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Supplementary Table S3. Prostatic gene expression significantly impacted by castration relative to sham operation

Supplemental Figure S1. Final urogenital tract weights and plasma lycopene concentrations in intact, castrated, and testosterone-repleted WT and TRAMP mice fed either control, tomato-, or lycopene-containing diets.

Supplemental References

Education can be viewed as a control theory problem in which students seek ongoing exogenous input—either through traditional classroom teaching or other alternative training resources—to minimize the discrepancies between their actual and target (reference) performance levels. Using illustrative data from n= 784 Dutch elementary school students as measured using the Math Garden, a web-based computer adaptive practice and monitoring system, we simulate and evaluate the outcomes of using off-line and finite memory linear quadratic controllers with constraints to forecast students’ optimal training durations. By integrating population standards with each student’s own latent change information, we demonstrate that adoption of the control theory-guided, person- and time-specific training dosages could yield increased training benefits at reduced costs compared to students’ actual observed training durations, and a fixed-duration training scheme. The control theory approach also outperforms a linear scheme that provides training recommendations based on observed scores under noisy and the presence of missing data. Design-related issues such as ways to determine the penalty cost of input administration and the size of the control horizon window are addressed through a series of illustrative and empirically (Math Garden) motivated simulations.

This is a synthesis article of the experience of six post-secondary institutions, Kwantlen Polytechnic University, Queen’s University, Ryerson University, Southeast Missouri State University, University of Glasgow, and The Ohio State University (the coordinating institution) that were brought together by the Carnegie Academy for the Scholarship of Teaching and Learning (CASTL ) under the Institutional Leadership initiative entitled Building Scholarly Communities. Over a four year period, these institutions, through the leadership of key individuals and with the support of teaching and learning centres at their institutions, worked to create a culture where the Scholarship of Teaching and Learning (SoTL) would be seen to be as important as the scholarship of discovery (research). In this synthesis article, common themes and unique experiences are identified based on the stories of the individual institutions. As well, challenges and lessons learned are described.

Cancer patients show the signs and symptoms of a failing circadian organization. Melatonin, secreted only during nightly darkness, promotes nightly sleep and synchronizes daily molecular and physio...

Undergraduate research experiences (UREs), whether within the context of a mentor-mentee experience or a classroom framework, represent an excellent opportunity to expose students to the independent scholarship model. The high impact of undergraduate research has received recent attention in the context of STEM disciplines. Reflecting a 2017 survey of statistics faculty, this article examines the perceived benefits of UREs, as well as barriers to the incorporation of UREs, specifically within the field of statistics. Viewpoints of students, faculty mentors, and institutions are investigated. Further, the article offers several strategies for leveraging characteristics unique to the field of statistics to overcome barriers and thereby provide greater opportunity for undergraduate statistics students to gain research experience.

This article describes the process used to develop and assess an NSF-funded instructional innovation: an online collection (https://www.CAUSEweb.org/smiles/) of 28 interactive songs of high esthetic quality designed to span literature-based learning objectives of introductory statistics that develop statistical literacy and reasoning. The interactive songs are also designed to reduce statistics anxiety and require little time or instructor expertise. The songs are interactive in that the interface solicits (and provides hints and feedback on) student contributions (concepts or examples) and then plays back the song with student inputs integrated and highlighted. After providing a brief background, this article describes requirements, challenges, and opportunities in educational songwriting for the mathematical sciences, then describes the intervention and how its special nature affected the development process. Pilot studies at a research university and at a majority Black two-year college showed that students found the innovation to be a good tool to help their learning, reduce their anxiety about statistics, have an easy to follow interface, and use high quality songs. Analysis of log files from the use of the software shows some evidence of better performance on assessments after use and informs improvements of the automated feedback. Supplemental materials for this article are available online.

Education can be viewed as a control theory problem in which students seek ongoing exogenous input-either through traditional classroom teaching or other alternative training resources-to minimize the discrepancies between their actual and target (reference) performance levels. Using illustrative data from [Formula: see text] Dutch elementary school students as measured using the Math Garden, a web-based computer adaptive practice and monitoring system, we simulate and evaluate the outcomes of using off-line and finite memory linear quadratic controllers with constraintsto forecast students' optimal training durations. By integrating population standards with each student's own latent change information, we demonstrate that adoption of the control theory-guided, person- and time-specific training dosages could yield increased training benefits at reduced costs compared to students' actual observed training durations, and a fixed-duration training scheme. The control theory approach also outperforms a linear scheme that provides training recommendations based on observed scores under noisy and the presence of missing data. Design-related issues such as ways to determine the penalty cost of input administration and the size of the control horizon window are addressed through a series of illustrative and empirically (Math Garden) motivated simulations.

Background This case seeks to highlight to endoscopists a rare benign disorder that may be encountered during endoscopy. Clinicians may be tempted to biopsy, which could lead to a catastrophic gastrointestinal haemorrhage. Case presentation A 66-year-old asymptomatic Caucasian male was referred for colonoscopy with a positive faecal occult blood test as part of the UK national bowel cancer screening programme. Relevant past medical history included atrial fibrillation for which he took Dabigatran. He had a normal haemoglobin, mean cell volume, platelet and clotting function. During colonoscopy, an unusual vascular pattern encompassing the entire rectum extending to the rectosigmoid junction was noted at intubation. The lesion demonstrated confluent circumferential purple discolouration indicating venous blood supply, with heaping up of the mucosa involving the entire rectum and rectosigmoid junction. There was no corresponding history of venothromboembolic disease or liver disease. The patient proceeded to have computed tomography (CT) which revealed a considerably thickened rectosigmoid wall with multiple small rounded punctate calcifications within it, and no other visceral involvement. Subsequent magnetic resonance (MR) scan of the pelvis demonstrated extensive diffuse thickening of the rectum and lower sigmoid with intermediate to high T2 signal, and an internal architecture of multiple ‘grapelike’ lobulations. Conclusion The findings were consistent with diffuse cavernous haemangiomatosis of the rectum (DCHR), an extremely rare benign submucosal vascular intestinal tumour originating from the dentate line. Misdiagnosis of DCHR is common and the macroscopic appearance of DCHR can mimic varices, haemorrhoids, polyps or proctitis. MR imaging is the gold standard for diagnosis. Common presentation is with haematochezia due to mucosal wall erosion. The treatment of choice for symptomatic DCHR is pull-through transection and colo-anal anastomosis. This case seeks to highlight a rare disorder that can be encountered incidentally during lower GI endoscopy. Injudicious biopsy is potentially catastrophic. In a patient who endoscopically has evidence of a DCHR, we advocate MR pelvis assessment to clarify the nature of the lesion to guide future management if required. The patient discussed remains well, asymptomatic, with no evidence of iron deficiency anaemia.

Dennis Pearl is Professor of Statistics at Pennsylvania State University and Director of the Consortium for the Advancement of Undergraduate Statistics Education (CAUSE). He is a Fellow of the Amer...

We studied multiple sequence alignment (MSA) consensus amino acid distributional patterns in 2844 amino acid sequences of the eight enzymes of the Kreb's oxidative tricarboxylic acid pathway (oTCA) in Archaea, Bacteria and Eukarya and 5545 sequences of 33 bacteria as geochronologically separated enzymes with MSA consensus site modal identities. The 33 bacteria were 20 presumptive examples of early-oldest (Hadean-Archaean) ('Epoch I') or 13 late-newest (contemporary) ('Epoch III') appearing enzymes on Earth. The enzyme's MSA consensus sites were identified by their modal identity, % Occupancy in one of nine-graded evolutionary-conservation zones (CZs) and the Euclidean distance (Å) from each of their consensus MSA Cɑs to the same atom (Anchor-atom) in their reported functional center. These MSA consensus sites are tetrad-data points called recovered-amino acids (RAA). Across Domains, the % Occupancies of the eight-dominant RAAs of the Kreb's cycle and the 33 bacteria were found to be similarly ranked. Compared to Trifonov's 'putative ranked temporal order of the appearance of amino acids on Earth' (TOAE), the greatest statistical concordance with tetrad-RAAs across Domains were those characterized as within the most-evolutionary conserved conservation zone (CZ9), typically nearest (Å) their enzyme's catalytic/active center. The geochronologically characterized early-oldest Hadean-Archaean Bacteria 'Epoch I' enzymes, compared to late-newest Bacteria enzymes, had greater average numbers of amino acid residues/sequence and a statistically significant larger variability in their RAA compositional-Å

The multispecies coalescent (MSC) model provides a compelling framework for building phylogenetic trees from multilocus DNA sequence data. The pure MSC is best thought of as a special case of so-called "multispecies network coalescent" models, in which gene flow is allowed among branches of the tree, whereas MSC methods assume there is no gene flow between diverging species. Early implementations of the MSC, such as "parsimony" or "democratic vote" approaches to combining information from multiple gene trees, as well as concatenation, in which DNA sequences from multiple gene trees are combined into a single "supergene," were quickly shown to be inconsistent in some regions of tree space, in so far as they converged on the incorrect species tree as more gene trees and sequence data were accumulated. The anomaly zone, a region of tree space in which the most frequent gene tree is different from the species tree, is one such region where many so-called "coalescent" methods are inconsistent. Second-generation implementations of the MSC employed Bayesian or likelihood models; these are consistent in all regions of gene tree space, but Bayesian methods in particular are incapable of handling the large phylogenomic data sets currently available. Two-step methods, such as MP-EST and ASTRAL, in which gene trees are first estimated and then combined to estimate an overarching species tree, are currently popular in part because they can handle large phylogenomic data sets. These methods are consistent in the anomaly zone but can sometimes provide inappropriate measures of tree support or apportion error and signal in the data inappropriately. MP-EST in particular employs a likelihood model which can be conveniently manipulated to perform statistical tests of competing species trees, incorporating the likelihood of the collected gene trees on each species tree in a likelihood ratio test. Such tests provide a useful alternative to the multilocus bootstrap, which only indirectly tests the appropriateness of competing species trees. We illustrate these tests and implementations of the MSC with examples and suggest that MSC methods are a useful class of models effectively using information from multiple loci to build phylogenetic trees.

There has been a recent emergence of scholarship on the use of fun in the college statistics classroom, with at least 20 modalities identified. While there have been randomized experiments that suggest that fun can enhance student achievement or attitudes in statistics, these studies have generally been limited to one particular fun modality or have not been limited to the discipline of statistics. To address the efficacy of fun items in teaching statistics, a student-randomized experiment was designed to assess how specific items of fun may cause changes in statistical anxiety and learning statistics content. This experiment was conducted at two institutions of higher education with different and diverse student populations. Findings include a significant increase in correct responses to questions among students who were assigned online content with a song insert compared with those assigned content alone.

Black raspberries (BRB) demonstrate potent inhibition of aerodigestive tract carcinogenesis in animal models. However, translational clinical trials evaluating the ability of BRB phytochemicals to impact molecular biomarkers in the oral mucosa remain limited. The present phase 0 study addresses a fundamental question for oral cancer food–based prevention: Do BRB phytochemicals successfully reach the targeted oral tissues and reduce proinflammatory and antiapoptotic gene expression profiles? Patients with biopsy-confirmed oral squamous cell carcinomas (OSCC) administered oral troches containing freeze-dried BRB powder from the time of enrollment to the date of curative intent surgery (13.9 ± 1.27 days). Transcriptional biomarkers were evaluated in patient-matched OSCCs and noninvolved high at-risk mucosa (HARM) for BRB-associated changes. Significant expression differences between baseline OSCC and HARM tissues were confirmed using a panel of genes commonly deregulated during oral carcinogenesis. Following BRB troche administration, the expression of prosurvival genes (AURKA, BIRC5, EGFR) and proinflammatory genes (NFKB1, PTGS2) were significantly reduced. There were no BRB-associated grade 3–4 toxicities or adverse events, and 79.2% (N = 30) of patients successfully completed the study with high levels of compliance (97.2%). The BRB phytochemicals cyanidin-3-rutinoside and cyanidin-3-xylosylrutinoside were detected in all OSCC tissues analyzed, demonstrating that bioactive components were successfully reaching targeted OSCC tissues. We confirmed that hallmark antiapoptotic and proinflammatory molecular biomarkers were overexpressed in OSCCs and that their gene expression was significantly reduced following BRB troche administration. As these molecular biomarkers are fundamental to oral carcinogenesis and are modifiable, they may represent emerging biomarkers of molecular efficacy for BRB-mediated oral cancer chemoprevention. Cancer Prev Res; 9(2); 159–71. ©2015 AACR.

Consumption of tomato products containing the carotenoid lycopene is associated with a reduced risk of prostate cancer. To identify gene expression patterns associated with early testosterone-driven prostate carcinogenesis, which are impacted by dietary tomato and lycopene, wild-type (WT) and transgenic adenocarcinoma of the mouse prostate (TRAMP) mice were fed control or tomato- or lycopene-containing diets from 4 to 10 weeks of age. Eight-week-old mice underwent sham surgery, castration, or castration followed by testosterone repletion (2.5 mg/kg/d initiated 1 week after castration). Ten-week-old intact TRAMP mice exhibit early multifocal prostatic intraepithelial neoplasia. Of the 200 prostate cancer–related genes measured by quantitative NanoString, 189 are detectable, 164 significantly differ by genotype, 179 by testosterone status, and 30 by diet type (P < 0.05). In TRAMP, expression of Birc5, Mki67, Aurkb, Ccnb2, Foxm1, and Ccne2 is greater compared with WT and is decreased by castration. In parallel, castration reduces Ki67-positive staining (P < 0.0001) compared with intact and testosterone-repleted TRAMP mice. Expression of genes involved in androgen metabolism/signaling pathways is reduced by lycopene feeding (Srd5a1) and by tomato feeding (Srd5a2, Pxn, and Srebf1). In addition, tomato feeding significantly reduced expression of genes associated with stem cell features, Aldh1a and Ly6a, whereas lycopene feeding significantly reduced expression of neuroendocrine differentiation–related genes, Ngfr and Syp. Collectively, these studies demonstrate a profile of testosterone-regulated genes associated with early prostate carcinogenesis that are potential mechanistic targets of dietary tomato components. Future studies on androgen signaling/metabolism, stem cell features, and neuroendocrine differentiation pathways may elucidate the mechanisms by which dietary tomato and lycopene impact prostate cancer risk. Cancer Prev Res; 7(12); 1228–39. ©2014 AACR.

A large body of work has been devoted to reducing assessment biases that distort inferences about students’ science understanding, particularly in multiple-choice instruments (MCI). Constructed-response instruments (CRI), however, have invited much less scrutiny, perhaps because of their reputation for avoiding many of the documented biases of MCIs. In this study we explored whether known biases of MCIs—specifically item sequencing and surface feature effects—were also apparent in a CRI designed to assess students’ understanding of evolutionary change using written explanation (Assessment of COntextual Reasoning about Natural Selection [ACORNS]). We used three versions of the ACORNS CRI to investigate different aspects of assessment structure and their corresponding effect on inferences about student understanding. Our results identified several sources of (and solutions to) assessment bias in this practice-focused CRI. First, along the instrument item sequence, items with similar surface features produced greater sequencing effects than sequences of items with dissimilar surface features. Second, a counterbalanced design (i.e., Latin Square) mitigated this bias at the population level of analysis. Third, ACORNS response scores were highly correlated with student verbosity, despite verbosity being an intrinsically trivial aspect of explanation quality. Our results suggest that as assessments in science education shift toward the measurement of scientific practices (e.g., explanation), it is critical that biases inherent in these types of assessments be investigated empirically.

Tomato and lycopene (c, c-carotene) consumption is hypothesized to protect against nonalcoholic steatohepatitis and hepatocarcinogenesis, processes that may depend upon diet and gene interactions. To investigate the interaction of tomato or lycopene feeding with b-carotene-9#,10#-monooxygenase (Bco2) on hepatic metabolic and signaling pathways, male wild-type (WT) and Bco2 2/2 mice (3-wk-old; n = 36) were fed semi-purified control, 10% tomato powder‐containing, or 0.25% lycopene beadlet‐containing diets for 3 wk. Serum lycopene concentrations were higher in lycopene- and tomato-fed Bco2 2/2 mice compared with WT (P = 0.03). Tomato- and lycopene-fed mice had detectable hepatic apo-6#-, apo-8#-, and apo-12#-lycopenal concentrations. Hepatic expression of b-carotene-15,15-monooxygenase was increased in Bco2 2/2 mice compared with WT (P = 0.02), but not affected by diet. Evaluation of hepatic gene expression by focused quantitative reverse transcriptase-polymerase chain reaction arrays for nuclear receptors and coregulators (84 genes) and stress and metabolism (82 genes) genes indicates that tomato feeding affected 31 genes ($1.5-fold, P < 0.05) and lycopene feeding affected 19 genes, 16 of which were affected by both diets. Lycopene down-regulation of 7 nuclear receptors and coregulators, estrogen-related receptor-a, histone deacetylase 3, nuclear receptor coactivator 4, RevErbAb, glucocorticoid receptor, peroxisome proliferator-activated receptor (PPAR)-a, and PPAR-g, coactivator 1 b was dependent upon interaction with Bco2 status. Lycopene and tomato feeding induced gene expression patterns consistent with decreased lipid uptake, decreased cell proliferation and mitosis, down-regulated aryl hydrocarbon receptor signaling, and decreased expression of genes involved in retinoid X receptor heterodimer activation. Tomato feeding also caused expression changes consistent with down-regulation of DNA synthesis and terpenoid metabolism. These data suggest tomato components, particularly lycopene, affect hepatic gene expression, potentially affecting hepatic responses to metabolic, infectious, or chemical stress. J. Nutr. doi: 10.3945/jn.113.186676.

The polyunsaturated fatty acids (PUFA) arachidonic acid (AA, n-6) and eicosapentaenoic acid (EPA, n-3) are precursors of eicosanoids and other lipid mediators which have critical roles in inflammation. The mediators formed from the different PUFA have different potencies. We hypothesised that metabolic changes associated with colonic mucosal inflammation would modify the bioavailability of the eicosanoid precursors AA and EPA.Colonic mucosa biopsies were obtained from patients with ulcerative colitis and from matched controls. Inflammation was graded endoscopically and histologically. Esterified and non-esterified fatty acids were determined within the biopsies using gas chromatography-mass spectrometry and liquid chromatography-mass spectrometry, respectively.Biopsy samples were collected from 69 UC patients (54 providing both inflamed and non-inflamed mucosa) and 69 controls. Inflamed mucosa had higher AA (p0.001) and lower EPA (p0.010) contents and a higher AA:EPA ratio (p0.001). Inflamed mucosa also had higher docosapentaenoic acid (DPA) and docosahexaenoic acid (DHA) and lower linoleic acid (LA) and α-linolenic acid (α-LNA) contents (all p0.001), compared to non-inflamed and controls. There were significant correlations between severity of inflammation and contents of AA, DPA and DHA (positive correlations) and of LA, α-LNA and EPA (negative correlations).Higher AA, AA:EPA ratio, DPA and DHA and lower LA, α-LNA and EPA are seen in inflamed mucosa in UC and correlate with severity of inflammation. This suggests an alteration in fatty acid metabolism in the inflamed gut mucosa, which may offer novel targets for intervention and should be considered if nutritional strategies are used.

The landscape of science education is being transformed by the new Framework for Science Education (National Research Council, A framework for K-12 science education: practices, crosscutting concepts, and core ideas. The National Academies Press, Washington, DC, 2012), which emphasizes the centrality of scientific practices— such as explanation, argumentation, and communication—in science teaching, learning, and assessment. A major chal- lenge facing the field of science education is developing assessment tools that are capable of validly and efficiently evaluating these practices. Our study examined the efficacy of a free, open-source machine-learning tool for evaluating the quality of students' written explanations of the causes of evolutionary change relative to three other approaches: (1) human-scored written explanations, (2) a multiple- choice test, and (3) clinical oral interviews. A large sample of undergraduates (n = 104) exposed to varying amounts of evolution content completed all three assessments: a clinical oral interview, a written open-response assessment, and a multiple-choice test. Rasch analysis was used to compute linear person measures and linear item measures on a single logit scale. We found that the multiple-choice test displayed poor person and item fit (mean square outfit (1.3), while both oral interview measures and computer- generated written response measures exhibited acceptable fit (average mean square outfit for interview: person 0.97, item 0.97; computer: person 1.03, item 1.06). Multiple- choice test measures were more weakly associated with interview measures (r = 0.35) than the computer-scored explanation measures (r = 0.63). Overall, Rasch analysis indicated that computer-scored written explanation mea- sures (1) have the strongest correspondence to oral inter- view measures; (2) are capable of capturing students' normative scientific and naive ideas as accurately as human-scored explanations, and (3) more validly detect understanding than the multiple-choice assessment. These findings demonstrate the great potential of machine-learn- ing tools for assessing key scientific practices highlighted in the new Framework for Science Education.

The distributions of amino acids at most-conserved sites nearest catalytic/active centers (C/AC) in 4,645 sequences of ten enzymes of the glycolytic Embden-Meyerhof-Parnas pathway in Archaea, Bacteria and Eukaryota are similar to the proposed temporal order of their appearance on Earth. Glycine, isoleucine, leucine, valine, glutamic acid and possibly lysine often described as prebiotic, i.e., existing or occurring before the emergence of life, were localized in positional and conservational defined aggregations in all enzymes of all Domains. The distributions of all 20 biologic amino acids in most-conserved sites nearest their C/ACs were quite different either from distributions in sites less-conserved and further from their C/ACs or from all amino acids regardless of their position or conservation. The major concentrations of glycine, e.g., perhaps the earliest prebiotic amino acid, occupies ≈ 16 % of all the most-conserved sites within a volume of ≈ 7-8 Å radius from their C/ACs and decreases linearly towards the molecule's peripheries. Spatially localized major concentrations of isoleucine, leucine and valine are in the mid-conserved and mid-distant sites from their C/ACs in protein interiors. Lysine and glutamic acid comprise ≈ 25-30 % of all amino acids within an irregular volume bounded by ≈ 24-28 Å radii from their C/ACs at the most-distant least-conserved sites. The unreported characteristics of these amino acids: their spatially and conservationally identified concentrations in Archaea, Bacteria and Eukaryota, suggest some common structural organization of glycolytic enzymes that may be relevant to their evolution and that of other proteins. We discuss our data in relation to enzyme evolution, their reported prebiotic putative temporal appearances on Earth, abundances, biological "cost", neighbor-sequence preferences or "ordering" and some thermodynamic parameters.

Using item-response theory, the authors evaluated differences in performance by gender on a constructed-response assessment about natural selection. The results identify relationships between item features and performance by gender and highlight the importance of examining gender effects on performance in written assessment tasks in biology., Understanding sources of performance bias in science assessment provides important insights into whether science curricula and/or assessments are valid representations of student abilities. Research investigating assessment bias due to factors such as instrument structure, participant characteristics, and item types are well documented across a variety of disciplines. However, the relationships among these factors are unclear for tasks evaluating understanding through performance on scientific practices, such as explanation. Using item-response theory (Rasch analysis), we evaluated differences in performance by gender on a constructed-response (CR) assessment about natural selection (ACORNS). Three isomorphic item strands of the instrument were administered to a sample of undergraduate biology majors and nonmajors (Group 1: n = 662 [female = 51.6%]; G2: n = 184 [female = 55.9%]; G3: n = 642 [female = 55.1%]). Overall, our results identify relationships between item features and performance by gender; however, the effect is small in the majority of cases, suggesting that males and females tend to incorporate similar concepts into their CR explanations. These results highlight the importance of examining gender effects on performance in written assessment tasks in biology.

Summary Background and aims Type 2 intestinal failure (IF) commonly results from post-operative short bowel leading to metabolic instability. Specialist multi-disciplinary management is often required for nutritional, fluid and/or electrolyte support, either intermediate term or until revision surgery. This can lead to prolonged or repeated acute hospital admission. Methods A virtual ward model was developed to address the need for on-going specialist support and facilitate home discharge. This provides an outreach specialist service with structured patient education, remote biochemical monitoring, telemedicine consultations and open access outpatient clinics. Patients' status is reviewed at multi-disciplinary virtual ward rounds. Results A prospective audit assessed effectiveness of the programme. Of 20 patients referred with post-operative type 2 IF and metabolic instability, 18 were discharged home for a total of 2731 days, with a mean readmission days of 2.0%. 12 patients were managed with modified enteral nutrition. Management was unsuccessful in only 1 patient due to non-compliance. A patient satisfaction study suggested high levels of patient satisfaction. Conclusions The IF virtual ward is associated with low levels of hospital readmission amongst complex and metabolically unstable IF patients. It provided integrated multi-disciplinary management and is associated with high levels of patient satisfaction.

Our study investigates the challenges introduced by students’ use of lexically ambiguous language in evolutionary explanations. Specifically, we examined students’ meaning of five key terms incorporated into their written evolutionary explanations: pressure, select, adapt, need, and must. We utilized a new technological tool known as the Assessment Cascade System (ACS) to investigate the frequency with which biology majors spontaneously used lexically ambiguous language in evolutionary explanations, as well as their definitions and explanations of what they meant when they used such terms. Three categories of language were identified and examined in this study: terms with Dual Ambiguity, Incompatible Ambiguity, and Unintended Ambiguity. In the sample of 1282 initial evolutionary explanations, 81 % of students spontaneously incorporated lexically ambiguous language at least once. Furthermore, the majority of these initial responses were judged to be inaccurate from a scientific point of view. While not significantly related to gender, age, or reading/writing ability, students’ use of contextually appropriate evolutionary language (pressure and adapt) was significantly associated with academic performance in biology. Comparisons of initial responses to follow-up responses demonstrated that the majority of student explanations were not reinterpreted after consideration of the follow-up response; nevertheless, a sizeable minority was interpreted differently. Most cases of interpretation change were a consequence of resolving initially ambiguous responses, rather than a change of accuracy, resulting in an increased understanding of students’ evolutionary explanations. We discuss a series of implications of lexical ambiguity for evolution education.

Objective To determine patients’ self-reported preferences and expectations for outpatient upper gastrointestinal (UGI) endoscopy, including patients’ priorities in obtaining a satisfactory healthcare experience, preprocedure anxiety and its causes, and preferred staff roles. Design A composite, dedicated endoscopy questionnaire was used. This included demographic information, validated Likert scale anxiety-related questions and a 15-point ranking scale of aspects of care (1=most important to satisfaction; 15=least important). Setting and patients Unselected patients attending for an elective UGI endoscopy at two separate units were surveyed on randomly identified days. Results A total of 202 out of 254 patients agreed to participate (79.5%). The values identified as most important to patients included technical skill (2.8) and personal manner of the endoscopist (4.9) and the nurses and support staff (5.8), control of discomfort (5.6) and adequacy of the preprocedure explanation (5.8). The factors considered least important included noise levels (12.5), privacy (10.7) and cleanliness (8.7). Moderate to severe anxiety was recorded in half of the patient cohort, predominantly due to anticipation of pain or the results of the procedure. Most patients preferred the endoscopist to discuss the findings of the endoscopy but expressed no preferences regarding the preprocedure explanation. Conclusion Patients undergoing UGI endoscopy appear to highly prioritise aspects of care relating to interaction with the endoscopist and the procedure itself. Environmental factors are considered to have much less value. These findings may assist in service redesign around patient-centred care and the development of patient satisfaction surveys in endoscopy.

Muscle soreness is a common symptom after novel exercise and may influence exercise adherence. This study examined the effect of an ibuprofen topical gel and the effect of age and sex on muscle soreness after a gym exercise.One hundred and six participants completed six sets of 10 repetitions of the elbow and knee flexor muscles. Thirty-six hours after exercise, participants were randomized to apply an ibuprofen topical gel or placebo treatment to the affected muscle groups. Soreness evaluations were taken each hour for the first 6 h (36-42 h), then at 48, 60, 66, 72, 84, 90, 96, and 108 h after exercise. Subjects then returned to the laboratory after 3 wk and repeated the same study protocol with the opposite arm/leg and treatment.We found no significant differences in soreness between the active ibuprofen gel and the placebo treatment and no difference in effectiveness between men and women or between older and younger subjects. For the placebo groups, there was no sex differences in muscle soreness; however, when the data were analyzed by dividing participants into young (18-29 yr) and old (40-65 yr) cohort, the old cohort reported significantly less soreness in response to the elbow flexion exercise than the young cohort (P0.01).The results of this study suggest that the topical application of ibuprofen is not an effective treatment for muscle soreness after an unaccustomed gym exercise. Furthermore, our results show that there is no sex difference in the soreness response and that older subjects have less soreness in response to a similar exercise stimulus as young subjects.

In alignments of 1969 protein sequences the amino acid glycine and others were found concentrated at most-conserved sites within approximately 15 A of catalytic/active centers (C/AC) of highly conserved kinases, dehydrogenases or lyases of Archaea, Bacteria and Eukaryota. Lysine and glutamic acid were concentrated at least-conserved sites furthest from their C/ACs. Logistic-regression analyses corroborated the "movement" of glycine towards and lysine away from their C/ACs: the odds of a glycine occupying a site were decreased by 19%, while the odds for a lysine were increased by 53%, for every 10 A moving away from the C/AC. Average conservation of MSA consensus sites was highest surrounding the C/AC and directly decreased in transition toward model's peripheries. Findings held with statistical confidence using sequences restricted to individual Domains or enzyme classes or to both. Our data describe variability in the rate of mutation and likelihoods for phylogenetic trees based on protein sequence data and endorse the extension of substitution models by incorporating data on conservation and distance to C/ACs rather than only using cumulative levels. The data support the view that in the most-conserved environment immediately surrounding the C/AC of taxonomically distant and highly conserved essential enzymes of central metabolism there are amino acids whose identity and degree of occupancy is similar to a proposed amino acid set and frequency associated with prebiotic evolution.

The estimation of species trees (phylogenies) is one of the most important problems in evolutionary biology, and recently, there has been greater appreciation of the need to estimate species trees directly rather than using gene trees as a surrogate. A Bayesian method constructed under the multispecies coalescent model can consistently estimate species trees but involves intensive computation, which can hinder its application to the phylogenetic analysis of large-scale genomic data. Many summary statistics-based approaches, such as shallowest coalescences (SC) and Global LAteSt Split (GLASS), have been developed to infer species phylogenies for multilocus data sets. In this paper, we propose 2 methods, species tree estimation using average ranks of coalescences (STAR) and species tree estimation using average coalescence times (STEAC), based on the summary statistics of coalescence times. It can be shown that the 2 methods are statistically consistent under the multispecies coalescent model. STAR uses the ranks of coalescences and is thus resistant to variable substitution rates along the branches in gene trees. A simulation study suggests that STAR consistently outperforms STEAC, SC, and GLASS when the substitution rates among lineages are highly variable. Two real genomic data sets were analyzed by the 2 methods and produced species trees that are consistent with previous results.

Several techniques, such as concatenation and consensus methods, are available for combining data from multiple loci to produce a single statement of phylogenetic relationships. However, when multiple alleles are sampled from individual species, it becomes more challenging to estimate relationships at the level of species, either because concatenation becomes inappropriate due to conflicts among individual gene trees, or because the species from which multiple alleles have been sampled may not form monophyletic groups in the estimated tree. We propose a Bayesian hierarchical model to reconstruct species trees from multiple-allele, multilocus sequence data, building on a recently proposed method for estimating species trees from single allele multilocus data. A two-step Markov Chain Monte Carlo (MCMC) algorithm is adopted to estimate the posterior distribution of the species tree. The model is applied to estimate the posterior distribution of species trees for two multiple-allele datasets--yeast (Saccharomyces) and birds (Manacus-manakins). The estimates of the species trees using our method are consistent with those inferred from other methods and genetic markers, but in contrast to other species tree methods, it provides credible regions for the species tree. The Bayesian approach described here provides a powerful framework for statistical testing and integration of population genetics and phylogenetics.

The desire to infer the evolutionary history of a group of species should be more viable now that a considerable amount of multilocus molecular data is available. However, the current molecular phylogenetic paradigm still reconstructs gene trees to represent the species tree. Further, commonly used methods of combining data, such as the concatenation method, are known to be inconsistent in some circumstances. In this paper, we propose a Bayesian hierarchical model to estimate the phylogeny of a group of species using multiple estimated gene tree distributions, such as those that arise in a Bayesian analysis of DNA sequence data. Our model employs substitution models used in traditional phylogenetics but also uses coalescent theory to explain genealogical signals from species trees to gene trees and from gene trees to sequence data, thereby forming a complete stochastic model to estimate gene trees, species trees, ancestral population sizes, and species divergence times simultaneously. Our model is founded on the assumption that gene trees, even of unlinked loci, are correlated due to being derived from a single species tree and therefore should be estimated jointly. We apply the method to two multilocus data sets of DNA sequences. The estimates of the species tree topology and divergence times appear to be robust to the prior of the population size, whereas the estimates of effective population sizes are sensitive to the prior used in the analysis. These analyses also suggest that the model is superior to the concatenation method in fitting these data sets and thus provides a more realistic assessment of the variability in the distribution of the species tree that may have produced the molecular information at hand. Future improvements of our model and algorithm should include consideration of other factors that can cause discordance of gene trees and species trees, such as horizontal transfer or gene duplication.

Seizures are a common complication of metastatic brain tumors (MBT), affecting approximately 27–50% of all patients during the course of their illness. Treatment of tumor-induced seizures is often inadequate with traditional antiepileptic drugs (AED) due to a variety of factors, including activation of glutamatergic NMDA receptors, alterations of neuronal input pathways, and tumor growth. Levetiracetam (LEV) is a 2nd generation non-enzyme inducing AED with a novel mechanism of action, binding to neuronal synaptic vesicle protein SV2A, that has been previously shown to reduce seizure activity in patients with primary brain tumors. Due to its unique mechanism of action, it has been postulated that LEV may also be effective in controlling seizures from MBT. A retrospective chart review was performed of all Neuro-Oncology Center patients with MBT who had received LEV for seizure control. Thirteen patients were reviewed with a median age of 55.1 years (range: 34–70). Six patients had breast cancer, five had lung cancer, and two had melanoma. LEV was used as an add-on AED in seven patients (54%) and as monotherapy in six patients (46%), with a median dose of 1,000 mg/day (range: 500–3,000). The baseline median seizure frequency was one ictal event every other day. After the addition of LEV, the median seizure frequency was reduced to 0 per week. The seizure frequency was reduced to less than 50% of the pre-LEV baseline in 100% of patients (P = 0.0002, Sign test), with 10 patients (77%; confidence interval: 46–95%) noting complete seizure control. The most common adverse event was somnolence and headache, noted in 3 of 13 patients (23%). LEV was very effective and well tolerated in MBT patients with seizures and should be considered for add-on therapy or as a substitute AED for monotherapy.