Waterloo Research

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Population-based estimate of hepatitis C virus prevalence in Ontario, Canada
(Public Library of Science, 2018-01-23) Bolotin, Shelly; Feld, Jordan J.; Garber, Gary; Wong, William W. L.; Guerra, Fiona M.; Mazzulli, Tony
Background Hepatitis C virus (HCV) is the most burdensome infectious illness in Canada. Current screening strategies miss a significant proportion of cases, leaving many undiagnosed. Elevated HCV prevalence in those born between 1945 and 1965 has prompted calls for birth-cohort screening in this group. However, Canada lacks population-level data to support this recommendation. We performed a serosurvey to obtain population-based HCV prevalence estimates in Ontario residents born between 1945-1974, to generate evidence for birth-cohort screening recommendations. Methods We tested anonymized residual sera in five-year age-sex bands from Ontario for anti-HCV antibody. We performed descriptive epidemiological analysis and used a logistic regression model to determine HCV risk-factors. Result Of 10,006 sera analyzed, 155 (1.55%, 95% confidence interval (CI) 1.32, 1.81) were positive for HCV antibody. Individuals born between 1950–1964 had a significantly higher combined prevalence of 1.92% (95% CI 1.56, 2.34) compared to 1.14% (95% CI 0.69, 1.77) (p = 0.04) for those born between 1970–1974. For males, comprising 107/155 (69.03%) of positive samples, the highest prevalence was 3.00% (95% CI 1.95, 4.39) for the 1960–1964 birth-cohort. For females, the highest prevalence was 1.56% (95% CI 0.83, 2.65) for those born between 1955–1959. Male sex was significantly associated with positive HCV serostatus. Interpretation HCV prevalence in Ontario is highest among those in this birth cohort, and higher than previous estimates. The prevalence estimates presented in our study provide important data to underpin birth-cohort screening recommendations.
Evaluating authentication options for mobile health applications in younger and older adults
(Public Library of Science, 2018-01-04) Grindrod, Kelly; Khan, Hassan; Hengartner, Urs; Ong, Stephanie; Logan, Alexander G.; Vogel, Daniel; Geboyts, Robert; Yang, Jilan
Objective Apps promoting patient self-management may improve health outcomes. However, methods to secure stored information on mobile devices may adversely affect usability. We tested the reliability and usability of common user authentication techniques in younger and older adults. Methodology Usability testing was conducted in two age groups, 18 to 30 years and 50 years and older. After completing a demographic questionnaire, each participant tested four authentication options in random order: four-digit personal identification number (PIN), graphical password (GRAPHICAL), Android pattern-lock (PATTERN), and a swipe-style Android fingerprint scanner (FINGERPRINT). Participants rated each option using the Systems Usability Scale (SUS). Results A total of 59 older and 43 younger participants completed the study. Overall, PATTERN was the fastest option (3.44s), and PIN had the fewest errors per attempt (0.02). Participants were able to login using PIN, PATTERN, and GRAPHICAL at least 98% of the time. FINGERPRINT was the slowest (26.97s), had an average of 1.46 errors per attempt, and had a successful login rate of 85%. Overall, PIN and PATTERN had higher SUS scores than FINGERPRINT and GRAPHICAL. Compared to younger participants, older participants were also less likely to find PATTERN to be tiring, annoying or time consuming and less likely to consider PIN to be time consuming. Younger participants were more likely to rate GRAPHICAL as annoying, time consuming and tiring than older participants. Conclusions On mobile devices, PIN and pattern-lock outperformed graphical passwords and swipe-style fingerprints. All participants took longer to authenticate using the swipe-style fingerprint compared to other options. Older participants also took two to three seconds longer to authenticate using the PIN, pattern and graphical passwords though this did not appear to affect perceived usability.
Behavioural patterns only predict concurrent BMI status and not BMI trajectories in a sample of youth in Ontario, Canada
(Public Library of Science, 2018-01-02) Laxer, Rachel E.; Cooke, Martin; Dubin, Joel A.; Brownson, Ross C.; Chaurasia, Ashok; Leatherdale, Scott T.
Background Youth are engaging in multiple risky behaviours, increasing their risk of overweight, obesity, and related chronic diseases. The objective of this study was to examine the effect of engaging in unique clusters of unhealthy behaviours on youths' body mass index (BMI) trajectories. Methods This study used a linked-longitudinal sample of Grades 9 and 10 students (13 to 17 years of age) participating in the COMPASS host study. Students reported obesity-related and other risky behaviours at baseline and height and weight (to derive BMI) at baseline (2012/2013) and annually for 2 years post-baseline (2013/14 and 2014/15). Students were grouped into behavioural clusters based on response probabilities. Linear mixed effects models, using BMI as a continuous outcome measure, were used to examine the effect of engaging in clusters of risky behaviours on BMI trajectories. Results There were significant differences in BMI of the four behavioural clusters at baseline that remained consistent over time. Higher BMI values were found among youth classified at baseline to be Typical High School Athletes (β = 0.232 kg/m2, [confidence interval (CI): 0.03–0.50]), Inactive High Screen-User (β = 0.348 kg/m2, CI: 0.11–0.59) and Moderately Active Substance Users (β = 0.759 kg/m2, CI: 0.36–1.15) compared to students classified as Health Conscious. Despite these baseline differences, BMI appeared to increase across all behavioural clusters annually by the same amount (β = 0.6097 kg/m2, (CI) = 0.57–0.64). Conclusions Although annual increases in BMI did not differ by behavioural clusters, membership in a particular behavioural cluster was associated with baseline BMI, and these differences remained consistent over time. Results indicate that intervening and modifying unhealthy behaviours earlier might have a greater impact than during adolescence. Health promotion strategies targeting the highest risk youth as they enter secondary school might be promising means to prevent or delay the onset of obesity.
Efficacy of a biomechanically-based yoga exercise program in knee osteoarthritis: A randomized controlled trial
(Public Library of Science, 2018-04-17) Kuntz, Alexander B.; Chopp-Hurley, Jaclyn N.; Brenneman, Elora C.; Karampatos, Sarah; Wiebenga, Emily G.; Adachi, Jonathan D.; Noseworthy, Michael D.; Maly, Monica R.
Objective Certain exercises could overload the osteoarthritic knee. We developed an exercise program from yoga postures with a minimal knee adduction moment for knee osteoarthritis. The purpose was to compare the effectiveness of this biomechanically-based yoga exercise (YE), with traditional exercise (TE), and a no-exercise attention-equivalent control (NE) for improving pain, self-reported physical function and mobility performance in women with knee osteoarthritis. Design Single-blind, three-arm randomized controlled trial. Setting Community in Southwestern Ontario, Canada. Participants A convenience sample of 31 women with symptomatic knee osteoarthritis was recruited through rheumatology, orthopaedic and physiotherapy clinics, newspapers and word-of-mouth. Interventions Participants were stratified by disease severity and randomly allocated to one of three 12-week, supervised intervention. YE included biomechanically-based yoga exercises; TE included traditional leg strengthening on machines; and NE included meditation with no exercise. Participants were asked to attend three 1-hour group classes/sessions each week. Measurements Primary outcomes were pain, self-reported physical function and mobility performance. Secondary outcomes were knee strength, depression, and health-related quality of life. All were assessed by a blinded assessor at baseline and immediately following the intervention. Results The YE group demonstrated greater improvements in KOOS pain (mean difference of 22.9 [95% CI, 6.9 to 38.8; p = 0.003]), intermittent pain (mean difference of -19.6 [95% CI, -34.8 to -4.4; p = 0.009]) and self-reported physical function (mean difference of 17.2 [95% CI, 5.2 to 29.2; p = 0.003]) compared to NE. Improvements in these outcomes were similar between YE and TE. However, TE demonstrated a greater improvement in knee flexor strength compared to YE (mean difference of 0.1 [95% CI, 0.1 to 0.2]. Improvements from baseline to follow-up were present in quality of life score for YE and knee flexor strength for TE, while both also demonstrated improvements in mobility. No improvement in any outcome was present in NE. Conclusions The biomechanically-based yoga exercise program produced clinically meaningful improvements in pain, self-reported physical function and mobility in women with clinical knee OA compared to no exercise. While not statistically significant, improvements in these outcomes were larger than those elicited from the traditional exercise-based program. Through this may suggest that the yoga program may be more efficacious for knee OA, future research studying a larger sample is required.
Assessing the efficacy of fathead minnows (Pimephales promelas) for mosquito control
(Public Library of Science, 2018-04-12) Watchorn, Ryan T.; Maechtle, Thomas; Fedy, Bradley C.
Mosquitoes function as important vectors for many diseases globally and can have substantial negative economic, environmental, and health impacts. Specifically, West Nile virus (WNv) is a significant and increasing threat to wildlife populations and human health throughout North America. Mosquito control is an important means of controlling the spread of WNv, as the virus is primarily spread between avian and mosquito vectors. This is of particular concern for avian host species such as the Greater sage-grouse (Centrocercus urophasianus), in which WNv negatively impacts fitness parameters. Most mosquito control methods focus on the larval stages. In North America, control efforts are largely limited to larvicides, which require repeated application and have potentially negative ecological impacts. There are multiple potential advantages to using indigenous fish species as an alternative for larval control including lowered environmental impact, decreased costs in terms of time and financial inputs, and the potential for the establishment of self-sustaining fish populations. We tested the efficacy of using fathead minnows (Pimephales promelas) as biological control for mosquito populations in livestock reservoirs of semiarid rangelands. We introduced minnows into 10 treatment reservoirs and monitored an additional 6 non-treated reservoirs as controls over 3 years. Adult mosquitoes of species known to transmit WNv (e.g., Culex tarsalis) were captured at each site and mosquito larvae were also present at all sites. Stable isotope analysis confirmed that introduced fathead minnows were feeding at the mosquito larvae trophic level in all but one treatment pond. Treatment ponds demonstrated suppressed levels of mosquito larva over each season compared to controls with a model-predicted 114% decrease in larva density within treatment ponds. Minnows established self-sustaining populations throughout the study in all reservoirs that maintained sufficient water levels. Minnow survival was not influenced by water quality. Though minnows did not completely eradicate mosquito larvae, minnows are a promising alternative to controlling mosquito larvae density within reservoirs. We caution that careful site selection is critical to avoid potential negative impacts, but suggest the introduction of fathead minnows in reservoirs can dramatically reduce mosquito larva abundance and potentially help mitigate vector-borne disease transmission.
Evaluation of the Leap Motion Controller during the performance of visually-guided upper limb movements
(Public Library of Science, 2018-03-12) Niechwiej-Szwedo, Ewa; Gonzalez, David; Nouredanesh, Mina; Tung, James
Kinematic analysis of upper limb reaching provides insight into the central nervous system control of movements. Until recently, kinematic examination of motor control has been limited to studies conducted in traditional research laboratories because motion capture equipment used for data collection is not easily portable and expensive. A recently developed markerless system, the Leap Motion Controller (LMC), is a portable and inexpensive tracking device that allows recording of 3D hand and finger position. The main goal of this study was to assess the concurrent reliability and validity of the LMC as compared to the Optotrak, a criterion-standard motion capture system, for measures of temporal accuracy and peak velocity during the performance of upper limb, visually-guided movements. In experiment 1, 14 participants executed aiming movements to visual targets presented on a computer monitor. Bland-Altman analysis was conducted to assess the validity and limits of agreement for measures of temporal accuracy (movement time, duration of deceleration interval), peak velocity, and spatial accuracy (endpoint accuracy). In addition, a one-sample t-test was used to test the hypothesis that the error difference between measures obtained from Optotrak and LMC is zero. In experiment 2, 15 participants performed a Fitts’ type aiming task in order to assess whether the LMC is capable of assessing a well-known speed-accuracy trade-off relationship. Experiment 3 assessed the temporal coordination pattern during the performance of a sequence consisting of a reaching, grasping, and placement task in 15 participants. Results from the t-test showed that the error difference in temporal measures was significantly different from zero. Based on the results from the 3 experiments, the average temporal error in movement time was 40±44 ms, and the error in peak velocity was 0.024±0.103 m/s. The limits of agreement between the LMC and Optotrak for spatial accuracy measures ranged between 2–5 cm. Although the LMC system is a low-cost, highly portable system, which could facilitate collection of kinematic data outside of the traditional laboratory settings, the temporal and spatial errors may limit the use of the device in some settings.
Structural, functional and blood perfusion changes in the rat retina associated with elevated intraocular pressure, measured simultaneously with a combined OCT+ERG system
(Public Library of Science, 2018-03-06) Tan, Bingyao; MacLellan, Benjamin; Mason, Erik; Bizheva, Kostadinka
Acute elevation of intraocular pressure (IOP) to ischemic and non-ischemic levels can cause temporary or permanent changes in the retinal morphology, function and blood flow/blood perfusion. Previously, such changes in the retina were assessed separately with different methods in clinical studies and animal models. In this study, we used a combined OCT+ ERG system in combination with Doppler OCT and OCT angiography (OCTA) imaging protocols, in order to evaluate simultaneously and correlate changes in the retinal morphology, the retinal functional response to visual stimulation, and the retinal blood flow/blood perfusion, associated with IOP elevation to ischemic and non-ischemic levels in rats. Results from this study suggest that the inner retina responds faster to IOP elevation to levels greater than 30 mmHg with significant reduction of the total retinal blood flow (TRBF), decrease of the capillaries’ perfusion and reduction of the ON bipolar cells contribution to the ERG traces. Furthermore, this study showed that ischemic levels of IOP elevation cause an additional significant decrease in the ERG photoreceptor response in the posterior retina. Thirty minutes after IOP normalization, retinal morphology, blood flow and blood perfusion recovered to baseline values, while retinal function did not recover completely.
Ten simple rules for collaborative lesson development
(Public Library of Science, 2018-03-01) Devenyi, Gabriel A.; Emonet, Remi; Harris, Rayna M.; Hertweck, Kate L.; Irving, Damien; Milligan, Ian; Wilson, Greg
Introduction Lessons take significant effort to build and even more to maintain. Most academics do this work on their own, but leveraging a community approach can make educational resource development more sustainable, robust, and responsive. Treating lessons as a community resource to be updated, adapted, and improved incrementally can free up valuable time while increasing quality.
Economic evaluations of eHealth technologies: A systematic review
(Public Library of Science, 2018-06-13) Sanyal, Chiranjeev; Stolee, Paul; Juzwishin, Don; Husereau, Don
Background Innovations in eHealth technologies have the potential to help older adult live independently, maintain their quality of life, and to reduce their health system dependency and health care expenditure. The objective of this study was to systematically review and appraise the quality of cost-effectiveness or utility studies assessing eHealth technologies in study populations involving older adults. Methods We systematically searched multiple databases (MEDLINE, EMBASE, CINAHL, NHS EED, and PsycINFO) for peer-reviewed studies published in English from 2000 to 2016 that examined cost-effectiveness (or utility) of eHealth technologies. The reporting quality of included studies was appraised using the Consolidated Health Economic Evaluation Reporting Standards statement. Results Eleven full text articles met the inclusion criteria representing public and private health care systems. eHealth technologies evaluated by these studies includes computerized decision support system, a web-based physical activity intervention, internet-delivered cognitive behavioral therapy, telecare, and telehealth. Overall, the reporting quality of the studies included in the review was varied. Most studied demonstrated efficacy and cost-effectiveness of an intervention using a randomized control trial and statistical modeling, respectively. This review found limited information on the feasibility of adopting these technologies based on economic and organizational factors. Conclusions This review identified few economic evaluations of eHealth technologies that included older adults. The quality of the current evidence is limited and further research is warranted to clearly demonstrate the long-term cost-effectiveness of eHealth technologies from the health care system and societal perspectives.
Sentiment in nursing notes as an indicator of out-of-hospital mortality in intensive care patients
(Public Library of Science, 2018-06-07) Waudby-Smith, Ian E. R.; Tran, Nam; Dubin, Joel A.; Lee, Joon
Background Nursing notes have not been widely used in prediction models for clinical outcomes, despite containing rich information. Advances in natural language processing have made it possible to extract information from large scale unstructured data like nursing notes. This study extracted the sentiment - impressions and attitudes - of nurses, and examined how sentiment relates to 30-day mortality and survival. Methods This study applied a sentiment analysis algorithm to nursing notes extracted from MIMIC-III, a public intensive care unit (ICU) database. A multiple logistic regression model was fitted to the data to correlate measured sentiment with 30-day mortality while controlling for gender, type of ICU, and SAPS-II score. The association between measured sentiment and 30-day mortality was further examined in assessing the predictive performance of sentiment score as a feature in a classifier, and in a survival analysis for different levels of measured sentiment. Results Nursing notes from 27,477 ICU patients, with an overall 30-day mortality of 11.02%, were extracted. In the presence of known predictors of 30-day mortality, mean sentiment polarity was a highly significant predictor in a multiple logistic regression model (Adjusted OR = 0.4626, p < 0.001, 95% Cl: [o.4244, 0.5041]) and led to improved predictive accuracy (AUROC = 0.8189 versus 0.8092, 95% BCl of difference: [0.0070, 0.0126]). The Kaplan Meier survival curves showed that mean sentiment polarity quartiles are positively correlated with patient survival (log-rank test: p < 0.001). Conclusions This study showed that quantitative measures of unstructured clinical notes, such as sentiment of clinicians, correlate with 30-day mortality and survival, thus can also serve as a predictor of patient outcomes in the ICU. Therefore, further research is warranted to study and make use of the wealth of data that clinical notes have to offer.
Assessing trade-offs in large marine protected areas
(Public Library of Science, 2018-04-18) Davies, Tammy E.; Epstein, Graham; Aguilera, Stacy E.; Brooks, Cassandra M.; Cox, Michael; Evans, Louisa S.; Maxwell, Sara M.; Nenadovic, Mateja; Ban, Natalie C.
Large marine protected areas (LMPAs) are increasingly being established and have a high profile in marine conservation. LMPAs are expected to achieve multiple objectives, and because of their size are postulated to avoid trade-offs that are common in smaller MPAs. However, evaluations across multiple outcomes are lacking. We used a systematic approach to code several social and ecological outcomes of 12 LMPAs. We found evidence of three types of trade-offs: trade-offs between different ecological resources (supply trade-offs); trade-offs between ecological resource conditions and the well-being of resource users (supply-demand trade-offs); and trade-offs between the well-being outcomes of different resource users (demand trade-offs). We also found several divergent outcomes that were attributed to influences beyond the scope of the LMPA. We suggest that despite their size, trade-offs can develop in LMPAs and should be considered in planning and design. LMPAs may improve their performance across multiple social and ecological objectives if integrated with larger-scale conservation efforts.
Do payments for forest ecosystem services generate double dividends? An integrated impact assessment of Vietnam's PES program
(Public Library of Science, 2018-08-01) Phan, Thu-Ha Dang; Brouwer, Roy; Hoang, Long Phi; Davidson, Marc David
Payments for ecosystem services (PES) often serve multiple objectives, such as carbon emission reduction and poverty alleviation. However, the effectiveness of PES as an instrument to achieve these multiple objectives, in particular in a conservation-development context, is often questioned. This study adds to the very limited empirical evidence base and investigates to what extent Vietnam’s move to PES has helped protect forest ecosystems and improve local livelihoods and income inequality. We zoom in on Lam Dong province, where PES was first introduced in Vietnam in 2009. Changes in forest cover are analysed using satellite images over a period of 15 years (2000–2014). Socio-economic impacts are assessed based on rural household interviews with PES participants and non-participants as a control group over a period of 7 years (2008–2014). Our results show that PES contributes significantly to forest cover, the improvement of local livelihoods, and the reduction of income inequality.
Prevalence of chronic comorbidities in dengue fever and West Nile virus: A systematic review and meta-analysis
(Public Library of Science, 2018-07-10) Badawi, Alaa; Velummailum, Russanthy; Ryoo, Seung Gwan; Senthinathan, Arrani; Yaghoubi, Sahar; Vasileva, Denitsa; Ostermeier, Emma; Plishka, Mikayla; Soosaipillai, Marcel; Arora, Paul
Background Flavivirius disease such as dengue fever (DENV), West Nile virus (WNV), Zike and yellow fever represent a substantial global public health concern. Preexisting chronic conditions such as cardiovascular diseases, diabetes, obesity, and asthma were thought to predict risk of progression to severe infections. Objective We aimed to quantify the frequency of chronic comorbidities in flavivirs diseases to provide an estimate for their prevalence in severe and non-severe infections and examine whether chronic diseases contribute to the increased risk of severe viral expression. Methods We conducted a comprehensive search in PudMed, Ovid MEDLINE(R), Embase and Embase Classic and grey literature databases to identify studies reporting prevalence estimates of comorbidities in flavivirus diseases. Study quality was assessed with the risk of bias tool. Age-adjusted odds ratios (ORs) were estimated for severe infection in the presence of chronic comorbidities. Results We identified 65 studies as eligible for inclusion for DENV (47 studies) and WNV (18 studies). Obesity and overweight (i.e., BMI> 25 kg/m2, prevalence: 24.5%, 95% CI: 18.6–31.6%), hypertension (17.1%, 13.3–21.8%) and diabetes (13.3%, 9.3–18.8%) were the most prevalent comorbidities in DENV. However, hypertension (45.0%, 39.1–51.0%), diabetes (24.7%, 20.2–29.8%) and heart diseases (25.6%, 19.5–32.7%) were the most prevalent in WNV. ORs of severe flavivirus diseases were about 2 to 4 in infected patients with comorbidities such as diabetes, hypertension and heart diseases. The small number of studies in JEV, YFV and Zika did not permit estimating the prevalence of comorbidities in these infections. Conclusion Higher prevalence of chronic comorbidities was found in severe cases of flavivirus diseases compared to non-severe cases. Findings of the present study may guide public health practitioners and clinicians to evaluate infection severity based on the presence of comorbidity, a critical public health measure that may avert severe disease outcome given the current dearth of clear prevention practices for some flavivirus diseases.
Global land use implications of dietary trends
(Public Library of Science, 2018-08-08) Rizvi, Sarah; Pagnutti, Chris; Fraser, Evan; Bauch, Chris T.; Anand, Madhur
Global food security and agricultural land management represent two urgent and intimately related challenges that humans must face. We quantify the changes in the global agricultural land footprint if the world were to adhere to the dietary guidelines put forth by the United States Department of Agriculture (USDA), while accounting for the land use change incurred by import/export required to meet those guidelines. We analyze data at country, continental, and global levels. USDA guidelines are viewed as an improvement on the current land-intensive diet of the average American, but despite this our results show that global adherence to the guidelines would require 1 gigahectare of additional land—roughly the size of Canada—under current agricultural practice. The results also show a strong divide between Eastern and Western hemispheres, with many Western hemisphere countries showing net land sparing under a USDA guideline diet, while many Eastern hemisphere countries show net land use increase under a USDA guideline diet. We conclude that national dietary guidelines should be developed using not just health but also global land use and equity as criteria. Because global lands are a limited resource, national dietary guidelines also need to be coordinated internationally, in much the same way greenhouse gas emissions are increasingly coordinated.
Franklin expedition lead exposure: New insights from high resolution confocal x-ray fluorescence imaging of skeletal microstructure
(Public Library of Science, 2018-08-23) Swanston, Treena; Varney, Tamara L.; Kozachuk, Madalena; Choudhury, Sanjukta; Bewer, Brian; Coulthard, Ian; Keenleyside, Anne; Nelson, Andrew; Martin, Ronald R.; Stenton, Douglas R.; Cooper, David M. L.
In the summer of 1845, under the command of Sir John Franklin, 128 officers and men aboard Royal Navy ships HMS Erebus and HMS Terror sailed into Lancaster Sound and entered the waters of Arctic North America. The goal of this expedition was to complete the discovery of a northwest passage by navigating the uncharted area between Barrow Strait and Simpson Strait. Franklin and his crew spent the first winter at Beechey Island, where three crewmen died and were buried. In September 1846, the ships became stranded in ice off the northwest coast of King William Island, where they remained until April 1848. At that time, the crew, reduced to 105, deserted the ships and retreated south along the island’s western and southern shores in a desperate attempt to reach the mainland and via the Back River, to obtain aid at a Hudson’s Bay Company Post. Sadly, not one individual survived. Previous analyses of bone, hair, and soft tissue samples from expedition remains found that crewmembers’ tissues contained elevated lead (Pb) levels, suggesting that Pb poisoning may have contributed to their demise; however, questions remain regarding the timing and degree of exposure and, ultimately, the extent to which the crewmembers may have been impacted. To address this historical question, we investigated three hypotheses. First, if elevated Pb exposure was experienced by the crew during the expedition, we hypothesized that those sailors who survived longer (King William Island vs. Beechey Island) would exhibit more extensive uptake of Pb in their bones and vice versa. Second, we hypothesized that Pb would be elevated in bone microstructural features forming at or near the time of death compared with older tissue. Finally, if Pb exposure played a significant role in the failure of the expedition we hypothesized that bone samples would exhibit evidence of higher and more sustained uptake of Pb than that of a contemporary comparator naval population from the 19th century. To test these hypotheses, we analyzed bone and dental remains of crew members and compared them against samples derived from the Royal Navy cemetery in Antigua. Synchrotron-based high resolution confocal X-ray fluorescence imaging was employed to visualize Pb distribution within bone and tooth microstructures at the micro scale. The data did not support our first hypothesis as Pb distribution within the samples from the two different sites was similar. Evidence of Pb within skeletal microstructural features formed near the time of death lent support to our second hypothesis but consistent evidence of a marked elevation in Pb levels was lacking. Finally, the comparative analysis with the Antigua samples did not support the hypothesis that the Franklin sailors were exposed to an unusually high level of Pb for the time period. Taken all together our skeletal microstructural results do not support the conclusion that Pb played a pivotal role in the loss of Franklin and his crew.
Spatial statistical tools for genome-wide mutation cluster detection under a microarray probe sampling system
(Public Library of Science, 2018-09-25) Luo, Bin; Edge, Alanna K.; Tolg, Cornelia; Turley, Eva A.; Dean, C. B.; Hill, Kathleen A.; Kulperger, R. J.
Mutation cluster analysis is critical for understanding certain mutational mechanisms relevant to genetic disease, diversity, and evolution. Yet, whole genome sequencing for detection of mutation clusters is prohibitive with high cost for most organisms and population surveys. Single nucleotide polymorphism (SNP) genotyping arrays, like the Mouse Diversity Genotyping Array, offer an alternative low-cost, screening for mutations at hundreds of thousands of loci across the genome using experimental designs that permit capture of de novo mutations in any tissue. Formal statistical tools for genome-wide detection of mutation clusters under a microarray probe sampling system are yet to be established. A challenge in the development of statistical methods is that microarray detection of mutation clusters is constrained to select SNP loci captured by probes on the array. This paper develops a Monte Carlo framework for cluster testing and assesses test statistics for capturing potential deviations from spatial randomness which are motivated by, and incorporate, the array design. While null distributions of the test statistics are established under spatial randomness via the homogeneous Poisson process, power performance of the test statistics is evaluated under postulated types of Neyman-Scott clustering processes through Monte Carlo simulation. A new statistic is developed and recommended as a screening tool for mutation cluster detection. The statistic is demonstrated to be excellent in terms of its robustness and power performance, and useful for cluster analysis in settings of missing data. The test statistic can also be generalized to any one dimensional system where every site is observed, such as DNA sequencing data. The paper illustrates how the informal graphical tools for detecting clusters may be misleading. The statistic is used for finding clusters of putative SNP differences in a mixture of different mouse genetic backgrounds and clusters of de novo SNP differences arising between tissues with development and carcinogenesis.
When too much isn't enough: Does current food production meet global nutritional needs?
(Public Library of Science, 2018-10-23) Bahadur KC, Krishna; Dias, Goretty M.; Veeramani, Anastasia; Swanton, Clarence J.; Fraser, David; Steinke, Dirk; Lee, Elizabeth; Wittman, Hannah; Farber, Jeffrey M.; Dunfield, Kari; McCann, Kevin; Anand, Madhur; Campbell, Malcolm; Rooney, Neil; Raine, Nigel E.; Van Acker, Rene; Hanner, Robert; Pascoal, Samantha; Sharif, Shayan; Benton, Tim G.; Graser, Evan D. G.
Sustainably feeding the next generation is often described as one of the most pressing “grand challenges” facing the 21st century. Generally, scholars propose addressing this problem by increasing agricultural production, investing in technology to boost yields, changing diets, or reducing food waste. In this paper, we explore whether global food production is nutritionally balanced by comparing the diet that nutritionists recommend versus global agricultural production statistics. Results show that the global agricultural system currently overproduces grains, fats, and sugars while production of fruits and vegetables and protein is not sufficient to meet the nutritional needs of the current population. Correcting this imbalance could reduce the amount of arable land used by agriculture by 51 million ha globally but would increase total land used for agriculture by 407 million ha and increase greenhouse gas emissions. For a growing population, our calculations suggest that the only way to eat a nutritionally balanced diet, save land and reduce greenhouse gas emissions is to consume and produce more fruits and vegetables as well as transition to diets higher in plant-based protein. Such a move will help protect habitats and help meet the Sustainable Development Goals.
Sialic acid facilitates binding and cytotoxic activity of the pore-forming Clostridium perfringens NetF toxin to host cells
(Public Library of Science, 2018-11-07) Gohari, Iman Mehdizadeh; Brefo-Mensah, Eric K.; Palmer, Michael; Boerlin, Patrick; Prescott, John F.
NetF-producing type A Clostridium perfringens is an important cause of canine and foal necrotizing enteritis. NetF, related to the β-sheet pore-forming Leukocidin/Hemolysin superfamily, is considered a major virulence factor for this disease. The main purpose of this work is to demonstrate the pore-forming activity of NetF and characterize the chemical nature of its binding site. Electron microscopy using recombinant NetF (rNetF) confirmed that NetF is able to oligomerize and form large pores in equine ovarian (EO) cell membranes and sheep red blood cells. These oligomeric pores appear to be about 4–6 nm in diameter, and the number of oligomer subunits to vary from 6 to 9. Sodium periodate treatment rendered EO cells non-susceptible to NetF, suggesting that NetF binding requires cell surface carbohydrates. NetF cytotoxicity was also inhibited by a lectin that binds sialic acid, by sialidase, and by free sialic acid in excess, all of which clearly implicate sialic acid-containing membrane carbohydrates in NetF binding and/or toxicity for EO cells. Binding of NetF to sheep red blood cells was not inhibited by the gangliosides GM1, GM2 and GM3, nor did the latter promote membrane permeabilization in liposomes, suggesting that they do not constitute the cellular receptors. In contrast, treatment of EO cells with different proteases reduced their susceptibility to NetF, suggesting that the NetF receptor is a sialic acid-containing glycoprotein.
Quantum++: A modern C++ quantum computing library
(Public Library of Science, 2018-12-10) Gheorghiu, Vlad
Quantum++ is a modern general-purpose multi-threaded quantum computing library written in C++11 and composed solely of header files. The library is not restricted to qubit systems or specific quantum information processing tasks, being capable of simulating arbitrary quantum processes. The main design factors taken in consideration were the ease of use, portability, and performance. The library’s simulation capabilities are only restricted by the amount of available physical memory. On a typical machine (Intel i5 8Gb RAM) Quantum++ can successfully simulate the evolution of 25 qubits in a pure state or of 12 qubits in a mixed state reasonably fast. The library also includes support for classical reversible logic, being able to simulate classical reversible operations on billions of bits. This latter feature may be useful in testing quantum circuits composed solely of Toffoli gates, such as certain arithmetic circuits.
An open-source k-mer based machine learning tool for fast and accurate subtyping of HIV-1 genomes
(Public Library of Science, 2018-11-14) Solis-Reyes, Stephen; Avino, Mariano; Poon, Art; Kari, Lila
For many disease-causing virus species, global diversity is clustered into a taxonomy of subtypes with clinical significance. In particular, the classification of infections among the subtypes of human immunodeficiency virus type 1 (HIV-1) is a routine component of clinical management, and there are now many classification algorithms available for this purpose. Although several of these algorithms are similar in accuracy and speed, the majority are proprietary and require laboratories to transmit HIV-1 sequence data over the network to remote servers. This potentially exposes sensitive patient data to unauthorized access, and makes it impossible to determine how classifications are made and to maintain the data provenance of clinical bioinformatic workflows. We propose an open-source supervised and alignment-free subtyping method (Kameris) that operates on k-mer frequencies in HIV-1 sequences. We performed a detailed study of the accuracy and performance of subtype classification in comparison to four state-of-the-art programs. Based on our testing data set of manually curated real-world HIV-1 sequences (n = 2, 784), Kameris obtained an overall accuracy of 97%, which matches or exceeds all other tested software, with a processing rate of over 1,500 sequences per second. Furthermore, our fully standalone general-purpose software provides key advantages in terms of data security and privacy, transparency and reproducibility. Finally, we show that our method is readily adaptable to subtype classification of other viruses including dengue, influenza A, and hepatitis B and C virus.

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