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Background Brucellosis, as a serious zoonotic infectious disease, has been recognized as a re-emerging disease in the developing countries worldwide. In china, the incidence of brucellosis is increasing each year, seriously threatening the health of humans as well as animal populations. Despite a quite number of diagnostic methods currently being used for brucellosis, innovative technologies are still needed for its rapid and accurate diagnosis, especially in area where traditional diagnostic is unavailable. Methodology/Principal findings In this study, a total of 22 B cell linear epitopes were predicted from five Brucella outer membrane proteins (OMPs) using an immunoinformatic approach. These epitopes were then chemically synthesized, and with the method of indirect ELISA (iELISA), each of them displayed a certain degree of capability in identifying human brucellosis positive sera. Subsequently, a fusion protein consisting of the 22 predicted epitopes was prokaryotically expressed and used as diagnostic antigen in a newly established brucellosis testing method, nano-ZnO modified paper-based ELISA (nano-p-ELISA). According to the verifying test using a collection of sera collected from brucellosis and non-brucellosis patients, the sensitivity and specificity of multiepitope based nano-p-ELISA were 92.38% and 98.35% respectively. The positive predictive value was 98.26% and the negative predictive value was 91.67%. The multiepitope based fusion protein also displayed significantly higher specificity than Brucella lipopolysaccharide (LPS) antigen. Conclusions B cell epitopes are important candidates for serologically testing brucellosis. Multiepitope fusion protein based nano-p-ELISA displayed significantly sensitivity and specificity compared to Brucella LPS antigen. The strategy applied in this study will be helpful to develop rapid and accurate diagnostic method for brucellosis in human as well as animal populations., Author summary Brucellosis is one of the most important zoonosis in the world and has caused tremendous economic losses in agriculture and animal husbandry in many countries. Developing rapid, sensitive and specific diagnostic methods is very important for early detection and treatment of brucellosis patients. In this study, a novel diagnostic technique, nano-ZnO modified paper ELISA, was established. The antigen used in this technique was a fusion protein containing multiple B cell epitopes, which were predicted from Brucella major outer membrane proteins such as Bp26, Omp31, Omp16, Omp2b and Omp25. Comparing to traditional LPS antigen, this multiepitope based antigen displayed considerably higher sensitivity and higher specificity in laboratory. With the strategy described in this paper, more efficient epitopes and protein antigen can be identified in the future. Currently, LPS antigen is only prepared from live Brucella, while protein antigen can be produced in large quantities in prokaryotic expression system. In addition to nano-p-ELISA, this protein antigen can also be used for development other methods such as fluorescent polarization assay (FPA) and immunochromatographic assay (ICA) to meet the varied demand for brucellosis testing.

Rabies is a lethal zoonotic encephalomyelitis that causes an estimated 59,000 human deaths yearly worldwide. Although developing countries of Asia and Africa bear the heaviest burden, surveillance and disease detection in these countries is often hampered by the absence of local laboratories able to diagnose rabies and/or the difficulties of sample shipment from low-access areas to national reference laboratories. Filter papers offer a convenient cost-effective alternative for the sampling, shipment, and storage of biological materials for the diagnosis of many pathogens including rabies virus, yet the properties of diagnostic tests using this support have not been evaluated thoroughly. Sensitivity and specificity of molecular diagnosis of rabies infection using a reverse transcription followed by a hemi-nested polymerase chain reaction (RT-hn-PCR) either directly on brain tissue or using brain tissue dried on filter paper were assessed on 113 suspected field animal samples in comparison to the direct fluorescent antibody test (FAT) recommended by the World Health Organization as one of the reference tests for rabies diagnosis. Impact of the duration of the storage was also evaluated. The sensitivity and the specificity of RT-hn-PCR i) on brain tissue were 96.6% (95% CI: [88.1–99.6]) and 92.7% (95% CI: [82.4–98.0]) respectively and ii) on brain tissue dried on filter paper 100% (95% CI: [93.8–100.0]) and 90.9% (95% CI: [80.0–97.0]) respectively. No loss of sensitivity of RT-hn-PCR on samples of brain tissue dried on filter paper left 7 days at ambient temperature was detected indicating that this method would enable analyzing impregnated filter papers sent to the national reference laboratory at ambient temperature within a 1-week shipment time. It could therefore be an effective alternative to facilitate storage and shipment of samples from low-access areas to enhance and expand rabies surveillance., Author summary Dogs are responsible for 99% of human rabies deaths. Facilitating diagnostic of rabid dogs can help further identify i) people who were exposed to rabies in order to encourage them to seek post exposure prophylaxis and ii) other exposed animals to break the transmission chain (i.e. prevent them from further transmitting the virus to other people and animals). Yet, the reference diagnostic method for animal rabies requires brain samples to be collected post-mortem and shipped under temperature-controlled conditions. The shipping of such samples is complex in low-access areas, especially in low income countries, which are often those that bear the heaviest rabies burden. Filter papers offer a convenient alternative for biological sample shipment and storage. Here the efficiency of a molecular diagnostic method applied to brain tissue dried on filter paper is compared to one of the reference methods, the direct fluorescent antibody test. Our results show it has an excellent sensitivity (it does not miss any positive samples), even when filter papers are left 7 days at ambient temperature. These results let us foresee a cost-effective alternative facilitating shipment, storage and testing of samples from rabies suspected animals from low-access areas. This could considerably enhance and expand rabies surveillance in low-income countries, allowing a more comprehensive evaluation of rabies burden, and thus reinforcing arguments for allocating funds to rabies control policies.

Background Global estimates for cholera annually approximate 4 million cases worldwide with 95,000 deaths. Recent outbreaks, including Haiti and Yemen, are reminders that cholera is still a global health concern. Cholera outbreaks can rapidly induce high death tolls by overwhelming the capacity of health facilities, especially in remote areas or areas of civil unrest. Recent studies demonstrated that stool specimens preserved on filter paper facilitate molecular analysis of Vibrio cholerae in resource limited settings. Specimens preserved in a rapid, low-cost, safe and sustainable manner for sequencing provides previously unavailable data about circulating cholera strains. This may ultimately contribute new information to shape public policy response on cholera control and elimination. Methodology/Principal findings Whole genome sequencing (WGS) recovered close to a complete sequence of the V. cholerae O1 genome with satisfactory genome coverage from stool specimens enriched in alkaline peptone water (APW) and V. cholerae culture isolates, both spotted on filter paper. The minimum concentration of V. cholerae DNA sufficient to produce quality genomic information was 0.02 ng/μL. The genomic data confirmed the presence or absence of genes of epidemiological interest, including cholera toxin and pilus loci. WGS identified a variety of diarrheal pathogens from APW-enriched specimen spotted filter paper, highlighting the potential for this technique to explore the gut microbiome, potentially identifying co-infections, which may impact the severity of disease. WGS demonstrated that these specimens fit within the current global cholera phylogenetic tree, identifying the strains as the 7th pandemic El Tor. Conclusions WGS results allowed for mapping of short reads from APW-enriched specimen and culture isolate spotted filter papers. This provided valuable molecular epidemiological sequence information on V. cholerae strains from remote, low-resource settings. These results identified the presence of co-infecting pathogens while providing rare insight into the specific V. cholerae strains causing outbreaks in cholera-endemic areas., Author summary Cholera affects more than 4 million people globally every year; people predominantly living in poverty or in resource-constrained conditions including political crises or natural disasters. Cholera’s typical presentation is characterized by rapid onset of acute watery diarrhea and vomiting which can progress from watery stool to shock in as little as four hours. Laboratory conditions needed for culture confirmation and strain preservation are rarely to never present in these affected areas. In fact, many cholera endemic areas in Sub-Saharan African are so remote that even treatment response alone is often challenging. Here we present the genomic analysis of DNA extracted from dried filter paper, which is a low-cost, low-tech and sustainable method. Previously this method has facilitated cholera confirmation by PCR, but we demonstrate that this method is also suitable for whole genome sequencing and subsequent strain characterization by presenting the analysis of samples from an outbreak in a remote area of Cameroon. This method will facilitate the understanding of the molecular epidemiology in cholera-prone areas, which were previously too challenging to attempt. It also introduces a method that can be used on a broader scale for diarrheal disease surveillance, including providing a window into co-infection and microbiome analyses.

We describe herein a method of recharging used commercial spin columns or assembling homemade spin columns using filter paper as binding material for cost-effective, low throughput nucleic acid purification. The efficiency of filter paper-based spin columns was evaluated for purification of nucleic acids from various sources. Following protocols of commercial kits, we found filter paper to be a useful binding material for purification of nucleic acids, including plant genomic DNA, plant total RNA, PCR products, and DNA from agarose gels. However, filter paper has a weak binding affinity to plasmid DNA in tested miniprep protocols. Protocols for the use of filter paper recharged spin columns or homemade spin columns for low throughput purification of plant genomic DNA and total RNA with unused commercial kit buffers or less expensive homemade buffers are presented.

Although regression models play a central role in the analysis of medical research projects, there still exist many misconceptions on various aspects of modeling leading to faulty analyses. Indeed, the rapidly developing statistical methodology and its recent advances in regression modeling do not seem to be adequately reflected in many medical publications. This problem of knowledge transfer from statistical research to application was identified by some medical journals, which have published series of statistical tutorials and (shorter) papers mainly addressing medical researchers. The aim of this review was to assess the current level of knowledge with regard to regression modeling contained in such statistical papers. We searched for target series by a request to international statistical experts. We identified 23 series including 57 topic-relevant articles. Within each article, two independent raters analyzed the content by investigating 44 predefined aspects on regression modeling. We assessed to what extent the aspects were explained and if examples, software advices, and recommendations for or against specific methods were given. Most series (21/23) included at least one article on multivariable regression. Logistic regression was the most frequently described regression type (19/23), followed by linear regression (18/23), Cox regression and survival models (12/23) and Poisson regression (3/23). Most general aspects on regression modeling, e.g. model assumptions, reporting and interpretation of regression results, were covered. We did not find many misconceptions or misleading recommendations, but we identified relevant gaps, in particular with respect to addressing nonlinear effects of continuous predictors, model specification and variable selection. Specific recommendations on software were rarely given. Statistical guidance should be developed for nonlinear effects, model specification and variable selection to better support medical researchers who perform or interpret regression analyses.

Microbial fuel cells (MFCs) can evolve in a viable technology if environmentally sound materials are developed and became available at low cost for these devices. This is especially important not only for the designing of large wastewater treatment systems, but also for the fabrication of low-cost, single-use devices. In this work we synthesized membranes by a simple procedure involving easily-biodegradable and economic materials such as poly (vinyl alcohol) (PVA), chitosan (CS) and the composite PVA:CS. Membranes were chemical and physically characterized and compared to Nafion®. Performance was studied using the membrane as separator in a typical H-Type MFCs showing that PVA:CS membrane outperform Nafion® 4 times (power production) while being 75 times more economic. We found that performance in MFC depends over interactions among several membrane characteristics such as oxygen permeability and ion conductivity. Moreover, we design a paper-based micro-scale MFC, which was used as a toxicity assay using 16 µL samples containing formaldehyde as a model toxicant. The PVA:CS membrane presented here can offer low environmental impact and become a very interesting option for point of need single-use analytical devices, especially in low-income countries where burning is used as disposal method, and toxic fluoride fumes (from Nafion®) can be released to the environment. Fil: Gonzalez Pabon, Maria Jesus. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina Fil: Figueredo, Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina Fil: Martínez Casillas, Diana Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina Fil: Corton, Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina

Amphimeriasis, a fish-borne zoonotic disease caused by the liver fluke Amphimerus spp., has recently been reported as an emerging disease affecting an indigenous Ameridian group, the Chachi, living in Ecuador. The only method for diagnosing amphimeriasis was the microscopic detection of eggs from the parasite in patients' stool samples with very low sensitivity. Our group developed an ELISA technique for detection of anti-Amphimerus IgG in human sera and a molecular method based on LAMP technology (named LAMPhimerus) for specific and sensitive parasite DNA detection. The LAMPhimerus method showed to be much more sensitive than classical parasitological methods for amphimeriasis diagnosis using human stool samples for analysis. The objective of this work is to demonstrate the feasibility of using dried stool samples on filter paper as source of DNA in combination with the effectiveness of our previously designed LAMPhimerus assay for successfully Amphimerus sp. detection in clinical stool samples. A total of 102 untreated and undiluted stool samples collected from Chachi population were spread as thin layer onto common filter paper for easily transportation to our laboratory and stored at room temperature for one year until DNA extraction. When LAMPhimerus method was applied for Amphimerus sp. DNA detection, a higher number of positive results was detected (61/102; 59.80%) in comparison to parasitological methods (38/102; 37.25%), including 28/61 (45.90%) microscopy-confirmed Amphimerus sp. infections. The diagnostic parameters for the sensitivity and specificity werecalculated for our LAMPhimerus assay, which were 79.17% and 65.98%, respectively. We demonstrate, for the first time, that common filter paper is useful for easy collection and long-term storage of human stool samples for later DNA extraction and molecular analysis of human-parasitic trematode eggs. This simple, economic and easily handling method combined with the specific and sensible LAMPhimerus assay has the potential to beused as an effective molecular large-scale screening test for amphimeriasis-endemic areas.

The present work was focused to design a cheap, rapid, portable and easy to use filter paper based assay for the qualitative and quantitate analysis of acetone. Sodium alginate gel was loaded with the acetone specific optical signal probe, and subsequently coated onto filter paper surface to design portable colorimetric assays for acetone monitoring. The color of the paper sensor strip was observed to change from dark yellow to light yellowish in the presence of varying concentrations of acetone. Three different color analyzing models including RGB, HSV, and LAB were employed to probe the output optical signal, and their performance was compared in terms of better interpretation of the generated signal. The LAB model was found to provide better analytical figures of merit with a linear response for the acetone concentration ranging from 2.5 to 1500 ppm, and a limit of detection of 0.5 ppm. Furthermore, the specificity of the designed filter paper based sensor was demonstrated against different common interfering compounds. The results demonstrated the potential of our proposed filter paper based sensor as a novel tool for the analysis of acetone.

Humans introduced paper mulberry (Broussonetia papyrifera) from Taiwan into the Pacific over 5000 years ago as a fiber source to make barkcloth textiles that were, and still are, important cultural artifacts throughout the Pacific. We have used B. papyrifera, a species closely associated to humans, as a proxy to understand the human settlement of the Pacific Islands. We report the first genetic analysis of paper mulberry textiles from historical and archaeological contexts (200 to 50 years before present) and compare our results with genetic data obtained from contemporary and herbarium paper mulberry samples. Following stringent ancient DNA protocols, we extracted DNA from 13 barkcloth textiles. We confirmed that the fiber source is paper mulberry in nine of the 13 textiles studied using the nuclear ITS-1 marker and by statistical estimates. We detected high genetic diversity in historical Pacific paper mulberry barkcloth with a set of ten microsatellites, showing new alleles and specific genetic patterns. These genetic signatures allow tracing connections to plants from the Asian homeland, Near and Remote Oceania, establishing links not observed previously (using the same genetic tools) in extant plants or herbaria samples. These results show that historic barkcloth textiles are cultural materials amenable to genetic analysis to reveal human history and that these artifacts may harbor evidence of greater genetic diversity in Pacific B. papyrifera in the past.

Introduction \ud Data collection using paper-based questionnaires can be time consuming and return errors affect data accuracy, completeness, and information quality in health surveys. We compared smartphone and paper-based data collection systems in the Burden of Obstructive Lung Disease (BOLD) study in rural Sudan. \ud Methods \ud This exploratory pilot study was designed to run in parallel with the cross-sectional household survey. The Open Data Kit was used to programme questionnaires in Arabic into smartphones. We included 100 study participants (83% women; median age = 41.5 ± 16.4 years) from the BOLD study from 3 rural villages in East-Gezira and Kamleen localities of Gezira state, Sudan. Questionnaire data were collected using smartphone and paper-based technologies simultaneously. We used Kappa statistics and inter-rater class coefficient to test agreement between the two methods. Results Symptoms reported included cough (24%), phlegm (15%), wheezing (17%), and shortness of breath (18%). One in five were or had been cigarette smokers. The two data collection methods varied between perfect to slight agreement across the 204 variables evaluated (Kappa varied between 1.00 and 0.02 and inter-rater coefficient between 1.00 and -0.12). Errors were most commonly seen with paper questionnaires (83% of errors seen) vs smartphones (17% of errors seen) administered questionnaires with questions with complex skip-patterns being a major source of errors in paper questionnaires. Automated checks and validations in smartphone-administered questionnaires avoided skip-pattern related errors. Incomplete and inconsistent records were more likely seen on paper questionnaires. \ud Conclusion \ud Compared to paper-based data collection, smartphone technology worked well for data collection in the study, which was conducted in a challenging rural environment in Sudan. This approach provided timely, quality data with fewer errors and inconsistencies compared to paper-based data collection. We recommend this method for future BOLD studies and other population-based studies in similar settings.

The breakthrough potentials of research papers can be explained by their boundary-spanning qualities. Here, for the first time, we apply the structural variation analysis (SVA) model and its affiliated metrics to investigate the extent to which such qualities characterize a group of Nobel Prize winning papers. We find that these papers share remarkable boundary-spanning traits, marked by exceptional abilities to connect disparate and topically-diverse clusters of research papers. Further, their publications exert structural variations on the scale that significantly alters the betweenness centrality distributions of existing intellectual space. Overall, SVA not only provides a set of leading indicators for describing future Nobel Prize winning papers, but also broadens our understanding of the similar prize-winning properties that may have been overlooked among other regular publications., 27 pages, 8 figures, 9 tables. Submitted to Frontiers in Research Metrics and Analytics

Rocky desertification is a bottleneck that reduces ecological and environmental security in karst areas. Paper mulberry, a unique deciduous tree, shows good performance in rocky desertification areas. Its resistance mechanisms are therefore of high interest. In this study, a lysine acetylation proteomics analysis of paper mulberry seedling leaves was conducted in combination with the purification of acetylated protein by high-precision nano LC-MS/MS. We identified a total of 7130 acetylation sites in 3179 proteins. Analysis of the modified sites showed a predominance of nine motifs. Six positively charged residues: lysine (K), arginine (R), and histidine (H), serine (S), threonine (T), and tyrosine (Y) occurred most frequently at the +1 position, phenylalanine (F) was both detected both upstream and downstream of the acetylated lysines; and the sequence logos showed a strong preference for lysine and arginine around acetylated lysines. Functional annotation revealed that the identified enzymes were mainly involved in translation, transcription, ribosomal structure and biological processes, showing that lysine acetylation can regulate various aspects of primary carbon and nitrogen metabolism and secondary metabolism. Acetylated proteins were enriched in the chloroplast, cytoplasm, and nucleus, and many stress response-related proteins were also discovered to be acetylated, including PAL, HSP70, and ERF. HSP70, an important protein involved in plant abiotic and disease stress responses, was identified in paper mulberry, although it is rarely found in woody plants. This may be further examined in research in other plants and could explain the good adaptation of paper mulberry to the karst environment. However, these hypotheses require further verification. Our data can provide a new starting point for the further analysis of the acetylation function in paper mulberry and other plants.

International audience; Background: Identification of the source of mosquito blood meals is an important component for disease control and surveillance. Recently, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) profiling has emerged as an effective tool for mosquito blood meal identification, using the abdomens of freshly engorged mosquitoes. In the field, mosquito abdomens are crushed on Whatman filter papers to determine the host feeding patterns by identifying the origin of their blood meals. The aim of this study was to test whether crushing engorged mosquito abdomens on Whatman filter papers was compatible with MALDI-TOF MS for mosquito blood meal identification. Both laboratory reared and field collected mosquitoes were tested.Material and methods: Sixty Anopheles gambiae Giles were experimentally engorged on the blood of six distinct vertebrate hosts (human, sheep, rabbit, dog, chicken and rat). The engorged mosquito abdomens were crushed on Whatman filter papers for MALDI-TOF MS analysis. 150 Whatman filter papers, with mosquitoes engorged on cow and goat blood, were preserved. A total of 77 engorged mosquito abdomens collected in the Comoros Islands and crushed on Whatman filter papers were tested with MALDI-TOF MS. Results The MS profiles generated from mosquito engorged abdomens crushed on Whatman filter papers exhibited high reproducibility according to the original host blood. The blood meal host was correctly identified from mosquito abdomens crushed on Whatman filter papers by MALDI-TOF MS. The MS spectra obtained after storage were stable regardless of the room temperature and whether or not they were frozen. The MS profiles were reproducible for up to three months. For the Comoros samples, 70/77 quality MS spectra were obtained and matched with human blood spectra. This was confirmed by molecular tools.Conclusion: The results demonstrated that MALDI-TOF MS could identify mosquito blood meals from Whatman filter papers collected in the field during entomological surveys. The application of MALDI-TOF MS has proved to be rapid and successful, making it a new and efficient tool for mosquito-borne disease surveillance.

Bisphenol A (BPA) is an endocrine disrupting chemical used in a wide range of consumer products including photoactive dyes used in thermal paper. Recent studies have shown that dermal absorption of BPA can occur when handling these papers. Yet, regulatory agencies have largely dismissed thermal paper as a major source of BPA exposure. Exposure estimates provided by agencies such as the European Food Safety Authority (EFSA) are based on assumptions about how humans interact with this material, stating that ‘typical’ exposures for adults involve only one handling per day for short periods of time (30% of individuals hold thermal paper with more than three fingertips, and >60% allow the paper to touch their palm. Only 11% of the participants we observed were consistent with the EFSA model for time of contact and dermal surface area. Mathematical modeling based on handling times we measured and previously published transfer coefficients, concentrations of BPA in paper, and absorption factors indicate the most conservative estimated intake from handling thermal paper in this population is 51.1 ng/kg/day, similar to EFSA’s estimates of 59 ng/kg/day from dermal exposures. Less conservative estimates, using published data on concentrations in thermal paper and transfer rates to skin, indicate that exposures are likely significantly higher. Based on our observational data, we propose that the current models for estimating dermal BPA exposures are not consistent with normal human behavior and should be reevaluated.

The Panama Papers comprise one of the most recent influential leaks containing detailed information on intermediary companies (such as law firms), offshore entities and company officers, and serve as a valuable source of insight into the operations of (approximately) 214,000 shell companies incorporated in tax havens around the globe over the past half century. Entities and relations in the papers can be used to construct a network that permits, in principle, a systematic and scientific study at scale using techniques developed in the computational social science and network science communities. In this paper, we propose such a study by attempting to quantify and profile the importance of entities. In particular, our research explores whether intermediaries are significantly more influential than offshore entities, and whether different centrality measures lead to varying, or even incompatible, conclusions. Some findings yield conclusions that resemble Simpson’s paradox. We also explore the role that jurisdictions play in determining entity importance.

Many complex physical systems exhibit a rich variety of discrete behavioural modes. Often, the system complexity limits the applicability of standard modelling tools. Hence, understanding the underlying physics of different behaviours and distinguishing between them is challenging. Although traditional machine learning techniques could predict and classify behaviour well, typically they do not provide any meaningful insight into the underlying physics of the system. In this paper we present a novel method for extracting physically meaningful clusters of discrete behaviour from limited experimental observations. This method obtains a set of physically plausible functions that both facilitate behavioural clustering and aid in system understanding. We demonstrate the approach on the V-shaped falling paper system, a new falling paper type system that exhibits four distinct behavioural modes depending on a few morphological parameters. Using just 49 experimental observations, the method discovered a set of candidate functions that distinguish behaviours with an error of 2.04%, while also aiding insight into the physical phenomena driving each behaviour. © 2019 Howison et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

BACKGROUND The lack of information regarding the burden of acute bacterial meningitis in Latin America leads to a reduction in the estimated incidence rates of the disease, and impairs public health decisions on the use and follow-up of preventive interventions, particularly, the evaluation of existing vaccination policies. The use of the real-time PCR in diagnostic routine procedures has resulted in a substantial increase in confirmed bacterial meningitis cases. However, in resource-poor countries, these assays are only available in reference laboratories. Sample transportation to these laboratories is a critical constraint, as it requires specialized, high cost courier services. To overcome this barrier we evaluated the use of FTATM Elute filter paper cards for the conservation and processing of samples under normal environmental conditions, as they would be when transported from remote and under-equipped healthcare facilities to the reference centers. A total of 401 samples received in 2015 as part of Sao Paulo's national surveillance for routine diagnosis were selected for this study. METHODS The sensitivity and specificity of real-time PCR were evaluated using fresh serum and cerebrospinal fluid (CSF) samples processed using our laboratory's standard DNA extraction, and processing the same samples after being dried and stored on FTATM card, and DNA extracted following the manufacturer's instructions. RESULTS The sensitivities for detection of Neisseria meningitidis, Streptococcus pneumoniae, and Haemophilus influenzae from CSF dried and stored on FTATM cards were 98%, 92%, and 100%, respectively, and with serum samples were 73%, 88%, and 100%, respectively. When compared to our laboratory's standard methodology, results showed high concordance, with Kappa index ranges of 0.9877-1.00 for CSF, and 0.8004-1.00 for serum samples. CONCLUSION The use of FTATM cards for CSF and serum conservation and transport represents a rapid, reliable, and cost-effective alternative that will allow obtaining valuable epidemiological information that would otherwise be lost.

This paper provides empirical evidence that individuals substantially revise their stated wealth redistribution preferences after fiscal scandals. The 2016 Panama Papers scandal revealed top-income tax evasion behaviour simultaneously worldwide. The empirical investigation exploits this event as a quasi-natural experiment. I rely on two original datasets, a UK household longitudinal dataset and a survey conducted in 22 European countries. I use a difference-in-differences strategy and find that pro-redistribution statements increased between 2% and 3.3% after the scandal. Responses are heterogeneous and larger for right-wing individuals and low-income individuals. This change in wealth redistribution preferences is likely to have been translated into a slight change in votes. The results suggest an increase in stated voting intentions for the left and a decrease for the right. Complementary estimations reveal that more media coverage and more individuals involved by country increase the magnitude of the response.

The success of a scientist depends on their production of scientific papers and the impact factor of the journal in which they publish. Because most major scientific journals are published in English, success is related to publishing in this language. Currently, 98% of publications in science are written in English, including researchers from English as a Foreign Language (EFL) countries. Colombia is among the countries with the lowest English proficiency in the world. Thus, understanding the disadvantages that Colombians face in publishing is crucial to reducing global inequality in science. This paper quantifies the disadvantages that result from the language hegemony in scientific publishing by examining the additional costs that communicating in English creates in the production of articles. It was identified that more than 90% of the scientific articles published by Colombian researchers are in English, and that publishing in a second language creates additional financial costs to Colombian doctoral students and results in problems with reading comprehension, writing ease and time, and anxiety. Rejection or revision of their articles because of the English grammar was reported by 43.5% of the doctoral students, and 33% elected not to attend international conferences and meetings due to the mandatory use of English in oral presentations. Finally, among the translation/editing services reviewed, the cost per article is between one-quarter and one-half of a doctoral monthly salary in Colombia. Of particular note, we identified a positive correlation between English proficiency and higher socioeconomic origin of the researcher. Overall, this study exhibits the negative consequences of hegemony of English that preserves the global gap in science. Although having a common language is important for science communication, generating multilinguistic alternatives would promote diversity while conserving a communication channel. Such an effort should come from different actors and should not fall solely on EFL researchers.

ObjectivesRecently, the results of two economic evaluations were published both of which seemingly demonstrate the cost-effectiveness of sofosbuvir-based regimens for the treatment of chronic hepatitis C genotype 1 infection in Germany. Both analyses were sponsored by the manufacturer of sofosbuvir and use a different methodology: Whereas one evaluation is based on a conventional cost-utility analysis, the other rests upon the efficiency-frontier method used by the German Institute for Quality and Efficiency in Health Care (IQWiG). The purpose of this study is to reanalysis the results of both economic evaluations in combination.DesignReanalysis of published decision modelling results.SettingPrimary care in Germany.ParticipantsPatients with chronic hepatitis C genotype 1 infection (treatment-naïve and -experienced, cirrhotic and non-cirrhotic).InterventionsSofosbuvir, other anti-hepatitis C virus drugs, and no treatment.Primary and secondary outcome measuresCost per unit of health benefit and cost per quality-adjusted life year.ResultsReanalysis of the results of both economic evaluations in combination reveals an unclear rationale for choosing the selected cost-effectiveness methods as well as a potential publication bias, favoring the product of the manufacturer. Based on the reanalysis, sofosbuvir is not cost-effective in treatment-experienced non-cirrhotic patients, potentially lacks cost-effectiveness in treatment-experienced cirrhotic patients, and is only partially cost-effective in treatment-naïve non-cirrhotic patients. Taken together, these results indicate a lack of cost-effectiveness in three quarters of the German patient population.ConclusionsTwo economic evaluations on sofosbuvir suggest, in combination, that sofosbuvir cannot be considered a cost-effective treatment in three quarters of the German patient population.

Pyocyanin is a toxin produced by Pseudomonas aeruginosa. Here we describe a novel paper-based electrochemical sensor for pyocyanin detection, manufactured with a simple and inexpensive approach based on electrode printing on paper. The resulting sensors constitute an effective electrochemical method to quantify pyocyanin in bacterial cultures without the conventional time consuming pretreatment of the samples. The electrochemical properties of the paper-based sensors were evaluated by ferri/ferrocyanide as a redox mediator, and showed reliable sensing performance. The paper-based sensors readily allow for the determination of pyocyanin in bacterial cultures with high reproducibility, achieving a limit of detection of 95 nM and a sensitivity of 4.30 μA/μM in standard culture media. Compared to the similar commercial ceramic based sensors, it is a 2.3-fold enhanced performance. The simple in-house fabrication of sensors for pyocyanin quantification allows researchers to understand in vitro adaptation of P. aeruginosa infections via rapid screenings of bacterial cultures that otherwise are expensive and time-consuming.

Background The use of filter paper as a simple, inexpensive tool for storage and transportation of blood, ‘Dried Blood Spots’ or Guthrie cards, for diagnostic assays is well-established. In contrast, there are a paucity of diagnostic evaluations of dried cerebrospinal fluid (CSF) spots. These have potential applications in low-resource settings, such as Laos, where laboratory facilities for central nervous system (CNS) diagnostics are only available in Vientiane. In Laos, a major cause of CNS infection is Japanese encephalitis virus (JEV). We aimed to develop a dried CSF spot protocol and to evaluate its diagnostic performance using the World Health Organisation recommended anti-JEV IgM antibody capture enzyme-linked immunosorbent assay (JEV MAC-ELISA). Methodology and Principal Findings Sample volumes, spotting techniques and filter paper type were evaluated using a CSF-substitute of anti-JEV IgM positive serum diluted in Phosphate Buffer Solution (PBS) to end-limits of detection by JEV MAC-ELISA. A conventional protocol, involving eluting one paper punch in 200μl PBS, did not detect the end-dilution, nor did multiple punches utilising diverse spotting techniques. However, pre-cut filter paper enabled saturation with five times the volume of CSF-substitute, sufficiently improving sensitivity to detect the end-dilution. The diagnostic accuracy of this optimised protocol was compared with routine, neat CSF in a pilot, retrospective study of JEV MAC-ELISA on consecutive CSF samples, collected 2009–15, from three Lao hospitals. In comparison to neat CSF, 132 CSF samples stored as dried CSF spots for one month at 25–30°C showed 81.6% (65.7–92.3 95%CI) positive agreement, 96.8% (91.0–99.3 95%CI) negative agreement, with a kappa coefficient of 0.81 (0.70–0.92 95%CI). Conclusions/Significance The novel design of pre-cut filter paper saturated with CSF could provide a useful tool for JEV diagnostics in settings with limited laboratory access. It has the potential to improve national JEV surveillance and inform vaccination policies. The saturation of filter paper has potential use in the wider context of pathogen detection, including dried spots for detecting other analytes in CSF, and other body fluids., Author Summary Japanese encephalitis virus infection is widespread in Asia, and primarily affects children in poor, rural areas. The virus spreads to the brain and spinal cord resulting in significant death and disability. Diagnosis requires testing for the immune response ‘antibody’ specific to Japanese encephalitis virus in the cerebrospinal fluid that surrounds the brain and spinal cord. However, in most areas where the infection occurs there are no laboratory facilities. In the absence of laboratory diagnosis, we have poor knowledge of the extent of the problem in these areas. Dried blood spots on filter paper have been used widely for many years as simple, cost-effective tools for transporting samples for testing. However, there have been few attempts at using dried cerebrospinal fluid spots. We developed a technique for using dried spots to store and test cerebrospinal fluid for antibodies to Japanese encephalitis virus. We compared the results of dried spots with routine neat cerebrospinal fluid in 132 patient samples, and demonstrated excellent agreement between the two tests. This novel method for saturating dried cerebrospinal fluid spots has the potential to enhance our knowledge of Japanese encephalitis virus epidemiology, and inform health policies where they are most needed. It could also be transferred for use in diagnosing other infectious diseases, including using other body fluid samples.

The cost of specialized scientific equipment can be high and with limited funding resources, researchers and students are often unable to access or purchase the ideal equipment for their projects. In the fields of materials science and mechanical engineering, fundamental equipment such as tensile testing devices can cost tens to hundreds of thousands of dollars. While a research lab often has access to a large-scale testing machine suitable for conventional samples, loading devices for meso- and micro-scale samples for in-situ testing with the myriad of microscopy tools are often hard to source and cost prohibitive. Open-source software has allowed for great strides in the reduction of costs associated with software development and open-source hardware and additive manufacturing have the potential to similarly reduce the costs of scientific equipment and increase the accessibility of scientific research. To investigate the feasibility of open-source hardware, a micro-tensile tester was designed with a freely accessible computer-aided design package and manufactured with a desktop 3D-printer and off-the-shelf components. To our knowledge this is one of the first demonstrations of a tensile tester with additively manufactured components for scientific research. The capabilities of the tensile tester were demonstrated by investigating the mechanical properties of Graphene Oxide (GO) paper and thin films. A 3D printed tensile tester was successfully used in conjunction with an atomic force microscope to provide one of the first quantitative measurements of GO thin film buckling under compression. The tensile tester was also used in conjunction with an atomic force microscope to observe the change in surface topology of a GO paper in response to increasing tensile strain. No significant change in surface topology was observed in contrast to prior hypotheses from the literature. Based on this result obtained with the new open source tensile stage we propose an alternative hypothesis we term 'superlamellae consolidation' to explain the initial deformation of GO paper. The additively manufactured tensile tester tested represents cost savings of >99% compared to commercial solutions in its class and offers simple customization. However, continued development is needed for the tensile tester presented here to approach the technical specifications achievable with commercial solutions.

Before organizing mixed-mode data collection for the self-administered questionnaire of the Belgian Health Interview Survey, measurement effects between the paper-and-pencil and the web-based questionnaire were evaluated. A two-period cross-over study was organized with a sample of 149 employees of two Belgian research institutes (age range 22-62 years, 72% female). Measurement agreement was assessed for a diverse range of health indicators related to general health, mental and psychosocial health, health behaviors and prevention with kappa coefficients and intraclass correlation (ICC). The quality of the data collected by both modes was evaluated by quantifying the missing, 'don't know' and inconsistent values and data entry mistakes. Good to very good agreement was found for all categorical indicators with kappa coefficients superior to 0.60, except for two mental and psychosocial health indicators namely the presence of a sleeping disorder and of a depressive disorder (kappa≥0.50). For the continuous indicators high to acceptable agreement was observed with ICC superior to 0.70. Inconsistent answers and data-entry mistakes were only occurring in the paper-and-pencil mode. There were no less missing values in the web-based mode compared to the paper-and-pencil mode. The study supports the idea that web-based modes provide, in general, equal responses to paper-and-pencil modes. However, health indicators based upon factual and objective items tend to have higher measurement agreement than indicators requiring an assessment of personal subjective feelings. A web-based mode greatly facilitates the data-entry process and guides the completing of a questionnaire. However, item non-response was not positively affected. ispartof: PLOS ONE vol:13 issue:5 ispartof: location:United States status: published

BackgroundMost research manuscripts are not accepted for publication on first submission. A major part of the resubmission process is reformatting to another journal's specific requirements, a process separate from revising the scientific content. There has been little research to understand the magnitude of the burden imposed by the current resubmission process.MethodsWe analyzed original research article submission requirements from twelve randomly selected journals in each of eight scientific and clinical focus areas from the InCites Journal Citation Reports database. From the 96 journals selected, we randomly identified three recently published manuscripts and sent surveys to those first and/or corresponding authors (288 total) to solicit information on time spent reformatting resubmissions and opinions on the process.FindingsThere was significant variation in manuscript submission requirements for journals within the same scientific focus and only 4% of journals offered a fully format-free initial submission. Of 203 authors responding (71.5% response rate), only 11.8% expressed satisfaction with the resubmission process and 91% desired reforming the current system. Time spent on reformatting delays most publications by at least two weeks and by over three months in about 20% of manuscripts. The effort to comply with submission requirements has significant global economic burden, estimated at over $1.1 billion dollars annually when accounting for a research team's time.InterpretationWe demonstrate that there is significant resource utilization associated with resubmitting manuscripts, heretofore not properly quantified. The vast majority of authors are not satisfied with the current process. Addressing these issues by reconciling reformatting requirements among journals or adopting a universal format-free initial submission policy would help resolve a major subject for the scientific research community and provide more efficient dissemination of findings.

India has the highest burden of Tuberculosis (TB) and multidrug-resistant TB (MDR-TB) worldwide. Innovative technology is the need of the hour to identify these cases that remain either undiagnosed or inadequately diagnosed due to the unavailability of appropriate tools at primary healthcare settings. We developed and evaluated 3 kits, namely ‘TB Detect’ (containing BioFM-Filter device), ‘TB Concentration and Transport’ (containing Trans-Filter device) and ‘TB DNA Extraction’ kits. These kits enable bio-safe equipment-free concentration of sputum on filters and improved fluorescence microscopy at primary healthcare centres, ambient temperature transport of dried inactivated sputum filters to central laboratories and molecular detection of drug resistance by PCR and DNA sequencing (Mol-DST). In a 2-site evaluation (n = 1190 sputum specimens) on presumptive TB patients, BioFM-Filter smear exhibited a significant increase in positivity of 7% and 4% over ZN smear and LED-FM smear (p

Early industrialization and the development of cheap production processes for paper have led to an exponential accumulation of paper-based documents during the last two centuries. Archives and libraries harbor vast amounts of ancient and modern documents and have to undertake extensive endeavors to protect them from abiotic and biotic deterioration. While services for mechanical preservation such as ex post de-acidification of historic documents are already commercially available, the possibilities for long-term protection of paper-based documents against fungal attack (apart from temperature and humidity control) are very limited. Novel processes for mechanical enhancement of damaged cellulosic documents use Ionic Liquids (IL) as essential process components. With some of these ILs having azole-functionalities similar to well-known fungicides such as Clotrimazole, the possibility of antifungal activities of these ILs was proposed but has not yet been experimentally confirmed.We evaluated the potency of four ILs with potential application in paper restoration for suppression of fungal growth on five relevant paper-infesting molds. The results revealed a general antifungal activity of all ILs, which increased with the size of the non-polar group. Physiological experiments and ultimate elemental analysis allowed to determine the minimal inhibitory concentration of each IL as well as the residual IL concentration in process-treated paper. These results provide valuable guidelines for IL-applications in paper restoration processes with antifungal activity as an added benefit. With azoles remaining in the paper after the process, simultaneous repair and biotic protection in treated documents could be facilitated.

PurposeThe aim of this experimental study was to investigate whether paper-and-pencil and computerized surveys administered in the school setting yield equivalent data quality indicators and risk behavior prevalence estimates.MethodsData were drawn from the European School Survey Project on Alcohol and Other Drugs (ESPAD®) carried out in Italy to monitor drug, alcohol, tobacco use and other risk-behaviors among Italian high school students aged 15-19 years. A sub-sample of schools was recruited for the study (1673 pupils). For each school, two entire randomly selected courses (from the first to the fifth grade) participated and were assigned randomly to the self-administered paper-and-pencil (N = 811) or computerized survey (N = 862). Differences in data quality were assessed using the following indicators: questionnaire completeness (missing gender and/or 50% of missing answers) and internal consistency (repetitive extreme response patterns). Separate logistic regression models were used to estimate the mode effect on the reporting of each risk behavior, controlling for gender and age. Finally, the prevalence estimates of the experimental study were compared to the results of the national ESPAD® study.ResultsThe computerized administration mode produced a higher proportion of invalid questionnaires, but the prevalence estimates generated from responses to the paper-and-pencil and computerized surveys were generally equivalent. Nevertheless, comparing these results with those of the national ESPAD® study, some differences in the prevalence rates were found.ConclusionsThe findings suggest that in a proctored school setting, the computerized survey mode yields almost the same results as the paper-and-pencil mode. However, because of the reliance on existing informatics facilities until when all schools in the country will be sufficiently equipped for the computerized data collection, they should be given the opportunity to choose between paper-and-pencil and computerized survey modes, in order to avoid a possible selection bias.

The UK is one of the largest funders of health research in the world, but little is known about how health funding is spent. Our study explores whether major UK public and charitable health research funders support the research of UK-based scientists producing the most highly-cited research. To address this question, we searched for UK-based authors of peer-reviewed papers that were published between January 2006 and February 2018 and received over 1000 citations in Scopus. We explored whether these authors have held a grant from the National Institute for Health Research (NIHR), the Medical Research Council (MRC) and the Wellcome Trust and compared the results with UK-based researchers who serve currently on the boards of these bodies. From the 1,370 papers relevant to medical, biomedical, life and health sciences with more than 1000 citations in the period examined, we identified 223 individuals from a UK institution at the time of publication who were either first/last or single authors. Of those, 164 are still in UK academic institutions, while 59 are not currently in UK academia (have left the country, are retired, or work in other sectors). Of the 164 individuals, only 59 (36%; 95% CI: 29-43%) currently hold an active grant from one of the three funders. Only 79 (48%; 95% CI: 41-56%) have held an active grant from any of the three funders between 2006-2017. Conversely, 457 of the 664 board members of MRC, Wellcome Trust, and NIHR (69%; 95% CI: 65-72%) have held an active grant in the same period by any of these funders. Only 7 out of 655 board members (1.1%) were first, last or single authors of an extremely highly-cited paper.\ud \ud There are many reasons why the majority of the most influential UK authors do not hold a grant from the country’s major public and charitable funding bodies. Nevertheless, the results are worrisome and subscribe to similar patterns shown in the US. We discuss possible implications and suggest ways forward.

We propose to use Twitter data as social-spatial sensors. This study deals with the question whether research papers on certain diseases are perceived by people in regions (worldwide) that are especially concerned by these diseases. Since (some) Twitter data contain location information, it is possible to spatially map the activity of Twitter users referring to certain papers (e.g., dealing with tuberculosis). The resulting maps reveal whether heavy activity on Twitter is correlated with large numbers of people having certain diseases. In this study, we focus on tuberculosis, human immunodeficiency virus (HIV), and malaria, since the World Health Organization ranks these diseases as the top three causes of death worldwide by a single infectious agent. The results of the social-spatial Twitter maps (and additionally performed regression models) reveal the usefulness of the proposed sensor approach. One receives an impression of how research papers on the diseases have been perceived by people in regions that are especially concerned by these diseases. Our study demonstrates a promising approach for using Twitter data for research evaluation purposes beyond simple counting of tweets.