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Type 1 diabetes (T1D) is increasing in incidence and predictable with measurement of serum islet autoantibodies (iAb) years prior to clinical disease onset. Identifying iAb positive individuals reduces diabetic ketoacidosis and identifies individuals for T1D prevention trials. However, large scale screening for iAb remains challenging as assays have varying sensitivities and specificities, insulin autoantibodies remain difficult to measure and venipuncture is generally required to obtain serum. We developed an approach to reliably measure all four major iAb, including insulin autoantibodies, from dried blood spots (DBS) on filter-paper. By spiking iAb positive serum into iAb negative whole blood in a dose titration, we optimized the conditions for autoantibody elution from filter paper as measured by fluid phase radioimmunoassays. After assessing stability of measuring iAb from DBS over time, we then screened iAb from DBS and the corresponding serum in new-onset T1D (n = 52), and controls (n = 72) which included first-degree relatives of T1D patients. iAb measured from eluted DBS in new-onset T1D strongly correlated with serum measurements (R2 = 0.96 for mIAA, GADA = 0.94, IA-2A = 0.85, ZnT8A = 0.82, p<0.01 for each autoantibody). There were no false positives in control subjects, and 5/6 with previously unknown iAb positivity in sera were detected using DBS. With further validation, measuring iAb from DBS can be a reliable method to screen for T1D risk. [ABSTRACT FROM AUTHOR]

Moderate-to-severe psoriasis is associated with significant comorbidity, an impaired quality of life, and increased medical costs, including those associated with treatments. Systematic reviews (SRs) and meta-analyses (MAs) of randomized clinical trials are considered two of the best approaches to the summarization of high-quality evidence. However, methodological bias can reduce the validity of conclusions from these types of studies and subsequently impair the quality of decision making. As co-authorship is among the most well-documented forms of research collaboration, the present study aimed to explore whether authors’ collaboration methods might influence the methodological quality of SRs and MAs of psoriasis. Methodological quality was assessed by two raters who extracted information from full articles. After calculating total and per-item Assessment of Multiple Systematic Reviews (AMSTAR) scores, reviews were classified as low (0-4), medium (5-8), or high (9-11) quality. Article metadata and journal-related bibliometric indices were also obtained. A total of 741 authors from 520 different institutions and 32 countries published 220 reviews that were classified as high (17.2%), moderate (55%), or low (27.7%) methodological quality. The high methodological quality subnetwork was larger but had a lower connection density than the low and moderate methodological quality subnetworks; specifically, the former contained relatively fewer nodes (authors and reviews), reviews by authors, and collaborators per author. Furthermore, the high methodological quality subnetwork was highly compartmentalized, with several modules representing few poorly interconnected communities. In conclusion, structural differences in author-paper affiliation network may influence the methodological quality of SRs and MAs on psoriasis. As the author-paper affiliation network structure affects study quality in this research field, authors who maintain an appropriate balance between scientific quality and productivity are more likely to develop higher quality reviews. [ABSTRACT FROM AUTHOR]

Background: Sponsors that seek to commercialize new drugs apply to the Food and Drug Administration (FDA) which independently analyzes the raw data and reports the results on its website. Objectives: This study sought to determine if there are differences between the FDA assessments and journal reports on biologic agents developed for the treatment of rheumatoid arthritis. Methods: Available data on FDA-approved drugs were extracted from the website, and a systematic literature search was conducted to identify matching studies in peer-reviewed medical journals. Outcome measures were the American College of Rheumatology response criteria ACR20 (efficacy) and withdrawal due to adverse events (safety). As effect size odds ratios were estimated for each active trial arm vs. control arm (i.e. for both sources: FDA and journal report), followed by calculation of the ratios of the FDA and journal report odds ratios. A ratio of odds ratios not equal to 1 was categorized as a discrepancy. Results: FDA reports were available for 8 of 9 FDA-approved biologic agents for rheumatoid arthritis; all identified trials (34) except one were published in peer-reviewed journals. Overall, discrepancies were noted for 20 of the 33 evaluated trials. Differences in the apparent benefit reporting were found in 39% (24/61) pairwise comparisons and in 11 cases these were statistically significant; the FDA report showed greater benefit than the journal publication in 15 comparisons and lesser benefit in 9. Differences in the reported harms were found in 51% (28/55) pairwise comparisons and were statistically significant in 5. The “signal” in FDA reports showed a less harmful effect than the journal publication in 17 comparisons whereas a more harmful effect in 11. The differences were attributed to differences in analytic approach, patient inclusion, rounding effect, and counting discrepancies. However, no differences were categorized as critical. Conclusion: There was no empirical evidence to suggest biased estimates between the two sources. Increased and detailed transparency in publications would improve the understanding and credibility of published results. Further, the FDA report was found to be a useful source when data are missing in the published report (i.e. reporting bias). [ABSTRACT FROM AUTHOR]

Background: In economic analyses of HIV interventions, South Africa is often used as a case in point, due to the availability of good epidemiological and programme data and the global relevance of its epidemic. Few analyses however use locally relevant cost data. We reviewed available cost data as part of the South African HIV Investment Case, a modelling exercise to inform the optimal use of financial resources for the country’s HIV programme. Methods: We systematically reviewed publication databases for published cost data covering a large range of HIV interventions and summarised relevant unit costs (cost per person receiving a service) for each. Where no data was found in the literature, we constructed unit costs either based on available information regarding ingredients and relevant public-sector prices, or based on expenditure records. Results: Only 42 (5%) of 1,047 records included in our full-text review reported primary cost data on HIV interventions in South Africa, with 71% of included papers covering ART. Other papers detailed the costs of HCT, MMC, palliative and inpatient care; no papers were found on the costs of PrEP, social and behaviour change communication, and PMTCT. The results informed unit costs for 5 of 11 intervention categories included in the Investment Case, with the remainder costed based on ingredients (35%) and expenditure data (10%). Conclusions: A large number of modelled economic analyses of HIV interventions in South Africa use as inputs the same, often outdated, cost analyses, without reference to additional literature review. More primary cost analyses of non-ART interventions are needed. [ABSTRACT FROM AUTHOR]

Background: To be meaningful, a core outcome set (COS) should be relevant to all stakeholders including patients and carers. This review aimed to explore the methods by which patients and carers have been included as participants in COS development exercises and, in particular, the use and reporting of qualitative methods. Methods: In August 2015, a search of the Core Outcomes Measures in Effectiveness Trials (COMET) database was undertaken to identify papers involving patients and carers in COS development. Data were extracted to identify the data collection methods used in COS development, the number of health professionals, patients and carers participating in these, and the reported details of qualitative research undertaken. Results: Fifty-nine papers reporting patient and carer participation were included in the review, ten of which reported using qualitative methods. Although patients and carers participated in outcome elicitation for inclusion in COS processes, health professionals tended to dominate the prioritisation exercises. Of the ten qualitative papers, only three were reported as a clear pre-designed part of a COS process. Qualitative data were collected using interviews, focus groups or a combination of these. None of the qualitative papers reported an underpinning methodological framework and details regarding data saturation, reflexivity and resource use associated with data collection were often poorly reported. Five papers reported difficulty in achieving a diverse sample of participants and two reported that a large and varied range of outcomes were often identified by participants making subsequent rating and ranking difficult. Conclusions: Consideration of the best way to include patients and carers throughout the COS development process is needed. Additionally, further work is required to assess the potential role of qualitative methods in COS, to explore the knowledge produced by different qualitative data collection methods, and to evaluate the time and resources required to incorporate qualitative methods into COS development. [ABSTRACT FROM AUTHOR]

Co-diagnosis of HIV and tuberculosis presents a treatment dilemma. Starting both treatments at the same time can cause a flood of immune response called immune reconstitution inflammatory syndrome (IRIS) which can be lethal. But, how long to delay HIV treatment is less understood. In 2011, based on the conclusions of three separate studies, WHO recommended starting HIV treatment earlier for those with later HIV disease progression. This paper conducts a replication study of one of the three studies, by Havlir and colleagues. Using their publicly available data, we were able to replicate most of the results presented in the original paper. In our measurement and estimation analyses we use different estimation techniques to assess the robustness of the results. We find that adjusting for loss to follow-up does not affect the main results of the paper. However, an ANCOVA estimation and an instrumental variable model weaken the main result of the paper of better outcomes with early HIV treatment only for those who are sicker, reducing significance from the 5% to the 10% level. A change-point analysis also detects no changes in effect by timing of HIV treatment initiation or different thresholds of CD4 count for the primary outcome. This result suggests that the choice of start time for HIV treatment initiation should be based on other factors including potential drug interactions, overlapping side effects, a high pill burden and severity of illness rather than CD4 threshold and preset timeframes. While we caution against overgeneralizing, the result of this replication is aligned with more recent studies that show no evidence that early initiation of HIV treatment reduces mortality for any patients. [ABSTRACT FROM AUTHOR]

Cholera rapid diagnostic tests (RDT) could play a central role in outbreak detection and surveillance in low-resource settings, but their modest performance has hindered their broad adoption. The addition of an enrichment step may improve test specificity. We describe the results of a prospective diagnostic evaluation of the Crystal VC RDT (Span Diagnostics, India) with enrichment step and of culture, each compared to polymerase chain reaction (PCR), during a cholera outbreak in South Sudan. RDTs were performed on alkaline peptone water inoculated with stool and incubated for 4–6 hours at ambient temperature. Cholera culture was performed from wet filter paper inoculated with stool. Molecular detection of Vibrio cholerae O1 by PCR was done from dry Whatman 903 filter papers inoculated with stool, and from wet filter paper supernatant. In August and September 2015, 101 consecutive suspected cholera cases were enrolled, of which 36 were confirmed by PCR. The enriched RDT had 86.1% (95% CI: 70.5–95.3) sensitivity and 100% (95% CI: 94.4–100) specificity compared to PCR as the reference standard. The sensitivity of culture versus PCR was 83.3% (95% CI: 67.2–93.6) for culture performed on site and 72.2% (95% CI: 54.8–85.8) at the international reference laboratory, where samples were tested after an average delay of two months after sample collection, and specificity was 98.5% (95% CI: 91.7–100) and 100% (95% CI: 94.5–100), respectively. The RDT with enrichment showed performance comparable to that of culture and could be a sustainable alternative to culture confirmation where laboratory capacity is limited. [ABSTRACT FROM AUTHOR]

Competitive pressure to maximize the current bibliometric measures of productivity is jeopardizing the integrity of the scientific literature. Efforts are underway to address the ‘reproducibility crisis’ by encouraging the use of more rigorous, confirmatory methods. However, as long as productivity continues to be defined by the number of discoveries scientists publish, the impact factor of the journals they publish in and the number of times their papers are cited, they will be reluctant to accept high quality methods and consistently conduct and publish confirmatory/replication studies. This exploratory study examined a sample of rigorous Phase II-IV clinical trials, including unpublished studies, to determine if more appropriate metrics and incentives can be developed. The results suggest that rigorous procedures will help reduce false positives, but to the extent that higher quality methods are accepted as the standard of practice, the current bibliometric incentives will discourage innovative studies and encourage scientists to shift their research to less informative studies of subjects that are already being more actively investigated. However, the results also suggest that it is possible to develop a more appropriate system of rewards. In contrast to the current bibliometric incentives, evaluations of the quality of the methods and reproducibility of the results, innovation and diversity of thought, and amount of information produced may serve as measures and incentives that maintain the integrity of the scientific literature and maximize scientific progress. [ABSTRACT FROM AUTHOR]

In this paper, we will investigate the effect of diffusion, which is ubiquitous in nature, on the immune system using a reaction-diffusion model in order to understand the dynamical behavior of complex patterns and control the dynamics of different patterns. Through control theory and linear stability analysis of local equilibrium, we obtain the optimal condition under which the system loses stability and a Turing pattern occurs. By combining mathematical analysis and numerical simulation, we show the possible patterns and how these patterns evolve. In addition, we establish a bridge between the complex patterns and the biological mechanism using the results from a previous study in Nature Cell Biology. The results in this paper can help us better understand the biological significance of the immune system. [ABSTRACT FROM AUTHOR]

B-spline functions are widely used in many industrial applications such as computer graphic representations, computer aided design, computer aided manufacturing, computer numerical control, etc. Recently, there exist some demands, e.g. in reverse engineering (RE) area, to employ B-spline curves for non-trivial cases that include curves with discontinuous points, cusps or turning points from the sampled data. The most challenging task in these cases is in the identification of the number of knots and their respective locations in non-uniform space in the most efficient computational cost. This paper presents a new strategy for fitting any forms of curve by B-spline functions via local algorithm. A new two-step method for fast knot calculation is proposed. In the first step, the data is split using a bisecting method with predetermined allowable error to obtain coarse knots. Secondly, the knots are optimized, for both locations and continuity levels, by employing a non-linear least squares technique. The B-spline function is, therefore, obtained by solving the ordinary least squares problem. The performance of the proposed method is validated by using various numerical experimental data, with and without simulated noise, which were generated by a B-spline function and deterministic parametric functions. This paper also discusses the benchmarking of the proposed method to the existing methods in literature. The proposed method is shown to be able to reconstruct B-spline functions from sampled data within acceptable tolerance. It is also shown that, the proposed method can be applied for fitting any types of curves ranging from smooth ones to discontinuous ones. In addition, the method does not require excessive computational cost, which allows it to be used in automatic reverse engineering applications. [ABSTRACT FROM AUTHOR]

Background: Biosensor-based detection provides a rapid and low-cost alternative to conventional analytical methods for revealing the presence of the contaminants in water as well as solid matrices. Although important to be detected, small analytes (few hundreds of Daltons) are an issue in biosensing since the signal they induce in the transducer, and specifically in a Quartz-Crystal Microbalance, is undetectable. A pesticide like parathion (M = 292 Da) is a typical example of contaminant for which a signal amplification procedure is desirable. Methods/Findings: The ballasting of the analyte by gold nanoparticles has been already applied to heavy target as proteins or bacteria to improve the limit of detection. In this paper, we extend the application of such a method to small analytes by showing that once the working surface of a Quartz-Crystal Microbalance (QCM) has been properly functionalized, a limit of detection lower than 1 ppb is reached for parathion. The effective surface functionalization is achieved by immobilizing antibodies upright oriented on the QCM gold surface by a simple photochemical technique (Photonic Immobilization Technique, PIT) based on the UV irradiation of the antibodies, whereas a simple protocol provided by the manufacturer is applied to functionalize the gold nanoparticles. Thus, in a non-competitive approach, the small analyte is made detectable by weighing it down through a “sandwich protocol” with a second antibody tethered to heavy gold nanoparticles. The immunosensor has been proved to be effective against the parathion while showing no cross reaction when a mixture of compounds very similar to parathion is analyzed. Conclusion/Significance: The immunosensor described in this paper can be easily applied to any small molecule for which polyclonal antibodies are available since both the functionalization procedure of the QCM probe surface and gold nanoparticle can be applied to any IgG, thereby making our device of general application in terms of target analyte. [ABSTRACT FROM AUTHOR]

Objective: Studies suggest that parenteral MTX may be more efficacious than the oral form at equivalent doses for the treatment of rheumatoid arthritis. We carried out a meta-analysis to compare the efficacy of oral versus parenteral MTX in RA. Methods: PubMed, Web of Science and Embase were systematically searched from inception to June 8th 2017 and reviewed following PRISMA 2009 guidelines, by two independent reviewers. To be included, trials had to study adults with RA randomized to the same dose of either oral or parenteral MTX. The primary endpoint was ACR20 at 6 months. Intention-to-treat analysis results were used when possible. Data from direct comparisons between oral and parenteral methotrexate quantitatively analyzed using maximum likelihood random effects meta-analysis. Relative treatment effects were generated as an odds ratio [OR] (OR>1 indicated a benefit for parenteral therapy). Results: The search yielded 357 papers or abstracts. After review of titles or abstracts and full text papers, we found 4 that met inclusion criteria with 703 patients randomized. Dose of MTX started at 15mg/week and increased up to 25mg/week. The summary OR for achieving ACR20 using parenteral vs. oral MTX was 3.02 (95% CI 1.41, 6.46), with no significant difference in the risk for all adverse events. Conclusion: Parenteral MTX therapy had significantly higher odds than oral MTX of achieving reduction in disease activity. We propose that parenteral MTX is more effective than weekly oral MTX; its widespread use may lead to better control of disease and a decrease in demand for biologic agents. [ABSTRACT FROM AUTHOR]

Background: CD4 cell counts is widely used as a biomarker for treatment progression when studying the efficacy of drugs to treat HIV-infected patients. In the past, it had been also used in determining eligibility to initiate antiretroviral therapy. The main aim of this was to model the evolution of CD4 counts over time and use this model for an early prediction of subject-specific time to cross a pre-specified CD4 threshold. Methods: Hospital based retrospective cohort study of HIV-infected patients was conducted from January 2009 to December 2014 at University of Gondar hospital, Northwest Ethiopia. Fractional polynomial random effect model is used to model the evolution of CD4 counts over time in response to treatment and to estimate the individual probability to be above a pre-selected CD4 threshold. Human subject research approval for this study was received from University of Gondar Research Ethics Committee and the medical director of the hospital. Results: A total of 1347 patients were included in the analysis presented in this paper. The cohort contributed a total of 236.58 per 100 person-years of follow-up. Later the data were divided into two periods: the first is the estimation period in which the parameters of the model are estimated and the second is the prediction period. Based on the parameters from the estimation period, model based prediction for the time to cross a threshold was estimated. The correlations between observed and predicted values of CD4 levels in the estimation period were 0.977 and 0.982 for Neverapine and Efavirenz containing regimens, respectively; while the correlation between the observed and predicted CD4 counts in the prediction period are 0.742 and 0.805 for NVP and EFV, respectively. Conclusions: The model enables us to estimate a subject-specific expected time to cross a CD4 threshold and to estimate a subject-specific probability to have CD4 count above a pre-specified threshold at each time point. By predicting long-term outcomes of CD4 count of the patients one can advise patient about the potential ART benefits that accrue in the long-term. [ABSTRACT FROM AUTHOR]

In epidemiology, gerontology, human development and the social sciences, age-period-cohort (APC) models are used to study the variability in trajectories of change over time. A well-known issue exists in simultaneously identifying age, period and birth cohort effects, namely that the three characteristics comprise a perfectly collinear system. That is, since age = period−cohort, only two of these effects are estimable at a time. In this paper, we introduce an alternative framework for considering effects relating to age, period and birth cohort. In particular, instead of directly modeling age in the presence of period and cohort effects, we propose a risk modeling approach to characterize age-related risk (i.e., a hybrid of multiple biological and sociological influences to evaluate phenomena associated with growing older). The properties of this approach, termed risk-period-cohort (RPC), are described in this paper and studied by simulations. We show that, except for pathological circumstances where risk is uniquely determined by age, using such risk indices obviates the problem of collinearity. We also show that the size of the chronological age effect in the risk prediction model associates with the correlation between a risk index and chronological age and that the RPC approach can satisfactorily recover cohort and period effects in most cases. We illustrate the advantages of RPC compared to traditional APC analysis on 27496 individuals from NHANES survey data (2005–2016) to study the longitudinal variability in depression screening over time. Our RPC method has broad implications for examining processes of change over time in longitudinal studies. [ABSTRACT FROM AUTHOR]

Objective: Clinical code sets are vital to research using routinely-collected electronic healthcare data. Existing code set engineering methods pose significant limitations when considering reproducible research. To improve the transparency and reusability of research, these code sets must abide by FAIR principles; this is not currently happening. We propose ‘term sets’, an equivalent alternative to code sets that are findable, accessible, interoperable and reusable. Materials and methods: We describe a new code set representation, consisting of natural language inclusion and exclusion terms (term sets), and explain its relationship to code sets. We formally prove that any code set has a corresponding term set. We demonstrate utility by searching for recently published code sets, representing them as term sets, and reporting on the number of inclusion and exclusion terms compared with the size of the code set. Results: Thirty-one code sets from 20 papers covering diverse disease domains were converted into term sets. The term sets were on average 74% the size of their equivalent original code set. Four term sets were larger due to deficiencies in the original code sets. Discussion: Term sets can concisely represent any code set. This may reduce barriers for examining and reusing code sets, which may accelerate research using healthcare databases. We have developed open-source software that supports researchers using term sets. Conclusion: Term sets are independent of clinical code terminologies and therefore: enable reproducible research; are resistant to terminology changes; and are less error-prone as they are shorter than the equivalent code set. [ABSTRACT FROM AUTHOR]

Understanding expression levels of proteins and their interactions is a key factor to diagnose and explain the Down syndrome which can be considered as the most prevalent reason of intellectual disability in human beings. In the previous studies, the expression levels of 77 proteins obtained from normal genotype control mice and from trisomic Ts65Dn mice have been analyzed after training in contextual fear conditioning with and without injection of the memantine drug using statistical methods and machine learning techniques. Recent studies have also pointed out that there may be a linkage between the Down syndrome and the immune system. Thus, the research presented in this paper aim at in silico identification of proteins which are significant to the learning process and the immune system and to derive the most accurate model for classification of mice. In this paper, the features are selected by implementing forward feature selection method after preprocessing step of the dataset. Later, deep neural network, gradient boosting tree, support vector machine and random forest classification methods are implemented to identify the accuracy. It is observed that the selected feature subsets not only yield higher accuracy classification results but also are composed of protein responses which are important for the learning and memory process and the immune system. [ABSTRACT FROM AUTHOR]

Malaria remains one the world’s most deadly infectious diseases, with almost half a million deaths and over 150 million clinical cases each year. An effective vaccine would contribute enormously to malaria control and will almost certainly be required for eventual eradication of the disease. However, the leading malaria vaccine candidate, RTS,S, shows only 30–50% efficacy under field conditions, making it less cost-effective than long-lasting insecticide treated bed nets. Other subunit malaria vaccine candidates, including TRAP-based vaccines, show no better protective efficacy. This has led to increased interest in combining subunit malaria vaccines as a means of enhancing protective efficacy. Mathematical models of the effect of combining such vaccines on protective efficacy can help inform optimal vaccine strategies and decision-making at all stages of the clinical process. So far, however, no such model has been developed for pre-clinical murine studies, the stage at which all candidate antigens and combinations begin evaluation. To address this gap, this paper develops a mathematical model of vaccine combination adapted to murine malaria studies. The model is based on simple probabilistic assumptions which put the model on a firmer theoretical footing than previous clinical models, which rather than deriving a relationship between immune responses and protective efficacy posit the relationship to be either exponential or Hill curves. Data from pre-clinical murine malaria studies are used to derive values for unknowns in the model which in turn allows simulations of vaccine combination efficacy and suggests optimal strategies to pursue. Finally, the ability of the model to shed light on fundamental biological variables of murine malaria such as the blood stage growth rate and sporozoite infectivity is explored. [ABSTRACT FROM AUTHOR]

Recent advances in the efficacy and tolerability of hepatitis C treatments and the introduction of a universal access scheme for the new Direct Acting Antiviral (DAA) therapies in March 2016, has resulted in a rapid increase in the uptake of hepatitis C treatment in Australia. Despite these positive developments, recent data suggest a plateauing of treatment numbers, indicating that more work may need to be done to identify and address ongoing barriers to hepatitis C treatment access and uptake. This paper aims to contribute to our understanding of the ongoing barriers to DAA therapies, with a focus on people who inject drugs. The paper draws on participant interview data from a qualitative research study based on a participatory research design that included a peer researcher with direct experience of both hepatitis C DAA treatment and injecting drug use at all stages of the research process. The study’s findings show that residual barriers to DAA treatment exist at personal, provider and system levels and include poor venous access, DAA treatments not considered ‘core-business’ by opioid substitution treatment (OST) providers, and patients having to manage multiple health and social priorities that interfere with keeping medical appointments such as childcare and poor access to transport services. Further, efforts to increase access to and uptake of DAA hepatitis C treatment over time will require a focus on reducing stigma and discrimination towards people who inject drugs as this remains as a major barrier to care for many people. [ABSTRACT FROM AUTHOR]

Measles is a highly transmissible disease and is one of the leading causes of death among young children under 5 globally. While the use of ongoing surveillance data and—recently—dynamic models offer insight on measles dynamics, both suffer notable shortcomings when applied to measles outbreak prediction. In this paper, we apply the Sequential Monte Carlo approach of particle filtering, incorporating reported measles incidence for Saskatchewan during the pre-vaccination era, using an adaptation of a previously contributed measles compartmental model. To secure further insight, we also perform particle filtering on an age structured adaptation of the model in which the population is divided into two interacting age groups—children and adults. The results indicate that, when used with a suitable dynamic model, particle filtering can offer high predictive capacity for measles dynamics and outbreak occurrence in a low vaccination context. We have investigated five particle filtering models in this project. Based on the most competitive model as evaluated by predictive accuracy, we have performed prediction and outbreak classification analysis. The prediction results demonstrate that this model could predict measles outbreak evolution and classify whether there will be an outbreak or not in the next month (Area under the ROC Curve of 0.89). We conclude that anticipating the outbreak dynamics of measles in low vaccination regions by applying particle filtering with simple measles transmission models, and incorporating time series of reported case counts, is a valuable technique to assist public health authorities in estimating risk and magnitude of measles outbreaks. It is to be emphasized that particle filtering supports estimation of (via sampling from) the entire state of the dynamic model—both latent and observable—for each point in time. Such approach offers a particularly strong value proposition for other pathogens with little-known dynamics, critical latent drivers, and in the context of the growing number of high-velocity electronic data sources. Strong additional benefits are also likely to be realized from extending the application of this technique to highly vaccinated populations. [ABSTRACT FROM AUTHOR]

Background & Aims: Extended esophageal endoscopic submucosal dissection (ESD) is highly responsible for esophageal stricture. We conducted a comparative study in a porcine model to evaluate the effectiveness of adipose tissue-derived stromal cell (ADSC) double cell sheet transplantation. Methods: Twelve female pigs were treated with 5 cm long hemi-circumferential ESD and randomized in two groups. ADSC group (n = 6) received 4 double cell sheets of allogenic ADSC on a paper support membrane and control group (n = 6) received 4 paper support membranes. ADSC were labelled with PKH-67 fluorophore to allow probe-based confocal laser endomicroscopie (pCLE) monitoring. After 28 days follow-up, animals were sacrificed. At days 3, 14 and 28, endoscopic evaluation with pCLE and esophagography were performed. Results: One animal from the control group was excluded (anesthetic complication). Animals from ADSC group showed less frequent alimentary trouble (17% vs 80%; P = 0.08) and higher gain weight on day 28. pCLE demonstrated a compatible cell signal in 4 animals of the ADSC group at day 3. In ADSC group, endoscopy showed that 1 out of 6(17%) animals developed a severe esophageal stricture comparatively to 100% (5/5) in the control group; P = 0.015. Esophagography demonstrated a decreased degree of stricture in the ADSC group on day 14 (44% vs 81%; P = 0.017) and day 28 (46% vs 90%; P = 0.035). Histological analysis showed a decreased fibrosis development in the ADSC group, in terms of surface (9.7 vs 26.1 mm²; P = 0.017) and maximal depth (1.6 vs 3.2 mm; P = 0.052). Conclusion: In this model, transplantation of allogenic ADSC organized in double cell sheets after extended esophegeal ESD is strongly associated with a lower esophageal stricture’s rate. [ABSTRACT FROM AUTHOR]

Background: The use of food supplements containing botanicals is increasing in European markets. Although intended to maintain the health status, several cases of adverse effects to Plant Food Supplements (PFS) have been described. Objectives: To describe the self-reported adverse effects collected during the European PlantLIBRA PFS Consumer Survey 2011–2012, with a critical evaluation of the plausibility of the symptomatology reported using data from the literature and from the PlantLIBRA Poisons Centers' survey. Subjects/Setting: From the total sample of 2359 consumers involved in the consumers' survey, 82 subjects reported adverse effects due to a total of 87 PFS. Results: Cases were self-reported, therefore causality was not classified on the basis of clinical evidence, but by using the frequency/strength of adverse effects described in scientific papers: 52 out of 87 cases were defined as possible (59.8%) and 4 as probable (4.6%). Considering the most frequently cited botanicals, eight cases were due to Valeriana officinalis (garden valerian); seven to Camellia sinensis (tea); six to Ginkgo biloba (Maidenhair tree) and Paullinia cupana (guarana). Most adverse events related to the gastrointestinal tract, nervous and cardiovascular systems. Conclusions: Comparing the data from this study with those published in scientific papers and obtained by the PlantLIBRA Poisons Centers' survey, some important conclusions can be drawn: severe adverse effects to PFS are quite rare, although mild or moderate adverse symptoms can be present. Data reported in this paper can help health professionals (and in particular family doctors) to become aware of possible new problems associated with the increasing use of food supplements containing botanicals. [ABSTRACT FROM AUTHOR]

Introduction: From 1990–2010, worldwide child mortality declined by 43%, and maternal mortality declined by 40%. This paper compares two sources of progress: improvements in societal coverage of health determinants versus improvements in the impact of health determinants as a result of technical change. Methods: This paper decomposes the progress made by 146 low- and middle-income countries (LMICs) in lowering childhood and maternal mortality into one component due to better health determinants like literacy, income, and health coverage and a second component due to changes in the impact of these health determinants. Health determinants were selected from eight distinct health-impacting sectors. Health determinants were selected from eight distinct health-impacting sectors. Regression models are used to estimate impact size in 1990 and again in 2010. Changes in the levels of health determinants were measured using secondary data. Findings: The model shows that respectively 100% and 89% of the reductions in maternal and child mortality since 1990 were due to improvements in nationwide coverage of health determinants. The relative share of overall improvement attributable to any single determinant varies by country and by model specification. However, in aggregate, approximately 50% of the mortality reductions were due to improvements in the health sector, and the other 50% of the mortality reductions were due to gains outside the health sector. Conclusions: Overall, countries improved maternal and child health (MCH) from 1990 to 2010 mainly through improvements in the societal coverage of a broad array of health system, social, economic and environmental determinants of child health. These findings vindicate efforts by the global community to obtain such improvements, and align with the post-2015 development agenda that builds on the lessons from the MDGs and highlights the importance of promoting health and sustainable development in a more integrated manner across sectors. [ABSTRACT FROM AUTHOR]

In palynology, the visual classification of pollen grains from different species is a hard task which is usually tackled by human operators using microscopes. Its complete automatization would save a high quantity of resources and provide valuable improvements especially for allergy-related information systems, but also for other application fields as paleoclimate reconstruction, quality control of honey based products, collection of evidences in criminal investigations or fabric dating and tracking. This paper presents three state-of-the-art deep learning classification methods applied to the recently published POLEN23E image dataset. The three methods make use of convolutional neural networks: the first one is strictly based on the idea of transfer learning, the second one is based on feature extraction and the third one represents a hybrid approach, combining transfer learning and feature extraction. The results from the three methods are indeed very good, reaching over 97% correct classification rates in images not previously seen by the models, where other authors reported around 70. [ABSTRACT FROM AUTHOR]

Established cell lines are widely used in research, however an appealing question is the comparability of the cells between various laboratories, their characteristics and stability in time. Problematic is also the cell line misidentification, genetic and phenotypic shift or Mycoplasma contamination which are often forgotten in research papers. The monocyte/macrophage-like cell line RAW 264.7 has been one of the most commonly used myeloid cell line for more than 40 years. Despite its phenotypic and functional stability is often discussed in literature or at various scientific discussion panels, their stability during the consecutive passages has not been confirmed in any solid study. So far, only a few functional features of these cells have been studied, for example their ability to differentiate into osteoclasts. Therefore, in the present paper we have investigated the phenotype and functional stability of the RAW 264.7 cell line from passage no. 5 till passage no. 50. We found out that the phenotype (expression of particular macrophage-characteristic genes and surface markers) and functional characteristics (phagocytosis and NO production) of RAW 264.7 cell line remains stable through passages: from passage no. 10 up to passage no. 30. Overall, our results indicated that the RAW 264.7 cell line should not be used after the passage no. 30 otherwise it may influence the data reliability. [ABSTRACT FROM AUTHOR]

Kaempferol (kae) and its glycosides are widely distributed in nature and show multiple bioactivities, yet few reports have compared them. In this paper, we report the antitumor, antioxidant and anti-inflammatory activity differences of kae, kae-7-O-glucoside (kae-7-O-glu), kae-3-O-rhamnoside (kae-3-O-rha) and kae-3-O-rutinoside (kae-3-O-rut). Kae showed the highest antiproliferation effect on the human hepatoma cell line HepG2, mouse colon cancer cell line CT26 and mouse melanoma cell line B16F1. Kae also significantly inhibited AKT phosphorylation and cleaved caspase-9, caspase-7, caspase-3 and PARP in HepG2 cells. A kae-induced increase in DPPH and ABTS radical scavenging activity, inhibition of concanavalin A (Con A)-induced activation of T cell proliferation and NO or ROS production in LPS-induced RAW 264.7 macrophage cells were also seen. Kae glycosides were used to produce kae via environment-friendly enzymatic hydrolysis. Kae-7-O-glu and kae-3-O-rut were hydrolyzed to kae by β-glucosidase and/or α-L-rhamnosidase. This paper demonstrates the application of enzymatic catalysis to obtain highly biologically active kae. This work provides a novel and efficient preparation of high-value flavone-related products. [ABSTRACT FROM AUTHOR]

In a previous paper we showed that the yeast Pichia pastoris X-33 grown in parboiled rice effluent supplemented with glycerol byproduct from the biodiesel industry improved the quality of the effluent. In this paper we show the validation of this yeast (PPE) as probiotic for broilers. Its effect on feed efficiency and immunomodulation was compared with the same yeast grown in yeast peptone dextrose medium (PPY), with Saccharomyces boulardii (SBY) and with the controls fed unsupplemented feed (CON). One-day-old female chicks were vaccinated against infectious bursal disease (IBD) and the titers of anti-IBD antibodies were measured by ELISA. PPE group had the highest mean titres on days 14 and 28 (p<0,05), and at 28 days, 64% of the animals showed seroconvertion. The PPE group also showed the best weight gains at 42 days of age, that, on days 7, 14 and 21 were 19%, 15%, and 8.7% higher, respectively, than the control group. The best feed conversion, 8.2% higher than the control group, was obtained by PPY at 42 days. Histopathological studies did not detect any undesirable effects in the supplemented animals. We concluded that Pichia pastoris X-33 when grown in effluents of the rice parboiling industry supplemented with glycerol byproduct from the biodiesel has probiotic properties for poultry. [ABSTRACT FROM AUTHOR]

The selection of seismic attributes is a key process in reservoir prediction because the prediction accuracy relies on the reliability and credibility of the seismic attributes. However, effective selection method for useful seismic attributes is still a challenge. This paper presents a novel selection method of seismic attributes for reservoir prediction based on the gray relational degree (GRD) and support vector machine (SVM). The proposed method has a two-hierarchical structure. In the first hierarchy, the primary selection of seismic attributes is achieved by calculating the GRD between seismic attributes and reservoir parameters, and the GRD between the seismic attributes. The principle of the primary selection is that these seismic attributes with higher GRD to the reservoir parameters will have smaller GRD between themselves as compared to those with lower GRD to the reservoir parameters. Then the SVM is employed in the second hierarchy to perform an interactive error verification using training samples for the purpose of determining the final seismic attributes. A real-world case study was conducted to evaluate the proposed GRD-SVM method. Reliable seismic attributes were selected to predict the coalbed methane (CBM) content in southern Qinshui basin, China. In the analysis, the instantaneous amplitude, instantaneous bandwidth, instantaneous frequency, and minimum negative curvature were selected, and the predicted CBM content was fundamentally consistent with the measured CBM content. This real-world case study demonstrates that the proposed method is able to effectively select seismic attributes, and improve the prediction accuracy. Thus, the proposed GRD-SVM method can be used for the selection of seismic attributes in practice. [ABSTRACT FROM AUTHOR]

In terms of public health, childhood vaccination programs have benefits that far outweigh risks. However, some parents decide not to vaccinate their children. This paper explores the ways in which such parents talked about the perceived risks and benefits incurred by vaccinating (or not vaccinating) their children. Between 2013–2016 we undertook 29 in-depth interviews with non-vaccinating and/or ‘vaccine hesitant’ parents in Australia. Interviews were conducted in an open and non-judgmental manner, akin to empathic neutrality. Interviews focused on parents talking about the factors that shaped their decisions not to (or partially) vaccinate their children. All interviews were transcribed and analysed using both inductive and deductive processes. The main themes focus on parental perceptions of: 1. their capacity to reason; 2. their rejection of Western medical epistemology; and 3. their participation in labour intensive parenting practices (which we term salutogenic parenting). Parents engaged in an ongoing search for information about how best to parent their children (capacity to reason), which for many led to questioning/distrust of traditional scientific knowledge (rejection of Western medical epistemology). Salutogenic parenting spontaneously arose in interviews, whereby parents practised health promoting activities which they saw as boosting the natural immunity of their children and protecting them from illness (reducing or negating the perceived need for vaccinations). Salutogenic parenting practices included breastfeeding, eating organic and/or home-grown food, cooking from scratch to reduce preservative consumption and reducing exposure to toxins. We interpret our data as a ‘logic of care’, which is seen by parents as internally consistent, logically inter-related and inter-dependent. Whilst not necessarily sharing the parents’ reasoning, we argue that an understanding of their attitudes towards health and well-being is imperative for any efforts to engage with their vaccine refusal at a policy level. [ABSTRACT FROM AUTHOR]

There is a growing concern both inside and outside the scientific community over the lack of reproducibility of experiments. The depth and detail of reported methods are critical to the reproducibility of findings, but also for making it possible to compare and integrate data from different studies. In this study, we evaluated in detail the methods reporting in a comprehensive set of trypanosomiasis experiments that should enable valid reproduction, integration and comparison of research findings. We evaluated a subset of other parasitic (Leishmania, Toxoplasma, Plasmodium, Trichuris and Schistosoma) and non-parasitic (Mycobacterium) experimental infections in order to compare the quality of method reporting more generally. A systematic review using PubMed (2000–2012) of all publications describing gene expression in cells and animals infected with Trypanosoma spp was undertaken based on PRISMA guidelines; 23 papers were identified and included. We defined a checklist of essential parameters that should be reported and have scored the number of those parameters that are reported for each publication. Bibliometric parameters (impact factor, citations and h-index) were used to look for association between Journal and Author status and the quality of method reporting. Trichuriasis experiments achieved the highest scores and included the only paper to score 100% in all criteria. The mean of scores achieved by Trypanosoma articles through the checklist was 65.5% (range 32–90%). Bibliometric parameters were not correlated with the quality of method reporting (Spearman's rank correlation coefficient <−0.5; p>0.05). Our results indicate that the quality of methods reporting in experimental parasitology is a cause for concern and it has not improved over time, despite there being evidence that most of the assessed parameters do influence the results. We propose that our set of parameters be used as guidelines to improve the quality of the reporting of experimental infection models as a pre-requisite for integrating and comparing sets of data. [ABSTRACT FROM AUTHOR]

Background: In November 2011, the GAVI Alliance made the decision to add HPV vaccine as one of the new vaccines for which countries eligible for its funding (less than $1520 per capita income) could apply to receive support for national HPV vaccination, provided they could demonstrate the ability to deliver HPV vaccines. This paper describes the data and analysis shared with GAVI policymakers for this decision regarding GAVI HPV vaccine support. The paper reviews why strategies and costs for HPV vaccine delivery are different from other vaccines and what is known about the cost components from available data that originated primarily from HPV vaccine delivery costing studies in low and middle income-countries. Methods: Financial costs of HPV vaccine delivery were compared across three sources of data: 1) vaccine delivery costing of pilot projects in five low and lower-middle income countries; 2) cost estimates of national HPV vaccination in two low income countries; and 3) actual expenditure data from national HPV vaccine introduction in a low income country. Both costs of resources required to introduce the vaccine (or initial one-time investment, such as cold chain equipment purchases) and recurrent (ongoing costs that repeat every year) costs, such as transport and health personnel time, were analyzed. The cost per dose, cost per fully immunized girl (FIG) and cost per eligible girl were compared across studies. Results: Costs varied among pilot projects and estimates of national programs due to differences in scale and service delivery strategy. The average introduction costs per fully immunized girl ranged from $1.49 to $18.94 while recurrent costs per girl ranged from $1.00 to $15.69, with both types of costs varying by delivery strategy and country. Evaluating delivery costs along programme characteristics as well as country characteristics (population density, income/cost level, existing service delivery infrastructure) are likely the most informative and useful for anticipating costs for HPV vaccine delivery. Conclusions: This paper demonstrates the importance of country level cost data to inform global donor policies for vaccine introduction support. Such data are also valuable for informing national decisions on HPV vaccine introduction. [ABSTRACT FROM AUTHOR]

Customized buses (CBs) are a new mode of public transportation and an important part of diversified public transportation, providing advanced, attractive and user-led service. The operational activity of a CB is planned by aggregating space–time demand and similar passenger travel demands. Based on an analysis of domestic and international research and the current development of CBs in China and considering passenger travel data, this paper studies the problems associated with the operation of CBs, such as stop selection, line planning and timetables, and establishes a model for the stop planning and timetables of CBs. The improved immune genetic algorithm (IIGA) is used to solve the model with regard to the following: 1) multiple population design and transport operator design, 2) memory library design, 3) mutation probability design and crossover probability design, and 4) the fitness calculation of the gene segment. Finally, a real-world example in Beijing is calculated, and the model and solution results are verified and analyzed. The results illustrate that the IIGA solves the model and is superior to the basic genetic algorithm in terms of the number of passengers, travel time, average passenger travel time, average passenger arrival time ahead of schedule and total line revenue. This study covers the key issues involving operational systems of CBs, combines theoretical research and empirical analysis, and provides a theoretical foundation for the planning and operation of CBs. [ABSTRACT FROM AUTHOR]

Background: Quality improvement collaboratives (QICs) have been used to improve health care for decades. Evidence on QIC effectiveness has been reported, but systematic reviews to date have little information from low- and middle-income countries (LMICs). Objective: To assess the effectiveness of QICs in LMICs. Methods: We conducted a systematic review following Cochrane methods, the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach for quality of evidence grading, and the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement for reporting. We searched published and unpublished studies between 1969 and March 2019 from LMICs. We included papers that compared usual practice with QICs alone or combined with other interventions. Pairs of reviewers independently selected and assessed the risk of bias and extracted data of included studies. To estimate strategy effectiveness from a single study comparison, we used the median effect size (MES) in the comparison for outcomes in the same outcome group. The primary analysis evaluated each strategy group with a weighted median and interquartile range (IQR) of MES values. In secondary analyses, standard random-effects meta-analysis was used to estimate the weighted mean MES and 95% confidence interval (CI) of the mean MES of each strategy group. This review is registered with PROSPERO (International Prospective Register of Systematic Reviews): CRD42017078108. Results: Twenty-nine studies were included; most (21/29, 72.4%) were interrupted time series studies. Evidence quality was generally low to very low. Among studies involving health facility-based health care providers (HCPs), for “QIC only”, effectiveness varied widely across outcome groups and tended to have little effect for patient health outcomes (median MES less than 2 percentage points for percentage and continuous outcomes). For “QIC plus training”, effectiveness might be very high for patient health outcomes (for continuous outcomes, median MES 111.6 percentage points, range: 96.0 to 127.1) and HCP practice outcomes (median MES 52.4 to 63.4 percentage points for continuous and percentage outcomes, respectively). The only study of lay HCPs, which used “QIC plus training”, showed no effect on patient care-seeking behaviors (MES -0.9 percentage points), moderate effects on non-care-seeking patient behaviors (MES 18.7 percentage points), and very large effects on HCP practice outcomes (MES 50.4 percentage points). Conclusions: The effectiveness of QICs varied considerably in LMICs. QICs combined with other invention components, such as training, tended to be more effective than QICs alone. The low evidence quality and large effect sizes for QIC plus training justify additional high-quality studies assessing this approach in LMICs. [ABSTRACT FROM AUTHOR]

The Epstein-Barr virus (EBV) induces B-cell proliferation with high efficiency through expression of latent proteins and microRNAs. This process takes place in vivo soon after infection, presumably to expand the virus reservoir, but can also induce pathologies, e.g. an infectious mononucleosis (IM) syndrome after primary infection or a B-cell lymphoproliferation in immunosuppressed individuals. In this paper, we investigated the growth characteristics of EBV-infected B-cells isolated from transplant recipients or patients with IM. We found that these cells grew and withstood apoptosis at highly variable rates, suggesting that the expansion rate of the infected B-cells widely varies between individuals, thereby influencing the size of the B-cell reservoir and the ability to form tumors in infected individuals. All viruses investigated were type 1 and genetically close to western strains. EBV-infected B-cells expressed the transforming EBV latent genes and microRNAs (miRNAs) at variable levels. We found that the B-cell growth rates positively correlated with the BHRF1 miRNA levels. Comparative studies showed that infected B-cells derived from transplant recipients with iEBVL on average expressed higher levels of EBV miR-BHRF1 miRNAs and grew more rapidly than B-cells from IM patients, suggesting infection by more transforming viruses. Altogether, these findings suggest that EBV infection has a highly variable impact on the B-cell compartment that probably reflects the genetic diversity of both the virus and the host. It also demonstrates the unexpected finding that B-cells from different individuals can grow at different speed under the influence of the same virus infection. [ABSTRACT FROM AUTHOR]

Objective: Systematic Review was used to evaluate the efficacy and safety of Dalfampridine (DAP) in the treatment of Mobility Disability (MS) in patients with Multiple Sclerosis. Methods: Clinical randomized controlled studies about DAP and placebo in the treatment of Mobility Disability in patients with Multiple Sclerosis until March 2019 were explored by searching Embase, PubMed, Cochrane, Web of Knowledge, and ClinicalTrials.gov. Literature screening, data extraction, quality assessment, and statistical analysis were performed by using Stata 14.0. Results: 10 papers were included in the meta-analysis, and the number of patients was 2100. In conclusion, the application of DAP in clinical can significantly improve the Mobility Disability of patients [OR = 2.73, 95%CI (1.66, 4.50), P<0.001, I2 = 74.1%] and boost the mobility speed of patients in Timing 24 Minute Walk Test (T24FW) [SMD = 3,08, 95%CI(1,58, 4.58), P<0.001, I2 = 98.7%]. There are no significant differences of the incidence of adverse events [RR = 1.06, 95%CI (0.99, 1.14), P = 0.928, I2 = 0.0%] and urinary tract infection [RR = 1.21, 95%CI(0.91, 1.60), P = 0.145, I2 = 37.2%] between the DAP test group (Doses≤10 mg) and the placebo control group, and the incidence of adverse events [RR = 1.14, 95%CI(1.02, 1.28), P = 0.793, I2 = 0.0%] and urinary tract infection[RR = 3.05, 95%CI(1.04, 8.99), P = 0.680, I2 = 0.0%] for the DAP test group (Doses>10 mg) is a litter higher than the placebo control group. Conclusion: DAP can effectively improve Mobility Disability in patients with Multiple Sclerosis, which is safe and reliable in specific DAP usage doses. [ABSTRACT FROM AUTHOR]

Vaccines remain one of the main tools to control infectious diseases in domestic livestock. Although a plethora of veterinary vaccines are on the market and routinely applied to protect animals against infection with particular pathogens, the disease in question often continues to persist, sometimes at high prevalence. The limited effectiveness of certain vaccines in the field leaves open questions regarding the required properties that an effective vaccine should have, as well as the most efficient vaccination strategy for achieving the intended goal of vaccination programmes. To date a systematic approach for studying the combined effects of different types of vaccines and vaccination strategies is lacking. In this paper, we develop a theoretical framework for modelling the epidemiological consequences of vaccination with imperfect vaccines of various types, administered using different strategies to herds with different replacement rates and heterogeneity in vaccine responsiveness. Applying the model to the Porcine Reproductive and Respiratory Syndrome (PRRS), which despite routine vaccination remains one of the most significant endemic swine diseases worldwide, we then examine the influence of these diverse factors alone and in combination, on within-herd virus transmission. We derive threshold conditions for preventing infection invasion in the case of imperfect vaccines inducing limited sterilizing immunity. The model developed in this study has practical implications for the development of vaccines and vaccination programmes in livestock populations not only for PRRS, but also for other viral infections primarily transmitted by direct contact. [ABSTRACT FROM AUTHOR]

The main goal of this paper is to study the effects of (1) trust in government medical experts and (2) proximity to a recent disease outbreak on vaccine propensity. More specifically, we explore how these variables affect attitudes with regards to measles. Using original survey data, collected in January/February 2017, we obtain three main empirical findings. First, contrary to our expectations, an individual’s proximity to a recent measles outbreak has no independent effect on vaccination attitudes. Second, corroborating previous studies in the field, we find that trust in institutions such as the CDC has a positive effect on our dependent variable. Third, there is a significant interactive relationship between proximity and trust in governmental medical experts. While distance from a previous measles outbreak has no effect on vaccination attitudes for respondents with medium or high levels of trust, the variable exerts a negative effect for subjects with little confidence in government medical experts. In other words: low-trust individuals who live farther away from a recent measles outbreak harbor less favorable views about vaccination for this particular disease than low-trust respondents who live close to an affected area. This implies that citizens who are skeptical of the CDC and similar institutions base their vaccination decision-making to some degree on whether or not a given disease occurs in close vicinity to their community. [ABSTRACT FROM AUTHOR]

Background: Developing countries still struggle with late detection and mortality from pertussis. A review of clinical case definitions is necessary for early disease detection. This paper aimed to study possible clinical characteristics for earlier pertussis detection in a sporadic setting. Methods: We conducted a retrospective review of medical and laboratory records in a general paediatric ward of a district hospital in a developing country. Inclusion criteria were all children hospitalised with nasopharyngeal swab taken for Bordetella pertussis. We compared sensitivity and specificity of World Health Organization diagnostic criteria with other clinical characteristics. Polymerase chain reaction Bordetella pertussis was the gold standard used. Results: Out of 207 eligible admissions, the study retrieved 128 complete records. Approximately half of the children were less than 3 months old. The World Health Organization diagnostic criteria had a low sensitivity (15%), but high specificity (92%). In comparison, combinations that included paroxysmal cough, ill contact and facial congestion had higher sensitivity. Increasing cough duration improved specificity while compromising sensitivity. Conclusion: Several clinical characteristics such as paroxysmal cough, facial congestion and a history of ill contact have potential for early clinical detection. Conventional emphasis on cough duration may hamper early detection. [ABSTRACT FROM AUTHOR]

The subset of pro-inflammatory B cells, called late memory, tissue-like or double negative (DN), accumulates in the blood of elderly individuals. Here we show that DN B cells do not proliferate and do not make antibodies to influenza antigens, but they secrete antibodies with autoimmune reactivity, in agreement with their membrane phenotype (CD95+CD21-CD11c+) and their spontaneous expression of the transcription factor T-bet. These cells also increase in the blood of individuals with obesity and autoimmune diseases, but causative mechanisms and signaling pathways involved are known only in part. In the present paper we compare frequencies and metabolic requirements of these cells in the blood of healthy individuals of different ages and in the blood and the subcutaneous adipose tissue (SAT) of individuals with obesity. Results show that DN B cells from young individuals have minimal metabolic requirements, DN B cells from elderly and obese individuals utilize higher amounts of glucose to perform autoimmune antibody production and enroll in aerobic glycolysis to support their function. DN B cells from the SAT have the highest metabolic requirements as they activate oxidative phosphorylation, aerobic glycolysis and fatty acid oxidation. DN B cells from the SAT also show the highest levels of ROS and the highest levels of phosphorylated AMPK (5’-AMP activated kinase) and Sestrin 1, both able to mitigate stress and cell death. This metabolic advantage drives DN B cell survival and function (secretion of autoimmune antibodies). [ABSTRACT FROM AUTHOR]

Streptococcus pneumonia is an important human pathogen that causes various severe diseases such as pneumonia, otitis and meningitis. Vaccination against S. pneumoniae is implemented in many developed countries. The presently used vaccines are safe, well tolerated but relatively expensive and require modification due to the immunological changes of the epidemic strains. This paper describes the development of a new pneumococcal vaccine candidate for immunization on mucosal surfaces. For this purpose the antigens of chimeric protein PSPF, previously suggested for an injectable S. pneumoniae vaccine, were expressed on the surface of the live probiotic strain Enterococcus faecium L3. Experiments on laboratory mice vaccinated with live bacteria demonstrated the appearance of the specific IgA and IgG which provide protection against the lethal S. pneumoniae infection. [ABSTRACT FROM AUTHOR]

Microscopic examination of peripheral blood plays an important role in the field of diagnosis and control of major diseases. Peripheral leukocyte recognition by manual requires medical technicians to observe blood smears through light microscopy, using their experience and expertise to discriminate and analyze different cells, which is time-consuming, labor-intensive and subjective. The traditional systems based on feature engineering often need to ensure successful segmentation and then manually extract certain quantitative and qualitative features for recognition but still remaining a limitation of poor robustness. The classification pipeline based on convolutional neural network is of automatic feature extraction and free of segmentation but hard to deal with multiple object recognition. In this paper, we take leukocyte recognition as object detection task and apply two remarkable object detection approaches, Single Shot Multibox Detector and An Incremental Improvement Version of You Only Look Once. To improve recognition performance, some key factors involving these object detection approaches are explored and the detection models are generated using the train set of 14,700 annotated images. Finally, we evaluate these detection models on test sets consisting of 1,120 annotated images and 7,868 labeled single object images corresponding to 11 categories of peripheral leukocytes, respectively. A best mean average precision of 93.10% and mean accuracy of 90.09% are achieved while the inference time is 53 ms per image on a NVIDIA GTX1080Ti GPU. [ABSTRACT FROM AUTHOR]

Many mRNA-based vaccines have been investigated for their specific potential to activate dendritic cells (DCs), the highly-specialized antigen-presenting cells of the immune system that play a key role in inducing effective CD4+ and CD8+ T-cell responses. In this paper we report a new vaccine/gene delivery platform that demonstrates the benefits of using a self-amplifying (“replicon”) mRNA that is protected in a viral-protein capsid. Purified capsid protein from the plant virus Cowpea Chlorotic Mottle Virus (CCMV) is used to in vitro assemble monodisperse virus-like particles (VLPs) containing reporter proteins (e.g., Luciferase or eYFP) or the tandem-repeat model antigen SIINFEKL in RNA gene form, coupled to the RNA-dependent RNA polymerase from the Nodamura insect virus. Incubation of immature DCs with these VLPs results in increased activation of maturation markers – CD80, CD86 and MHC-II – and enhanced RNA replication levels, relative to incubation with unpackaged replicon mRNA. Higher RNA uptake/replication and enhanced DC activation were detected in a dose-dependent manner when the CCMV-VLPs were pre-incubated with anti-CCMV antibodies. In all experiments the expression of maturation markers correlates with the RNA levels of the DCs. Overall, these studies demonstrate that: VLP protection enhances mRNA uptake by DCs; coupling replicons to the gene of interest increases RNA and protein levels in the cell; and the presence of anti-VLP antibodies enhances mRNA levels and activation of DCs in vitro. Finally, preliminary in vivo experiments involving mouse vaccinations with SIINFEKL-replicon VLPs indicate a small but significant increase in antigen-specific T cells that are doubly positive for IFN and TFN induction. [ABSTRACT FROM AUTHOR]

Ghana has made significant stride towards universal health coverage (UHC) by implementing the National Health Insurance Scheme (NHIS) in 2003. This paper investigates the progress of UHC indicators in Ghana from 1995 to 2015 and makes future predictions up to 2030 to assess the probability of achieving UHC targets. National representative surveys of Ghana were used to assess health service coverage and financial risk protection. The analyses estimated the coverage of 13 prevention and four treatment service indicators at the national level and across wealth quintiles. In addition, we calculated catastrophic health payments and impoverishment to assess financial hardship and used a Bayesian regression model to estimate trends and future projections as well as the probabilities of achieving UHC targets by 2030. Wealth-based inequalities and regional disparities were also assessed. At the national level, 14 out of the 17 health service indicators are projected to reach the target of 80% coverage by 2030. Across wealth quintiles, inequalities were observed amongst most indicators with richer groups obtaining more coverage than their poorer counterparts. Subnational analysis revealed while all regions will achieve the 80% coverage target with high probabilities for the prevention services, the same cannot be applied to the treatment services. In 2015, the proportion of households that suffered catastrophic health payments and impoverishment at a threshold of 25% non-food expenditure were 1.9% (95%CrI: 0.9–3.5) and 0.4% (95%CrI: 0.2–0.8), respectively. These are projected to reduce to 0.4% (95% CrI: 0.1–1.3) and 0.2% (0.0–0.5) respectively by 2030. Inequality measures and subnational assessment revealed that catastrophic expenditure experienced by wealth quintiles and regions are not equal. Significant improvements were seen in both health service coverage and financial risk protection over the years. However, inequalities across wealth quintiles and regions continue to be cause of concerns. Further efforts are needed to narrow these gaps. [ABSTRACT FROM AUTHOR]