Waterloo Research

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From the ground up: Global nitrous oxide sources are constrained by stable isotope values
(Public Library of Science, 2015-03-26) Snider, David M.; Venkiteswaran, Jason J.; Schiff, Sherry L.; Spoelstra, John
Rising concentrations of nitrous oxide (N2O) in the atmosphere are causing widespread concern because this trace gas plays a key role in the destruction of stratospheric ozone and it is a strong greenhouse gas. The successful mitigation of N2O emissions requires a solid understanding of the relative importance of all N2O sources and sinks. Stable isotope ratio measurements (δ15N-N2O and δ18O-N2O), including the intramolecular distribution of 15N (site preference), are one way to track different sources if they are isotopically distinct. ‘Top-down’ isotope mass-balance studies have had limited success balancing the global N2O budget thus far because the isotopic signatures of soil, freshwater, and marine sources are poorly constrained and a comprehensive analysis of global N2O stable isotope measurements has not been done. Here we used a robust analysis of all available in situ measurements to define key global N2O sources. We showed that the marine source is isotopically distinct from soil and freshwater N2O (the continental source). Further, the global average source (sum of all natural and anthropogenic sources) is largely controlled by soils and freshwaters. These findings substantiate past modelling studies that relied on several assumptions about the global N2O cycle. Finally, a two-box-model and a Bayesian isotope mixing model revealed marine and continental N2O sources have relative contributions of 24–26% and 74–76% to the total, respectively. Further, the Bayesian modeling exercise indicated the N2O flux from freshwaters may be much larger than currently thought.
High intensity interval and endurance training have opposing effects on markers of heart failure and cardiac remodeling in hypertensive rats
(Public Library of Science, 2015-03-24) Holloway, Tanya M.; Bloemberg, Darin; da Silva, Mayne L.; Simpson, Jeremy A.; Quadrilatero, Joe; Spriet, Lawrence L.
There has been re-emerging interest and significant work dedicated to investigating the metabolic effects of high intensity interval training (HIIT) in recent years. HIIT is considered to be a time efficient alternative to classic endurance training (ET) that elicits similar metabolic responses in skeletal muscle. However, there is a lack of information on the impact of HIIT on cardiac muscle in disease. Therefore, we determined the efficacy of ET and HIIT to alter cardiac muscle characteristics involved in the development of diastolic dysfunction, such as ventricular hypertrophy, fibrosis and angiogenesis, in a well-established rodent model of hypertension-induced heart failure before the development of overt heart failure. ET decreased left ventricle fibrosis by ~40% (P < 0.05), and promoted a 20% (P<0.05) increase in the left ventricular capillary/fibre ratio, an increase in endothelial nitric oxide synthase protein (P<0.05), and a decrease in hypoxia inducible factor 1 alpha protein content (P<0.05). In contrast, HIIT did not decrease existing fibrosis, and HIIT animals displayed a 20% increase in left ventricular mass (P<0.05) and a 20% decrease in cross sectional area (P<0.05). HIIT also increased brain natriuretic peptide by 50% (P<0.05), in the absence of concomitant angiogenesis, strongly suggesting pathological cardiac remodeling. The current data support the longstanding belief in the effectiveness of ET in hypertension. However, HIIT promoted a pathological adaptation in the left ventricle in the presence of hypertension, highlighting the need for further research on the widespread effects of HIIT in the presence of disease.
Depth profilometry via multiplexed optical high-coherence interferometry
(Public Library of Science, 2015-03-24) Kazemzadeh, Farnoud; Wong, Alexander; Behr, Bradford B.; Hajian, Arsen R.
Depth Profilometry involves the measurement of the depth profile of objects, and has significant potential for various industrial applications that benefit from non-destructive sub-surface profiling such as defect detection, corrosion assessment, and dental assessment to name a few. In this study, we investigate the feasibility of depth profilometry using an Multiplexed Optical High-coherence Interferometry MOHI instrument. The MOHI instrument utilizes the spatial coherence of a laser and the interferometric properties of light to probe the reflectivity as a function of depth of a sample. The axial and lateral resolutions, as well as imaging depth, are decoupled in the MOHI instrument. The MOHI instrument is capable of multiplexing interferometric measurements into 480 one-dimensional interferograms at a location on the sample and is built with axial and lateral resolutions of 40 μm at a maximum imaging depth of 700 μm. Preliminary results, where a piece of sand-blasted aluminum, an NBK7 glass piece, and an optical phantom were successfully probed using the MOHI instrument to produce depth profiles, demonstrate the feasibility of such an instrument for performing depth profilometry.
A controlled quasi-experimental study of an educational intervention to reduce the unnecessary use of antimicrobials for asymptomatic bacteriuria
(Public Library of Science, 2015-07-16) Irfan, Neal; Brooks, Annie; Mithoowani, Siraj; Celetti, Steve J.; Main, Cheryl; Mertz, Dominik
Background Asymptomatic bacteriuria (ABU) should only be treated in cases of pregnancy or in-patients undergoing urologic procedures; however, unnecessary treatment of ABU is common in clinical practice. Objective To identify risk factors for unnecessary treatment and to assess the impact of an educational intervention focused on these risk factors on treatment of ABU. Design Quasi-experimental study with a control group. Setting Two tertiary teaching adult care hospitals. Participants Consecutive patients with positive urine cultures between January 30th and April 17th, 2012 (baseline) and January 30th and April 30th, 2013 (intervention). Intervention In January 2013, a multifaceted educational intervention based on risk factors identified during the baseline period was provided to medical residents (monthly) on one clinical teaching unit (CTU) at one hospital site, with the CTU of the other hospital serving as the control. Results During the baseline period, 160/341 (46.9%) positive urine cultures were obtained from asymptomatic patients at the two hospitals, and 94/160 (58.8%) were inappropriately treated with antibiotics. Risk factors for inappropriate use included: female gender (OR 2.1, 95% CI 1.1-4.3), absence of a catheter (OR 2.5, 1.2-5), bacteriuria versus candiduria (OR 10.6, 3.8-29.4), pyuria (OR 2.0, 1.1-3.8), and positive nitrites (OR 2.2, 1.1-4.5). In 2013, only 2/24 (8%) of ABU patients were inappropriately treated on the intervention CTU as compared to 14/29 (52%) on the control CTU (OR 0.10; 95% CI 0.02-0.49). A reduction was also observed as compared to baseline on the intervention CTU (OR 0.1, 0.02-0.7) with no significant change noted on the control CTU (OR 0.47, 0.13-1.7). Conclusions A multifaceted educational intervention geared towards medical residents with a focus on identified risk factors for inappropriate management of ABU was effective in reducing unnecessary antibiotic use.
Hydrophobic gating of ion permeation in magnesium channel CorA
(Public Library of Science, 2015-07-16) Neale, Chris; Chakrabarti, Nilmadhab; Pomorski, Pawel; Pai, Emil F.; Pomes, Regis
Ion channels catalyze ionic permeation across membranes via water-filled pores. To understand how changes in intracellular magnesium concentration regulate the influx of Mg2+ into cells, we examine early events in the relaxation of Mg2+ channel CorA toward its open state using massively-repeated molecular dynamics simulations conducted either with or without regulatory ions. The pore of CorA contains a 2-nm-long hydrophobic bottleneck which remained dehydrated in most simulations. However, rapid hydration or “wetting” events concurrent with small-amplitude fluctuations in pore diameter occurred spontaneously and reversibly. In the absence of regulatory ions, wetting transitions are more likely and include a wet state that is significantly more stable and more hydrated. The free energy profile for Mg2+ permeation presents a barrier whose magnitude is anticorrelated to pore diameter and the extent of hydrophobic hydration. These findings support an allosteric mechanism whereby wetting of a hydrophobic gate couples changes in intracellular magnesium concentration to the onset of ionic conduction.
Genome regions associated with functional performance of soybeam stem fibers in polypropylene thermoplastic composites
(Public Library of Science, 2015-07-13) Reinprecht, Yarmilla; Arif, Muhammad; Simon, Leonardo C.; Pauls, K. Peter
Plant fibers can be used to produce composite materials for automobile parts, thus reducing plastic used in their manufacture, overall vehicle weight and fuel consumption when they replace mineral fillers and glass fibers. Soybean stem residues are, potentially, significant sources of inexpensive, renewable and biodegradable natural fibers, but are not curretly used for biocomposite production due to the functional properties of their fibers in composites being unknown. The current study was initiated to investigate the effects of plant genotype on the performance characteristics of soybean stem fibers when incorporated into a polypropylene (PP) matrix using a selective phenotyping approach. Fibers from 50 lines of a recombinant inbred line population (169 RILs) grown in different environments were incorporated into PP at 20% (wt/wt) by extrusion. Test samples were injection molded and characterized for their mechanical properties. The performance of stem fibers in the composites was significantly affected by genotype and environment. Fibers from different genotypes had significantly different chemical compositions, thus composites prepared with these fibers displayed different physical properties. This study demonstrates that thermoplastic composites with soybean stem-derived fibers have mechanical properties that are equivalent or better than wheat straw fiber composites currently being used for manufacturing interior automotive parts. The addition of soybean stem residues improved flexural, tensile and impact properties of the composites. Furthermore, by linkage and in silico mapping we identified genomic regions to which quantitative trait loci (QTL) for compositional and functional properties of soybean stem fibers in thermoplastic composites, as well as genes for cell wall synthesis, were co-localized. These results may lead to the development of high value uses for soybean stem residue.
Stress-immune-growth interactions: Cortisol modulates suppressors of cytokine signaling and JAK/STAT pathway in rainbow trout liver
(Public Library of Science, 2015-06-17) Philip, Anju M.; Vijayan, Mathilakath M.
Chronic stress is a major factor in the poor growth and immune performance of salmonids in aquaculture. However, the molecular mechanisms linking stress effects to growth and immune dysfunction is poorly understood. The suppressors of cytokine signaling (SOCS), a family of genes involved in the inhibition of JAK/STAT pathway, negatively regulates growth hormone and cytokine signaling, but their role in fish is unclear. Here we tested the hypothesis that cortisol modulation of SOCS gene expression is a key molecular mechanism leading to growth and immune suppression in response to stress in fish. Exposure of rainbow trout (Oncorhynchus mykiss) liver slices to cortisol, mimicking stress level, upregulated SOCS-1 and SOCS-2 mRNA abundance and this response was abolished by the glucocorticoid receptor antagonist mifepristone. Bioinformatics analysis confirmed the presence of putative glucocorticoid response elements in rainbow trout SOCS-1 and SOCS-2 promoters. Prior cortisol treatment suppressed acute growth hormone (GH)-stimulated IGF-1 mRNA abundance in trout liver and this involved a reduction in STAT5 phosphorylation and lower total JAK2 protein expression. Prior cortisol treatment also suppressed lipopolysaccharide (LPS)-induced IL-6 but not IL-8 transcript levels; the former but not the latter cytokine expression is via JAK/STAT phosphorylation. LPS treatment reduced GH signaling, but this was associated with the downregulation of GH receptors and not due to the upregulation of SOCS transcript levels by this endotoxin. Collectively, our results suggest that upregulation of SOCS-1 and SOCS-2 transcript levels by cortisol, and the associated reduction in JAK/STAT signaling pathway, may be a novel mechanism leading to growth reduction and immune suppression during stress in trout.
Bacterial acclimation inside an aqueous battery
(Public Library of Science, 2015-06-12) Dong, Dexian; Chen, Baoling; Chen, P.
Specific environmental stresses may lead to induced genomic instability in bacteria, generating beneficial mutants and potentially accelerating the breeding of industrial microorganisms. The environmental stresses inside the aqueous battery may be derived from such conditions as ion shuttle, pH gradient, free radical reaction and electric field. In most industrial and medical applications, electric fields and direct currents are used to kill bacteria and yeast. However, the present study focused on increasing bacterial survival inside an operating battery. Using a bacterial acclimation strategy, both Escherichia coli and Bacillus subtilis were acclimated for 10 battery operation cycles and survived in the battery for over 3 days. The acclimated bacteria changed in cell shape, growth rate and colony color. Further analysis indicated that electrolyte concentration could be one of the major factors determining bacterial survival inside an aqueous battery. The acclimation process significantly improved the viability of both bacteria E. coli and B. subtilis. The viability of acclimated strains was not affected under battery cycle conditions of 0.18-0.80 mA cm-2 and 1.4-2.1 V. Bacterial addition within 1.0×1010 cells mL-1 did not significantly affect battery performance. Because the environmental stress inside the aqueous battery is specific, the use of this battery acclimation strategy may be of great potential for the breeding of industrial microorganisms.
Temporal and spatial variation in the abundance of total and pathogenic Vibrio parahaemolyticus in shellfish in China
(Public Library of Science, 2015-06-10) Han, Haihong; Li, Fengqin; Yan, Weixing; Guo, Yunchang; Li, Ning; Liu, Xiumei; Zhu, Jianghui; Xu, Jin; Chen, Yan; Li, Xiugui; Lv, Hong; Zhang, Yiqian; Cai, Te; Chen, Yuzhen
We investigated the abundance of total and pathogenic Vibrio parahaemolyticus in shellfish sampled from four provinces in China during May 2013 and March 2014 using the most probable number-polymerase chain reaction (MPN-PCR) method. Total V. parahaemolyticus was detected in 67.7% of 496 samples. A total of 38.1% and 10.1% of samples exceeded 1,000 MPN g-1 and 10,000 MPN g-1, respectively. V. parahaemolyticus densities followed a seasonal and geographical trend, with Guangxi and Sichuan shellfish possessing total V. parahaemolyticus levels that were 100-fold higher than those of the Liaoning and Shandong regions. Moreover, the levels of V. parahaemolyticus were at least 10-fold higher in the summer and autumn than in the cooler seasons. Pathogenic V. parahaemolyticus levels were generally lower than total V. parahaemolyticus levels by several log units and tended to be high in samples contaminated with high total V. parahaemolyticus levels. The aqua farms had a lower prevalence but higher abundance of total V. parahaemolyticus compared to retail markets. The catering markets showed the lowest levels of total V. parahaemolyticus, but 20.0% of samples exceeded 1,000 MPN g-1. The levels of both total and pathogenic V. parahaemolyticus in oysters were higher than in clams. The log-transformed abundance of V. parahaemolyticus was significantly correlated with both water temperature and air temperature but not water salinity. These results provide baseline contamination data of V. parahaemolyticus in shellfish in China, which can be applied to local risk assessments to prioritize risk control to key sectors and evaluate the effectiveness of future control measures.
Catchment legacies and time lags: A parsimonious watershed model to predict the effects of legacy storage on nitrogen export
(Public Library of Science, 2015-05-18) Van Meter, Kimberly J.; Basu, Nandita B.
Nutrient legacies in anthropogenic landscapes, accumulated over decades of fertilizer application, lead to time lags between implementation of conservation measures and improvements in water quality. Quantification of such time lags has remained difficult, however, due to an incomplete understanding of controls on nutrient depletion trajectories after changes in land-use or management practices. In this study, we have developed a parsimonious watershed model for quantifying catchment-scale time lags based on both soil nutrient accumulations (biogeochemical legacy) and groundwater travel time distributions (hydrologic legacy). The model accurately predicted the time lags observed in an Iowa watershed that had undergone a 41% conversion of area from row crop to native prairie. We explored the time scales of change for stream nutrient concentrations as a function of both natural and anthropogenic controls, from topography to spatial patterns of land-use change. Our results demonstrate that the existence of biogeochemical nutrient legacies increases time lags beyond those due to hydrologic legacy alone. In addition, we show that the maximum concentration reduction benefits vary according to the spatial pattern of intervention, with preferential conversion of land parcels having the shortest catchment-scale travel times providing proportionally greater concentration reductions as well as faster response times. In contrast, a random pattern of conversion results in a 1:1 relationship between percent land conversion and percent concentration reduction, irrespective of denitrification rates within the landscape. Our modeling framework allows for the quantification of tradeoffs between costs associated with implementation of conservation measures and the time needed to see the desired concentration reductions, making it of great value to decision makers regarding optimal implementation of watershed conservation measures.
Personalized mortality prediction driven by electronic medical data and a patient similarity metric
(Public Library of Science, 2015-05-15) Lee, Joon; Maslove, David M.; Dubin, Joel A.
Background Clinical outcome prediction normally employs statis, one-size-fits-all models that perform well for the average patient but are sub-optimal for individual patients with unique characteristics. In the era of digital healthcare, it is feasible to dynamically personalize decision support by identifying and analyzing similar past patients, in a way that is analogous to personalized product recommendation in e-commerce. Our objectives were: 1) to prove that analyzing only similar patients leads to better outcome prediction performance than analyzing all available patients, and 2) to characterize the trade-off between training data size and the degree of similarity between the training data and the index patient for whom prediction is to be made. Methods and Findings We deployed a cosine-similarity-based patient similarity metric (PSM) to an intensive care unit (ICU) database to identify patients that are most similar to each patient and subsequently to custom-build 30-day mortality prediction models. Rich clinical and administrative data from the first day in the ICU from 17,152 adult ICU admissions were analyzed. The results confirmed that using data from only a small subset of most similar patients for training improves predictive performance in comparison with using data from all available patients. The results also showed that when too few similar patients are used for training, predictive performance degrades due to the effects of small sample sizes. Our PSM-based approach outperformed well-known ICU severity of illness scores. Although the improved prediction performance is achieved at the cost of increased computational burden, Big Data technologies can help realize personalized data-driven decision support at the point of care. Conclusions The present study provides crucial empirical evidence for the promising potential of personalized data-driven decision support systems. With the increasing adoption of electronic medical record (EMR) systems, our novel medical data analytics contributes to meaningful use of EMR data.
What are priorities for deprescribing for elderly patients? Capturing the voice of practitioners: A modified Delphi process
(Public Library of Science, 2015-04-07) Farrell, Barbara; Tsang, Corey; Raman-Wilms, Lalitha; Irving, Hannah; Conklin, James; Pottie, Kevin
Polypharmacy and inappropriate medication use among older adults contribute to adverse drug reactions, falls, cognitive impairment, noncompliance, hospitalization and mortality. While deprescribing - tapering, reducing or stopping a medication - is feasible and relatively safe, clinicians find it difficult to carry out. Deprescribing guidelines would facilitate this process. The aim of this paper is to identify and prioritize medication classes where evidence-based deprescribing guidelines would be of benefit to clinicians. A modified Delphi approach included a literature review to identify potentially inappropriate medications for the elderly, an expert panel to develop survey content and three survey rounds to seek consensus on priorities. Panel participants included three pharmacists, two family physicians and one social scientist. Sixty-five Canadian geriatrics experts (36 pharmacists, 19 physicians and 10 nurse practitioners) participated in the survey. Twenty-nine drugs/drug classes were included in the first survey with 14 reaching the required (≥ 70%) level of consensus, and 2 new drug classes added from qualitative comments. Fifty-three participants completed round two, and 47 participants completed round three. The final five priorities were benzodiazepines, atypical antipsychotics, statins, tricyclic antidepressants, and proton pump inhibitors; nine other drug classes were also identified as being in need of evidence-based deprescribing guidelines. The Delphi consensus process identified five priority drug classes for which expert clinicians felt guidance is needed for deprescribing. The classes of drugs that emerged strongly from the rankings dealt with mental health, cardiovascular, gastroenterological, and neurological conditions. The results suggest that deprescribing and overtreatment occurs through the full spectrum of primary care, and that evidence-based deprescribing guidelines are a priority in the care of the elderly.
Going against the Herd: Psychological and cultura factors underlying the 'vaccination confidence gap'
(Public Library of Science, 2015-09-01) Browne, Matthew; Thomson, Patricia; Rockloff, Matthew Justus; Pennycook, Gordon
By far the most common strategy used in the attempt to modify negative attitudes toward vaccination is to appeal to evidence-based reasoning. We argue, however, that focusing on science comprehension is inconsistent with one of the key facts of cognitive psychology: Humans are biased information processors and often engage in motivated reasoning. On this basis, we hypothesised that negative attitudes can be explained primarily by factors unrelated to the empirical evidence for vaccination; including some shared attitudes that also attract people to complementary and alternative medicine (CAM). In particular, we tested psychosocial factors associated with CAM endorsement in past research; including aspects of spirituality, intuitive (vs analytic) thinking styles, and the personality trait of openness to experience. These relationships were tested in a cross-sectional, stratified CATI survey (N = 1256, 624 Females). Whilst educational level and thinking style did not predict vaccination rejection, psychosocial factors including: preferring CAM to conventional medicine (OR .49, 95% CI .36–.66), endorsement of spirituality as a source of knowledge (OR .83, 95% CI .71–.96), and openness (OR .86, 95% CI .74–.99), all predicted negative attitudes to vaccination. Furthermore, for 9 of the 12 CAMs surveyed, utilisation in the last 12 months was associated with lower levels of vaccination endorsement. From this we suggest that vaccination scepticism appears to be the outcome of a particular cultural and psychological orientation leading to unwillingness to engage with the scientific evidence. Vaccination compliance might be increased either by building general confidence and understanding of evidence-based medicine, or by appealing to features usually associated with CAM, e.g. ‘strengthening your natural resistance to disease’.
Integration of semi-circular canal and otolith cues for direction discrimination during eccentric rotations
(Public Library of Science, 2015-08-31) Soyka, Florian; Bulthoff, Heinrich H.; Barnett-Cowan, Michael
Humans are capable of moving about the world in complex ways. Every time we move, our self-motion must be detected and interpreted by the central nervous system in order to make appropriate sequential movements and informed decisions. The vestibular labyrinth consists of two unique sensory organs the semi-circular canals and the otoliths that are specialized to detect rotation and translation of the head, respectively. While thresholds for pure rotational and translational self-motion are well understood surprisingly little research has investigated the relative role of each organ on thresholds for more complex motion. Eccentric (off-center) rotations during which the participant faces away from the center of rotation stimulate both organs and are thus well suited for investigating integration of rotational and translational sensory information. Ten participants completed a psychophysical direction discrimination task for pure head-centered rotations, translations and eccentric rotations with 5 different radii. Discrimination thresholds for eccentric rotations reduced with increasing radii, indicating that additional tangential accelerations (which increase with radius length) increased sensitivity. Two competing models were used to predict the eccentric thresholds based on the pure rotation and translation thresholds: one assuming that information from the two organs is integrated in an optimal fashion and another assuming that motion discrimination is solved solely by relying on the sensor which is most strongly stimulated. Our findings clearly show that information from the two organs is integrated. However the measured thresholds for 3 of the 5 eccentric rotations are even more sensitive than predictions from the optimal integration model suggesting additional non-vestibular sources of information may be involved.
A deep-structured conditional random field model for object silhouette tracking
(Public Library of Science, 2015-08-27) Shafiee, Mohammad Javad; Azimifar, Zohreh; Wong, Alexander
In this work, we introduce a deep-structured conditional random field (DS-CRF) model for the purpose of state-based object silhouette tracking. The proposed DS-CRF model consists of a series of state layers, where each state layer spatially characterizes the object silhouette at a particular point in time. The interactions between adjacent state layers are established by inter-layer connectivity dynamically determined based on inter-frame optical flow. By incorporate both spatial and temporal context in a dynamic fashion within such a deep-structured probabilistic graphical model, the proposed DS-CRF model allows us to develop a framework that can accurately and efficiently track object silhouettes that can change greatly over time, as well as under different situations such as occlusion and multiple targets within the scene. Experiment results using video surveillance datasets containing different scenarios such as occlusion and multiple targets showed that the proposed DS-CRF approach provides strong object silhouette tracking performance when compared to baseline methods such as mean-shift tracking, as well as state-of-the-art methods such as context tracking and boosted particle filtering.
Inability and obligation in moral judgment
(Public Library of Science, 2015-08-21) Buckwalter, Wesley; Turri, John
It is often thought that judgments about what we ought to do are limited by judgments about what we can do, or that “ought implies can.” We conducted eight experiments to test the link between a range of moral requirements and abilities in ordinary moral evaluations. Moral obligations were repeatedly attributed in tandem with inability, regardless of the type (Experiments 1–3), temporal duration (Experiment 5), or scope (Experiment 6) of inability. This pattern was consistently observed using a variety of moral vocabulary to probe moral judgments and was insensitive to different levels of seriousness for the consequences of inaction (Experiment 4). Judgments about moral obligation were no different for individuals who can or cannot perform physical actions, and these judgments differed from evaluations of a non-moral obligation (Experiment 7). Together these results demonstrate that commonsense morality rejects the “ought implies can” principle for moral requirements, and that judgments about moral obligation are made independently of considerations about ability. By contrast, judgments of blame were highly sensitive to considerations about ability (Experiment 8), which suggests that commonsense morality might accept a “blame implies can” principle.
Environmental interactions and epistasis are revealed in the proteomic responses to complex stimuli
(Public Library of Science, 2015-08-06) Samir, Parimal; Rahul; Slaughter, James C.; Link, Andrew J.
Ultimately, the genotype of a cell and its interaction with the environment determine the cell’s biochemical state. While the cell’s response to a single stimulus has been studied extensively, a conceptual framework to model the effect of multiple environmental stimuli applied concurrently is not as well developed. In this study, we developed the concepts of environmental interactions and epistasis to explain the responses of the S. cerevisiae proteome to simultaneous environmental stimuli. We hypothesize that, as an abstraction, environmental stimuli can be treated as analogous to genetic elements. This would allow modeling of the effects of multiple stimuli using the concepts and tools developed for studying gene interactions. Mirroring gene interactions, our results show that environmental interactions play a critical role in determining the state of the proteome. We show that individual and complex environmental stimuli behave similarly to genetic elements in regulating the cellular responses to stimuli, including the phenomena of dominance and suppression. Interestingly, we observed that the effect of a stimulus on a protein is dominant over other stimuli if the response to the stimulus involves the protein. Using publicly available transcriptomic data, we find that environmental interactions and epistasis regulate transcriptomic responses as well.
Strengthening access to and confidence in COVID-19 vaccines among equity-deserving populations across Canada: An exploratory qualitative study
(Public Library of Science, 2026-04-27) Bashir, Kainat; Ouedraogo, Mariame O.; Dharma, Christoffer; Sobers, Mercedes; Atukorale, Vajini; Mauer-Vakil, Dane; Ataullahjan, Anushka; Fadel, Shaza A.; Allin, Sara
Introduction There is a need to reflect on the COVID-19 vaccine distribution plans across Canada and the extent to which they considered equity-deserving populations, as lessons from the rollout can inform future emergency responses and foster trust in public health. This paper examined and compared strategies implemented by six Canadian provinces to increase access and promote the uptake of COVID-19 vaccines among selected priority populations. We also explored the factors that impacted the implementation of these strategies. Methods In six provinces (Alberta, British Columbia, Manitoba, Nova Scotia, Ontario, and Quebec), we conducted an environmental scan of provincial rollout documents and media sources reporting vaccine distribution among selected priority populations: First Nations, Inuit, and Métis; Black communities; essential workers; people experiencing homelessness; and people with disabilities. We subsequently interviewed 39 key informants to validate the environmental scan results, identify additional strategies to increase COVID-19 vaccine uptake, and uncover perceptions of the facilitators and challenges that influenced the strategies implementation. Results We identified that provincial health authorities employed several strategies to overcome structural, geographical, and attitudinal barriers to COVID-19 vaccines experienced by the priority populations. Most provinces implemented walk-in, mobile, and pop-up vaccination clinics, mobilized their public and private health workforce, and designed multilingual communication materials. Facilitators in implementing COVID-19 vaccination strategies included harmonizing communication efforts, leveraging existing relationships and networks, and ensuring representation and leadership of community partners. Challenges to implementing COVID-19 vaccination strategies included uncoordinated communication efforts, inadequate distribution of vaccines to areas with the greatest need, mistrust in the government and healthcare system, vaccine hesitancy, and lack of cultural competence by vaccine providers. Conclusions This study highlights the divide between well-intentioned strategies and interventions and the reality of on-the-ground implementation. The findings offer valuable insights and can inform the implementation of strategies to distribute vaccines equitably in future large-scale vaccination efforts in Canada and globally.
Use of administrative data for evaluating trends in medically-attended Lyme disease, Manitoba, Canada, 2010-2021
(Public Library of Science, 2026-04-13) Major, Maria; Horton, Susan; Nightingale, Natalie; Halsby, Kate; Angulo, Frederick J.; Stark, James; Yu, Holly; Loeb, Mark; Wang, Irene; Nair, Saranya; Neish, Calum S.; Thomas, Doneal; McDonald, Chloe; Torres-Florez, Samuel; Grajales, Ana G.; Willis, Sarah J.
While Lyme disease (LD) is the most common tick-borne disease reported to public health surveillance in North America and is increasingly recognized as a public health threat in Canada, it’s incidence may be underreported. Our study aims to estimate medically-attended LD incidence in Manitoba, Canada, using administrative health data. We identified medically-attended LD cases in Manitoba from 2010 − 2021 in a claims database (Manitoba Population Research Data Repository), which contains the health records of >95% of the residents of Manitoba, using diagnostic codes, antibiotic dispensations, and laboratory results. The incidence of claims-based LD cases ranged from 8.4 to 28.5 per 100,000 population per year, 5.1 to 11.0 times higher than the incidence of surveillance-reported LD cases. The incidence of claims-based LD cases was particularly higher than the incidence of surveillance-reported LD cases in females and health regions with a low surveillance-reported incidence. Our study suggests that medically attended LD is more common than reported in surveillance. Further study is required to identify barriers to reporting. Interventions are needed to reduce the substantial burden of LD in Manitoba.
Silicone toothbrushes: A scoping review of an underutilized tool in global oral health
(Public Library of Science, 2026-04-22) Cummins, Aoife; Bennett, Alexa; Carrier, Kathryn; Mehta, Sujay A. J.; Gudsoorkar, Priyanka
Oral diseases are the most prevalent non-communicable diseases worldwide, affecting 3.5 billion people, with a disproportionate impact on those living in low- and middle-income countries. Despite being largely preventable through proper oral hygiene, current oral health promotion strategies rely heavily on plastic and nylon toothbrushes, which present both environmental and accessibility challenges. In response to the growing need for sustainable and affordable preventive oral health solutions, there has been increasing interest in alternatives to conventional toothbrushes. This scoping review aimed to summarize the global literature on silicone toothbrushes, an underutilized tool in preventive oral care. A systematic search of five databases, supplemented by reference screening, identified ten English-language studies investigating silicone toothbrushes. Findings suggest that silicone toothbrushes are effective in plaque removal, have a lower risk of gingival trauma, are well-suited for specific populations, and perform better in environmental impact assessments. This review also demonstrated that silicone toothbrushes remain under-researched and underutilized, highlighting the need for further high-quality studies to evaluate their effectiveness, safety, and broader implementation.

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