, and research in the field is very dynamic. Proactively, The European Medicines Agency (EMA) organized a virtual conference on February 2, 2023 to promote the development of RNA-based medicines. The initiative addresses the goal of the EMA Regulatory Science Strategy to 2025 to "catalyse the integration of science and technology in medicines development." The conference focused on RNA technologies (excluding RNA vaccines) and involved different stakeholders, including representatives from academia, industry, regulatory authorities, and patient organizations. The conference comprised presentations and discussion sessions conducted by panels of subject matter experts. In this meeting report, we summarize the presentations and recap the main themes of the panel discussions.

Assessing the pattern electroretinogram as a proxy measure for dopamine in the context of iron deficiency.

OBJECTIVES: Animal studies have suggested that dietary iron deficiency (ID) negatively affects dopamine (DA) synthesis and re-uptake, which in turn negatively affects memory and cognition. This study was intended to assess whether the pattern electroretinogram (pattern ERG) could be used as an indirect measure of DA in college-age women with and without ID by determining the extent to which features of the ERG were sensitive to iron status and were related to other indirect measures of DA. METHODS: The pattern ERG was measured in 21 iron deficient non-anemic (IDNA) and 21 iron sufficient (IS) women, who also performed a contrast detection and probabilistic selection task, both with concurrent electroencephalography (EEG). Both spontaneous and task-related blink rates were also measured. RESULTS: The implicit times of the A- and B-waves were significantly longer for the IDNA than for the IS women. Both the amplitudes and implicit times of the A- and B-waves were significantly correlated with levels of serum ferritin (sFt). Only the amplitude of the A-wave was correlated with spontaneous blink rate. It was possible to accurately identify a woman's iron status solely on the basis of the implicit time of the B-wave. Finally, the implicit times of the ERG features mediated the relationship between iron levels and accuracy in the probabilistic selection task. CONCLUSIONS: Results suggest the utility of the pattern ERG in testing the hypothesis that iron deficiency affects DA levels in humans and that this may be one of the mechanisms by which iron deficiency negatively affects cognition.

The Effect of Iron-Fortified Lentils on Blood and Cognitive Status among Adolescent Girls in Bangladesh.

BACKGROUND: Iron deficiency is highly prevalent in South Asia, especially among women and children in Bangladesh. Declines in cognitive performance are among the many functional consequences of iron deficiency. OBJECTIVE: We tested the hypothesis that, over the course of a 4-month iron fortification trial, cognitive performance would improve, and that improvement would be related to improvements in iron status. METHODS: Participants included 359 adolescent girls attending Bangladesh Rural Advancement Committee (BRAC) clubs as a subsample of a larger double-blind, cluster-randomized community trial in which participants were assigned to one of three conditions: a condition in which no lentils were supplied (NL, n = 118, but which had the usual intake of lentils), a control (non-fortified) lentil condition (CL, n = 124), and an iron-fortified lentil condition (FL, n = 117). In the FL and CL conditions, approximately 200 g of cooked lentils were served five days per week for a total of 85 feeding days. In addition to biomarkers of iron status, five cognitive tasks were measured at baseline (BL) and endline (EL): simple reaction time task (SRT), go/no-go task (GNG), attentional network task (ANT), the Sternberg memory search Task (SMS), and a cued recognition task (CRT). RESULTS: Cognitive performance at EL was significantly better for those in the FL relative to the CL and NL conditions, with this being true for at least one variable in each task, except for the GNG. In addition, there were consistent improvements in cognitive performance for those participants whose iron status improved. Although there were overall declines in iron status from BL to EL, the declines were smallest for those in the FL condition, and iron status was significantly better for those in FL condition at EL, relative to those in the CL and NL conditions. CONCLUSIONS: the provision of iron-fortified lentils provided a protective effect on iron status in the context of declines in iron status and supported higher levels of cognitive performance for adolescent girls at-risk of developing iron deficiency.

Effect of Nudges to Clinicians, Patients, or Both to Increase Statin Prescribing: A Cluster Randomized Clinical Trial.

Importance: Statins reduce the risk of major adverse cardiovascular events, but less than one-half of individuals in America who meet guideline criteria for a statin are actively prescribed this medication. Objective: To evaluate whether nudges to clinicians, patients, or both increase initiation of statin prescribing during primary care visits. Design, Setting, and Participants: This cluster randomized clinical trial evaluated statin prescribing of 158 clinicians from 28 primary care practices including 4131 patients. The design included a 12-month preintervention period and a 6-month intervention period between October 19, 2019, and April 18, 2021. Interventions: The usual care group received no interventions. The clinician nudge combined an active choice prompt in the electronic health record during the patient visit and monthly feedback on prescribing patterns compared with peers. The patient nudge was an interactive text message delivered 4 days before the visit. The combined nudge included the clinician and patient nudges. Main Outcomes and Measures: The primary outcome was initiation of a statin prescription during the visit. Results: The sample comprised 4131 patients with a mean (SD) age of 65.5 (10.5) years; 2120 (51.3%) were male; 1210 (29.3%) were Black, 106 (2.6%) were Hispanic, 2732 (66.1%) were White, and 83 (2.0%) were of other race or ethnicity, and 933 (22.6%) had atherosclerotic cardiovascular disease. In unadjusted analyses during the preintervention period, statins were prescribed to 5.6% of patients (105 of 1876) in the usual care group, 4.8% (97 of 2022) in the patient nudge group, 6.0% (104 of 1723) in the clinician nudge group, and 4.7% (82 of 1752) in the combined group. During the intervention, statins were prescribed to 7.3% of patients (75 of 1032) in the usual care group, 8.5% (100 of 1181) in the patient nudge group, 13.0% (128 of 981) in the clinician nudge arm, and 15.5% (145 of 937) in the combined group. In the main adjusted analyses relative to usual care, the clinician nudge significantly increased statin prescribing alone (5.5 percentage points; 95% CI, 3.4 to 7.8 percentage points; P = .01) and when combined with the patient nudge (7.2 percentage points; 95% CI, 5.1 to 9.1 percentage points; P = .001). The patient nudge alone did not change statin prescribing relative to usual care (0.9 percentage points; 95% CI, -0.8 to 2.5 percentage points; P = .32). Conclusions and Relevance: Nudges to clinicians with and without a patient nudge significantly increased initiation of a statin prescription during primary care visits. The patient nudge alone was not effective. Trial Registration: ClinicalTrials.gov Identifier: NCT04307472.

Don't be a Square: The processing mechanisms characterising the elemental dimensions of width and height.

What are the geometric and information processing characteristics of elementary figures composed of simple physical dimensions? There have been a number of investigations of perception of rectangles, including debate about configurality (e.g., integrality and gestalt properties) as well as the prime perceptual dimensions. Yet, because of ambiguity even in the "right" definition of configurality and an absence of penetrating methodologies, there is still little known concerning the information processing of these patterns. To this end, the present study brings together two separate theory-driven methodologies, general recognition theory (GRT) and systems factorial technology (SFT). The first attacks the problem of dimensional interactions while the latter seeks to uncover process characteristics such as architecture, decisional stopping rules, and workload capacity. The same observers and as much as possible, the same stimuli were used in both approaches. Through our GRT analyses, we found strong evidence for dependencies between the percepts of height and width on both within-stimulus and cross-stimulus bases. Height perception was better with narrow widths and width perception was superior with short heights. In addition, a significant positive within-trial correlation of dimensions was evidenced within squares but not with rectangles. Our SFT initiative uncovered consistent signatures of parallelism paired with super capacity, the latter appearing both through the traditional conditioning on being correct and still present when modest speed accuracy trade-off was accounted for. Thus, the SFT and GRT inferences were quite compatible with a plausible cause of the positive correlations being across-channel facilitatory interactions which led to super capacity processing.

Modeling relationships between iron status, behavior, and brain electrophysiology: evidence from a randomized study involving a biofortified grain in Indian adolescents.

BACKGROUND: Iron deficiency (ID) and iron deficiency anemia (IDA) are highly-prevalent nutrient deficiencies and have been shown to have a range of negative effects on cognition and brain function. Human intervention studies including measures at three levels-blood, brain, and behavior-are rare and our objective was to model the relationships among measures at these three levels in school-going Indian adolescents. METHODS: Male and female adolescents in rural India were screened for ID/IDA. Subjects consumed 2 meals/day for 6 months; half were randomly assigned to consume meals made from a standard grain (pearl millet) and half consumed meals made from an iron biofortified pearl millet (BPM). Prior to and then at the conclusion of the feeding trial, they completed a set of cognitive tests with concurrent electroencephalography (EEG). RESULTS: Overall, serum ferritin (sFt) levels improved over the course of the study. Ten of 21 possible measures of cognition showed improvements from baseline (BL) to endline (EL) that were larger for those consuming BPM than for those consuming the comparison pearl millet (CPM). Critically, the best model for the relationship between change in iron status and change in cognition had change in brain measures as a mediating factor, with both change in serum ferritin as a primary predictor and change in hemoglobin as a moderator. CONCLUSIONS: A dietary intervention involving a biofortified staple grain was shown to be efficacious in improving blood iron biomarkers, behavioral measures of cognition, and EEG measures of brain function. Modeling the relationships among these variables strongly suggests multiple mechanisms by which blood iron level affects brain function and cognition. TRIAL REGISTRATION: Registered at ClinicalTrials.gov, NCT02152150 , 02 June 2014.

Identifying Electronic Nicotine Delivery System Brands and Flavors on Instagram: Natural Language Processing Analysis.

BACKGROUND: Electronic nicotine delivery system (ENDS) brands, such as JUUL, used social media as a key component of their marketing strategy, which led to massive sales growth from 2015 to 2018. During this time, ENDS use rapidly increased among youths and young adults, with flavored products being particularly popular among these groups. OBJECTIVE: The aim of our study is to develop a named entity recognition (NER) model to identify potential emerging vaping brands and flavors from Instagram post text. NER is a natural language processing task for identifying specific types of words (entities) in text based on the characteristics of the entity and surrounding words. METHODS: NER models were trained on a labeled data set of 2272 Instagram posts coded for ENDS brands and flavors. We compared three types of NER models-conditional random fields, a residual convolutional neural network, and a fine-tuned distilled bidirectional encoder representations from transformers (FTDB) network-to identify brands and flavors in Instagram posts with key model outcomes of precision, recall, and F1 scores. We used data from Nielsen scanner sales and Wikipedia to create benchmark dictionaries to determine whether brands from established ENDS brand and flavor lists were mentioned in the Instagram posts in our sample. To prevent overfitting, we performed 5-fold cross-validation and reported the mean and SD of the model validation metrics across the folds. RESULTS: For brands, the residual convolutional neural network exhibited the highest mean precision (0.797, SD 0.084), and the FTDB exhibited the highest mean recall (0.869, SD 0.103). For flavors, the FTDB exhibited both the highest mean precision (0.860, SD 0.055) and recall (0.801, SD 0.091). All NER models outperformed the benchmark brand and flavor dictionary look-ups on mean precision, recall, and F1. Comparing between the benchmark brand lists, the larger Wikipedia list outperformed the Nielsen list in both precision and recall. CONCLUSIONS: Our findings suggest that NER models correctly identified ENDS brands and flavors in Instagram posts at rates competitive with, or better than, others in the published literature. Brands identified during manual annotation showed little overlap with those in Nielsen scanner data, suggesting that NER models may capture emerging brands with limited sales and distribution. NER models address the challenges of manual brand identification and can be used to support future infodemiology and infoveillance studies. Brands identified on social media should be cross-validated with Nielsen and other data sources to differentiate emerging brands that have become established from those with limited sales and distribution.

Electrophysiological resting state brain network and episodic memory in healthy aging adults.

Recent studies have emphasized the changes in large-scale brain networks related to healthy aging, with the ultimate purpose to aid in differentiating normal neurocognitive aging from neurodegenerative disorders that also arise with age. Emerging evidence from functional Magnetic Resonance Imaging (fMRI) indicates that connectivity patterns within specific brain networks, especially the Default Mode Network (DMN), distinguish those with Alzheimer's disease from healthy individuals. In addition, disruptive alterations in the large-scale brain systems that support high-level cognition are shown to accompany cognitive decline at the behavioral level, which is commonly observed in the aging populations, even in the absence of disease. Although fMRI is useful for assessing functional changes in brain networks, its high costs and limited accessibility discourage studies that need large populations. In this study, we investigated the aging-effect on large-scale networks of the human brain using high-density electroencephalography and electrophysiological source imaging, which is a less costly and more accessible alternative to fMRI. In particular, our study examined a group of healthy subjects in the age range from middle- to older-aged adults, which is an under-studied range in the literature. Employing a high-resolution computation model, our results revealed age associations in the connectivity pattern of DMN in a consistent manner with previous fMRI findings. Particularly, in combination with a standard battery of cognitive tests, our data showed that in the posterior cingulate / precuneus area of DMN higher brain connectivity was associated with lower performance on an episodic memory task. The findings demonstrate the feasibility of using electrophysiological imaging to characterize large-scale brain networks and suggest that changes in network connectivity are associated with normal aging.

Follicular Lymphoma Treated with First-Line Immunochemotherapy: A Review of PET/CT in Patients Who Did Not Achieve a Complete Metabolic Response in the GALLIUM Study.

Complete metabolic response (CMR) on PET/CT was the sole independent predictor of overall survival in the PET substudy of the phase III GALLIUM trial (NCT01332968) in first-line treatment of high-tumor-burden follicular lymphoma. The aim of this analysis was to further investigate the outcome of patients not achieving CMR. Methods: Two international experts rereviewed PET/CT scans from patients failing to achieve CMR assessed by the Independent Review Committee masked otherwise to committee results. Metabolic response category and Deauville score were assigned. Progression-free survival (PFS) was investigator-assessed with contrast-enhanced CT. Kaplan-Meier methodology was used to estimate landmark PFS and time to next treatment from end of induction by Deauville score. Patients who experienced CT-based progressive disease at the end of induction were excluded. Results: Fifty-four patients were reviewed. Six had CMR, 37 had a partial metabolic response, 2 had no metabolic response, and 9 had progressive metabolic disease. Patients were reassigned to CMR because 18F-FDG uptake was considered inflammatory (n = 2), was considered incidental neoplasia (n = 2), or was visually close to liver uptake but quantitatively lower (n = 2). There was a trend for shorter PFS and time to next treatment for patients with a Deauville score of 5 than a score of 4. High-grade mesenteric uptake at the end of induction was common, occurring in 20 patients with non-CMR, 14 of whom achieved CMR at all other sites. Only 3 of 14 (21%) patients with mesenteric uptake as the only site of disease experienced progression or death within 24 mo, whereas 4 of 6 patients (67%) with mesenteric and additional sites of 18F-FDG-avid disease experienced progression or death within 24 mo. All patients with early progression had measurable disease on contrast-enhanced CT at 18F-FDG-avid sites at the end of induction. Conclusion: After induction immunochemotherapy, CMR was assigned after reassessment in some patients, in whom increased 18F-FDG uptake was considered due to inflammation or incidental neoplasia rather than to lymphoma. Quantitative assessment to confirm the visual impression of residual uptake in lesions is suggested. Isolated mesenteric 18F-FDG uptake is likely a common false-positive finding at the end of induction and does not warrant changes in clinical management or disease surveillance unless there is measurable disease on contrast-enhanced CT or clinical suspicion of active disease.

Effects of shifts in response preferences on characteristics of representation and real-time processing: An application to the Hering illusion.

The multidimensional generalization of signal detection theory known as General Recognition Theory (GRT, Ashby & Townsend, Psychological Review, 93, 154-179 1986) has been used to model and characterize the ways in which changes in encoded perceptual information and the application of decisional operators can produce patterns in behavior that are consistent with notions such as configural processing and representation. In particular, a set of studies (e.g., Cornes et al.,, 2011; Wenger & Ingvalson; 2002, 2003) have shown how decisional influences might exert themselves in situations of configural perception, such that effects such as the Thatcher illusion can be obtained by way of shifts in decisional criteria. The present investigation brought to bear the combined tools of GRT and Systems Factorial Technology (SFT, Little et al.,, 2017; Townsend & Nozawa, 1995) with a classical illusion, to show that it is possible to induce a shift in a decisional criterion by way of varying payoffs and that this shift is accompanied by regular changes in the workload capacity statistic. The combined sets of analyses on the same stimuli reveal orderly effects on the decisional criteria (i.e., the signal detection parameter c), report independence (suggesting perceptual independence), invariant measures of sensitivity (i.e., the signal detection parameter [Formula: see text]),and exhaustive parallel processing accompanied by super capacity. We therefore propose wider use of the combined sets of tools, further exploration of the ability of decisional alterations to affect processing times while leaving accuracy largely unscathed, and reaching out to explore more of the information processing mechanisms of classical illusions.

Limited Shared Variance among Measures of Cognitive Performance Used in Nutrition Research: The Need to Prioritize Construct Validity and Biological Mechanisms in Choice of Measures.

BACKGROUND: The literature on correlates of nutrition has seen an increase in studies focused on functional consequences at the levels of neural, perceptual, and cognitive functioning. A range of measurement methodologies have been used in these studies, and investigators and funding agencies have raised the questions of how and if these various methodologies are at all comparable. OBJECTIVE: The aim was to determine the extent to which 3 different sets of cognitive measures provide comparable information across 2 subsamples that shared culture and language but differed in terms of socioeconomic status (SES) and academic preparation. METHODS: A total of 216 participants were recruited at 2 US universities. Each participant completed 3 sets of cognitive measures: 1 custom-designed set based on well-understood laboratory measures of cognition [cognitive task battery (COGTASKS)] and 2 normed batteries [Cambridge Neuropsychological Test Automated Battery (CANTAB), Weschler Adult Intelligence Scale, fourth edition (WAIS-IV)] designed for assessing general cognitive function. RESULTS: The 3 sets differed with respect to the extent to which SES and educational preparation affected the results, with COGTASKS showing no differences due to testing location and WAIS-IV showing substantial differences. There were, at best, weak correlations among tasks sharing the same name or claiming to measure the same construct. CONCLUSIONS: Comparability of measures of cognition cannot be assumed, even if measures have the same name or claim to assess the same construct. In selecting and evaluating different measures, construct validity and underlying biological mechanisms need to be at least as important as population norms and the ability to connect with existing literatures.

A beginning quantitative taxonomy of cognitive activation systems and application to continuous flow processes.

Much progress has been made in the investigation of perceptual, cognitive, and action mechanisms under the assumption that when one subprocess precedes another, the first one starts and finishes before the other begins. We call such processes "Dondersian" after the Dutch physiologist who first formulated this concept. Serial systems obey this precept (e.g., Townsend, 1974). However, most dynamic systems in nature do not: instead, each subprocess communicates its state to its immediate successors continuously. Although the mathematics for physical systems has received extensive treatment over the last three centuries, applications to human cognition have been exiguous. Therefore, the pioneering papers by Charles Eriksen and colleagues on continuous flow dynamics (e.g., Eriksen & Schulz, Perception & Psychophysics, 25, 249-263, 1979; Coles et al.,, Journal of Experimental Psychology: Human Perception and Performance, 11(5), 529, 1985) must be viewed as truly revolutionary. Surprisingly, there has been almost no advancement on this front since. With the goal of bringing this theme back into the scientific consciousness and extending and deepening our understanding of such systems, we develop a taxonomy that emphasizes the fundamental characteristics of continuous flow dynamics. Subsequently, we complexify the treated systems in such a way as to illustrate the popular cascade model (Ashby, Psychological Review, 89, 599-607, 1982; McClelland, Psychological Review, 86, 287-330, 1979) and use it to simulate the classic findings of Eriksen and colleagues (Eriksen & Hoffman, Perception & Psychophysics, 12(2), 201-204, 1972).

The misrepresentation of spatial uncertainty in visual search: Single- versus joint-distribution probability cues.

The present study used information theory to quantify the extent to which different spatial cues conveyed the entropy associated with the identity and location of a visual search target. Single-distribution cues reflected the probability that the target would appear at one fixed location whereas joint-distribution cues reflected the probability that the target would appear at the location where another cue (arrow) pointed. The present study used a novel demand-selection paradigm to examine the extent to which individuals explicitly preferred one type of probability cue over the other. Although both cues conveyed equal entropy, the main results suggested representation of greater target entropy for joint- than for single-distribution cues based on a comparison between predicted and observed probability cue choices across four experiments. The present findings emphasize the importance of understanding how individuals represent basic information-theoretic quantities that underlie more complex decision-theoretic processes such as Bayesian and active inference.

Perceptual learning produces perceptual objects.

In their seminal study of chess expertise, Simon and Chase (Chase & Simon, 1973; Simon & Chase, 1973) proposed that perceptual learning was a necessary component of skill acquisition. In their view, acquisition of skill results from the strategic use of learning at multiple levels to adaptively overcome inherent limitations. The knowledge acquired by way of perceptual learning that supported increasingly sophisticated perceptual discrimination processes, according to Simon and Chase, was referred to as a chunk. The chunk was conceptualized as a meaningful complex set of features that abstracted the notion of a perceptual object. Simon and Chase further suggested that meaningful combinations of chunks could be combined to form configurations (Simon & Chase, 1973, p. 399). The present study addresses this idea by framing the notion of a chunk in terms of two formal metatheories, one that addresses representation (Ashby & Townsend, 1986) and one that addresses processing (Townsend & Nozawa, 1995), and tests the prediction that perceptual learning produces organized perceptual objects (chunks). Two experiments combine behavioral and electroencephelographic (EEG) measures to show that perceptual learning produces (a) a shift from perceptual independence and separability to violations of separability, and (b) shifts from limited-capacity serial processing to supercapacity parallel processing. The evidence from both experiments is strong and consistent: perceptual learning does indeed induce chunking-the production of perceptual objects, and the foundation of perceptual expertise. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

Polatuzumab vedotin or pinatuzumab vedotin plus rituximab in patients with relapsed or refractory non-Hodgkin lymphoma: final results from a phase 2 randomised study (ROMULUS).

BACKGROUND: Antibody-drug conjugates (ADCs) polatuzumab vedotin (pola) and pinatuzumab vedotin (pina) showed clinical activity and tolerability in phase 1 trials. The aim of this multicentre, open-label, phase 2 study was to compare rituximab plus pola (R-pola) or pina (R-pina) in patients with relapsed or refractory diffuse large B-cell lymphoma and follicular lymphoma. METHODS: In this phase 2 randomised study at 39 investigational sites in six countries, patients were randomly assigned (1:1), by use of a dynamic hierarchical randomisation scheme, to receive R-pola or R-pina (375 mg/m2 rituximab plus 2·4 mg/kg ADCs) every 21 days until disease progression or unacceptable toxicity up to 1 year. Treatment allocations were not masked to the investigator, patients or sponsor after the patients were enrolled and randomly assigned. The primary objectives were safety and tolerability, and antitumour response. The study is registered with ClinicalTrials.gov, number NCT01691898, and is closed to accrual. FINDINGS: 81 patients with diffuse large B-cell lymphoma and 42 with follicular lymphoma were recruited between Sept 27, 2012, and Oct 10, 2013, and were assigned to treatment. 81 patients with diffuse large B-cell lymphoma and 41 patients with follicular lymphoma were eligible for analysis. Of the 42 patients with diffuse large B-cell lymphoma who received R-pina, 25 (60%, 95% CI 43-74) achieved an objective response and 11 (26%, 95% CI 14-42) achieved a complete response. Of the 39 patients in this cohort who received R-pola, 21 (54%, 95% CI 37-70) achieved an objective response, and eight (21%, 95% CI 9-36) achieved a complete response. Of the 21 patients in the follicular lymphoma cohort who received R-pina, 13 (62%, 95% CI 38-82) achieved an objective response, and one (5%, 95% CI 0·1-24) achieved a complete response. Of the 20 patients in this cohort who received R-pola, 14 (70%, 95% CI 46-88) achieved an objective response, and nine (45%, 95% CI 23-68) achieved a complete response. In the diffuse large B-cell lymphoma cohort, grade 3-5 adverse events occurred in 33 (79%) of 42 patients receiving R-pina (most common were neutropenia [29%] and hyperglycaemia [10%]; nine [21%] grade 5 adverse events, five of which were infection-related), and in 30 (77%) of 39 patients receiving R-pola (most common were neutropenia [23%], anaemia [8%] and diarrhoea [8%]; no grade 5 adverse events). In the follicular lymphoma cohort, grade 3-5 adverse events occurred in 13 (62%) of 21 patients receiving R-pina (most common were neutropenia [29%] and hyperglycaemia [14%]; no grade 5 adverse events) and in ten (50%) of 20 patients receiving R-pola (most common were neutropenia [15%] and diarrhoea [10%]; one grade 5 adverse event). INTERPRETATION: R-pina and R-pola are potential treatment options in patients with relapsed or refractory diffuse large B-cell lymphoma and follicular lymphoma. Pola was selected by the study funder for further development in non-Hodgkin lymphoma, partly because of longer durations of response than pina, and an overall benefit-risk favouring R-pola. FUNDING: F Hoffmann-La Roche.