Recent evidence suggests hospitals fail to meet guideline specified time to percutaneous coronary intervention (PCI) for a proportion of ST elevation myocardial infarction (STEMI) presentations. Implicit in achieving this time is the rapid assembly of crucial catheter laboratory staff. As a proof-of-concept, we set out to create regional maps that graphically show the impact of traffic congestion and distance to destination on staff recall travel times for STEMI, thereby producing a resource that could be used by staff to improve reperfusion time for STEMI.Travel times for staff recalled to one inner and one outer metropolitan hospital at midnight, 6 p.m., and 7 a.m. were estimated using Google Maps Application Programming Interface. Computer modeling predictions were overlaid on metropolitan maps showing color coded staff recall travel times for STEMI, occurring within non-peak and peak hour traffic congestion times.p < 0.001). At 7 a.m., the mean difference was 9.5 min to the inner and 3.6 min to the outer metropolitan hospital (p < 0.001). Only 45% of inner metropolitan staff were predicted to arrive within 30 min at 6 p.m. compared with 100% at midnight (p < 0.001), and 56% of outer metropolitan staff at 6 p.m. (p = 0.021).Inner metropolitan hospital staff recall travel times were more affected by traffic congestion compared with outer metropolitan times, and the latter was more affected by distance. The estimated mean travel times to hospital during peak hour were greater than midnight travel times by 13.4 min to the inner and 6.0 min to the outer metropolitan hospital at 6 p.m. (Our results show that integration of map software with traffic congestion data, distance to destination and travel time can predict optimal residence of staff when on-call for PCI. Despite major improvements in the timely treatment of acute myocardial infarction, recent evidence suggests that guideline specified time to percutaneous coronary intervention (PCI) for a proportion ST elevation myocardial infarction (STEMI) presentations is not being met , 2. IdeaThus far, evidence has consistently demonstrated that time-to-reperfusion has an impact on infarct size, left ventricular function and ultimately mortality –9. ThereOut-of-hours, catheter laboratory staff recall travel times realistically form an important component of system-delay and to date, this variable has not been investigated. In this article, we introduce methods for objectively estimating staff travel times and perform a proof-of-concept study comparing these times between two metropolitan settings under different traffic conditions. We hypothesized that recall staff travel times to an inner metropolitan hospital would be affected by traffic congestion to a much greater degree than to an outer metropolitan hospital. We also predicted that a proportion of staff who reside in locations most affected by traffic would not be able to return to hospital during peak traffic conditions, within a target time frame of 30 min following catheter laboratory activation—a time frame set out in the Mayo Clinic STEMI protocol . Using nTwo high volume PCI centers were selected in Melbourne, the capital city of the state of Victoria in Australia, one in an inner metropolitan (~2 km from Melbourne City center) and the other in an outer metropolitan setting (~60 km from city center).Known staff home postcodes were selected, however true addresses were not used to protect the anonymity of staff. To predict staff recall travel times to the hospital in question, we first randomly generated ten addresses for each known staff home postcode, using Google Maps Application Programming Interface (API).To generate staff recall travel times and travel distance, we used the ggmap  interfacSelected recall times were midnight, 6 p.m., and 7 a.m., to represent recall outside the normal working hours of 8:30 a.m. to 4:30 p.m. Times of 6 p.m. and 7 a.m. were chosen to highlight the effect of traffic congestion based on AusRoads  the pea. Google R statistical environment  was usedPeak hour travel times were compared to midnight travel times using multilevel mixed effects models to account for paired data (same source and destination addresses at different times of travel) and correlated measures (different addresses within the same postcodes). Similar models, without paired data, were used to compare inner metropolitan to outer metropolitan travel times, at the selected times.A test of equal proportions was used to compare the number of staff arriving within 30 min during peak hour to those arriving within 30 min at midnight. This method was also used to compare the number of staff arriving at the inner metropolitan hospital within 30 min to the outer metropolitan hospital at selected time points.All statistical analyses were performed using R statistical environment .via Google Maps API and 220 addresses for the outer metropolitan postcodes. Results are further summarized in Table Inner metropolitan staff who were rostered for STEMI recall lived in 17 different postcodes compared to outer metropolitan staff who lived in 22 different postcodes. Therefore, 170 inner metropolitan addresses were randomly generated p < 0.001). This was also true for outer metropolitan staff, however the mean additional time traveled was smaller (Table p < 0.001). At 7 a.m. inner metropolitan staff traveled a mean 5.9 ± 1.4 min more compared to outer metropolitan staff (p < 0.001).The maximum staff travel time to arrive at the inner metropolitan hospital was 57.0 min at 7 a.m. and to the outer metropolitan hospital was 57.6 min at 6 p.m. Mean travel times were longest at 6 p.m. for both hospitals, 30.5 min for inner metropolitan staff and 30.0 min for outer metropolitan staff. Inner metropolitan staff traveled a statistically significnant mean additional 13.4 min at 6 p.m. and 9.5 min at 7 a.m. relative to midnight travel  and 60.0 vs. 59.1 at 7 a.m. (p = 0.529)] clearly demonstrates that inner metropolitan staff are more affected by traffic delay at 6 p.m. (Graph The proportion of inner metropolitan hospital staff arriving within the stipulated 30-min time frame during peak hour compared to outer metropolitan [45.3 vs. 56.1 at 6 p.m. p = 0.01 and 60.Although the main variable analyzed in our study was traffic congestion on time to destination, we were also able to demonstrate the effect of distance on this outcome. We observed that despite the assumption that outer metropolitan hospitals would be less affected by traffic congestion, only 70.9% of staff arrived within 30 min at midnight. This can be explained by the longer mean distance staff traveled to reach the outer metropolitan hospital compared to the inner metropolitan hospital. Overall, we found outer metropolitan staff are more affected by distance traveled than traffic congestion.With the continued advancement of patient care and improvement in STEMI outcomes, small improvements in minimizing ischemic time become important, with an emphasis on reducing first medical contact to device time. Current guidelines recommend for a ≤90 min time window . HistoriThe delay observed between first medical contact and reperfusion therapy in STEMI requiring coronary intervention is known as “system-delay,” and has significant impacts on patient mortality . With ouGoogle Maps API estimated travel time data was not assessed against real travel time data as resource limitations would not have rendered the collection of this information feasible. We have previously demonstrated that the use of optimistic travel time resulted in accurate estimations within 3.5 ± 2.5 min of outer metropolitan real world emergency vehicle travel times . HoweverWe have provided proof-of-concept that novel mapping technology can be used to predict the effect of the environment outside a hospital on the timely treatment of patients. We have shown, as an example of this, that novel mapping technology can predict the impact of both traffic congestion and distance on hospital staff recall travel time. This technology also has broader applications in the provision of other time-dependent medical services as well as addressing other forms of system-delay that contribute to prolonged time to reperfusion in STEMI.All authors meet the editor’s requirements for authorship. RB, TP, and VS have previously published using these concepts and study design . All othThe authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer RN and handling editor declared their shared affiliation.


Porphyromonas gingivalis peptidylarginine deiminase (PPAD) is the focus of several studies due to its ability to citrullinate in vitro human proteins, which have been linked to the aetiopathogenesis of rheumatoid arthritis (RA). The aim of this work was the generation by homologous recombination and characterisation of a P. gingivalis W50 mutant lacking pad gene (PG1424) to study the role of PPAD in RA. To confirm the absence of PPAD activity in P. gingivalis PG1424, cells were incubated with arginine-containing substrates and citrullination of L-arginine measured using a colorimetric assay and thin-layer chromatography. Furthermore, arginine and lysine protease (gingipain) activities were assessed and immunoblotting was performed using monoclonal antibody 1B5 (mAb1B5) and a commercial anti-modified citrulline antibody (AMC) to detect differences in virulence factor expression. The deletion of pad gene in P. gingivalis PG1424 completely abolished the ability to autocitrullinate P. gingivalis proteins in the mutant strain and also the citrullination of used substrates but not free L-arginine. Moreover, the wild-type and mutant strains had similar total gingipain activities and reactivity with mAb1B5. In conclusion, this work has produced a well-characterised PPAD-deleted P. gingivalis strain, which can be used to help determine the role of citrullination by this microorganism in RA.


Hemodynamic instability frequently occurs in critically ill patients. Pathophysiological rationale suggests that hemodynamic monitoring (HM) may identify the presence and causes of hemodynamic instability and therefore may allow targeting therapeutic approaches. However, there is a discrepancy between this pathophysiological rationale to use HM and a paucity of formal evidence (as defined by the strict criteria of evidence-based medicine (EBM)) for its use. In this editorial, we discuss that this paucity of formal evidence that HM can improve patient outcome may be explained by both the shortcomings of the EBM methodology in the field of intensive care medicine and the shortcomings of HM itself. Hemodynamic monitoring (HM) plays a central role in the care of critically ill patients, and yet the evidence that HM improves patient outcome is either small or, more often, non-existent , 2. WithSince its introduction in 1992, EBM has become a “holy grail” for rational clinical practice guided by scientific clinical research findings. EBM was meant to initiate a paradigm shift in clinical decision making which should be based on “formal rules of evidence evaluating the clinical literature” . EBM alsThe hemodynamic status of critically ill patients is complex; it may include varying degrees of hypovolemia, left and right ventricular dysfunction, abnormalities of vascular tone, and microvascular dysfunction. These acute cardiovascular impairments are often further complicated by chronic co-morbidities. Physical examination and conventional HM cannot adequately assess the nature and extent of such hemodynamic dysfunction –7. HM caThe lack of evidence behind our practice of HM may be explained by the significant limitations of EBM. There is a shortage of relevant, high-quality evidence that shows a beneficial effect of any intervention on mortality in ICU patients . One of However, the lack of evidence for our practice of HM may also be due to the inherent limitations of HM itself. First and foremost, the monitoring of physiological variables per se cannot improve outcome unless it is followed by correct therapeutic interventions. Making the “correct” decision is not always straightforward even when advanced HM is applied, due to the frequent misinterpretation of the monitored parameters, the failure to identify their relative importance, and the remaining uncertainty regarding the exact nature of the physiological impairment. The resulting variability of care precludes the assessment of the value of that particular monitoring modality per se by a formal RCT. In addition, each hemodynamic variable has inherent limitations and confounding factors. The monitoring of cardiac output (CO), for instance, may be crucial in many instances of hemodynamic instability. However, the CO value in and by itself may not necessarily lead to the “correct” therapeutic decision, since the optimal CO cannot always be determined: a high CO may not be high enough, and a low CO does not tell us what to do . The correct application of hemodynamic data necessitates the integration of various variables that may complement each other in order to provide the whole clinical picture. On the other hand, such a multiparametric approach to decision making based on HM may introduce another source of variability which can further complicate any study design that is aimed at establishing the value of HM in general, and of any specific variable in particular. In addition, HM may increase the tendency to normalize (or even maximize) the measured physiological variables, although “normalcy” of hemodynamic variables does not necessarily mean “adequacy”. Last but not least, monitoring technologies need to be meticulously validated with regard to their measurement performance before they should be used in clinical studies aiming to demonstrate an impact on outcome.HM supplies invaluable insights about the patient’s hemodynamic status and is essential for the correct individual management of critically ill patients. The paucity of formal evidence showing that HM is improving patient outcome may be explained by both the shortcomings of EBM and HM itself. The honest and open acknowledgement of these shortcomings should become an integral part of the education of clinicians who take care of critically ill patients.


Lactobacillus curvatus by 16S rDNA analysis. Then, genes analysis and high-performance liquid chromatography (HPLC) analysis were performed to evaluate the BAs formation and degradation abilities of as-selected strains. All L. curvatus strains were confirmed to harbor the genes encoding the tyrosine decarboxylase and ornithine decarboxylase, and they could produce tyramine, β-phenethylamine, putrescine, and cadaverine. In comparison, the lowest concentration of total BAs was obtained in L. curvatus G-1. Meanwhile, all L. curvatus strains were positive in amines oxidase gene analysis, and they could also degrade six common BAs, especially the L. curvatus G-1 with the highest degradation percentage (above 40%) for each BA. Furthermore, fermented meat model analysis verified that the L. curvatus G-1 could significantly reduce BAs. In conclusion, L. curvatus G-1 shows a low BAs-producing ability, as well as a high BAs-degrading ability, and this study provides a promising candidate for potential BAs control in fermented meat products.Control of biogenic amines (BAs) is critical to guarantee the safety of fermented meat products. The aim of this study is to evaluate the BAs formation and degradation abilities of lactic acid bacteria from Chinese bacon to obtain the beneficial candidate for BAs control. Seven lactic acid bacteria were selected from the typical Chinese bacon products, identified as  Biogenic amines (BAs), a group of low-molecular-weight nitrogenous compounds, are mainly produced through amino acid decarboxylation, which exists in most fermented foods such as cheese, yoghurt, sausage, wine, and beer . The BAsBiogenic amines have been broadly reported as potentially toxic substances in fermented meat products ,b. LactiChinese bacon products, such as Guangdong, Sichuan, and Hunan bacon, are the traditional and popular fermented meat products due to their unique flavor and texture . ChineseQualitative and quantitative tests of BAs have been broadly reported. High-performance liquid chromatography (HPLC) analysis can acquire reliable qualitative and quantitative data of individual amines . In addiBacon samples were obtained from the supermarkets of Chengdu (Sichuan), Hunan (Changsha), Hubei (Wuhan), Guangdong (Guangzhou), Shanxi (Xian), and Gansu (Lanzhou) of China at the March of 2017. All samples were collected in three replicates, and stored at -20°C. The standard substances  were purchased from Sigma–Aldrich Co., LLC . Other chemicals were bought from Sinopharm Chemical Reagent Co., Ltd. .2HPO4 2 g/L, MgSO4 0.2 g/L, MnSO4 0.04 g/L, Tween 80 1 g/L, agar 14 g/L, pH = 5.7) added with 20 g/L CaCO3, and cultured at 37°C for 24 h in a vacuum bag. The single colony with the big dissolved calcium zone was selected as the potential lactic acid bacterium.Bacon samples (5 g) were crushed and added into 45 mL sterile water and rotated at 37°C and 140 rpm for 40 min. The liquid mixtures were diluted, spread onto the solid MRS medium  according to the manufacturer’s instructions, and the DNA concentration and quality were estimated on a Nano Drop2000 spectrophotometer . The 16S rDNA sequence analysis was carried out according to our previous report . The 16ShdcA), tyrosine decarboxylase (tyrdc), ornithine decarboxylase (odc), agmatine deiminase (aguA and aguD), lysine decarboxylase (ldc), and multi-copper oxidase (sufI). The primers used in this study were listed in Table 1. PCR amplification is performed in 25 μL reaction mixture containing 2 μL of template DNA, 2.5 μL Easy-Taq Buffer, 2.5 μL dNTPs, 1 μL of each primer, and 0.3 μL Easy-Taq enzyme wherein nuclease-free water was added to reach 25 μL. The reactions were performed according to the parameters shown in Table 2. The PCR products were analyzed by electrophoresis on a 0.8% agarose gel and revealed under UV after staining with ethidium bromide. And the PCR amplicons were purified, recovered, and gene sequencing was performed by the Tsingke Biological Technology Co., Ltd. . The sequence similarity analysis was conducted through the Blastn program2.Polymerase chain reaction amplification and sequence analysis were performed to confirm the presence of BAs-related genes of histidine decarboxylase  and re-suspended (OD650 = 0.4) in 0.05 mol/L phosphate buffer consisting of 100 mg/L of histamine, tyramine, tryptamine, β-phenethylamine, putrescine, and cadaverine. The phosphate buffer without inoculation of Lactobacillus curvatus was used as the control. After static incubation at 37°C for 24 h, the concentrations of BAs were determined. The value of BA-degradation rate was determined based on an equation, i.e., M = [(A-B)/A] × 100%, where M is the percentage of BAs degradation, and A and B represent the initial BAs content and residual BAs content, respectively.To evaluate the BAs-producing ability, as-selected strains were inoculated into the MRS broth, respectively, incubated statically at 37°C for 24 h as the seed cultures, which were further transferred into 5 mL MRS broth supplemented with 1 g/L of histidine, tyrosine, tryptophan, phenylalanine, ornithine monohydrochloride, lysine, or agmatine sulfate salt. After static culturing at 37°C for 48 h, the concentrations of BAs were determined. For the BAs-degrading ability analysis, the 24 h cultures of each strain were harvested by centrifugation at 6000 ×650 = 0.8), which were then transferred  into the fresh pork slices (10 g) added with 2% salt, 1% glucose, and 4% sucrose in sterilized flasks (50 mL). The cells were inoculated into the MRS broth, statically cultured at 37°C for 24 h as the seed cultures, which were then transferred into 10 g fresh pork slices containing 2% salt, 1% glucose, and 4% sucrose in sterilized flasks (50 mL). Thereafter, the mixtures were incubated at 37°C for 7 days, and the total BAs concentration of each sample was analyzed by HPLC. The fermented experiments were performed by inoculation with L. curvatus G-1 and L. curvatus B-1, respectively, as well as mixed L. curvatus G-1 and L. curvatus B-1, and the sample inoculated with equal volume of sterilized water was used as the control.The fermented meat model was constructed to evaluate the BAs-controlling abilities of selected strains. The cells were inoculated into the MRS broth, statically cultured at 37°C for 24 h as the liquid seed cultures , which was mixed with 25 μL of NaOH (2 M) and 75 μL of saturated NaHCO3 and then reacted at 50°C for 45 min after supplement with 500 μL of dansyl chloride (5 mg/mL). Then, 25 μL of NH4OH (25%) was added into the reactant to remove the residual dansyl chloride, and the final volume was increased to 1.5 mL with acetonitrile. The final reaction system was centrifuged at 2500 ×g for 5 min to obtain the supernatant, which was filtered by a 0.22 μm membrane for further analysis. The HPLC analysis was operated on an Agilent 1260 system under the parameters of Zorbax Eclipse XDB-C18 , column temperature (30°C), flow rate (1 mL/min), and detection wavelength (254 nm). Using acetonitrile and H2O as mobile phase A and B, the solvent linear gradient procedure was set as: 50% A (0–3 min), 50–90% A (3–20 min), 90% A (20–29 min), 90–50% (29–32 min), and 50% A (32–35 min).Analysis of BAs was performed according to a previous study . BrieflyThe data were analyzed by one-way analysis of variance (ANOVA) using the statistical software SPSS 17.0, and means were compared by Duncan’s multiple range test at 5%.3 can be dissolved by lactic acid bacteria to generate transparent zones, which is usually used to screen the candidates. Many clones showed the ability of dissolving calcium, and seven yellowish clones with big transparent zones were selected, named N-1, N-2, B-1, B-2, G-1, G-2, and GAN. The 16S rDNA fragments were amplified and sequenced to further identify the strains. Sequencing results revealed that the lengths of fragments were about 1468 bp, and all the sequences exhibited about 99% identity with that of the L. curvatus strains from the GenBank database (Table 3). The phylogenetic tree was shown in Figure 1, and as-selected seven strains were closely clustered with L. curvatus. The above results confirmed that these seven strains all belonged to L. curvatus, and corresponding 16S rDNA sequences were deposited in Genbank .The typical Chinese bacon samples, including Sichuan bacon, Hunan bacon, Hubei bacon, Guangdong bacon, Shanxi, and Gansu bacon, were collected to isolate lactic acid bacteria. The BAs profiles of these samples were analyzed, and common six kinds of BAs were detected from different samples  and agmatine deiminase (aguA and aguD). None of the L. curvatus strains was positive in histidine decarboxylase gene (hdcA), agmatine deiminase gene (aguA and aguD), and lysine decarboxylase gene (ldc) screenings with the primers HdC1/HdC2, AgmSq1/AgmSq2, AgD1/AgD2, and Cad2F/Cad2R. These results indicated that the L. curvatus strains isolated might not have cadaverine and histamine formation ability, and they might not produce putrescine via agmatine. Figure 2A shows that all the L. curvatus strains were positive in tyrosine decarboxylase gene detection, and the resulting PCR amplicons were about 1100 bp , highly homologous (about 99%) with the tyrdc gene from L. curvatus HSCC1737 (AB086652). All the strains also indicated the positive results in detection of the ornithine decarboxylase gene , and the fragments were about 500 bp , showing high similarity (about 80%) with the odc gene from Oenococcus oeni (FR751077). The above results revealed that all the L. curvatus strains might have the abilities of generating tyramine and putrescine.To evaluate the BAs-producing abilities of seven L. curvatus strains, including tyramine, β-phenethylamine, putrescine, and cadaverine, and histamine and tryptamine were not detected. The dominant BA produced by L. curvatus strains was tyramine, followed by putrescine. Both ornithine and agmatine served as the precursors of putrescine, and the abilities of producing putrescine via ornithine were much higher than that of agmatine in our selected strains (Table 4). Additionally, all L. curvatus strains showed low cadaverine formation abilities. In comparison, the L. curvatus G-1 produced the lowest concentration of total BAs, especially the relative low level of tyramine and putrescine.The BAs-producing abilities of all strains were detected in MRS broth supplemented with corresponding precursors. After eliminating the BAs generated from MRS medium without precursors, four BAs were confirmed to be produced by all the Figure 3), and the lengths of corresponding PCR products were about 350 bp . Moreover, all PCR amplicons showed a high similarity above 95% with the multi-copper oxidase gene from Lactobacillus paracasei CB9CT (KU962939). Above results indicated all L. curvatus strains probably possessed the multi-copper oxidase for degrading BAs. Therefore, the BAs degradation abilities of all L. curvatus strains were further analyzed.In lactic acid bacteria, the multi-copper oxidase showed a high ability of degrading BAs . TherefoL. curvatus strains to degrade BAs were assayed through the degradation test using the substrates of histamine, tyramine, tryptamine, β-phenethylamine, putrescine, and cadaverine. The BAs contents in broth and their corresponding controls were analyzed by HPLC. All the strains had the degradation abilities for each BA, especially for the tyramine, and different strains showed different degradation abilities (Table 5). In comparison, the L. curvatus G-1 demonstrated the highest degradation percentage, with the degradation efficiencies above 40% for all the BAs. In a whole, L. curvatus G-1 showed the highest BAs-degrading ability, as well as the lowest BAs-producing ability, and thus it exhibited the promising potential to control BAs.The capacities of all L. curvatus G-1 might be the potential candidate for controlling the BAs due to its low BAs-producing ability and high BAs-degrading ability. Thus, we evaluated its BAs-controlling capacity in a fermented meat model. After culture at 37°C for 7 days, the total BAs contents of samples were analyzed and are shown in Figure 4. The control sample without inoculation of L. curvatus cells showed the highest total BAs content (1044.04 mg/kg), which was due to fermentation of native microbes in fresh meat. Inoculation with L. curvatus cells reduced the total BAs concentrations in each treatment. The lowest BAs concentration (318.19 mg/kg) was found in the sample inoculated with L. curvatus G-1, and it was much lower than that of L. curvatus B-1 (784.68 mg/kg), which agreed with their difference in BAs-producing and BAs-degrading abilities. The above results indicated that the L. curvatus G-1 had an excellent capacity for controlling BAs in fermented meat model.The The fermented meat products, usually processed from raw meat under open environment, undoubtedly consist of complex microorganisms, which are responsible for formation of good flavor and organoleptic characteristics. During the ripening of fermented meat products, proteins undergo degradation to generate large peptides, which are further hydrolyzed into oligopeptides and free amino acids . Some amL. curvatus, which was reported as the predominant starter in some fermented meat products (L. curvatus had no potential to produce histamine. Consistently, none of as-selected L. curvatus strains harbored histidine decarboxylase gene and produced histamine. Similar to previous reports (L. curvatus strains, which agreed with the fact that all the strains could synthesize tyramine and putrescine. The enterococcal tyrosine decarboxylase was reported to be able to synthesize phenylethylamine from phenylalanine, which is structurally similar to tyrosine (L. curvatus strains were reported to be highly related to tyramine and β-phenylethylamine (L. curvatus strains isolated in this study may also result from the tyrosine decarboxylase. In addition, all isolated L. curvatus strains produced low level cadaverine, which is consistent with a previous study (L. curvatus strains. Similarly, low level of putrescine was produced via agmatine, while agmatine deiminase genes were also negative in all isolated strains. These results indicate that unknown lysine decarboxylase or agmatine deiminase with low activities may exist in L. curvatus, which will be further investigated in the future. L. curvatus G-1 shows the lowest BAs-producing ability, which may be due to its low amino acid decarboxylase activity.In order to screen a strain with low BAs formation and high BAs degradation ability, seven lactic acid bacteria were isolated from Chinese bacon. Based on 16S rDNA analysis, these seven strains were all identified as products . Freidin reports , the tyrtyrosine , and Lanhylamine . Therefous study , while tL. curvatus was also reported to reduce the BAs in fermented vegetable and fermented sausage (L. curvatus strains isolated were confirmed to harbor multi-copper oxidase genes, and the sequences obtained were highly similar to that of L. paracasei CB9CT (L. curvatus strains isolated could degrade six common BAs. In comparison, the BAs-degrading capacity of L. curvatus G-1 was much higher than other strains. Therefore, L. curvatus G-1 was further assessed in a fermented meat product model, and our results show that L. curvatus G-1 can be used as starter cultures for reducing BAs in fermented meat product.Bacteria with amine oxidase have the potential to reduce BAs in fermented meat products . The ami sausage . Herein,ei CB9CT . The BAsL. curvatus strains from Chinese bacon, and they possess different BAs-producing and degrading abilities. Importantly, the L. curvatus G-1 not only indicates a relative low BAs-producing ability, but also exhibits a high BAs-degrading activity. Moreover, L. curvatus G-1 can efficiently control the BAs in the fermented meat model. This study provides a promising BAs-controlling strain of L. curvatus G-1, which will be further investigated as the starter cultures in the practical production of fermented meat products.This study obtains seven XuW, LW, and LL designed the study. XiW and LL executed the experimental work and analyzed the data. XuW and LW contributed reagents and materials. LL, XuW, ZW, SC, and LW wrote and revised the manuscript. All authors read and approved the final manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


While portfolios are increasingly used to assess competence, the validity of such portfolio-based assessments has hitherto remained unconfirmed. The purpose of the present research is therefore to further our understanding of how assessors form judgments when interpreting the complex data included in a competency-based portfolio. Eighteen assessors appraised one of three competency-based mock portfolios while thinking aloud, before taking part in semi-structured interviews. A thematic analysis of the think-aloud protocols and interviews revealed that assessors reached judgments through a 3-phase cyclical cognitive process of acquiring, organizing, and integrating evidence. Upon conclusion of the first cycle, assessors reviewed the remaining portfolio evidence to look for confirming or disconfirming evidence. Assessors were inclined to stick to their initial judgments even when confronted with seemingly disconfirming evidence. Although assessors reached similar final (pass–fail) judgments of students’ professional competence, they differed in their information-processing approaches and the reasoning behind their judgments. Differences sprung from assessors’ divergent assessment beliefs, performance theories, and inferences about the student. Assessment beliefs refer to assessors’ opinions about what kind of evidence gives the most valuable and trustworthy information about the student’s competence, whereas assessors’ performance theories concern their conceptualizations of what constitutes professional competence and competent performance. Even when using the same pieces of information, assessors furthermore differed with respect to inferences about the student as a person as well as a (future) professional. Our findings support the notion that assessors’ reasoning in judgment and decision-making varies and is guided by their mental models of performance assessment, potentially impacting feedback and the credibility of decisions. Our findings also lend further credence to the assertion that portfolios should be judged by multiple assessors who should, moreover, thoroughly substantiate their judgments. Finally, it is suggested that portfolios be designed in such a way that they facilitate the selection of and navigation through the portfolio evidence. With the rise of competency-based assessment, portfolios are increasingly seen as the linchpin of assessment systems. Although their format and content may differ, generally they all contain reporting on work done, feedback received from peers and faculty, progress made, and goals and plans on how to further improve competence  program of Maastricht University, the Netherlands. The MiM curriculum spans a 3-year period following the bachelor’s in Medicine. It consists of clerkships, a research project, and electives. The curriculum has been designed according to the principles of competency-based education and assessment, using the CanMEDS framework as overarching assessment framework  developed three mock portfolios representing three different student profiles, each reflecting varying levels of competency achievement. In our student profiles we chose to make a distinction between de medical expert competency and other competencies because previous research has shown that assessors have difficulty assessing the non-medical expert competencies , progress test results, and a curriculum vitae. Each portfolio comprised narrative feedback, competency ratings and qualifications  as well as test results pertaining to each of the individual CanMEDS competencies. Figure Two recent medical graduates provided feedback on the first portfolio drafts. We also invited three assessors to take part in a dry run prior to data collection, to ensure that the information and instructions were clear, and the portfolio versions were authentic, and fit for the study purpose. On the basis of these dry runs and student feedback, we made some adaptations to the portfolios and constructed the final portfolios.We obtained ethical approval from the Ethical Review Board of the Netherlands Association for Medical Education (ERB-NVMO file number 474).Data were collected between October, 2015 and January, 2016.We invited 24 mentor–assessors via e-mail to participate and obtained their consent prior to participation. Eighteen assessors responded to our invitation. Each assessor was presented one of the three portfolio versions, each portfolio version was therefore assessed by six assessors. Assessors were instructed to carefully read it and provide a holistic judgment of the student’s overall professional competence by rating it as ‘insufficient,’ ‘sufficient,’ or ‘good.’ Although assessors were allowed to comment on individual competencies, they did not need to rate each competency domain separately. We did not instruct assessors on how to evaluate the portfolio; they were free to read or skip any portfolio evidence as they deemed appropriate.To capture assessors’ cognitive processing during portfolio evaluation, we employed the think-aloud method .All sessions were audiotaped and transcribed verbatim.In the next phase, we performed a thematic analysis of the think-aloud and interview transcripts  judgment of the student’s competence.Upon conclusion of the first round, assessors reviewed the remaining portfolio evidence to look for additional confirming or disconfirming data thereby repeating the information acquisition phase which, in turn, influenced the organization and integration of information. This iterative process was repeated every time the assessor reviewed new portfolio evidence, until assessors felt they had obtained enough information to make a judgment about the student’s competence. By comparing different pieces of evidence from multiple sources, assessors gradually came to recognize patterns in the student’s competence.A salient finding, moreover, was that assessors were inclined to stick to their initial judgments even when confronted with seemingly disconfirming evidence: Although their final judgments were, indeed, more elaborate and detailed compared to their preliminary judgments, they were not substantially different from their initial judgments. Differences between student profiles did not seem to affect the judgment process or assessors’ overall judgment of the student’s competence: Most assessors rated the students’ competence as sufficient.Analysis of the think-aloud protocols revealed that, from the onset of the judgment process, assessors relied on different kinds of portfolio evidence to inform their judgment. Likewise, the amount of portfolio evidence assessors took into account to arrive at decisions about student competence exhibited between-assessor differences: While some assessors read the entire portfolio before providing their final judgment, others mainly relied on either the student’s self-evaluation or workplace-based assessment data to inform their judgment, largely ignoring additional portfolio evidence.These divergent approaches were rooted in assessors’ varying assessment beliefs, performance theories , and inferences. As a result, assessors’ reasoning behind their judgments and judgments of individual competencies were strongly governed by their unique personal profiles and differed accordingly. The following paragraphs will discuss each of these three inter-assessor differences in more detail.First it should be noted that assessors mainly relied on narrative feedback to inform their judgment, because this provided meaningful and detailed information about the student’s development, strengths and weaknesses, as well as specific suggestions for improvement as provided by others. Grades and qualifications were merely used to confirm impressions based on narratives. For example, if assessors suspected insufficient competence within the medical expert competence domain, they would purposefully select those workplace-based assessments for which the student had received an insufficient score because this would probably provide more insight into the reasons for their underperformance.Despite this commonality, assessors had varying assessment beliefs about what kind of narrative evidence gave the most valuable and credible information about the student’s competence.Assessors, for instance, chose different pieces of narrative evidence to start their evaluation: some selected narrative comments on workplace-based assessments, believing that these would generate the most authentic evidence of students’ abilities; Other, however, started reading the student’s self-evaluations and reflective writings as they assumed these would contain reference to salient feedback comments and assessment forms which they consequently read to check if the student’s claims were justifiable.The source also appeared to matter in deciding on the credibility of evidence: Some assessors mainly relied on feedback from physicians because they perceived them as content experts most likely to provide accurate and meaningful feedback on student competence; Others, in contrast, preferred feedback from fellow students and nurses who, they presumed, had worked more closely with students and therefore had more opportunities to directly observe them.At least in my department we try as much as possible to match the interns with one staff member. And also strictly have this person assess presentations and CATs [Critical Appraisals of a Topic] and those sort of things. What you clearly see then, is a pattern and that actually became much less evident from those mini-CEX assessments.(Assessor 4)Between-assessor differences in source preferences also stemmed from assessors’ frames of reference and the presumed impact of student-supervisor relationships. During the interviews, for instance, multiple assessors expressed their belief that student’s progress could be established more reliably when the student had received feedback from the same person at different points in time, especially since they found it hard to interpret fragmented and divergent feedback:As a student, in our department at least, you can be quite selective in who you ask […] So you yourself can choose to team up with your buddies and they give you positive feedback. But in the case of such a 360-degree assessment. That is very comprehensive. And anonymous. And that is, that does give you, I think, the most truthful answers.(Assessor 11)At the same time, other assessors did value the input from multiple assessors, which they estimated to be more reliable and more informative compared to single-person feedback. In explaining their preferences, several assessors invoked perceptions of selection bias  and feedback providers’ reluctance to write down negative comments so as to avoid conflicts:Finally, the assessment data in the portfolio also induced different impressions about the quality of supervision. When a supervisor, for instance, failed to provide detailed written feedback, several assessors assumed that the supervisor had probably written down the essential comments and had provided more elaborate feedback verbally. Others, however, believed that the student had gone unobserved and therefore questioned the credibility of the supervisors’ assessments.We also observed inconsistencies between assessors’ conceptualizations of ‘competence’. As a result of these variable interpretations of what constitutes competence, assessors thought differently about what they needed to know about the student to be able to form a judgment. Interestingly, these so-called ‘performance theories’ tended to deviate from the formal assessment criteria. In the following we will outline the performance theories that prevailed.What I expect the student to do is to make a strengths/weaknesses analysis of the competencies before the internship, a plan of action, like “how am I going to pay attention to that analysis, those strong points?”. In the interim or final assessment an answer to those questions, “Did I accomplish that? Did I live up to that? And why not?” And “What is my assessment of myself when I look at myself, am I satisfied and have I mastered that competency to the level I aimed for?”(Assessor 14)One group of assessors defined students’ competence in terms of the extent to which they actively engaged in their own learning process and effectively used feedback for competence improvement. More specifically, they considered active engagement in learning and assessment a key quality of a good student. Hence, to establish growth, they often read the portfolio evidence in chronological order to check if aspects that did not go well in the beginning of the clinical rotation had improved over time. In the same fashion, they screened the workplace-based assessments and feedback to verify whether the student had followed-up on all the aspects that needed to improve. In their perusal, they also included the student’s self-assessment and learning goals as they felt that it was vital to know if students did follow up on learning goals and appointments. According to this group of assessors, the student’s competence did not necessarily have to be up to standard as long as there was enough evidence that the student had sufficiently improved over time and actively tried to improve:Because I think it is really very good if a person has self-knowledge about his own weaknesses. I appreciate that a lot, because that is where it all starts. When you yourself want to improve. When other people feel that you have weaknesses in a given competency and you yourself disagree, I think that is – that is a scary person.(Assessor 11)Other assessors measured students’ level of competence by their ability to reflect on their own competencies. Consequently, they started by reviewing the student’s self-reflections, considering it a no–no when a student was not aware of his or her competence in one or more areas:[…] in the domain of health advocate, for example, if someone already understands that there is more to being a health advocate than just, well, repeating to someone that he should quit smoking. Who also identifies where those problems - those difficult situations are in the workplace. Well, that’s where I see an above-average person […] Well, of all students, I think, the above-average ones know what to fill out under ‘scholar,’ ‘professional,’ and ‘health advocate,’ under those less obvious [competencies] that is.(Assessor 7)A final distinction we found between assessors’ interpretations of ‘competence’ was reflected in the way they weighted and valued the various CanMEDS competency domains in the portfolio. While most assessors, regardless of portfolio version, specifically targeted ‘medical expert’, ‘manager’, and ‘communicator’ competencies and scanned the remaining competencies, others sought to bring into focus the full range of competencies. This latter tactic allowed them to differentiate between students, as collecting valuable feedback on the less well defined competencies  is quite a challenge for students. Hence, students who were able to do so and reflected on this evidence were considered to be above average and eager to learn:And then I realize how hard it is to deliver that emphatic ‘insufficient.’ You are inclined to soften the blow for that person and then it is very difficult to give a one(Assessor 12)Throughout the entire judgment process assessors lent their own meanings to the evidence included in the portfolio, leading to different inferences about the student’s competence and attitude. More specifically, based on the same pieces of information assessors drew different conclusions, for instance about students’ responsibility for their competence and achievement: An insufficient rating on a workplace-based assessment of a specific student, was construed by one assessor as the result of a lack of knowledge, while another attributed it to insecurity. Conversely, sufficient ratings over a prolonged period of time were construed as underperformance by some, since they had learned from experience as an assessor and supervisor that written assessments were generally on the positive side be as supervisors eschew failing a student:Anyway, the reason why I do that from time to time is that you look, what kind of side jobs did this person have? Is he a member of an association? Is it someone who looks around him? I’d rather have people who travel, play music and sports, look around them, speak foreign languages, read three newspapers, and pass by the narrowest margin. Than someone who receives outstanding grades but does not leave his room, you see? Then it is not about what I want, but it is about, I just want to have the full picture of such a person.(Assessor 9)Yet other assessors felt they could not make an accurate interpretation of the assessment feedback in the portfolio without having some background information about the student. These assessors were also interested in the student’s extracurricular activities, interests, and hobbies. In an effort to know more about the student’s background, some assessors actually commenced their portfolio review by reading the student’s curriculum vitae:The above-named different interpretations of performance data led to varying inferences about a student’s performance and to equally dissimilar judgments about specific components in the competency framework. Although we described each of the three inter-assessor differences separately, they actually acted in concert to mediate assessor’s decision-making process. When reading portfolio A, for instance, assessor 1 attached great importance to the ‘medical expert’ role and therefore specifically looked for all portfolio evidence about this competency. Consequently, this assessor believed that the most reliable information about this competence came from doctors and could be found in the workplace-based assessments. In the end, the assessor inferred that the student’s competence was problematic since the student lacked competence in the medical expert domain. Assessor 2, however, who read the same portfolio, was more interested in determining the student’s progress. This assessor believed that by reading the comments in the multisource feedback he would be able to do so, because this feedback contained opinions of multiple people about the student’s competence over a longer period of time. Although acknowledging that the student should pay attention to the medical expert competency, the assessor was not concerned because the student had improved considerably during the clinical rotation.The present study has sought to enhance our understanding of how assessors form judgments of students’ professional competence based on the evidence collated in a competency-based portfolio.Our findings suggest that assessors’ information processing is characterized by iterative phases of acquiring, organizing and integrating information. Previous research on rater cognition has found similar phases (Gauthier et al. We also found that assessors’ selection of evidence and the extent to which they let this evidence influence their judgment were strongly governed by their beliefs about the credibility of the portfolio evidence. This judgment of credibility is not exclusive to assessors, as it resulted from a study by Watling et al.  who askeOur findings also revealed that assessors held different performance theories which guided their beliefs about what they needed to know about a student to be able to make a well-informed decision. Confirming previous research where decision-making was based on direct observations (Ginsburg et al. Judgments based on direct observations inherently involve automatic decision-making processes. It has been demonstrated that automatic decision-making processes involving the categorization of people could lead to conversion errors and assessors’ inability to differentiate between competencies (Kolars et al. In a previous study, Moonen-van Loon et al.  tested tSeveral limitations are worthy of mention. First, we conducted this research at Maastricht University where a specific portfolio is used. Since portfolios differ substantially in content and format, it is advised that this study be replicated in other settings where different portfolio types are used.Next, the think-aloud procedure inherently harbours a limitation in that various thought processes cannot be verbalized because they are either automatic or happen so quickly that there is no time to verbalize them Charters . AlthougThird, the assessors in our study were not used to evaluating the student’s competence based on portfolio evidence alone: Usually, they also knew the student personally and had regular face-to-face meetings with the student. Although assessors did mention they missed this personal contact, they indicated to feel able to provide a judgment based solely on the portfolio evidence. This practice of providing judgments based exclusively on portfolio evidence, moreover, ties in with the idea that reviewers who take care of the summative portfolio assessment should not be the same as those providing the formative assessment. In this way the confidentiality of personal reflections is not compromised by the rigor and judgments necessary for making promotion decisions (Dannefer and Henson This study reiterates the importance of assessors explaining their judgments about students’ competence. Differences between assessors’ explanations suggest that decisions should not be made individually, but should result from group discussions. Although multiple assessors may reach the same general judgment about a student’s competence, they do differ in their judgments of individual competencies and the reasoning behind their overall judgments.Also, discussing judgment policies of other assessors will make assessors aware of the fact that their method of assessment is not universally shared. It will help them to become acquainted with other views of competence and portfolio interpretation. This enables assessors to incorporate assessment practices of other assessors into their own assessment process, and to build ‘shared mental models’ for competence assessment.Our findings suggest implications for assessor training. Assessor training should focus on raising assessors’ awareness of their own beliefs, performance theories, and inferences. If they gain more insight into their own decision-making process and get acquainted with those of other assessors their decision making may improve. Furthermore, training should focus on the effect of group member composition and group processes on the decision-making processes as described by Hauer et al. .Furthermore, since assessors have different approaches to the selection and use of portfolio evidence, it is important that portfolios be designed in such a way that they facilitate the selection of and navigation through the portfolio evidence. Captions are important as well, for they summarize the context in which the competency feedback was provided to the student (Van Tartwijk and Driessen The present study described the process whereby assessors reach judgments, when reviewing the evidence collated in a competency-based portfolio. Assessors were able to form a judgment based on the portfolio evidence alone. Although they reached the same overall judgments, they differed in the way they processed the evidence and in the reasoning behind their judgments. Differences sprung from assessors’ divergent assessment beliefs, performance theories, and inferences acting in concert. These findings support the notion that portfolios should be judged by multiple assessors who should, moreover, thoroughly substantiate their judgments. Also, assessors should receive training that provides insight into factors influencing their own decision making process and group decisions. Finally, it was proposed that portfolios be designed in such a way that they facilitate the selection of and navigation through the portfolio evidence.


Universal health coverage (UHC) is high on the global health agenda, and priority setting is fundamental to the fair and efficient pursuit of this goal. In a recent editorial, Rob Baltussen and colleagues point to the need to go beyond evidence on cost-effectiveness and call for evidence-informed deliberative processes when setting priorities for UHC. Such processes are crucial at every step on the path to UHC, and hopefully we will see intensified efforts to develop and implement processes of this kind in the coming years. However, if this does happen, it will be essential to ensure a sufficiently broad scope in at least two respects. First, the design of evidence-informed priority-setting processes needs to go beyond a simple view on the relationship between evidence and policy and adapt to a diverse set of factors shaping this relationship. Second, these processes should go beyond a focus on clinical services to accommodate also public health interventions. Together, this can help strengthen priority-setting processes and bolster progress towards UHC and the Sustainable Development Goals. Correspondingly, Baltussen and colleagues see “evidence-informed” and “deliberation” as the two essential elements in achieving legitimacy in priority setting.1Universal health coverage (UHC) is high on the global health agenda, and priority setting is fundamental to the fair and efficient pursuit of this goal. In a recent editorial, Rob Baltussen and colleagues point to the need to go beyond evidence on cost-effectiveness and call for evidence-informed deliberative processes when setting priorities for UHC.We agree that processes of this kind are crucial at every step on the path to UHC, and hopefully the years ahead will bring intensified efforts to develop and implement such processes. However, if this does happen, it will be essential to ensure a sufficiently broad scope in at least two respects. First, the design of evidence-informed priority-setting processes needs to go beyond a simple view on the relationship between evidence and policy and adapt to a diverse set of factors shaping this relationship. Second, the processes should go beyond a focus on clinical services to accommodate also public health interventions.Baltussen and colleagues affirm that priority setting is a political process and mention bargaining among different lobbies. This hints at the complex relationship between evidence and policy; a relationship that is forged by a diverse set of factors. To be effective, priority-setting processes need to be adequately tailored to these.6 On the evidence-supply side, an evidence-informed process can be promoted by conducting research that speaks directly to the needs of the policy-making process, communicating this research effectively, making the research evidence available in a timely manner, and convening deliberative dialogues that are informed by research evidence.5 On the evidence-demand side, strategies include creating institutional mechanisms that privilege the use of research evidence, demanding effective communication of high-quality, locally relevant and actionable research evidence, and creating prompts for the use of research evidence in decision-making.5 One example of the latter is the mandatory completion of an evidence checklist, documenting where evidence was searched for, what types of evidence were found, and how evidence was used before a decision was made.5 These strategies can all contribute to improving the interaction between researchers and policy-makers, and this factor was identified by a recent systematic review to be one of the most important ones for increasing the likelihood of policy-making being evidence-informed.6The probably simplest view on evidence-informed policy is that researchers just need to publish their findings and then policy-makers will pick them up and craft their policies accordingly. While some of today’s practice and behavior seem to align with this view, few, if anyone, profess such a view. Moreover, a sizable body of knowledge now exist about strategies that go beyond the “simplest view” and can help translate evidence into policy.7 It is claimed that these strategies fail to account for the truly complex relationship between evidence and policy and for the diverse set of factors shaping it; factors that are better captured by other explanatory models.10While these strategies clearly go beyond the “simplest view,” many critical commentators still deem them too narrow and too rooted in a linear model, where policies are seen as the direct result of a “chain of research, evidence, and recommendations.”9 She highlights four additional factors—framed as ways of conceptualizing the relationship between evidence and policy beyond a linear model—that affects how evidence informs policy. First, evidence can inform policy through policy entrepreneurs (who may be researchers or an actor engaged by researchers), who exploit policy windows to craft and put forward evidence-informed policy solutions. Second, evidence can inform policy when it appeals to the normative interests and ideological positions of the stakeholders involved . Third, evidence can inform policy when it contributes to shifting how an issue is conceptualized and perceived. Finally, evidence can inform policy through research-informed ideas, including broader concepts describing how a policy problem should be addressed.This landscape of models of policy change has been reviewed by Katherine Smith as part of a large body of work examining the relationship between public health research and policy.13 Frameworks like the frequently applied Shiffman and Smith framework for analyzing determinants of political priority for global health issues can also help better understand how priority-setting processes best can be designed.14While much of this literature on how evidence informs policy is geared towards broad policies, it comes with important insights for priority setting, and somewhat similar analyses have been done also for priority-setting processes more directly.15 Priority setting in health is characterized by a rapidly evolving evidence base, controversy over values, a demand for consistency to ensure fairness, and the involvement of a multitude of stakeholders, many of which have strong political or financial interests in how priorities are set. These circumstances suggest that any poorly institutionalized priority-setting process will struggle to ensure an effective and fair path towards UHC, and especially a path that is sensitive to the voices of the poor and marginalized. It is, therefore, timely that new initiatives, such as the International Decision Support Initiative (iDSI), are working to strengthen institutions for priority setting at national and global levels.16A more comprehensive view on how evidence informs policy can also help demonstrate why priority-setting processes for UHC need to be firmly positioned within robust institutions.18 Multi-criteria decision analysis considered by Baltussen and colleagues to be integral to an evidence-informed deliberative process.1 This suggests that the processes Baltussen and colleagues propose can address public health interventions, understood as population-based, preventive measures. In addition to taxes and subsidies , such interventions include laws and regulations , informational campaigns , and improvements in the built environment . Most of the discussion on priority setting in health have, however, focused on services targeted at individuals and often clinical services. Similarly, discussions on UHC tend to concentrate on such services.20 Thus, there is a “double danger” that the future development of priority-setting processes for UHC will pay limited attention to public health interventions.Baltussen and colleagues do not specify exactly what kinds of interventions are to be considered through the envisaged processes. However, they have earlier described how multi-criteria decision analysis has been used to evaluate broad interventions such as smoking cessation programs and alcohol taxation.Given the importance of public health interventions for population health outcomes and the wider Sustainable Development Goals, priority-setting processes should plausibly be designed in a way that can accommodate also such interventions. These interventions, however, differ from individual, clinical services in multiple ways that can influence how these interventions should be assessed.21 This does not call for one comprehensive metric subsuming all kinds of relevant outcomes, as this is currently impracticable. However, it does call for an evaluative process in which non-health benefits are systematically screened for, systematically assessed if found to be potentially substantial, and systematically exhibited to the relevant decision-makers.First, many public health interventions provide economic or educational benefits alongside health benefits. School feeding programs, for example, tend to improve energy intake and micronutrient status but also school attendance.22 Third, public health interventions can often have substantial impact on health inequalities, through the social determinants of health or more directly. Increases in tobacco price, for example, tend to have a pro-equity effect on socioeconomic disparities in smoking.23Second, many public health interventions require collaboration and often co-financing across sectors. Efforts to reduce air pollution, for example, normally requires involvement of the environmental and transport sector. The evaluation process itself can facilitate inter-sectoral collaboration and financing by exposing benefits accruing outside the health sector, by including stakeholders from other sectors in the process, and by linking evaluation to various forms of joint budgeting.Overall, this suggests that for priority-setting processes to adequately accommodate public health interventions, they need to take non-health outcomes into account, include non-health stakeholders in the deliberations, and capture distributional impacts, all of which are done only to a limited extent today. At the same time, the special features of public health interventions may generate dynamics for evidence-informed policy-making quite different from those of clinical services. This difference is partly generated, partly reinforced by the fact that public health interventions, compared to clinical services, have a more sparse and qualitatively different evidence base, more often require large structural changes and changes pertaining to opposing ideals and ideologies, and typically engage different interests groups, with less involvement by the pharmaceutical industry or patient advocacy groups. This, in turn, just underscores the importance of tailoring priority-setting processes to the diverse set of factors shaping the relationship between evidence and policy.Development and implementation of evidence-informed deliberative processes for UHC will hopefully take off over the coming years. With a sufficiently broad scope, these efforts can accelerate progress towards UHC and the Sustainable Development Goals.Not applicable.Authors declare that they have no competing interests.Both authors contributed equally to the writing of this paper.1Oslo Group on Global Health Policy, Department of Community Medicine and Global Health and Centre for Global Health, University of Oslo, Oslo, Norway. 2Department of International Public Health, Norwegian Institute of Public Health, Oslo, Norway.


Methods on developing new (de novo) clinical practice guidelines (CPGs) have received substantial attention. However, the volume of literature is not matched by research into alternative methods of CPG development using existing CPG documents—a specific issue for guideline development groups in low- and middle-income countries. We report on how we developed a context specific prehospital CPG using an alternative guideline development method. Difficulties experienced and lessons learnt in applying existing global guidelines’ recommendations to a national context are highlighted.The project produced the first emergency care CPG for prehospital providers in Africa. It included > 270 CPGs and produced over 1000 recommendations for prehospital emergency care. We encountered various difficulties, including (1) applicability issues: few pre-hospital CPGs applicable to Africa, (2) evidence synthesis: heterogeneous levels of evidence classifications and (3) guideline quality. Learning points included (1) focusing on key CPGs and evidence mapping, (2) searching other resources for CPGs, (3) broad representation on CPG advisory boards and (4) transparency and knowledge translation. Re-inventing the wheel to produce CPGs is not always feasible. We hope this paper will encourage further projects to use existing CPGs in developing guidance to improve patient care in resource-limited settings.The online version of this article (10.1186/s13104-018-3210-3) contains supplementary material, which is available to authorized users. Clinical practice guidelines (CPGs) form the cornerstone of providing synthesised systematic evidence-based guidance to patients, healthcare practitioners and managers. Methods on developing new (de novo) CPGs have, of late, received substantial attention . HoweverConsequently, alternative approaches to de novo CPG development have been proposed, using existing high-quality clinical guidelines to make recommendations relevant to local contexts through a process of adopting, adapting or contextualising , 4. ThesSouth African prehospital emergency care providers are currently practicing based on protocols that are more than a decade old . These pThe primary focus of the project was to create a contextually appropriate evidence based CPG for prehospital emergency care providers and managers. The guideline needed to be patient-centred, realistic and enhance the continuation of care through the emergency system from prehospital to patient discharge. The detailed aims and scope of the project have been reported elsewhere .Developing a comprehensive prehospital CPG is a daunting project that would take years to complete de novo. Due to limitations in time, funding and the sheer scope of the project, this was not an option. We thus adopted a novel approach allowing us to work within our resource constraints . This alComprehensive searching for CPGs was performed and followed systematic review methods, including comprehensive searching of the literature  and as such, we found significant heterogeneity between recommendation reporting systems. This made reporting recommendations difficult, as each has a different and often indistinguishable classification system. In response to this, we opted to report the original plain language meaning for each classification. For example, level I evidence was simply reported as ‘evidence obtained from a systematic review of all relevant randomised controlled trials’, taken verbatim from the original classification description. Guideline developers should use a single, robust and clear recommendations classification system, such as GRADE.The quality of included CPGs varied significantly, with many scoring so poorly on AGREE-II that they were excluded. We screened more than 1000 ‘guidelines’, but the majority were excluded simply due to the absence of any reported methods or not using a systematic process of synthesising evidence. There was significant variation between guidelines developed by professional societies compared to collaborative groups. Guidelines from larger organisations, such as Guidelines International Network (G-I-N), National Institute for Health and Care Excellence (NICE) and the National Guidelines Clearinghouse (NGC) were often the highest quality.Guidelines teams should focus on selecting only a couple of key high-quality, relevant, up-to-date CPGs for adoption or adaptation to save considerable time and effort when extracting relevant recommendations. This should only be done within the background of having clearly clarified the guideline scope and prioritisation of clinical questions. Despite doing this, guidelines teams could still end up with large numbers of guidelines that have relevant recommendations linked to multiple clinical questions. To mitigate this confusion, guideline teams should map and match clinical guidelines to the a priori defined clinical questions and focus areas. This could take the form of a database or an electronic mind map, which assist with cross-referencing, identifying evidence gaps, and grouping recommendations for the various guidelines within clinical questions and overarching topics.PubMed, EMBASE and equivalent medical literature databases are traditionally the first port of call for finding evidence. However, we found that these traditional databases alone yielded very poor results. Out of the 276 CPGs included, only three originated from PubMed. The majority were identified in guideline clearing houses (e.g. NGC), databases (e.g. G-I-N or NICE), or Google. Guidelines teams should thus use alternative sources to traditional electronic databases when searching for CPGs.To promote wide input and buy-in from key role players, it was important that representatives from a range of fields within and relating to emergency care were involved . These iTransparency in guideline development is of utmost importance, especially in complex processes and decision-making events such as incorporating advisory board input, adapting methods to respond to the political environment and engaging project sponsors. Keeping clear records of such events, decisions and processes is essential in producing a robust and trustworthy CPG. Regular feedback around processes and interim progress reports to sponsors provide mechanisms to ensure a complete product.Although CPGs act as a vehicle for change and knowledge translation, focusing on clear dissemination and implementation strategies, including end-user content, is paramount to enabling successful uptake of guidelines. Regrettably, these elements were outside the scope of this project, as time and budget were limited; however, guideline teams should strongly consider incorporating guideline implementation and dissemination strategies as part of the initial conversation on scope and timeframe.Looking to the future, this project seeks to further validate and strengthen alternative guideline development methods for resource-limited settings, and to conduct further research to support guideline implementers in formulating a national guideline implementation and dissemination strategy by investigating local barriers and solutions among paramedics to promote guideline uptake together with decision makers. Re-inventing the wheel to produce CPGs is not always feasible. We hope this paper will encourage further projects to use existing CPGs in developing guidance to improve patient care in resource-limited settings.The African Federation for Emergency Medicine (AFEM) project only included clinical practice guidelines to adapt, adopt or contextualise that were of high-quality, up-to-date and that fit the strict Institute of Medicine definition of clinical practice guidelines. Other guidance documents such as protocols, end-user guides or patient pathways were excluded.Additional file 1. Search strategy and example search string.Additional file 2. Suitcase analogy for adopting, adapting and contextualising guidelines.Additional file 3. Example recommendations: adopting, adapting and contextualising.Additional file 4. De novo vs African Federation for Emergency Medicine (AFEM) alternative guideline development approach.Additional file 5. Guideline inclusion flow diagram.


The concept of evidence-based practice is globally relevant in current healthcare climates. However, students and teachers struggle with integrating evidence based practice effectively into a curriculum. This has implications for nurse education and in particular the way in which research is presented and delivered to students.A new undergraduate Evidence Based Practice module (Evidence Based Nursing 1) was developed in a large University within the United Kingdom. It commenced in October 2014 running in year one of a 3 year undergraduate nursing programme. This study sought to formally evaluate attitudes and beliefs, knowledge level and utilization of evidence based practice though using two validated questionnaires: Evidence Based Practice Beliefs Scale© and Evidence Based Practice Implementation Scale©.n = 311) at two time points. Time 1: pre-module in September 2014; and Time 2: post –module in August 2015. All data was collected via Survey Monkey.This was a pilot study using quantitative pre and post-test design. Anonymised data was collected from Year 1 undergraduate student nurses in the September 2014 intake (p < 0.05) in both the Evidence Based Practice Beliefs Scale (7/16 categories) and the Evidence Based Practice Implementation Scale (13 / 18 categories).Results demonstrate that the educational initiative positively impacted on both the beliefs and implementation of evidence based practice. Analysis highlighted statistically significant changes (The significance of integrating evidence based practice into undergraduate nurse education curriculum cannot be underestimated if evidence based practice and its positive impact of patient care are to be appreciated in healthcare settings internationally. Evidence based practice (EBP) is defined as p.71) “‘the conscientious, explicit and judicious use of current best evidence in making decisions about the care of the individual patient. It means integrating individual clinical expertise with the best available external clinical evidence from systematic research’”  “‘the co however Integrating evidence based practice when teaching research to undergraduate nursing students can help improve research knowledge.. NeverthEvidence based practice is not a new concept in nursing; indeed the Briggs report  suggesteCurrent research demonstrates that student nurses generally acknowledge the role that EBP plays in clinical practice. Indeed a recent study of undergraduate student nurses noted that most participants reported a positive attitude towards EBP, with a majority indicating that it was important for practice and quality of patient car . AdditioThe evidence above was instrumental for module coordinators (JR and CL) when designing a new EBP module  for year 1 of a 3 year undergraduate nursing degree programme. This was a core module, accounting for 40 CATS of an undergraduate year 1 programme, made up of 24 h of tutorials and 48 h of lectures. The coordinators took steps to ensure the content was grounded in practice. These steps included discrete slides per lecture on applicability to practice; a theory to practice link on each page of a specially designed EBN 1 e-resource; and a video or audio clip from a current member of staff discussing how their own research directly informs practice. This innovative approach and focus on practice ensured the module co-ordinators were utilising different skills to help teach EBP . Indeed,The overall aim of this pilot study was to use a pre-test post-testdesign to evaluate evidence-based practice at the start and on completion of year 1 undergraduate levelwithin a School of Nursing and Midwifery at a large University within the United Kingdom.To ascertain the attitudes and beliefs, knowledge level and utilization of evidence based practice of undergraduate students at the start of their degree programme and prior to undertaking evidence based practice training (Evidence Based Nursing 1 Module)To ascertain the attitudes and beliefs, knowledge level and utilization of evidence based practice of undergraduate students at the end of the first year of a degree programme which incorporated completing evidence based practice training (Evidence Based Nursing 1 Module)Evidence based practice is a seven step process : (1) culThis pilot pre-test post-test study used a prospective descriptive exploratory approach using non-probability convenience sampling of all undergraduate student nurses taking the compulsory “Evidence Based Nursing Modules 1” at a large teaching university within the United Kingdom was conducted from September 2014 to September 2015. This research involved students anonymously completing two validated scales  and Evidence Based Practice Implementation Scale© (EBPI))  online vEvidence Based Nursing 1 is core module (1/4 of the year 1 undergraduate course) in undergraduate nursing education within the recruiting university. The module runs across the entirety of year 1 undergraduate nurse education. The module utilises a blended learning approach using lectures, small group teaching and an online eResource (with formative and summative assessment built in).n = 311) undertaking the core module of “Evidence Based Nursing 1” at the recruiting University.The sampling frame for this study comprised all year 1 undergraduate student nurses in the September 2014 cohort (Data collection was at two time points: Time 1 prior to undertaking the Evidence Based Nursing 1 (September 2014); and Time 2 on completion of year 1 (August 2015) and Evidence Based Nursing Module 1). Students were emailed an invitation letter from the principle investigator (JR) with a link to the data collection site. All data was collected anonymously online via SurveyMonkey.Demographic data including specialism studied , gender and age was collected from all participants. Students were also asked to complete two scales:  will not have an effect on their assessment or marks; only the investigator would have access to the raw data; that the results from this study would be published and presented at conferences; and that involvement would be anonymous. Potential participants were emailed a link to the SurveyMonkey site where all data was collected at Time 1 and 2. Submission of the completed questionnaire on Survey Monkey was taken as consent.All data was collected and automatically collated online via SurveyMonkey. Quantitative descriptive and non-parametric statistics (Mann-Whitney U test) were used to summarise and interpret the findings of this study. All data was collected anonymously via survey monkey and then transferred into SPSS for data analysis. All anonymised data was analysed independent of the chief investigator (JR), by a third party outside the research team (DS).n = 311) using validated tools  “used evidence to change my practice”; “used a EBP guideline”; indicating that even after 1 year of exposure to EBP education, alongside completing three six-week clinical placements, nursing students were able to use evidence and EBP guidelines to change their practice.The absence of significant changes between Time 1 and Time 2 for the highly rated categories in the EBP beliefs scale such as: Significant changes in were also evident in items which questioned some of the more practical issues of implementing EBP such as critical appraisal (Question 2), generating a PICO question (Question 3), and accessing the Cochrane Database of Systematic Reviews (Question 12). This is promising given that a lack of skills in literature searching and critical appraisal is often cited as a barrier to effective implementation of EBP in nursing., 22.This pre-test post-test pilot study demonstrates that through completing year 1 of an undergraduate nursing degree which contains an educational module on EBP, undergraduate student nurses can increase their understanding and utility of EBP. However, this may not translate into their approach as subsequently qualified nurses in practice. This is indeed a notable issue as a recent study of over 1000 newly qualified nurses suggested that they have only a modest level of intention to utilise and integrate research evidence into their future practice [As with any study there are limitations to this work. Firstly, this study did not include a control group and thus it is impossible to distinguish between the effect of providing the first year of a nursing degree programme without providing EBN1 and these results presented within this paper (first year of degree programme which incorporated EBN1). This data was anonymously submitted by students and therefore we can’t be sure that the people who provided data at follow-up actually gave baseline data; additionally responders may not be typical of the class as a whole. Additionally, the total numbers of undergraduate student nurses in this cohort was 311 and of this only 124 completed data collection at Time 1 and 56 at Time 2, thus data may not be comparable to all students. Finally, because we cannot look at individual pairs but have to look at pre and post groups the study may be under-powered, but we are constrained in this regard by the number of students per intake and the voluntary participation that is a requirement of this study. Nonetheless, these very positive set of findings, even given the limitations, illustrate that attending the EBN1 module has a major impact on EBP beliefs and implementation scores, which have direct applicability to the learning outcomes of the module.The drive towards equipping nurses with the skills of EBP is supported internationally by nursing registration bodies and global nursing associations, such as the International Council of Nurses who actively promote and support evidence-based practice. As nurse educators we have a unique opportunity to teach the nurses of the future the skills and necessity of being evidence based practitioners. Data from this study demonstrates that targeted education on EBP can enhance undergraduate student nurses understanding and utility of EBP. The EBN nursing modules that run within the recruiting University across years 1, 2 and 3 of the undergraduate program, focus on complementary and cumulative learning thus increasing student nurses capacity to work as evidence based practitioners. Further research is needed on how this education, delivered at undergraduate level, influences nursing care delivery post registration.


Nutrigenetic research examines the effects of inter-individual differences in genotype on responses to nutrients and other food components, in the context of health and of nutrient requirements. A practical application of nutrigenetics is the use of personal genetic information to guide recommendations for dietary choices that are more efficacious at the individual or genetic subgroup level relative to generic dietary advice. Nutrigenetics is unregulated, with no defined standards, beyond some commercially adopted codes of practice. Only a few official nutrition-related professional bodies have embraced the subject, and, consequently, there is a lack of educational resources or guidance for implementation of the outcomes of nutrigenetic research. To avoid misuse and to protect the public, personalised nutrigenetic advice and information should be based on clear evidence of validity grounded in a careful and defensible interpretation of outcomes from nutrigenetic research studies. Evidence requirements are clearly stated and assessed within the context of state-of-the-art ‘evidence-based nutrition’. We have developed and present here a draft framework that can be used to assess the strength of the evidence for scientific validity of nutrigenetic knowledge and whether ‘actionable’. In addition, we propose that this framework be used as the basis for developing transparent and scientifically sound advice to the public based on nutrigenetic tests. We feel that although this area is still in its infancy, minimal guidelines are required. Though these guidelines are based on semi-quantitative data, they should stimulate debate on their utility. This framework will be revised biennially, as knowledge on the subject increases. Personalised nutrition (PN), based on an individual’s genotype, is not new. Individuals with rare genetic disorders such as phenylketonuria, galactosemia and hereditary fructose intolerance –3) as weMany sectors of modern society increasingly focus on personalising services or products to enable individuals to control more aspects of their lives. Public interest in personalised health has spurred growth in nutrigenetic testing services not only for disease susceptibilities but, especially, for optimising nutrition. Genetic testing is a largely unregulated market with many unsupported claims and inadequate explanations of the results and implications –11. It iThe general objective of PN is to maintain or improve health by using genetic, phenotypic, clinical, dietary and other information to provide more precise and more efficacious personalised healthy eating advice and to motivate appropriate dietary changes. For example, about 15 years ago, it was proposed that:“With the identification of polymorphisms, or common mutations, in vitamin metabolism, large percentages of the population may have higher requirements for specific vitamins .”Research since then has resulted in significant progress and has identified some well-defined gene × diet interactions supporting the concept that diets tailored to the individual’s genotype might result in long-term health benefits , 13, 14.www.food4me.org), which was initiated to examine several aspects of PN including business models, market readiness, ethics and public perceptions, and to perform a Europe-wide proof of principle intervention study on the effectiveness of PN approaches  or even ‘strong’ [convincing], if there are multiple small case reports or studies that are all supportive with no contradictory studies’ .Study deAll studies reporting on genetic interactions should adhere to the STREGA guidelines . STREGA 2.Biological plausibilityOnly studies that include STREGA guidelines should be considered when assessing a gene-diet interaction. In addition to the STREGA guidelines, the intake of the dietary component of interest should be reported quantitatively; for the description on the quantification of diet intake, see .2.Biolog‘a gene–environment interaction will only be accepted if it can be reproduced in two or more studies and also seems plausible at the biological level.’ ).The nutrigenetics research community organised in the ‘global personalised nutrigenetics knowledge network’ can contribute to the translation of the accumulating knowledge into practice by using these proposed guidelines. Regular reviews  of current knowledge of the most studied polymorphisms may generate additional, scientifically valid associations and hence provide recommendations about which polymorphisms may inform genotype-based dietary advice. We will also include reviews of genetic variants that do not meet these standards. The practical output for this exercise will be the publication of nutrient-gene cards in this journal Table Adoption of nutrigenetics and genetic testing has been slow in the healthcare system, and we hope that these guidelines accelerate informative genetic testing for education and practice. In a recent survey of 373 Canadian registered dietitians, 76% responded that they do not have sufficient knowledge of nutrigenetics. In spite of this, the majority stated ‘that genetic testing and their results have poor accuracy, and that there is a lack of scientific evidence’ . These cA genetic test for disease risk prediction would require different levels of evidence since disease risk predictions require the contribution of many SNPs. Determining risks relies on SNPs identified from genome-wide association studies (GWAS), many of which are in introns or gene deserts and have unknown functions. Since all GWAS and most nutrigenetic testing is based on (study) population averages, converting population attributable risk to personal risk is not possible . A risk In the commercial environment, the field of personal genetics and nutrigenetics are under increasing scrutiny from regulators. For example, the US Food and Drug Administration (FDA) and the Federal Trade Commission (FTC) limited the scope of direct to consumer products and services . Many cOur approach has some limitations and strengths. One limitation is the general heterogeneity and mixed quality of studies combining both genetic and nutritional analysis, often making it difficult to compare apparently similar studies analysing the same genetic variants and dietary components. Nutrition research in general is prone to inconsistency because of the high complexity and the subtle effects of nutrition on long-term health, the difficulties in accurate dietary assessment, food-food or nutrient-nutrient interactions, environmental context which can alter nutrient hosts interactions and compliance to a specific diet. These same issues also restrict the use of findings from meta-analysis. Inevitably, any assessment of nutrition and nutrigenetics can be only semi-quantitative at best. We consider that our approach has the benefit of creating a formal and generic model for the assessment of such evidence and will guide more focussed debates on specific points, which may be judged in different ways. Moreover, the framework and associated resources will allow stakeholders such as dieticians, nutritionists and genetic counsellors to improve their knowledge of nutrigenetics and at the same time will provide a resource to assess the various tests that are offered. This framework may encourage a greater standardisation of research protocols, supporting other initiatives such as PhenX , as well