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Background The study tests the effects of data collection modes on patient responses associated with the multi-item measures such as Patient-Reported Outcomes Measurement System (PROMIS®), and single-item measures such as Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE), and Numerical Rating Scale (NRS) measures. Methods Adult cancer patients were recruited from five cancer centers and administered measures of anxiety, depression, fatigue, sleep disturbance, pain intensity, pain interference, ability to participate in social roles and activities, global mental and physical health, and physical function. Patients were randomized to complete the measures on paper (595), interactive voice response (IVR, 596) system, or tablet computer (589). We evaluated differential item functioning (DIF) by method of data collection using the R software package, lordif. For constructs that showed no DIF, we concluded equivalence across modes if the equivalence margin, defined as ± 0.20 × pooled SD, completely surrounds 95% confidence intervals (CI's) for difference in mean score. If the 95% CI fell totally outside the equivalence margin, we concluded systematic score difference by modes. If the 95% CI partly overlaps the equivalence margin, we concluded neither equivalence nor difference. Results For all constructs, no DIF of any kind was found for the three modes. The scores on paper and tablet were more comparable than between IVR and other modes but none of the 95% CI’s were completely outside the equivalence margins, in which we established neither equivalence nor difference. Percentages of missing values were comparable for paper and tablet modes. Percentages of missing values were higher for IVR (2.3% to 6.5% depending on measures) compared to paper and tablet modes (0.7% to 3.3% depending on measures and modes), which was attributed to random technical difficulties experienced in some centers. Conclusion Across all mode comparisons, there were some measures with CI’s not completely contained within the margin of small effect. Two visual modes agreed more than visual-auditory pairs. IVR may induce differences in scores unrelated to constructs being measured in comparison with paper and tablet. The users of the surveys should consider using IVR only when paper and computer administration is not feasible.

Background Microfluidic chip detection technology is considered a potent tool for many bioanalytic applications. Rapid detection of foodborne pathogens in the early stages is imperative to prevent the outbreak of foodborne diseases, known as a severe threat to human health. Conventional bacterial culture methods for detecting foodborne pathogens are time-consuming, laborious, and lacking in pathogen diagnosis. To overcome this problem, we have created an embedded paper-based microchip based on isothermal loop amplification (LAMP), which can rapidly and sensitively detect foodborne pathogens. Results We embed paper impregnated with LAMP reagent and specific primers in multiple reaction chambers of the microchip. The solution containing the target pathogen was injected into the center chamber and uniformly distributed into the reaction chamber by centrifugal force. The purified DNA of Escherichia coli O157:H7, Salmonella spp., Staphylococcus aureus, and Vibrio parahaemolyticus has been successfully amplified and directly detected on the microchip. The E. coli O157:H7 DNA was identified as low as 0.0134 ng μL− 1. Besides, the potential of this microchip in point-of-care testing was further tested by combining the on-chip sample purification module and using milk spiked with Salmonella spp.. The pyrolyzed milk sample was filtered through a polydopamine-coated paper embedded in the inside of the sample chamber. It was transported to the reaction chamber by centrifugal force for LAMP amplification. Then direct chip detection was performed in the reaction chamber embedded with calcein-soaked paper. The detection limit of Salmonella spp. in the sample measured by the microchip was approximately 12 CFU mL− 1. Conclusion The paper embedded LAMP microchip offers inexpensive, user-friendly, and highly selective pathogen detection capabilities. It is expected to have great potential as a quick, efficient, and cost-effective solution for future foodborne pathogen detection.

Background The discovery of bioactive compounds in traditional Chinese medicine (TCM) has become an important field in TCM modernization. Ligand fishing is a suitable method for discovery of bioactive compounds in complex mixtures such as TCM with high selectivity. Because of unique advantage of low cost and convenience, paper-based microdevices can be good carriers for enzyme immobilized ligand fishing. Methods As an important enzyme for glucose metabolism, α-glucosidase was immobilized on polycaprolactone–chitosan-modified paper to prepare the microdevice with unique microfluid structure generated by 3D printing technology, which can be easily applied to screen active compounds in herbal extracts. The preparation conditions of the paper microarray were optimized. The activity of immobilized α-glucosidase was verified by colorimetric reactions which can be easily monitored by cellphone. The paper microarray with α-glucosidase immobilized was used to screen active compounds in the water extracts of mulberry leaves and lotus leaves. Results Several key parameters including Na2CO3 solution concentration, Na2CO3 solution volume, glutaraldehyde concentration, crosslinking time of glutaraldehyde and time of α-glucosidase immobilization were optimized. The proposed paper-based microarray was successfully applied in screening active compounds in two herbal extracts. Four compounds including chlorogenic acid, quercetin-3-O-glucuronide, isoquercetin, and quercetin were identified as α-glucosidase inhibitors. The compounds with significant non-specific adsorption caused by chitosan, such as isoquercitrin, astragalin, quercetin, were also found to be active compounds. Conclusions An enzyme immobilized paper microarray was designed and fabricated in this work. Polycaprolactone and chitosan were used to modify filter paper to prepare paper microarrays. Parameters of paper device preparation were optimized. Our findings suggested that 3D-printing paper-based microarrays can be a simple and low-cost approach for discovery of active compounds of TCM. Electronic supplementary material The online version of this article (10.1186/s13020-019-0236-y) contains supplementary material, which is available to authorized users.

Background COVID-19, caused by SARS-CoV-2 has become the most threatening issue to all populations around the world. It is, directly and indirectly, affecting all of us and thus, is an emerging topic dealt in global health. To avoid the infection, various studies have been done and are still ongoing. COVID-19 cases are reported all over the globe, and among the millions of cases, genetic similarity may be seen. The genetical common features seen within confirmed cases may help outline the tendency of infection and degree severity of the disease. Here, we reviewed multiple papers on SNPs related to SARS-CoV-2 infection and analyzed their results. Methods The PubMed databases were searched for papers discussing SNPs associated with SARS-CoV-2 infection and severity. Clinical studies with human patients and statistically showing the relevance of the SNP with virus infection were included. Quality Assessment of all papers was done with Newcastle Ottawa Scale. Results In the analysis, 21 full-text literature out of 2956 screened titles and abstracts, including 63,496 cases, were included. All were human-based clinical studies, some based on certain regions gathered patient data and some based on big databases obtained online. ACE2, TMPRSS2, and IFITM3 are the genes mentioned most frequently that are related to SARS-CoV-2 infection. 20 out of 21 studies mentioned one or more of those genes. The relevant genes according to SNPs were also analyzed. rs12252-C, rs143936283, rs2285666, rs41303171, and rs35803318 are the SNPs that were mentioned at least twice in two different studies. Conclusions We found that ACE2, TMPRSS2, and IFITM3 are the major genes that are involved in SARS-CoV-2 infection. The mentioned SNPs were all related to one or more of the above-mentioned genes. There were discussions on certain SNPs that increased the infection and severity to certain groups more than the others. However, as there is limited follow-up and data due to a shortage of time history of the disease, studies may be limited.

Radiology has not been spared in recent economic crises with a substantial reduction in the turnover of imaging equipment. These problems are exacerbated by increasing demand for healthcare across Europe. Therefore, using existing radiological services while rigorously following evidence-based guidelines might improve patient care. Thus, diagnostic pathways should be assessed not only for technical and diagnostic performance but also for their impact on medical and social outcome. In this paper, we report the advice of the Research Committee of ESSR on how we may guide musculoskeletal radiological research towards studies that have useful clinical impact. The ESSR Research Committee intends to encourage research with potential to influence treatment, patient outcome, and social impact. Key Points • Research in medical imaging has the potential to improve human health. • High-level studies have the potential to place radiology at the pinnacle of quality in evidence-based practice. • The ESSR Research Committee intends to encourage research with potential to influence treatment, patient outcome, and social impact.

Background Social support services such as day care centres are important in post-diagnostic dementia care to enable people living with dementia stay at home for longer. Little research has addressed potential inequalities in access, with no research on variations before and since COVID-19. The aim of this study was to explore inequalities in social support service usage before and since the pandemic. Methods Unpaid carers and people living with dementia were interviewed over the phone about their experiences of accessing social support services before and since the COVID-19 pandemic. Transcripts were analysed for key themes using inductive and deductive thematic analysis. Results Fifty participants (42 unpaid carers; eight people living with dementia) were interviewed, and five themes identified: (1) Service issues; (2) Access issues; (3) Relying on own initiative; (4) New inequalities due to COVID-19; and (5) Missing out on the benefits of support services. Participants reported transport, finances, and location as factors reducing their ability to access support service pre-COVID, with inequalities remaining and at times exacerbated since. Carers and people living with dementia also reported struggling with accessing basic necessities during COVID, including food and medicines. Conclusions Considering the benefits of accessing support services, resourced procedures and facilities are needed to maintain access to support services with more accessible remote support provision, enabling people from all backgrounds to access the care they need.

This study is the first comprehensive investigation of enzyme-producing bacteria isolated from four sludge samples (primary, secondary, press and machine) collected in a Kraft paper mill. Overall, 41 strains encompassing 11 different genera were identified by 16S rRNA gene analysis and biochemical testing. Both biodiversity and enzymatic activities were correlated with sludge composition. Press sludge hosted the largest variety of bacterial strains and enzymatic activities, which included hydrolytic enzymes and ligninolytic enzymes. In contrast, strains isolated from secondary sludge were devoid of several enzymatic activities. Most strains were found to metabolize Kraft liquor at its alkaline pH and to decolorize industrial lignin-mimicking dyes. Resistance to lignin or the ability to metabolize this substrate is a prerequisite to survival in any paper mill sludge type. We demonstrate here that the bacterial strains found in a typical Kraft paper mill represent a source of potential novel enzymes for both industrial applications and bioremediation. Electronic supplementary material The online version of this article (doi:10.1186/s40064-016-3147-8) contains supplementary material, which is available to authorized users.

Background Isothermal amplification techniques are emerging as a promising method for malaria diagnosis since they are capable of detecting extremely low concentrations of parasite target while mitigating the need for infrastructure and training required by other nucleic acid based tests. Recombinase polymerase amplification (RPA) is promising for further development since it operates in a short time frame (

Background This is the third in a series of three papers describing the use of qualitative evidence syntheses (QES) to inform the development of clinical and health systems guidelines. WHO has recognised the need to improve its guideline methodology to ensure that decision-making processes are transparent and evidence based, and that the resulting recommendations are relevant and applicable to end users. In addition to the standard data on effectiveness, WHO guidelines increasingly use evidence derived from QES to provide information on acceptability and feasibility and to develop important implementation considerations. Methods WHO convened a group drawn from the technical teams involved in formulating recent (2010–2018) guidelines employing QES. Using a pragmatic and iterative approach that included feedback from WHO staff and other stakeholders, the group reflected on, discussed and identified key methods and research implications from designing QES and using the resulting findings in guideline development. As members of WHO guideline technical teams, our aim in this paper is to explore how we have used findings from QES to develop implementation considerations for these guidelines. Results For each guideline, in addition to using systematic reviews of effectiveness, the technical teams used QES to gather evidence of the acceptability and feasibility of interventions and, in some cases, equity issues and the value people place on different outcomes. This evidence was synthesised using standardised processes. The teams then used the QES to identify implementation considerations combined with other sources of information and input from experts. Conclusions QES were useful sources of information for implementation considerations. However, several issues for further development remain, including whether researchers should use existing health systems frameworks when developing implementation considerations; whether researchers should take confidence in the evidence into account when developing implementation considerations; whether qualitative evidence that reveals implementation challenges should lead guideline panels to make conditional recommendations or only point to implementation considerations; and whether guideline users find it helpful to have challenges pointed out to them or whether they also need solutions. Finally, we need to explore how QES findings can be incorporated into derivative products to aid implementation.

Background Skin neurofibromas represent one of the main clinical manifestations of neurofibromatosis 1, and their number varies greatly between individuals. Quantifying their number is an important step in the methodology of many clinical studies, but counting neurofibromas one by one in individuals with thousands of tumors is arduous, time-consuming, and subject to intra and interexaminer variability. We aimed to evaluate the efficacy of a new methodology for skin neurofibromas quantification using paper frames. Methods The sample comprised 92 individuals with NF1. Paper frames, with a central square measuring 100 cm2, were placed on the back, abdomen and thigh. Images were taken, transferred to a computer and two independent examiners counted the neurofibromas. The average number of neurofibromas/100 cm2 of skin was obtained from the mean of the three values. The differences in the quantity of neurofibromas counted by two examiners were evaluated with Intraclass correlation coefficient (ICC), paired t-test, Bland-Altman and survival-agreement plots. To evaluate the predictive value of the method in obtaining the total number of neurofibromas, 49 participants also had their tumors counted one by one. Reproducibility was assessed with Pearson’s correlation coefficients and simple linear regression model. Results There was excellent agreement between examiners (ICC range 0.992-0.997) and the total number of skin neurofibromas could be predicted by the adhesive frames technique using a specific formula (P

Objective We assessed the measurement equivalence and feasibility of the paper-and-pencil and touch-screen modes of administration of the Taiwan Chinese version of the EORTC QLQ-PR25, a commonly used questionnaire to evaluate the health-related quality of life (HRQOL) in patients with prostate cancer in Taiwan. Methods A cross-over design study was conducted in 99 prostate cancer patients at an urology outpatient clinic. Descriptive exact and global agreement percentages, intraclass correlation, and equivalence test based on minimal clinically important difference (MCID) approach were used to examine the equity of HRQOL scores between these two modes of administration. We also evaluated the feasibility of computerized assessment based on patients’ acceptability and preference. Additionally, we used Rasch rating scale model to assess differential item functioning (DIF) between the two modes of administration. Results The percentages of global agreement in all domains were greater than 85% in the EORTC QLQ-PR25. All results from equivalence tests were significant, except for Sexual functioning, indicating good equivalence. Only one item exhibited DIF between the two modes. Although nearly 80% of the study patients had no prior computer-use experience, the overall proportion of acceptance and preference for the touch-screen mode were quite high and there was no significant difference across age groups or between computer-use experience groups. Conclusions The study results showed that the data obtained from the modes of administration were equivalent. The touch-screen mode of administration can be a feasible and suitable alternative to the paper-and-pencil mode for assessment of patient-reported outcomes in patients with prostate cancer.

Blood paper cards provide an effective DNA storage method. In this study, we used three DNA dissolving reagents (Tris-EDTA [TE] buffer, Tris–HCl buffer, and water) and one common commercially available kit (DN131 from MRC Inc) to elute DNA from 105 human blood paper cards collected up to 10 years ago. These DNA samples were used as templates for amplification of a single nucleotide polymorphism (SNP, C125T) region of human caspase-12 by PCR and a specific Taqman genotyping assay using the same amount of DNA. We show that DNA isolated by Tris–HCl buffer has higher yield and quality in comparison to DN131 solution. PCR success rate to amplify caspase-12 C125T SNP using Tris–HCl is comparable to the method using DN131 (89.5% vs 87.6%). The Taqman genotyping success rate using Tris–HCl is higher than using DN131 (81.9% vs 70.5%). Using TE or water, PCR success rates are lower than using DN131 (73.3% [TE]; 72.4% [H2O]), but Taqman genotyping success rates are comparable to the method using DN131 (70.5% [TE]; 79.1% [H2O]). We concluded that using Tris–HCl is a reliable and effective method to elute DNA from old human blood paper cards. The crude DNA isolated by Tris–HCl can be used to study genetic polymorphisms in human populations.

Introduction The vast difference in the abundance of different proteins in biological samples limits the determination of the complete proteome of a cell type, requiring fractionation of proteins and peptides before MS analysis. Methods We present a method consisting of electrophoresis of complex mixtures of peptides using a strip of filter paper cut into 20 sections laid end to end over a 24-cm-long IPG strip, the pH gradient of which would drive the electrophoresis. Peptides absorbed onto individual paper pads after electrophoresis are subsequently recovered into a buffer solution, thus dividing a complex peptide mixture according to pI into 20 liquid fractions. This paper-based IEF method (PIEF) was compared side-by-side with a similar but liquid-based Offgel electrophoresis (OGE) by analyzing iTRAQ-labeled peptide mixtures of membrane proteins from four different cell types. Results PIEF outperformed OGE in resolving acidic peptides, whereas OGE did a better job in recovering relatively basic peptides. OGE and PIEF were quite comparable in their coverage, identifying almost equal number of distinct proteins (PIEF =1174; OGE = 1080). Interestingly, however, only 675 were identified by both of them, each method identifying many unique proteins (PIEF = 499; OGE = 415). Thus, the two methods uncovered almost 40% more proteins compared to what is obtained by only one method. Conclusion: This initial investigation demonstrates the technical feasibility of PIEF for complementing OGE. PIEF uses standard IPG IEF equipment, requires no specialized apparatus (e.g., OGE fractionator) and may be integrated into peptide mapping strategies for clinical samples.

Background As South Africa strives to achieve malaria elimination by 2018 (zero local cases) the country needs to strengthen its disease surveillance system by reducing the timeliness from case diagnosis to notification of key stakeholders in the malaria programme. This study evaluated the feasibility of a 24-h mobile reporting system, designed for speeding up malaria notifications, from primary healthcare facilities to district, provincial, and national malaria programmes in South Africa. Methods A prospective descriptive study utilizing primary data collected from structured interviews with healthcare workers in public healthcare facilities was used to compare two reporting systems (24-h mobile reporting system and the paper-based reporting system) in malaria endemic provinces (Limpopo, Mpumalanga and KwaZulu-Natal). Data on completeness of reporting, simplicity, user acceptability and technical limitations were analysed. A Wilcoxon signed-rank test was used to compare the time difference between the two reporting systems. Results There were 1819 cases of malaria reported through the paper-based system, and 63.2% (1149) of those cases were also reported through the 24-h mobile reporting system. Out of the 272 healthcare workers who were interviewed, 40% (108) had seen malaria patients and reported a case through the 24-h mobile reporting system. The median time for cases to be reported through the 24-h mobile reporting system was significantly shorter at 39 days) (p

To determine journal publication rates of scientific papers presented orally at the European Congress of Radiology (ECR) 2010, with comparison of country data to ECR 2000. All oral presentations from ECR 2010 were evaluated for publication between 2010 and 2014 using the MEDLINE database. Countries, collaborations, subspecialties, modalities and study design were ranked by publication percentage. Chi-square tests were used to compare publication percentages for each category of variables. Hazard ratios (HR) were calculated for each country relative to the host nation, Austria. ECR 2010 country statistics were compared with analogous data from ECR 2000. In total, 360/840 abstracts were subsequently published (43 %). The author’s country of origin (p = 0.02), subspecialty (p = 0.02) and study design (p = 0.001) were significantly associated with subsequent publication. Switzerland, the Netherlands, France and Germany were among the top six countries by publication percentage in 2000 and 2010. In 2010, Switzerland had the highest publication rate (62 %) and HR in comparison to Austria (HR 2.62 [1.31–5.25], p = 0.01). Three Asian nations increased relative publication rates over the 10-year period. Several European nations consistently convert relatively high percentages of oral abstracts at ECR into publications, and the influence of Asian countries is increasing. • Certain European nations consistently publish high percentages of orally presented abstracts at ECR. • The influence of several Asian countries on ECR is increasing. • Country, subspecialty and study design are significantly associated with journal publication. • Authors collaborating internationally have the highest publication rates and mean impact factors. • Among all modalities, PET-CT, MRI and CT have the highest publication percentages.

In 2014, the European Medicines Agency (EMA) released for comment a draft reflection paper on the use of patient-reported outcome (PRO) measures in oncology studies. A twelve-member International Society for Quality of Life Research (ISOQOL) taskforce was convened to coordinate the ISOQOL response. Twenty-one ISOQOL members provided detailed comments and suggestions on the paper: 81 % from academia and 19 % from industry. Taskforce members consolidated and further refined these comments and shared the recommendations with the wider ISOQOL membership. A final response was submitted to the EMA in November 2014. The impending publication of the EMA reflection paper presents a valuable opportunity for ISOQOL to comment on the current direction of EMA PRO guidance and strategy. The EMA paper, although focused on cancer, could serve as a model for using PROs in other conditions, as it provides a useful update surrounding some of the design issues common to all trial research including PRO endpoints. However, we believe there are a number of additional areas in need of greater consideration. The purpose of this commentary is therefore to highlight the strengths of this timely and potentially useful document, but also to outline areas that may warrant further discussion.

IntroductionAposematism is a defense system against predators consisting of the toxicity warning using conspicuous coloration. If the toxin production and aposematic coloration is costly, only individuals in good physical condition could simultaneously produce abundant poison and striking coloration. In such cases, the aposematic coloration not only indicates that the animal is toxic, but also the toxicity level of individuals. The costs associated with the production of aposematic coloration would ensure that individuals honestly indicate their toxicity levels. In the present study, we examine the hypothesis that a positive correlation exists between the brightness of warning coloration and toxicity level using as a model the paper wasp (Polistes dominula).ResultsWe collected wasps from 30 different nests and photographed them to measure the brightness of warning coloration in the abdomen. We also measured the volume of the poison gland, as well as the length, and the width of the abdomen. The results show a positive relationship between brightness and poison-gland size, which remained positive even after controlling for the body size and abdomen width.ConclusionThe results suggest that the coloration pattern of these wasps is a true sign of toxicity level: wasps with brighter colors are more poisonous (they have larger poison glands).

Rock phosphate (RP) addition in cow-dung waste-paper mixtures at rates above 2% P has been reported to increase the rate of bio-transformation and humification of organic waste mixtures during vermicomposting to produce organic fertilizer for organic farming. However, the optimization of RP for vermicomposting was not established. The objective of this study was to determine the optimal amount of RP integration rates for effective bio-transformation of cow-dung waste-paper mixtures. Arrays of RP integration degrees (0, 0.5, 1, 1.5, 2, and 4% P as RP) were thoroughly mixed with cow- dung waste-paper mixtures to achieve an optimized C:N ratio of 30 and allowed to vermidegrade following the introduction of earthworms at a stocking mass of 12.5 g-worms kg−1. The bio-transformation of the waste mixtures was examined by measuring C:N ratios and humification index (HI) and per cent ash and volatile solids. Application of 1% P as RP resulted in fast bio-transformation and maturation of cow-dung waste-paper mixtures. A scanning electron microscopy (SEM) was used to evaluate the morphological properties of the different vermicomposts affected by rates of RP showing the degree of degradation of initial compacted aggregates of cellulose and protein fibres in the mixtures at maturity. A germination test was used to further determine phytotoxicity of the final composts and microbial biomass assessment. The final vermicompost (organic fertilizer) had a C:N ratio of 7, MBC of 900 mg kg−1 and HI of 27.1%. The RP incorporation rate of 1% P of RP investigated is therefore, recommended for efficient vermidegradation and humification of cow-dung waste-paper mixtures. However, higher rates of RP incorporation should be considered where greater P enrichment of the final vermicompost (organic fertilizer) is desired.

Background PRO-CTCAE is a library of items that measure cancer treatment-related symptomatic adverse events (NCI Contracts: HHSN261201000043C and HHSN 261201000063C). The objective of this study is to examine the equivalence and acceptability of the three data collection modes (Web-enabled touchscreen tablet computer, Interactive voice response system [IVRS], and paper) available within the US National Cancer Institute (NCI) Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) measurement system. Methods Participants (n = 112; median age 56.5; 24 % high school or less) receiving treatment for cancer at seven US sites completed 28 PRO-CTCAE items (scoring range 0–4) by three modes (order randomized) at a single study visit. Subjects completed one page (approx. 15 items) of the EORTC QLQ-C30 between each mode as a distractor. Item scores by mode were compared using intraclass correlation coefficients (ICC); differences in scores within the 3-mode crossover design were evaluated with mixed-effects models. Difficulties with each mode experienced by participants were also assessed. Results 103 (92 %) completed questionnaires by all three modes. The median ICC comparing tablet vs IVRS was 0.78 (range 0.55–0.90); tablet vs paper: 0.81 (0.62–0.96); IVRS vs paper: 0.78 (0.60–0.91); 89 % of ICCs were ≥0.70. Item-level mean differences by mode were small (medians [ranges] for tablet vs. IVRS = −0.04 [−0.16–0.22]; tablet vs paper = −0.02 [−0.11–0.14]; IVRS vs paper = 0.02 [−0.07–0.19]), and 57/81 (70 %) items had bootstrapped 95 % CI around the effect sizes within +/−0.20. The median time to complete the questionnaire by tablet was 3.4 min; IVRS: 5.8; paper: 4.0. The proportion of participants by mode who reported “no problems” responding to the questionnaire was 86 % tablet, 72 % IVRS, and 98 % paper. Conclusions Mode equivalence of items was moderate to high, and comparable to test-retest reliability (median ICC = 0.80). Each mode was acceptable to a majority of respondents. Although the study was powered to detect moderate or larger discrepancies between modes, the observed ICCs and very small mean differences between modes provide evidence to support study designs that are responsive to patient or investigator preference for mode of administration, and justify comparison of results and pooled analyses across studies that employ different PRO-CTCAE modes of administration. Trial registration NCT Clinicaltrials.gov identifier: NCT02158637

Background In about one in 10,000 cases, a published article is retracted. This very often means that the results it reports are flawed. Several authors have voiced concerns about the presence of retracted research in the memory of science. In particular, a retracted result is propagated by citing it. In the published literature, many instances are given of retracted articles that are cited both before and after their retraction. Even worse is the possibility that these articles in turn are cited in such a way that the retracted result is propagated further. Methods We have conducted a case study to find out how a retracted article is cited and whether retracted results are propagated through indirect citations. We have constructed the entire citation network for this case. Results We show that directly citing articles is an important source of propagation of retracted research results. In contrast, in our case study, indirect citations do not contribute to the propagation of the retracted result. Conclusions While admitting the limitations of a study involving a single case, we think there are reasons for the non-contribution of indirect citations that hold beyond our case study. Electronic supplementary material The online version of this article (doi:10.1186/s41073-016-0008-5) contains supplementary material, which is available to authorized users.

In May 2013, the WHO Member States requested the WHO to establish a Global Observatory on Health Research and Development (R&D), as part of a strategic work-plan to promote innovation, build capacity, improve access, and mobilize resources to address diseases that disproportionately affect the world’s poorest countries. The rationale for establishing a Global Observatory on Health R&D is to provide a mechanism to monitor and analyse health R&D resource flows, product pipelines, and research outputs, aiming to contribute to the identification of gaps to inform priority-setting for new R&D investments to be operationalized through a new global financing and coordination mechanism for health R&D and utilized by all stakeholders informing health research policy decisions in countries, civil society, and the private sector. As one of the mechanisms to achieve the goals of the Global Observatory on Health R&D, the WHO is launching a Call for Papers to be published as a Thematic Series in Health Research Policy and Systems to contribute state-of-the-art knowledge and innovative approaches to analyse, interpret, and report on health R&D information. Further, to serve as a key resource to inform the future WHO-convened coordination mechanism, which will be utilized to generate evidence-informed priorities for new R&D investments to be financed through a proposed new global financing and coordination mechanism for health R&D. Electronic supplementary material The online version of this article (doi:10.1186/1478-4505-13-9) contains supplementary material, which is available to authorized users.

Background Ethanol production from paper sludge (PS) by simultaneous saccharification and fermentation (SSF) is considered to be the most appropriate way to process PS, as it contains negligible lignin. In this study, SSF was conducted using a cellulase produced from PS by the hypercellulase producer, Acremonium cellulolyticus C-1 for PS saccharification, and a thermotolerant ethanol producer Saccharomyces cerevisiae TJ14 for ethanol production. Using cellulase of PS origin minimizes biofuel production costs, because the culture broth containing cellulase can be used directly. Results When 50 g PS organic material (PSOM)/l was used in SSF, the ethanol yield based on PSOM was 23% (g ethanol/g PSOM) and was two times higher than that obtained by a separate hydrolysis and fermentation process. Cellulase activity throughout SSF remained at around 60% of the initial activity. When 50 to 150 g PSOM/l was used in SSF, the ethanol yield was 21% to 23% (g ethanol/g PSOM) at the 500 ml Erlenmeyer flask scale. Ethanol production and theoretical ethanol yield based on initial hexose was 40 g/l and 66.3% (g ethanol/g hexose) at 80 h, respectively, when 161 g/l of PSOM, 15 filter paper units (FPU)/g PSOM, and 20% inoculum were used for SSF, which was confirmed in the 2 l scale experiment. This indicates that PS is a good raw material for bioethanol production. Conclusions Ethanol concentration increased with increasing PSOM concentration. The ethanol yield was stable at PSOM concentrations of up to 150 g/l, but decreased at concentrations higher than 150 g/l because of mass transfer limitations. Based on a 2 l scale experiment, when 1,000 kg PS was used, 3,182 kFPU cellulase was produced from 134.7 kg PS. Produced cellulase was used for SSF with 865.3 kg PS and ethanol production was estimated to be 51.1 kg. Increasing the yeast inoculum or cellulase concentration did not significantly improve the ethanol yield or concentration.

Background Previously, we showed that the intake of trans fatty acids during pregnancy and lactation triggers a pro-inflammatory status in the offspring. On the other hand, prebiotics can alter the intestinal environment, reducing serum lipopolysaccharides (LPS) concentrations. This study evaluated the effect of the oligofructose 10% diet supplementation in the presence or absence of hydrogenated vegetable fat during pregnancy and lactation on the development, endotoxemia and bacterial composition of 21-d-old offspring. Methods On the first day of pregnancy rats were divided into four groups: control diet (C), control diet supplemented with 10% oligofructose (CF), diet enriched with hydrogenated vegetable fat, rich in TFA (T) or diet enriched with hydrogenated vegetable fat supplemented with 10% oligofructose (TF). Diets were maintained during pregnancy and lactation. At birth, 7th, 14th and 21th, pups were weighed and length was measured. Serum concentrations of LPS and free fatty acids (FFA) were performed by specific kits. Bacterial DNA present in faeces was determined by real-time PCR. Data were expressed as mean ± standard error of the mean and the statistical analysis was realized by ANOVA two-way and ANOVA for repeated measures. p

Background We assessed the metrics used in claims about disease importance made in the introductory sections of scientific papers published in 1993 and 2003. We were interested in the choice of metric in circumstances where establishing the relative social importance of a disease was, presumptively, a primary objective. Methods This study consisted of a textual examination of the introductory statements from papers retrieved from MEDLINE. Papers were published in the New England Journal of Medicine, The Lancet, and the Journal of the American Medical Association during the first halves of 1993 and 2003, and were selected on the basis of keywords found in a pilot study to be associated with claims about disease importance. Results We found 143 papers in 1993 and 264 papers in 2003 included claims about disease importance in their introductory sections, and characteristics of these claims were abstracted. Of the quotes identified in the papers and articles examined, most used counts, prevalence, or incidence measurements. Some also used risk estimates and economic quantities to convey the importance of the disease. There was no change in the types of metrics used between 1993 and 2003. Very few articles, even in 2003, used metrics that weighted disease onsets by the expected consequent loss of healthy time -- such as years of life lost, quality-adjusted life years, and/or disability-adjusted life years. Conclusions Claims about the relative importance of diseases continued to be overwhelmingly expressed in terms of counts (of deaths and disease onsets) and comparisons of counts, rates, and risks. Where the aim is to convey the burden that a given disease imposes on a society, "event-based" metrics might be less fit for the purpose than "time-based" metrics. More attention is needed to how the choice of metric should relate to the purpose at hand.

This report is the SOSORT Consensus Paper on School Screening for Scoliosis discussed at the 4th International Conference on Conservative Management of Spinal Deformities, presented by SOSORT, on May 2007. The objectives were numerous, 1) the inclusion of the existing information on the issue, 2) the analysis and discussion of the responses by the meeting attendees to the twenty six questions of the questionnaire, 3) the impact of screening on frequency of surgical treatment and of its discontinuation, 4) the reasons why these programs must be continued, 5) the evolving aim of School Screening for Scoliosis and 6) recommendations for improvement of the procedure.

Background Indonesia's recent economic and political history has left a legacy of widespread poverty and serious health problems, and has contributed to marked inequalities in health care. One means of responding to these challenges has been through a reconsideration of the professional roles of nurses, to enable them to deal with the range and complexity of health problems. However, there are currently a number of obstacles to achieving these aims: there is a serious shortfall in trained nurses; the majority of nurses have only limited education and preparation for the role; and there is no central registration of nurses, which means that it is impossible to regulate either the profession or the standards of care. This study aimed to establish the occupational profiles of each grade of nurse, identify their training and development needs and ascertain whether any differences existed between nurses working in different regions or within hospital or community settings. Methods An established and psychometrically valid questionnaire was administered to 524 nurses, covering three grades and coming from five provinces. Results Significant differences in job profile were found in nurses from different provinces, suggesting that the nature of the role is determined to some degree by the geographical location of practice. The roles of hospital and community nurses, and the different grades of nurse, were fairly similar. All nurses reported significant training needs for all 40 tasks, although these did not vary greatly between grade of nurse. The training needs of nurses from each of the provinces were quite distinct, while those of hospital nurses were greater than those of community nurses. Conclusion The results suggest that the role of the nurse is not as diverse as might be expected, given the different levels of preparation and training and the diversity of their work environments. This may reflect the lack of a central registration system and quality framework, which would normally regulate clinical activities according to qualifications. The differences in training needs between subsections of the sample highlight the importance of identifying skills deficits and using this information to develop customized post-registration education programmes. Together, these results provide a rigorous and reliable approach to defining the occupational roles and continuing education needs of Indonesian nurses.

Background Despite recent developments, health care provision in Indonesia remains suboptimal. Difficult terrain, economic crises, endemic diseases and high population numbers, coupled with limited availability of qualified health care professionals, all contribute to poor health status. In a country with a population of 220 million, there are currently an estimated 50 nurses and 26 midwives per 100 000 people. In line with government initiatives, this series of studies was undertaken to establish the training and development needs of nurses and midwives working within a variety of contexts in Indonesia, with the ultimate aim of enhancing care provision within these domains. Methods An established, psychometrically valid and reliable training needs instrument was modified for use within the Indonesian context. While this technique has had widespread international use in the developed world, its application for developing countries has not yet been established. The standard form consists of a biographical cover sheet and a core set of 30 items (all health-related tasks), which have to be rated along two seven-point scales. The first of these scales asks respondents to assess how important the task is to their job and the second scale is a self-assessment of respondents' current performance level of the task. By comparing the importance rating with the performance rating, an index of training need can be obtained (high importance and low performance indicating a significant training need). The modifications incorporated for use in this series of studies were a further 10 items, which were constructed following expert group and focus group discussions and a review of the relevant literature. Pilot trials with 109 respondents confirmed its feasibility and acceptability. The instrument was then administered to 524 nurses and 332 midwives across Indonesia. Results The data were subjected to a retrospective factor analysis, using a Varimax rotation and Cronbach's α to check the instrument's validity and reliability following modification. The results yielded six factors, which accounted for >53% of the variance, each of which had a Cronbach's α score of between 0.8644 and 0.7068. Conclusion The results suggest that the modified instrument remained valid and reliable for use in the Indonesian nursing and midwifery context.

THE formation of more than one zone containing phosphate when the sodium orthophosphates are chromatographed on paper suggests that these spots contain different molecular species originating in proton transfer equilibria of the kind: where B−n is a base1,2. The speed of proton transfers, for example, the half-life for the reaction of hydronium and hydroxyl ions is 10−8 sec3, argues against this as such equilibria yield multiple spots only if the transition time is comparable with the time required for the formation of the chromatogram4. It is natural to question next if the zones are actually of different species since discontinuities in either the immobile or mobile phases can also produce the result4. Chromatograms of orthophosphoric acid and of the primary, secondary, and tertiary sodium salts were formed on 55 cm × 2.8 cm strips of Whatman No. 1 filter paper, acid washed, which had also been washed in 2 M acetic acid followed by three successive rinsings in distilled water5. The chromatograms were formed either with pyridine/ethyl acetate/water (the faster solvent) or butanol/water. Fig. 1 is a photograph of 10 µl. of 0.01 M trisodium phosphate (No. 321) and 10 µl. of 0.01 M sodium dihydrogen phosphate (No. 322) formed simultaneously with BuOH/15 per cent H2O. The origin was the vertical pencil line adjacent to the numbers. When revealed, the colour process was that employing ammonium molybdate and benzidine hydrochloride6. In certain select cases, the multiple spots were irradiated in the University's Triga reactor7,8. Both sodium and phosphorus undergo (n,γ)·reactions to form radioactive isotopes which decay as follows9,10

Background Removing user fees in primary health care services is one of the most critical policy issues being considered in Africa. User fees were introduced in many African countries during the 1980s and their impacts are well documented. Concerns regarding the negative impacts of user fees have led to a recent shift in health financing debates in Africa. Kenya is one of the countries that have implemented a user fees reduction policy. Like in many other settings, the new policy was evaluated less that one year after implementation, the period when expected positive impacts are likely to be highest. This early evaluation showed that the policy was widely implemented, that levels of utilization increased and that it was popular among patients. Whether or not the positive impacts of user fees removal policies are sustained has hardly been explored. We conducted this study to document the extent to which primary health care facilities in Kenya continue to adhere to a 'new' charging policy 3 years after its implementation. Methods Data were collected in two districts (Kwale and Makueni). Multiple methods of data collection were applied including a cross-sectional survey (n = 184 households Kwale; 141 Makueni), Focus Group Discussions (n = 12) and patient exit interviews (n = 175 Kwale; 184 Makueni). Results Approximately one third of the survey respondents could not correctly state the recommended charges for dispensaries, while half did not know what the official charges for health centres were. Adherence to the policy was poor in both districts, but facilities in Makueni were more likely to adhere than those in Kwale. Only 4 facilities in Kwale adhered to the policy compared to 10 in Makueni. Drug shortage, declining revenue, poor policy design and implementation processes were the main reasons given for poor adherence to the policy. Conclusion We conclude that reducing user fees in primary health care in Kenya is a policy on paper that is yet to be implemented fully. We recommend that caution be taken when deciding on how to reduce or abolish user fees and that all potential consequences are carefully considered.

IN the course of a paper chromatographie study to detect possible crop residues of an organophosphorus insecticide it became apparent that benzene extracts of untreated check samples of a red variety of Irish potatoes. sugar beets, Valencia oranges and Staymen apples produced cholinesterase-inhibiting spots.

PROTEINS of the lens tissue of the eye have been extensively examined because of their relationship with cataract formation. In all forms of cataract a decrease was found in the total amount of lens proteins as compared with normal lens of the same age1. Changes in the proportion of the soluble proteins of the lens measured by electrophoresis have been reported in different kinds of cataract; but, according to van Heyningen2, no consistent patterns have emerged from these investigations. The work recorded here was carried out to determine the behaviour on paper electrophoresis of soluble lens proteins of the rat, as well as the possible changes in the proportion of the different fractions during lactose feeding.

This paper argues that abductive reasoning has a central place in theorizing Health Professions Education. At the root of abduction lies a fundamental debate: How do we connect practice, which is always singular and unique, with theory, which describes the world in terms of rules, generalizations, and universals? While abduction was initially seen as the ‘poor cousin’ of deduction and induction, ultimately it has something important to tell us about the role of imagination and humility in theorizing Health Professions Education. It is that which makes theory possible, because it allows us to ask what might be the case and calls attention to the role of creative leaps in theory. Becoming aware of the abductive reasoning we already perform in our research allows us to take the role of imagination—something rarely associated with theory—seriously.

THE recent publication of a device for applying liquids to paper chromatograms1 prompts this report of a simple arrangement for the reproducible transfer of small volumes which is in routine use in this laboratory for the application of steroid standards to paper chromatograms. It consists of a lambda pipette clamped in the vertical position with the pipette tip firmly against the surface of the chromatography paper which is supported on a perforated metal disk. A stream of compressed air for drying passes through holes in the metal disk against the lower surface of the paper (Fig. 1). In practice the pipette is filled with solvent and positioned while keeping a finger over the upper orifice to prevent leakage. Gradual transfer of solvent to paper begins when the finger is released. A Medtec Spotting Device was employed, but a simpler device for support of the paper and delivery of a gas stream would serve the purpose.

Numerous lung nodule candidates can be produced through an automated lung nodule detection system. Classifying these candidates to reduce false positives is an important step in the detection process. The objective during this paper is to predict real nodules from a large number of pulmonary nodule candidates. Facing the challenge of the classification task, we propose a novel 3D convolution neural network (CNN) to reduce false positives in lung nodule detection. The novel 3D CNN includes embedded multiple branches in its structure. Each branch processes a feature map from a layer with different depths. All of these branches are cascaded at their ends; thus, features from different depth layers are combined to predict the categories of candidates. The proposed method obtains a competitive score in lung nodule candidate classification on LUNA16 dataset with an accuracy of 0.9783, a sensitivity of 0.8771, a precision of 0.9426, and a specificity of 0.9925. Moreover, a good performance on the competition performance metric (CPM) is also obtained with a score of 0.830. As a 3D CNN, the proposed model can learn complete and three-dimensional discriminative information about nodules and non-nodules to avoid some misidentification problems caused due to lack of spatial correlation information extracted from traditional methods or 2D networks. As an embedded multi-branch structure, the model is also more effective in recognizing the nodules of various shapes and sizes. As a result, the proposed method gains a competitive score on the false positive reduction in lung nodule detection and can be used as a reference for classifying nodule candidates.

Background Low-cost raw materials such as lignocellulosic materials have been utilized in second-generation ethanol production process. However, the sequential and slow conversion of xylose into target products remains one of the main challenges for realizing efficient industrial lignocellulosic biorefinery. Results By applying different constant potentials to different microbial electrolysis cells with xylose as the sole carbon source, we analyzed the output of metabolites, microbial community structures, electron flow, and carbon flow in the process of xylose electro-fermentation by domesticated activated sludge. The bioreactors produced currents when applying positive potentials. The peak currents of the + 0.242 V, + 0.542 V and + 0.842 V reactors were 0.96 × 10–6 A, 3.36 × 10–6 A and 6.43 × 10–6 A, respectively. The application of potentials promoted the xylose consumption, and the maximum consumption rate in the + 0.542 V reactor was 95.5%, which was 34.8 times that of the reactor without applied potential. The potential application also promoted the production of ethanol and acetate. The maximum ethanol yield (0.652 mol mol−1 xylose) was obtained in the + 0.842 V reactor. The maximum acetate concentration (1,874 µmol L−1) was observed in the + 0.842 V reactor. The optimal potential for ethanol production was + 0.842 V with the maximum ethanol yield and energy saving. The application of positive potential caused the microorganisms to carry out ethanol fermentation, and the application of negative potential forced the microorganisms to carry out acetic fermentation. The potential application changed the diversity and community structure of microorganisms in the reactors, and the two most significantly changed families were Paenibacillaceae and Bacillaceae. Conclusion The constructed microbial electrolysis cells with different potentials obtained better production yield and selectivity compared with the reactor without applied potential. Our work provides strategies for the subsequent fermentation processes with different needs.

BackgroundEthanol biorefineries need to lower their overall production costs to become economically feasible. Two strategies to achieve this are to reduce costs using cheaper feedstocks or to increase the ethanol production yield. Low-cost feedstocks usually have high non-structural components (NSC) content; therefore, a new process is necessary to accommodate these feedstocks and overcome the negative effects of NSC. This study developed a novel ethanol biorefinery process including a biomass preprocessing step that enabled the use of lower-cost feedstocks while improving ethanol production without detoxification (overliming). Two types of poplar feedstocks were used, low-quality whole-tree chips (WTC) and high-quality clean pulp chips (CPC), to determine if the proposed process is effective while using feedstocks with different NSC contents.ResultsTechnical assessment showed that acidic preprocessing increased the monomeric sugar recovery of WTC from 73.2% (untreated) to 87.5% due to reduced buffering capacity of poplar, improved sugar solubilization during pretreatment, and better enzymatic hydrolysis conversion. Preprocessing alone significantly improved the fermentability of the liquid fraction from 1–2% to 49–56% for both feedstocks while overliming improved it to 45%. Consequently, it was proposed that preprocessing can substitute for the detoxification step. The economic assessment revealed that using poplar WTC via the new process increased annual ethanol production of 10.5 million liters when compared to using CPC via overliming (base case scenario). Also, savings in total operating costs were about $10 million per year when using cheaper poplar WTC instead of CPC, and using recycled water for preprocessing lowered its total operating costs by 45-fold.ConclusionsThe novel process developed in this study was successful in increasing ethanol production while decreasing overall costs, thus facilitating the feasibility of lignocellulosic ethanol biorefineries. Key factors to achieving this outcome included substituting overliming by preprocessing, enabling the use of lower-quality feedstock, increasing monomeric sugar recovery and ethanol fermentation yield, and using recycled water for preprocessing. In addition, preprocessing enabled the implementation of an evaporator-combustor downstream design, resulting in a low-loading waste stream that can be treated in a wastewater treatment plant with a simple configuration.

Background Biomass pre-treatment is gaining attention as a standalone process to improve the qualitative aspect of the lignocellulosic material. It has been gaining ground in the power station by replacing the coal with the pre-treated biomass. In this context, this paper enlightens the operating condition of carrying out the torrefaction so that the process can be made relatively more effective. The influence of physico-chemical characteristics on the heat of reaction of pyrolysis reactions, mass loss and temperature regimes are evaluated by thermogravimetry of the pre-treated samples of the pinecone; whereas, the structural transformation in the basic constituents is determined via knowing the fractional change in cellulose, hemicellulose and acid-insoluble lignin contents of the pine cone. The thermogravimetric (TGA) and differential thermal analysis (DTA) were performed to determine the physical as well as the thermal behaviour of the thermally processed biomass. The samples had undergone thermal decomposition at heating rates of 5 °C min−1, 10 °C min−1 and 15 °C min−1. Nitrogen gas was used as a purge gas for the pyrolysis of the pre-treated samples. The volumetric rate of 200 ml min−1 was pre-set for the thermal decomposition of the samples at 600 °C; whereas, the selected torrefaction temperature range varied from 210 to 250 °C. Results The heat of reaction for the pre-treated samples was found to vary from 1.04 to 1.52 MJ kg−1; whereas, it was 0.91–1.54 MJ kg−1 for the raw samples. The total annual production cost of processing 3.6 Mg of fuel in a year at a pilot scale was $ 36.72; whereas, the fiscal burden per kilogram of fuel during thermal degradation of the processed fuel was reduced by 0.08–1.5ȼ. The entropy of the system decreased with an increasing ramp rate. The exergetic gain in the system increased by 1–2%. The loss of energy during the energy-intensive processing of the pre-treated fuel was relatively low at a heating rate of 5 °C min−1. Conclusion By the physico-chemical assessment, it was determined that pinecones required the highest torrefaction temperature and time to provide the upgraded pinecones. It was concluded that the duration of the torrefaction should be at least 15 min for a temperature of 250 °C so that the chemical exergy of the system, energy yield and the energy density of the processed material are qualitatively improved. The volatile and ash contents were noticed to decrease during the torrefaction process. The least fractional change in the volatile content was estimated at 210 °C for a torrefaction time of 15 min; whereas, the ash content was minimum at 210 °C for a torrefaction time of 5 min.

Background Biodiesel is an eco-friendly and renewable energy source and a valuable substitute for petro-diesel. Sago processing wastewater (SWW), a by-product of the cassava processing industry, has starch content ranging from 4 to 7 g L–1 and serves as an outstanding source for producing microbial lipids by the oleaginous microorganisms. In the present study, Candida tropicalis ASY2 was employed to optimize single-cell oil (SCO) production using SWW and subsequent transesterification by response surface methodology. Variables such as starch content, yeast extract, airflow rate, pH, and temperature significantly influenced lipid production in a preliminary study. The lipid production was scaled up to 5 L capacity airlift bioreactor and its optimization was done by response surface methodology. The dried yeast biomass obtained under optimized conditions from 5 L bioreactor was subjected to a direct transesterification process. Biomass: methanol ratio, catalyst concentration, and time were the variables used to attain higher FAME yield in the transesterification optimization process. Results Under optimized conditions, the highest lipid yield of 2.68 g L–1 was obtained with 15.33 g L–1 of starch content, 0.5 g L–1 of yeast extract, and 5.992 L min–1 of airflow rate in a bioreactor. The optimized direct transesterification process yielded a higher FAME yield of 86.56% at 1:20 biomass: methanol ratio, 0.4 M catalyst concentration, and a time of 6.85 h. Conclusions Thus, this optimized process rendered the microbial lipids derived from C. tropicalis ASY2 as potentially alternative oil substitutes for sustainable biodiesel production to meet the rising energy demands.

16 p.-5 fig.-6 tab., Background: Rhodospirillum rubrum is a purple non-sulphur bacterium that produces H2 by photofermentation of several organic compounds or by water gas-shift reaction during CO fermentation. Successful strategies for both processes have been developed in light-dependent systems. This work explores a dark fermentation bioprocess for H2 production from water using CO as the electron donor., Results: The study of the influence of the stirring and the initial CO partial pressure (pCO) demonstrated that the process was inhibited at pCO of 1.00 atm. Optimal pCO value was established in 0.60 atm. CO dose adaptation to bacterial growth in fed-batch fermentations increased the global rate of H2 production, yielding 27.2 mmol H2 l−1 h−1 and reduced by 50% the operation time. A kinetic model was proposed to describe the evolution of the molecular species involved in gas and liquid phases in a wide range of pCO conditions from 0.10 to 1.00 atm., Conclusions: Dark fermentation in R. rubrum expands the ways to produce biohydrogen from CO. This work optimizes this bioprocess at lab-bioreactor scale studying the influence of the stirring speed, the initial CO partial pressure and the operation in batch and fed-batch regimes. Dynamic CO supply adapted to the biomass growth enhances the productivity reached in darkness by other strategies described in the literature, being similar to that obtained under light continuous syngas fermentations. The kinetic model proposed describes all the conditions tested., The European Union’s Horizon 2020 research and innovation program under grant agreement no. 679050 (CELBICON), the Community of Madrid (P2018/NMT4389) and the Spanish Ministry of Science, Innovation and Universities (BIO2017-83448-R) supported this work.

Working in an interdisciplinary manner at the crossroads of alcohol and HIV research is a challenge. This paper presents six novel approaches that could be applied to activities at the intersection of alcohol and HIV. These approaches are (i) address the fact that the availability of new technology is unevenly distributed around the world, (ii) use technology to move beyond both paper and digital surveys, (iii) introduce a focus on advocacy and partnerships with large technology companies, (iv) harness technological innovation to utilise digital counselling, (v) explore the use of virtual reality in both research and delivering interventions, and (vi) consider alternative funding models to those currently in existence to improve efficiencies and innovations. Aiming to understand the interplay of alcohol and HIV will require creativity. The six approaches outlines in this paper provide possible directions from which new approaches may emerge.

Background For novel tobacco products that potentially reduce the risk of tobacco harm, post-market surveillance is important to observe population usage and behaviours associated with everyday use. This pilot study was performed to examine the use of tobacco products in three Japanese urban regions. Methods This study was a cross-sectional epidemiological survey administered in Sendai, Tokyo and Osaka, Japan, from May 19th to June 25th, 2018. Participants were selected with a three-stage probability random sampling process that first identified primary sampling units, then households and finally individuals. Eligible participants were aged at least 20 years who were willing to participate after information about the study was provided. People younger than 20 years and those living in institutions were excluded. Questionnaires were paper based and administered door to door. Results Responses were obtained from 4154 participants. Sixty-five percent self-reported being never, 19% current and 16% former users of any tobacco product at the time of the survey. Combustible tobacco products (almost all being cigarette) were used most (16%) followed by HTPs (5%). In the categories of combustible tobacco users and HTP users, 70% and 16%, respectively, used these products exclusively. Dual use was reported by 11% of respondents. Compared with 12 months before the survey, 12% of sole combustible tobacco products users were using HTPs exclusively or as dual users and 6% had quit tobacco products completely; 94% of sole HTP users remained sole users and 4% had quit tobacco products completely; and amongst dual users 12% had reverted to exclusive use of combustible tobacco products, 14% had switched to sole use of HTPs and 4% had quit tobacco products completely. Conclusion HTPs seem to be accepted as an alternative tobacco product amongst combustible tobacco users. Given complex findings for dual use, improved understanding of the motivations underlying this behaviour would be of interest.

Background Future expansion of corn-derived ethanol raises concerns of sustainability and competition with the food industry. Therefore, cellulosic biofuels derived from agricultural waste and dedicated energy crops are necessary. To date, slow and incomplete saccharification as well as high enzyme costs have hindered the economic viability of cellulosic biofuels, and while approaches like simultaneous saccharification and fermentation (SSF) and the use of thermotolerant microorganisms can enhance production, further improvements are needed. Cellulosic emulsions have been shown to enhance saccharification by increasing enzyme contact with cellulose fibers. In this study, we use these emulsions to develop an emulsified SSF (eSSF) process for rapid and efficient cellulosic biofuel production and make a direct three-way comparison of ethanol production between S. cerevisiae, O. polymorpha, and K. marxianus in glucose and cellulosic media at different temperatures. Results In this work, we show that cellulosic emulsions hydrolyze rapidly at temperatures tolerable to yeast, reaching up to 40-fold higher conversion in the first hour compared to microcrystalline cellulose (MCC). To evaluate suitable conditions for the eSSF process, we explored the upper temperature limits for the thermotolerant yeasts Kluyveromyces marxianus and Ogataea polymorpha, as well as Saccharomyces cerevisiae, and observed robust fermentation at up to 46, 50, and 42 °C for each yeast, respectively. We show that the eSSF process reaches high ethanol titers in short processing times, and produces close to theoretical yields at temperatures as low as 30 °C. Finally, we demonstrate the transferability of the eSSF technology to other products by producing the advanced biofuel isobutanol in a light-controlled eSSF using optogenetic regulators, resulting in up to fourfold higher titers relative to MCC SSF. Conclusions The eSSF process addresses the main challenges of cellulosic biofuel production by increasing saccharification rate at temperatures tolerable to yeast. The rapid hydrolysis of these emulsions at low temperatures permits fermentation using non-thermotolerant yeasts, short processing times, low enzyme loads, and makes it possible to extend the process to chemicals other than ethanol, such as isobutanol. This transferability establishes the eSSF process as a platform for the sustainable production of biofuels and chemicals as a whole.

Background Slow degradation kinetics of long-chain fatty acids (LCFA) and their accumulation in anaerobic digesters disrupt methanogenic activity and biogas production at high loads of waste lipids. In this study, we evaluated the effect of effluent solids recirculation on microbial LCFA (oleate) degradation capacity in continuous stirred-tank sludge digesters, with the overall aim of providing operating conditions for efficient co-digestion of waste lipids. Furthermore, the impacts of LCFA feeding frequency and sulfide on process performance and microbial community dynamics were investigated, as parameters that were previously shown to be influential on LCFA conversion to biogas. Results Effluent solids recirculation to municipal sludge digesters enabled biogas production of up to 78% of the theoretical potential from 1.0 g oleate l−1 day−1. In digesters without effluent recirculation, comparable conversion efficiency could only be reached at oleate loading rates up to 0.5 g l−1 day−1. Pulse feeding of oleate (supplementation of 2.0 g oleate l−1 every second day instead of 1.0 g oleate l−1 every day) did not have a substantial impact on the degree of oleate conversion to biogas in the digesters that operated with effluent recirculation, while it marginally enhanced oleate conversion to biogas in the digesters without effluent recirculation. Next-generation sequencing of 16S rRNA gene amplicons of bacteria and archaea revealed that pulse feeding resulted in prevalence of fatty acid-degrading Smithella when effluent recirculation was applied, whereas Candidatus Cloacimonas prevailed after pulse feeding of oleate in the digesters without effluent recirculation. Combined oleate pulse feeding and elevated sulfide level contributed to increased relative abundance of LCFA-degrading Syntrophomonas and enhanced conversion efficiency of oleate, but only in the digesters without effluent recirculation. Conclusions Effluent solids recirculation improves microbial LCFA degradation capacity, providing possibilities for co-digestion of larger amounts of waste lipids with municipal sludge.