Moderate Bias Research Articles

The effectiveness of nudging: A meta-analysis of choice architecture interventions across behavioral domains

Over the past decade, choice architecture interventions or so-called nudges have received widespread attention from both researchers and policy makers. Built on insights from the behavioral sciences, this class of behavioral interventions focuses on the design of choice environments that facilitate personally and socially desirable decisions without restricting people in their freedom of choice. Drawing on more than 200 studies reporting over 450 effect sizes (n = 2,149,683), we present a comprehensive analysis of the effectiveness of choice architecture interventions across techniques, behavioral domains, and contextual study characteristics. Our results show that choice architecture interventions overall promote behavior change with a small to medium effect size of Cohen's d = 0.45 (95% CI [0.39, 0.52]). In addition, we find that the effectiveness of choice architecture interventions varies significantly as a function of technique and domain. Across behavioral domains, interventions that target the organization and structure of choice alternatives (decision structure) consistently outperform interventions that focus on the description of alternatives (decision information) or the reinforcement of behavioral intentions (decision assistance). Food choices are particularly responsive to choice architecture interventions, with effect sizes up to 2.5 times larger than those in other behavioral domains. Overall, choice architecture interventions affect behavior relatively independently of contextual study characteristics such as the geographical location or the target population of the intervention. Our analysis further reveals a moderate publication bias toward positive results in the literature. We end with a discussion of the implications of our findings for theory and behaviorally informed policy making.

Population Pharmacokinetic Model Development of Tacrolimus in Pediatric and Young Adult Patients Undergoing Hematopoietic Cell Transplantation.

Background: With a notably narrow therapeutic window and wide intra- and interindividual pharmacokinetic (PK) variability, initial weight-based dosing along with routine therapeutic drug monitoring of tacrolimus are employed to optimize its clinical utilization. Both supratherapeutic and subtherapeutic tacrolimus concentrations can result in poor outcomes, thus tacrolimus PK variability is particularly important to consider in the pediatric population given the differences in absorption, distribution, metabolism, and excretion among children of various sizes and at different stages of development. The primary goals of the current study were to develop a population PK (PopPK) model for tacrolimus IV continuous infusion in the pediatric and young adult hematopoietic cell transplant (HCT) population and implement the PopPK model in a clinically available Bayesian forecasting tool. Methods: A retrospective chart review was conducted of 111 pediatric and young adult patients who received IV tacrolimus by continuous infusion early in the post-transplant period during HCT from February 2016 to July 2020 at our institution. PopPK model building was performed in NONMEM. The PopPK model building process included identifying structural and random effects models that best fit the data and then identifying which patient-specific covariates (if any) further improved model fit. Results: A total of 1,648 tacrolimus plasma steady-state trough concentrations were included in the PopPK modeling process. A 2-compartment structural model best fit the data. Allometrically-scaled weight was a covariate that improved estimation of both clearance and volume of distribution. Overall, model predictions only showed moderate bias, with minor under-prediction at lower concentrations and minor over-prediction at higher predicted concentrations. The model was implemented in a Bayesian dosing tool and made available at the point-of-care. Discussion: Novel therapeutic drug monitoring strategies for tacrolimus within the pediatric and young adult HCT population are necessary to reduce toxicity and improve efficacy in clinical practice. The model developed presents clinical utility in optimizing the use of tacrolimus by enabling model-guided, individualized dosing of IV, continuous tacrolimus via a Bayesian forecasting platform.

Antimicrobial stewardship for surgical antibiotic prophylaxis and surgical site infections: a systematic review.

Background Surgical site infections account for 14-17% of all healthcare-associated infections. Antimicrobial stewardship (AMS) are complementary strategies developed to optimize the use of antimicrobials. Aim to evaluate the effectiveness of AMS in promoting adherence to surgical antibiotic prophylaxis protocols in hospitalized patients, reducing surgical site infection rate and cost-benefit ratio. Method This systematic review of randomized clinical trials, non-randomized clinical trials and before and after studies was performed using Pubmed, Cochrane, Web of Science, Scopus, Embase, Google Scholar and ClinicalTrials.gov, in addition to reference lists of included studies. The risk of bias of studies was measured by the ROBINS-I checklist and the quality of the evidence synthesis by GRADE. Results Fourteen before and after design studies were included. In 85.7% of the studies, AMS was effective in increasing adherence to surgical antibiotic prophylaxis protocols and in 28.5%, there was reduction in surgical site infection rate. Three studies evaluated cost-benefit ratio and found a favorable impact. Eight (57%) studies were at risk of moderate bias and six had severe bias. The evaluation of the synthesis of evidence showed quality ranging from low to very low. Conclusion AMS, such as audit, feedback, education, implementation of a protocol, and a computer-assisted decision support methodology, appear to be effective in promoting adherence to surgical antibiotic prophylaxis protocols, reducing surgical site infection rate with a positive economic impact. However, more studies, particularly randomized clinical trials, are needed to improve the level of evidence of available information on AMS in order to favor decision-making.

Development of a model of medication review for use in clinical practice: Bristol medication review model

BackgroundMedication review is a core aspect of medicine optimisation, yet existing models of review vary substantially in structure and content and are not necessarily easy to implement in clinical practice. This study aimed to use evidence from the existing literature to identify key medication review components and use this to inform the design of an improved review model.MethodsA systematic review was conducted (PROSPERO: CRD42018109788) to identify randomised control trials of stand-alone medication review in adults (18+ years). The review updated that by Huiskes et al. (BMC Fam Pract. 18:5, 2017), using the same search strategy implemented in MEDLINE and Embase. Studies were assessed using the Cochrane risk of bias tool. Key review components were identified, alongside relevant clinical and health service outcomes. A working group (patients, doctors and pharmacists) developed the model through an iterative consensus process (appraisal of documents plus group discussions), working from the systematic review findings, brief evidence summaries for core review components and examples of previous models, to agree on the main purpose of the review model, overarching model structure, review components and supporting material.ResultsWe identified 28 unique studies, with moderate bias overall. Consistent medication review components included reconciliation (26 studies), safety assessment (22), suboptimal treatment (19), patient knowledge/preferences (18), adherence (14), over-the-counter therapy (13) and drug monitoring (10). There was limited evidence from studies for improvement in key clinical outcomes. The review structure was underpinned by patient values and preferences, with parallel information gathering and evaluation stages, feeding into the final decision-making and implementation. Most key components identified in the literature were included. The final model was considered to benefit from a patient-centred, holistic approach, which captured both patient-orientated and medication-focused problems, and aligned with traditional consultation methods thus facilitating implementation in practice.ConclusionsThe Bristol Medication Review Model provides a framework for standardised delivery of structured reviews. The model has the potential for use by all healthcare professionals with relevant clinical experience and is designed to offer flexibility of implementation not limited to a particular healthcare setting.

Rethinking the Egyptian–Israeli Peace Treaty: Perceptions and Receptions Within Egyptian Society (1977–1982)

The Egyptian–Israeli peace treaty marked a new era in the history of the Arab–Israeli conflict. Relying methodologically on the history of ideas and diplomatic history, this article sheds light on the diversity of the perceptions and receptions of peace and relations with Israel as manifested by two influential Egyptian public opinion shapers who represented polar approaches—the mouthpiece of the Muslim Brothers—the journal Al-Da‘wa and Rūz al-Yūsuf, the semi-independent liberal weekly with a moderate left bias. The timeframe is 1977–1982—from Sadat’s historical visit to Jerusalem to the Israeli invasion of Lebanon and its impact on the budding Israeli–Egyptian relations.

Does Emotional Expression Moderate Implicit Racial Bias? Examining Bias Following Smiling and Angry Primes

Given the pervasiveness of prejudice, researchers have become increasingly interested in examining racial bias at the intersection of race and other social and perceptual categories that have the potential to disrupt these negative attitudes. Across three studies, we examined whether the emotional expression of racial exemplars would moderate implicit racial bias. We found that racial bias on the Affect Misattribution Procedure only emerged in response to angry but not smiling Black male faces in comparison to White (Study 1) or White and Asian (Study 3) male faces with similar emotional expressions. Racial bias was also found toward Asian targets (Studies 2 and 3), but not only following angry primes. These findings suggest that negative stereotypes about Black men can create a contrast effect, making racial bias toward smiling faces less likely to be expressed in the presence of angry Black male faces.

A Bayesian meta-analysis of infants' ability to perceive audio-visual congruence for speech.

This paper quantifies the extent to which infants can perceive audio-visual congruence for speech information and assesses whether this ability changes with native language exposure over time. A hierarchical Bayesian robust regression model of 92separate effect sizes extracted from 24studies indicates a moderate effect size in a positive direction (0.35, CI [0.21: 0.50]). This result suggests that infants possess a robust ability to detect audio-visual congruence for speech. Moderator analyses, moreover, suggest that infants' audio-visual matching ability for speech emerges at an early point in the process of language acquisition and remains stable for both native and non-native speech throughout early development. A sensitivity analysis of the meta-analytic data, however, indicates that a moderate publication bias for significant results could shift the lower credible interval to include null effects. Based on these findings, we outline recommendations for new lines of enquiry and suggest ways to improve the replicability of results in future investigations.

Leptospirosis in pregnancy: A systematic review.

Leptospirosis is a leading zoonotic disease worldwide with more than 1 million cases in the general population per year. With leptospirosis being an emerging infectious disease and as the world's environment changes with more floods and environmental disasters, the burden of leptospirosis is expected to increase. The objectives of the systematic review were to explore how leptospirosis affects pregnancy, its burden in this population, its effects on maternal and fetal outcomes and the evidence base surrounding treatment options. We performed a systematic review of published and unpublished literature using automated and manual methods to screen nine electronic databases since inception, with no language restriction. Two reviewers independently screened articles, completed the data extraction and assessment of risk of bias. Due to significant heterogeneity and paucity of data, we were unable to carry out a meta-analysis, but we conducted a pooled analysis of individual patient data from the case reports and case series to examine the patient and disease characteristics, diagnostic methods, differential diagnoses, antibiotic treatments, and outcomes of leptospirosis in pregnancy. The protocol for this review was registered on the International Prospective Register of Systematic Reviews, PROSPERO: CRD42020151501. We identified 419 records, of which we included eight observational studies, 21 case reports, three case series and identified four relevant ongoing studies. Overall the studies were with moderate bias and of 'fair' quality. We estimated the incidence of leptospirosis in pregnancy to be 1.3 per 10,000 in women presenting with fever or with jaundice, but this is likely to be higher in endemic areas. Adverse fetal outcomes were found to be more common in pregnant patients who presented in the second trimester compared with patients who presented in the third trimester. There is overlap between how leptospirosis presents in pregnancy and in the general population. There is also overlap between the signs, symptoms and biochemical disturbances associated with leptospirosis in pregnancy and the presentation of pregnancy associated conditions, such as Pre-Eclampsia (PET), Acute Fatty Liver of Pregnancy (AFLP) and HELLP Syndrome (Haemolysis Elevated Liver enzymes Low Platelets). In 94% of identified cases with available data, there was an indicator in the patient history regarding exposure that could have helped include leptospirosis in the clinician's differential diagnosis. We also identified a range of suitable antibiotic therapies for treating leptospirosis in pregnancy, most commonly used were penicillins. This is the first systematic review of leptospirosis in pregnancy and it clearly shows the need to improve early diagnosis and treatment by asking early, treating early, and reporting well. Ask early-broaden differential diagnoses and ask early for potential leptospirosis exposures and risk factors. Treat early-increase index of suspicion in pregnant patients with fever in endemic areas and combine with rapid field diagnosis and early treatment. Report well-need for more good quality epidemiological studies on leptospirosis in pregnancy and better quality reporting of cases in literature.

Biases in air quality models capturing ozone trends at the urban, regional and national scales: Impacts on Relative Response Factors (RRFs)

Chemical transport models (CTMs) are widely used in scientific studies and air quality management. A particular application is to assess how pollutant concentrations, particularly ozone and PM, respond to emission controls. As part of a dynamic evaluation, two widely used CTMs, CMAQ and CAMx, were evaluated for how well they captured trends in observed surface ozone, as well as the changes in associated concentrations, between 2001 to 2011 and 2011 to 2016. Those periods were chosen as additional effort was used to improve emissions estimates for all three years. Prior studies found that both emissions inventories and observations indicate reductions in both ozone and NO2 during these periods, but studies have found that NO2 observations have not agreed as well with estimated emissions. In general, given the efforts to harmonize model inputs, the two models performed very similarly and captured the ozone declines for both the 2001–2011 and 2011–2016 periods at the national level, though moderate biases were found in some locations. At the national scale, ozone trends for the 2011–2016 period were better captured by the models than those for the 2001–2011 period. Both models overestimated the observed decrease in ground level NO2 at the higher end of the concentration spectrum. This is linked to, and can cause, the detected tendency of the models to have larger than observed increases in ozone at the lower end over time. At the metropolitan statistical area (MSA) level, the performance of capturing the ozone trends varied. For some MSA's, the models estimated the wrong direction in the trends; e.g., in Denver, where maximum 8-hr average ozone levels increased from 2001 to 2011, the models predicted a decrease. The US EPA recommends location specific Relative Response Factors (RRFs) to adjust results when applying the models for air quality management purposes. At the regional level, the simulated ozone RRFs were up to 8% larger than the observed RRFs for the 2001–2011 period, suggesting that the models underestimated the ozone decrease. For the 2011–2016 period, with a couple of exceptions, the simulated RRFs were up to 9% smaller than observed RRFs, indicating a negative bias in the simulated trend. For individual MSAs, the ratio of the simulated to observed RRFs ranged between 0.86 (Knoxville for 2001–2011) and 1.40 (Los Angeles for 2001–2011). This is possibly linked to potential biases in the estimated emissions trends. Such high biases could lead to similar biases in the estimated emissions controls required for an area to attain the air quality standards. The results indicate that there are both spatial and temporal biases in how well the two models have captured the observed ozone and NO2 trends. Air quality planning agencies should aim to diagnose and reduce such biases before using model results for air quality management.

Ni Schottky barrier on heavily doped phosphorous implanted 4H-SiC

The electrical behavior of Ni Schottky barrier formed onto heavily doped (N D > 1019 cm−3) n-type phosphorous implanted silicon carbide (4H-SiC) was investigated, with a focus on the current transport mechanisms in both forward and reverse bias. The forward current–voltage characterization of Schottky diodes showed that the predominant current transport is a thermionic-field emission mechanism. On the other hand, the reverse bias characteristics could not be described by a unique mechanism. In fact, under moderate reverse bias, implantation-induced damage is responsible for the temperature increase in the leakage current, while a pure field emission mechanism is approached with bias increasing. The potential application of metal/4H-SiC contacts on heavily doped layers in real devices is discussed.

Tonotopic distribution and inferior colliculus projection pattern of inhibitory and excitatory cell types in the lateral superior olive of Mongolian gerbils.

Sound localization critically relies on brainstem neurons that compare information from the two ears. The conventional role of the lateral superior olive (LSO) is extraction of intensity differences; however, it is increasingly clear that relative timing, especially of transients, is also an important function. Cellular diversity within the LSO that is not well understood may underlie its multiple roles. There are glycinergic inhibitory and glutamatergic excitatory principal neurons in the LSO, however, there is some disagreement regarding their relative distribution and projection pattern. Here we employ in situ hybridization to definitively identify transmitter types combined with retrograde labeling of projections to the inferior colliculus (IC) to address these questions. Excitatory LSO neurons were more numerous (76%) than inhibitory ones. A smaller proportion of inhibitory neurons were IC-projecting (45% vs. 64% for excitatory) suggesting that inhibitory LSO neurons may have more projections to other regions such the lateral lemniscus or more distributed IC projections. Inhibitory LSO neurons almost exclusively projected ipsilaterally making up a sizeable proportion (41%) of the transmitter type-labeled ipsilateral IC projection from LSO and exhibited a moderate low frequency bias (10% difference H-L). Two thirds of excitatory neurons projected contralaterally and had a slight high frequency bias (4%). One third of excitatory LSO neurons projected ipsilaterally to the IC and these cells were strongly biased toward the low frequency limb of the LSO (37%). This projection appears to be species specific in animals with good low frequency hearing suggesting that it may be a specialization for such ability.

An Anatomically Constrained Model of V1 Simple Cells Predicts the Coexistence of Push-Pull and Broad Inhibition.

The spatial organization and dynamic interactions between excitatory and inhibitory synaptic inputs that define the receptive field (RF) of simple cells in the cat primary visual cortex (V1) still raise the following paradoxical issues: (1) stimulation of simple cells in V1 with drifting gratings supports a wiring schema of spatially segregated sets of excitatory and inhibitory inputs activated in an opponent way by stimulus contrast polarity and (2) in contrast, intracellular studies using flashed bars suggest that although ON and OFF excitatory inputs are indeed segregated, inhibitory inputs span the entire RF regardless of input contrast polarity. Here, we propose a biologically detailed computational model of simple cells embedded in a V1-like network that resolves this seeming contradiction. We varied parametrically the RF-correlation-based bias for excitatory and inhibitory synapses and found that a moderate bias of excitatory neurons to synapse onto other neurons with correlated receptive fields and a weaker bias of inhibitory neurons to synapse onto other neurons with anticorrelated receptive fields can explain the conductance input, the postsynaptic membrane potential, and the spike train dynamics under both stimulation paradigms. This computational study shows that the same structural model can reproduce the functional diversity of visual processing observed during different visual contexts.SIGNIFICANCE STATEMENT Identifying generic connectivity motives in cortical circuitry encoding for specific functions is crucial for understanding the computations implemented in the cortex. Indirect evidence points to correlation-based biases in the connectivity pattern in V1 of higher mammals, whereby excitatory and inhibitory neurons preferentially synapse onto neurons respectively with correlated and anticorrelated receptive fields. A recent intracellular study questions this push-pull hypothesis, failing to find spatial anticorrelation patterns between excitation and inhibition across the receptive field. We present here a spiking model of V1 that integrates relevant anatomic and physiological constraints and shows that a more versatile motif of correlation-based connectivity with selectively tuned excitation and broadened inhibition is sufficient to account for the diversity of functional descriptions obtained for different classes of stimuli.

Insight of Codon usage bias and Evolutionary rate among the genes C, E, prM and NS5 of the Kyasanur Forest Disease virus

Kyasanur Forest Disease was first evolved in the Kyasanur forest, Karnataka. The transmission of the virus has occurred from the monkey to the human by the tick vector. On the early day of viral spread, the disease was restricted to the surrounded region of Kyasanur forest, Shimoga district. But in the present days, the disease has been spreading to neighboring districts and states as well. So, this study involves estimation of codon bias among the gene C, gene E, gene prM, and gene NS5 of the KFD virus and rate of evolution with phylogenetic analysis. The codon usage analysis has revealed the moderate codon bias among all the selected genes and the role of mutation pressure in genes- C and E and natural selection in genes- prM and NS5. Also, the tMRCA age was 1942, 1982, 1975, and 1931 of genes- C, E, prM, and NS5, respectively, of the KFD virus. The integrated analysis of codon usage bias and evolutionary rate analysis signifies that both mutational pressure and natural selection among the selected genes of the KFD virus.

Opportunities for the use of routinely collected data for the generation of large randomized evidence in Colombia

Randomized clinical trials are the cornerstone design for the evaluation of the safety and efficacy of health interventions. Furthermore, morbidity and mortality rates could be reduced if evidence of better interventions is sought and used to inform medical practice. However, only small to moderate, yet worthwhile, effects can be expected from such interventions. Therefore, moderate random error and moderate biases must be avoided during the design, conduct and analysis of trials. Routinely collected data, such as vital statistics, hospital episode statistics and surveillance data, could be used to enhance recruitment and follow-up a large number of patients, reducing both random error and moderate biases. Here, we discuss the opportunities and challenges for the use of these data for clinical studies in Colombia.

Moderating Effects of Herding Bias on the Relationship Between Parental Monitoring and Problem Gambling of Youths.

One critical issue in problem gambling is its variation as a function of psychosocial factors. We used empirical data from Nigerian youth Soccer gamblers (N = 238) to explore gambling herding bias as a moderator of the relationship between parental monitoring and problem gambling. Specifically, examine how changes in parental monitoring influence changes in problem gambling, and how this influence is a function of levels of herding bias. Hayes PROCESS macro analysis results revealed that increase in parental monitoring was associated with decrease in problem gambling, whereas increase in herding bias was associated with increase in problem gambling. Herding bias positively moderated the relationship between parental monitoring and problem gambling such that, for respondents who had high and moderate herding bias scores, the relationship between parental monitoring and problem gambling was positive and strong, whereas, for repondents with low herding bias scores, the relationship between parental monitoring and problem gambling was negative. The present study reaffirms the negative and positive influences of parental monitoring and herding bias, respectively, on problem gambling among youths.

Voltage Dependent Barrier Height, Ideality Factor and Surface States in Au/(NiS-PVP)/n-Si (MPS) type Schottky Barrier Diodes

Metal-Polymer-Semiconductor (MPS) Schottky Barrier Diodes (SBD) were manufactured and their basic electrical parameters were obtained by the measurement of the forward and reverse bias current-voltage (I-V) in the wide bias voltage range (±3V) to determine the voltage dependent effects on Nickel-Sulphur (NiS) doped Poly Vinyl Pyrrolidone (PVP) polymer interlayer. The saturation current (I0), zero-bias barrier height (ΦB0), rectifying rate (RR), ideality factor (n) and the real value of series - shunt resistances (Rs - Rsh) were calculated. The voltage dependent profile of n (V), ΦB(V), and Rs (V) were derived. The forward bias ln I-V plot of the MPS type SBD indicates a good rectifier behaviour and it has two distinctive linear parts with different slopes which correspond to low (0.288 ≤V ≤0.625 V) and moderate (0.672 ≤ V ≤ 0.960 V) bias voltages and then deviates from linearity due to Rs and interlayer at high forward bias voltages. Energy dependent profile of Nss was obtained from the forward bias I-V data by considering voltage dependent barrier height (ΦB) and n. Nss plot represents U-shape behaviour in the forbidden bandgap. The mean value of Nss was found at about 7.0x1012 eV-1 cm-2 and this value is in the acceptable limit for a semiconductor device and such lower values of Nss are the consequences of the passivation effect on the surface states.

Validation of Maternal Recall of Iron Folic Supplementation During Antenatal Care in Rural Southern Nepal

ObjectivesThis study’s primary objective is to examine the validity of maternal recall of iron folate supplementation during antenatal care and factors associated with accuracy of maternal recall. MethodsA longitudinal cohort design was employed for the validation study. The direct observation of all iron folate supplementation (IFA) received during all antenatal care visits at the five study health posts served as the “gold standard” to the maternal report of IFA received collected during a postpartum interview. Individual-level validity was assessed by calculating indicator sensitivity, specificity and area under the receiver operating curve (AUC). The inflation factor (IF) measured population-level bias, comparing the true coverage to the survey measure (maternal report) coverage of IFA. A multivariable log-binomial model was used to assess factors associated with accurate recall. ResultsThe majority (95.8%) of women were observed receiving IFA during pregnancy. Women overreported the number IFA tablets received compared to what was observed during ANC visits. On average the reported number of tablets received was 45 tablets greater than the number observed. Individual-level accuracy of maternal report of any IFA receipt was moderate (AUC = 0.60) and population bias was low (IF = 1.01). However, the individual-level validity was poor across the seven IFA tablet count categories; the AUC for categories ranged from 0.47 to 0.58, indicating a performance that at best was slightly better than a random guess and at worst, misleading. Driven by the trend of maternal overreport, the inflation factor indicated that the survey measure drastically underestimated the prevalence of lower tablet categories and overestimated the prevalence of higher tablet counts. Accuracy of maternal report was not associated with months since last ANC observation nor any maternal characteristics. ConclusionsMaternal report of the amount IFA supplementation received during pregnancy produced extremely biased population prevalence and performed comparably to or worse than a random guess for individual level validity. It’s imperative to improve this indicator for future use, as it is included in global frameworks, initiatives and national program planning. Funding SourcesThis research was funded by the Bill and Melinda Gates Foundation.

Benefits and Harms of Low-Dose Rivaroxaban in Asian Patients With Atrial Fibrillation: A Systematic Review and Meta-analysis of Real-World Studies

Background: Low-dose prescription of rivaroxaban was common among patients with atrial fibrillation (AF) in Asia. However, the benefits and harms of rivaroxaban at a low dosage in Asian patients with AF remains unclear. Accordingly, we aimed to collect and summarize all available evidence to fill this important knowledge gap. Methods: In this systematic review and meta-analysis, we systematically searched databases of MEDLINE, EMBASE, and Cochrane Library for relevant studies from inception until February 23, 2021. Eligible retrospective nationwide or health insurance database studies or prospective registration studies that reported efficacy (stroke/systemic embolism), safety (major bleeding, intracranial hemorrhage, gastrointestinal bleeding), or other outcomes (myocardial infarction, death) of low-dose rivaroxaban in comparison with warfarin in AF patients were enrolled. Data extraction and study quality assessment were conducted by two authors independently. Low dosing of rivaroxaban (15/10 mg) was defined as the received dose lower than the recommended dose (20 mg) approved in most districts. Hazard ratio (HR) with 95% confidence intervals (95% CIs) was pooled using a random-effect model. Subgroup analyses were conducted according to different dose regimens. Sensitivity analyses were conducted by sequential elimination of each study from the pool. Since potential effect modifiers (patient demographics, differences of each study, and others) may lead to bias in primacy outcomes, we performed a meta-regression analysis to explore the influence of these factors on the primary efficacy and safety outcomes. Results: Totally, 12 studies involving 292,815 Asian patients with AF were included. All studies were detected as low to moderate risk bias. Low-dose rivaroxaban treatment in Asian AF patients was associated with a reduced risk of stroke/systemic embolism (HR: 0.76, 95% CI: 0.70–0.84, I 2: 57.8%), major bleeding (HR: 0.72, 95% CI: 0.62–0.84, I 2: 81.5%), and all-cause death (HR: 0.65, 95% CI: 0.58–0.73, I 2: 81.7%) when compared with warfarin. Furthermore, consistent results were observed among different dose regimens (10/15/20 mg) in all the clinical outcomes (P interaction > 0.05 for each outcome). Meta-regression analysis failed to detect any potential confounding to impact the primacy outcomes. Conclusion: Insights from the present meta-analysis, we found that low-dose rivaroxaban, even at a dosage of 10 mg daily, was associated with a reduced risk of stroke/SE and bleeding than warfarin in Asian AF patients. However, owing to considerable heterogeneity among included studies, further prospective studies are required to confirm these findings.

Satellite remote sensing to assess cyanobacterial bloom frequency across the United States at multiple spatial scales

Cyanobacterial blooms can have negative effects on human health and local ecosystems. Field monitoring of cyanobacterial blooms can be costly, but satellite remote sensing has shown utility for more efficient spatial and temporal monitoring across the United States. Here, satellite imagery was used to assess the annual frequency of surface cyanobacterial blooms, defined for each satellite pixel as the percentage of images for that pixel throughout the year exhibiting detectable cyanobacteria. Cyanobacterial frequency was assessed across 2,196 large lakes in 46 states across the continental United States (CONUS) using imagery from the European Space Agency’s Ocean and Land Colour Instrument for the years 2017 through 2019. In 2019, across all satellite pixels considered, annual bloom frequency had a median value of 4% and a maximum value of 100%, the latter indicating that for those satellite pixels, a cyanobacterial bloom was detected by the satellite sensor for every satellite image considered. In addition to annual pixel-scale cyanobacterial frequency, results were summarized at the lake- and state-scales by averaging annual pixel-scale results across each lake and state. For 2019, average annual lake-scale frequencies also had a maximum value of 100%, and Oregon and Ohio had the highest average annual state-scale frequencies at 65% and 52%. Pixel-scale frequency results can assist in identifying portions of a lake that are more prone to cyanobacterial blooms, while lake- and state-scale frequency results can assist in the prioritization of sampling resources and mitigation efforts. Satellite imagery is limited by the presence of snow and ice, as imagery collected in these conditions are quality flagged and discarded. Thus, annual bloom frequencies within nine climate regions were investigated to determine whether missing data biased results in climate regions more prone to snow and ice, given that their annual summaries would be weighted toward the summer months when cyanobacterial blooms tend to occur. Results were unbiased by the time period selected in most climate regions, but a large bias was observed for the Northwest Rockies and Plains climate region. Moderate biases were observed for the Ohio Valley and the Southeast climate regions. Finally, a clustering analysis was used to identify areas of high and low cyanobacterial frequency across CONUS based on average annual lake-scale cyanobacterial frequencies for 2019. Several clusters were identified that transcended state, watershed, and eco-regional boundaries. Combined with additional data, results from the clustering analysis may offer insight regarding large-scale drivers of cyanobacterial blooms.

Resource Uptake and the Evolution of Moderately Efficient Enzymes.

Enzymes speed up reactions that would otherwise be too slow to sustain the metabolism of selfreplicators. Yet, most enzymes seem only moderately efficient, exhibiting kinetic parameters orders of magnitude lower than their expected physically achievable maxima and spanning over surprisingly large ranges of values. Here, we question how these parameters evolve using a mechanistic model where enzyme efficiency is a key component of individual competition for resources. We show that kinetic parameters are under strong directional selection only up to a point, above which enzymes appear to evolve under near-neutrality, thereby confirming the qualitative observation of other modeling approaches. While the existence of a large fitness plateau could potentially explain the extensive variation in enzyme features reported, we show using a population genetics model that such a widespread distribution is an unlikely outcome of evolution on a common landscape, as mutation–selection–drift balance occupy a narrow area even when very moderate biases towards lower efficiency are considered. Instead, differences in the evolutionary context encountered by each enzyme should be involved, such that each evolves on an individual, unique landscape. Our results point to drift and effective population size playing an important role, along with the kinetics of nutrient transporters, the tolerance to high concentrations of intermediate metabolites, and the reversibility of reactions. Enzyme concentration also shapes selection on kinetic parameters, but we show that the joint evolution of concentration and efficiency does not yield extensive variance in evolutionary outcomes when documented costs to protein expression are applied.