The built and natural environment and health are inextricably linked. However, there is considerable debate surrounding the strength and quality of the evidence base underpinning principles of good practice for built and natural environment design in promoting health. This umbrella review aimed to assess relationships between the built and natural environment and health, concentrating on five topic areas: neighbourhood design, housing, food environment, natural and sustainable environment, and transport.A structured search was conducted for quantitative systematic reviews and stakeholder reviews published between January 2005 and April 2016. Seven databases and the websites of 15 relevant and respected stakeholder organisations known to publish review-level documentation were searched. Searches were limited to English-language publications and duplicate references were removed. Evidence quality and strength was appraised using validated techniques. Findings were used to develop a diagram for each topic area, illustrating relationships between built and natural environment planning principles and health-related outcomes.A total of 117 systematic reviews and review-level documents were eligible for inclusion. The quality of evidence was mixed; much of the evidence examined relied on findings from cross-sectional studies, making it difficult to draw clear causal links between built environment exposures and health-related impacts and outcomes. Fourteen actionable planning principles associated with positive health-related outcomes were identified across the five topic areas. For example, neighbourhoods that enhanced walkability, were complete and compact in design, and those which enhanced connectivity through safe and efficient infrastructure were associated with better health-related outcomes relating to physical activity, social engagement, mental health, perceptions of crime, and road traffic collisions. Evidence for the effectiveness of planning principles across different topic areas and on reducing health inequalities was sparse and inconclusive.Findings provide an up-to-date overview of relationships between the built and natural environment and health and present logical, evidence-based messages to aid communication between public health and planning professionals.The online version of this article (10.1186/s12889-018-5870-2) contains supplementary material, which is available to authorized users. The built and natural environment encompasses objective and subjective features of the physical environment in which people live, work and play,  and therEstablishing a causal relationship between built and natural environment characteristics and health outcomes is not easy. Much of the evidence to date relies on findings from observational epidemiological studies which highlight associations between the built and natural environment and health. However, the broadly cross-sectional nature of the evidence base means it is often difficult to determine cause and effect relationships between built environment exposures and health-related impacts and outcomes, and the potential effectiveness of interventions , 4. It hThe translation of research evidence into practice has been hindered by the sheer complexity of relationships between the built environment and health, in that they are both influenced by numerous, and sometimes conflicting factors , and theDespite these challenges, the volume of literature published in the last decade on links between the built and natural environment and health cannot be ignored. There is a need to take stock of the existing evidence base to consolidate our understanding and, where appropriate, to make recommendations to support those working in public health and planning professions. It was in response to this need that in January 2016 Public Health England (PHE) commissioned this umbrella review. The emergence of umbrella reviews in recent years has provided an attractive strategy for organising and assessing a wide range of review-level evidence , 8. The A structured search of the Cochrane Database of Systematic Reviews, EPPI-Centre, MEDLINE, PsycINFO, SafetyLit, Transport Research Information Service, and Applied Social Sciences Index and Abstracts was conducted in April 2016 to identify quantitative systematic reviews Table . ReferenIf a review presented findings on more than one of the five built environment categories or on more than one health outcome, these were assessed and reported separately. Reviews reporting on adults and children  were considered for inclusion, as were all health-related outcomes . Reviews published between January 2005 and April 2016 and conducted in high- and middle-income countries  were eligible. Searches were limited to English-language publications and duplicates were removed. Evidence from qualitative systematic reviews was excluded. In line with previous umbrella reviews, , 10 systPotentially eligible papers were screened for inclusion by one reviewer (JI) according to title and abstract. A 10% sample of search results was independently assessed by a second reviewer (EB). Full text articles and stakeholder documentation were then obtained and assessed by two reviewers  against the inclusion criteria. Descriptive data were extracted using a data extraction tool  and key findings).The Methodological Quality Checklist (MQC),  a 7-itemThe quality of empirical evidence informing each of the reviews was categorised according to one of three groups: high, moderate, and low. In most cases, allocation of quality rating was based on the rating provided by the original author(s) of each review. However, in some cases a quality rating was not provided by the original authors of a review, and as such, the quality of the empirical evidence could not be determined. In such instances, a quality rating of ‘not reported’ was used.Findings from each review were grouped according to presence of what we defined as a ‘modifiable feature’. This is a feature of the built and natural environment that, if altered in some way, is associated with a positive impact upon people’s behaviours or lifestyles, and/or health outcomes. For example, an improvement in lighting within the home environment (modifiable feature) was found to be associated with improved social outcomes  and reduced fall-related injuries among older adults . Each modifiable feature was then categorised into a broader theme, known as a ‘planning principle’. For example, the modifiable feature ‘improved residential lighting’ was categorised into the broader planning principle ‘improved quality of housing’. In some instances, more than one piece of review-level evidence reporting on the same health impacts and/or outcomes was identified. To avoid possible duplication or over-stating of results, planning principles and modifiable features were generated from the review-level evidence deemed to be of the highest methodological quality. This process was followed for all documentation included in this review, according to each of the five topics of interest.N = 32), housing (N = 23), healthier food environment (N = 20), natural and sustainable environment (N = 49), and, transport (N = 29). A full reference list of included studies, details of study characteristics and quality can be found in the online additional material. Figures Figure Eligible reviews were based on empirical evidence utilising a range of study designs and were targeted at a variety population groups. The quality of evidence was mixed as much of the evidence examined relied on findings from cross-sectional studies, making it difficult to draw clear causal links between specific built and natural environment principles and features and health-related outcomes: one review included original empirical studies deemed to be high quality (1%), 11 reviews contained evidence of moderate-to-high quality (9%), 25 of moderate quality (25%), 14 of low-to-moderate quality (12%), 9 of low quality (8%), and for 52 reviews the quality of evidence from original empirical studies was not reported by review authors (45%). In considering the evidence presented here, policy makers should be mindful that an absence of high quality evidence does not mean an association between a planning principle and health outcome does not exist. Further, many planning interventions can be expected to confer co-benefits either to both health and other outcomes, or across a number of health outcomes. Only four reviews eligible for inclusion focused on health inequalities; some positive results were reported, but the overall picture on associations between the built environment and health inequalities was inconclusive. The planning principles, modifiable features, and health-related outcomes identified for each built and natural environment domain, alongside an assessment of evidence quality, are summarised in the text below and in Table As shown in Fig. Improvements in housing quality, such as increased energy efficiency, were found to be associated with positive general health, mental health, asthma, and mortality outcomes  . This file lists the stakeholder organisation websites searched for eligible review level documentation. (DOCX 14 kb)Additional file 2:Characteristics of eligible review-level evidence, according to domain of interest. This file details the characteristics of eligible review-level evidence included within the umbrella review, and includes study population characteristics and quality appraisal outcomes. (DOCX 47 kb)Additional file 3:Reference list of eligible review-level evidence. This file contains the full reference list for eligible review-level documentation included within this umbrella review. (DOCX 43 kb)


Investigation of drug safety signals is one of the major tasks in pharmacovigilance. Among many potential signals identified, only a few reflect adverse drug reactions requiring regulatory actions, such as product information (PI) update. Limited information is available regarding the signal characteristics that might predict PI update following signal evaluation. The objective of this study was to identify signal characteristics associated with PI updates following signal evaluation by the European Medicines Agency Pharmacovigilance Risk Assessment Committee during 2012 to 2016.A comparative study was performed based on data from 172 safety signals. Characteristics of signals were extracted from the European Pharmacovigilance Issues Tracking Tool database. Multivariable logistic regression analysis was used to assess the relationship between signal characteristics and the decision to update the PI.P < 0.05).Multivariable logistic regression analysis showed that the presence of evidence in multiple types of data sources ; mechanistic plausibility of the drug‐event association ; seriousness of the event ; and age of drugs ≤5 years  were associated with the decision to change the PI (This study identified 4 characteristics of drug safety signals that have shown to be associated with PI changes as outcome of signal evaluation. These characteristics may be used as criteria for selection and prioritization of potential signals that are more likely to necessitate product information updates. Studies investigating drugs safety signals characteristics that might predict safety‐related product information changes are lacking.Confirmation of the signals in multiple types of data sources, the presence of mechanistic plausibility of a drug‐event association, seriousness of the events, and age of drugs ≤5 years were associated with the decision to update the product information.These criteria may be used for the selection or prioritization of the signals that are more likely to provide new safety information.1During the development of medicinal products, identification of adverse reactions, particularly rare adverse reactions and those with long latency, is limited. Pre‐approval trials are typically conducted with relatively small number of patients in a limited length of time. Selective enrollment of participants may also limit the generalizability in the postmarketing environment. Continuous safety surveillance is thus essential to ensure patient safety.A safety signal is defined as the information suggesting a new potential association or new aspects of a known association between medicines and adverse event(s) that warrant further investigation.In the European Union, the decision‐making process related to safety signals is coordinated by the European Medicines Agency (EMA) Pharmacovigilance Risk Assessment Committee (PRAC).Several signal characteristics have been postulated to help in signal assessment, including strength of evidence, public health impact, and the novelty of drugs and/or safety issues.2The list of safety signals discussed at the PRAC since September 2012 until May 2016 was obtained from the publicly available data on the website of the EMA.2.1Characteristics that are potentially important during signal assessment were pre‐defined and classified in 3 categories, namely the strength of evidence, public health impact, and the novelty of the drug. The rationale and definitions used for categorization of the signals are provided below.2.1.1Source of evidenceMechanistic plausibilityThe presence of signals in a wide range of additional sources may strengthen the evidence supportive of the signals.Presence of disproportionate reportingThe presence of mechanistic plausibility is an important factor supporting the association.Positive dechallenge or rechallengeIncreased frequencies of the case reports concerning a specific drug‐event association in comparison with general reporting frequencies may indicate a new potential signal.Possible class effectThe presence of positive dechallenge and rechallenge might be important in establishing causality based on individual narratives of the reported cases. Knowledge that drugs from the same pharmacological class produce the same adverse effect might strengthen the evidence for a signal. The signals were classified as reflecting possible class effects if during signal assessment it was mentioned that the suspected event is labeled for other drugs from the same class.2.22.2.1Serious events usually have an increased public health importance compared with non‐serious ones.2.2.2New risks are more likely to be observed in newer drugs.3P‐value<0.1 in the first analysis were then included in a multivariate logistic regression model. Subgroup analysis was performed to investigate whether different signal characteristics were associated with the updates of section P < 0.05 defined statistical significance in the main analysis, while for subgroup analysis, statistical significance was set at P < 0.1. Analysis was performed using Stata 11.2.Descriptive analysis was used to compare characteristics of signals between the groups which resulted in safety‐related PI changes and without. To assess the influence of various characteristics on the PI update, first, a univariate logistic regression analysis was performed. Criteria that were associated with PI changes with a 4n = 94), signals which resulted in regulatory actions other than PI updates (n = 20), signals assessments were still ongoing (n = 4), and signals for which a full assessment could not be retrieved (n = 10), 172 signals remained for the analysis. The most frequently identified ADR were related to skin and subcutaneous tissue disorders (10%). Most frequently involved drugs were antineoplastic and immunomodulating drugs (31%) (Table During the study period (September 2012–May 2016), 300 signals were assessed at the PRAC. After excluding non‐eligible signals, ie, signals which were further investigated in other regulatory procedures n = 9, signalsSpontaneous case reports were the most common source of evidence, supporting 87% of the signals. We also found that 43% of the signals which resulted in PI updates were assessed based on evidence coming from spontaneous case reports only. In the univariate logistic regression model, the presence of evidence from spontaneous case reports was associated with PI update . Greater magnitude of difference was seen in the signals supported by ≥3 types of sources . The presence of biological plausibility of the drug‐event association led to more PI updates .Although the proportion of positive dechallenge and rechallenge results was higher among the signals resulted in PI updates, the differences were not statistically significant. The proportion of serious events was significantly higher among the signals resulted in PI update . Signals concerning younger products, ie, ≤ 5 years old, resulted more often in PI updates  , the mechanistic plausibility of drug‐event association , seriousness of the events , and age of drugs ≤5 years   resulted more often in PI updates. At the time of drugs approval, only partial safety information was obtained due to several known limitations in pre‐marketing clinical studies., information regarding medical history of the patient, time to onset, the use of concomitant drugs, etc, are strongly suggestive of causal association and therefore signals with reported positive dechallenge and rechallenge are more likely to result in update of section Although positive dechallenge and rechallenge observed in individual spontaneous reports are important factors in establishing causality,Our study showed that the presence of disproportionate reporting in safety databases was not necessarily associated with the decision to update the PI. Disproportionality analysis is subject to well‐known limitations, such as limited database quality inherent in voluntary reporting system, various confounding factors, and inability to provide actual denominator, ie, number of subjects who consumed drug of interest. These limitations might contribute to the occurrence of false signal of disproportionate reporting or alternatively true safety signals may appear without disproportional reporting.There have been a few attempts to combine criteria for signal prioritization in algorithms or frameworks to support the drug signal selection and prioritization process by different organizations responsible in managing drug safety issues.The strength of our study is that it is the first study investigating the predictive value of drug safety signals characteristics in terms of predicting whether the signals represent ADR requiring PI updates. In addition, we included signals investigated during the first 3.8 years since the establishment of the PRAC. Nevertheless, this study also had some limitations. We did not include signals addressed in other regulatory procedures, eg, the PSUR assessment procedure. However, because it was considered that the conduct of assessment was relatively similar, no significant change is expected. Furthermore, the performance of these characteristics is based on the signal assessment performed in the European Union. These criteria may perform differently in other databases comprising safety evaluation conducted in other geographic regions. Therefore, further studies are recommended if these variables are to be used in a different setting.6Our study highlighted that the presence of evidence in multiple type of sources, mechanistic plausibility, seriousness of the event, and age of drugs ≤5 years were the predictors of safety‐related PI changes. The characteristics related to the strength of evidence were particularly important for the update of section The authors state that no ethical approval was needed.All authors have no conflicts of interests in this research. The views expressed in this article are the personal views of the author(s) and may not be understood or quoted as being made on behalf of or reflecting the position of the Dutch Medicines Evaluation Board or the European Medicines Agency or one of its committees or working parties.


This study analysed fruits of cranberry cultivars: Ben Lear, Bergman, Early Richard, Pilgrim and Stevens and compared them with wild-grown cranberry fruits. The fruits were characterised in terms of dimensions, colour, content of total phenolic compounds, flavonoids, proanthocyanidins and anthocyanins, and hydroxyl radical and trypsin inhibition activities. It was shown that the wild-grown cranberry fruits were characterised by much smaller dimensions and redder colour than fruits of the cranberry cultivars. The most phenolic compounds were found in the Early Richard fruits (357.6 mg/100 g fw), and they showed the highest antitrypsin activity. The highest anthocyanin content (60.6 mg/100 g fw) was determined in the Pilgrim fruits, while the Ben Lear fruits were the richest source of proanthocyanidins (27.9 mg/100 g fw). The antioxidant activity was correlated with the content of phenolic compounds, flavonoids and proanthocyanidins, while the antitrypsin activity was correlated with phenolic compounds and anthocyanin contents. Vaccinium macrocarpon), also known as large cranberry, belongs to the Ericaceae family [Vaccinium oxycoccus), which is characterised by smaller fruits compared to large cranberry fruits [American cranberry , minerals , as well as lutein and β-carotene . The mosnfection , 11. It nfection . Cranberh ulcers , 5, 11. h ulcers . It has h ulcers , 6, 8.Due to the growing interest in large-fruited cranberry cultivation in Poland, the characterization of five cultivars was conducted in terms of geometric features, colour, and content of total phenolic compounds, flavonoids, proanthocyanidins, anthocyanins. These physical and chemical properties were correlated with antioxidant activity and also antitrypsin activity, which has not been previously studied in the cranberry fruits. Additionally, the anthocyanin content in fruit peels was also determined. The reference sample consisted of wild-grown cranberry fruits.The research material comprised the fruits of five cultivars of large cranberry: Ben Lear, Bergman, Early Richard, Pilgrim and Stevens. The fruits came from the Experimental Field of Blueberries in the Department of Horticulture and Natural Basics of Horticulture at SGGW in the village of Błonie near Piaseczno. The fruit harvest was carried out in 2016 after berries were ripe for consumption. The fruits of wild-grown cranberry collected from the natural environment near Olsztyn were then compared.The geometrical features  and surface colour  of cranberries were measured using digital image analysis (DIA) according to the method described. The images were acquired by a high resolution, low-noise CCD (charge-coupled device) Nikon DXM-1200 colour camera  and analysed by LUCIA v. 4.8 software . The frame grabber was at a resolution of 1280 × 1024 pixels. The light source was a Kaiser RB 5004 HF – High Frequency Daylight Copy Light set with 4 × 36 W fluorescent light tubes (colour temperature about 5400 K) . Before analyses, the calibration to a standard white reflective plate was done.per 100 g of fresh weight (fw). The total flavonoid content was determined according to the method described by Lamaison and Carnat [per 100 g fw. The total anthocyanin content in fruits and peels was determined using the pH differential method according to the method given by Borowska et al. [per 100 g fw. Determination of the total content of proanthocyanidins was carried out according to the procedure using 1-butanol-HCl reagent described by Mole and Waterman [per 100 g fw. The anthocyanin profile in fruits was determined according to the procedure of Borowska et al. [v/v/v). The flow rate was 1.1 ml/min and the temperature of the oven column was 30 °C. The wavelength was set to 520 nm. The identification was made by comparing peak retention times of the samples with anthocyanin standards and literature data. The amount of anthocyanins was calculated from the calibration curves. The calibration curve was plotted for each standard. The concentration of the standard ranged from 10 to 100.03 mg/l. The correlation of the calibration curve was r2 = 0.9899. The content of individual anthocyanins was expressed in milligrams per 100 g fw.Methanol (80% solution containing 0.1% hydrochloric acid) was used to prepare phenolic extracts based on the procedure reported by Borowska et al. . The cond Carnat . The resa et al. . To deteWaterman . The proa et al. . The antper g fw. The antitrypsin activity was determined according to the method given by Guillamón et al. [A scavenging of the hydroxyl radical (OH) was measured by the deoxyribose method . The resn et al. . The actThe obtained data were analysed statistically using Statistica 12.0 PL software . A one-way analysis of variance (ANOVA) with the Tukey test was used. Pearson’s correlation coefficients were also determined to establish the relationship between phenolics and colour as well as antioxidant and antitrypsin activities. The statistical significance was set at the 5% level.P ≤ 0.05) in terms of their dimensions. The average diameter values ranged from 12.35 mm for fruits of the Ben Lear cultivar to 17.20 mm for the fruit of the Pilgrim cultivar. The average width and length values for fruits of cranberry cultivars were 11.95–15.60 mm and 12.99–19.04 mm, respectively . The content of flavonoids in wild-grown cranberry was 136.0 mg in 100 g of fruits.Smaller differences between the cranberry cultivars were found in the flavonoid content Table . The BerAs can be seen from the data presented in Table The studied cranberry fruits contained from 44.6 to 60.6 mg anthocyanins in 100 g fw Table . The fruUsing the HPLC technique, five anthocyanins were identified in the studied cranberry fruits: cyanidin-3-galactoside, cyanidin-3-glucoside, cyanidin-3-arabinoside, peonidin-3-galactoside and peonidin-3-glucoside Table . In the The fruits of studied cranberry cultivars were characterised in terms of scavenging hydroxyl radicals, and the results are shown in Table Although low molecular weight protein fractions are responsible for antitrypsin activity, phenolic compounds may also have such properties . While tThe correlations between selected features of the cranberry fruits are presented in Table This study found large variation in the physical properties, content of phenolic compounds as well as antioxidant and antitrypsin activities of cranberry fruits. The fruits of cranberry cultivars were characterised by much higher dimensions than fruits of the wild-grown cranberry. Furthermore, the fruits of wild-grown cranberry had the most red colour and, at the same time, the least yellow colour. In turn, the fruits of the Ben Lear cultivar were characterised by the lightness colour, and the fruits of Early Richard cultivar were the darkest. The Early Richard cranberry sample was also the most heterogeneous in terms of fruit peel colour, while the wild-grown cranberry sample was the most homogeneous. The richest source of polyphenols was the Early Richard cranberry. The fruits of this cultivar were also distinguished by the strongest antitrypsin activity. The fruits of the Bergman cultivar contained the most flavonoids, while the Ben Lear cultivar had the least. The Ben Lear cranberry fruits were distinguished by the highest concentration of proanthocyanidins, while the fruits of the Stevens cultivar contained more than three times less of these compounds. The highest concentration of anthocyanins was determined in the Pilgrim cultivar, while the highest levels of these compounds were found in peels of the Bergman cultivar. The use of the HPLC technique allowed differences in the quantitative composition of individual anthocyanins in the fruits to be shown and, regardless of the cultivar, peonidin-3-galactoside predominated in the fruits. Based on the determined correlation relationships, it was noted that the redder fruits contained more anthocyanins, but fewer other phenolic compounds, which was responsible for their lower antioxidant and antitrypsin activities.


Although note taking during trials is known to enhance jurors’ recall of trial evidence, little is known about whether individual differences in note taking underpin this effect. Individual differences in handwriting speed, working memory, and attention may influence juror’s note taking. This, in turn, may influence their recall. It may also be the case that if jurors note down and recall more incriminating than non-incriminating evidence (or vice versa), then this may predict their verdict. Three studies examined the associations between the aforementioned individual differences, the amount of critical evidence jurors noted down during a trial, the amount of critical evidence they recalled, and the verdicts they reached. Participants had their handwriting speed, short-term memory, working memory, and attention assessed. They then watched a trial video (some took notes), reached a verdict, and recalled as much trial information as possible. We found that jurors with faster handwriting speed (Study 1), higher short-term memory capacity (Study 2), and higher sustained attention capacity (Study 3) noted down, and later recalled, the most critical trial evidence. However, working memory storage capacity, information processing ability (Study 2) and divided attention (Study 3) were not associated with note taking or recall. Further, the type of critical evidence jurors predominantly recalled predicted their verdicts, such that jurors who recalled more incriminating evidence were more likely to reach a guilty verdict, and jurors who recalled more non-incriminating evidence were less likely to do so. The implications of these findings are discussed. During trials, jurors need to encode the evidence, legal arguments, and judicial instructions presented to them, store these in memory throughout the trial, and recall them during deliberation to reach a fair verdict. Jurors’ recall of trial evidence, however, has been found to be incomplete and inaccurate –3. TheseIn educational psychology research, undergraduate students with faster handwriting speed make better quality notes, as measured by completeness of explanations for each topic mentioned during a lecture . MoreoveNote taking is cognitively effortful as it involves temporary storing and manipulating information in memory . Thus, iWorking memory refers to the storage, manipulation and updating of incoming information ,16. It iTo our best knowledge, no study has explored the relationship between note taking and short-term memory capacity by using traditional short-term memory span tasks. Thus, we used a letter span task to examine whether jurors’ short-term memory capacity was associated with the amount of notes they made during a trial, and whether it was also indirectly associated with the amount of trial evidence they subsequently recalled.Furthermore, complex span tasks (such as the listening span task) have been used to assess working memory storage capacity. No association has been found between students’ working memory storage capacity and the amount of lecture ideas recorded in notes . HoweverLastly, information processing tasks (such as the word reordering task) have been used to assess the cognitive ability to process/manipulate information. Students’ scores on the word reordering task have been found to predict the number of propositions and main ideas they note down during a lecture . The numDuring trials, it is crucial that jurors stay attentive and focus on the evidence presented as they need to encode as much information as possible to be able to remember it when reaching verdicts. Trials vary in length and can last from a few hours to a few months. Thus, jurors’ ability to use their limited cognitive resources  over lonIn the educational psychology literature, sustained attention has been found to be positively related to the amount of notes taken during a lecture . FurtherIt is currently unknown whether note taking can act as a form of divided attention that is detrimental to encoding of new information for those with low divided attention capacity. In the wider memory literature, the impact of divided attention on memory of simple material , has been studied extensively using a dual-task paradigm. Typically, participants are required to study word lists under a full attention condition or a divided attention condition . Divided attention, when compared to full attention, during encoding generally decreases participants’ free recall, cued recall, and recognition of words lists –28.We acknowledge that the aforementioned studies examined divided attention using tasks that typically divert attention away from the to-be-learned information during encoding which is detrimental to memory. However, note taking typically focuses jurors’ attention on the to-be-learned information at encoding which may benefit memory. It is, however, reasonable to question whether jurors with lower divided attention capacity will find it harder to divide attention between taking notes and encoding the trial content, which could have a negative impact on their note taking and subsequent recall of trial information.Jurors’ recall of trial evidence can be incomplete. For instance, Costabile and Klein  found thIrrespective of whether or not jurors take notes, the type of critical evidence they recall  may predict their verdicts. Whilst reaching verdicts, jurors may remember more incriminating (or non-incriminating) trial evidence and may then find a defendant guilty (not guilty) because of this. To date, no study has examined whether a bias towards recalling more incriminating or non-incriminating evidence can predict jurors’ verdicts. Therefore, we assessed the association between the type of critical evidence jurors predominantly recalled and the verdicts they reached.The purpose of the three studies was to investigate (1) the impact of individual differences on juror note taking and recall of critical trial evidence, and (2) the impact of the type of trial evidence recalled on verdicts. In relation to the first of these, Study 1 focused on individual differences in handwriting speed, Study 2 focused on individual differences in short-term memory, working memory, and information processing ability, and Study 3 focused on individual differences in divided and sustained attention.The principal aims of Study 1 were to investigate the associations between mock jurors’ handwriting speed, the amount of critical evidence they noted down during a trial, the amount of critical evidence they recalled, and whether the type of evidence recalled predicts their verdicts. We measured handwriting speed before the jurors watched a trial video . Then all jurors reached a verdict and recalled as much trial information as possible. The non-note takers were our control group which helped us determine whether note taking enhances recall of trial information, as has been found previously ,8.We used a mediation model to test our novel hypothesis regarding whether handwriting speed would be associated with the amount of critical evidence jurors recalled, via the amount of critical evidence they noted down during the trial. It was expected that jurors with faster handwriting speed would note down the most critical evidence during the trial, which would increase the amount of critical evidence they recalled, in line with findings from educational psychology . FurtherOf importance to juror decision making, we tested whether the type of critical evidence (incriminating or non-incriminating) that jurors predominantly recall predicts their verdicts. That is, the analysis assessed whether jurors who recalled more incriminating evidence were more likely to reach a guilty verdict, and whether those who recalled more non-incriminating evidence were more likely to reach a not guilty verdict. In line with previous studies , it was M = 20.33, SD = 6.26). Participants were drawn from undergraduate student sample and staff at a northwest English university. All met the eligibility criteria for jury service in England and Wales . Prior to testing, all participants provided written consent confirming they wished to take part in the study. All received a payment in the form of course credit or a £10 voucher . The study was approved by the Health and Life Sciences Committee on Research Ethics of the University of Liverpool.One hundred forty-one participants acted as mock jurors  . All were between 18 and 66 years of age (Participants were assigned to one of three conditions: note taking without access to notes during the memory test (N = 60), note taking with access to notes during the memory test (N = 54) and no note taking N = 27). Previous findings . Previou have shoParticipants were allocated to conditions in a quasi-random method, whereby testing for each condition took place on fixed days of the week. For instance, if participants completed the study on a Monday they were allocated to a non-note taking condition, whereas if participants took part in the study on a Tuesday they were in the note taking condition. Participants signed up for a session in groups of up to 3 without knowing what condition they would be in.The Alphabet Fluency Task  was usedJurors watched a 30-min video of a 1992 murder re-trial with the case name New Jersey vs. Daniel Bias. Trials are not broadcast in England and Wales, thus, footage from a US trial was used. In this trial, the defendant was accused of murdering his wife by shooting her in the head. The defendant claimed he is innocent and that his wife shot herself. The video was edited so that it contained the opening statements, the cross-examination of six witnesses and the defendant, the closing statements, and the judicial instructions. The verdict is not shown. Past research shows jurors are evenly split between guilty and not guilty verdicts for this trial  and thatConsistent with real trials in England and Wales , jurors Jurors were tested in a computer lab in groups of up to three. In each session, all participants were in the same condition. Each participant was seated at an individual PC. Throughout the study, they were unable to see each other performing the tasks due to desktop screen dividers. First, all jurors completed the Alphabet Fluency task. They were then informed that they would watch a trial video and once it was over they would reach a verdict and answer questions about the trial. No explicit reference was made to a memory test. They were then told whether or not they would be allowed to take notes during the trial. Note takers were then provided with a notepad and pen and the trial video commenced. After the video, they were asked to complete the demographic/verdict questionnaire. Next, all jurors completed the free recall test with no time limit. They were instructed to write down as much trial evidence as they could remember. Half of the note takers were allowed to access their notes throughout the memory test, the other half had their notes confiscated before the test. The participants were not informed prior to taking notes whether or not they would be allowed access to their notes during the memory test. In practice, we did not measure whether jurors looked at or used their notes during the memory test. Upon completion of the free recall test, all jurors were debriefed and the study ended. The study lasted approximately 60 mins.The amount of critical evidence noted down and freely recalled was scored as follows. A coding sheet for critical evidence was based on the pilot study where participants identified the most important trial evidence. In the pilot study, thirty-three participants were asked to watch the trial video and then write down the ten most important pieces of trial evidence they believed could impact upon jurors’ verdicts. They were also asked to indicate whether each piece of evidence implied that the defendant was guilty or not guilty. Moreover, they were asked to rank these pieces of evidence from the most important to the least important. The pilot study used non-legal professionals (lay members of the public) to assess what they thought was the most important evidence presented during the trial. We believe this enables us to examine the evidence that potential jurors may feel is important to focus on when reaching verdicts. Combined, the participants identified 16 unique pieces of trial evidence that they believed could influence real jurors’ verdicts. Half of these implied that the defendant was guilty  whereas the other half implied that he was not guilty . For instance, the fact that the victim was right handed but was shot on left hand side of her head implies the defendant was guilty, so is an example of incriminating evidence. Conversely, the fact that the victim had previously threatened to kill herself implies that the defendant was not guilty, so is an example of non-incriminating evidence. In the present study, the lead author tallied the pieces of incriminating evidence (out of eight) and non-incriminating evidence (out of eight) noted down and freely recalled by participants.All notes and free recall responses were also scored for the overall amount of correct information noted down and recalled, irrespective of whether it is critical evidence or not. A coding sheet containing all information that appeared in the trial video  was useTwenty percent of jurors’ notes and free recall responses were checked for inter-rater reliability by two independent raters who were blind to the aims of the study. One rater coded the notes and the other rater coded the free recall responses. The inter-rater agreement between the lead author and independent raters was 84% for notes and 85% for free recall. All disagreements were resolved by the lead author and an independent reviewer who compared them and determined the correct score.Correlational analyses were used to examine the associations between handwriting speed, the volume of critical evidence noted down and recalled, and amount of correct information noted down and recalled see .A simple mediation analysis was conducted to assess (1) the direct effect of handwriting speed on the amount of critical evidence recalled, and (2) the indirect effect of handwriting speed on recall through the amount of critical evidence noted down. The model included only those jurors who took notes during the trial.2, which is an effect size for indirect effects in mediations [PM, which is a ratio of the indirect effect to the total effect [2 and PM values were calculated using the MBESS package (version 4.4.3) [All analyses were conducted using PROCESS (Version 2.16.1) for SPSS . The resdiations , and PM,l effect . κ2 and n 4.4.3)  in R (ven 4.4.3) .2 = 0.11, PM = 3.43 (κ2 indicates a medium effect size). More specifically, jurors with faster handwriting speed recalled a greater amount of critical evidence, via writing down the most critical evidence during the trial.Handwriting speed was found to be positively associated with the amount of critical evidence noted down during the trial see . There w2(2) = 31.64, Cox & Snell 2R = .31, Nagelkerke 2R = .43, p < .001). The amount of incriminating evidence recalled statistically predicted jurors reaching a guilty verdict, B = .72 (SE = .22), Wald = 10.96, p = .001; OR = 2.05, 95% CI = 1.34, 3.14, such that for every additional piece of incriminating evidence recalled, jurors were 2.05 times more likely to reach a guilty verdict. Furthermore, the amount of non-incriminating evidence recalled negatively predicted jurors reaching a guilty verdict, B = -.75 (SE = .23), Wald = 10.91, p = .001; OR = 0.47, 95% CI = 0.30, 0.74, such that for every piece of non-incriminating evidence recalled, jurors were 2.13 times less likely to reach a guilty verdict.A logistic regression was conducted to assess whether the amount of incriminating evidence and the amount of non-incriminating evidence jurors recalled predicted their verdicts . The overall model significantly predicted the likelihood of jurors reaching a guilty verdict, correctly identifying 77.6% of cases (χ2(1) = .26, Cox & Snell R2 = .005, Nagelkerke R2 = .007, p = .40).Seventy-three percent of jurors believed that the defendant was guilty: 78% in the access to notes during retrieval condition, 70% in the no access to notes condition, and 70% in the non-note taking condition. A logistic regression analysis was conducted to evaluate whether the condition that the jurors were in  was associated with their verdict. The regression revealed that the condition did not predict verdicts,  than jurors who did not take notes , t(139) = 3.27, p = .001 , d = 0.71.An independent t-test was used to examine whether note-taking jurors recalled more correct trial information than non-note taking jurors. Note taking jurors recalled significantly more correct trial information  and those who could not , t(112) = 0.81, p = .42, d = 0.15.We also examined whether note-taking jurors who could access their notes during the memory test recalled more correct trial information than note-taking jurors who did not have access to their notes during the memory test. There was no significant difference between the amount of trial information recalled by those who could access their notes during the memory test  acted as mock jurors. Prior to testing, all participants provided written consent confirming they wished to take part in the study. As in Study 1, they were a combination of undergraduate students and staff at the first author’s university and received payment in the form of either course credit or a £10 voucher. They were assigned to one of two conditions: a note taking (N = 58) or a non-note taking condition (N = 27). Participants were assigned to conditions as in Study 1. The study was approved by the Health and Life Sciences Committee on Research Ethics of the University of Liverpool.Eighty-five jurors who were eligible for jury service in England and Wales  between 18 and 61 years of age  to each juror who was instructed to immediately repeat them back in the same order. If he/she repeated all letters correctly, they passed the trial and were given a list of four letters . Each trial increased by one letter. If jurors failed at the first attempt , they were given a second attempt using the same number  of a different set of letters. If they failed at the second attempt, the task was terminated. The length of the longest list a juror repeated correctly was his/her short-term memory capacity score.s could range from zero to six.The Listening Span task  is a meaThe Word Reordering task  measuresThe same trial footage, demographic/verdict questionnaire, note taking materials, and memory test used in Study 1 were also used in Study 2.The procedure was similar to that of Study 1 except that instead of handwriting measures, the participants completed the tasks in the following order: the Letter Span task, the Listening Span task, and the Word Reordering. As Study 1  found no differences in the amount of trial information recalled between those who were and were not allowed to access notes during the free recall task, we removed the access to notes condition from the study design. All note taking jurors had their notes confiscated when the trial video was over. Thus, they were not able to access their notes during the memory test.The coding procedure of notes and free recall responses was the same as in Study 1. The inter-rater agreement between the lead author and independent raters was 98% for notes and 95% for free recall. All disagreements were resolved by the lead author and an independent reviewer who compared them and determined the correct score.Correlational analyses were used to examine the associations between short-term memory capacity, working memory storage capacity, information processing ability, the amount of critical evidence noted down and recalled, and the amount of correct trial information noted down and recalled see .Three simple mediation analyses were conducted to assess (1) the direct effect of short-term memory capacity, working memory storage capacity, and information processing ability on the amount of critical evidence recalled, and (2) the indirect effect of short-term memory capacity, working memory storage capacity, and information processing ability on recall through the volume of critical evidence noted down. The models included only those jurors who took notes during the trial.p = .21, 95% CI = -.12, .55. However, there was a significant indirect effect of short-term memory capacity on recall through the amount of critical evidence noted down during the trial, unstandardized estimate = .09 (0.07), 95% CI = .01, .29, κ2 = 0.07, PM = 0.29, (κ2 indicates a medium effect size). More specifically, jurors with higher levels of short-term memory capacity recalled a greater amount of critical evidence, through writing down the most critical evidence during the trial.A positive association was found between the amount of critical evidence jurors noted down and the amount of critical evidence recalled see . There wp = .61, 95% CI = -.26, .43. The indirect effect of working memory storage capacity on recall, through the amount of critical evidence noted down during the trial, was also not significant, unstandardized estimate = -0.02 (0.06), 95% CI = -.18, .08, κ2 = 0.01, PM = -0.26.There was a positive association between the amount of critical evidence noted down and the amount of critical evidence recalled see . We founp = .05, 95% CI = -.09, .001. Additionally, there was a non-significant indirect effect of information processing recall, through the amount of critical evidence noted down during the trial, unstandardized estimate = 0.01 (0.01), 95% CI = -.01, .04, κ2 = 0.06, PM = 0.25.We found a positive association between the amount of critical evidence noted down and the amount of critical evidence recalled see . There w2(2) = 31.64, Cox & Snell R2 = .31, Nagelkerke R2 = .43, p < .001). The amount of incriminating evidence recalled statistically predicted guilty verdicts reached by jurors, B = .72 (SE = .22), Wald = 10.96, p = .001; OR = 2.05, 95% CI = 1.34, 3.14, such that for every additional piece of incriminating evidence recalled, jurors were 2.05 times more likely to reach a guilty verdict. The amount of non-incriminating evidence recalled again negatively predicted jurors’ guilty verdicts, B = -.75 (SE = .23), Wald = 10.91, p = .001; OR = 0.47, 95% CI = 0.30, 0.74, such that for every piece of non-incriminating evidence recalled, jurors were 2.13 times less likely to reach a guilty verdict.As in Study 1, we conducted a logistic regression to determine whether the amount of incriminating evidence and the amount of non-incriminating evidence jurors recalled predicted their verdict . The model significantly predicted the likelihood of jurors reaching a guilty verdict, correctly identifying 77.6% of cases (χ2(1) = 0.01, Cox & Snell R2 < .01, Nagelkerke R2 < .01, p = .92).Sixty-six per cent of jurors reached a guilty verdict: 65% in the note-taking condition and 67% in the non-note taking condition. To examine whether the condition that these jurors were in predicted their verdict, we conducted a logistic regression. As expected, and as found in Study 1, no effect was observed  than jurors who did not take notes , t(83) = 2.75, p = .007 , d = 0.64.An independent t-test was used to examine whether note-taking jurors recalled more correct trial information than non-note taking jurors. Again we found note taking jurors recalled significantly more correct trial information  acted as mock jurors. All were eligible for jury service in England and Wales. Prior to testing, all participants provided written consent confirming they wished to take part in the study. They were a combination of undergraduate students and staff at the first author’s university and received payment in the form of either course credit or a £10 voucher. Jurors were assigned to one of three conditions: note taking with notes available during the memory test (N = 54), note taking with notes unavailable during the memory test (N = 53), and non-note taking (N = 27). Participants were assigned to conditions as in Studies 1 and 2. The study was approved by the Health and Life Sciences Committee on Research Ethics of the University of Liverpool.One hundred thirty-four participants  between 18 and 59 years of age . The interference in RT was calculated by subtracting the baseline RT from the Dual RT. This provided the final divided attention score which is a measure of cognitive effort devoted to writing while listening. Both RT tasks lasted approximately 20 minutes.The same trial footage, demographic/verdict questionnaire, note taking materials, and memory test used in Studies 1 and 2 were also used in Study 3.The procedure was similar to that of Studies 1 and 2, except that jurors completed the Lottery subtest of the Test of Everyday Attention and the Dual-Task before they watched the trial video.The coding procedure for the notes and free recall responses was the same as in Study 1. The inter-rater agreement between the lead author and independent raters was 83% for notes and 81% for free recall. All disagreements were resolved by the lead author and an independent reviewer who compared them and determined the correct score.Correlational analyses were used to examine the associations between sustained attention, divided attention, critical evidence noted down and recalled, and correct trial information noted down and recalled see .Two simple mediation analyses were conducted to assess (1) the direct effect of jurors’ sustained and divided attention capacity on the amount of critical evidence recalled, and (2) the indirect effect of sustained and divided attention capacity on recall through the amount of critical evidence noted down. The models included only those jurors who took notes during the trial.2 = 0.14, PM = 0.57 (κ2 indicates a medium effect size).Jurors with higher sustained attention capacity noted down a greater amount of critical evidence. There was also a positive association between the amount of critical evidence jurors noted down and the amount of critical evidence they recalled. 2 = 0.07, PM = 0.37.Divided attention capacity was not associated with the amount of critical evidence noted down during the trial, which was unexpected. However, as above, jurors who noted down a greater amount of critical evidence recalled a greater amount of critical evidence. 2(2) = 29.86, Cox & Snell R2 = .20, Nagelkerke R2 = .27, p < .001). The amount of incriminating evidence recalled statistically and positively predicted the likelihood of guilty verdicts being reached by jurors, B = .44 (SE = .14), Wald = 9.24, p = .002; OR = 1.55, 95% CI = 1.17, 2.04, such that for every additional piece of incriminating evidence recalled, jurors were 1.55 times more likely to reach a guilty verdict. Further, the amount of non-incriminating evidence recalled negatively predicted the likelihood of guilty verdicts, B = -.48 (SE = .13), Wald = 14.71, p < .001; OR = 0.62, 95% CI = 0.48, 0.79, such that for every piece of non-incriminating evidence recalled, jurors were 1.61 times less likely to reach a guilty verdict.We conducted a logistic regression to assess whether the amount of incriminating evidence and the amount of non-incriminating evidence jurors recalled predicted their verdict , as in the Studies 1 and 2. The overall model significantly predicted the likelihood of jurors reaching a guilty verdict, correctly identifying 67.2% of cases (χ2(2) = 5.52, Cox & Snell R2 = .04, Nagelkerke R2 = .05, p = .06).Fifty-three per cent of jurors reached a guilty verdict: 41% in the access to notes during retrieval condition, 60% in the no access to notes during retrieval condition and 63% in the non-note taking condition. A logistic regression was conducted to test whether the condition predicted verdicts. In line with our previous findings, no effect was observed  than non-note taking jurors , t(132) = 3.75, p < .001 , d = 0.88.An independent t-test was carried out to examine whether jurors who took notes during the trial recalled more correct trial information than those who did not take notes. Note taking jurors recalled significantly more correct trial information , and those who had access to their notes during the memory test , t(105) = .03, p = .98, d = 0.01.An independent t-test was used to examine whether jurors who were able to access their notes during the memory test recalled more information than those who were not permitted to access their notes. Consistent with Study 1, there was no significant difference in the amount of information recalled by note takers who could not access their notes during the memory test . Therefore, it is surprising that this association was not found in the present study.It is possible that the working memory task we used (listening span) does not accurately measure the demands placed on working memory by note taking. This is the most likely explanation for the lack of significant associations between working memory capacity and notes demonstrated by the present and previous studies ,11. WorkThe lack of association found between jurors’ information processing ability, notes, and recall contradicts previous findings . HoweverStudy 3 showed that jurors with higher levels of sustained attention recalled more critical evidence, which was via noting down more critical evidence while they watched the trial. This supports previous findings  and exteWe did not find a significant association between jurors’ divided attention capacity and the amount of critical evidence they noted down during the trial or their subsequent recall of that evidence. The reason why sustained attention predicted jurors’ note taking and recall but divided attention did not is unclear. One possible explanation is that the act of note taking focuses jurors’ attention on the trial so that their attention is not truly divided, and thus note taking/recall are subsequently unaffected. Alternatively, this null result may be a consequence of the sample used here. The undergraduate students who took part in our studies would have had experience of note taking during presentations . Research suggests that individuals who have extensive practice at simultaneously reading stories and writing dictated words are less affected by the demands of dividing attention between these tasks . It may The present findings showed no difference in recall between jurors who were able to access their notes during the memory test and those who did not have access to their notes. This is in line with prior research ,8. It maOne limitation of the present study, which poses a threat to the ecological validity of the findings, is that the trial lasted only 30 minutes. Real trials can last days or weeks. Note taking over longer periods of time may impose more cognitive demands on jurors’ attention . Additionally, it may impose more physical demands on jurors’ handwriting speed . Note taking behaviours over extended periods of time have not yet been investigated. Nevertheless, we did find significant indirect effects of individual differences and these may be even more evident in real and longer trials. In addition, the constraints of laboratory settings affect all laboratory-based juror studies . Of impoThe present studies assessed the effects of note taking on individual jurors’ recall of trial evidence. However, future studies should aim to examine the effects of note taking on deliberations, and the effects of deliberation on recall of trial evidence. It is important to assess whether note taking facilitates or impairs deliberation. It should also be assessed whether deliberation facilitates or impairs jurors’ recall of trial evidence. Addition, it would be interesting to examine the potential impact of biases  on note taking and the recall of trial information. Jurors who have been exposed to pre-trial publicity may selectively note down the evidence that is consistent with their biases. Future studies should also consider using a trial video with a less ambiguous outcome  to examine whether the findings from the present study can be replicated in these circumstances. Future researchers could also examine whether informing participants that they will be able to access their notes during the memory test will have an impact on their note taking strategies. The current studies did not measure whether jurors used or looked at their notes during the memory test, and thus future research should consider investigating this and its impact upon recall. In addition, since our studies tested the various individual differences in isolation, researchers are encouraged to study all of those factors together in a single study in order to assess any potential covariance among the individual differences. Lastly, future research should also examine whether other individual differences may influence juror note taking and recall, for instance prior experience of note taking, language comprehension, and age.The findings from the present study have an important applied value. Although note taking has been found to improve recall of trial information, some judicial systems deny jurors the opportunity to take notes during trials. The present studies show that note taking increases recall of critical evidence. When jurors remember more trial information they presumably have a greater chance of reaching a just verdict. Based on our findings, all jurors should be permitted to take notes during trials. Furthermore, the present studies show that jurors with faster handwriting speeds, higher short-term memory capacity, and higher sustained attention capacity benefit from note taking by recalling greater amounts of critical evidence. Since we identified handwriting speed as a feature of note taking that affects recall, it may be that providing instructions for speeded writing may help potential jurors note down more trial information and subsequently reach more informed verdicts. In addition, the current findings demonstrated that sustained attention was associated with how much critical evidence jurors recalled. Currently, jurors in the US are often required to attend court sessions of no less than 80 minutes after which they are allowed a 15-minute break. Thus, note-taking jurors with lower sustained attention levels may benefit from taking more regular breaks to ensure that they stay focused on the trial evidence and to prevent them from missing critical evidence which could then impact upon their decision making.Additionally, the current findings have an important theoretical value. Little was known about individual differences in note taking aside from a small number of studies from the educational psychology literature. We demonstrate that the impact of handwriting speed and sustained attention on note taking and recall generalise to another domain. In addition, we identify that short-term memory capacity is also an important factor that is associated with note taking and recall.The present studies demonstrated that jurors with faster handwriting speed, higher short-term memory capacity, and higher sustained attention recalled greater amounts of critical evidence, and this effect was mediated by the amount of critical evidence they noted down during the trial. However, working memory storage capacity, information processing ability, and divided attention were not found to be significantly associated with note taking and recall. In addition, all studies found that the type of evidence jurors recalled predicted their verdicts. The current findings have an important theoretical value, such that they identify individual differences that can predict the positive association between juror note taking and recall. This is particularly important given that jurors who recalled more incriminating evidence were more likely to reach a guilty verdict, and jurors who recalled more non-incriminating evidence were less likely to find the defendant guilty.S1 Dataset(ZIP)Click here for additional data file.


The founding tenet of evidence-based medicine is to combine best evidence with clinical expertise. As David Sackett opined ‘Without clinical expertise, practice risks becoming tyrannised by evidence’. Rigid protocols and mandates, based on an inconclusive and low-level evidence base, cannot suit the physiological, biochemical and biological heterogeneity displayed by the individual septic patient. Indeed, clear proof of outcome benefit through adoption of an inflexible management approach is lacking and will certainly be detrimental to some. Therapy thus needs to be tailored to meet the individual patient’s needs. The same principle should be applied to clinical trials; the continued disappointments of multiple investigational strategies trialled over three decades, despite (often) a sound biological rationale, suggest a repeated methodological failure that does not account for the marked heterogeneity within the septic patient’s biological phenotype and thus marked variation in their host response. The increasing availability of rapid point-of-care diagnostics and theranostics should facilitate better patient selection and titrated optimization of the therapeutic intervention. The history of intensive care has been littered with too many false dawns. Old management dogma, now derided, have been replaced by new and equally resolute convictions, many of which will, in time, undoubtedly follow a similar course. Retired bundles of care have been replaced by new bundles driven by clinical evangelists and government diktat. Yet these too lack a strong evidence base and can be readily challenged. Homogenizing treatment given to a highly heterogenous patient population that fall under the wide syndromic umbrella of sepsis may offer a minimum standard of care though at the potential cost of compromising outcomes in an individual patient. Likewise, the repeated multicentre trial failures of novel interventional strategies over many decades highlight the need to focus more precisely on the individual’s biological phenotype and adopt a personalized treatment approach. This article will briefly cover these issues and offer directions for the future.‘Good doctors use both individual clinical expertise and the best available external evidence, and neither alone is enough. Without clinical expertise, practice risks becoming tyrannised by evidence, for even excellent external evidence may be inapplicable to or inappropriate for an individual patient.’‘Evidence based medicine is not “cookbook” medicine. Because it requires a bottom up approach that integrates the best external evidence with individual clinical expertise and patients’ choice, it cannot result in slavish, cookbook approaches to individual patient care. External clinical evidence can inform, but can never replace, individual clinical expertise, and it is this expertise that decides whether the external evidence applies to the individual patient at all and, if so, how it should be integrated into a clinical decision. Similarly, any external guideline must be integrated with individual clinical expertise in deciding whether and how it matches the patient’s clinical state, predicament, and preferences, and thus whether it should be applied. Clinicians who fear top down cookbooks will find the advocates of evidence based medicine joining them at the barricades.’Evidence-based medicine is intended to offer best treatment and represents a worthy aim to raise standards and homogenize care. It offers a framework when basic expertise is lacking. An excellent example is the Advanced Trauma Life Support course, established by an orthopaedic surgeon (James Styner) after a plane crash in rural Nebraska in 1976 on finding medical care for his injured children was disorganized and suboptimal. However, one size does not, and should not, fit all. While providing structure is clearly important, especially for less-experienced healthcare providers, it must be tailored to the individual patient. To cite David Sackett, one of the ‘godfathers’ of evidence-based medicine )As an example, those with a strong pro-inflammatory phenotype may benefit from an appropriate degree of suppression . HoweverThe advent of rapid point-of-care diagnostics will facilitate appropriate selection of biologically suitable patients into studies, and optimization of drug dosing . There is no guarantee of success as the derangement in biomarker level may be epiphenomenal rather than integral to a causative pathway, or may even be part of an adaptive process. However, the theranostic targeting of a specific biomarker can be tested a priori for proof-of-principle in appropriate animal models .


To review the literature on built environment interventions to increase active travel, focusing on work since 2000 and on methodological choices and challenges affecting studies.Increasingly, there is evidence that built environment interventions can lead to more walking or cycling. Evidence is stronger for cycling than for walking interventions, and there is a relative lack of evidence around differential impacts of interventions. Some of the evidence remains methodologically weak, with much work in the ‘grey’ literature.While evidence in the area continues to grow, data gaps remain. Greater use of quasi-experimental techniques, improvements in routine monitoring of smaller schemes, and the use of new big data sources are promising. More qualitative research could help develop a more sophisticated understanding of behaviour change. This review examines recent literature on built environment interventions and their impact on active travel. Its aim is to assess the current state of the research field, including methodological and data availability issues affecting the quality of the evidence. Structurally, it begins with a summary of recent evidence, before moving on to consider key challenges, focusing on the increasingly popular ‘natural experiment’ approach. It ends by suggesting pathways for future research to improve the quality of future evidence.‘Built environment interventions’ here means changes such as the provision of cycle infrastructure, the pedestrianisation of shopping streets, or the creation of local parks which create or improve active travel routes. Literature generally refers to active travel as walking and/or cycling, rather than (for instance) jogging or use of newer semi-active or electric-assisted modes (such as e-scooters). Public transport is usually seen as non-active, although trips to access public transport hubs may involve walking or cycling.Much cross-sectional literature examines built environment factors correlated with levels of walking and cycling. Broadly there are two types of factors: (i) qualities of the built environment thought to improve walking and cycling experiences , and (ii) the presence of relevant destinations within a reasonable distance . While this evidence suggests that good active travel environments and destination proximity are associated with more walking and cycling, association does not necessarily imply causality –3.The same problem exists for the large number of studies exploring preferences for different types of environment, in relation to walking or cycling. This broadly supports the cross-sectional literature: people can distinguish between and express preferences for built environment factors seen as better for walking and cycling, such as wide footways and protected cycle infrastructure , 5. HoweBut will this happen? Even if causality exists, pathways to change may not be transferable. For instance, it seems plausible that many people cycle in the Netherlands primarily because of a supportive environment, including but not limited to high quality cycling infrastructure . HoweverRecently we have seen a rise in intervention studies  and systematic reviews assessing these , 10, helTo summarise, current evidence increasingly suggests that changing the built environment can affect levels of active travel. Increasingly studies cover actual interventions, rather than only cross-sectional associations, preferences or participant views about what would influence their future behaviour. However, there is a need for more studies with gaps remaining particularly for walking, and for evidence around distributional impacts and subgroup differences. The next section of the paper discusses methodological issues affecting the field, including strengths and tensions arising from its interdisciplinary nature.The literature on built environment interventions and active travel uptake exists at the intersection of health and transport planning. The different disciplinary traditions have implications for what we value and measure, and differences in approach to evidence and key outcomes are discussed further below. However, transport and health agendas have come together in recent years, at an academic and a policy level. While public health is interested in any physical activity, it is increasingly recognised that our best hope of reducing dangerously high levels of physical inactivity is to build active travel into everyday life, rather than it being a separate activity that people must take time out of their lives to complete. Conversely, transport authorities are increasingly seeing health as a core part of their remit, such as the ‘Healthy Streets’ approach developed by Transport for London .Transport and health fields have different traditions within which to view monitoring and evaluation. Within transport, monitoring and evaluation have traditionally depended on estimating or measuring impacts on car users, usually time savings, to the exclusion of many other issues from environmental damage to delays to pedestrians . This foTransport authorities do often conduct their own monitoring of active travel schemes, and they or their consultants write reports on outcomes. When evaluated by academic standards such research (understandably) suffers by comparison to ‘gold standard’ evidence. Known issues include the lack of longer-term follow-up, and a lack of control sites or comparators. This is crucial because weather affects walking and cycling levels, so without a control strategy, a year-on-year change in active travel might simply be due to changes in weather. In the ‘grey literature’ there is frequently a failure to effectively measure changes in active travel. Instead, organisations may use count data as a measure of new trip generation, whereas it could simply represent diversion •. The acRising interest in this area among public health researchers has encouraged the identification of a range of potential biases associated with existing grey or academic literature assessing impacts of interventions . HoweverWhile not necessarily a bad thing (knowing that a new facility exists is likely to be part of its pathway to impact) this does make traditional quality measures such as blinding participants to their treatment group inappropriate. Avoiding the ‘placebo effect’ has traditionally been fundamental to design of medical and public health interventions: but what might a ‘placebo effect’ even mean in the context of built environment? We would need a clearer understanding of the relative contributions of pathways to effects to theorise this. Some fields have used the ‘placebo’ concept to understand pathways to impact in their area. For instance, within environmental psychology a ‘placebo effect’ has been identified whereby an ‘eco-label’ rating affects perceptions of product performance . If we cAnother issue affecting the interdisciplinary evidence base relates to the outcomes prioritised and valued in different fields. While both public health and transport planning are interested in active travel, the supplementary objectives may vary. For transport planning, end goals are generally transport-focused. While some interventions may primarily improve conditions for existing cyclists or walkers , this maThese different foci lead to different methods for measuring behaviour change. Public health literature is more sceptical of self-reported physical activity , due forUse of objective measurement, either through ordinary operation of a smartphone or specific apps, looks increasingly promising for measuring use of different modes –26. ThisWhile RCTs may not be appropriate for built environment interventions in general, epidemiological methods are increasingly contributing to their evaluation. Natural experiments in particular are increasingly used to study various types of intervention, including those related to cycling and walking environments ••. By trA further challenge for these and related types of intervention study is that often interventions are multi-faceted; indeed, policy-makers are recommended to introduce multi-faceted interventions  as more A second, related, challenge covers how we characterise interventions in the first place. City authorities often brand interventions or use ill-defined terms to describe them; for instance, as ‘cycle superhighways’, ‘complete streets’, ‘bicycle boulevards’, or ‘traffic calming’, and these terms are often then also used in academic literature. All are somewhat amorphous and may represent very different route environments or interventions even within the same city, let alone in different cities, countries, and regions. In the London, UK, case, a cycle superhighway variously might imply a wide one- or two-way cycle track separated from motor traffic and pedestrians; a designated route along supposedly quiet side streets; a blue painted cycle lane; or a shared bus lane.The stated preference literature suggests these different facility types have very different levels of attractiveness to users , which mThere is also the question of distinguishing ‘carrot’ and ‘stick’ interventions. These colloquial names for interventions aimed at (i) increasing active travel and (ii) discouraging driving are poorly chosen. Interventions that offer better conditions for walking or cycling often necessarily discourage driving: for instance, by re-purposing car parking spaces as pocket parks or cycle infrastructure. Limited amounts of space and time, and competing modes, mean that this is often unavoidable. Yet to what extent, for instance, do wider footways increase walking uptake (if they do) by comparison with a reduction in motor traffic entailed by the associated reduction in space for cars? At present, there is limited evidence specifically how reducing space, time, or facilities for motor traffic affects walking and cycling. Within transport studies, some work deals with its impact on driving. A 1998 review concluded that if space for cars is cut, much motor traffic will often simply disappear . ‘Traffito somewhere . Studies often use distance to specific interventions, such as new cycle routes or walking/cycling infrastructure [Even where interventions are easier to define, there is a broader challenge of identifying the population exposed to an intervention, given travel is often tructure , 40, altA study of London ‘mini-Holland programmes’  in threeDespite all the methodological challenges, the natural experiment approach provides one model for how public health approaches can be adapted for use in studying the built environment. These studies have advanced the evidence base by providing better evidence around causality than that which can be delivered through cross-sectional studies, case study research, and stated preference studies. They are not the only useful studies, and I will suggest in the conclusion that they need to be supplemented, including by innovative qualitative work, and by attempts to develop more rigorous classifications of intervention typologies and their likely effects.It is usual for such reviews to conclude with a call for more, high-quality studies. This would indeed be useful. We still need more natural experiments and other high-quality studies, particularly covering subgroup differences and impacts on walking. However, other work needs to be done to strengthen the underlying models shaping our understanding of travel behaviour . Much woThis understanding could in turn help shape how and what we measure, and length of follow-up, often relatively short even in academic studies. The London study of ‘mini-Holland schemes’ referred to above  found noResearch could usefully do more to tease out and separate the possible impacts of different components of the built environment that affect walking and cycling. Given the variety of factors affecting how, when, and where we travel, this seems like a big ask, especially given cross-cultural variation in design of different aspects of the street environment. However, there is a role here for relatively low-cost preference-based research. Asking people what types of environment they would prefer to walk or cycle in does not necessarily tell us about take-up. It might, however, allow us to better understand what components of a walking or cycling environment are perceived as more or less important, and why, by different sub-groups and in different contexts. This in turn can allow a more systematic approach to categorising and evaluating interventions. The ability to use visual material  within online or computer-assisted surveys means that such research can be done in a much more sophisticated manner than in the past, where people were simply asked their views on ‘a cycle lane’ .Finally, more work could be done considering the extent to which medical research models could and should be adapted to deal with transport research and policy-making. The involvement and contribution of public health disciplines has substantially enhanced the field, highlighting the sometimes biased and/or limited nature of evidence within the transport field. But should transport research be adopting an identical hierarchy of evidence to that developed within medical science? For individual-level interventions, presumed to operate independent of knowledge and belief , the double-blinded RCT is seen to represent the pinnacle of research excellence, by isolating the impact of the intervention from ‘irrelevant’ context.


Vaccinium macrocarpon) are known to have virulence attenuating effects against several cariogenic virulence properties responsible for dental caries pathogenesis. In particular, cranberry A-type proanthocyanidins and flavonols have demonstrated potent inhibitory effects against cariogenic virulence targets such as bacterial acidogenicity, aciduricity, glucan synthesis, and hydrophobicity. Cranberry phenols have the ability to disrupt these cariogenic virulence properties without being bactericidal, a key quality essential for retaining the benefits of the symbiotic resident oral microbiome and preventing the emergence of resistant microbes. This review discusses the cariostatic mechanisms of specific cranberry phytochemicals and their potential use as therapeutic agents against cariogenic bacteria in the prevention and control of dental caries.Bioactive polyphenol components of cranberry ( There has been an increasing global interest in the potential therapeutic uses of plant-derived natural products to prevent oral diseases. Phytodentistry is based on long-standing evidence showing population groups that habitually consume polyphenol-rich diets have significantly better oral health . TraditiThe Global Burden of Diseases report highlighted that dental caries is the most common human disease condition worldwide . Newer aVaccinium macrocarpon , Vaccinium microcarpom , Vaccinium oxycoccus (common cranberry or northern cranberry), and Vaccinium erythrocarpum (southern mountain cranberry) [Escherichia coli to the mucosa of the urinary tract and Helicobacter pylori to the gastric mucosa [Cranberry is a small red fruit that is cultivated almost exclusively in the cooler climes of the American Northeast, Canada, and Chile. Four species have been described: anberry) . The Amec mucosa ,9. Thesec mucosa . Other pc mucosa ,12.With regards to oral health, in vitro studies have shown that cranberry constituents can exert beneficial effects on gingival and periodontal health by inhibiting the host inflammatory response, suppressing bacterial biofilm formation, and reducing the activity of periopathogenic proteolytic enzymes ,13,14. SStreptococcus mutans and Streptococcus sobrinus) to synthesise copious amounts of insoluble glucans is critical for caries pathogenesis [Dental caries is a polymicrobial multifactorial disease that develops when the acidogenic and aciduric members of the resident oral flora obtain a selective ecological advantage over other commensal microorganisms, disrupting the homeostatic balance of the plaque biofilm, and initiating the disease process . While togenesis . The firS. mutans glucosyltransferases (Gtfs) are exoenzymes that are primarily responsible for orchestrating the virulent plaque biofilm matrix. In the presence of sucrose, different Gtfs  synthesise extracellular carbohydrate polymers called glucans. These glucans confer structural integrity and bulk to plaque biofilms, enhance bacterial adhesion and accumulation, and provide a readily metabolisable carbohydrate source for sustained acid production [S. mutans, targeting Gtf enzyme activity should significantly disrupt the development of dental caries [The oduction . The gluoduction . As the l caries .An important attribute of cariogenic microorganisms is their proficiency in producing large amounts of organic acids as a by-product of carbohydrate metabolism. These acids (particularly lactic acid) lower the pH of the plaque fluid, causing demineralization of the tooth structure and lesion initiation. Sustained low pH within the plaque biofilm will favour the survival and growth of acidogenic and aciduric bacteria, which start to dominate the plaque microbial community, displacing many of the health-associated commensal oral microflora . Disrupt1F0-ATPases play a major role in protecting the bacterial glycolytic and sugar transport system enzymes from the environmental stress caused by biofilm acidification. Inhibiting the F1F0-ATPase proton pump can result in cytoplasmic acidification and thus affect the optimal functioning of the intracellular acid-sensitive glycolytic enzymes.The ability to survive and thrive in low pH environments is a key characteristic of MS. Proton translocating FS. mutans-derived Gtfs (particularly GtfC) are adsorbed onto salivary pellicle-coated tooth surfaces and rapidly generate an amorphous glucan layer that facilitates initial bacterial adhesion. Gtf exoenzymes (particularly GtfB) also have great affinity for cell surfaces of other microorganisms, converting them into de facto glucan producers in the presence of sucrose. The glucans formed in situ provide enhanced binding sites for MS, resulting in further bacterial aggregation, and favouring cohesive microcolonies [S. mutans is believed to be mainly associated with its cell surface proteins [The colonies . While tproteins . TargetiThe cranberry fruit is a unique and rich source of bioactive polyphenol compounds. Among the different classes of polyphenols, the flavonoid family has the largest variety of compounds with pharmacological activity. The three major flavonoids found in whole cranberries are the flavonols, anthocyanins, and the flavanols that include monomeric flavan-3-ols and the polymeric flavan-3-ols called proanthocyanidins . Very miCranberry flavonols occur mainly as glycosylated forms of quercetin, myricetin, and kaempferol . The tot1F0-ATPase, and of cytoplasmic glycolytic enzymes within S. mutans [1F0-ATPase activity that is critical to the survival of acidogenic bacteria in the low pH biofilm environment they create [Cranberry flavonols, especially the most abundant quercetin glycosides, were found to be significant inhibitors of GtfB, GtfC, F. mutans ,16. Flav. mutans . Quercety create .E. coli and H. pylori, whereas B-type PACs were devoid of anti-adhesion properties. PACs  are oligomers or polymers of flavan-3-ols that are distinctive in terms of their size, high molecular weight, and free hydroxyl groups. These structural properties determine their bioactivity, including the ability to precipitate or denature polypeptides and proline-rich proteins . Binding1F0-ATPase enzymes [S. mutans enzyme activity are likely to be related to their unique rigidity-conferring A-type linkages, as PACs from non-cranberry fruits that lacked A-type linkages did not affect these enzymes [Among the different cranberry flavonoids, the A-PACs have exhibited the most potent effects against bacterial glycolytic, Gtf, and F enzymes ,32. The  enzymes ,17,32.2 [The PACs in cranberry are predominantly found in oligomeric forms (up to 13 monomeric units), although smaller PAC dimers are also seen. The bioactivity of the A-PACs are also strongly associated with their degree-of-polymerisation (DP). A-PACs with DP 4 and DP 8 to 13 are optimal for interaction and inhibition of Gtfs and glucan-mediated adhesion . On the 2 . It is uCranberry A-PACs have been shown to significantly reduce the incidence and severity of smooth surface caries in an animal caries model, suggesting they may have value as a supplement to fluoride for dental caries prevention . OverallS. mutans found that A-PACs exhibited the greatest biological activity, followed by the flavonols, while the ACY extract did not have any significant effects [ACYs such as cyanidin and peonidin are present at concentrations of approximately 100–900 mg/kg of the fruit and are responsible for the distinctive red colour of the fruit . While A effects .A number of studies have reported beneficial effects from a high molecular weight fraction of cranberry that remains after dialysis of concentrated cranberry juice using membranes with a molecular weight cut-off of 12,000–15,000 . ChemicaS. mutans and S. sobrinus and promotes desorption of the bacteria from biofilms [A mouthwash supplemented with NDM has been found to significantly reduce salivary MS counts following six weeks of usage . In vitrbiofilms ,36,37. Tbiofilms .S. mutans biofilm virulence properties. While tea (Camellia sinensis) also contains high levels of biologically active phenolic compounds, studies have shown cranberry polyphenols have the ability to effect a more powerful disruption of cariogenic virulence factors [Cranberry polyphenols may have a number of advantages over other suggested cariostatic natural products. A comparison of three dark-coloured berries  showed that cranberry extracts had the greatest effects against  factors . The greCurcuma xanthorrhizha) and macelignan from nutmeg (Myristica fragrans) have also shown significant growth inhibitory effects against oral bacteria [Isolated phytochemicals like xanthorrrhizol from Javanese turmeric (bacteria ,39,40. HA common problem with using natural products as therapeutic agents is their compositional variability. In this regard, cranberry is a particularly feasible and sustainable source of standardised bioactive compounds, as it is a chemically and genetically well-characterised fruit, with highly standardised methods for extracting the biologically active components .Cranberry polyphenols have enormous potential for development as adjunctive anti-caries agents. However, the cariostatic effects of cranberry have mostly been demonstrated in laboratory studies. There is a need for well-designed clinical trials to evaluate whether the proposed cariostatic effects of cranberry phenols can actually translate into preventing dental caries in high-risk individuals and population groups. The combination of virulence-attenuating standardised cranberry extracts and remineralising agents in a single oral care product could hold great promise in the global fight against dental caries.