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Individuals with schizophrenia are at higher risk of physical illnesses, which are a major contributor to their 20-year reduced life expectancy. It is currently unknown what causes the increased risk of physical illness in schizophrenia.
To link genetic data from a clinically ascertained sample of individuals with schizophrenia to anonymised National Health Service (NHS) records. To assess (a) rates of physical illness in those with schizophrenia, and (b) whether physical illness in schizophrenia is associated with genetic liability.
We linked genetic data from a clinically ascertained sample of individuals with schizophrenia (Cardiff Cognition in Schizophrenia participants, n = 896) to anonymised NHS records held in the Secure Anonymised Information Linkage (SAIL) databank. Physical illnesses were defined from the General Practice Database and Patient Episode Database for Wales. Genetic liability for schizophrenia was indexed by (a) rare copy number variants (CNVs), and (b) polygenic risk scores.
Individuals with schizophrenia in SAIL had increased rates of epilepsy (standardised rate ratio (SRR) = 5.34), intellectual disability (SRR = 3.11), type 2 diabetes (SRR = 2.45), congenital disorders (SRR = 1.77), ischaemic heart disease (SRR = 1.57) and smoking (SRR = 1.44) in comparison with the general SAIL population. In those with schizophrenia, carrier status for schizophrenia-associated CNVs and neurodevelopmental disorder-associated CNVs was associated with height (P = 0.015–0.017), with carriers being 7.5–7.7 cm shorter than non-carriers. We did not find evidence that the increased rates of poor physical health outcomes in schizophrenia were associated with genetic liability for the disorder.
This study demonstrates the value of and potential for linking genetic data from clinically ascertained research studies to anonymised health records. The increased risk for physical illness in schizophrenia is not caused by genetic liability for the disorder.
The nature and degree of cognitive impairments in schizoaffective disorder is not well established. The aim of this meta-analysis was to characterise cognitive functioning in schizoaffective disorder and compare it with cognition in schizophrenia and bipolar disorder. Schizoaffective disorder was considered both as a single category and as its two diagnostic subtypes, bipolar and depressive disorder.
Following a thorough literature search (468 records identified), we included 31 studies with a total of 1685 participants with schizoaffective disorder, 3357 with schizophrenia and 1095 with bipolar disorder. Meta-analyses were conducted for seven cognitive variables comparing performance between participants with schizoaffective disorder and schizophrenia, and between schizoaffective disorder and bipolar disorder.
Participants with schizoaffective disorder performed worse than those with bipolar disorder (g = −0.30) and better than those with schizophrenia (g = 0.17). Meta-analyses of the subtypes of schizoaffective disorder showed cognitive impairments in participants with the depressive subtype are closer in severity to those seen in participants with schizophrenia (g = 0.08), whereas those with the bipolar subtype were more impaired than those with bipolar disorder (g = −0.23) and less impaired than those with schizophrenia (g = 0.29). Participants with the depressive subtype had worse performance than those with the bipolar subtype but this was not significant (g = 0.25, p = 0.05).
Cognitive impairments increase in severity from bipolar disorder to schizoaffective disorder to schizophrenia. Differences between the subtypes of schizoaffective disorder suggest combining the subtypes of schizoaffective disorder may obscure a study's results and hamper efforts to understand the relationship between this disorder and schizophrenia or bipolar disorder.
It is not clear to what extent associations between schizophrenia, cannabis use and cigarette use are due to a shared genetic etiology. We, therefore, examined whether schizophrenia genetic risk associates with longitudinal patterns of cigarette and cannabis use in adolescence and mediating pathways for any association to inform potential reduction strategies.
Associations between schizophrenia polygenic scores and longitudinal latent classes of cigarette and cannabis use from ages 14 to 19 years were investigated in up to 3925 individuals in the Avon Longitudinal Study of Parents and Children. Mediation models were estimated to assess the potential mediating effects of a range of cognitive, emotional, and behavioral phenotypes.
The schizophrenia polygenic score, based on single nucleotide polymorphisms meeting a training-set p threshold of 0.05, was associated with late-onset cannabis use (OR = 1.23; 95% CI = 1.08,1.41), but not with cigarette or early-onset cannabis use classes. This association was not mediated through lower IQ, victimization, emotional difficulties, antisocial behavior, impulsivity, or poorer social relationships during childhood. Sensitivity analyses adjusting for genetic liability to cannabis or cigarette use, using polygenic scores excluding the CHRNA5-A3-B4 gene cluster, or basing scores on a 0.5 training-set p threshold, provided results consistent with our main analyses.
Our study provides evidence that genetic risk for schizophrenia is associated with patterns of cannabis use during adolescence. Investigation of pathways other than the cognitive, emotional, and behavioral phenotypes examined here is required to identify modifiable targets to reduce the public health burden of cannabis use in the population.
Working consistently through one's early 60s is key to retirement security. However, workers without access to retirement plans and health insurance will likely struggle to achieve such security. This paper uses the Health and Retirement Study to identify nontraditional jobs – which lack these benefits – and applies sequence analysis to explore how workers aged 50–62 use them. The results suggest that most nontraditional jobs are used by workers consistently, and that fewer workers use these jobs briefly or as a bridge to retirement. Workers consistently in nontraditional jobs end up with less retirement income and are more likely to be depressed.
Cognitive behavioural therapy (CBT) is an important treatment in conjunction with psychopharmacotherapy in schizophrenia. However, there is only very little research on the effects of such interventions on brain function.
Recent studies have suggested that jumping to conclusions and a specific attributional bias is a predominant cognitive style in patients which might lead to the development of delusions. In this multi-centre fMRI trial, we investigated the effect of nine months of CBT on neural correlates of “jumping to conclusions” and the “attributional style” in patients with psychosis. Eighty patients and 80 control subjects were recruited in six centres and measured with 3-Tesla functional magnetic imaging (fMRI) before and after CBT.
It could be shown that CBT ameliorates differences in brain activations between patients and controls after nine months.
These results support the feasibility of fMRI multicenter trials and sheds further light into the mechanisms relating psychotherapy to brain function in Schizophrenia.
There is evidence that patients with persecutory delusions tend to attribute excessively hypothetical positive events to internal causes and hypothetical negative events to external causes, arrive at hasty conclusions and fail in gathering and assessing adequate feedback, particularly when emotionally salient material is involved. Research on the neural correlates of the corresponding neural correlates and even more so on the potential effects of cognitive behavioral therapy (CBT) on the associated cerebral networks is almost unavailable.
The first and preliminary results of a multicentre fMRI study will be presented.
In this study eighty schizophrenia patients from the POSITIVE clinical trial and eighty healthy subjects were recruited at six German university hospitals (Bonn, Duisburg-Essen, Düsseldorf, Frankfurt, Cologne, Tubingen). After nine months of therapy (either with CBT or Supportive Therapy) patients and controls were re-examined enabling the study correlates of cerebral reorganization processes.
We found reliable differences in brain activation relating to phenomena of decision making under uncertainty, and biased attribution (self- vs. external reference of emotional events).
The comparison of both groups revealed significant decreased activation in key areas for decision making, self-reflection, self-relevance and agency attribution of patients with schizophrenia.
The preliminary data analysis of the still blinded treatment arms shows significantly increased activations in these areas after nine months of CBT. This suggest neuroplasitic changes according to relearning strategies in psychotic patients with schizophrenia and will hopefully give rise to a more widespread application of CBT in treatment of schizophrenia.
La couverture médiatique d’un fait suicidaire influence le taux de suicide par le biais d’un effet d’incitation, aussi nommé « effet Werther » (EW) ou d’un potentiel rôle préventif via « l’effet Papageno » (EP) . L’objectif du programme national français Papageno est d’améliorer les propriétés qualitatives du contenu médiatique dont dépendent principalement l’EW et l’EP, via l’application des recommandations de l’Organisation mondiale de la Santé (OMS) pour un traitement journalistique plus responsable du suicide. L’évaluation de l’efficacité du programme est donc un enjeu de prévention qui nécessite un outil d’analyse fidèle à ces recommandations.
Élaborer et valider une grille d’analyse qualitative permettant, pour chaque article de presse traitant du suicide, de mesurer le degré de compliance aux recommandations de l’OMS et de quantifier le risque d’EW et le potentiel EP.
La grille d’évaluation PReSS (Print media Reporting on Suicide Scale) combine 10 items descriptifs et 19 items qualitatifs issus de l’opérationnalisation des 11 recommandations de l’OMS. La validation de la fiabilité interjuges a été obtenue par séries de double cotation-correction de 25 articles traitant du suicide. Les critères de satisfaction des items ont été affinés après chaque série jusqu’à obtention d’un coefficient de kappa ≥ 0.7 pour chacun. À titre d’illustration, le traitement médiatique du supposé suicide du pilote d’avion A. Lubitz en mars 2015 a été analysé grâce à la PReSS.
Trois séries de cotation-correction ont été nécessaires pour valider la grille. L’analyse de la couverture du suicide présumé d’A. Lubitz montre un compliance faible aux recommandations, un score Papageno bas et un score Werther élevé.
La grille d’évaluation PReSS est un outil fiable et utile pour mesurer la compliance aux recommandations de l’OMS concernant la couverture médiatique du suicide.
L’accès aux soins des personnes à risque constitue un pilier essentiel de la prévention du suicide. Cependant, les idées reçues véhiculées autour des conduites suicidaires y opposent un obstacle significatif. Afin de cibler au mieux les campagnes d’information qui dissiperaient ces mythes, et pour en évaluer l’efficacité, les connaissances sur le suicide devraient pouvoir être quantifiées de façon fiable. À ce jour, seules quelques études anglo-saxonnes dédiées ont été validées. La limite décisive à leur interprétation tient cependant à ce qu’elles ne permettent pas d’approche normative. En effet, l’exactitude de leurs propositions n’est validée par aucun étalon officiel, alors même que certaines relèvent plus de l’expérience clinique que de connaissances issues de la littérature. Notre objectif consiste à palier cette limite en proposant une échelle dont la cotation est adaptée à l’évaluation d’un savoir normé. Le Questionnaire d’Évaluation des Connaissances sur le Suicide (QECS) est un auto-questionnaire qui explore, en 35 items, les principales connaissances relatives à l’épidémiologie et aux mythes communs concernant le suicide. Les réponses y sont recueillies par échelle visuelle analogique. La cotation finale se fait en confrontant ces réponses à celles d’un panel de référence constitué de spécialistes en suicidologie (n = 47). Nous présentons ici les résultats de ce panel, ainsi qu’une illustration des potentialités d’interprétation du QECS, via l’évaluation des connaissances d’un échantillon test d’étudiants en journalisme (n = 111). Les réponses du panel de référence étaient significativement différentes de « ni accord, ni désaccord » pour 27 des 29 items dédiés aux mythes. Pour 25 de ces items, une différence significative était retrouvée entre l’échantillon test et le panel de référence. Ainsi attestée, l’existence d’un avis expertal spécifique a servi d’étalon pour 2 modes de cotation des réponses de l’échantillon test : un score de véracité et un score de concordance aux experts.
Second-generation antipsychotics (SGAs) are a frequently and effectively used treatment in schizophrenia and psychotic disorders. Other than First-generation antipsychotics (FGAs), which mainly exert their pharmacologic effect in subcortical dopaminergic systems, SGAs additionally affect partly serotonergically innervated structures within prefrontal areas, such as the Anterior Cingulate Cortex (ACC). However, only few controlled, randomized studies have so far investigated direct and indirect effects of SGAs on the ACC.
The present study investigated differential effects of one SGA (quetiapine) and one FGA (flupentixol) on the human action monitoring system.
ACC function in 18 quetiapine-medicated patients and 13 flupentixol-treated patients suffering from schizophrenia was assessed by means of the error-related negativity (ERN), a neurophysiological marker of ACC function, in a pre-post design. Results Between-group comparisons revealed different effects of quetiapine and flupentixol on ACC function despite similar improvement in psychopathology, cognitive performance and quality of life. Whereas SGA treatment was associated with an increase in amplitudes over time, there were prolonged ERN peak latencies in patients treated with the FGA. Moreover, treatment effects depended on baseline PFC function in both groups.
We conclude that both flupentixol and quetiapine improve prefrontal function especially in patients with weak initial ACC function which might be due to their shared affinity for 5HT-receptors in frontal brain regions. However, since this affinity is more pronounced for SGAs, patients treated with quetiapine seemed to profit more evidently concerning PFC function compared to patients of the flupentixol group, who exhibited a compensatory prolongation of processes.
Pedophilia is a disorder where sexual preferences of adults are directed towards children. This disorder impacts society with 1–2 out of every 10 children being sexually approached by an adult, often resulting in prolonged negative psychological effects. Prior research reported structural and functional amygdala alterations in pedophilia. As the neurophenomenological model of sexual arousal suggests the importance of the amygdala in the emotional component, we focused on amygdala functional connectivity in pedophilia.
To investigate amygdala functional connectivity (FC) modulated by expectancy and salient stimuli in pedophilic patients.
Thirteen pedophilic patients and 13 matched healthy controls underwent a salience expectancy task in a 7T ultra high fMRI study. Subjects perceived pictures of naked adults and children. Half of the pictures were preceded by an expectancy cue. Participants were instructed to actively expect the picture depending on the cue. We conducted psychophysiological analysis (PPI) to examine amygdala FC changes in two amygdala sub-regions for child/adult stimuli during the expectancy period and the visual stimuli consummation period using as seed regions the basolateral (BLA) and central nucleus of the amygdala (CeA).
Healthy controls, relative to patients showed significant stronger left CeA to right post-central gyrus FC during expectancy of adult > child picture. For picture condition (adult > child picture) we found significant stronger left CeA to left dorsolateral prefrontal cortex FC in patients compared to healthy controls.
These findings add to the recent literature by indicating that amygdala dysfunctional connectivity is involved in development of deviant sexual behavior.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
Misalignment of day/night and feeding rhythms has been shown to increase fat deposition and the risk for metabolic disorders in humans and rodents. In most studies, however, food intake and intake patterns are not controlled. We studied the effects of circadian misalignment on energy expenditure in pigs while controlling for food intake as well as intake patterns. Twelve groups of five male pigs were housed in respiration chambers and fed either during the day (10.00–18.00 hours; DF) or night (22.00–06.00 hours; NF), bihourly the same sequential meals, representing 15, 10, 25, 30 and 20 % of the daily allowance. Paired feeding was applied to ensure equal gross energy intake between treatments. Apparent total tract digestibility, energy balances and heat partitioning were measured and analysed using a mixed linear model. Apparent total tract energy and DM digestibility tended to be lower for NF-pigs than DF-pigs (P < 0·10). Heat production was 3 % lower for NF-pigs than DF-pigs (P < 0·026), increasing fat retention by 7 % in NF-pigs (P = 0·050). NF-pigs were less active than DF-pigs during the feeding period, but more active during the fasting period. RMR was greater for DF-pigs than NF-pigs during the fasting period. Methane production was 30 % greater in NF-pigs than DF-pigs (P < 0·001). In conclusion, circadian misalignment has little effect on nutrient digestion, but alters nutrient partitioning, ultimately increasing fat deposition. The causality of the association between circadian misalignment and methane production rates remains to be investigated.
A new fossil site in a previously unexplored part of western Madagascar (the Beanka Protected Area) has yielded remains of many recently extinct vertebrates, including giant lemurs (Babakotia radofilai, Palaeopropithecus kelyus, Pachylemur sp., and Archaeolemur edwardsi), carnivores (Cryptoprocta spelea), the aardvark-like Plesiorycteropus sp., and giant ground cuckoos (Coua). Many of these represent considerable range extensions. Extant species that were extirpated from the region (e.g., Prolemur simus) are also present. Calibrated radiocarbon ages for 10 bones from extinct primates span the last three millennia. The largely undisturbed taphonomy of bone deposits supports the interpretation that many specimens fell in from a rock ledge above the entrance. Some primates and other mammals may have been prey items of avian predators, but human predation is also evident. Strontium isotope ratios (87Sr/86Sr) suggest that fossils were local to the area. Pottery sherds and bones of extinct and extant vertebrates with cut and chop marks indicate human activity in previous centuries. Scarcity of charcoal and human artifacts suggests only occasional visitation to the site by humans. The fossil assemblage from this site is unusual in that, while it contains many sloth lemurs, it lacks ratites, hippopotami, and crocodiles typical of nearly all other Holocene subfossil sites on Madagascar.
Introduction and regular application of multiplex polymerase chain reaction analysis of bronchoalveolar specimens for community-acquired respiratory viruses in January 2017 led to the identification of adenovirus in multiple patients in a surgical intensive unit in July 2017, which was attributed to a pseudo-outbreak.
To evaluate associations of demographic and socio-economic factors with diet quality among population subgroups in Bosnia and Herzegovina (B&H).
A cross-sectional analysis of 2017 B&H dietary survey data. Diet quality was assessed by the Prime Diet Quality Score (PDQS) utilizing data from two non-consecutive 24 h diet recalls. Socio-economic variables were extracted from the 2015 B&H Household Budget Survey. Homogeneity of means across population subgroups was evaluated using multivariable regression.
B&H population survey.
A population-based sample of 853 adults.
The mean PDQS was 15·8 (range 7–28 out of a possible 42 points). In general, Bosnian adults had low PDQS due to high intakes of refined grains, high-fat dairy and processed meats, and low intakes of whole grains, nuts and fish. The PDQS was significantly higher (P < 0·0001) among older individuals (17·0) compared with those in the youngest group (14·5), among individuals living in the central and northern regions (16·5) compared with those living in the south (15·1; P < 0·0001), and among people who are married/cohabitating (16·1) v. single (14·8; P = 0·02). In energy-adjusted models, socio-economic status (P = 0·04) and tertiles of household spending (P = 0·002) were inversely associated with the PDQS.
Diet quality in this population was low. Young and middle-aged individuals, singles and those living in the south had significantly lower quality diets compared with other subgroups. Public health action is needed to promote higher consumption of whole grains, nuts and fish, and a higher variety of fruits and vegetables.
Previous research showed that automatic emotion regulation is associated with activation of subcortical areas and subsequent feedforward processes to cortical areas. In contrast, cognitive awareness of emotions is mediated by negative feedback from cortical to subcortical areas. Pregenual anterior cingulate cortex (pgACC) is essential in the modulation of both affect and alexithymia. We considered the interplay between these two mechanisms in the pgACC and their relationship with alexithymia.
In 68 healthy participants (30 women, age = 26.15 ± 4.22) we tested associations of emotion processing and alexithymia with excitation/inhibition (E/I) balance represented as glutamate (Glu)/GABA in the pgACC measured via magnetic resonance spectroscopy in 7 T.
Alexithymia was positively correlated with the Glu/GABA ratio (N = 41, p = 0.0393). Further, cognitive self-awareness showed an association with Glu/GABA (N = 52, p = 0.003), which was driven by a correlation with GABA. In contrast, emotion regulation was only correlated with glutamate levels in the pgACC (N = 49, p = 0.008).
Our results corroborate the importance of the pgACC as a mediating region of alexithymia, reflected in an altered E/I balance. Furthermore, we could specify that this altered balance is linked to a GABA-related modulation of cognitive self-awareness of emotions.
The objectives of this paper are to: (1) identify contextual factors such as policy that impacted the implementation of community-based primary health care (CBPHC) innovations among 12 Canadian research teams and (2) describe strategies used by the teams to address contextual factors influencing implementation of CBPHC innovations. In primary care settings, consideration of contextual factors when implementing change has been recognized as critically important to success. However, contextual factors are rarely recorded, analyzed or considered when implementing change. The lack of consideration of contextual factors has negative implications not only for successfully implementing primary health care (PHC) innovations, but also for their sustainability and scalability. For this evaluation, data collection was conducted using self-administered questionnaires and follow-up telephone interviews with team representatives. We used a combination of directed and conventional content analysis approaches to analyze the questionnaire and interview data. Representatives from all 12 teams completed the questionnaire and 11 teams participated in the interviews; 40 individuals participated in this evaluation. Four themes representing contextual factors that impacted the implementation of CBPHC innovations were identified: (I) diversity of jurisdictions (II) complexity of interactions and collaborations (III) policy, and (IV) the multifaceted nature of PHC. The teams used six strategies to address these contextual factors including: (1) conduct an environmental scan at the beginning (2) maintaining engagement among partners and stakeholders by encouraging open and inclusive communication; (3) contextualizing the innovation for different settings; (4) anticipating and addressing changes, delays, and the need for additional resources; (5) fostering a culture of research and innovation among partners and stakeholders; and (6) ensuring information about the innovation is widely available. Implementing CBPHC innovations across jurisdictions is complex and involves navigating through multiple contextual factors. Awareness of the dynamic nature of context should be considered when implementing innovations.
Childhood maltreatment (CM) plays an important role in the development of major depressive disorder (MDD). The aim of this study was to examine whether CM severity and type are associated with MDD-related brain alterations, and how they interact with sex and age.
Within the ENIGMA-MDD network, severity and subtypes of CM using the Childhood Trauma Questionnaire were assessed and structural magnetic resonance imaging data from patients with MDD and healthy controls were analyzed in a mega-analysis comprising a total of 3872 participants aged between 13 and 89 years. Cortical thickness and surface area were extracted at each site using FreeSurfer.
CM severity was associated with reduced cortical thickness in the banks of the superior temporal sulcus and supramarginal gyrus as well as with reduced surface area of the middle temporal lobe. Participants reporting both childhood neglect and abuse had a lower cortical thickness in the inferior parietal lobe, middle temporal lobe, and precuneus compared to participants not exposed to CM. In males only, regardless of diagnosis, CM severity was associated with higher cortical thickness of the rostral anterior cingulate cortex. Finally, a significant interaction between CM and age in predicting thickness was seen across several prefrontal, temporal, and temporo-parietal regions.
Severity and type of CM may impact cortical thickness and surface area. Importantly, CM may influence age-dependent brain maturation, particularly in regions related to the default mode network, perception, and theory of mind.
Lymphatic filariasis (LF) threatens nearly 20% of the world's population and has handicapped one-third of the 120 million people currently infected. Current control and elimination programs for LF rely on mass drug administration of albendazole plus diethylcarbamazine (DEC) or ivermectin. Only the mechanism of action of albendazole is well understood. To gain a better insight into antifilarial drug action in vivo, we treated gerbils harbouring patent Brugia malayi infections with 6 mg kg−1 DEC, 0.15 mg kg−1 ivermectin or 1 mg kg−1 albendazole. Treatments had no effect on the numbers of worms present in the peritoneal cavity of treated animals, so effects on gene expression were a direct result of the drug and not complicated by dying parasites. Adults and microfilariae were collected 1 and 7 days post-treatment and RNA isolated for transcriptomic analysis. The experiment was repeated three times. Ivermectin treatment produced the most differentially expressed genes (DEGs), 113. DEC treatment yielded 61 DEGs. Albendazole treatment resulted in little change in gene expression, with only 6 genes affected. In total, nearly 200 DEGs were identified with little overlap between treatment groups, suggesting that these drugs may interfere in different ways with processes important for parasite survival, development, and reproduction.
To describe the process by which the 12 community-based primary health care (CBPHC) research teams worked together and fostered cross-jurisdictional collaboration, including collection of common indicators with the goal of using the same measures and data sources.
A pan-Canadian mechanism for common measurement of the impact of primary care innovations across Canada is lacking. The Canadian Institutes for Health Research and its partners funded 12 teams to conduct research and collaborate on development of a set of commonly collected indicators.
A working group representing the 12 teams was established. They undertook an iterative process to consider existing primary care indicators identified from the literature and by stakeholders. Indicators were agreed upon with the intention of addressing three objectives across the 12 teams: (1) describing the impact of improving access to CBPHC; (2) examining the impact of alternative models of chronic disease prevention and management in CBPHC; and (3) describing the structures and context that influence the implementation, delivery, cost, and potential for scale-up of CBPHC innovations.
Nineteen common indicators within the core dimensions of primary care were identified: access, comprehensiveness, coordination, effectiveness, and equity. We also agreed to collect data on health care costs and utilization within each team. Data sources include surveys, health administrative data, interviews, focus groups, and case studies. Collaboration across these teams sets the foundation for a unique opportunity for new knowledge generation, over and above any knowledge developed by any one team. Keys to success are each team’s willingness to engage and commitment to working across teams, funding to support this collaboration, and distributed leadership across the working group. Reaching consensus on collection of common indicators is challenging but achievable.