Reliability of the picture description task of the Western Aphasia Battery - revised in Laurentian French persons without brain injury.

Objective: Limited normative data (including psychometric properties) are currently available on discourse tasks in non-dominant languages such as Laurentian (Quebec) French. The lack of linguistic and cultural adaptation has been identified as a barrier to discourse assessment. The main aim of this study is to document inter-rater and test-retest reliability properties of the picnic scene of the Western Aphasia Battery - Revised (WAB-R), including the cultural adaptation of an information content unit (ICU) list, and provide a normative reference for persons without brain injury (PWBI). Method: To do so, we also aimed to adapt an ICU checklist culturally and linguistically for Laurentian French speakers. Discourse samples were collected from 66 PWBI using the picture description task of the WAB-R. The ICU list was first adapted into Laurentian French. Then, ICUs and thematic units (TUs) were extracted manually, and microstructural variables were extracted using CLAN. Inter-rater reliability and test-retest reliability were determined. Results: Excellent inter-rater reliability was obtained for ICUs and TUs, as well as for all microstructural variables, except for mean length of utterance, which was found to be good. Conversely, test-retest reliability ranged from poor to moderate for all variables. Conclusion: The present study provides a validated ICU checklist for clinicians and researchers working with Laurentian French speakers when assessing discourse with the picnic scene of the WAB-R. It also addresses the gap in available psychometric data regarding inter-rater and test-retest reliability in PWBI.

Mindfulness-Based Mobile Health to Address Unhealthy Eating Among Middle-Aged Sexual Minority Women With Early Life Adversity: Mixed Methods Feasibility Trial.

BACKGROUND: Sexual minority women (lesbian, gay, bisexual, pansexual, queer, and other nonheterosexual women) remain considerably underrepresented in health research despite being at a higher risk for diabetes and obesity as well as stigma and psychological distress than their heterosexual peers. In addition, early life adversity (ELA) is prevalent among sexual minority women, which further increases risks for obesity, psychological distress, and poor cardiovascular health. App-based mindfulness interventions are potentially promising for this group in mitigating the adverse health effects of ELA, reducing food craving and unhealthy eating, addressing the risks associated with obesity. OBJECTIVE: This mixed methods feasibility trial aimed to test a mindfulness-based mobile health approach for middle-aged sexual minority women (aged 30-55 years) with ELA and overweight or obesity (BMI ≥25 kg/m2) to improve health outcomes. METHODS: The single-arm trial was advertised on social media and various lesbian, gay, bisexual, transgender, and queer web-based groups. At baseline, after the intervention (2 months), and at the 4-month follow-up, participants completed assessments of primary outcomes (food craving, emotional eating, and weight via a mailed scale) and secondary outcomes (depression, anxiety, mindfulness, and emotion dysregulation). A standardized weight measure was mailed to participants for weight reporting. Feasibility and acceptability were assessed after the intervention via surveys and semistructured exit interviews. RESULTS: We screened 442 individuals, among which 30 eligible sexual minority women (mean age 40.20, SD 7.15 years) from various US regions were enrolled in the study. At baseline, 86% (26/30) and 80% (24/30) of participants had elevated depressive and anxiety symptoms, respectively. Among the 30 enrolled participants, 20 (66%) completed all intervention modules, 25 (83%) were retained at the 2-month follow-up, and 20 (66%) were retained at the 4-month follow-up. None reported adverse effects. From baseline to the 4-month follow-up, large effects were found in food craving (Cohen d=1.64) and reward-based eating (Cohen d=1.56), whereas small effects were found with weight (Cohen d=0.20; 4.21 kg on average). Significant improvements were also found in the secondary outcomes (depression, Cohen d=0.98; anxiety, Cohen d=0.50; mindfulness, Cohen d=0.49; and emotion dysregulation, Cohen d=0.44; all P<.05). Participants with higher levels of parental verbal and emotional abuse were particularly responsive to the intervention. Participants reported that the program aligned with their goals and expectations, was easy to use, and facilitated changes in eating behavior and mental health. Barriers to engagement included the need for diverse teachers, individualized support, and body positive language. CONCLUSIONS: This early phase feasibility trial provides proof-of-concept support for a mindfulness mobile health approach to improve obesity-related outcomes among sexual minority women and warrants a larger randomized controlled trial in the future. The findings also suggest the need to address trauma and psychological health when addressing weight-related outcomes among sexual minority women.

Cluster-based psychological phenotyping and differences in anxiety treatment outcomes.

The identification of markers of mental health illness treatment response and susceptibility using personalized medicine has been elusive. In the context of psychological treatment for anxiety, we conducted two studies to identify psychological phenotypes with distinct characteristics related to: psychological intervention modalities (mindfulness training/awareness), mechanism of action (worry), and clinical outcome (generalized anxiety disorder scale scores). We also examined whether phenotype membership interacted with treatment response (Study 1) and mental health illness diagnosis (Studies 1-2). Interoceptive awareness, emotional reactivity, worry, and anxiety were assessed at baseline in treatment-seeking individuals (Study 1, n = 63) and from the general population (Study 2, n = 14,010). In Study 1, participants were randomly assigned to an app-delivered mindfulness program for anxiety for two months or treatment as usual. Changes in anxiety were assessed 1 and 2 months post-treatment initiation. In studies 1-2, three phenotypes were identified: 'severely anxious with body/emotional awareness' (cluster 1), 'body/emotionally unaware' (cluster 2), and 'non-reactive and aware' (cluster 3). Study 1's results revealed a significant treatment response relative to controls (ps < 0.001) for clusters 1 and 3, but not for cluster 2. Chi-square analyses revealed that phenotypes exhibited significantly different proportions of participants with mental health diagnoses (studies 1-2). These results suggest that psychological phenotyping can bring the application of personalized medicine into clinical settings.Registry name and URL: Developing a novel digital therapeutic for the treatment of generalized anxiety disorder https://clinicaltrials.gov/ct2/show/NCT03683472?term=judson+brewer&draw=1&rank=1 .Trial registration: Registered at clinicaltrials.gov (NCT03683472) on 25/09/2018.

Analyzing the Impact of Mobile App Engagement on Mental Health Outcomes: Secondary Analysis of the Unwinding Anxiety Program.

BACKGROUND: App-based interventions provide a promising avenue for mitigating the burden on mental health services by complimenting therapist-led treatments for anxiety. However, it remains unclear how specific systems' use of app features may be associated with changes in mental health outcomes (eg, anxiety and worry). OBJECTIVE: This study was a secondary analysis of engagement data from a stage 1 randomized controlled trial testing the impact of the Unwinding Anxiety mobile app among adults with generalized anxiety disorder. The aims of this study were 2-fold: to investigate whether higher microengagement with the primary intervention feature (ie, educational modules) is associated with positive changes in mental health outcomes at 2 months (ie, anxiety, worry, interoceptive awareness, and emotional reactivity) and to investigate whether the use of adjunctive app features is also associated with changes in mental health outcomes. METHODS: We analyzed the intervention group during the stage 1 trial of the Unwinding Anxiety mobile app. The total use of specific mobile app features and the use specific to each feature were calculated. We used multivariate linear models with a priori significance of α=.05 to investigate the impact of cumulative app use on anxiety, worry, interoceptive awareness, and emotional regulation at 2 months, controlling for baseline scores, age, and education level in all models. Significant relationships between system use metrics and baseline participant characteristics were assessed for differences in use groupings using between-group testing (ie, 2-tailed t tests for continuous data and chi-square analyses for categorical data). RESULTS: The sample was primarily female (25/27, 93%), and the average age was 42.9 (SD 15.6) years. Educational module completion, the central intervention component, averaged 20.2 (SD 11.4) modules out of 32 for the total sample. Multivariate models revealed that completing >75% of the program was associated with an average 22.6-point increase in interoceptive awareness (b=22.6; SE 8.32; P=.01; 95% CI 5.3-39.8) and an 11.6-point decrease in worry (b=-11.6; SE 4.12; P=.01; 95% CI -20.2 to -3.1). In addition, a single log unit change in the total number of meditations was associated with a 0.62-point reduction in the Generalized Anxiety Disorder-7 scale scores (b=0.62; SE 0.27; P=.005; 95% CI -1.2 to -0.6), whereas a single log unit use of the stress meter was associated with an average of a 0.5-point increase in emotional regulation scores (Five Facet Mindfulness Questionnaire; b=0.5; SE 0.21; P=.03; 95% CI 0.1-0.9). CONCLUSIONS: This study offers a clearer understanding of the impact of engagement with app features on broader engagement with the health outcomes of interest. This study highlights the importance of comprehensive investigations of engagement during the development of evidence-based mobile apps.

Denitrification in foraminifera has an ancient origin and is complemented by associated bacteria.

Benthic foraminifera are unicellular eukaryotes that inhabit sediments of aquatic environments. Several foraminifera of the order Rotaliida are known to store and use nitrate for denitrification, a unique energy metabolism among eukaryotes. The rotaliid Globobulimina spp. has been shown to encode an incomplete denitrification pathway of bacterial origin. However, the prevalence of denitrification genes in foraminifera remains unknown, and the missing denitrification pathway components are elusive. Analyzing transcriptomes and metagenomes of 10 foraminiferal species from the Peruvian oxygen minimum zone, we show that denitrification genes are highly conserved in foraminifera. We infer the last common ancestor of denitrifying foraminifera, which enables us to predict the ability to denitrify for additional foraminiferal species. Additionally, an examination of the foraminiferal microbiota reveals evidence for a stable interaction with Desulfobacteraceae, which harbor genes that complement the foraminiferal denitrification pathway. Our results provide evidence that foraminiferal denitrification is complemented by the foraminifera-associated microbiome. The interaction of foraminifera with their resident bacteria is at the basis of foraminiferal adaptation to anaerobic environments that manifested in ecological success in oxygen depleted habitats.

Targeting Anxiety to Improve Sleep Disturbance: A Randomized Clinical Trial of App-Based Mindfulness Training.

OBJECTIVE: Sleep disturbance is experienced by nearly 20% of Americans and is highly comorbid with anxiety. Sleep disturbances may predict the development of anxiety disorders. Mindfulness training (MT) has shown efficacy for anxiety yet remains limited by in-person-based delivery. Digitally delivered MT may target habitual worry processes, yet its effects on sleep have not been studied. This study tested if app-based MT for anxiety could reduce worry and improve sleep and examined the underlying mechanisms. METHODS: Individuals reporting worry interfering with sleep were randomized to treatment as usual (TAU; n = 40) or TAU + app-based MT (n = 40). Treatment-related changes in worry-related sleep disturbances (WRSDs), worry, nonreactivity, and anxiety were evaluated via self-report questionnaires at 1 and 2 months after treatment initiation. Fitbit devices were used to record total sleep time and estimate sleep efficiency. At 2 months, TAU received access to app-based MT, and both groups were reassessed at 4 months. RESULTS: In a modified intent-to-treat analysis, WRSD scores decreased by 27% in TAU + MT (n = 36) and 6% in TAU (n = 35) at 2 months (median [IQR] change = 11 [4.3] versus 15 [5.0], p = .001). These WRSD reductions were mediated by decreased worry, particularly improved nonreactivity (p values < .001). At 4 months, TAU reported a significant 29% reduction after beginning app-based MT at 2 months and TAU + MT maintained its gains. No significant between-group differences in average estimated total sleep time or sleep efficiency were found after 2 months of using the app. CONCLUSIONS: Few mindfulness-related apps have been evaluated for clinical efficacy and/or mechanism. Results from this study demonstrate a mechanistic link between MT and increased emotional nonreactivity, decreased worry, and reduction in reported sleep disturbances, suggesting that app-based MT may be a viable option to help individuals who report that worry interferes with their sleep.Trial Registration: ClinicalTrials.gov identifier: NCT03684057.

Clinical Efficacy and Psychological Mechanisms of an App-Based Digital Therapeutic for Generalized Anxiety Disorder: Randomized Controlled Trial.

BACKGROUND: Current treatments for generalized anxiety disorder (GAD) often yield suboptimal outcomes, partly because of insufficient targeting of underlying psychological mechanisms (eg, avoidance reinforcement learning). Mindfulness training (MT) has shown efficacy for anxiety; yet, widespread adoption has been limited, partly because of the difficulty in scaling in-person-based delivery. Digital therapeutics are emerging as potentially viable treatments; however, very few have been empirically validated. OBJECTIVE: The aim of this study is to test the efficacy and mechanism of an app-delivered MT that was designed to target a potential mechanism of anxiety (reinforcement learning), based on which previous studies have shown concern regarding feedback and the perpetuation of anxiety through negative reinforcement. METHODS: Individuals with GAD were recruited using social media advertisements and randomized during an in-person visit to receive treatment as usual (n=33) or treatment as usual+app-delivered MT (Unwinding Anxiety; n=32). The latter was composed of 30 modules to be completed over a 2-month period. Associated changes in outcomes were assessed using self-report questionnaires 1 and 2 months after treatment initiation. RESULTS: We randomized 65 participants in this study, and a modified intent-to-treat approach was used for analysis. The median number of modules completed by the MT group was 25.5 (IQR 17) out of 30; 46% (13/28) of the participants completed the program. In addition, the MT group demonstrated a significant reduction in anxiety (GAD-7) compared with the control group at 2 months (67% vs 14%; median change in GAD-7: -8.5 [IQR 6.5] vs -1.0 [IQR 5.0]; P<.001; 95% CI 6-10). Increases in mindfulness at 1 month (nonreactivity subscale) mediated decreases in worry at 2 months (Penn State Worry Questionnaire; P=.02) and decreases in worry at 1 month mediated reductions in anxiety at 2 months (P=.03). CONCLUSIONS: To our knowledge, this is the first report on the efficacy and mechanism of an app-delivered MT for GAD. These findings demonstrate the clinical efficacy of MT as a digital therapeutic for individuals with anxiety (number needed to treat=1.6). These results also link recent advances in our mechanistic understanding of anxiety with treatment development, showing that app-delivered MT targets key reinforcement learning pathways, resulting in tangible, clinically meaningful reductions in worry and anxiety. Evidence-based, mechanistically targeted digital therapeutics have the potential to improve health at a population level at a low cost. TRIAL REGISTRATION: ClinicalTrials.gov NCT03683472; https://clinicaltrials.gov/ct2/show/NCT03683472.

Can Approaching Anxiety Like a Habit Lead to Novel Treatments?

Anxiety disorders make up the most prevalent class of mental illnesses. Given the growing prevalence of anxiety in the United States and beyond, there is an urgent clinical need to develop nonpharmacologic treatments that effectively treat and reduce its core symptoms (eg, worry). A leading theory posits that although worrying may be unpleasant, the immediate emotions that are avoided by concentrating on worry are often perceived as more aversive (eg, fear, anger, grief). From a mechanistic perspective, worry is thought to be learned and reinforced in a similar manner to other types of positively and negatively reinforced behaviors: habits. Mindfulness training, a practice that brings awareness to cognitive, affective, and physiological experiences, when delivered in-person via programs such as mindfulness-based stress reduction (MBSR) and mindfulness-based cognitive therapy (MBCT), has demonstrated effectiveness in reducing anxiety, but is difficult to scale in this manner. In this review, we explore novel approaches to using mindfulness training to specifically target the theoretical mechanisms underlying the perpetuation of anxiety (eg, worry as a habit), and the emergence of mobile health platforms (eg, digital therapeutics) as potential vehicles for remote delivery of treatment.

Awareness drives changes in reward value which predict eating behavior change: Probing reinforcement learning using experience sampling from mobile mindfulness training for maladaptive eating.

BACKGROUND AND AIMS: Maladaptive eating habits are a major cause of obesity and weight-related illness. The development of empirically-based approaches, such as mindfulness training (MT) that target accurate mechanisms of action to address these behaviors is therefore critical. Two studies were conducted to examine the impact of MT on maladaptive eating and determine the involvement of reinforcement learning mechanisms underlying these effects. METHODS: In Study1, maladaptive eating behaviors were assessed using self-report questionnaires at baseline and 8 weeks after an app-based MT intervention (n = 46). A novel mindful eating craving tool was embedded in our intervention to assess: eating behaviors (intake frequency/magnitude), and reward (contentment ratings) experienced after eating. Using a well-established reinforcement learning (Rescorla-Wagner) model, expected reward values (EV) were estimated as a function of contentment levels reported after eating. In Study2 (n = 1,119), craving tool assessments were examined in an independent sample using the app in a real-world naturalistic context. RESULTS: Study 1's results revealed a significant decrease in EV and eating behaviors across craving tool uses. In addition, changes in reward values predicted decreases in eating behaviors. Finally, Study 1's results revealed significant pre-post intervention reductions in self-reported eating behaviors. In Study2, we observed a significant decrease in EV, but not in eating behaviors, across craving tool uses. Study 2 also revealed a predictive relationship between EV and eating behaviors. DISCUSSION AND CONCLUSIONS: These results support the implementation of MT to prevent and treat maladaptive eating behaviors, which target reinforcement learning processes as mechanisms of action.

The Transfer of the Ferredoxin Gene From the Chloroplast to the Nuclear Genome Is Ancient Within the Paraphyletic Genus Thalassiosira.

Ferredoxins are iron-sulfur proteins essential for a wide range of organisms because they are an electron transfer mediator involved in multiple metabolic pathways. In phytoplankton, these proteins are active in the mature chloroplasts, but the petF gene, encoding for ferredoxin, has been found either to be in the chloroplast genome or transferred to the nuclear genome as observed in the green algae and higher plant lineage. We experimentally determined the location of the petF gene in 12 strains of Thalassiosira covering three species using DNA sequencing and qPCR assays. The results showed that petF gene is located in the nuclear genome of all confirmed Thalassiosira oceanica strains (CCMP0999, 1001, 1005, and 1006) tested. In contrast, all Thalassiosira pseudonana (CCMP1012, 1013, 1014, and 1335) and Thalassiosira weissflogii (CCMP1010, 1049, and 1052) strains studied retained the gene in the chloroplast genome, as generally observed for Bacillariophyceae. Our evolutionary analyses further extend the dataset on the localization of the petF gene in the Thalassiosirales. The realization that the petF gene is nuclear-encoded in the Skeletonema genus allowed us to trace the petF gene transfer back to a single event that occurred within the paraphyletic genus Thalassiosira. Phylogenetic analyses revealed the need to reassess the taxonomic assignment of the Thalassiosira strain CCMP1616, since the genes used in our study did not cluster within the T. oceanica lineage. Our results suggest that this strains' diversification occurred prior to the ferredoxin gene transfer event. The functional transfer of petF genes provides insight into the evolutionary processes leading to chloroplast genome reduction and suggests ecological adaptation as a driving force for such chloroplast to nuclear gene transfer.

Can mindfulness mechanistically target worry to improve sleep disturbances? Theory and study protocol for app-based anxiety program.

OBJECTIVE: Anxiety is associated with sleep disturbance and insomnia. Mindfulness-based interventions, such as mindfulness-based stress reduction, have shown consistent anxiety reduction. Mindfulness training has been theorized to affect reinforcement learning, affecting habitual behaviors such as smoking and overeating, but a direct mechanistic link between the use of mindfulness training for anxiety reduction and improvement in sleep has not been studied. Moreover, the mechanisms by which mindfulness might affect worry and subsequent sleep disturbances have not been elucidated. This study protocol evaluates the impact an app-based mindfulness training program for anxiety might have on decreasing worry and improvement in sleep. METHOD: A randomized controlled study will be conducted in approximately 80 adults with worry that interferes with their sleep. Participants will be randomly allocated (1:1) to two groups: treatment-as-usual (TAU) or TAU + App-Based Mindfulness Training (Unwinding Anxiety app). The primary outcomes will be the non-reactivity subscale of the Five Facet Mindfulness Questionnaire and Patient-Reported Outcomes Measurement Information System sleep quality measures (Baer et al., 2008; Yu et al., 2011). Secondary outcomes will include the Penn State Worry Questionnaire, Generalized Anxiety Disorder-7, and Multidimensional Assessment of Interoceptive Awareness Scale (Mehling et al., 2012; Meyer, Miller, Metzger, & Borkovec, 1990; Spitzer, Kroenke, Williams, & Löwe, 2006). DISCUSSION: This study will be the first to test the mechanism of app-based mindfulness training on worry and sleep disturbance. Testing the mechanistic effects of mindfulness training using the science of behavior change framework will help move the field forward both in further elucidation of potential mechanisms of mindfulness (e.g., targeting reinforcement learning) and determining whether such a platform might be a viable method for delivering high-fidelity treatment at scale and for a low cost. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Physician Anxiety and Burnout: Symptom Correlates and a Prospective Pilot Study of App-Delivered Mindfulness Training.

BACKGROUND: Physician burnout is on the rise, yet little is known about its relationship to anxiety. Mindfulness-based stress reduction has demonstrated decreases in anxiety, yet physicians have reported reluctance to engage in it due to significant time commitments. OBJECTIVE: The aims of this study are to assess whether app-based mindfulness training can reduce anxiety in physicians and to explore if anxiety and burnout are correlated, thus leading to a reduction in both anxiety and burnout. METHODS: This was a nonrandomized pilot study comprised of 34 physicians who worked in a large US health care network and reported having anxiety. The intervention was an app-based mindfulness program. The main outcome measure was anxiety, measured by the Generalized Anxiety Disorder-7 (GAD-7). The secondary outcome measures assessed burnout: cynicism and emotional exhaustion items from the Maslach Burnout Inventory. RESULTS: GAD-7 scores decreased significantly at posttreatment (1 month after treatment initiation, 48% reduction, P<.001) and at the 3-month follow-up (57% reduction, P<.001). There was a significant correlation between anxiety and burnout (cynicism: r=.43; P=.01; emotional exhaustion: r=.71; P<.001). There was also a significant decrease in cynicism (50% reduction, P=.003 at posttreatment; 50% reduction, P=.009 at follow-up) and emotional exhaustion at both time points (20% reduction, P<.001 at posttreatment; 20% reduction, P=.003 at follow-up). CONCLUSIONS: This pilot study is the first to test an app-based mindfulness training program targeted at reducing anxiety with physicians and to demonstrate that in physicians, anxiety is correlated with burnout. These findings suggest that this may be an effective tool to reduce anxiety and burnout in physicians. TRIAL REGISTRATION: ClinicalTrials.gov NCT04137081; https://www.clinicaltrials.gov/ct2/show/NCT04137081.

Quitting starts in the brain: a randomized controlled trial of app-based mindfulness shows decreases in neural responses to smoking cues that predict reductions in smoking.

Current treatments for smoking yield suboptimal outcomes, partly because of an inability to reduce cue-induced smoking. Mindfulness training (MT) has shown preliminary efficacy for smoking cessation, yet its neurobiological target remains unknown. Our prior work with nonsmokers indicates that MT reduces posterior cingulate cortex (PCC) activity. In individuals who smoke, the PCC, consistently a main hub of the "default mode network," activates in response to smoking cues. In this randomized controlled trial, we tested the effects of app-delivered MT on PCC reactivity to smoking cues and whether individual differences in MT-mediated PCC changes predicted smoking outcomes. Smoking cue-induced PCC reactivity was measured using functional magnetic resonance imaging at baseline and 1 month after receiving smartphone app-based MT (n = 33) vs. an active control (National Cancer Institute's QuitGuide, n = 34). Whether individual differences in treatment-related changes in PCC activity predicted smoking behavior was assessed. The MT group demonstrated a significant correlation between a reduction in PCC reactivity to smoking cues and a decline in cigarette consumption (r = 0.39, p = 0.02). No association was found in the control group (r = 0.08, p = 0.65). No effects of group alone were found in PCC or cigarette reduction. Post hoc analysis revealed this association is sex specific (women, r = 0.49, p = 0.03; men: r = -0.08, p = 0.79). This initial report indicates that MT specifically reduces smoking cue-induced PCC activity in a subject-specific manner, and the reduction in PCC activity predicts a concurrent decline in smoking. These findings link the hypothesized behavioral effects of MT for smoking to neural mechanisms particularly in women. This lays the groundwork for identifying individuals who may benefit from targeted digital therapeutic treatments such as smartphone-based MT, yielding improved clinical outcomes.

Metabolic preference of nitrate over oxygen as an electron acceptor in foraminifera from the Peruvian oxygen minimum zone.

Benthic foraminifera populate a diverse range of marine habitats. Their ability to use alternative electron acceptors-nitrate (NO3-) or oxygen (O2)-makes them important mediators of benthic nitrogen cycling. Nevertheless, the metabolic scaling of the two alternative respiration pathways and the environmental determinants of foraminiferal denitrification rates are yet unknown. We measured denitrification and O2 respiration rates for 10 benthic foraminifer species sampled in the Peruvian oxygen minimum zone (OMZ). Denitrification and O2 respiration rates significantly scale sublinearly with the cell volume. The scaling is lower for O2 respiration than for denitrification, indicating that NO3- metabolism during denitrification is more efficient than O2 metabolism during aerobic respiration in foraminifera from the Peruvian OMZ. The negative correlation of the O2 respiration rate with the surface/volume ratio is steeper than for the denitrification rate. This is likely explained by the presence of an intracellular NO3- storage in denitrifying foraminifera. Furthermore, we observe an increasing mean cell volume of the Peruvian foraminifera, under higher NO3- availability. This suggests that the cell size of denitrifying foraminifera is not limited by O2 but rather by NO3- availability. Based on our findings, we develop a mathematical formulation of foraminiferal cell volume as a predictor of respiration and denitrification rates, which can further constrain foraminiferal biogeochemical cycling in biogeochemical models. Our findings show that NO3- is the preferred electron acceptor in foraminifera from the OMZ, where the foraminiferal contribution to denitrification is governed by the ratio between NO3- and O2.

From research to clinic: A sensor reduction method for high-density EEG neurofeedback systems.

OBJECTIVE: To accurately deliver a source-estimated neurofeedback (NF) signal developed on a 128-sensors EEG system on a reduced 32-sensors EEG system. METHODS: A linearly constrained minimum variance beamformer algorithm was used to select the 64 sensors which contributed most highly to the source signal. Monte Carlo-based sampling was then used to randomly generate a large set of reduced 32-sensors montages from the 64 beamformer-selected sensors. The reduced montages were then tested for their ability to reproduce the 128-sensors NF. The high-performing montages were then pooled and analyzed by a k-means clustering machine learning algorithm to produce an optimized reduced 32-sensors montage. RESULTS: Nearly 4500 high-performing montages were discovered from the Monte Carlo sampling. After statistically analyzing this pool of high performing montages, a set of refined 32-sensors montages was generated that could reproduce the 128-sensors NF with greater than 80% accuracy for 72% of the test population. CONCLUSION: Our Monte Carlo reduction method was used to create reliable reduced-sensors montages which could be used to deliver accurate NF in clinical settings. SIGNIFICANCE: A translational pathway is now available by which high-density EEG-based NF measures can be delivered using clinically accessible low-density EEG systems.

Improving efficiency in neuroimaging research through application of Lean principles.

INTRODUCTION: "Lean" is a set of management principles which focus on increasing value and efficiency by reducing or avoiding waste (e.g., overproduction, defects, inventory, transportation, waiting, motion, over processing). It has been applied to manufacturing, education, and health care, leading to optimized process flow, increased efficiency and increased team empowerment. However, to date, it has not been applied to neuroimaging research. METHODS: Lean principles, such as Value stream mapping (e.g. a tool with which steps in the workflow can be identified on which to focus improvement efforts), 5S (e.g. an organizational method to boost workplace efficiency and efficacy) and Root-cause analysis (e.g. a problem-solving approach to identify key points of failure in a system) were applied to an ongoing, large neuroimaging study that included seven research visits per participant. All team members participated in a half-day exercise in which the entire project flow was visualized and areas of inefficiency were identified. Changes focused on removing obstacles, standardization, optimal arrangement of equipment and root-cause-analysis. A process for continuous improvement was also implemented. Total time of an experiment was recorded before implementation of Lean for two participants and after implementation of Lean for two participants. Satisfaction of team members was assessed anonymously on a 5-item Likert scale, ranging from much worsened to much improved. RESULTS: All team members (N = 6) considered the overall experience of conducting an experiment much improved after implementation of Lean. Five out of six team members indicated a much-improved reduction in time, with the final team member considering this somewhat improved. Average experiment time was reduced by 13% after implementation of Lean (from 142 and 147 minutes to 124 and 128 minutes). DISCUSSION: Lean principles can be successfully applied to neuroimaging research. Training in Lean principles for junior research scientists is recommended.

A Novel Eukaryotic Denitrification Pathway in Foraminifera.

Benthic foraminifera are unicellular eukaryotes inhabiting sediments of aquatic environments. Several species were shown to store and use nitrate for complete denitrification, a unique energy metabolism among eukaryotes. The population of benthic foraminifera reaches high densities in oxygen-depleted marine habitats, where they play a key role in the marine nitrogen cycle. However, the mechanisms of denitrification in foraminifera are still unknown, and the possibility of a contribution of associated bacteria is debated. Here, we present evidence for a novel eukaryotic denitrification pathway that is encoded in foraminiferal genomes. Large-scale genome and transcriptomes analyses reveal the presence of a denitrification pathway in foraminifera species of the genus Globobulimina. This includes the enzymes nitrite reductase (NirK) and nitric oxide reductase (Nor) as well as a wide range of nitrate transporters (Nrt). A phylogenetic reconstruction of the enzymes' evolutionary history uncovers evidence for an ancient acquisition of the foraminiferal denitrification pathway from prokaryotes. We propose a model for denitrification in foraminifera, where a common electron transport chain is used for anaerobic and aerobic respiration. The evolution of hybrid respiration in foraminifera likely contributed to their ecological success, which is well documented in palaeontological records since the Cambrian period.

Genome and low-iron response of an oceanic diatom adapted to chronic iron limitation.

BACKGROUND: Biogeochemical elemental cycling is driven by primary production of biomass via phototrophic phytoplankton growth, with 40% of marine productivity being assigned to diatoms. Phytoplankton growth is widely limited by the availability of iron, an essential component of the photosynthetic apparatus. The oceanic diatom Thalassiosira oceanica shows a remarkable tolerance to low-iron conditions and was chosen as a model for deciphering the cellular response upon shortage of this essential micronutrient. RESULTS: The combined efforts in genomics, transcriptomics and proteomics reveal an unexpected metabolic flexibility in response to iron availability for T. oceanica CCMP1005. The complex response comprises cellular retrenchment as well as remodeling of bioenergetic pathways, where the abundance of iron-rich photosynthetic proteins is lowered, whereas iron-rich mitochondrial proteins are preserved. As a consequence of iron deprivation, the photosynthetic machinery undergoes a remodeling to adjust the light energy utilization with the overall decrease in photosynthetic electron transfer complexes. CONCLUSIONS: Beneficial adaptations to low-iron environments include strategies to lower the cellular iron requirements and to enhance iron uptake. A novel contribution enhancing iron economy of phototrophic growth is observed with the iron-regulated substitution of three metal-containing fructose-bisphosphate aldolases involved in metabolic conversion of carbohydrates for enzymes that do not contain metals. Further, our data identify candidate components of a high-affinity iron-uptake system, with several of the involved genes and domains originating from duplication events. A high genomic plasticity, as seen from the fraction of genes acquired through horizontal gene transfer, provides the platform for these complex adaptations to a low-iron world.

Recent transfer of an iron-regulated gene from the plastid to the nuclear genome in an oceanic diatom adapted to chronic iron limitation.

BACKGROUND: Although the importance and widespread occurrence of iron limitation in the contemporary ocean is well documented, we still know relatively little about genetic adaptation of phytoplankton to these environments. Compared to its coastal relative Thalassiosira pseudonana, the oceanic diatom Thalassiosira oceanica is highly tolerant to iron limitation. The adaptation to low-iron conditions in T. oceanica has been attributed to a decrease in the photosynthetic components that are rich in iron. Genomic information on T. oceanica may shed light on the genetic basis of the physiological differences between the two species. RESULTS: The complete 141790 bp sequence of the T. oceanica chloroplast genome [GenBank: GU323224], assembled from massively parallel pyrosequencing (454) shotgun reads, revealed that the petF gene encoding for ferredoxin, which is localized in the chloroplast genome in T. pseudonana and other diatoms, has been transferred to the nucleus in T. oceanica. The iron-sulfur protein ferredoxin, a key element of the chloroplast electron transport chain, can be replaced by the iron-free flavodoxin under iron-limited growth conditions thereby contributing to a reduction in the cellular iron requirements. From a comparison to the genomic context of the T. pseudonana petF gene, the T. oceanica ortholog can be traced back to its chloroplast origin. The coding potential of the T. oceanica chloroplast genome is comparable to that of T. pseudonana and Phaeodactylum tricornutum, though a novel expressed ORF appears in the genomic region that has been subjected to rearrangements linked to the petF gene transfer event. CONCLUSIONS: The transfer of the petF from the cp to the nuclear genome in T. oceanica represents a major difference between the two closely related species. The ability of T. oceanica to tolerate iron limitation suggests that the transfer of petF from the chloroplast to the nuclear genome might have contributed to the ecological success of this species.