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Designer Sinorhizobium meliloti strains and multi-functional vectors enable direct inter-kingdom DNA transfer
(Public Library of Science, 2019-06-17) Brumwell, Stephanie L.; MacLeod, Michael R.; Huang, Tony; Cochrane, Ryan R.; Meaney, Rebecca S.; Zamani, Maryam; Matysiakiewicz, Ola; Dan, Kaitlyn N.; Janakirama, Preetam; Edgell, David R.; Charles, Trevor C.; Finan, Turlough M.; Karas, Bogumil J.
Storage, manipulation and delivery of DNA fragments is crucial for synthetic biology applications, subsequently allowing organisms of interest to be engineered with genes or pathways to produce desirable phenotypes such as disease or drought resistance in plants, or for synthesis of a specific chemical product. However, DNA with high G+C content can be unstable in many host organisms including Saccharomyces cerevisiae. Here, we report the development of Sinorhizobium meliloti, a nitrogen-fixing plant symbioticα-Proteobacterium, as a novel host that can store DNA, and mobilize DNA to E. coli, S. cerevisiae, and the eukaryotic microalgae Phaeodactylum tricornutum. To achieve this, we deleted the hsdR restriction-system in multiple reduced genome strains of S. meliloti that enable DNA transformation with up to 1.4 x 105 and 2.1 x 103 CFU μg-1 of DNA efficiency using electroporation and a newly developed polyethylene glycol transformation method, respectively. Multi-host and multi-functional shuttle vectors (MHS) were constructed and stably propagated in S. meliloti, E. coli, S. cerevisiae, and P. tricornutum. We also developed protocols and demonstrated direct transfer of these MHS vectors via conjugation from S. meliloti to E. coli, S. cerevisiae, and P. tricornutum. The development of S. meliloti as a new host for inter-kingdom DNA transfer will be invaluable for synthetic biology research and applications, including the installation and study of genes and biosynthetic pathways into organisms of interest in industry and agriculture.
Statistical methods for classification of 5hmC levels based on the Illumina Inifinium HumanMethylation450 (450k) array data, under the paired bisulfite (BS) and oxidative bisulfite (oxBS) treatment
(Public Library of Science, 2019-06-13) Slynko, Alla; Benner, Axel
Hydroxymethylcytosine (5hmC) methylation is a well-known epigenetic mark that is involved in gene regulation and may impact genome stability. To investigate a possible role of 5hmC in cancer development and progression, one must be able to detect and quantify its level first. In this paper, we address the issue of 5hmC detection at a single base resolution, starting with consideration of the well-established 5hmC measure Δβ and, in particular, with an analysis of its properties, both analytically and empirically. Then we propose several alternative hydroxymethylation measures and compare their properties with those of Δβ. In the absence of a gold standard, the (pairwise) resemblance of those 5hmC measures to Δβ is characterized by means of a similarity analysis and relative accuracy analysis. All results are illustrated on matched healthy and cancer tissue data sets as derived by means of bisulfite (BS) and oxidative bisulfite converting (oxBS) procedures.
High rates of health care utilization in pediatric multiple sclerosis: A Canadian population-based study
(Public Library of Science, 2019-06-11) Marrie, Ruth Ann; O'Mahony, Julia; Maxwell, Colleen J.; Ling, Vicki; Yeh, E. Ann; Arnold, Douglas L.; Bar-Or, Amit; Banwell, Brenda
We aimed to compare health care utilization of children with pediatric-onset multiple sclerosis to that of age, sex and geographically-matched children without multiple sclerosis. Using population-based administrative data from Ontario, Canada for the period 2003–2014, we applied a validated case definition to identify persons aged ≤18 years with multiple sclerosis. We identified up to 5 children without multiple sclerosis matched on sex, age, and region of residence. In each cohort, we determined annual rates of any hospitalization and physician services use. Using general linear models we compared utilization rates adjusting for age, sex, region, socioeconomic status and year. Subsequently, we limited the analysis to incident cases of multiple sclerosis and their matches, and compared rates of utilization in the year of multiple sclerosis diagnosis, and the three years thereafter. We identified 659 youth with multiple sclerosis (428 incident cases), and 3,294 matched controls. Two-thirds of both cohorts were female. After adjustment for sociodemographic factors and year, the multiple sclerosis cohort was more likely to be hospitalized than the matched cohort (odds ratio 15.2; 95%CI: 12.0, 19.1), and had higher rates of ambulatory physician visits (rate ratio 4.58; 95%CI: 4.26, 4.92). The odds of hospitalization (odds ratio 40.1; 95%CI: 27.1, 59.5) and physician visits (rate ratio 5.14; 95%CI: 4.63, 5.71) were markedly elevated in the year of MS diagnosis, declining thereafter but remaining elevated versus the matched cohort. Children with multiple sclerosis have substantially elevated rates of health care utilization as compared to matched children without multiple sclerosis, over calendar time and throughout the early disease course.
Charting pathways to climate change mitigation in a coupled socio-climate model
(Public Library of Science, 2019-06-06) Bury, Thomas M.; Bauch, Chris T.; Anand, Madhur
Geophysical models of climate change are becoming increasingly sophisticated, yet less effort is devoted to modelling the human systems causing climate change and how the two systems are coupled. Here, we develop a simple socio-climate model by coupling an Earth system model to a social dynamics model. We treat social processes endogenously—emerging from rules governing how individuals learn socially and how social norms develop—as well as being influenced by climate change and mitigation costs. Our goal is to gain qualitative insights into scenarios of potential socio-climate dynamics and to illustrate how such models can generate new research questions. We find that the social learning rate is strongly influential, to the point that variation of its value within empirically plausible ranges changes the peak global temperature anomaly by more than 1°C. Conversely, social norms reinforce majority behaviour and therefore may not provide help when we most need it because they suppress the early spread of mitigative behaviour. Finally, exploring the model’s parameter space for mitigation cost and social learning suggests optimal intervention pathways for climate change mitigation. We find that prioritising an increase in social learning as a first step, followed by a reduction in mitigation costs provides the most efficient route to a reduced peak temperature anomaly. We conclude that socio-climate models should be included in the ensemble of models used to project climate change.
A local optimization framework for addressing conservation conflicts in mosaic ecosystems
(Public Library of Science, 2019-05-31) Nowack, Shane; Bauch, Chris T.; Anand, Madhur
An effective strategy to resolve conservation conflicts on lands outside of nature reserves is to consider the spatial arrangement of agricultural and native vegetation parcels such that the ecological value of the landscape is improved without reducing the amount of land used for agricultural production. Global optimization methods have been used to identify the best spatial arrangement of land parcels for a given project goal, but these methods are not designed to provide pathways to reach the optimum from the initial landscape. Here we describe how local search algorithms can be used to develop land parcel rearrangement pathways to obtain a landscape that sustains greater species richness than the initial landscape without changing the amount of land used for agricultural production. To demonstrate how the local optimization framework can be applied, an ecological setting based on a forest-grassland mosaic ecosystem in Rio Grande do Sul, Brazil was constructed. Plant samples collected from this region were used to construct species area curves. Multiple locally optimal solutions that improved the modeled species richness of the landscape almost to globally optimal levels were identified. To support the results, the algorithm was also applied to a 306,250 ha forest-grassland region of Rio Grande do Sul. The case study results suggested that conservation polices solely based on landowners satisfying a legal reserve percentage on their property should be revised to consider landscape-level connectivity. Providing multiple possible solutions for landscape configurations using local optimization methods may improve managerial flexibility for decision-makers, compared to global optimization approaches providing a single solution. Furthermore, the algorithm details the parcel exchange pathways that are required to reach the optimal land state. We conclude that local and global optimization approaches can be used in combination to improve land use decision-making for conservation, in mosaic ecosystems as well as other terrestrial ecosystems
An acoustic source model for asymmetric intraglottal flow with application to reduced-order models of the vocal folds
(Public Library of Science, 2019-07-25) Erath, Byron D.; Peterson, Sean D.; Weiland, Kelley S.; Plesniak, Michael W.; Zanartu, Matias
The complex three-way interaction between airflow, tissue, and sound, for asymmetric vocal fold vibration, is not well understood. Current modeling efforts are not able to explain clinical observations where drastic differences in sound production are often observed, with no noticeable differences in the vocal fold kinematics. To advance this understanding, an acoustical model for voiced sound generation in the presence of asymmetric intraglottal flows is developed. The source model operates in conjunction with a wave reflection analog propagation scheme and an asymmetric flow description within the glottis. To enable comparison with prior work, the source model is evaluated using a well-studied two-mass vocal fold model. The proposed source model is evaluated through acoustic measures of interest, including radiated sound pressure level, maximum flow declination rate, and spectral tilt, and also via its effects on the vocal fold dynamics. The influence of the model, in comparison to the standard symmetric Bernoulli flow description, results in an increased transfer of energy from the fluid to the vocal folds, increased radiated sound pressure level and maximum flow declination rate, and decreased spectral tilt. These differences are most pronounced for asymmetric vocal fold configurations that mimic unilateral paresis and paralysis, where minor kinematic changes can result in significant acoustic and aerodynamic differences. The results illustrate that fluid effects arising from asymmetric glottal flow can play an important role in the acoustics of pathological voiced speech.
How to build a fruit: Transcriptomics of a novel fruit type in the Brassiceae
(Public Library of Science, 2019-07-18) Carey, Shane; Mendler, Kerrin; Hall, Jocelyn C.
Comparative gene expression studies are invaluable for predicting how existing genetic pathways may be modified or redeployed to produce novel and variable phenotypes. Fruits are ecologically important organs because of their impact on plant fitness and seed dispersal, modifications in which results in morphological variation across species. A novel fruit type in the Brassicaceae known as heteroarthrocarpy enables distinct dispersal methods in a single fruit through segmentation via a lateral joint and variable dehiscence at maturity. Given the close relationship to Arabidopsis, species that exhibit heteroarthrocarpy are powerful models to elucidate how differences in gene expression of a fruit patterning pathway may result in novel fruit types. Transcriptomes of distal, joint, and proximal regions from Erucaria erucarioides and Cakile lanceolata were analyzed to elucidate within fruit and between species differences in whole transcriptome, gene ontology, and fruit patterning expression profiles. Whole transcriptome expression profiles vary between fruit regions in patterns that are consistent with fruit anatomy. These transcriptomic variances do not correlate with changes in gene ontology, as they remain generally stable within and between both species. Upstream regulators in the fruit patterning pathway, FILAMENTOUS FLOWER and YABBY3, are expressed in the distal and proximal regions of E. erucarioides, but not in the joint, implicating alterations in the pathway in heteroarthrocarpic fruits. Downstream gene, INDEHISCENT, is significantly upregulated in the abscissing joint region of C. lanceolata, which suggests repurposing of valve margin genes for novel joint disarticulation in an otherwise indehiscent fruit. In summary, these data are consistent with modifications in fruit patterning genes producing heteroarthrocarpic fruits through different components of the pathway relative to other indehiscent, non-heteroarthrocarpic, species within the family. Our understanding of fruit development in Arabidopsis is now extended to atypical siliques within the Brassicaceae, facilitating future studies on seed shattering in important Brassicaceous crops and pernicious weeds.
An enhanced heuristic XoR network coding-based method for high quality video streaming over VANETs
(Public Library of Science, 2019-06-28) Mosaarab, Maryam; Barekatain, Behrang; Raahemifar, Kaamran; Movahednejad, Homa
One of the most important challenges in live video streaming in mobile vehicular networks is the optimal use of broadband and point-to-point packet delay. Recent studies show that the sheer use of frames flow compression methods (such as H.264 or HEVC) and the proper communication overlay, such as Peer-to-Peer (P2P), has no absolute influence on increasing the quality of received video in VANET networks. Therefore, the use of an appropriate data exchange method, such as network coding, seems to be of great importance. Compared to Random Network Coding (RNC), XoR Network Coding (XNC) method has the least computational load for the network which is an important factor in optimal use of limited energy of nodes in a wireless network. The basic problem in XNC is that when a node is supposed to combine several frames and transmit them through an encoded frame, how this combination could be made to enable other nodes of the network to be broadcasted through receiving this packet and how can the available packets in their buffers decode as well as extract the largest number of frames in order to experience a higher video quality. To fulfil this aim, an encoding intelligent method is required which is based on the buffers’ status of neighbours. In the proposed method in this article, the best frame combination is reached through buffers status of neighbours and AHP methods or AHP-TOPSIS methods, and the encoded frames are broadcasted through XNC. Simulation results show that due to the reduction in number of transmitted packets in the network, parameters such as congestion and point-to-point delay are significantly reduced and vehicles experience a higher video quality compared with other similar methods.
Spatial optimization for radiation therapy of brain tumours
(Public Library of Science, 2019-06-28) Meaney, Cameron; Stastna, Marek; Kardar, Mehran; Kohandel, Mohammad
Glioblastomas are the most common primary brain tumours. They are known for their highly aggressive growth and invasion, leading to short survival times. Treatments for glioblastomas commonly involve a combination of surgical intervention, chemotherapy, and external beam radiation therapy (XRT). Previous works have not only successfully modelled the natural growth of glioblastomas in vivo, but also show potential for the prediction of response to radiation prior to treatment. This suggests that the efficacy of XRT can be optimized before treatment in order to yield longer survival times. However, while current efforts focus on optimal scheduling of radiotherapy treatment, they do not include a similarly sophisticated spatial optimization. In an effort to improve XRT, we present a method for the spatial optimization of radiation profiles. We expand upon previous results in the general problem and examine the more physically reasonable cases of 1-step and 2-step radiation profiles during the first and second XRT fractions. The results show that by including spatial optimization in XRT, while retaining a constant prescribed total dose amount, we are able to increase the total cell kill from the clinically-applied uniform case.
The Flooring for Injury Prevention (FLIP) Study of complaint flooring for the prevention of fall-related injuries in long-term care: A randomized trial
(Public Library of Science, 2019-06-24) Mackey, Dawn C.; Lachance, Chantelle C.; Wang, Peiwei T.; Feldman, Fabio; Laing, Andrew C.; Leung, Pet M.; Hu, X. Joan; Robinovitch, Stephen N.
Background Fall-related injuries exert an enormous health burden on older adults in long0term care (LTC). Softer landing surfaces, such as those provided by low-stiffness "compliant" flooring, may prevent fall-related injuries by decreasing the forces applied to the body during fall impact. Our primary objective was to assess the clinical effectiveness of compliant flooring at preventing serious fall-related injuries among LTC residents. Methods and findings The Flooring for Injury Prevention (FLIP) Study was a 4-year, randomized superiority trial in 150 single-occupancy resident rooms at a single Canadian LTC site. In April 2013, resident rooms were block randomized (1:1) to installation of intervention compliant flooring (2.54 cm SmartCells) or rigid control flooring (2.54 cm plywood) covered with identical hospital-grade vinyl. The primary outcome was serious fall-related injury over 4 years that required an emergency department visit or hospital admission and a treatment procedure or diagnostic evaluation in hospital. Secondary outcomes included minor fall-related injury, any fall-related injury, falls, and fracture. Outcomes were ascertained by blinded assessors between September 1, 2013 and August 31, 2017 and analyzed by intention to treat. Adverse outcomes were not assessed. During follow-up, 184 residents occupied 74 intervention rooms, and 173 residents occupied 76 control rooms. Residents were 64.3% female with mean (SD) baseline age 81.7 (9.5) years (range 51.1 to 104.6 years), body mass index 25.9 (7.7) kg/m2, and follow-up 1.64 (1.39) years. 1,907 falls were reported; 23 intervention residents experienced 38 serious injuries (from 29 falls in 22 rooms), while 23 control residents experienced 47 serious injuries (from 34 falls in 23 rooms). Compliant flooring did not affect odds of ≥1 serious fall-related injury (12.5% intervention versus 13.3% control, odds ratio [OR]: 0.98, 95% CI: 0.52 to 1.84, p = 0.950) or ≥2 serious fall-related injuries (5.4% versus 7.5%, OR: 0.74, 95% CI: 0.31 to 1.75, p = 0.500). Compliant flooring did not affect rate of serious fall-related injuries (0.362 versus 0.422 per 1,000 bed nights, rate ratio [RR]: 1.04, 95% CI: 0.45 to 2.39, p = 0.925; 0.038 versus 0.053 per fall, RR: 0.81, 95% CI: 0.38 to 1.71, p = 0.560), rate of falls with ≥1 serious fall-related injury (0.276 versus 0.303 per 1,000 bed nights, RR: 0.97, 95% CI: 0.52 to 1.79, p = 0.920), or time to first serious fall-related injury (0.237 versus 0.257, hazard ratio [HR]: 0.92, 95% CI: 0.52 to 1.62, p = 0.760). Compliant flooring did not affect any secondary outcome in this study. Study limitations included the following: findings were specific to 2.54 cm SmartCells compliant flooring installed in LTC resident rooms, standard fall and injury prevention interventions were in use throughout the study and may have influenced the observed effect of compliant flooring, and challenges with concussion detection in LTC residents may have prevented estimation of the effect of compliant flooring on fall-related concussions. Conclusions In contrast to results from previous retrospective and nonrandomized studies, this study found that compliant flooring underneath hospital-grade vinyl was not effective at preventing serious fall-related injuries in LTC. Future studies are needed to identify effective methods for preventing fall-related injuries in LTC.
Re-evaluating whether bilateral eye movements influence memory retrieval
(Public Library of Science, 2020-01-27) Roberts, Brady R. T.; Fernandes, Myra A.; MacLeod, Colin M.
Several recent studies have reported enhanced memory when retrieval is preceded by repetitive horizontal eye movements, relative to vertical or no eye movements. The reported memory boost has been referred to as the Saccade-Induced Retrieval Enhancement (SIRE) effect. Across two experiments, memory performance was compared following repetitive horizontal or vertical eye movements, as well as following a control condition of no eye movements. In Experiment 1, we conceptually replicated Christman and colleagues’ seminal study, finding a statistically significant SIRE effect, albeit with weak Bayesian evidence. We therefore sought to conduct another close extension. In Experiment 2, horizontal and vertical eye movement conditions were manipulated separately, and sample size was increased. No evidence of a SIRE effect was found: Bayesian statistical analyses demonstrated significant evidence for a null effect. Taken together, these experiments suggest that the SIRE effect is inconsistent. The current experiments call into question the generalizability of the SIRE effect and suggest that its presence is very sensitive to experimental design. Future work should further assess the robustness of the effect before exploring related theories or underlying mechanisms.
Young women's reproductive health conversations: Roles of maternal figures and clinical practices
(Public Library of Science, 2020-01-23) Richards, Nicole K.; Crockett, Elizabeth; Morley, Christopher P.; Levandowski, Brooke A.
Objective To explore the role of clinical providers and mothers on young women's ability to have confidential, candid reproductive health conversations with their providers. Methods We conducted 14 focus groups with 48 women aged 15-28 years (n = 9), and 32 reproductive healthcare workers (n = 5). Focus groups were audio recorded and transcribed. Data were analyzed using inductive coding and thematic analyses. We examined findings through the lens of paternalism, a theory that illustrates adults' role in children's autonomy and wellbeing. Results Mothers have a substantial impact on young women's health values, knowledge, and empowerment. Young women reported bringing information from their mothers into patient-provider health discussions. Clinical best practices included intermingled components of office policies, state laws, and clinical guidelines, which supported health workers' actions to have confidential conversations. There were variations in how health workers engaged young women in a confidential conversation within the exam room. Conclusions Both young women and health workers benefit from situations in which health workers firmly ask the parent to leave the exam room for a private conversation with the patient. Young women reported this improves their comfort in asking the questions they need to make the best decision for themselves. Clinic leadership needs to ensure that confidentiality surrounding young women's reproductive health is uniform throughout their practice and integrated into patient flow.
Linguistic Z-number weighted averaging operators and their application to portfolio selection problem
(Public Library of Science, 2020-01-23) Mahmoodi, Amir Hosein; Sadjadi, Seyed Jafar; Sadi-Nezhad, Soheil; Soltani, Roya; Sobhani, Forzad Movahedi
Z-numbers can generate a more flexible structure to model the real information because of capturing expert’s reliability. Moreover, various semantics can flexibly be reflected by linguistic terms under various circumstances. Thus, this study aims to model the portfolio selection problems based on aggregation operators under linguistic Z-number environment. Therefore, a multi-stage methodology is proposed and linguistic Z-numbers are applied to describe the assessment information. Moreover, the weighted averaging (WA) aggregation operator, the ordered weighted averaging (OWA) aggregation operator and the hybrid weighted averaging (HWA) aggregation operator are developed to fuse the input arguments under the linguistic Z-number environment. Then, using the max-score rule and the score-accuracy trade-off rule, three qualitative portfolio models are presented to allocate the optimal assets. These models are suitable for general investors and risky investors. Finally, to illustrate the validity of the proposed qualitative approach, a real case including 20 corporations of Tehran stock exchange market in Iran is provided and the obtained results are analyzed. The results show that combining linguistic Z-numbers with portfolio selection processes can increase the tendencies and capabilities of investors in the capital market and it helps them manage their portfolios efficiently.
Modeling migration patterns in the USA under sea level rise
(Public Library of Science, 2020-01-22) Robinson, Caleb; Dilkina, Bistra; Moreno-Cruz, Juan
Sea level rise in the United States will lead to large scale migration in the future. We propose a framework to examine future climate migration patterns using models of human migration. Our framework requires that we distinguish between historical versus climate driven migration and recognizes how the impacts of climate change can extend beyond the affected area. We apply our framework to simulate how migration, driven by sea level rise, differs from baseline migration patterns. Specifically, we couple a sea level rise model with a data-driven model of human migration and future population projections, creating a generalized joint model of climate driven migration that can be used to simulate population distributions under potential future sea level rise scenarios. The results of our case study suggest that the effects of sea level rise are pervasive, expanding beyond coastal areas via increased migration, and disproportionately affecting some areas of the United States.
Pupil response to noxious corneal stimulation
(Public Library of Science, 2020-01-17) Alabi, Emmanuel B.; Simpson, Trefford L.
Purpose Ocular somatosensory-automatic reflexes play critical roles in maintaining homeostasis of the eye. The purpose of this study was to investigate the pupil response to nociceptive corneal stimuli. Methods A Waterloo-Belmonte pneumatic esthesiometer was used to determine detection thresholds and randomly deliver mechanical and chemical stimuli from levels of detection threshold to twice the threshold in 50% steps to the central cornea of 15 healthy subjects. For each stimulus, imaging of the stimulated/unstimulated eye was performed using two modified/calibrated Logitech c920 digital cameras for 4 seconds each, pre/post stimulus capture. The data were processed with a custom segmentation algorithm to help identify the pupils and pupil diameter was measured using ImageJ software. Pupil dilation response differences between the ipsi- and contralateral eye was analyzed using dependent t-tests. The effect of stimulus intensity, modality and sex of subjects were analyzed using repeated measures. Results In mechanical and chemical stimulation experiments, there was no difference in pupil responses between the stimulated eye and the unstimulated eye, (all dependent T-test p > 0.05). On average, pupil diameter increased from baseline as the corneal stimulus intensity increased. This happened regardless of whether mechanical or chemical stimulation occurred (ANOVA p < 0.05). At 200% threshold, pupil diameter was greater than at all stimulus intensities (Tukey HSD, all p < 0.05). Based on stimulus intensity, females had greater pupil diameters than males at levels of 150% threshold and 200% threshold (ANOVA p < 0.05, all Tukey HSD p < 0.05). Conclusion This study serves as a basis for the characterization of the local stimulus-response neural circuitry relating nociceptive stimuli to autonomic responses and in combination with our work on completely separate autonomic circuits of bulbar conjunctival vessel dilation and reflex tearing suggests that the monotonic measurements of redness, tearing and pupils provide accurate, separable responses that reflect painful stimulus intensity.
Loading... loading... The influence of download time on information search
(Public Library of Science, 2019-12-06) Smith, Alyssa C.; Ralph, Brandon C. W.; Marty-Dugas, Jeremy; Smilek, Daniel
When browsing online, there is considerable variation in the amount of time that one has to wait for content to appear once the link to that content has been activated (i.e., clicked). In two experiments we examined how ‘download time’–a potential barrier to information access–influences search behaviour. In both experiments, participants completed a video-watching task in which they were presented with a screen containing six clickable icons, each of which represented a unique video. When participants clicked an icon, a video would begin to load and then play. The participants’ task was to gain as much information from the videos as possible for a later memory test. Critically, however, the ‘download time’ (i.e., the time between the click on the icon and the video beginning to play) of the available videos in a given search session varied. In Experiment 1, these download times were 0 (instant), 2, or 30 seconds, and in Experiment 2, they were 5, 15, or 30 seconds. In general, we found that participants terminated and avoided videos with longer download times than videos with shorter download times. Interestingly, this effect was attenuated when the experienced download times were more similar to each other (Experiment 2) than when they were more different from each other (Experiment 1).
Feature identification in time-indexed model output
(Public Library of Science, 2019-12-04) Shaw, Justin; Stastna, Marek
We present a method for identifying features (time periods of interest) in data sets consisting of time-indexed model output. The method is used as a diagnostic to quickly focus the attention on a subset of the data before further analysis methods are applied. Mathematically, the infinity norm errors of empirical orthogonal function (EOF) reconstructions are calculated for each time output. The result is an EOF reconstruction error map which clearly identifies features as changes in the error structure over time. The ubiquity of EOF-type methods in a wide range of disciplines reduces barriers to comprehension and implementation of the method. We apply the error map method to three different Computational Fluid Dynamics (CFD) data sets as examples: the development of a spontaneous instability in a large amplitude internal solitary wave, an internal wave interacting with a density profile change, and the collision of two waves of different vertical mode. In all cases the EOF error map method identifies relevant features which are worthy of further study.
A model-based framework for chronic hepatitis C prevalence estimation
(Public Library of Science, 2019-11-21) Hamadeh, Abdullah; Feng, Zeny; Krahn, Murray; Wong, William W. L.
Chronic hepatitis C (CHC) continues to be a highly burdensome disease worldwide. The often-asymptomatic nature of early-stage CHC means that the disease often remains undiagnosed, leaving its prevalence highly uncertain. This generates significant uncertainty in the planning of hepatitis C eradication programs to meet WHO targets. The aim of this work is to establish a mathematical framework for the estimation of a geographic locale’s CHC prevalence and the proportion of its CHC population that remains undiagnosed. A Bayesian MCMC approach is taken to infer these populations from the observed occurrence of CHC-related events using a recently published natural history model of the disease. Using the Canadian context as a specific example, this study estimates that in 2013, the CHC prevalence rate in Canada was 0.63% (95% CI: 0.53% - 0.72%), with 27.1% (95% CI: 19.3% - 36.1%) of the infected population undiagnosed.
Suppressive impact of metronomic chemotherapy using UFT and/or cyclophosphamide on mediators of breast cancer dissemination and invasion
(Public Library of Science, 2019-09-19) Munoz, Raquel; Hileeto, Denise; Cruz-Munoz, William; Wood, Geoffrey A.; Xu, Ping; Man, Shan; Viloria-Petit, Alicia; Kerbel, Robert S.
Metronomic chemotherapy using the 5-FU prodrug uracil-tegafur (UFT) and cyclophosphamide (CTX) was previously shown to only modestly delay primary tumor growth, but nevertheless markedly suppressed the development of micro-metastasis in an orthotopic breast cancer xenograft model, using the metastatic variant of the MDA-MB-231 cell line, 231/LM2-4. Furthermore, a remarkable prolongation of survival, with no toxicity, was observed in a model of postsurgical advanced metastatic disease. A question that has remained unanswered is the seemingly selective anti-metastatic mechanisms of action responsible for this treatment. We assessed the in vivo effect of metronomic UFT, CTX or their combination, on vascular density, collagen deposition and c-Met (cell mediators or modulators of tumor cell invasion or dissemination) via histochemistry/immunohistochemistry of primary tumor sections. We also assessed the effect of continuous exposure to low and non-toxic doses of active drug metabolites 5-fluorouracil (5-FU), 4-hydroperoxycyclophosphamide (4-HC) or their combination, on 231/LM2-4 cell invasiveness in vitro. In the in vivo studies, a significant reduction in vascular density and p-Met[Y1003] levels was associated with UFT+CTX treatment. All treatments reduced intratumoral collagen deposition. In the in vitro studies, a significant reduction of collagen IV invasion by all treatments was observed. The 3D structures formed by 231/LM2-4 on Matrigel showed a predominantly Mass phenotype under treated conditions and Stellate phenotype in untreated cultures. Taken together, the results suggest the low-dose metronomic chemotherapy regimens tested can suppress several mediators of tumor invasiveness highlighting a new perspective for the anti-metastatic efficacy of metronomic chemotherapy.
Socioeconomic patterns of smoking cessation behavior in low and middle-income countries: Emerging evidence from the Global Adult Tobacco Surveys and International Tobacco Control Surveys
(Public Library of Science, 2019-09-06) Nargis, Nigar; Yong, Hua-Hie; Driezen, Pete; Mbulo, Lazarous; Zhao, Luhua; Fong, Geoffrey T.; Thompson, Mary E.; Borland, Ron; Palipudi, Krishna M.; Giovino, Gary A.; Thrasher, James F.; Siahpush, Mohammad
Introduction Tobacco smoking is often more prevalent among those with lower socio-economic status (SES) in high-income countries, which can be driven by the inequalities in initiation and cessation of smoking. Smoking is a leading contributor to socio-economic disparities in health. To date, the evidence for any socio-economic inequality in smoking cessation is lacking, especially in low- and middle-income countries (LMICs). This study examined the association between cessation behaviours and SES of smokers from eight LMICs. Methods Data among former and current adult smokers aged 18 and older came from contemporaneous Global Adult Tobacco Surveys (2008–2011) and the International Tobacco Control Surveys (2009–2013) conducted in eight LMICs (Bangladesh, Brazil, China, India, Mexico, Malaysia, Thailand and Uruguay). Adjusted odds ratios (AORs) of successful quitting in the past year by SES indicators (household income/wealth, education, employment status, and rural-urban residence) were estimated using multivariable logistic regression controlling for socio-demographics and average tobacco product prices. A random effects meta-analysis was used to combine the estimates of AORs pooled across countries and two concurrent surveys for each country. Results Estimated quit rates among smokers (both daily and occasional) varied widely across countries. Meta-analysis of pooled AORs across countries and data sources indicated that there was no clear evidence of an association between SES indicators and successful quitting. The only exception was employed smokers, who were less likely to quit than their non-employed counterparts, which included students, homemakers, retirees, and the unemployed (pooled AOR≈0.8, p<0.10). Conclusions Lack of clear evidence of the impact of lower SES on adult cessation behaviour in LMICs suggests that lower-SES smokers are not less successful in their attempts to quit than their higher-SES counterparts. Specifically, lack of employment, which is indicative of younger age and lower nicotine dependence for students, or lower personal disposable income and lower affordability for the unemployed and the retirees, may be associated with quitting. Raising taxes and prices of tobacco products that lowers affordability of tobacco products might be a key strategy for inducing cessation behaviour among current smokers and reducing overall tobacco consumption. Because low-SES smokers are more sensitive to price increases, tobacco taxation policy can induce disproportionately larger decreases in tobacco consumption among them and help reduce socio-economic disparities in smoking and consequent health outcomes.

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