Beyond active learning: Using 3-Dimensional learning to create scientifically authentic, student-centered classrooms.

In recent years, much of the emphasis for transformation of introductory STEM courses has focused on "active learning", and while this approach has been shown to produce more equitable outcomes for students, the construct of "active learning" is somewhat ill-defined and is often used as a "catch-all" that can encompass a wide range of pedagogical techniques. Here we present an alternative approach for how to think about the transformation of STEM courses that focuses instead on what students should know and what they can do with that knowledge. This approach, known as three-dimensional learning (3DL), emerged from the National Academy's "A Framework for K-12 Science Education", which describes a vision for science education that centers the role of constructing productive causal accounts for phenomena. Over the past 10 years, we have collected data from introductory biology, chemistry, and physics courses to assess the impact of such a transformation on higher education courses. Here we report on an analysis of video data of class sessions that allows us to characterize these sessions as active, 3D, neither, or both 3D and active. We find that 3D classes are likely to also involve student engagement (i.e. be active), but the reverse is not necessarily true. That is, focusing on transformations involving 3DL also tends to increase student engagement, whereas focusing solely on student engagement might result in courses where students are engaged in activities that do not involve meaningful engagement with core ideas of the discipline.

Can laboratory HIV and infectious syphilis data inform future pre-exposure prophylaxis use in women in Ontario, Canada?

OBJECTIVES: Infectious syphilis has been proposed as an indication for HIV pre-exposure prophylaxis (PrEP) in women. We explored how many women experienced HIV seroconversion after being diagnosed with syphilis in Ontario between 20 April 2010 and 31 December 2021. METHODS: Through deterministic linkage of laboratory data at the Public Health Ontario laboratory, which conducts the vast majority of syphilis and HIV testing in Ontario, we quantified the number of females with positive syphilis diagnoses who subsequently exhibited HIV seroconversion between April 2010 and December 2021. New HIV cases were identified by diagnostic serology or HIV viral load test result of ≥20 copies/mL at least 60 days after the positive syphilis test. We report aggregate numbers of women with new laboratory evidence of HIV infection after their first positive syphilis test. RESULTS: Among 7957 women with positive syphilis tests during the study period, 6554 (82.4%) had linkable HIV serology tests and 133 (1.7%) ever tested HIV positive. With further linkage to viral load data, the number of women who ever had laboratory evidence of HIV infection increased to 184 (2.3%). However, when restricting to women whose first positive HIV test or HIV viral load occurred after their first positive syphilis test, this number decreased to 34 (0.4%). The median (IQR) time between the positive syphilis test and the first laboratory evidence of HIV was 551 (IQR=226-1159) days. CONCLUSION: Although it is clinically appropriate to recommend HIV PrEP to women with syphilis, Ontario surveillance data suggest that the population-level impact of this strategy on the HIV epidemic in Ontario would have been modest during this 11-year period. Future studies should explore additional ways of prioritising women for PrEP.

Abuse liability of two electronic nicotine delivery systems compared with combustible cigarettes and nicotine gum from an open-label randomized crossover study.

An assessment of the likelihood of use and abuse potential for new tobacco products is an important part of tobacco product regulation in the United States and abroad. This paper reports the results of a randomized, open-label, crossover clinical study that assessed factors related to product adoption and abuse liability (AL), comparing two closed electronic nicotine delivery system (ENDS) products to combustible cigarettes and nicotine gum, high- and low-AL comparator products, respectively. During an 11-day confinement period that included multiple product familiarization sessions, healthy adult smokers participated in AL test sessions to evaluate the abuse liability of each product. During these test sessions, changes in subjective measures; speed and amount of nicotine uptake; and maximum changes in physiological effects before, during, and after use of each assigned product were assessed over 4 h. Positive subjective effects measures scores such as product-liking and overall intent to use again were highest for cigarettes, followed by the Vuse ENDS, with nicotine gum consistently having the lowest scores. The PK results (Cmax and Tmax) of the Vuse ENDS products are between UB cigarettes and nicotine gum, which correlates with the subjective effects. All nicotine uptake measures for the Vuse ENDS products were lower than that of usual brand (UB) cigarettes, including peak nicotine uptake and overall nicotine uptake, and were either similar to or lower than nicotine gum. The time course of nicotine uptake after use of the ENDS was more similar to that of combustible cigarettes than nicotine gum. The results indicate that the AL of each ENDS product is lower than that of UB cigarettes and similar to that of nicotine gum.

ORFanID: A web-based search engine for the discovery and identification of orphan and taxonomically restricted genes.

With the numerous genomes sequenced today, it has been revealed that a noteworthy percentage of genes in a given taxon of organisms in the phylogenetic tree of life do not have orthologous sequences in other taxa. These sequences are commonly referred to as "orphans" or "ORFans" if found as single occurrences in a single species or as "taxonomically restricted genes" (TRGs) when found at higher taxonomic levels. Quantitative and collective studies of these genes are necessary for understanding their biological origins. However, the current software for identifying orphan genes is limited in its functionality, database search range, and very complex algorithmically. Thus, researchers studying orphan genes must harvest their data from many disparate sources. ORFanID is a graphical web-based search engine that facilitates the efficient identification of both orphan genes and TRGs at all taxonomic levels, from DNA or amino acid sequences in the NCBI database cluster and other large bioinformatics repositories. The software allows users to identify genes that are unique to any taxonomic rank, from species to domain, using NCBI systematic classifiers. It provides control over NCBI database search parameters, and the results are presented in a spreadsheet as well as a graphical display. The tables in the software are sortable, and results can be filtered using the fuzzy search functionality. The visual presentation can be expanded and collapsed by the taxonomic tree to its various branches. Example results from searches on five species and gene expression data from specific orphan genes are provided in the Supplementary Information.

Changes in Biomarkers of Exposure and Potential Harm in Smokers Switched to Vuse Vibe or Vuse Ciro Electronic Nicotine Delivery Systems.

Electronic nicotine delivery systems (ENDS) have the potential to provide nicotine to tobacco consumers while reducing exposure to combustion-related toxicants. Here, we report changes in biomarkers of exposure (BoE) and biomarkers of potential harm (BoPH) in smokers who completely switched to Vuse Vibe and Vuse Ciro ENDS products, or to smoking abstinence in a randomized, controlled clinical study. Thirteen BoE (12 urinary and one blood) that indicate exposure to harmful and potentially harmful toxicants (HPHCs) were evaluated at baseline on day 5. Urinary BoPH linked to oxidative stress, platelet activation, and inflammation were also assessed at baseline, and on day 5 and day 7. Nicotine exposure was lower in Vuse Vibe and Vuse Ciro groups compared to baseline values. Urinary non-nicotine BoE decreased significantly (52.3-96.7%) in the Vuse ENDS groups, and the reductions were similar in magnitude to those observed in the abstinence group. Blood carboxyhemoglobin decreased 52.8-55.0% in all study groups. Decreases (10-50%) in BoPH were observed in all study groups. Thus, smokers who switch exclusively to Vuse Vibe or Vuse Ciro products or completely abstain from smoking are exposed to substantially lower levels of HPHCs, and experience improvements in BoPH of oxidative stress and inflammation pathways.

Part two: an unblinded, parallel, randomized study to assess nicotine pharmacokinetics of four Vuse Solo ENDS flavors in smokers.

We report the findings from a randomized, parallel study designed to evaluate nicotine pharmacokinetics (PK) following 10 min of ad libitum use of electronic nicotine delivery system (ENDS) in four flavor variants. Subjects were randomized an investigational product (IP) and blood samples were collected for PK assessments during a test session. Primary endpoints were baseline-adjusted values of maximum plasma nicotine concentration (Cmax) and area under the nicotine concentration-vs-time curve up to 60 min (AUCnic0-60). Baseline-adjusted mean Cmax ranged from 6.53 to 8.21 ng/mL, and mean AUCnic0-60 ranged from 206.87 to 263.52 ng min/mL for all ENDS IPs. Results of geometric mean Cmax and AUCnic0-60 values were within 95% confidence intervals (CI) among the ENDS IP flavor variants tested.

Pulmonary Nontuberculous Mycobacteria, Ontario, Canada, 2020.

We measured annual prevalence of microbiologically defined nontuberculous mycobacterial lung disease in Ontario, Canada. Mycobacterium avium prevalence was 13 cases/100,000 persons in 2020, a 2.5-fold increase from 2010, indicating a large increase in true M. avium lung disease. During the same period, M. xenopi decreased nearly 50%, to 0.84 cases/100,000 persons.

Differential Retention of Pfam Domains Contributes to Long-term Evolutionary Trends.

Protein domains that emerged more recently in evolution have a higher structural disorder and greater clustering of hydrophobic residues along the primary sequence. It is hard to explain how selection acting via descent with modification could act so slowly as not to saturate over the extraordinarily long timescales over which these trends persist. Here, we hypothesize that the trends were created by a higher level of selection that differentially affects the retention probabilities of protein domains with different properties. This hypothesis predicts that loss rates should depend on disorder and clustering trait values. To test this, we inferred loss rates via maximum likelihood for animal Pfam domains, after first performing a set of stringent quality control methods to reduce annotation errors. Intermediate trait values, matching those of ancient domains, are associated with the lowest loss rates, making our results difficult to explain with reference to previously described homology detection biases. Simulations confirm that effect sizes are of the right magnitude to produce the observed long-term trends. Our results support the hypothesis that differential domain loss slowly weeds out those protein domains that have nonoptimal levels of disorder and clustering. The same preferences also shape the differential diversification of Pfam domains, thereby further impacting proteome composition.

Part one: abuse liability of Vuse Solo (G2) electronic nicotine delivery system relative to combustible cigarettes and nicotine gum.

Abuse liability (AL) of electronic nicotine delivery systems (ENDS) is relevant as the category increases in popularity as a potentially less-harmful alternative to cigarette smoking. AL assessments are important to the FDA in determining if a new product is appropriate for the protection of public health. This paper reports the results for Vuse Solo (G2 cartridge design) compared to high and low AL-comparators evaluated in an open-label, randomized crossover confinement AL study. The confinement design was adapted from previous ambulatory studies of Vuse Solo (G1 cartridge design) and included product familiarization sessions before each four-hour test session in which subjective measures, nicotine pharmacokinetics (PK), and physiological endpoints were assessed following a single 10-min ad libitum product use session. Product liking, intent to use again, suppression of urge to smoke, and nicotine PK were lower after use of Vuse Solo compared to cigarettes and higher after use of Vuse Solo compared to nicotine gum. No significant differences in blood pressure or heart rate were observed between the products pre- to post-product use. These data reinforce previous research and provide the scientific evidence to support regulatory decisions demonstrating that Vuse Solo has an AL profile lower than that of combustible cigarettes but higher than that of nicotine gum and, therefore, may be a suitable replacement for cigarette smoking for some adult smokers.

Part three: a randomized study to assess biomarker changes in cigarette smokers switched to Vuse Solo or Abstinence.

Biomarkers of exposure (BoE) can help evaluate exposure to combustion-related, tobacco-specific toxicants after smokers switch from cigarettes to potentially less-harmful products like electronic nicotine delivery systems (ENDS). This paper reports data for one (Vuse Solo Original) of three products evaluated in a randomized, controlled, confinement study of BoE in smokers switched to ENDS. Subjects smoked their usual brand cigarette ad libitum for two days, then were randomized to one of three ENDS for a 7-day ad libitum use period, or to smoking abstinence. Thirteen BoE were assessed at baseline and Day 5, and percent change in mean values for each BoE was calculated. Biomarkers of potential harm (BoPH) linked to oxidative stress, platelet activation, and inflammation were also assessed. Levels decreased among subjects randomized to Vuse Solo versus Abstinence, respectively, for the following BoE: 42-96% versus 52-97% (non-nicotine constituents); 51% versus 55% (blood carboxyhemoglobin); and 29% versus 96% (nicotine exposure). Significant decreases were observed in three BoPH: leukotriene E4, 11-dehydro-thromboxane B2, and 2,3-dinor thromboxane B2 on Day 7 in the Vuse Solo and Abstinence groups. These findings show that ENDS use results in substantially reduced exposure to toxicants compared to smoking, which may lead to reduced biological effects.

Genomic prediction for the Germplasm Enhancement of Maize project.

The Germplasm Enhancement of Maize (GEM) project was initiated in 1993 as a cooperative effort of public- and private-sector maize (Zea mays L.) breeders to enhance the genetic diversity of the U.S. maize crop. The GEM project selects progeny lines with high topcross yield potential from crosses between elite temperate lines and exotic parents. The GEM project has released hundreds of useful breeding lines based on phenotypic selection within selfing generations and multienvironment yield evaluations of GEM line topcrosses to elite adapted testers. Developing genomic selection (GS) models for the GEM project may contribute to increases in the rate of genetic gain. Here we evaluated the prediction ability of GS models trained on 6 yr of topcross evaluations from the two GEM programs in Raleigh, NC, and Ames, IA, documenting prediction abilities ranging from 0.36 to 0.75 for grain yield and from 0.78 to 0.96 for grain moisture when models were cross-validated within program and heterotic group. Predicted genetic gain from GS ranged from 0.95 to 2.58 times the gain from phenotypic selection. Prediction ability across program and heterotic group was generally poorer than within groups. Based on observed genomic relationships between GEM breeding lines and their tropical ancestors, GS for either yield or moisture would reduce recovery of exotic germplasm only slightly. Using GS models trained within program, the GEM programs should be able to more effectively deliver on its mission to broaden the genetic base of U.S. germplasm.

Nitrogen fertilizer rate but not form affects the severity of Fusarium wilt in banana.

Nitrogen (N) fertilizers are routinely applied to bananas (Musa spp.) to increase production but may exacerbate plant diseases like Fusarium wilt of banana (FWB), which is the most economically important disease. Here, we characterized the effects of N rate and form on banana plant growth, root proteome, bacterial and fungal diversity in the rhizosphere, the concentration of Fusarium oxysporum f.sp. cubense (Foc) in the soil, and the FWB severity. Banana plants (Musa subgroup ABB) were grown under greenhouse conditions in soil with ammonium or nitrate supplemented at five N rates, and with or without inoculation with Foc. The growth of non-inoculated plants was positively correlated with the N rate. In bananas inoculated with Foc, disease severity increased with the N rate, resulting in the Foc-inoculated plant growth being greatest at intermediate N rates. The abundance of Foc in the soil was weakly related to the treatment conditions and was a poor predictor of disease severity. Fungal diversity was consistently affected by Foc inoculation, while bacterial diversity was associated with changes in soil pH resulting from N addition, in particular ammonium. N rate altered the expression of host metabolic pathways associated with carbon fixation, energy usage, amino acid metabolism, and importantly stress response signaling, irrespective of inoculation or N form. Furthermore, in diseased plants, Pathogenesis-related protein 1, a key endpoint for biotic stress response and the salicylic acid defense response to biotrophic pathogens, was negatively correlated with the rate of ammonium fertilizer but not nitrate. As expected, inoculation with Foc altered the expression of a wide range of processes in the banana plant including those of defense and growth. In summary, our results indicate that the severity of FWB was negatively associated with host defenses, which was influenced by N application (particularly ammonium), and shifts in microbial communities associated with ammonium-induced acidification.

Characteristics of SARS-CoV-2 testing for rapid diagnosis of COVID-19 during the initial stages of a global pandemic.

Accurate SARS-CoV-2 diagnosis is essential to guide prevention and control of COVID-19. Here we examine SARS-CoV-2 molecular-based test performance characteristics and summarize case-level data related to COVID-19 diagnosis. From January 11 through April 22, 2020, Public Health Ontario conducted SARS-CoV-2 testing of 86,942 specimens collected from 80,354 individuals, primarily using real-time reverse-transcription polymerase chain reaction (rRT-PCR) methods. We analyzed test results across specimen types and for individuals with multiple same-day and multi-day collected specimens. Nasopharyngeal compared to throat swabs had a higher positivity (8.8% vs. 4.8%) and an adjusted estimate 2.9 Ct lower (SE = 0.5, p<0.001). Same-day specimens showed high concordance (98.8%), and the median Ct of multi-day specimens increased over time. Symptomatic cases had rRT-PCR results with an adjusted estimate 3.0 Ct (SE = 0.5, p<0.001) lower than asymptomatic/pre-symptomatic cases. Overall test sensitivity was 84.6%, with a negative predictive value of 95.5%. Molecular testing is the mainstay of SARS-CoV-2 diagnosis and testing protocols will continue to be dynamic and iteratively modified as more is learned about this emerging pathogen.

Prevalence of Co-Infections with Respiratory Viruses in Individuals Investigated for SARS-CoV-2 in Ontario, Canada.

BACKGROUND: Co-infections of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with respiratory viruses, bacteria and fungi have been reported to cause a wide range of illness. OBJECTIVES: We assess the prevalence of co-infection of SARS-CoV-2 with seasonal respiratory viruses, document the respiratory viruses detected among individuals tested for SARS-CoV-2, and describe characteristics of individuals with respiratory virus co-infection detected. METHODS: Specimens included in this study were submitted as part of routine clinical testing to Public Health Ontario Laboratory from individuals requiring testing for SARS-CoV-2 and/or seasonal respiratory viruses. RESULTS: Co-infection was detected in a smaller proportion (2.5%) of individuals with laboratory confirmed SARS-CoV-2 than those with seasonal respiratory viruses (4.3%); this difference was not significant. Individuals with any respiratory virus co-infection were more likely to be younger than 65 years of age and male than those with single infection. Those with SARS-CoV-2 co-infection manifested mostly mild respiratory symptoms. CONCLUSIONS: Findings of this study may not support routine testing for seasonal respiratory viruses among all individuals tested for SARS-CoV-2, as they were rare during the study period nor associated with severe disease. However, testing for seasonal respiratory viruses should be performed in severely ill individuals, in which detection of other viruses may assist with patient management.

Universal and taxon-specific trends in protein sequences as a function of age.

Extant protein-coding sequences span a huge range of ages, from those that emerged only recently to those present in the last universal common ancestor. Because evolution has had less time to act on young sequences, there might be 'phylostratigraphy' trends in any properties that evolve slowly with age. A long-term reduction in hydrophobicity and hydrophobic clustering was found in previous, taxonomically restricted studies. Here we perform integrated phylostratigraphy across 435 fully sequenced species, using sensitive HMM methods to detect protein domain homology. We find that the reduction in hydrophobic clustering is universal across lineages. However, only young animal domains have a tendency to have higher structural disorder. Among ancient domains, trends in amino acid composition reflect the order of recruitment into the genetic code, suggesting that the composition of the contemporary descendants of ancient sequences reflects amino acid availability during the earliest stages of life, when these sequences first emerged.

APDS Task Force on Resident Transfers: Guidelines for Program Directors.

OBJECTIVE: Resident attrition from the field of General Surgery has been extensively studied. Attrition from one General Surgery program to the benefit of another has not. General Surgery programs can be negatively affected when a resident decides to leave the program for another. When a resident in a general surgery residency program decides to attempt transfer to another program several decisions must be made. The resident applies for the open position, interviews and then may be offered a position in that program. If an offer is made and the resident accepts, at what point is the resident's current Program Director notified? At what point in the process does the resident leave his/her current program to begin the new program? At what point does the new Program Director obtain a summative evaluation of the resident? Does the resident experience retribution as a result of informing his/her fellow residents and faculty that s/he is leaving? These are all questions that Program Directors struggle with when they find themselves with an unexpected opening to fill. The APDS Task Force on Resident Transfers attempted to answer these and other questions. DESIGN: A 19-question survey was distributed via the APDS to all General Surgery Program Directors who utilize the list serve. The survey asked questions related to the following: acceptable reasons for transfer; timeline for the application, interview and transfer process; retaliation against residents who chose to transfer; and transparency in the transfer process. SETTING: The survey was distributed via e-mail nationwide. PARTICIPANTS: General Surgery Residency Program Directors are participated in the survey. RESULTS: The majority of the 99 respondents agreed to the following guidelines: (1) Program Directors must promote transparency in the transfer process; (2) Program Directors must make a statement against retaliation; (3) personal or family preference is the most acceptable reason for transfer; (4) an established transfer date must be agreeable to both programs; and, (5) a recruitment timeline should be established for both programs. All data are included below. CONCLUSIONS: The reasons that a resident chooses to leave a program and the effect this has on the program and the other residents requires further study. Program Directors should educate residents about the transfer process and that procedure should be available as a written policy. When a resident desires transfer to another program, following these guidelines may make the transition easier for all involved. The APDS supports putting them into practice.

Defensive Symbiosis and the Evolution of Virulence.

AbstractA microbiome rife with enemies of the host should cause selection for defensive traits in symbionts, yet such complex environments are also predicted to select for greater symbiont virulence. Why then do we so often observe defensive mutualists that protect hosts while causing little to no damage? To address this question, we build a symbiont-centered model that incorporates the evolution of two independent symbiont traits: defense and virulence. Virulence is modeled as a continuous trait spanning parasitism (positive virulence) and mutualism (negative virulence), thus accounting for the entire range of direct effects that symbionts have on host mortality. Defense is modeled as a continuous trait that ameliorates the costs to the host associated with infection by a deleterious parasite. We show that the evolution of increased defense in one symbiont may lead to the evolution of lower virulence in both symbionts and even facilitate pathogens evolving to mutualism. However, results are context dependent, and when defensive traits are costly, the evolution of greater defense may also lead to the evolution of greater virulence, breaking the common expectation that defensive symbionts are necessarily mutualists toward the host.

Catheter-induced acute Blalock-Taussig shunt thrombosis and bailout.

Modified Blalock-Taussig shunt thrombosis is a life-threatening event. We describe an extremely rare catheter-induced shunt thrombosis in an infant with complex CHD and its successful treatment utilising a single low dose of local recombinant tissue plasminogen activator in conjunction with balloon angioplasty.

Characterizing college science instruction: The Three-Dimensional Learning Observation Protocol.

The importance of improving STEM education is of perennial interest, and to this end, the education community needs ways to characterize transformation efforts. Three-dimensional learning (3DL) is one such approach to transformation, in which core ideas of the discipline, scientific practices, and crosscutting concepts are combined to support student development of disciplinary expertise. We have previously reported on an approach to the characterization of assessments, the Three-Dimensional Learning Assessment Protocol (3D-LAP), that can be used to identify whether assessments have the potential to engage students in 3DL. Here we present the development of a companion, the Three-Dimensional Learning Observation Protocol (3D-LOP), an observation protocol that can reliably distinguish between instruction that has potential for engagement with 3DL and instruction that does not. The 3D-LOP goes beyond other observation protocols, because it is intended not only to characterize the pedagogical approaches being used in the instructional environment, but also to identify whether students are being asked to engage with scientific practices, core ideas, and crosscutting concepts. We demonstrate herein that the 3D-LOP can be used reliably to code for the presence of 3DL; further, we present data that show the utility of the 3D-LOP in differentiating between instruction that has the potential to promote 3DL from instruction that does not. Our team plans to continue using this protocol to evaluate outcomes of instructional transformation projects. We also propose that the 3D-LOP can be used to support practitioners in developing curricular materials and selecting instructional strategies to promote engagement in three-dimensional instruction.

Extraction of metals from mildly acidic tropical soils: Interactions between chelating ligand, pH and soil type.

Naturally occurring and synthetic chelating ligands can act as suppressants for fungal pathogens, nematodes and weeds, based on their ability to alter micronutrient bioavailability in soil, particularly iron. Chelators are also used as detergents, for remediation of heavy metal contamination and for supplying metals as fertiliser. The aim of this work was to test the ability of chelators to solubilise metals, in particular iron, in tropical soils over an environmentally relevant pH range. Six topsoils from farms in North Queensland, Australia were adjusted to pH 5, 6 and 7 and then extracted with CaCl2, EDTA, DTPA, EDDHA and mimosine. The extracts were analysed for concentrations of aluminium, copper, iron, magnesium, manganese, potassium, strontium and zinc. EDDHA solubilised iron effectively under all of the conditions tested, indicating its likely suitability for pest suppression. The concentration of aluminium in EDDHA extracts was positively correlated with pH, and at pH 7 the concentration of aluminium was far greater than that of iron. An increase in the mobility of aluminium from EDDHA application to soil may lead to aluminium toxicity in plants, which should be considered further in any practical application of EDDHA. Mimosine, which is also a strong chelator, was a poor extractor of all metals, possibly due to adsorption to the soil.