RNA-seq is revolutionizing the way we study transcriptomes. mRNA can be surveyed without prior knowledge of gene transcripts. Alternative splicing of transcript isoforms and the identification of ...previously unknown exons are being reported. Initial reports of differences in exon usage, and splicing between samples as well as quantitative differences among samples are beginning to surface. Biological variation has been reported to be larger than technical variation. In addition, technical variation has been reported to be in line with expectations due to random sampling. However, strategies for dealing with technical variation will differ depending on the magnitude. The size of technical variance, and the role of sampling are examined in this manuscript.
In this study three independent Solexa/Illumina experiments containing technical replicates are analyzed. When coverage is low, large disagreements between technical replicates are apparent. Exon detection between technical replicates is highly variable when the coverage is less than 5 reads per nucleotide and estimates of gene expression are more likely to disagree when coverage is low. Although large disagreements in the estimates of expression are observed at all levels of coverage.
Technical variability is too high to ignore. Technical variability results in inconsistent detection of exons at low levels of coverage. Further, the estimate of the relative abundance of a transcript can substantially disagree, even when coverage levels are high. This may be due to the low sampling fraction and if so, it will persist as an issue needing to be addressed in experimental design even as the next wave of technology produces larger numbers of reads. We provide practical recommendations for dealing with the technical variability, without dramatic cost increases.
Severe obesity afflicts between 4% and 6% of all youth in the United States, and the prevalence is increasing. Despite the serious immediate and long-term cardiovascular, metabolic, and other health ...consequences of severe pediatric obesity, current treatments are limited in effectiveness and lack widespread availability. Lifestyle modification/behavior-based treatment interventions in youth with severe obesity have demonstrated modest improvement in body mass index status, but participants have generally remained severely obese and often regained weight after the conclusion of the treatment programs. The role of medical management is minimal, because only 1 medication is currently approved for the treatment of obesity in adolescents. Bariatric surgery has generally been effective in reducing body mass index and improving cardiovascular and metabolic risk factors; however, reports of long-term outcomes are few, many youth with severe obesity do not qualify for surgery, and access is limited by lack of insurance coverage. To begin to address these challenges, the purposes of this scientific statement are to (1) provide justification for and recommend a standardized definition of severe obesity in children and adolescents; (2) raise awareness of this serious and growing problem by summarizing the current literature in this area in terms of the epidemiology and trends, associated health risks (immediate and long-term), and challenges and shortcomings of currently available treatment options; and (3) highlight areas in need of future research. Innovative behavior-based treatment, minimally invasive procedures, and medications currently under development all need to be evaluated for their efficacy and safety in this group of patients with high medical and psychosocial risks.
Summary
Objective
We aimed to assess the roles of the cortex and thalamus (centromedian nucleus CM) during epileptic activity in Lennox‐Gastaut syndrome (LGS) patients undergoing deep brain ...stimulation (DBS) surgery as part of the ESTEL (Electrical Stimulation of the Thalamus for Epilepsy of Lennox‐Gastaut Phenotype) trial.
Methods
Twelve LGS patients (mean age = 26.8 years) underwent bilateral CM‐DBS implantation. Intraoperatively, simultaneous electroencephalogram (EEG) was recorded (range = 10‐34 minutes) from scalp electrodes and bilateral thalamic DBS electrodes. Temporal onsets of epileptic discharges (generalized paroxysmal fast activity GPFA and slow spike‐and‐wave SSW) were manually marked on recordings from scalp (ie, "cortex") and thalamus (ie, CM‐DBS electrodes). Phase transfer entropy (PTE) analysis quantified the degree of information transfer from cortex to thalamus within different frequency bands around GPFA events.
Results
GPFA was captured in eight of 12 patients (total event number across patients = 168, cumulative duration = 358 seconds). Eighty‐six percent of GPFA events were seen in both scalp and thalamic recordings. In most events (83%), onset occurred first at scalp, with thalamic onset lagging by a median of 98 milliseconds (interquartile range = 78.5 milliseconds). Results for SSW were more variable and seen in 11 of 12 patients; 25.4% of discharges were noted in both scalp and thalamus. Of these, 74.5% occurred first at scalp, with a median lag of 75 milliseconds (interquartile range = 228 milliseconds). One to 0.5 seconds and 0.5‐0 seconds before GPFA onset, PTE analysis showed significant energy transfer from scalp to thalamus in the delta (1‐3 Hz) frequency band. For alpha (8‐12 Hz) and beta (13‐30 Hz) frequencies, PTE was greatest 1‐0.5 seconds before GPFA onset.
Significance
Epileptic activity is detectable in CM of thalamus, confirming that this nucleus participates in the epileptic network of LGS. Temporal onset of GPFA mostly occurs earlier at the scalp than in the thalamus. This supports our prior EEG–functional magnetic resonance imaging results and provides further evidence for a cortically driven process underlying GPFA in LGS.
Surveys are often based on a sample drawn from a list frame. In recent years, the percentage of target population units on the list frames has been decreasing, making it important to adjust for this ...undercoverage in the estimation process. Multiple-frame methods generally assume that the union of the available list frames is equal to the target population; however, this assumption is often not satisfied, especially for hard-to-survey populations. The United States Department of Agriculture’s (USDA’s) National Agricultural Statistics Service has explored the use of web-scraped list frames to assess undercoverage of the NASS list frame, which is comprised of all known farms and potential farms in the USA. In 2020, NASS conducted the National Farmers Market Mangers Survey. Because NASS does not include farmers markets on its list frame, the USDA Agricultural Marketing Service (AMS) business register of farmers markets was the only list frame initially available. To assess its undercoverage, a web-scraped list frame was developed, and capture-recapture methods provided the foundation for estimation. This study made two advances in the use of capture-recapture methods when conducting a survey with two list frames. First, because record linkage was conducted prior to drawing the samples, the sample design incorporated information identifying records on only the AMS business register, on only the web-scraped list frame, or on both frames. Second, a composite estimator for this overlap design allowed full use of all sample information to produce survey estimates. Directions for future research are highlighted. Supplementary materials accompanying this paper appear online.
This study examined whether the effects of student-faculty interaction on a range of student outcomes—i.e., college GPA, degree aspiration, integration, critical thinking and communication, cultural ...appreciation and social awareness, and satisfaction with college experience—vary by student gender, race, social class, and first-generation status. The study utilized data on 58,281 students who participated in the 2006 University of California Undergraduate Experience Survey (UCUES). The findings reveal differences in the frequency of student-faculty interaction across student gender, race, social class and first-generation status, and differences in the effects of student-faculty interaction (i.e., conditional effects) that depended on each of these factors except first-generation status. The findings provide implications for educational practice on how to maximize the educational efficacy of student-faculty interaction by minimizing the gender, race, social class, and first-generation differences associated with it.
Crop forecasting is important to national and international trade and food security. Although sample surveys continue to have a role in many national crop forecasting programs, the increasing ...challenges of list frame undercoverage, declining response rates, increasing response burden, and increasing costs are leading government agencies to replace some or all of survey data with data from other sources. This article reviews the primary approaches currently being used to produce official statistics, including surveys, remote sensing, and the integration of these with meteorological, administrative, or other data. The research opportunities for improving current methods of forecasting crop yield and quantifying the uncertainty associated with the prediction are highlighted.
The USDA National Agricultural Statistics Service (NASS) and other federal statistical agencies have used probability-based surveys as the foundation for official statistics for over half a century. ...Non-survey data that can be used to improve the accuracy and precision of estimates such as administrative, remotely sensed, and retail data have become increasingly available. Both frequentist and Bayesian models are used to combine survey and non-survey data in a principled manner. NASS has recently adopted Bayesian subarea models for three of its national programs: farm labor, crop county estimates, and cash rent county estimates. Each program provides valuable estimates at multiple scales of geography. For each program, technical challenges had to be met and a strenuous review completed before models could be adopted as the foundation for official statistics. Moving models out of the research phase into production required major changes in the production process and a cultural shift. With the implemented models, NASS now has measures of uncertainty, transparency, and reproducibility of its official statistics.
Using cross-classified multilevel modeling, this study attempted to improve our understanding of the group-level conditional effects of student–faculty interaction by examining the function of ...academic majors in explaining the effects of student–faculty interaction on students' academic self-concept. The study utilized data on 11,202 undergraduate students who completed both the 2003 Freshman Survey and the 2007 College Senior Survey at 95 baccalaureate institutions nationwide. The results show that the strength of the relationship between having been a guest in a professor's home and students' academic self-concept varies by academic major. Findings also suggest that some aspects of departmental climate, such as a racially more diverse student body and greater faculty accessibility, can possibly magnify the beneficial effects of student–faculty interaction. The study discusses the theoretical and practical implications of the findings.
Abstract
The emerging sectors of agriculture, such as organics, urban, and local food, tend to be dominated by farms that are smaller, more transient, more diverse, and more dispersed than the ...traditional farms in the rural areas of the United States. As a consequence, a list frame of all farms within one of these sectors is difficult to construct and, even with the best of efforts, is incomplete. The United States Department of Agriculture’s (USDA’s) National Agricultural Statistics Service (NASS) maintains a list frame of all known and potential U.S. farms and uses this list frame as the sampling frame for most of its surveys. Traditionally, NASS has used its area frame to assess undercoverage. However, getting a good measure of the incompleteness of the NASS list frame using an area frame is cost prohibitive for farms in these emerging sectors that tend to be located within and near urban areas. In 2016, NASS conducted the Local Food Marketing Practices (LFMP) survey. Independent samples were drawn from (1) the NASS list frame and (2) a web-scraped list of local food farms. Using these two samples and capture–recapture methods, the total number and sales of local food operations at the United States, regional, and state levels were estimated. To our knowledge, the LFMP survey is the first survey in which a web-scraped list frame has been used to assess undercoverage in a capture–recapture setting to produce official statistics. In this article, the methods are presented, and the challenges encountered are reviewed. Best practices and open research questions for conducting surveys using web-scraped list frames and capture–recapture methods are discussed.
A Scientific Integrity Consortium developed a set of recommended principles and best practices that can be used broadly across scientific disciplines as a mechanism for consensus on scientific ...integrity standards and to better equip scientists to operate in a rapidly changing research environment. The two principles that represent the umbrella under which scientific processes should operate are as follows: (1) Foster a culture of integrity in the scientific process. (2) Evidence-based policy interests may have legitimate roles to play in influencing aspects of the research process, but those roles should not interfere with scientific integrity. The nine best practices for instilling scientific integrity in the implementation of these two overarching principles are (1) Require universal training in robust scientific methods, in the use of appropriate experimental design and statistics, and in responsible research practices for scientists at all levels, with the training content regularly updated and presented by qualified scientists. (2) Strengthen scientific integrity oversight and processes throughout the research continuum with a focus on training in ethics and conduct. (3) Encourage reproducibility of research through transparency. (4) Strive to establish open science as the standard operating procedure throughout the scientific enterprise. (5) Develop and implement educational tools to teach communication skills that uphold scientific integrity. (6) Strive to identify ways to further strengthen the peer review process. (7) Encourage scientific journals to publish unanticipated findings that meet standards of quality and scientific integrity. (8) Seek harmonization and implementation among journals of rapid, consistent, and transparent processes for correction and/or retraction of published papers. (9) Design rigorous and comprehensive evaluation criteria that recognize and reward the highest standards of integrity in scientific research.
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