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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.

Social interactions have large effects on individual physiology and fitness. In the immediate sense, social stimuli are often highly salient and engaging. Over longer time scales, competitive interactions often lead to distinct social ranks and differences in physiology and behavior. Understanding how initial responses lead to longer-term effects of social interactions requires examining the changes in responses over time. Here we examined the effects of social interactions on transcriptomic signatures at two times, at the end of a 45-minute interaction and 4 hours later, in female Polistes fuscatus paper wasp foundresses. Female P. fuscatus have variable facial patterns that are used for visual individual recognition, so we separately examined the transcriptional dynamics in the optic lobe and the non-visual brain. Results demonstrate much stronger transcriptional responses to social interactions in the non-visual brain compared to the optic lobe. Differentially regulated genes in response to social interactions are enriched for memory-related transcripts. Comparisons between winners and losers of the encounters revealed similar overall transcriptional profiles at the end of an interaction, which significantly diverged over the course of 4 hours, with losers showing changes in expression levels of genes associated with aggression and reproduction in paper wasps. On nests, subordinate foundresses are less aggressive, do more foraging and lay fewer eggs compared to dominant foundresses and we find losers shift expression of many genes in the non-visual brain, including vitellogenin, related to aggression, worker behavior, and reproduction within hours of losing an encounter. These results highlight the early neurogenomic changes that likely contribute to behavioral and physiological effects of social status changes in a social insect., Author summary Aggressive interactions often create inequalities–some individuals win while others lose. Winning versus losing can lead to large physiological differences between individuals, including different neurogenomic profiles between winners and losers. How this information about contest outcome leads to distinct neurogenomic profiles is poorly understood. Here we examine gene expression in response to aggressive social encounters in paper wasps, which naturally form dominance hierarchies on their nests in the wild. Shortly following encounters winners and losers have similar expression profiles, likely because similar mechanisms are engaged by social experiences. Four hours later, we find divergent neurogenomic profiles between winners and losers, with losers showing larger shifts in expression compared to winners. Many of the most dynamically expressed genes have been previously associated with dominance and caste differences in paper wasps showing how a single interaction can engage many of the same genomic networks that are involved in mediating more dramatic differences in queen-worker behavioral differences are also involved in responses shortly following social interactions.

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.

Various data sharing platforms are being developed to enhance the sharing of cohort data by addressing the fragmented state of data storage and access systems. However, policy challenges in several domains remain unresolved. The euCanSHare workshop was organized to identify and discuss these challenges and to set the future research agenda. Concerns over the multiplicity and long-term sustainability of platforms, lack of resources, access of commercial parties to medical data, credit and recognition mechanisms in academia and the organization of data access committees are outlined. Within these areas, solutions need to be devised to ensure an optimal functioning of platforms.

Objective To survey the knowledge, attitude, and practices of Vietnamese pharmacists regarding the COVID-19 pandemic. Method This cross-sectional, paper-based study was conducted from June to August 2020. A validated questionnaire (Cronbach’s alpha = 0.84) was used to interview 1,023 pharmacists in nine provinces of Vietnam. Analysis of covariance was employed to identify factors associated with the knowledge of pharmacists. The best model was chosen by using the Bayesian Model Averaging method in R software version 4.0.4. Results The mean knowledge score was 12.02 ± 1.64 (range: 6–15), which indicated that 93.4% of pharmacists had good knowledge of COVID-19. There was no difference in the average score between males and females (p > 0.05). The multivariate linear regression model revealed that the knowledge was significantly associated with pharmacists’ age, education level, and residence (p < 0.001). About attitude and practices, pharmacists daily sought and updated information on the COVID-19 pandemic through mass media and the internet (social network and online newspapers). Nearly 48% of them conceded that they communicated with customers when at least one person did not wear a face mask at the time of the COVID-19 outbreak. At medicine outlets, many measures were applied to protect pharmacists and customers, such as equipping pharmacists with face masks and hand sanitizers (95.0%), using glass shields (83.0%), and maintaining at least one-meter distance between two people (85.2%). Conclusion The pharmacists’ knowledge of COVID-19 transmission, symptoms, and prevention was good. Many useful measures against the spread of this perilous virus were applied in medicine outlets. However, pharmacists should restrict forgetting to wear face masks in communication with medicine purchasers. The government and health agencies should have practical remedies to reduce the significant differences in the COVID-19 knowledge of pharmacists among provinces and education-level groups.

Background In 2005, Bangladesh, India and Nepal agreed to eliminate visceral leishmaniasis (VL) as a public health problem. The approach to this was through improved case detection and treatment, and controlling transmission by the sand fly vector Phlebotomus argentipes, with indoor residual spraying (IRS) of insecticide. Initially, India applied DDT with stirrup pumps for IRS, however, this did not reduce transmission. After 2015 onwards, the pyrethroid alpha-cypermethrin was applied with compression pumps, and entomological surveillance was initiated in 2016. Methods Eight sentinel sites were established in the Indian states of Bihar, Jharkhand and West Bengal. IRS coverage was monitored by household survey, quality of insecticide application was measured by HPLC, presence and abundance of the VL vector was monitored by CDC light traps, insecticide resistance was measured with WHO diagnostic assays and case incidence was determined from the VL case register KAMIS. Results Complete treatment of houses with IRS increased across all sites from 57% in 2016 to 70% of houses in 2019, rising to >80% if partial house IRS coverage is included (except West Bengal). The quality of insecticide application has improved compared to previous studies, average doses of insecticide on filters papers ranged from 1.52 times the target dose of 25mg/m2 alpha-cypermethrin in 2019 to 1.67 times in 2018. Resistance to DDT has continued to increase, but the vector was not resistant to carbamates, organophosphates or pyrethroids. The annual and seasonal abundance of P. argentipes declined between 2016 to 2019 with an overall infection rate of 0.03%. This was associated with a decline in VL incidence for the blocks represented by the sentinel sites from 1.16 per 10,000 population in 2016 to 0.51 per 10,000 in 2019. Conclusion Through effective case detection and management reducing the infection reservoirs for P. argentipes in the human population combined with IRS keeping P. argentipes abundance and infectivity low has reduced VL transmission. This combination of effective case management and vector control has now brought India within reach of the VL elimination targets., Author summary Visceral Leishmaniasis (VL), also known as kala-azar, is a major parasitic disease in South Asia (Indian subcontinent), with 85% of the disease incidence in India. Historically VL had been controlled and almost eliminated with Indoor Residual Spraying (IRS) using dichlorodiphenyltrichloroethane (DDT). However, reinitiating this approach in 2015 failed due to high insecticide resistance in the sand fly vector and poor IRS quality, meaning that VL elimination targets were not met. To improve this the National Vector Borne Disease Control Programme changed to an effective insecticide, alpha-cypermethrin and altered the mode of application to compression pumps. Sentinel sites were established to monitor the entomological indicators, these showed the positive impact of these changes from 2016 to 2019. During this period the overall incidence of disease has decreased, and India is now on track to reach it’s target incidence for VL of less than 1/1000 people at the sub-district (block) level.

The highly contagious nature of SARS-CoV-2 has led to several studies on the transmission of the virus. A little studied potential fomite of great concern in the community is currency, which has been shown to harbor microbial pathogens in several studies. Since the onset of the COVID-19 pandemic, many businesses in the United States have limited the use of banknotes in favor of credit cards. However, SARS-CoV-2 has shown greater stability on plastic in several studies. Herein, the stability of SARS-CoV-2 at room temperature on banknotes, money cards and coins was investigated. In vitro studies with live virus suggested SARS-CoV-2 was highly unstable on banknotes, showing an initial rapid reduction in viable virus and no viral detection by 24 hours. In contrast, SARS-CoV-2 displayed increased stability on money cards with live virus detected after 48 hours. Environmental swabbing of currency and money cards on and near the campus of Brigham Young University supported these results, with no detection of SARS-CoV-2 RNA on banknotes, and a low level on money cards. However, no viable virus was detected on either. These preliminary results suggest that the use of money cards over banknotes in order to slow the spread of this virus may be ill-advised. These findings should be investigated further through larger environmental studies involving more locations.

Since the innovation of our new half-piece elastometric respirator, this type of filtering facepiece respirator (FFR) has been used widely in Thailand. Decontamination methods including ultraviolet C (UVC) germicidal irradiation and 70% alcohol have been implemented to decontaminate these respirators. We then examined the inactivation potential of different decontamination processes on porcine epidemic diarrhea virus (PEDV) and numerous bacterial strains, most of which were skin-derived. To enable rigorous integrity of the masks after repeated decontamination processes, fit tests by the Bitrex test, tensile strength and elongation at break were also evaluated. Our results showed that UVC irradiation at a dose of 3 J/cm2 can eradicate bacteria after 60 min and viruses after 10 min. No fungi were found on the mask surface before decontamination. The good fit test results, tensile strength and elongation at break were still maintained after multiple cycles of decontamination. No evidence of physical degradation was found by gross visual inspection. Alcohol (70%) is also an easy and effective way to eradicate microorganisms on respirators. As the current pandemic is expected to continue for months to years, the need to supply adequate reserves of personnel protective equipment (PPE) and develop effective PPE reprocessing methods is crucial. Our studies demonstrated that the novel silicone mask can be safely reprocessed and decontaminated for many cycles by UVC irradiation, which will help ameliorate the shortage of important protective devices in the COVID-19 pandemic era.

Acknowledgements: We thank Veronica Phillips, Assistant Librarian, University of Cambridge Medical Library, for her help developing the search strategy., Background Introduction of risk stratification within population-based cancer screening programmes has the potential to optimise resource allocation by targeting screening towards members of the population who will benefit from it most. Endorsement from healthcare professionals is necessary to facilitate successful development and implementation of risk-stratified interventions. Therefore, this review aims to explore whether using risk stratification within population-based cancer screening programmes is acceptable to healthcare professionals and to identify any requirements for successful implementation. Methods We searched four electronic databases from January 2010 to October 2021 for quantitative, qualitative, or primary mixed methods studies reporting healthcare professional and/or other stakeholder opinions on acceptability of risk-stratified population-based cancer screening. Quality of the included studies was assessed using the Mixed Methods Appraisal Tool. Data were analysed using the Joanna Briggs Institute convergent integrated approach to mixed methods analysis and mapped onto the Consolidated Framework for Implementation Research using a ‘best fit’ approach. PROSPERO record CRD42021286667. Results A total of 12,039 papers were identified through the literature search and seven papers were included in the review, six in the context of breast cancer screening and one considering screening for ovarian cancer. Risk stratification was broadly considered acceptable, with the findings covering all five domains of the framework: intervention characteristics, outer setting, inner setting, characteristics of individuals, and process. Across these five domains, key areas that were identified as needing further consideration to support implementation were: a need for greater evidence, particularly for de-intensifying screening; resource limitations; need for staff training and clear communication; and the importance of public involvement. Conclusions Risk stratification of population-based cancer screening programmes is largely acceptable to healthcare professionals, but support and training will be required to successfully facilitate implementation. Future research should focus on strengthening the evidence base for risk stratification, particularly in relation to reducing screening frequency among low-risk cohorts and the acceptability of this approach across different cancer types.

Background Neglected tropical diseases (NTDs) primarily affect the poorest populations, often living in remote, rural areas, urban slums or conflict zones. Arboviruses are a significant NTD category spread by mosquitoes. Dengue, Chikungunya, and Zika are three arboviruses that affect a large proportion of the population in Latin and South America. The clinical diagnosis of these arboviral diseases is a difficult task due to the concurrent circulation of several arboviruses which present similar symptoms, inaccurate serologic tests resulting from cross-reaction and co-infection with other arboviruses. Objective The goal of this paper is to present evidence on the state of the art of studies investigating the automatic classification of arboviral diseases to support clinical diagnosis based on Machine Learning (ML) and Deep Learning (DL) models. Method We carried out a Systematic Literature Review (SLR) in which Google Scholar was searched to identify key papers on the topic. From an initial 963 records (956 from string-based search and seven from a single backward snowballing procedure), only 15 relevant papers were identified. Results Results show that current research is focused on the binary classification of Dengue, primarily using tree-based ML algorithms. Only one paper was identified using DL. Five papers presented solutions for multi-class problems, covering Dengue (and its variants) and Chikungunya. No papers were identified that investigated models to differentiate between Dengue, Chikungunya, and Zika. Conclusions The use of an efficient clinical decision support system for arboviral diseases can improve the quality of the entire clinical process, thus increasing the accuracy of the diagnosis and the associated treatment. It should help physicians in their decision-making process and, consequently, improve the use of resources and the patient’s quality of life., Author summary Neglected tropical diseases (NTDs) primarily affect the poorest populations, often living in remote, rural areas, urban slums or conflict zones. Arboviruses are a significant NTD category spread by mosquitoes. Dengue, Chikungunya, and Zika are three arboviruses that affect a large proportion of the population in Latin and South America. The clinical diagnosis of these arboviral diseases is a difficult task due to the concurrent circulation of several arboviruses which present similar symptoms and, sometimes, inaccurate test results. In this paper, we present the state of the art of studies investigating the automatic classification of arboviral diseases based on Machine Learning (ML) and Deep Learning (DL) models. Results show that current research is focused on the classification of Dengue, primarily using tree-based ML algorithms. The use of an efficient clinical decision support system for arboviral diseases can improve the quality of the entire clinical process, thus increasing the accuracy of the diagnosis and the associated treatment. It should help physicians in their decision-making process and, consequently, improve the use of resources and the patient’s quality of life.

Extensive research shows that residential segregation has severe health consequences for racial and ethnic minorities. Most research to date has operationalized segregation in terms of either poverty or race/ethnicity rather than a synergy of these factors. A novel version of the Index of Concentration at the Extremes (ICERace-Income) specifically assesses racialized economic segregation in terms of spatial concentrations of racial and economic privilege (e.g., wealthy white people) versus disadvantage (e.g., poor Black people) within a given area. This multidimensional measure advances a more comprehensive understanding of residential segregation and its consequences for racial and ethnic minorities. The aim of this paper is to critically review the evidence on the association between ICERace-Income and health outcomes. We implemented the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to conduct a rigorous search of academic databases for papers linking ICERace-Income with health. Twenty articles were included in the review. Studies focused on the association of ICERace-Income with adverse birth outcomes, cancer, premature and all-cause mortality, and communicable diseases. Most of the evidence indicates a strong association between ICERace-Income and each health outcome, underscoring income as a key mechanism by which segregation produces health inequality along racial and ethnic lines. Two of the reviewed studies examined racial disparities in comorbidities and health care access as potential explanatory factors underlying this relationship. We discuss our findings in the context of the extant literature on segregation and health and propose new directions for future research and applications of the ICERace-Income measure.

Background & methods National protests in the summer of 2020 drew attention to the significant presence of police in marginalized communities. Recent social movements have called for substantial police reforms, including “defunding the police,” a phrase originating from a larger, historical abolition movement advocating that public investments be redirected away from the criminal justice system and into social services and health care. Although research has demonstrated the expansive role of police to respond a broad range of social problems and health emergencies, existing research has yet to fully explore the capacity for health insurance policy to influence rates of arrest in the population. To fill this gap, we examine the potential effect of Medicaid expansion under the Affordable Care Act (ACA) on arrests in 3,035 U.S. counties. We compare county-level arrests using FBI Uniform Crime Reporting (UCR) Program Data before and after Medicaid expansion in 2014–2016, relative to counties in non-expansion states. We use difference-in-differences (DID) models to estimate the change in arrests following Medicaid expansion for overall arrests, and violent, drug, and low-level arrests. Results Police arrests significantly declined following the expansion of Medicaid under the ACA. Medicaid expansion produced a 20–32% negative difference in overall arrests rates in the first three years. We observe the largest negative differences for drug arrests: we find a 25–41% negative difference in drug arrests in the three years following Medicaid expansion, compared to non-expansion counties. We observe a 19–29% negative difference in arrests for violence in the three years after Medicaid expansion, and a decrease in low-level arrests between 24–28% in expansion counties compared to non-expansion counties. Our main results for drug arrests are robust to multiple sensitivity analyses, including a state-level model. Conclusions Evidence in this paper suggests that expanded Medicaid insurance reduced police arrests, particularly drug-related arrests. Combined with research showing the harmful health consequences of chronic policing in disadvantaged communities, greater insurance coverage creates new avenues for individuals to seek care, receive treatment, and avoid criminalization. As police reform is high on the agenda at the local, state, and federal level, our paper supports the perspective that broad health policy reforms can meaningfully reduce contact with the criminal justice system under historic conditions of mass criminalization.

Background The ligaments in the knee are prone to injury especially during dynamic activities. The resulting instability can have a profound impact on a patient’s daily activities and functional capacity. Musculoskeletal knee modelling provides a non-invasive tool for investigating ligament force-strain behaviour in various dynamic scenarios, as well as potentially complementing existing pre-planning tools to optimise surgical reconstructions. However, despite the development and validation of many musculoskeletal knee models, the effect of modelling parameters on ligament mechanics has not yet been systematically reviewed. Objectives This systematic review aimed to investigate the results of the most recent studies using musculoskeletal modelling techniques to create models of the native knee joint, focusing on ligament mechanics and modelling parameters in various simulated movements. Data sources PubMed, ScienceDirect, Google Scholar, and IEEE Xplore. Eligibility criteria for selecting studies Databases were searched for articles containing any numerical ligament strain or force data on the intact, ACL-deficient, PCL-deficient, or lateral extra-articular reconstructed (LER) knee joints. The studies had to derive these results from musculoskeletal modelling methods. The dates of the publications were between 1 January 1995 and 30 November 2021. Method A customised data extraction form was created to extract each selected study’s critical musculoskeletal model development parameters. Specific parameters of the musculoskeletal knee model development used in each eligible study were independently extracted, including the (1) musculoskeletal model definition (i.e., software used for modelling, knee type, source of geometry, the inclusion of cartilage and menisci, and articulating joints and joint boundary conditions (i.e., number of degrees of freedom (DoF), subjects, type of activity, collected data and type of simulation)), (2) specifically ligaments modelling techniques (i.e., ligament bundles, attachment points, pathway, wrapping surfaces and ligament material properties such as stiffness and reference length), (3) sensitivity analysis, (4) validation approaches, (5) predicted ligament mechanics (i.e., force, length or strain) and (6) clinical applications if available. The eligible papers were then discussed quantitatively and qualitatively with respect to the above parameters. Results and discussion From the 1004 articles retrieved by the initial electronic search, only 25 met all inclusion criteria. The results obtained by aggregating data reported in the eligible studies indicate that considerable variability in the predicted ligament mechanics is caused by differences in geometry, boundary conditions and ligament modelling parameters. Conclusion This systematic review revealed that there is currently a lack of consensus on knee ligament mechanics. Despite this lack of consensus, some papers highlight the potential of developing translational tools using musculoskeletal modelling. Greater consistency in model design, incorporation of sensitivity assessment of the model outcomes and more rigorous validation methods should lead to better agreement in predictions for ligament mechanics between studies. The resulting confidence in the musculoskeletal model outputs may lead to the development of clinical tools that could be used for patient-specific treatments.

This study assesses the practices and views of Scottish dairy farmers relating to pasture-based and indoor systems. There are the debates about the environmental, economic and animal welfare implications of these systems. Indoor dairy farming is a contentious practice among the public. While this controversy is sometimes represented as a lack of public understanding, there is a need for more research on farmers’ views to facilitate discussion in the industry. A survey was posted to 909 dairy farmers in Scotland with questions about their grazing practices and attitudes to grazing and indoor systems. 254 surveys were completed, online and in paper form. There was a 26% response rate to the paper version of the survey. The results showed that 19% of respondents housed some or all the cows all year-round. 68% agreed or strongly agreed that cows should graze for part of the year and 51% agreed or strongly agreed that welfare was better if cows grazed for part of the year. These views coexisted with the view that management was more important than the type of system for determining profitability or welfare outcomes (83% and 82% strongly agree or agree respectively). Respondents whose system involved grazing and respondents who had spent longer in farming were moderately more likely to agree that cows should have access to pasture, and slightly less likely to agree that management was more important than system for determining welfare outcomes. The results indicate that the picture is more complicated than the public rejecting indoor dairy farming and those in the industry accepting it. The results showed that a majority preference for cows to graze co-existed with the view that management was more important than system. In terms of industry and policy recommendations, the research suggests that measures should be taken to safeguard farmers’ ability to graze through for instance research and advisory support on grazing; ensuring different systems are not penalised in the development of dairy sector environmental measures and recommendations; and potentially supply chains that financially rewards farmers for grazing.

Introduction Pure Neural Leprosy (PNL) is a rare clinical form of leprosy in which patients do not present with the classical skin lesions but have a high burden of the disability associated with the disease. Clinical characteristics and follow up of patients in PNL are still poorly described in the literature. Objective This paper aims to describe the clinical, electrophysiological and histopathological characteristics of PNL patients, as well as their evolution after multidrug therapy (MDT). Methods Fifty-two PNL patients were selected. Clinical, nerve conduction studies (NCS), histopathological and anti-PGL-1serology were evaluated. Patients were also assessed monthly during the MDT. At the end of the MDT, all of the patients had a new neurological examination and 44 were submitted to another NCS. Results Paresthesia was the complaint most frequently reported by patients, and in the neurological examination the most common pattern observed was impairment in sensory and motor examination and a mononeuropathy multiplex. Painful nerve enlargement, a classical symptom of leprosy neuropathy, was observed in a minority of patients and in the motor NCS axonal injuries, alone or in combination with demyelinating features, were the most commonly observed. 88% of the patients did not present any leprosy reaction during MDT. There was no statistically significant difference between the neurological examinations, nor the NCS pattern, performed before and after the MDT. Discussion The classical hallmarks of leprosy neuropathy are not always present in PNL making the diagnosis even more challenging. Nerve biopsy is an important tool for PNL diagnosis as it may guide therapeutic decisions. This paper highlights unique characteristics of PNL in the spectrum of leprosy in an attempt to facilitate the diagnosis and management of these patients., Author summary Neuropathy is responsible for most of the disability associated with leprosy disease. The pure neural leprosy (PNL), in spite of being a rare clinical presentation of that, has some singular characteristics that are still poorly studied. In this study, we selected 52 patients at the diagnosis to describe their clinical, neurophysiological and histopathological presentation patterns as well as their evolution during the multidrug therapy (MDT). We confirmed that sensitive symptoms were the most commonly described by PNL patients but neural pain is rare. Also confirmed that mononeuropathy mutiplex was the most common pattern observed at neurological examination and at the nerve conduction studies at the moment of the diagnosis. However we showed that painful nerve enlargement other cardinal signs of leprosy, besides the skin lesions, is not common in this group of patients, There was no statistically significant difference between the neurological examination and NCS performed before and after the MDT.During the MDT88.4% of the patients did not have any leprosy reaction. This may suggest that that MDT was effective in stopping disease progression. Our results highlight the difficulties in the diagnosis of PNL and the progression following MDT in an attempt to prevent further disability in PNL patients.

The aim of this article is to assess both the economic and social value of balneotherapy and spa tourism, being the first paper in carrying out this analysis. The study has been conducted in Maresme, a region of Catalonia, Spain. On the one hand, an Input-Output (IO) model with a Social Accounting Matrix (SAM) has been carried out to assess the economic value. On the other hand, a Cost-Benefit Analysis (CBA) has been used to monetise the social value in this region, taking into account, among other concepts, direct and indirect health profits, given that balneotherapy helps to alleviate various diseases. The results show that whereas the economic multiplier is 1.529 considering the direct and indirect effects and 1.712 taking into account also the induced effects, which are similar to health and medical tourism multipliers, social value generates additional positive value, given that the cost-benefit ratio is 1.858. The theoretical implications of the paper as well as the findings’ implications for policy so as to encourage investments in spa tourism are discussed.

Background Ward-Based Outreach Teams’ (WBOTs) use of mobile technologies can promote better quality and improved health services for populations in low- and middle-income countries. However, the implementation of such systems is fraught with threats to sustainability. Purpose The purpose of this study was to gain a deeper understanding of users’ views and experiences of the implementation of mHealth in a selected sub-district in North West Province, South Africa. Methods The study was qualitative, exploratory and descriptive. Data were collected from community health workers (CHWs) (n = 24) and outreach team leaders (OTLs) (n = 4) who used mobile devices loaded with the Mobenzi application through semi-structured focus group interviews, using an interview guide. Creswell’s stages of thematic analysis were used for data analysis, and codes, categories and themes were validated with the participants. Results Three themes emerged from the findings, namely the transition from a paper-based system to an electronic system; the use of the application; and reverting to paper-based documentation. The findings revealed that WBOTs considered the mHealth application as useful, easy to use, and supportive to their workflow. They experienced some technical challenges and lamented the inaccessibility of technicians. The mobile initiative’s termination caused distress among the participants, especially CHWs who had to revert to paper-based documentation to capture community health data. OTLs were concerned about the quality of health data being captured in the absence of the application. Conclusions The study concluded that community-based health care programmes that use WBOTs and mHealth technologies are essential in strengthening the health care system. WBOTs are facilitators for improving access to health care. Policy-makers and district managers will gain useful insights if they engage application users in discussions regarding future mobile health interventions for household and community-based care.

Background Work to control the gambiense form of human African trypanosomiasis (gHAT), or sleeping sickness, is now directed towards ending transmission of the parasite by 2030. In order to supplement gHAT case-finding and treatment, since 2011 tsetse control has been implemented using Tiny Targets in a number of gHAT foci. As this intervention is extended to new foci, it is vital to understand the costs involved. Costs have already been analysed for the foci of Arua in Uganda and Mandoul in Chad. This paper examines the costs of controlling Glossina palpalis palpalis in the focus of Bonon in Côte d’Ivoire from 2016 to 2017. Methodology/Principal findings Some 2000 targets were placed throughout the main gHAT transmission area of 130 km2 at a density of 14.9 per km2. The average annual cost was USD 0.5 per person protected, USD 31.6 per target deployed of which 12% was the cost of the target itself, or USD 471.2 per km2 protected. Broken down by activity, 54% was for deployment and maintenance of targets, 34% for tsetse surveys/monitoring and 12% for sensitising populations. Conclusions/Significance The cost of tsetse control per km2 of the gHAT focus protected in Bonon was more expensive than in Chad or Uganda, while the cost per km2 treated, that is the area where the targets were actually deployed, was cheaper. Per person protected, the Bonon cost fell between the two, with Uganda cheaper and Chad more expensive. In Bonon, targets were deployed throughout the protected area, because G. p. palpalis was present everywhere, whereas in Chad and Uganda G. fuscipes fuscipes was found only the riverine fringing vegetation. Thus, differences between gHAT foci, in terms of tsetse ecology and human geography, impact on the cost-effectiveness of tsetse control. It also demonstrates the need to take into account both the area treated and protected alongside other impact indicators, such as the cost per person protected., Author summary Sleeping sickness is a fatal disease in Africa caused by trypanosomes transmitted by the bite of infected tsetse flies. The World Health Organization has set the absence of new infections as a goal for 2030. To achieve this, screening and treatment of patients is supplemented by tsetse control. Tiny Targets are small insecticide-impregnated panels of blue cloth and black netting which attract and kill tsetse. To maintain the momentum in these last stages of eliminating the disease, it is important to understand the costs of vector control. This paper presents the results of two years’ cost monitoring in Bonon, an area covering 130 km2, home to 120,000 people. Since 2016, ~2,000 Tiny Targets have been deployed annually at a cost of USD 471 per km2 per year. Bonon is a degraded forested area and a relatively high number of targets was required as tsetse are present throughout. Nevertheless, the cost comes to only USD 0.5 per person protected per year. Compared to operations using Tiny Targets in Uganda and Chad, the cost was higher per km2 protected, reflecting the need to place targets throughout the area, but low per person protected compared to Chad, highlighting the need to use a range of comparators.

Background Coronavirus (COVID-19) has severely impacted lifestyles worldwide. Responses to COVID-19 have intentionally restricted the factors that encourage regular and frequent PA; opportunity, capability and motivation. However, the effects of these restrictions are likely to have differed by gender and age and different intensities of PA. This rapid review builds on previous evidence by synthesising the global impact of COVID-19 on adult PA through specific intensities and types of PA and evaluating this by gender and age. Methods A rapid systematic search of seven electronic databases (PubMed, MEDLINE, CINAHL, SPORTDiscus, Academic Search Complete, APA PsycInfo, and APA PsycArticles) was performed from December 2019 to January 2021. Studies investigating adult change in PA, exercise or sedentary behaviour due to COVID-19 were included. Results From an initial database search identifying 3,863 articles, 66 remained for synthesis after applying eligibility criteria. Results demonstrate decreases among all intensities and types of PA—walking (6 out of 7 papers), moderate-only (5 out of 6 papers), vigorous-only (5 out of 6 papers) and MVPA (4 out of 5 papers); as well as overall PA (14–72% participants reported a decrease). Reflecting that COVID-19 responses were designed to have universal effects, they also achieved whole-society decreases in PA behaviour, accented in older age groups. Conclusion There is a universal need to address the low levels of PA post-COVID-19. The consequences of decreased PA across all intensities has powerful, potentially recoverable, impacts. Universal declines have implications for public health officials and PA advocates for post-COVID-19 initiatives to promote PA.

The design of efficient combination therapies is a difficult key challenge in the treatment of complex diseases such as cancers. The large heterogeneity of cancers and the large number of available drugs renders exhaustive in vivo or even in vitro investigation of possible treatments impractical. In recent years, sophisticated mechanistic, ordinary differential equation-based pathways models that can predict treatment responses at a molecular level have been developed. However, surprisingly little effort has been put into leveraging these models to find novel therapies. In this paper we use for the first time, to our knowledge, a large-scale state-of-the-art pan-cancer signaling pathway model to identify candidates for novel combination therapies to treat individual cancer cell lines from various tissues (e.g., minimizing proliferation while keeping dosage low to avoid adverse side effects) and populations of heterogeneous cancer cell lines (e.g., minimizing the maximum or average proliferation across the cell lines while keeping dosage low). We also show how our method can be used to optimize the drug combinations used in sequential treatment plans—that is, optimized sequences of potentially different drug combinations—providing additional benefits. In order to solve the treatment optimization problems, we combine the Covariance Matrix Adaptation Evolution Strategy (CMA-ES) algorithm with a significantly more scalable sampling scheme for truncated Gaussian distributions, based on a Hamiltonian Monte-Carlo method. These optimization techniques are independent of the signaling pathway model, and can thus be adapted to find treatment candidates for other complex diseases than cancers as well, as long as a suitable predictive model is available., Author summary Combination therapies are a promising approach to counter complex diseases such as cancers. Two key difficulties in the design of effective cancer combination therapies are the large number of available drugs and the heterogeneity of cancers which render exhaustive laboratory studies impractical. In recent years, sophisticated signaling pathway models that can predict responses to combination treatments at a molecular level have been developed. This motivates the question of how one can leverage mechanistic models to identify candidates for novel combination treatments. In this paper we propose a combination treatment optimization framework which employs a large-scale pan-cancer pathway model. We formulate treatment optimization problems for single cell lines and heterogeneous populations of cancer cells. We further investigate sequential treatment plans and combine an existing evolutionary algorithm with an efficient Hamiltonian Monte-Carlo based sampling scheme. During extensive simulation studies our approach identified combination therapies which are predicted to be more effective than conventional treatments. We hope that one day in silico experiments will be used to identify a small set of promising treatment candidates which can then form a starting point for laboratory studies, allowing for an efficient use of limited resources and accelerated discovery of effective therapies.

The analysis of brain-imaging data requires complex and often non-linear transformations to support findings on brain function or pathologies. And yet, recent work has shown that variability in the choices that one makes when analyzing data can lead to quantitatively and qualitatively different results, endangering the trust in conclusions1–3. Even within a given method or analytical technique, numerical instabilities could compromise findings4–7. We instrumented a structural-connectome estimation pipeline with Monte Carlo Arithmetic8, 9, a technique to introduce random noise in floating-point computations, and evaluated the stability of the derived connectomes, their features10, 11, and the impact on a downstream analysis12, 13. The stability of results was found to be highly dependent upon which features of the connectomes were evaluated, and ranged from perfectly stable (i.e. no observed variability across executions) to highly unstable (i.e. the results contained no trustworthy significant information). While the extreme range and variability in results presented here could severely hamper our understanding of brain organization in brain-imaging studies, it also leads to an increase in the reliability of datasets. This paper highlights the potential of leveraging the induced variance in estimates of brain connectivity to reduce the bias in networks alongside increasing the robustness of their applications in the detection or classification of individual differences. This paper demonstrates that stability evaluations are necessary for understanding error and bias inherent to scientific computing, and that they should be a component of typical analytical workflows.

Background During the Coronavirus Disease 2019 (COVID-19) pandemic, the number of consultations and diagnoses in primary care and referrals to specialist care declined substantially compared to prepandemic levels. Beyond deferral of elective non-COVID-19 care by healthcare providers, it is unclear to what extent healthcare avoidance by community-dwelling individuals contributed to this decline in routine healthcare utilisation. Moreover, it is uncertain which specific symptoms were left unheeded by patients and which determinants predispose to healthcare avoidance in the general population. In this cross-sectional study, we assessed prevalence of healthcare avoidance during the pandemic from a patient perspective, including symptoms that were left unheeded, as well as determinants of healthcare avoidance. Methods and findings On April 20, 2020, a paper COVID-19 survey addressing healthcare utilisation, socioeconomic factors, mental and physical health, medication use, and COVID-19–specific symptoms was sent out to 8,732 participants from the population-based Rotterdam Study (response rate 73%). All questionnaires were returned before July 10, 2020. By hand, prevalence of healthcare avoidance was subsequently verified through free text analysis of medical records of general practitioners. Odds ratios (ORs) for avoidance were determined using logistic regression models, adjusted for age, sex, and history of chronic diseases. We found that 1,142 of 5,656 included participants (20.2%) reported having avoided healthcare. Of those, 414 participants (36.3%) reported symptoms that potentially warranted urgent evaluation, including limb weakness (13.6%), palpitations (10.8%), and chest pain (10.2%). Determinants related to avoidance were older age (adjusted OR 1.14 [95% confidence interval (CI) 1.08 to 1.21]), female sex (1.58 [1.38 to 1.82]), low educational level (primary education versus higher vocational/university 1.21 [1.01 to 1.46), poor self-appreciated health (per level decrease 2.00 [1.80 to 2.22]), unemployment (versus employed 2.29 [1.54 to 3.39]), smoking (1.34 [1.08 to 1.65]), concern about contracting COVID-19 (per level increase 1.28 [1.19 to 1.38]) and symptoms of depression (per point increase 1.13 [1.11 to 1.14]) and anxiety (per point increase 1.16 [1.14 to 1.18]). Study limitations included uncertainty about (perceived) severity of the reported symptoms and potentially limited generalisability given the ethnically homogeneous study population. Conclusions In this population-based cross-sectional study, 1 in 5 individuals avoided healthcare during lockdown in the COVID-19 pandemic, often for potentially urgent symptoms. Healthcare avoidance was strongly associated with female sex, fragile self-appreciated health, and high levels of depression and anxiety. These results emphasise the need for targeted public education urging these vulnerable patients to timely seek medical care for their symptoms to mitigate major health consequences., Marije J. Splinter and colleagues assess the prevalence of healthcare avoidance during the COIVD-19 pandemic and investigate related determinants, Author summary Why was this study done? ➢ During the Coronavirus Disease 2019 (COVID-19) pandemic, consultation rates in both primary and specialist care declined compared to prepandemic levels, which can partially be attributed to the postponement or cancellation of elective and nonurgent medical care. ➢ It is unclear to what extent these declines in consultation rates could be related to healthcare avoidance by patients in the general population. ➢ To evaluate the collateral health damage of the COVID-19 pandemic, it is important to not only assess the prevalence of healthcare avoidance, but also for what symptoms healthcare was avoided and which determinants are associated with this behaviour. What did the researchers do and find? ➢ We sent out a paper questionnaire to 8,732 participants of the population-based Rotterdam Study containing several COVID-19–related subjects, such as healthcare utilisation, work status, mental and physical health, and concerns about contracting COVID-19. ➢ About 6,241 participants (73%) returned the questionnaire, of whom 5,656 participants (90.6%) were included in our analyses. We found that 1,142 of them (20.2%) avoided healthcare during the COVID-19 pandemic, often for symptoms that might have needed urgent medical evaluation, such as limb weakness (13.6%), palpitations (10.8%), and chest pain (10.2%). ➢ Determinants that were most strongly associated with healthcare avoidance were female sex, poor self-appreciated health, and high levels of depression and anxiety. What do these findings mean? ➢ The results of this population-based study suggest that healthcare avoidance contributed to the decline in consultation rates during the COVID-19 pandemic. Importantly, our findings suggest that this behaviour may be associated with certain vulnerable groups within the population. ➢ These findings should be interpreted in light of the limitations of this study, which include that the actual severity of the symptoms that were reported by participants is unknown, since they were not medically evaluated when they experienced these symptoms. ➢ The findings of this study can be used to develop policy interventions targeted to vulnerable individuals who may be more likely to exhibit healthcare avoiding behaviours.

Distracted driving behavior is one of the main factors of road accidents. Accurately predicting the risk of driving behavior is of great significance to the active safety of road transportation. The large amount of information collected by the sensors installed on the vehicle can be identified by the algorithm to obtain the distracted driving behavior data, which can be used to predict the driving behavior risk of the vehicle and the area. In this paper, a new neural network named Driving Behavior Risk Prediction Neural Network (DBRPNN) is developed for prediction based on the distracted driving behavior data. The network consists of three modules: the Feature Processing Module, the Memory Module, and the Prediction Module. In this process, attribute data (time in a day, daily driving time, and daily driving mileage) that can reflect external factors and driver statuses, are added to the network to increase the accuracy of the model. We predicted the driving behavior risk of different objects (Vehicle and Area). For the applicability improvement of the model, we further classify the distracted driving behavior categories, and DBRPNN can provide more accurate risk prediction. The results show that compared with traditional models (Classification and Regression Tree, Support Vector Machines, Recurrent Neural Network, and Long Short-Term Memory), DBRPNN has better prediction performance. The method proposed in this paper has been fully verified and may be transplanted into active safety early warning system for more accurate and flexible application.

Background Medicine quality screening devices hold great promise for post-market surveillance (PMS). However, there is little independent evidence on their field utility and usability to inform policy decisions. This pilot study in the Lao PDR tested six devices’ utility and usability in detecting substandard and falsified (SF) medicines. Methodology/principal findings Observational time and motion studies of the inspections by 16 Lao medicine inspectors of 1) the stock of an Evaluation Pharmacy (EP), constructed to resemble a Lao pharmacy, and 2) a sample set of medicines (SSM); were conducted without and with six devices: four handheld spectrometers (two near infrared: MicroPHAZIR RX, NIR-S-G1 & two Raman: Progeny, Truscan RM); one portable mid-infrared spectrometer (4500a), and single-use paper analytical devices (PAD). User experiences were documented by interviews and focus group discussions. Significantly more samples were wrongly categorised as pass/fail with the PAD compared to the other devices in EP inspections (p, Author summary Substandard and falsified (SF) medicines threaten the lives of millions of people, especially where pharmaceutical legislation and regulation are limited. Screening for SF medicines in supply chains (‘post-market surveillance’) by medicine inspectors is crucial but currently relies only on subjective visual inspection of medicines in most countries. Many innovative portable screening technologies now exist and could be key additional assets to the current practice, but none have been extensively evaluated for medicine quality post-market surveillance. We assessed the utility and usability of six screening devices in the hands of Lao medicines inspectors in a pharmacy constructed to resemble a Lao pharmacy. Five spectrometers showed promising accuracies to identify falsified medicines, but difficulties to correctly set them up before running tests were observed. Reading and interpreting colour barcodes of the ‘paper analytical cards’–a lab-on-a-chip test by inspectors were difficult, leading to lower accuracy than with spectrometers. The study suggests that overconfidence in devices may cause harm by reducing inspectors’ investment in visual inspection—a crucial step to identify falsified medicines. Advantages/limitations of the devices are also documented to inform policy.

Introduction Degenerative Cervical Myelopathy (DCM) is a common and disabling condition, with a relatively modest research capacity. In order to accelerate knowledge discovery, the AO Spine RECODE-DCM project has recently established the top priorities for DCM research. Uptake of these priorities within the research community will require their effective dissemination, which can be supported by identifying key opinion leaders (KOLs). In this paper, we aim to identify KOLs using artificial intelligence. We produce and explore a DCM co-authorship network, to characterise researchers’ impact within the research field. Methods Through a bibliometric analysis of 1674 scientific papers in the DCM field, a co-authorship network was created. For each author, statistics about their connections to the co-authorship network (and so the nature of their collaboration) were generated. Using these connectedness statistics, a neural network was used to predict H-Index for each author (as a proxy for research impact). The neural network was retrospectively validated on an unseen author set. Results DCM research is regionally clustered, with strong collaboration across some international borders (e.g., North America) but not others (e.g., Western Europe). In retrospective validation, the neural network achieves a correlation coefficient of 0.86 (p Discussion Analysis of the neural network shows that the nature of collaboration strongly impacts an author’s research visibility, and therefore suitability as a KOL. This also suggests greater collaboration within the DCM field could help to improve both individual research visibility and global synergy.

Grounding systems are critical in safeguarding people and equipment from power system failures. A grounding system’s principal goal is to offer the lowest impedance path for undesired fault current. Optimization of the grounding grid designs is important in satisfying the minimum cost of the grounding system and safeguarding those people who work in the surrounding area of the grounded installations. Currently, there is no systematic guidance or standard for grounding grid designs that include two-layer soil and its effects on grounding grid systems, particularly vertically layered soil. Furthermore, while numerous studies have been conducted on optimization, relatively limited study has been done on the problem of optimizing the grounding grid in two-layer soil, particularly in vertical soil structures. This paper presents the results of optimization for substation grounding systems using the Simulated Annealing (SA) algorithm in different soil conditions which conforms to the safety requirements of the grounding system. Practical features of grounding grids in various soil conditions discussed in this paper (uniform soil, two-layer horizontal soil, and two-layer vertical soil) are considered during problem formulation and solution algorithm. The proposed algorithm’s results show that the number of grid conductors in the X and Y directions (Nx and Ny), as well as vertical rods (Nr), can be optimized from initial numbers of 35% for uniform soil, 57% for horizontal two-layer soil for ρ1> ρ2, and 33% for horizontal two-layer soil for ρ1< ρ2, and 29% for vertical two-layer soil structure. In other words, the proposed technique would be able to utilize square and rectangle-shaped grounding grids with a number of grid conductors and vertical rods to be implemented in uniform, two-layer horizontal and vertical soil structure, depending on the resistivity of the soil layer.

Mathematical models are powerful tools in HIV epidemiology, producing quantitative projections of key indicators such as HIV incidence and prevalence. In order to improve the accuracy of predictions, such models need to incorporate a number of behavioural and biological heterogeneities, especially those related to the sexual network within which HIV transmission occurs. An individual-based model, which explicitly models sexual partnerships, is thus often the most natural type of model to choose. In this paper we present PopART-IBM, a computationally efficient individual-based model capable of simulating 50 years of an HIV epidemic in a large, high-prevalence community in under a minute. We show how the model calibrates within a Bayesian inference framework to detailed age- and sex-stratified data from multiple sources on HIV prevalence, awareness of HIV status, ART status, and viral suppression for an HPTN 071 (PopART) study community in Zambia, and present future projections of HIV prevalence and incidence for this community in the absence of trial intervention., Author summary In this paper we present PopART-IBM, an individual-based model used to simulate HIV transmission in communities in high prevalence settings. We show that PopART-IBM can simulate transmission over a span of decades in a large community in less than a minute. This computational efficiency allows us to calibrate the model within an inference framework, and we show an illustrative example of calibration using an adaptive population Monte Carlo Approximate Bayesian Computation algorithm for a community in Zambia that was part of the HPTN-071 (PopART) trial. We compare the detailed model output to real-world data collected during the trial from this community. Finally, we project how the HIV epidemic would have changed over time in this community if no intervention from the trial had occurred.

Deep brain stimulation (DBS) is a well-established treatment option for a variety of neurological disorders, including Parkinson’s disease and essential tremor. The symptoms of these disorders are known to be associated with pathological synchronous neural activity in the basal ganglia and thalamus. It is hypothesised that DBS acts to desynchronise this activity, leading to an overall reduction in symptoms. Electrodes with multiple independently controllable contacts are a recent development in DBS technology which have the potential to target one or more pathological regions with greater precision, reducing side effects and potentially increasing both the efficacy and efficiency of the treatment. The increased complexity of these systems, however, motivates the need to understand the effects of DBS when applied to multiple regions or neural populations within the brain. On the basis of a theoretical model, our paper addresses the question of how to best apply DBS to multiple neural populations to maximally desynchronise brain activity. Central to this are analytical expressions, which we derive, that predict how the symptom severity should change when stimulation is applied. Using these expressions, we construct a closed-loop DBS strategy describing how stimulation should be delivered to individual contacts using the phases and amplitudes of feedback signals. We simulate our method and compare it against two others found in the literature: coordinated reset and phase-locked stimulation. We also investigate the conditions for which our strategy is expected to yield the most benefit., Author summary In this paper we use computer models of brain tissue to derive an optimal control algorithm for a recently developed new generation of deep brain stimulation (DBS) devices. DBS is a treatment for a variety of neurological disorders including Parkinson’s disease, essential tremor, depression and pain. There is a growing amount of evidence to suggest that delivering stimulation according to feedback from patients, or closed-loop, has the potential to improve the efficacy, efficiency and side effects of the treatment. An important recent development in DBS technology are electrodes with multiple independently controllable contacts and this paper is a theoretical study into the effects of using this new technology. On the basis of a theoretical model, we devise a closed-loop strategy and address the question of how to best apply DBS across multiple contacts to maximally desynchronise neural populations. We demonstrate using numerical simulation that, for the systems we consider, our methods are more effective than two well-known alternatives, namely phase-locked stimulation and coordinated reset. We also predict that the benefits of using multiple contacts should depend strongly on the intrinsic neuronal response. The insights from this work should lead to a better understanding of how to implement and optimise closed-loop multi-contact DBS systems which in turn should lead to more effective and efficient DBS treatments.

Depending on the strategy of "Healthy China", more and more people pay attention to health issues. The integration and development of sports industry and health service industry is an inevitable outcome of industrial transformation and upgrading and healthy life in the new era. Through constructing the evaluation index system of the coupling and coordination development degree between sports industry and health service industry, using entropy evaluation method and coupling and coordination degree model, this paper explore the comprehensive level and coupling and coordination development status of sports industry and health service industry in thirty-one provinces, municipality cities and autonomous regions of China from 2013 to 2017. The results of this paper show that the comprehensive China’s sports industry and health service industry both present an incremental development trend year by year, and are characterized by the distribution of "high in the east and low in the west" in space. The government’s policy support provides superior industrial supporting conditions for the development of sports industry. However, it is not conducive to the promotion of industrial economic benefits. In the health service industry, the rapid development of health insurance is beneficial to the integration of industrial resources and the perfection of industrial chain. Whereas as the core content of health service industry, health service has greater space for development; the coupling and coordination degree between the two industries rises from mild maladjustment to basic coordination, which is characterized by the distribution of "high in the east and low in the west" in space; among provinces, with Beijing, the Yangtze River Delta and Guangdong as the three development center points, it shows the spatial evolutionary process from "dispersion-type plaques" to "gathering type scattered surfaces".

Against the current COVID-19 pandemic, governments worldwide have devised a variety of non-pharmaceutical interventions to suppress it, but the efficacy of distinct measures is not yet well quantified. In this paper, we propose a novel tool to achieve this quantification. In fact, this paper develops a new extended epidemic SEIR model, informed by a socio-political classification of different interventions, to assess the value of several suppression approaches. First, we inquire the conceptual effect of suppression parameters on the infection curve. Then, we illustrate the potential of our model on data from a number of countries, to perform cross-country comparisons. This gives information on the best synergies of interventions to control epidemic outbreaks while minimising impact on socio-economic needs. For instance, our results suggest that, while rapid and strong lock-down is an effective pandemic suppression measure, a combination of social distancing and contact tracing can achieve similar suppression synergistically. This quantitative understanding will support the establishment of mid- and long-term interventions, to prepare containment strategies against further outbreaks. This paper also provides an online tool that allows researchers and decision makers to interactively simulate diverse scenarios with our model.

The microscopic agglutination test (MAT) is the standard serological reference test for the diagnosis of leptospirosis, despite being a technically demanding and laborious procedure. The use of a locally optimised MAT panel is considered essential for proper performance and interpretation of results. This paper describes the procedure of selecting such an optimised panel for Sri Lanka, a country hyper-endemic for leptospirosis. MAT was performed using 24 strains on 1132 serum samples collected from patients presenting with acute undifferentiated fever. Of 24 strains, 15 were selected as the optimised panel, while only 11% of serum samples showed positivity. A geographical variation in predominantly reactive serovars was observed, whereas reactivity was low with the saprophytic strain Patoc. Testing with paired sera yielded a higher sensitivity but provided only a retrospective diagnosis. Serological tests based on ELISA with complementary molecular diagnosis using PCR are a feasible and robust alternative approach to diagnose leptospirosis in countries having a higher burden of the disease., Author summary Microscopic agglutination test is the most commonly used serological test in the diagnosis of leptospirosis. The test uses a live panel of Leptospira representing main serogroups and for proper performance of the test, an optimised panel which react well with patient samples need to be selected. This paper describes the procedure of selecting such an optimised panel for Sri Lanka which is a country hyper-endemic for leptospirosis. The test was done on serum samples collected from patients presented with acute undifferentiated fever with 24 panel of serogroups and 15 were selected as the optimised panel. The test was found to have a low sensitivity in the acute stage and ELISA based serological tests with molecular diagnosis using PCR assays would be a better way for diagnosis of leptospirosis.

Construction of not in my back yard (NIMBY) facility Public Private Partnership (PPP) projects are feasible measures to realize sustainable urbanization. In order to ensure the smooth development of the NIMBY facility PPP projects, the problem of choosing the most suitable operation mode among many PPP modes is still scarce and unscientific. In order to select the operation mode of the PPP projects that best fits the characteristics of the project, this paper constructs the operation mode selection of the NIMBY facility PPP project. Firstly, the index system of operation mode selection of the NIMBY facility PPP project is determined. G1 subjective weighting method and information entropy objective weighting method are introduced to solve the optimal weight of each index. Grey correlation theory is used to improve TOPSIS method, and the calculation form of relative proximity degree is optimized to determine the most suitable operation mode for the project. In this paper, combined weighting and TOPSIS method are applied to the research of NIMBY facility PPP project, and the operation mode selection of NIMBY facility PPP project is established, which makes up the blank of this part. Finally, a PPP project in Qingdao, Shandong Province, China, is taken as an example to verify the applicability of the model. The effectiveness of this model was tested by comparing the results of TOPSIS method, Grey target model, Extended matter-element mode and GRA-TOPSIS. It is hoped to provide useful reference for the operation mode selection of NIMBY facility PPP project.

Background Cambodia is widely credited for its successful HIV epidemic control. However, in recent years there have been signs of increasing HIV prevalence among men who have sex with men (MSM) and transgender women (TGW). This paper reviews HIV epidemiological, social science and HIV program implementation studies conducted over the past 20 years to explore possible reasons for the rising HIV prevalence among these groups and to formulate recommendations for improved policies, HIV programmatic interventions and further research. Methods For this scoping review, we searched the PubMed and Google Scholar databases for scientific publications related to HIV and MSM and TGW in Cambodia published since 1999. From each of the returned citations we subsequently studied reference lists to find additional data sources. We also searched websites for reports commissioned by national and international governmental and non-governmental organizations. Results Twenty-seven relevant studies and papers were found and reviewed; most were epidemiological in nature. Recent epidemiological studies and reports show an increase in HIV prevalence among Cambodian MSM and TGW. The epidemiology of HIV infection in these groups has been relatively well-described and analyzed. While initially MSM and TGW were grouped together, in more recent years they have been studied in their own right, recognizing their specific HIV and other prevention needs. Few studies were found investigating Cambodian same-sex cultures and social and cultural contexts in which HIV transmission among MSM and TGW occurs. A few evaluation studies were found, but it remains unknown how effective current HIV service implementation modalities are, or how successful strategies to increase access to essential HIV prevention, testing and treatment services have been employed for MSM and TGW in Cambodia. Conclusions Research about Cambodian MSM and TGW in the context of HIV primarily concerns bio-behavioral knowledge generation. Cambodia is unlikely to achieve control of the HIV epidemic among MSM and TGW without doing better in-depth social science research on its multiple sexual- and gender minority cultures, and without understanding what differentiated implementation modalities, strategies and approaches are most effective to address HIV among its increasingly diverse MSM and TGW populations.

Surveillance is critical to mounting an appropriate and effective response to pandemics. However, aggregated case report data suffers from reporting delays and can lead to misleading inferences. Different from aggregated case report data, line list data is a table contains individual features such as dates of symptom onset and reporting for each reported case and a good source for modeling delays. Current methods for modeling reporting delays are not particularly appropriate for line list data, which typically has missing symptom onset dates that are non-ignorable for modeling reporting delays. In this paper, we develop a Bayesian approach that dynamically integrates imputation and estimation for line list data. Specifically, this Bayesian approach can accurately estimate the epidemic curve and instantaneous reproduction numbers, even with most symptom onset dates missing. The Bayesian approach is also robust to deviations from model assumptions, such as changes in the reporting delay distribution or incorrect specification of the maximum reporting delay. We apply the Bayesian approach to COVID-19 line list data in Massachusetts and find the reproduction number estimates correspond more closely to the control measures than the estimates based on the reported curve., Author summary Interventions meant to control infectious diseases are often determined and judged using surveillance data on the number of new cases of disease. In many diseases, there are substantial delays between the time when an individual is infected or shows symptoms and when the case is actually reported to a public health authority, such as the CDC. This reported data often collects information on symptom onset dates for some individuals. In this paper, we describe a method that imputes missing onset dates for all individuals and recreates the history of the disease progression in a population according to symptom onset dates, which are the best observable proxy available for infection dates. Our method also estimates the instantaneous reproduction number and is robust to many deviations from the assumptions of the model. We show, using a COVID-19 dataset from Massachusetts that our method accurately follows the implementation of control measures in the state.

Background As the world’s largest coal producer, China was accounted for about 46% of global coal production. Among present coal mining risks, methane gas (called gas in this paper) explosion or ignition in an underground mine remains ever-present. Although many techniques have been used, gas accidents associated with the complex elements of underground gassy mines need more robust monitoring or warning systems to identify risks. This paper aimed to determine which single method between the PCA and Entropy methods better establishes a responsive weighted indexing measurement to improve coal mining safety. Methods Qualitative and quantitative mixed research methodologies were adopted for this research, including analysis of two case studies, correlation analysis, and comparative analysis. The literature reviewed the most-used multi-criteria decision making (MCDM) methods, including subjective methods and objective methods. The advantages and disadvantages of each MCDM method were briefly discussed. One more round literature review was conducted to search publications between 2017 and 2019 in CNKI. Followed two case studies, correlation analysis and comparative analysis were then conducted. Research ethics was approved by the Shanxi Coking Coal Group Research Committee. Results The literature searched a total of 25,831publications and found that the PCA method was the predominant method adopted, and the Entropy method was the second most widely adopted method. Two weighting methods were compared using two case studies. For the comparative analysis of Case Study 1, the PCA method appeared to be more responsive than the Entropy. For Case Study 2, the Entropy method is more responsive than the PCA. As a result, both methods were adopted for different cases in the case study mine and finally deployed for user acceptance testing on 5 November 2020. Conclusions The findings and suggestions were provided as further scopes for further research. This research indicated that no single method could be adopted as the better option for establishing indexing measurement in all cases. The practical implication suggests that comparative analysis should always be conducted on each case and determine the appropriate weighting method to the relevant case. This research recommended that the PCA method was a dimension reduction technique that could be handy for identifying the critical variables or factors and effectively used in hazard, risk, and emergency assessment. The PCA method might also be well-applied for developing predicting and forecasting systems as it was sensitive to outliers. The Entropy method might be suitable for all the cases requiring the MCDM. There is also a need to conduct further research to probe the causal reasons why the PCA and Entropy methods were applied to each case and not the other way round. This research found that the Entropy method provides higher accuracy than the PCA method. This research also found that the Entropy method demonstrated to assess the weights of the higher dimension dataset was higher sensitivity than the lower dimensions. Finally, the comprehensive analysis indicates a need to explore a more responsive method for establishing a weighted indexing measurement for warning applications in hazard, risk, and emergency assessments.

Enterprises acquire heterogeneous knowledge through external knowledge search and adapt to the change of external environment, which is of great significance to enterprise breakthrough innovation. This paper takes the innovation ecosystem as the boundary of the research paradigm. Based on innovation ecosystem theory, knowledge management theory and enterprise innovation theory, this paper constructs a moderated mediation model of the enterprise knowledge search, knowledge integration and breakthrough innovation under the characteristics of innovation ecosystem network. This model is tested on the survey data of 344 technology enterprise and manufacturing industries including R&D departments in the Beijing-Tianjin-Hebei region. The research results show that: knowledge integration plays part of the intermediary role between knowledge search and enterprise breakthrough innovation; the larger the network scale, the stronger the network connection, the stronger the intermediary role of knowledge integration on the relationship between knowledge search and enterprise breakthrough innovation. The research results reveal the important role of the innovation ecosystem in enterprise breakthrough innovation. At the same time, the research on knowledge search and enterprise breakthrough innovation should consider the network characteristics of innovation ecosystem and the ability of enterprise knowledge integration.

With the increase of patients with retinopathy, retinopathy recognition has become a research hotspot. In this article, we describe the etiology and symptoms of three kinds of retinal diseases, including drusen(DRUSEN), choroidal neovascularization(CNV) and diabetic macular edema(DME). In addition, we also propose a hybrid attention mechanism to classify and recognize different types of retinopathy images. In particular, the hybrid attention mechanism proposed in this paper includes parallel spatial attention mechanism and channel attention mechanism. It can extract the key features in the channel dimension and spatial dimension of retinopathy images, and reduce the negative impact of background information on classification results. The experimental results show that the hybrid attention mechanism proposed in this paper can better assist the network to focus on extracting thr fetures of the retinopathy area and enhance the adaptability to the differences of different data sets. Finally, the hybrid attention mechanism achieved 96.5% and 99.76% classification accuracy on two public OCT data sets of retinopathy, respectively.

This paper analyzes the dynamics of the labor market in Latin America during the COVID-19 pandemic. After a decade of a virtuous circle of growth with the creation of formal jobs, the pandemic has had an considerable impact on the region’s labor market, generating an unparalleled increase in the proportion of the inactive population, considerable reductions in informality, and, in contrast, smaller fluctuations in formal jobs. In this context, the formal sector, given its lower flexibility, became a "social safety net" that preserved the stability of employment and wages. Based on the findings presented in this paper, it is projected that, starting in 2021, informality will grow to levels higher than those of the pre-COVID-19 era–with 7.56 million additional informal jobs–as a result of the population returning to the labor market to compensate for the declines in incomes. According to the simulations presented, postponing or forgiving income tax payments and social security contributions conditional on the generation of formal jobs could reduce the growth of informality by 50 to 75 percent. Achieving educational improvements has the potential to reduce it by 50 percent.

In this paper, the algebraic topological characteristics of brain networks composed of electroencephalogram(EEG) signals induced by different quality images were studied, and on that basis, a neurophysiological image quality assessment approach was proposed. Our approach acquired quality perception-related neural information via integrating the EEG collection with conventional image assessment procedures, and the physiologically meaningful brain responses to different distortion-level images were obtained by topological data analysis. According to the validation experiment results, statistically significant discrepancies of the algebraic topological characteristics of EEG data evoked by a clear image compared to that of an unclear image are observed in several frequency bands, especially in the beta band. Furthermore, the phase transition difference of brain network caused by JPEG compression is more significant, indicating that humans are more sensitive to JPEG compression other than Gaussian blur. In general, the algebraic topological characteristics of EEG signals evoked by distorted images were investigated in this paper, which contributes to the study of neurophysiological assessment of image quality.

An unbiased, widely accepted estimate of the rate of occurrence of new cases of autism over time would facilitate progress in understanding the causes of autism. The same may also apply to other disorders. While incidence is a widely used measure of occurrence, birth prevalence—the proportion of each birth year cohort with the disorder—is the appropriate measure for disorders and diseases of early childhood. Studies of autism epidemiology commonly speculate that estimates showing strong increases in rate of autism cases result from an increase in diagnosis rates rather than a true increase in cases. Unfortunately, current methods are not sufficient to provide a definitive resolution to this controversy. Prominent experts have written that it is virtually impossible to solve.This paper presents a novel method, time-to-event birth prevalence estimation (TTEPE), to provide accurate estimates of birth prevalence properly adjusted for changing diagnostic factors. It addresses the shortcomings of prior methods. TTEPE is based on well-known time-to-event (survival) analysis techniques. A discrete survival process models the rates of incident diagnoses by birth year and age. Diagnostic factors drive the probability of diagnosis as a function of the year of diagnosis. TTEPE models changes in diagnostic criteria, which can modify the effective birth prevalence when new criteria take effect. TTEPE incorporates the development of diagnosable symptoms with age. General-purpose optimization software estimates all parameters, forming a non-linear regression. The paper specifies all assumptions underlying the analysis and explores potential deviations from assumptions and optional additional analyses.A simulation study shows that TTEPE produces accurate parameter estimates, including trends in both birth prevalence and the probability of diagnosis in the presence of sampling effects from finite populations. TTEPE provides high power to resolve small differences in parameter values by utilizing all available data points.

Background Self-management is a promising approach to improve quality of life after stroke. However, evidence for the appropriateness and effectiveness of self-management for stroke survivors with aphasia is limited. This article reports on the process used to develop a supported self-management intervention for stroke survivors with aphasia (SSWA) using co-production and behaviour change theory. Preparatory research included systematic reviews, and qualitative interviews and focus groups with SSWA, family members and speech and language therapists (SLTs). Materials and methods We conducted six, 2 hour long intervention development workshops with key stakeholders. The workshops were informed by principles of co-production and the intervention development process outlined by the Behaviour Change Wheel (BCW). We also incorporated the findings of our preparatory research within workshops. Each workshop included an introduction, 1–2 co-production tasks and time for feedback at the end of the session. Data were analysed on an ongoing basis so that findings could be used to feed in to subsequent workshops and intervention development. Results Workshop participants (n = 12) included; SSWA (n = 5), family members (n = 3) and SLTs (n = 4). Together, participants engaged with accessible and participatory co-production tasks which aligned with the BCW framework. Participants engaged in discussion to define self-management in behavioural terms (behavioural diagnosis) and to identify what needed to change to support self-management. Participant’s co-produced solutions for supporting self-management and discussed options to implement these in practice. Prototype materials were generated by the research team and evaluated by participants. Intervention functions and behaviour change techniques (BCTs) were mapped to the solutions generated by participants by the research team, after the final workshop. A supported self-management intervention for SSWA was developed which will be delivered by SLTs through community stroke services. Conclusions This paper reports the process we used to integrate co-production work with behaviour change theory to develop a complex self-management intervention. This is of relevance for researchers looking to harness the strengths of co-production methods and theory in intervention design. Future research will feasibility test the supported self-management intervention developed. This paper provides transparency to our intervention development process which will help others to better interpret the findings of our feasibility work.

Complement proteins can form membrane attack complex (MAC) pores that directly kill Gram-negative bacteria. MAC pores assemble by stepwise binding of C5b, C6, C7, C8 and finally C9, which can polymerize into a transmembrane ring of up to 18 C9 monomers. It is still unclear if the assembly of a polymeric-C9 ring is necessary to sufficiently damage the bacterial cell envelope to kill bacteria. In this paper, polymerization of C9 was prevented without affecting binding of C9 to C5b-8, by locking the first transmembrane helix domain of C9. Using this system, we show that polymerization of C9 strongly enhanced damage to both the bacterial outer and inner membrane, resulting in more rapid killing of several Escherichia coli and Klebsiella strains in serum. By comparing binding of wildtype and ‘locked’ C9 by flow cytometry, we also show that polymerization of C9 is impaired when the amount of available C9 per C5b-8 is limited. This suggests that an excess of C9 is required to efficiently form polymeric-C9. Finally, we show that polymerization of C9 was impaired on complement-resistant E. coli strains that survive killing by MAC pores. This suggests that these bacteria can specifically block polymerization of C9. All tested complement-resistant E. coli expressed LPS O-antigen (O-Ag), compared to only one out of four complement-sensitive E. coli. By restoring O-Ag expression in an O-Ag negative strain, we show that the O-Ag impairs polymerization of C9 and results in complement-resistance. Altogether, these insights are important to understand how MAC pores kill bacteria and how bacterial pathogens can resist MAC-dependent killing., Author summary In this paper, we focus on how complement proteins, an essential part of the immune system, kill Gram-negative bacteria via so-called membrane attack complex (MAC) pores. The MAC is a large pore that consists of five different proteins. The final component, C9, assembles a ring of up to 18 C9 molecules that damages the bacterial cell envelope. Here, we aimed to better understand if this polymeric-C9 ring is necessary to kill bacteria and if bacteria can interfere in its assembly. We uncover that polymerization of C9 increased the damage to the entire bacterial cell envelope, which resulted in more rapid killing of several Gram-negative species. We also show that some clinical Escherichia coli strains can block polymerization of C9 and survive MAC-dependent killing by modifying sugars in the bacterial cell envelope, namely the O-antigen of lipopolysaccharide. These insights help us to better understand how the immune system kills bacteria and how pathogenic bacteria can survive killing.

The paper examines the interest of the commercial banks' stakeholders in Pillar 3 disclosures and their behaviour during the timing of serious market turbulence. The aim is to discover to which extent current banking regulation supports stakeholders' interest in the information required by regulators to be disclosed. The examined data consists of log files that were pre-processed using web mining techniques and from which were extracted frequent item sets by quarters and evaluated in terms of quantity. The authors have proposed a methodology to evaluate frequent item sets of web parts over a dedicated time. Based on the verification of applied methodology on two commercial banks, the results show that stakeholders' interest in disclosures is highest in the first quarter at each year and after turbulent times in 2009 their interests decreased. Moreover, the results suggest that stakeholders expressed higher interest than in regulatory required Pillar 3 information in the following group of information: Pillar3 related information, Annual reports, Information on Group. Following our results, the paper contributes to cover the gap in the research by analysing Pillar 3 disclosures and their compliance with regulatory requirements, which also increase the interest of the relevant stakeholders to conduce them as an effective market discipline tool. Článek zkoumá zájem zainteresovaných stran komerčních bank o zveřejňování informací podle 3. pilíře a jejich chování v době vážných tržních turbulencí. Cílem je zjistit, do jaké míry současná bankovní regulace podporuje zájem zainteresovaných stran o informace, jejichž zveřejnění regulátoři vyžadují. Zkoumaná data se skládají z logů, které byly předem zpracovány pomocí technik web miningu a z nichž byly extrahovány soubory častých položek podle čtvrtletí a vyhodnoceny z hlediska kvantity. Autoři navrhli metodiku vyhodnocování sad častých položek webových částí za vyhrazený čas. Na základě ověření aplikované metodiky na dvou komerčních bankách výsledky ukazují, že zájem zainteresovaných stran o zveřejňované informace je v každém roce nejvyšší v prvním čtvrtletí a po turbulentním období v roce 2009 jejich zájem poklesl. Výsledky dále naznačují, že zainteresované strany projevily vyšší zájem než o regulatorně požadované informace 3. pilíře o následující skupinu informací: Informace související s pilířem 3, Výroční zprávy, Informace o skupině. V návaznosti na naše výsledky přispívá tento článek k pokrytí mezery ve výzkumu analýzou informací zveřejňovaných v rámci Pilíře 3 a jejich souladu s regulatorními požadavky, což také zvyšuje zájem příslušných zainteresovaných stran o jejich vedení jako účinného nástroje tržní disciplíny.

High-throughput data such as metabolomics, genomics, transcriptomics, and proteomics have become familiar data types within the “-omics” family. For this work, we focus on subsets that interact with one another and represent these “pathways” as graphs. Observed pathways often have disjoint components, i.e., nodes or sets of nodes (metabolites, etc.) not connected to any other within the pathway, which notably lessens testing power. In this paper we propose the Pathway Integrated Regression-based Kernel Association Test (PaIRKAT), a new kernel machine regression method for incorporating known pathway information into the semi-parametric kernel regression framework. This work extends previous kernel machine approaches. This paper also contributes an application of a graph kernel regularization method for overcoming disconnected pathways. By incorporating a regularized or “smoothed” graph into a score test, PaIRKAT can provide more powerful tests for associations between biological pathways and phenotypes of interest and will be helpful in identifying novel pathways for targeted clinical research. We evaluate this method through several simulation studies and an application to real metabolomics data from the COPDGene study. Our simulation studies illustrate the robustness of this method to incorrect and incomplete pathway knowledge, and the real data analysis shows meaningful improvements of testing power in pathways. PaIRKAT was developed for application to metabolomic pathway data, but the techniques are easily generalizable to other data sources with a graph-like structure., Author summary PaIRKAT is a tool for improving testing power on high dimensional data by including graph topography in the kernel machine regression setting. Studies on high-dimensional data can struggle to include the complex relationships between variables. The semi-parametric kernel machine regression model is a powerful tool for capturing these types of relationships. They provide a framework for testing for relationships between outcomes of interest and high dimensional data such as metabolomic, genomic, or proteomic pathways. Our paper proposes a kernel machine method for including known biological connections between high dimensional variables by representing them as edges of ‘graphs’ or ‘networks.’ It is common for nodes (e.g., metabolites) to be disconnected from all others within the graph, which leads to meaningful decreases in testing power when graph information is ignored. We include a graph regularization or ‘smoothing’ approach for managing this issue. We demonstrate the benefits of this approach through simulation studies and an application to the metabolomic data from the COPDGene study.

Read-depths (RDs) are frequently used in identifying structural variants (SVs) from sequencing data. For existing RD-based SV callers, it is difficult for them to determine breakpoints in single-nucleotide resolution due to the noisiness of RD data and the bin-based calculation. In this paper, we propose to use the deep segmentation model UNet to learn base-wise RD patterns surrounding breakpoints of known SVs. We integrate model predictions with an RD-based SV caller to enhance breakpoints in single-nucleotide resolution. We show that UNet can be trained with a small amount of data and can be applied both in-sample and cross-sample. An enhancement pipeline named RDBKE significantly increases the number of SVs with more precise breakpoints on simulated and real data. The source code of RDBKE is freely available at https://github.com/yaozhong/deepIntraSV., Author summary In this paper, we used the deep segmentation model UNet to alleviate the bin size limitation of RD-based SV callers. UNet was initially proposed for image data. Here, we demonstrated that the UNet model could also be applied for one-dimensional genomic data. We formalized the breakpoint prediction as a segmentation task and inferred breakpoints in single-nucleotide resolution from predicted label marks. Through a set of experiments on both simulated and real WGS data, we demonstrated that the UNet model could be trained with a small amount of data, and an enhancement pipeline called RDBKE significantly increased the number of SVs with more precise breakpoints.

Selecting a target journal is a universal decision faced by authors of scientific papers. Components of the decision, including expected turnaround time, journal acceptance rate, and journal impact factor, vary in terms of accessibility. In this study, I collated recent turnaround times and impact factors for 82 journals that publish papers in the field of fisheries sciences. In addition, I gathered acceptance rates for the same journals when possible. Findings indicated clear among-journal differences in turnaround time, with median times-to-publication ranging from 79 to 323 days. There was no clear correlation between turnaround time and acceptance rate nor between turnaround time and impact factor; however, acceptance rate and impact factor were negatively correlated. I found no field-wide differences in turnaround time since the beginning of the COVID-19 pandemic, though some individual journals took significantly longer or significantly shorter to publish during the pandemic. Depending on their priorities, authors choosing a target journal should use the results of this study as guidance toward a more informed decision.

Fake news is a complex problem that leads to different approaches used to identify them. In our paper, we focus on identifying fake news using its content. The used dataset containing fake and real news was pre-processed using syntactic analysis. Dependency grammar methods were used for the sentences of the dataset and based on them the importance of each word within the sentence was determined. This information about the importance of words in sentences was utilized to create the input vectors for classifications. The paper aims to find out whether it is possible to use the dependency grammar to improve the classification of fake news. We compared these methods with the TfIdf method. The results show that it is possible to use the dependency grammar information with acceptable accuracy for the classification of fake news. An important finding is that the dependency grammar can improve existing techniques. We have improved the traditional TfIdf technique in our experiment.

Drowning is a global public health problem, but accurately estimating drowning risk remains a challenge. Coastal drowning comprises a significant proportion of the drowning burden in Australia and is influenced by a range of behavioural factors (e.g. risk perception, knowledge, attitudes and behaviours) that are poorly understood. These factors, along with those that impact exposure (e.g. coastal visitation and activity participation) all impact on drowning risk. While excellent mortality and morbidity data exists in Australia, a lack of coastal participation data presents challenges to identifying high-risk groups or activities and prioritising prevention efforts. This methods paper describes the development and evolution of an ongoing, annual, nationally representative online survey as an effective tool used to capture valuable data about the Australian population’s relationship with the coast. This paper explores how the survey is structured (12–14 sections spanning multiple topics and themes), the different question types used (including open text, 4-digit responses and categorical questions), the sample size (1400–1600 respondents), sampling strategy (using demographic quota sampling which can then be post-weighted to the population if required) and how topics and themes have changed over time to enhance the quality of data collected (i.e., wording changes to enhance participant comprehension or data usability and changing issue-specific ‘feature’ topics of interest such as campaign evaluation). How the survey is implemented online is described, both practically through to third-party recruitment processes and ethically to maximise anonymity of respondents and ensure data quality. Interim analyses indicate the impact of considering exposure when calculating fatal drowning rates, especially by activity (e.g., crude boating drowning rate 0.12 per 100,000 population vs 0.95 per 100,000 exposed population [relative risk = 8.01; 95% confidence interval: 4.55–14.10]). This study highlights lessons learned in the process of conducting a nationally representative coastal participation survey as well as the strengths and limitations of adopting this approach. Data collected will provide more detailed information on the skills, behaviours, knowledge and attitudes of coastal activity participants. Analyses of this unique dataset will inform research that will underpin development and evaluation of coastal drowning prevention initiatives prioritising those most at risk. It is hoped that the methods detailed within this study may be useful for other countries to develop similar approaches to understanding their own population.

In this paper, we propose a hierarchical statistical model for a single repairable system subject to several failure modes (competing risks). The paper describes how complex engineered systems may be modelled hierarchically by use of Bayesian methods. It is also assumed that repairs are minimal and each failure mode has a power-law intensity. Our proposed model generalizes another one already presented in the literature and continues the study initiated by us in another published paper. Some properties of the new model are discussed. We conduct statistical inference under an objective Bayesian framework. A simulation study is carried out to investigate the efficiency of the proposed methods. Finally, our methodology is illustrated by two practical situations currently addressed in a project under development arising from a partnership between Petrobras and six research institutes.

Background During uncertainties associated with the COVID-19 pandemic, effectively improving people’s health literacy is more important than ever. Drawing knowledge maps of health literacy research through data mining and visualized measurement technology helps systematically present the research status and development trends in global academic circles. Methods This paper uses CiteSpace to carry out a metric analysis of 9,492 health literacy papers included in Web of Science through mapping knowledge domains. First, based on the production theory of scientific knowledge and the data mining of citations, the main bodies (country, institution and author) that produce health literacy knowledge as well as their mutual cooperation (collaboration network) are both clarified. Additionally, based on the quantitative framework of cocitation analysis, this paper introduces the interdisciplinary features, development trends and hot topics of the field. Finally, by using burst detection technology in the literature, it further reveals the research frontiers of health literacy. Results The results of the BC measures of the global health literacy research collaboration network show that the United States, Australia and the United Kingdom are the major forces in the current international collaboration network on health literacy. There are still relatively very few transnational collaborations between Eastern and Western research institutions. Collaborations in public environmental occupational health, health care science services, nursing and health policy services have been active in the past five years. Research topics in health literacy research evolve over time, mental health has been the most active research field in recent years. Conclusions A systematic approach is needed to address the challenges of health literacy, and the network framework of cooperation on health literacy at regional, national and global levels should be strengthened to further promote the application of health literacy research. In the future, we anticipate that this research field will expand in two directions, namely, mental health literacy and eHealth literacy, both of which are closely linked to social development and issues. The results of this study provide references for future applied research in health literacy.