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Abstract The classification of neuronal subpopulations has significantly advanced, yet its relevance for behavior remains unclear. The highly organized flocculus of the cerebellum, known to fine-tune multi-axial eye movements, is an ideal substrate for the study of potential functions of neuronal subpopulations. Here, we demonstrate that its recently identified subpopulations of 9+ and 9- Purkinje cells exhibit an intermediate Aldolase C expression and electrophysiological profile, providing evidence for a graded continuum of intrinsic properties among PC subpopulations. By identifying and utilizing two Cre-lines that genetically target these floccular domains, we show with high spatial specificity that these subpopulations of Purkinje cells participate in separate micromodules with topographically organized connections. Finally, optogenetic excitation of the respective subpopulations results in movements around the same axis in space, yet with distinct kinematic profiles. These results indicate that Purkinje cell subpopulations integrate in discrete circuits and mediate particular parameters of single movements.

Because our civilization has relied on pesticides to fight weeds, insects, and diseases since antiquity, the use of these chemicals has become natural and exclusive. Unfortunately, the use of pesticides has progressively had alarming effects on water quality, biodiversity, and human health. This paper proposes to improve farming practices by replacing pesticides with a laser-based robotic approach. This study focused on the neutralization of aphids, as they are among the most harmful pests for crops and complex to control. With the help of deep learning, we developed a mobile robot that spans crop rows, locates aphids, and neutralizes them with laser beams. We have built a prototype with the sole purpose of validating the localization-neutralization loop on a single seedling row. The experiments performed in our laboratory demonstrate the feasibility of detecting different lines of aphids (50% detected at 3 cm/s) and of neutralizing them (90% mortality) without impacting the growth of their host plants. The results are encouraging since aphids are one of the most challenging crop pests to eradicate. However, enhancements in detection and mainly in targeting are necessary to be useful in a real farming context. Moreover, robustness regarding field conditions should be evaluated.

In a fully developed sea, the significant wave height (Hs) and wind speed (U10) are conventionally related to a pure quadratic equation. This relation is often violated, since in the field the measured local Hs is often contaminated by the swell, which is propagated from distant places. Therefore, a swell partition is required before the establishment of the wind-wave relation. The Spectra Energy Partition (SEP) is regarded as the best way to isolate the swell and the wind wave relation: it is based on the identification of a separation frequency in the ocean wave spectrum. However, for most field observations, the wave spectra information is unavailable, and thus the SEP is inapplicable. This work proposes a probability-based algorithm to identify the averaged swell without knowing the wave spectrum a priori. The local wind-wave relation is established by either a linear or an energy-conserved decomposition. We also find that the local wind-wave relation is a power-law when the wind speed U10 is above 4 m/s. The proposed method is first validated by applying the SEP method to buoy collected wave spectra data. The global pattern of the swell and the local wind waves is retrieved by applying the proposed method to a 17-year wind and wave database from the JASON satellite. Strong seasonal and spatial variations are obtained. Finally, a prediction model based on the empirical wind-wave relation is shown to successfully retrieve the wave field when the wind field is available.

Background: Globally, noncommunicable diseases (NCD) demand a higher healthcare expenditure. Among NCDs, diabetes mellitus is often associated with multiple, co-existing chronic conditions. In low- and middle-income countries where most of the healthcare expenditure is borne out of pocket, diabetes management may pose a significant financial stress. Methods: A cross-sectional study was conducted in 17 urban primary healthcare facilities of Bhubaneswar to assess the healthcare utilization and out-of-pocket expenditure among type 2 diabetes patients attending these facilities. Healthcare utilization was determined by the number of visits to healthcare facilities in the last 6 months, and out-of-pocket expenditure was assessed by outpatient consultation fees, medicines, travels to health care facilities, and diagnostic tests. Total out-of-pocket expenditure was defined as the sum of these costs. Results: The median number of visits in 6 months for diabetes patients with any comorbidity was 4 and 5 for diabetes patients with more than 4 comorbidities. Among the comorbid conditions, depression, stroke, auditory impairment, and acid peptic disease were associated with higher healthcare utilization. The total out-of-pocket expense was 2.3 times higher among diabetes patients with any comorbid condition compared to patients with diabetes only. The total median expenditure was higher for diabetes patients having stroke, heart diseases, kidney diseases, and cancer compared with other comorbid conditions. The association of comorbidity in diabetes patients with health care utilization and out-of-pocket expenditure is statistically significant after adjustment for sociodemographic characteristics and diabetes duration. Conclusion: Considerable expenditure is incurred by diabetes patients attending primary healthcare facilities for the management of diabetes and other chronic conditions. This is a significant burden for diabetes patients below the poverty line and with limited or no insurance cover. There is a need to increase the coverage of insurance schemes to address the chronic conditions management expenditure of outpatients.

In fully developed turbulence, there is a flux of energy from large to small scales in the inertial range until the dissipation at small scales. It is associated with irreversibility, i.e., a breaking of the time reversal symmetry. Such turbulent flows are characterized by scaling properties, and we consider here how irreversibility depends on the scale. Indicators of time-reversal symmetry for time series are tested involving triple correlations in a non-symmetric way. These indicators are built so that they are zero for a time-reversal symmetric time series, and a departure from zero is an indicator of irreversibility. We study these indicators applied to two fully developed turbulence time series, from flume tank and wind tunnel databases. It is found that irreversibility occurs in the inertial range and has scaling properties with slopes close to one. A maximum value is found around the injection scale. This confirms that the irreversibility is associated with the turbulent cascade in the inertial range and shows that the irreversibility is maximal at the injection scale, the largest scale of the turbulent cascade.

Green spaces contribute to a significant improvement in quality of life and maintain the sustainability of cities. In Benin, despite the political willingness regarding greening, municipalities are experiencing technical issues in finding suitable spaces to achieve this goal. This study should therefore be applicable to many other towns in Benin. It aims at identifying suitable areas for green spaces to integrate landscaping into urban planning in Abomey-Calavi district. Multi-criteria analysis combining GIS and the hierarchical classification approach was performed. Six factors (land use, altitude, slope, distance from main roads, proximity to urban centres and distance from flood zones, water bodies) were combined using the ArcGIS “Spatial Analysis” extension to generate a map of green space suitability. The results show large areas of land, of which 23.27% is very suitable and 26.06% is suitable for landscaping in this municipality. The ranking of the factors revealed that elevation, proximity to road networks, large conurbations and distance from wetlands accounted for 18%, compared with 14% for the other factors regarding the study environment. However, the use of these results must take into account the existing inhabited areas for a good site selection. These outputs provide guidance for decision-makers in choosing suitable sites for green spaces and integrating them into sustainable development.

Axonal swellings have been found on Purkinje cell axons in the cerebellum both during development and disease. The authors show that axons with swellings propagate action potentials with higher fidelity than those without and that mice with more axonal swellings learn cerebellar-related tasks better.

Abstract Background Cardiometabolic diseases (CMD) are the major cause of death worldwide and are associated with a lower quality of life and high healthcare costs. To prevent a further rise in CMD and related healthcare costs, early detection and adequate management of individuals at risk could be an effective preventive strategy. The objective of this study was to determine long-term cost-effectiveness of stepwise CMD risk assessment followed by individualized treatment if indicated compared to care as usual. A computer-based simulation model was used to project long-term health benefits and cost-effectiveness, assuming the prevention program was implemented in Dutch primary care. Methods A randomized controlled trial in a primary care setting in which 1934 participants aged 45–70 years without recorded CMD or CMD risk factors participated. The intervention group was invited for stepwise CMD risk assessment through a risk score (step 1), additional risk assessment at the practice in case of increased risk (step 2) and individualized follow-up treatment if indicated (step 3). The control group was not invited for risk assessment, but completed a health questionnaire. Results of the effectiveness analysis on systolic blood pressure (− 2.26 mmHg; 95% CI − 4.01: − 0.51) and total cholesterol (− 0.15 mmol/l; 95% CI − 0.23: − 0.07) were used in this analysis. Outcome measures were the costs and benefits after 1-year follow-up and long-term (60 years) cost-effectiveness of stepwise CMD risk assessment compared to no assessment. A computer-based simulation model was used that included data on disability weights associated with age and disease outcomes related to CMD. Analyses were performed taking a healthcare perspective. Results After 1 year, the average costs in the intervention group were 260 Euro higher than in the control group and differences were mainly driven by healthcare costs. No meaningful change was found in EQ 5D-based quality of life between the intervention and control groups after 1-year follow-up (− 0.0154; 95% CI − 0.029: 0.004). After 60 years, cumulative costs of the intervention were 41.4 million Euro and 135 quality-adjusted life years (QALY) were gained. Despite improvements in blood pressure and cholesterol, the intervention was not cost-effective (ICER of 306,000 Euro/QALY after 60 years). Scenario analyses did not allow for a change in conclusions with regard to cost-effectiveness of the intervention. Conclusions Implementation of this primary care-based CMD prevention program is not cost-effective in the long term. Implementation of this program in primary care cannot be recommended. Trial registration Dutch Trial Register NTR4277 , registered on 26 November 2013

Jean-Bernard Auliac,1 Florian Guisier,2 Acya Bizieux,3 Pascal Assouline,4 Marie Bernardini,5 Régine Lamy,6 Grégoire Justeau,7 Geraldine François,8 Diane Damotte,9,10 Christos Chouaïd1,11 1Pneumology Department, Centre Hospitalier Intercommunal de Créteil, Créteil, France; 2Pulmonology, Thoracic Oncology and Respiratory Department, Rouen University Hospital, Rouen, France; 3Pneumology Department, Centre Hospitalier de Vendée, La Roche-sur-Yon, France; 4Pneumology Department, Centre Hospitalier de Bligny, Bligny, France; 5Pneumology Department, Centre Hospitalier d’Aix-En-Provence, Aix-en-Provence, France; 6Pneumology Department, Centre Hospitalier de Bretagne-Sud, Lorient, France; 7Pneumology Department, Centre Hospitalier Universitaire d’Angers, Angers, France; 8Pneumology Department, Centre Hospitalier Universitaire d’Amiens, Amiens, France; 9Department of Pathology, Hôpital Cochin, APHP, Paris, France; 10University Paris Descartes, Paris, France; 11Inserm U955, UPEC, IMRB, Équipe CEpiA, Créteil, FranceCorrespondence: Jean-Bernard AuliacService de Pneumologie, CHI Créteil, 40, Avenue de Verdun, Créteil Cedex 94010, FranceEmail jean-bernard.auliac@chicreteil.frBackground: Few data have been published on the clinical and histopathological characteristics of advanced non-small–cell lung cancer (NSCLC) patients with high PD-L1 expression versus intermediate or none and the prognostic value of PD-L1 expression for patients treated with chemotherapy is unknown. This study was undertaken to prospectively assess the prognostic value of tumor-cell (TC) and immune-cell (IC) PD-L1 expressions for advanced NSCLC patients.Methods: It was a prospective, multicenter study on advanced NSCLC patients, with performance status 0/1, scheduled, consecutively, to receive first-line platin-based chemotherapy. PD-L1 expression was determined immunochemically (Dako Autostainer and monoclonal antibody 22C3) and its impact on progression-free survival (PFS) and overall survival (OS) assessed.Results: Among 198 patients screened in 19 centers, 140 were included median age: 66.5 ± 10 years; 76.4% men; 79.3% Caucasians; 10.7% nonsmokers; 63.6% adenocarcinomas; < 1%, 1– 50% and ≥ 50% TC PD-L1–expression rates were 47.1%, 25.7% and 27.2% of patients, respectively; respective null, intermediate and high rates on ICs were 35.7%, 38.6% and 25.7%. Second- and third-line chemotherapies were administered to 58.6% and 26.4% of the patients, respectively. None received immunotherapy. First-, second- and third-line median (95% CI) PFS lasted 4.6 (3.6– 5.2), 3.7 (2.3– 4.7) and 2.2 (1.5– 4.3) months, respectively; median OS was 16.9 (11.4– 19.9) months. No significant PFS and OS differences were observed according to TC or IC PD-L1 expression.Conclusion: According to the results of this prospective, multicenter study, neither TC nor IC PD-L1 expression appears to be prognostic for chemotherapy-managed advanced NSCLC patients.Keywords: chemotherapy, immunotherapy, non-small–cell lung cancer, PD-L1, prognostic

Abstract Background Prevention programs for cardiometabolic diseases (CMD), including cardiovascular disease, diabetes mellitus and chronic kidney disease are feasible, but evidence for the cost-effectiveness of selective CMD prevention programs is lacking. Response rates have an important role in effectiveness, but methods to increase response rates have received insufficient attention. The aim of the current study is to determine the feasibility and the success rate of a variety of response enhancing strategies to increase the participation in a selective prevention program for CMD. Methods The INTEGRATE study is a Dutch randomised controlled trial to assess the effectiveness and cost-effectiveness of a stepwise program for CMD prevention. During the INTEGRATE study we developed ten different response enhancing strategies targeted at different stages of non-response and different patient populations and evaluated these in 29 general practices. Results A face-to-face reminder by the GP increased the response significantly. Digital reminders targeted at patients with an increased CMD risk showed a positive trend towards participation. Sending invitations and reminders by e-mail generated similar response rates, but at lower costs and time investment than the standard way of dissemination. Translated materials, information gatherings at the practice, self-management toolkits, reminders by telephone, information letters, local media attention and SMS text reminders did not increase the response to our program. Conclusions Inviting or reminding patients by e-mail or during GPs consultation may enhance response rates in a selective prevention program for CMD. Different response-enhancing strategies have different patient target populations and implementation issues, therefore practice characteristics need to be taken into account when implementing such strategies. Trial registration Dutch trial Register number NTR4277 . Registered 26 November 2013.

Abstract Background The communication of relevant patient information between general practitioners (GPs) and medical specialists is important in order to avoid fragmentation of care thus achieving a higher quality of care and ensuring physicians’ and patients’ satisfaction. However, this communication is often not carried out properly. The objective of this study is to assess whether communication between GPs and medical specialists in the referral process is associated with the organisation of primary care within a country, the characteristics of the GPs, and the characteristics of the primary care practices themselves. Methods An analysis of a cross-sectional survey among GPs in 34 countries was conducted. The odds ratios of the features that were expected to relate to higher rates of referral letters sent and communications fed back to GPs were calculated using ordered logistic multilevel models. Results A total of 7183 GPs from 34 countries were surveyed. Variations between countries in referral letters sent and feedback communication received did occur. Little of the variance between countries could be explained. GPs stated that they send more referral letters, and receive more feedback communications from medical specialists, in countries where they act as gatekeepers, and when, in general, they interact more with specialists. GPs reported higher use of referral letters when they had a secretary and/or a nurse in their practice, used health information technologies, and had greater job satisfaction. Conclusions There are large differences in communication between GPs and medical specialists. These differences can partly be explained by characteristics of the country, the GP and the primary care practice. Further studies should also take the organisation of secondary care into account.

Abstract Background Poor communication between general practitioners (GPs) and medical specialists can lead to poorer quality, and continuity, of care. Our study aims to assess patients’ perceptions of communication at the interface between primary and secondary care in 34 countries. It will analyse, too, whether this communication is associated with the organisation of primary care within a country, and with the characteristics of GPs and their patients. Methods We conducted a cross-sectional survey among patients in 34 countries. Following a GP consultation, patients were asked two questions. Did they take to understand that their GP had informed medical specialists about their illness upon referral? And, secondly, did their GP know the results of the treatment by a medical specialist? We used multi-response logistic multilevel models to investigate the association of factors related to primary care, the GP, and the patient, with the patients’ perceptions of communication at the interface between primary and secondary care. Results In total, 61,931 patients completed the questionnaire. We found large differences between countries, in both the patients’ perceptions of information shared by GPs with medical specialists, and the patients’ perceptions of the GPs’ awareness of the results of treatment by medical specialists. Patients whose GPs stated that they ‘seldom or never’ send referral letters, also less frequently perceived that their GP communicated with their medical specialists about their illness. Patients with GPs indicating they ‘seldom or never’ receive feedback from medical specialists, indicated less frequently that their GP would know the results of treatment by a medical specialist. Moreover, patients with a personal doctor perceived higher rates of communication in both directions at the interface between primary and secondary care. Conclusion Generally, patients perceive there to be high rates of communication at the interface between primary and secondary care, but there are large differences between countries. Policies aimed at stimulating personal doctor arrangements could, potentially, enhance the continuity of care between primary and secondary care.

Abstract Background and aims Since cardiometabolic diseases (CMD) are a frequent cause of death worldwide, preventive strategies are needed. Recruiting adults for a health check could facilitate the identification of individuals at risk for CMD. For successful results, participation is crucial. We aimed to identify factors related to unwillingness to participate in CMD health checks. Methods We performed a cross‐sectional study in the Czech Republic, Denmark, Greece, the Netherlands, and Sweden. A questionnaire was distributed among persons without known CMD consulting general practice between January and July 2017 within the framework of the SPIMEU study. Results In total, 1354 persons responded. Nine percent was unwilling to participate in a CMD health check. Male gender, smoking, higher self‐rated health, never been invited before, and not willing to pay were related to unwillingness to participate. The most mentioned reason for unwillingness to participate was “I think that I am healthy” (57%). Among the respondents who were willing to participate, 94% preferred an invitation by the general practitioner and 66% was willing to pay. Conclusion A minority of the respondents was unwilling to participate in a CMD health check with consistent results within the five countries. This provides a promising starting point to increase participation in CMD health checks in primary care.

Background: Selective prevention of cardiometabolic diseases (CMD)—that is, preventive measures specifically targeting the high-risk population—may represent the most effective approach for mitigating rising CMD rates. Objectives: To develop a universal concept of selective CMD prevention that can guide implementation within European primary care. Methods: Initially, 32 statements covering different aspects of selective CMD prevention programmes were identified based on a synthesis of evidence from two systematic literature reviews and surveys conducted within the SPIMEU project. The Rand/UCLA appropriateness method (RAM) was used to find consensus on these statements among an international panel consisting of 14 experts. Before the consensus meeting, statements were rated by the experts in a first round. In the next step, during a face-to-face meeting, experts were provided with the results of the first rating and were then invited to discuss and rescore the statements in a second round. Results: In the outcome of the RAM procedure, 28 of 31 statements were considered appropriate and three were rated uncertain. The panel deleted one statement. Selective CMD prevention was considered an effective approach for preventing CMD and a proactive approach was regarded as more effective compared to case-finding alone. The most efficient method to implement selective CMD prevention systematically in primary care relies on a stepwise approach: initial risk assessment followed by interventions if indicated. Conclusion: The final set of statements represents the key characteristics of selective CMD prevention and can serve as a guide for implementing selective prevention actions in European primary care.

Abstract Background Incidence rates and prevalence proportions are commonly used to express the populations health status. Since there are several methods used to calculate these epidemiological measures, good comparison between studies and countries is difficult. This study investigates the impact of different operational definitions of numerators and denominators on incidence rates and prevalence proportions. Methods Data from routine electronic health records of general practices contributing to NIVEL Primary Care Database was used. Incidence rates were calculated using different denominators (person-years at-risk, person-years and midterm population). Three different prevalence proportions were determined: 1 year period prevalence proportions, point-prevalence proportions and contact prevalence proportions. Results One year period prevalence proportions were substantially higher than point-prevalence (58.3 - 206.6%) for long-lasting diseases, and one year period prevalence proportions were higher than contact prevalence proportions (26.2 - 79.7%). For incidence rates, the use of different denominators resulted in small differences between the different calculation methods (-1.3 - 14.8%). Using person-years at-risk or a midterm population resulted in higher rates compared to using person-years. Conclusions All different operational definitions affect incidence rates and prevalence proportions to some extent. Therefore, it is important that the terminology and methodology is well described by sources reporting these epidemiological measures. When comparing incidence rates and prevalence proportions from different sources, it is important to be aware of the operational definitions applied and their impact.

Background: Owing to the rising disease burden of cardiometabolic diseases (CMD), prevention programmes for CMD are increasingly implemented in primary care. Organisational practice characteristics and availability of preventive services may be associated with a more effective programme. Aim: To identify possible organisational success factors from general practices related to an effective primary prevention programme for CMD. Design & setting: A prospective intervention study involving 37 Dutch general practices was undertaken. Method: Patients aged 45–70 years without known CMD, hypertension, or hypercholesterolemia were invited for the prevention programme. The outcome measures were an improvement (yes/no) in four different CMD risk factors between baseline and 1-year follow-up on an individual level (body mass index [BMI], smoking, systolic blood pressure, and cholesterol ratio). Multivariate logistic regression analysis was used for assessing associations between practice organisational characteristics and outcomes. Results: Just over half of the participants showed an improvement on one or more risk factors. Marginal differences were found in the four different outcomes between the practices with different organisational characteristics. None of the practice characteristics that were tested showed a significant association with an improvement in one of the outcome measures. Conclusion: In this study, general practice organisational and preventive service characteristics showed no impact on the effectiveness of a CMD prevention programme. Possible explanations could be the effectiveness of protocolised pharmaceutical treatment and only limited contribution of lifestyle programmes on the improvement of CMD risk factors.

Non-response in prevention programs for cardiometabolic diseases (CMD) in primary care is often overlooked. The aim for this study was to define factors that influence the primary response to a selective CMD prevention program and to determine response-enhancing strategies that influence the willingness to participate. We conducted a non-response analysis within a randomized controlled trial evaluating a selective CMD prevention program, the study was conducted from 2013 to 2018 in Netherlands. A random sample of 5616 patients from 15 general practices were invited to complete a risk score (RS) as initial step of the program. Non-responders received an additional questionnaire. The response on the risk score was 51% (n = 2872). From the 3558 non-response questionnaires sent, 786 (22%) were returned. In a multivariable multilevel regression analysis smoking was independently associated with non-response. Of all reported reasons for non-response ‘forgot/no time’ accounted for 45%. In total, 73% of the non-responders indicated to reconsider participation when approached differently. A personal approach by the patients’ own GP, using advertisements and informative campaigns are potentially the best methods to enhance the response. Although a relatively high proportion did not respond to the invitation for the risk score, the majority of them indicated to be willing to participate if a different invitation strategy would be used. With more time and energy, response rates for CMD prevention programs could possibly increase substantially. A next logical step in this process is to test potential response enhancing strategies in research setting.

Comparison of graph structure is a ubiquitous task in data analysis and machine learning, with diverse applications in fields such as neuroscience, cyber security, social network analysis, and bioinformatics, among others. Discovery and comparison of structures such as modular communities, rich clubs, hubs, and trees yield insight into the generative mechanisms and functional properties of the graph. Often, two graphs are compared via a pairwise distance measure, with a small distance indicating structural similarity and vice versa. Common choices include spectral distances and distances based on node affinities. However, there has of yet been no comparative study of the efficacy of these distance measures in discerning between common graph topologies at different structural scales. In this work, we compare commonly used graph metrics and distance measures, and demonstrate their ability to discern between common topological features found in both random graph models and real world networks. We put forward a multi-scale picture of graph structure wherein we study the effect of global and local structures on changes in distance measures. We make recommendations on the applicability of different distance measures to the analysis of empirical graph data based on this multi-scale view. Finally, we introduce the Python library NetComp that implements the graph distances used in this work.

BACKGROUND:Variations in childbirth interventions may indicate inappropriate use. Most variation studies are limited by the lack of adjustments for maternal characteristics and do not investigate variations in adverse outcomes. This study aims to explore regional variations in the Netherlands and their correlations with referral rates, birthplace, interventions, and adverse outcomes, adjusted for maternal characteristics. METHODS:In this nationwide retrospective cohort study, using a national data register, intervention rates were analysed between twelve regions among single childbirths after 37 weeks' gestation in 2010-2013 (n = 614,730). These were adjusted for maternal characteristics using multivariable logistic regression. Primary outcomes were intrapartum referral, birthplace, and interventions used in midwife- and obstetrician-led care. Correlations both between primary outcomes and between adverse outcomes were calculated with Spearman's rank correlations. FINDINGS:Intrapartum referral rates varied between 55-68% (nulliparous) and 20-32% (multiparous women), with a negative correlation with receiving midwife-led care at the onset of labour in two-thirds of the regions. Regions with higher referral rates had higher rates of severe postpartum haemorrhages. Rates of home birth varied between 6-16% (nulliparous) and 16-31% (multiparous), and was negatively correlated with episiotomy and postpartum oxytocin rates. Among midwife-led births, episiotomy rates varied between 14-42% (nulliparous) and 3-13% (multiparous) and in obstetrician-led births from 46-67% and 14-28% respectively. Rates of postpartum oxytocin varied between 59-88% (nulliparous) and 50-85% (multiparous) and artificial rupture of membranes between 43-52% and 54-61% respectively. A north-south gradient was visible with regard to birthplace, episiotomy, and oxytocin. CONCLUSIONS:Our study suggests that attitudes towards interventions vary, independent of maternal characteristics. Care providers and policy makers need to be aware of reducing unwarranted variation in birthplace, episiotomy and the postpartum use of oxytocin. Further research is needed to identify explanations and explore ways to reduce unwarranted intervention rates.

BackgroundPrevious studies identified demographic, reproduction-related and psychosocial correlates of suboptimal mother-to-infant bonding. Their joint informative value was still unknown. This study aimed to develop a multivariable model to screen early in pregnancy for suboptimal postnatal mother-to-infant bonding and to transform it into a risk classification model.MethodsProspective cohort study conducted at 116 midwifery centers between 2010-2014. 634 women reported on the Mother-to-Infant Bonding questionnaire in 2015-2016. A broad range of determinants before 13 weeks of gestation were considered. Missing data were described, analyzed and imputed by multiple imputation. Multivariable logistic regression with backward elimination was used to develop a screening model. The explained variance, the Area Under the Curve of the final model were calculated and a Hosmer and Lemeshow test performed. Finally, we designed a risk classification model.ResultsThe prevalence of suboptimal mother-to-infant bonding was 11%. The estimated probability of suboptimal mother-to-infant can be calculated: P(MIBS≥4) = 1/(1+exp(-(-4.391+(parity× 0.519)+(Adult attachment avoidance score× 0.040))). The explained variance was 14% and the Area Under the Curve was 0.750 (95%CI 0.690-0.809). The Hosmer and Lemeshow test had a p-value of 0.21. This resulted in a risk classification model.ConclusionParity and adult attachment avoidance were the strongest independent determinants. Higher parity and higher levels of adult attachment avoidance are associated with an increased risk of suboptimal mother-to-infant bonding. The model and risk classification model should be externally validated and optimized before use in daily practice. Future research should include an external validation study, a study into the additional value of non-included determinants and finally a study on the impact and feasibility of the screening model.

Abstract Background Fear of childbirth may reduce the womens’ pain tolerance during labour and may have impact on the mother-infant interaction. We aimed to assess (1) the association between fear of childbirth antepartum and subsequent request for pharmacological pain relief, and (2) the association between the used method of pain relief and experienced fear of childbirth as reported postpartum in low risk labouring women. Methods Secondary analysis of the RAVEL study, a randomised controlled trial comparing remifentanil patient controlled analgesia (PCA) and epidural analgesia to relieve labour pain. The RAVEL study included 409 pregnant women at low risk for obstetric complications at 18 midwifery practices and six hospitals in The Netherlands (NTR 3687). We measured fear of childbirth antepartum and experienced fear of childbirth reported postpartum, using the Wijma Delivery Expectancy/Experience Questionnaire. Results Women with fear of childbirth antepartum more frequently requested pain relief compared to women without fear of childbirth antepartum, but this association did not reach statistical significance (adjusted odds ratio (aOR2.0; 95% confidence interval (CI) 0.8–4.6). Women who received epidural analgesia more frequently reported fear of childbirth postpartum compared to women who did not receive epidural analgesia (aOR3.5; CI 1.5–8.2), while the association between remifentanil-PCA and fear of childbirth postpartum was not statistically significant (aOR1.7; CI 0.7–4.3). Conclusions Women with fear of childbirth antepartum more frequently requested pain relief compared to women without fear of childbirth antepartum, but this association was not statistically significant. Women who received pharmacological pain relief more frequently reported that they had experienced fear of childbirth during labour compared to women who did not receive pain relief. Based on our data epidural analgesia with continuous infusion does not seem to be preferable over remifentanil-PCA as method of pain relief when considering fear of childbirth postpartum. Trial registration Netherlands Trial Register 3687; Register date: 5 Nov 2012.

B-cell precursors (BCP) arise from hematopoietic stem cells in bone marrow (BM). Identification and characterization of the different BCP subsets has contributed to the understanding of normal B-cell development. BCP first rearrange their immunoglobulin (Ig) heavy chain (IGH) genes to form the pre-B-cell receptor (pre-BCR) complex together with surrogate light chains. Appropriate signaling via this pre-BCR complex is followed by rearrangement of the Ig light chain genes, resulting in the formation, and selection of functional BCR molecules. Consecutive production, expression, and functional selection of the pre-BCR and BCR complexes guide the BCP differentiation process that coincides with corresponding immunophenotypic changes. We studied BCP differentiation in human BM samples from healthy controls and patients with a known genetic defect in V(D)J recombination or pre-BCR signaling to unravel normal immunophenotypic changes and to determine the effect of differentiation blocks caused by the specific genetic defects. Accordingly, we designed a 10-color antibody panel to study human BCP development in BM by flow cytometry, which allows identification of classical preB-I, preB-II, and mature B-cells as defined via BCR-related markers with further characterization by additional markers. We observed heterogeneous phenotypes associated with more than one B-cell maturation pathway, particularly for the preB-I and preB-II stages in which V(D)J recombination takes place, with asynchronous marker expression patterns. Next Generation Sequencing of complete IGH gene rearrangements in sorted BCP subsets unraveled their rearrangement status, indicating that BCP differentiation does not follow a single linear pathway. In conclusion, B-cell development in human BM is not a linear process, but a rather complex network of parallel pathways dictated by V(D)J-recombination-driven checkpoints and pre-BCR/BCR mediated-signaling occurring during B-cell production and selection. It can also be described as asynchronous, because precursor B-cells do not differentiate as full population between the different stages, but rather transit as a continuum, which seems influenced (in part) by V-D-J recombination-driven checkpoints.

Abstract Background Shared decision-making (SDM) in the management of metastatic breast cancer care is associated with positive patient outcomes. In daily clinical practice, however, SDM is not fully integrated yet. Initiatives to improve the implementation of SDM would be helpful. The aim of this review was to assess the availability and effectiveness of tools supporting SDM in metastatic breast cancer care. Methods Literature databases were systematically searched for articles published since 2006 focusing on the development or evaluation of tools to improve information-provision and to support decision-making in metastatic breast cancer care. Internet searches and experts identified additional tools. Data from included tools were extracted and the evaluation of tools was appraised using the GRADE grading system. Results The literature search yielded five instruments. In addition, two tools were identified via internet searches and consultation of experts. Four tools were specifically developed for supporting SDM in metastatic breast cancer, the other three tools focused on metastatic cancer in general. Tools were mainly applicable across the care process, and usable for decisions on supportive care with or without chemotherapy. All tools were designed for patients to be used before a consultation with the physician. Effects on patient outcomes were generally weakly positive although most tools were not studied in well-designed studies. Conclusions Despite its recognized importance, only two tools were positively evaluated on effectiveness and are available to support patients with metastatic breast cancer in SDM. These tools show promising results in pilot studies and focus on different aspects of care. However, their effectiveness should be confirmed in well-designed studies before implementation in clinical practice. Innovation and development of SDM tools targeting clinicians as well as patients during a clinical encounter is recommended.

Objective: Current guidelines acknowledge the need for cardiometabolic disease (CMD) prevention and recommend five-yearly screening of a targeted population. In recent years programs for selective CMD-prevention have been developed, but implementation is challenging. The question arises if general practices are adequately prepared. Therefore, the aim of this study is to assess the organizational preparedness of Dutch general practices and the facilitators and barriers for performing CMD-prevention in practices currently implementing selective CMD-prevention. Design: Observational study. Setting: Dutch primary care. Subjects: General practices. Main outcome measures: Organizational characteristics. Results: General practices implementing selective CMD-prevention are more often organized as a group practice (49% vs. 19%, p = .000) and are better organized regarding chronic disease management compared to reference practices. They are motivated for performing CMD-prevention and can be considered as ‘frontrunners’ of Dutch general practices with respect to their practice organization. The most important reported barriers are a limited availability of staff (59%) and inadequate funding (41%). Conclusions: The organizational infrastructure of Dutch general practices is considered adequate for performing most steps of selective CMD-prevention. Implementation of prevention programs including easily accessible lifestyle interventions needs attention. All stakeholders involved share the responsibility to realize structural funding for programmed CMD-prevention. Aforementioned conditions should be taken into account with respect to future implementation of selective CMD-prevention.Key Points There is need for adequate CMD prevention. Little is known about the organization of selective CMD prevention in general practices. • The organizational infrastructure of Dutch general practices is adequate for performing most steps of selective CMD prevention. • Implementation of selective CMD prevention programs including easily accessible services for lifestyle support should be the focus of attention. • Policy makers, health insurance companies and healthcare professionals share the responsibility to realize structural funding for selective CMD prevention.

Abstract Background To compare experienced continuity of care among women who received midwife-led versus obstetrician-led care. Secondly, to compare experienced continuity of care with a. experienced quality of care during labor and b. perception of labor. Methods We conducted a questionnaire survey in a region in the Netherlands in 2014 among 790 women after they gave birth. To measure experienced continuity of care, the Nijmegen Continuity Questionnaire was used. Quality of care during labor was measured with the Pregnancy and Childbirth Questionnaire, and to measure perception of labor we used the Childbirth Perception Scale. Results Three hundred twenty five women consented to participate (41%). Of these, 187 women completed the relevant questions in the online questionnaire. 136 (73%) women were in midwife-led care at the onset of labor, 15 (8%) were in obstetrician-led care throughout pregnancy and 36 (19%) were referred to obstetrician-led care during pregnancy. Experienced personal and team continuity of care during pregnancy were higher for women in midwife-led care compared to those in obstetrician-led care at the onset of labor. Experienced continuity of care was moderately correlated with experienced quality of care although not significantly so in all subgroups. A weak negative correlation was found between experienced personal continuity of care by the midwife and perception of labor. Conclusion This study suggests that experienced continuity of care depends on the care context and is significantly higher for women who are in midwife-led compared to obstetrician-led care during labor. It will be a challenge to maintain the high level of experienced continuity of care in an integrated maternity care system. Experienced continuity of care seems to be a distinctive concept that should not be confused with experienced quality of care or perception of labor and should be considered as a complementary aspect of quality of care.

In this work, we evaluated the conformational effect promoted by the isosteric exchange of sulfur by selenium in the heteroaromatic ring of new N-acylhydrazone (NAH) derivatives (3–8, 13, 14), analogues of the cardioactive compounds LASSBio-294 (1) and LASSBio-785 (2). NMR spectra analysis demonstrated a chemical shift variation of the iminic Csp2 of NAH S/Se-isosters, suggesting a stronger intramolecular chalcogen interaction for Se-derivatives. To investigate the pharmacological profile of these compounds at the adenosine A2A receptor (A2AR), we performed a previously validated functional binding assay. As expected for bioisosteres, the isosteric-S/Se replacement affected neither the affinity nor the intrinsic efficacy of our NAH derivatives (1–8). However, the N-methylated compounds (2, 6–8) presented a weak partial agonist profile at A2AR, contrary to the non-methylated counterparts (1, 3–5), which appeared as weak inverse agonists. Additionally, retroisosterism between aromatic rings of NAH on S/Se-isosters mimicked the effect of the N-methylation on intrinsic efficacy at A2AR, while meta-substitution in the phenyl ring of the acyl moiety did not. This study showed that the conformational effect of NAH-N-methylation and aromatic rings retroisosterism changed the intrinsic efficacy on A2AR, indicating the S/Se-chalcogen effect to drive the conformational behavior of this series of NAH.

Barred macrotidal beaches are affected by continuous horizontal displacements of different hydrodynamic zones associated with wave transformation (shoaling, breaker and surf zones) due to significant tide-induced water level changes. A series of wave and current meters, complemented by a video imagery system, were deployed on a barred beach of northern France during a 6-day experiment in order to characterize the spatial and temporal variability of wave-induced processes across the beach. Wave and current spectral analyses and analyses of cross-shore current direction and asymmetry resulted in the identification of distinct hydrodynamic processes, including the development of infragravity waves and offshore-directed flows in the breaker and surf zones. Our results revealed a high spatial variability in the hydrodynamic processes across the beach, related to the bar-trough topography, as well as significant variations in the directions and intensity of cross-shore currents at fixed locations due to the horizontal translation of the different hydrodynamic zones resulting from continuous changes in water level due to tides.

Objectives: To describe how principles of self-regulation and social support could be integrated in a group intervention to improve self-management of people with type 2 diabetes mellitus in the early phase of illness and to pilot its suitability in a primary care setting. Methods: Principles of the Common-Sense Model of Self-Regulation, Social Cognitive Theory of Self-Regulation and social support theories were integrated in the intervention. Based on this, a three-session group course was developed to challenge illness perceptions of participants that discourage adequate self-management, to practice goal-setting and behavioural actions and to create a supportive environment. The intervention was piloted with persons with early-stage (1–3 years post diagnosis) type 2 diabetes mellitus selected in general practice in the Netherlands. Data about the suitability of the intervention were retrieved by means of observation and audio-recording of the sessions, an evaluation form filled in by the participants and an evaluation meeting with the group leaders. Results: In total, 16 type 2 diabetes mellitus patients participated in the pilot, who were divided into a group of single participants (N = 8) and a group (N = 8) who participated with their partner. Discrepancies between perceptions of one’s own condition and type 2 diabetes mellitus in general were observed. Goal-setting and developing action plans appeared to be difficult tasks for many participants, whereas others felt these exercises were not useful as they did not feel a need to make changes in living with diabetes. The group-based format was appreciated as was the participation of partners. Conclusion: Challenging the illness perceptions of persons with early-stage type 2 diabetes mellitus by a brief interactive group course is feasible and important, as many of these people tend to underestimate the seriousness of their diabetes. However, motivating persons with early-stage type 2 diabetes mellitus to participate in self-management interventions remains a challenge. Offering the intervention as an integral part of type 2 diabetes mellitus management in primary care is desirable.

AIMS:To evaluate the immediate and six-month effectiveness of a group-based self-management support program for people diagnosed with type 2 diabetes (1-3 years post diagnosis) on diabetes self-care, distress and cognitions. METHODS:People with type 2 diabetes were randomized into the intervention (four group-based interactive sessions) or the control group (a single educational lecture) with their partners. Outcomes were measured at baseline, immediately after the third course session and six months later using validated questionnaires on diabetes self-care, distress, illness perceptions, diabetes-related attitudes, empowerment and partner support. Multilevel analyses were conducted according to the intention-to-treat principle using the data from 82 intervention and 86 control group participants, to test for differences in changes over time between the two groups. RESULTS:The intervention group showed a significantly higher increase in physical activity and fruit and vegetable intake immediately after the program, whereas the low baseline levels of diabetes distress remained unaffected. Furthermore, the intervention group believed their illness to be more likely to be caused by chance/bad luck, but also felt more empowered to handle their condition and its treatment immediately after the program compared with the control group. Six months later, only the differences in empowerment had persisted. CONCLUSIONS:Group-based self-management support results in favorable short-term behavioral changes and more persistent alterations in (perceived) empowerment in people living in the first years of type 2 diabetes. In order to achieve more sustainable behavioral changes, more prolonged support is necessary. This could be achieved by integrating attention to patients' illness perceptions and continuous self-management support in regular diabetes care. TRIAL REGISTRATION:Netherlands Trial Registry NL3158.

BACKGROUND:Mother-to-infant bonding is defined as the emotional tie experienced by a mother towards her child, which is considered to be important for the socio-emotional development of the child. Numerous studies on the correlates of both prenatal and postnatal mother-to-infant bonding quality have been published over the last decades. An up-to-date systematic review of these correlates is lacking, however. OBJECTIVE:To systematically review correlates of prenatal and postnatal mother-to-infant bonding quality in the general population, in order to enable targeted interventions. METHODS:MEDLINE, Embase, CINAHL, and PsychINFO were searched through May 2018. Reference checks were performed. Case-control, cross-sectional or longitudinal cohort studies written in English, German, Swedish, Spanish, Norwegian, French or Dutch defining mother-to-infant bonding quality as stipulated in the protocol (PROSPERO CRD42016040183) were included. Two investigators independently reviewed abstracts, full-text articles and extracted data. Methodological quality was assessed using the National Institute of Health Quality Assessment Tool for Observational Cohort and Cross-sectional studies and was rated accordingly as poor, fair or good. Clinical and methodological heterogeneity were examined. MAIN RESULTS:131 studies were included. Quality was fair for 20 studies, and poor for 111 studies. Among 123 correlates identified, 3 were consistently associated with mother-to-infant bonding quality: 1) duration of gestation at assessment was positively associated with prenatal bonding quality, 2) depressive symptoms were negatively associated with postnatal mother-to-infant bonding quality, and 3) mother-to-infant bonding quality earlier in pregnancy or postpartum was positively associated with mother-to-infant bonding quality later in time. CONCLUSION:Our review suggests that professionals involved in maternal health care should consider monitoring mother-to-infant bonding already during pregnancy. Future research should evaluate whether interventions aimed at depressive symptoms help to promote mother-to-infant bonding quality. More high-quality research on correlates for which inconsistent results were found is needed.

Objective: Evidence regarding the benefits of strong primary care has influenced health policy and practice. This study focuses on changes in the breadth of services provided by general practitioners (GPs) in Europe between 1993 and 2012 and offers possible explanations for these changes. Design: Data on the breadth of service profiles were used from two cross-sectional surveys in 28 countries: the 1993 European GP Task Profile study (6321 GPs) and the 2012 QUALICOPC study (6044 GPs). GPs’ involvement in four areas of clinical activity (first contact care, treatment of diseases, medical procedures, and prevention) was established using ecometric analyses. The changes were measured by the relative increase in the breadth of service profiles. Associations between changes and national-level conditions were examined though regression analyses. Data on the national conditions were used from various other public databases including the World Databank and the PHAMEU (Primary Health care Activity Monitor) database. Setting: A total of 28 European countries. Subjects: GPs. Main outcome measure: Changes in the breadth of GP service profiles. Results: A general trend of increased involvement of European GPs in treatment of diseases and decreased involvement in preventive activities was observed. Conditions at the national level were associated with changes in the involvement of GPs in first contact care, treatment of diseases and, to a limited extent, prevention. Especially in countries with stronger growth of health care expenditures between 1993 and 2012 the service profiles have expanded. In countries where family values are more dominant the breadth in service profiles decreased. A stronger professional status of GPs was positively associated with the change in first contact care. Conclusions: GPs in former communist countries and Turkey have increased their involvement in the provision of services. Developments in Western Europe were less evident. The developments in the service profiles could only to a very limited extent be explained by national conditions. A main driver of reform seems to be the changes in health care expenditure, which may indicate a notion of urgency because there may be a pressure to curb the rising expenditures. Key points Broad GP service profiles are an indicator of strong primary care in a country. It is expected that developments in the breadth of GP service profiles are influenced by various national conditions related to the urgency to reform, politics, and means. Between 1993 and 2012 the involvement of GPs in European countries in treatment of diseases increased and their involvement preventive activities decreased. The national conditions were found to be associated with changes in GPs’ involvement as first contact of care, treatment of diseases, and, to a limited extent, prevention. More specifically, in countries with a stronger growth in health care expenditures, service profiles of European GPs have expanded more in the past decades.

The Taylor power law (or temporal fluctuation scaling), is a scaling relationship of the form σ ~ (P)λ where !! is the standard deviation and hPi the mean value of a sample of a time series has been observed for power output data sampled at 5 min and 1 s and from five wind farms and a single wind turbine, located at different places. Furthermore, an analogy with the turbulence field is performed, consequently allowing the establishment of a scaling relationship between the turbulent production IP and the mean value (P).

Sea breeze (SB) phenomena may strongly influence air quality and lead to important effects on human health. In order to study the impact of SB dynamics on the properties and toxicity of aerosols, an atmospheric mobile unit was deployed during a field campaign performed in an urbanized and industrialized coastal area in Northern France. This unit combines aerosol samplers, two scanning lidars (Doppler and elastic) and an air-liquid interface (ALI, Vitrocell®) in vitro cell exposure device. Our study highlights that after the passage of an SB front, the top of the atmospheric boundary layer collapses as the thermal internal boundary layer (TIBL) develops, which leads to high aerosol extinction coefficient values (>0.4 km−1) and an increase of PM2.5 and NOx concentrations in the SB current. The number-size distribution of particles indicates a high proportion of fine particles (with diameter below 500 nm), while the volume-size distribution shows a major mode of coarse particles centered on 2−3 µm. Individual particle analyses performed by cryo-transmission scanning electron microscopy (cryo-TSEM)-EDX highlights that submicronic particles contained a high fraction of secondary compounds, which may result from nucleation and/or condensation of condensable species (vapors or gaseous species after photo-oxidation). Secondary aerosol (SA) formation can be enhanced in some areas, by the interaction between the SB flow and the upper continental air mass, particularly due to the effect of both turbulence and temperature/humidity gradients between these two contrasting air masses. Potential areas of SA formation are located near the ground, during the SB front passage and in the vicinity of the SB current top. During the sea breeze event, an increase in the oxidative stress and inflammation processes in exposed lung cells, compared to the unexposed cells, can also be seen. In some instances, short singularity periods are observed during SB, corresponding to a double flow structure. It consists of two adjacent SB currents that induce an important increase of the TIBL top, improving the pollutants dispersion. This is associated with a substantial decrease of aerosol mass concentrations.

Background: Collaboration between medical professionals from separate organisations is necessary to deliver good patient care. This care is influenced by professionals’ perceptions about their collaboration. Until now, no instrument to measure such perceptions was available in the Netherlands. A questionnaire developed and validated in Spain was translated to assess perceptions about clinicians’ collaboration in primary and secondary care in the Dutch setting. Aim: Validation in the Dutch setting of a Spanish questionnaire that aimed to assess perceptions of clinicians about interorganisational collaboration. Design & setting: After translation, cultural adaptation, and pre-testing, the questionnaire was sent to GPs and secondary care clinicians (SCCs) in three regions in the Netherlands. The responses of 445 responders were used to assess the validity and reliability of the questionnaire. Method: A confirmatory factor analysis (CFA) and an exploratory factor analysis (EFA) were performed to study the construct validity of the hypothesised factor model underlying the questionnaire. Test-retest reliability was evaluated using weighted Kappa statistics. Results: Results of the CFA indicated poor fit of the hypothesised factor structure. EFA, executed separately for each region, showed a highly unstable factor structure. The test-retest reliability analysis demonstrated low re-test reliability. Conclusion: The underlying factor structure of a Spanish questionnaire could not be reproduced. The construct validity and reliability of this questionnaire were insufficient to warrant use in the Dutch setting. This study demonstrates the need for evaluating validity and reliability of questionnaires in local settings.

Immunological aging remodels the immune system at several levels. This has been documented in particular for the T-cell receptor (TCR)αβ+ T-cell compartment, showing reduced naive T-cell outputs and an accumulation of terminally differentiated clonally expanding effector T-cells, leading to increased proneness to autoimmunity and cancer development at older age. Even though TCRαβ+ and TCRγδ+ T-cells follow similar paths of development involving V(D)J-recombination of TCR genes in the thymus, TCRγδ+ T-cells tend to be more subjected to peripheral rather than central selection. However, the impact of aging in shaping of the peripheral TRG/TRD repertoire remains largely elusive. Next-generation sequencing analysis methods were optimized based on a spike-in method using plasmid vector DNA-samples for accurate TRG/TRD receptor diversity quantification, resulting in optimally defined primer concentrations, annealing temperatures and cycle numbers. Next, TRG/TRD repertoire diversity was evaluated during TCRγδ+ T-cell ontogeny, showing a broad, diverse repertoire in thymic and cord blood samples with Gaussian CDR3-length distributions, in contrast to the more skewed repertoire in mature circulating TCRγδ+ T-cells in adult peripheral blood. During aging the naive repertoire maintained its diversity with Gaussian CDR3-length distributions, while in the central and effector memory populations a clear shift from young (Vγ9/Vδ2 dominance) to elderly (Vγ2/Vδ1 dominance) was observed. Together with less clear Gaussian CDR3-length distributions, this would be highly suggestive of differentially heavily selected repertoires. Despite the apparent age-related shift from Vγ9/Vδ2 to Vγ2/Vδ1, no clear aging effect was observed on the Vδ2 invariant T nucleotide and canonical Vγ9–Jγ1.2 selection determinants. A more detailed look into the healthy TRG/TRD repertoire revealed known cytomegalovirus-specific TRG/TRD clonotypes in a few donors, albeit without a significant aging-effect, while Mycobacterium tuberculosis-specific clonotypes were absent. Notably, in effector subsets of elderly individuals, we could identify reported TRG and TRD receptor chains from TCRγδ+ T-cell large granular lymphocyte leukemia proliferations, which typically present in the elderly population. Collectively, our results point to relatively subtle age-related changes in the human TRG/TRD repertoire, with a clear shift in Vγ/Vδ usage in memory cells upon aging.

Objective To investigate patients’ perceptions of improvement potential in primary care in 34 countries. Methods We did a cross-sectional survey of 69 201 patients who had just visited general practitioners at primary-care facilities. Patients rated five features of person-focused primary care – accessibility/availability, continuity, comprehensiveness, patient involvement and doctor–patient communication. One tenth of the patients ranked the importance of each feature on a scale of one to four, and nine tenths of patients scored their experiences of care received. We calculated the potential for improvement by multiplying the proportion of negative patient experiences with the mean importance score in each country. Scores were divided into low, medium and high improvement potential. Pair-wise correlations were made between improvement scores and three dimensions of the structure of primary care – governance, economic conditions and workforce development. Findings In 26 countries, one or more features of primary care had medium or high improvement potentials. Comprehensiveness of care had medium to high improvement potential in 23 of 34 countries. In all countries, doctor–patient communication had low improvement potential. An overall stronger structure of primary care was correlated with a lower potential for improvement of continuity and comprehensiveness of care. In countries with stronger primary care governance patients perceived less potential to improve the continuity of care. Countries with better economic conditions for primary care had less potential for improvement of all features of person-focused care. Conclusion In countries with a stronger primary care structure, patients perceived that primary care had less potential for improvement.