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Abstract Background Over the last two decades, substantial investments have been directed towards supporting fundamental and applied research in Alzheimer’s disease (AD), breast cancer (BC), and prostate cancer (PC), which continue to pose significant health challenges. Recently, the Joint Research Centre (JRC) of the European Commission (EC) conducted a retrospective analysis to examine the major scientific advancements resulting from EU-funded research in these disease areas and their impact on society. Methods Building upon this analysis, our subsequent investigation delves into the methodological approaches—both animal and non-animal models and methods—employed in AD, BC, and PC research funded under past EU framework programs (FP5, FP6, FP7, and H2020), and explored the notable research outputs associated with these approaches. Results Our findings indicate a prevalent use of animal-based methodologies in AD research, particularly evident in projects funded under H2020. Notably, projects focused on drug development, testing, or repurposing heavily relied on animal models. Conversely, research aimed at clinical trial design, patient stratification, diagnosis and diagnostic tool development, lifestyle interventions, and prevention—outputs with potential societal impact—more frequently utilised non-animal methods. Advanced investigations leveraging imaging, computational tools, biomarker discovery and organ/tissue chip technologies predominantly favoured non-animal strategies. Conclusions These insights highlight a correlation between methodological choices and the translational potential of research outcomes, suggesting the need for a reconsideration of research strategy planning in future framework programs.

ABSTRACTThe tetanus-diphtheria-acellular pertussis (Tdap) vaccine has been indicated for pregnant women in Quebec, Canada since 2018. Recent literature suggests maternal Tdap interferes with the pneumococcal vaccine response in children exposed in utero because of maternally transferred anti-diphtheria antibodies, a phenomenon known as blunting. Using an indirect cohort study, we investigated whether maternal Tdap vaccination could alter the protection of PCV vaccines against serotype 19A/F IPD (conjugated to diphtheria toxoid in PCV10). Thirty-seven immunized IPD cases (serotype 19A/F) and 90 immunized IPD controls (non-vaccine serotypes) were analyzed using multivariate logistic regression. Our analyses did not identify antenatal Tdap exposure as a risk factor for IPD in vaccinated children, with and odds ratio close to the null (odds ratio = 0.82, 95%CI = 0.32–2.07). As this study is the first to assess the impact of maternal immunization on pneumococcal disease risk, future investigations involving a larger number of cases should be conducted to confirm or infirm our findings.

Abstract Alzheimer’s disease (AD), breast cancer (BC) and prostate cancer (PC) continue to be high in the research and innovation agenda of the European Commission (EC). This is due to their exceptionally large burden to the national health systems, the profound economic effects of opportunity costs attributable to decreased working ability, premature mortality and the ever-increasing demand for both hospital and home-based medical care. Over the last two decades, the EC has been steadily increasing both the number of proposals being funded and the amounts of financial resources being allocated to these fields of research. This trend has continued throughout four consecutive science funding cycles, namely framework programme (FP)5, FP6, FP7 and Horizon 2020 (H2020). We performed a retrospective assessment of the outputs and outcomes of EC funding in AD, BC and PC research over the 1999–2019 period by means of selected indicators. These indicators were assessed for their ability to screen the past, present and future for an array of causal relationships and long-term trends in clinical, epidemiological and public health sphere, while considering also the broader socioeconomic impact of funded research on the society at large. This analysis shows that public–private partnerships with large industry and university-based consortia have led to some of the most impactful proposals being funded over the analysed time period. New pharmaceuticals, small molecules and monoclonal antibodies alike, along with screening and prevention, have been the most prominent sources of innovation in BC and PC, extending patients’ survival and enhancing their quality of life. Unlike oncology, dementia drug development has been way less successful, with only minor improvements related to the quality of supportive medical care for symptoms and more sensitive diagnostics, without any ground-breaking disease-modifying treatment(s). Significant progresses in imaging diagnostics and nanotechnology have been largely driven by the participation of medical device industry multinational companies. Clinical trials funded by the EC were conducted, leading to the development of brand-new drug molecules featuring novel mechanisms of action. Some prominent cases of breakthrough discoveries serve as evidence for the European capability to generate cutting-edge technological innovation in biomedicine. Less productive areas of research may be reconsidered as priorities when shaping the new agenda for forthcoming science funding programmes.

In the past decade, significant European calls for research proposals have supported translational collaborative research on non-communicable and infectious diseases within the biomedical life sciences by bringing together interdisciplinary and multinational consortia. This research has advanced our understanding of disease pathophysiology, marking considerable scientific progress. Yet, it is crucial to retrospectively evaluate these efforts’ societal impact. Research proposals should be thoughtfully designed to ensure that the research findings can be effectively translated into actionable policies. In addition, the choice of scientific methods plays a pivotal role in shaping the societal impact of research discoveries. Understanding the factors responsible for current unmet public health issues and medical needs is crucial for crafting innovative strategies for research policy interventions. A multistakeholder survey and a roundtable helped identify potential needs for consideration in the EU research and policy agenda. Based on survey findings, mental health disorders, metabolic syndrome, cancer, antimicrobial resistance, environmental pollution, and cardiovascular diseases were considered the public health challenges deserving prioritisation. In addition, early diagnosis, primary prevention, the impact of environmental pollution on disease onset and personalised medicine approaches were the most selected unmet medical needs. Survey findings enabled the formulation of some research-policies interventions (RPIs), which were further discussed during a multistakeholder online roundtable. The discussion underscored recent EU-level activities aligned with the survey-derived RPIs and facilitated an exchange of perspectives on public health and biomedical research topics ripe for interdisciplinary collaboration and warranting attention within the EU’s research and policy agenda. Actionable recommendations aimed at facilitating the translation of knowledge into transformative, science-based policies are also provided.

Storing and accessing memories is required to successfully perform day-to-day tasks, for example for engaging in a meaningful conversation. Previous studies in both rodents and primates have correlated hippocampal cellular activity with behavioral expression of memory. A key role has been attributed to awake hippocampal replay – a sequential reactivation of neurons representing a trajectory through space. However, it is unclear if awake replay impacts immediate future behavior, gradually creates and stabilizes long-term memories over a long period of time (hours and longer), or enables the temporary memorization of relevant events at an intermediate time scale (seconds to minutes). In this study, we aimed to address the uncertainty around the timeframe of impact of awake replay by collecting causal evidence from behaving rats. We detected and disrupted sharp wave ripples (SWRs) - signatures of putative replay events - using electrical stimulation of the ventral hippocampal commissure in rats that were trained on three different spatial memory tasks. In each task, rats were required to memorize a new set of locations in each trial or each daily session. Interestingly, the rats performed equally well with or without SWR disruptions. These data suggest that awake SWRs - and potentially replay - does not affect the immediate behavior nor the temporary memorization of relevant events at a short timescale that are required to successfully perform the spatial tasks. Based on these results, we hypothesize that the impact of awake replay on memory and behavior is long-term and cumulative over time.

Abstract Biomedical research on Alzheimer’s disease (AD), breast cancer (BC) and prostate cancer (PC) has globally improved our understanding of the etiopathological mechanisms underlying the onset of these diseases, often with the goal to identify associated genetic and environmental risk factors and develop new medicines. However, the prevalence of these diseases and failure rate in drug development remain high. Being able to retrospectively monitor the major scientific breakthroughs and impact of such investment endeavors is important to re-address funding strategies if and when needed. The EU has supported research into those diseases via its successive framework programmes for research, technological development and innovation. The European Commission (EC) has already undertaken several activities to monitor research impact. As an additional contribution, the EC Joint Research Centre (JRC) launched in 2020 a survey addressed to former and current participants of EU-funded research projects in the fields of AD, BC and PC, with the aim to understand how EU-funded research has contributed to scientific innovation and societal impact, and how the selection of the experimental models may have underpinned the advances made. Further feedback was also gathered through in-depth interviews with some selected survey participants representative of the diverse pre-clinical models used in the EU-funded projects. A comprehensive analysis of survey replies, complemented with the information derived from the interviews, has recently been published in a Synopsis report. Here we discuss the main findings of this analysis and propose a set of priority actions that could be considered to help improving the translation of scientific innovation of biomedical research into societal impact.

Background: Residents of long-term care facilities (LTCFs) and private residences for seniors (PRSs) were given priority for vaccination against coronavirus disease 2019 (COVID-19). Given the shortage of vaccine in the winter of 2021, the Comité sur l’immunisation du Québec recommended postponing the administration of second doses to ensure more rapid and widespread administration of first doses. The objective of this study was to measure the impact of first-dose vaccination on 1) the incidence of cases and complications in LTCFs and PRSs and 2) the frequency of outbreaks in LTCFs. Methods: In this ecological study, COVID-19 incidence and complications in residents of LTCFs and PRSs in Québec were compared with the general (community) population at a point in time when there was still only limited eligibility for vaccination. Results: After vaccination in LTCFs, the incidence rate of COVID-19 decreased by 92% compared with 49% in the community, and deaths decreased by 95%. By six weeks post-vaccination, almost no facility reported five or more cases per 100 beds per week. The incidence rate decreased by 91% in PRSs compared with 2% in the community. Hospitalizations and deaths in PRSs decreased by 94% and 90%, respectively. Conclusion: As a result of 1) vaccination of residents with one dose, 2) natural immunity already acquired in LTCFs and PRSs, 3) vaccination of healthcare workers and 4) other non-pharmaceutical prevention measures implemented, the circulation of the coronavirus in these settings was largely interrupted.

Contexte : Les résidents de centres d’hébergement et de soins de longue durée (CHSLD) et de résidences privées pour aînés (RPA) ont été vaccinés en priorité contre la maladie à coronavirus 2019 (COVID-19). Vu la pénurie de vaccins de l’hiver 2021, le Comité sur l’immunisation du Québec a recommandé le report de l’administration des deuxièmes doses pour augmenter plus rapidement la couverture vaccinale avec une dose. L’objectif de cette étude est de mesurer l’impact de la vaccination avec une première dose sur 1) l’incidence des cas et des complications en CHSLD et en RPA ainsi que 2) sur la fréquence des éclosions en CHSLD. Méthodes : Dans cette étude écologique, le taux d’incidence et de complications de la COVID-19 chez les résidents de CHSLD et de RPA du Québec, ont été comparés à la population générale à un moment où l’éligibilité à la vaccination était encore limitée. Résultats : Après la vaccination en CHSLD, le taux d’incidence de la COVID-19 a diminué de 92 %, contre 49 % dans la communauté, et le nombre de décès a diminué de 95 %. À six semaines post-vaccination, presqu’aucune installation ne rapportait cinq cas ou plus par 100 lits par semaine. En RPA, le taux d’incidence a diminué de 91 %, contre 2 % dans la communauté durant la même période. Les hospitalisations et les décès ont diminué de 94 % et 90 %, respectivement. Conclusion : Suite à 1) la vaccination avec une dose des résidents 2) l’immunité naturelle déjà acquise en CHSLD et en RPA, 3) la vaccination des travailleurs de la santé ainsi que 4) d’autres mesures de prévention non-pharmaceutiques mises en place, la circulation du coronavirus dans ces milieux de vie a été largement interrompue.

Summary: Background: Respiratory viruses have been previously suspected to trigger invasive pneumococcal disease (IPD). After progressive non-pharmaceutical interventions (NPI) lifting, an unusual RSV outbreak has been observed in the Fall 2021, raising concerns about the possible consequences on IPD. We aimed to analyse the evolution of IPD incidence across age-groups since NPI lifting, and its temporal association with respiratory viral infections. Methods: We conducted a time-series analysis using 1) population-based IPD surveillance data and 2) statistics from the laboratory surveillance network of respiratory viruses in the province of Quebec, Canada, from January 2013 to January 2022. The monthly IPD incidence was analysed by quasi-Poisson regression models across age-groups. The fraction of IPD incidence change potentially attributable to different viruses in 2021–2022 was estimated. Findings: A total of 7712 IPD cases were included. After a major decrease in IPD incidence from April 2020, IPD rate started to increase in

Background: In 2008, a school-based human papilloma virus (HPV) vaccination program was implemented in the province of Québec. Grade 4 girls (9–10 years old) are routinely vaccinated and grade 9 to 12 girls (14–17 years old) were eligible for the catch-up vaccination. Vaccine coverage of the targeted cohorts was estimated at 76–81%. To assess if HPV vaccination is associated with an increase in GBS hospitalisation, we compared the hospitalization rates of GBS in HPV vaccination targeted and non-targeted groups. Methods: Hospital discharge records with a GBS code as the main diagnosis during the 1999–2014 period were retrieved. Incidence rates according to program eligibility were computed and adjusted relative risk in the targeted groups was estimated by Poisson regression. Results: The overall incidence rate in the 7 to 17 year-olds was 0.73/100,000 p-y. There was no increase in GBS incidence in HPV vaccination targeted groups (adjusted IRR = 0.81, 95%CI: 0.29–2.26). Conclusion: No signal of increase GBS hospitalisation incidence in the HPV-vaccine targeted group was detected in the hospitalisation database.

The finding of reasonably consistent spatial and temporal productions of actions across different body parts has been used to argue in favor of the existence of a high-order representation of motor programs. In these terms, a generalized motor program consists of an abstract memory structure apt to specify a class of non-specific instructions used to guide a broad range of movements (e.g., “grasp,” “bite”). Although a number of studies, using a variety of tasks, have assessed the issue of effector independence in terms of action execution, little is known regarding the issue of effector independence within an action observation context. Here corticospinal excitability (CSE) of the right hand’s first dorsal interosseous (FDI) and abductor digiti minimi (ADM) muscles was assessed by means of single-pulse transcranial magnetic stimulation (spTMS) during observation of a grasping action performed by the hand, the foot, the mouth, the elbow, or the knee. The results indicate that observing a grasping action performed with different body parts activates the effector typically adopted to execute that action, i.e., the hand. We contend that, as far as grasping is concerned, motor activations by action observation are evident in the muscles typically used to perform the observed action, even when the action is executed with another effector. Nevertheless, some exceptions call for a deeper analysis of motor coding.

Dementia and cancer are becoming increasingly prevalent in Western countries. In the last two decades, research focused on Alzheimer’s disease (AD) and cancer, in particular, breast cancer (BC) and prostate cancer (PC), has been substantially funded both in Europe and worldwide. While scientific research outcomes have contributed to increase our understanding of the disease etiopathology, still the prevalence of these chronic degenerative conditions remains very high across the globe. By definition, no model is perfect. In particular, animal models of AD, BC, and PC have been and still are traditionally used in basic/fundamental, translational, and preclinical research to study human disease mechanisms, identify new therapeutic targets, and develop new drugs. However, animals do not adequately model some essential features of human disease; therefore, they are often unable to pave the way to the development of drugs effective in human patients. The rise of new technological tools and models in life science, and the increasing need for multidisciplinary approaches have encouraged many interdisciplinary research initiatives. With considerable funds being invested in biomedical research, it is becoming pivotal to define and apply indicators to monitor the contribution to innovation and impact of funded research. Here, we discuss some of the issues underlying translational failure in AD, BC, and PC research, and describe how indicators could be applied to retrospectively measure outputs and impact of funded biomedical research.

Using an organotypic culture system termed human Fetal Testis Assay (hFeTA) we previously showed that 0.01 μM BPA decreases basal, but not LH-stimulated, testosterone secreted by the first trimester human fetal testis. The present study was conducted to determine the potential for a long-term antiandrogenic effect of BPA using a xenograft model, and also to study the effect of BPA on germ cell development using both the hFETA and xenograft models.Using the hFeTA system, first trimester testes were cultured for 3 days with 0.01 to 10 μM BPA. For xenografts, adult castrate male nude mice were injected with hCG and grafted with first trimester testes. Host mice received 10 μM BPA (~ 500 μg/kg/day) in their drinking water for 5 weeks. Plasma levels of total and unconjugated BPA were 0.10 μM and 0.038 μM respectively. Mice grafted with second trimester testes received 0.5 and 50 μg/kg/day BPA by oral gavage for 5 weeks.With first trimester human testes, using the hFeTA model, 10 μM BPA increased germ cell apoptosis. In xenografts, germ cell density was also reduced by BPA exposure. Importantly, BPA exposure significantly decreased the percentage of germ cells expressing the pluripotency marker AP-2γ, whilst the percentage of those expressing the pre-spermatogonial marker MAGE-A4 significantly increased. BPA exposure did not affect hCG-stimulated androgen production in first and second trimester xenografts as evaluated by both plasma testosterone level and seminal vesicle weight in host mice.Exposure to BPA at environmentally relevant concentrations impairs germ cell development in first trimester human fetal testis, whilst gonadotrophin-stimulated testosterone production was unaffected in both first and second trimester testis. Studies using first trimester human fetal testis demonstrate the complementarity of the FeTA and xenograft models for determining the respective short-term and long term effects of environmental exposures.

Background. In Canada, the current recommendation is to offer PPV23 to adults ≥ 65 years. PCV13 is now licensed for adults. Methods. Invasive pneumococcal disease (IPD) cases in adults 65–74 years of age in the Quebec notifiable diseases registry were classified into five serotype categories. Poisson regression models were fitted to monthly rates observed in 2000–2014 and predictions were made for 2015–2024, using theoretical assumptions regarding indirect effects of childhood vaccination and serotype replacement. Results. IPD rates caused by PCV7 serotypes decreased markedly since PCV7 introduction for children in December 2004. This trend is also underway for additional PCV13 serotypes except serotype 3. Additional PPV23 serotypes and nonvaccine serotypes have been on rise since 2004 and this is expected to continue. A small decrease in overall IPD incidence in the next decade is predicted. The proportion of PCV13 serotypes represented 33% of IPD cases in 2014 and would be 20% (95% CI: 15% to 28%) in 2024. PPV23 coverage was 53% in 2014 and is expected to be 47% (95% CI: 26% to 85%) in 2024. Conclusion. The potential usefulness of a combined PCV13 + PPV23 program for elderly adults would decrease over time but PCV13 would be the only option to prevent serotype 3 IPD.

Few studies have been undertaken to assess the possible effects of bisphenol A (BPA) on the reproductive hormone balance in animals or humans with often contradictory results. We investigated possible direct endocrine disruption by BPA of the fetal testes of 2 rat strains (14.5-17.5 days post-coitum) and humans (8-12 gestational weeks) and under different culture conditions. BPA concentrations of 10(-8)M and 10(-5)M for 72 h reduced testosterone production by the Sprague-Dawley fetal rat testes, while only 10-5M suppressed it in the Wistar strain. The suppressive effects at 10-5M were seen as early as 24h and 48 h in both strains. BPA at 10(-7)-10(-5)M for 72 h suppressed the levels of fetal rat Leydig cell insulin-like factor 3 (INSL3). BPA exposure at 10(-8)M, 10(-7)M, and 10(-5)M for 72 h inhibited testosterone production in fetal human testes. For the lowest doses, the effects observed occurred only when no gonadotrophin was added to the culture media and were associated with a poorly preserved testicular morphology. We concluded that (i) BPA can display anti-androgenic effects both in rat and human fetal testes; (ii) it is essential to ascertain that the divergent effects of endocrine disruptors between species in vitro do not result from the culture conditions used, and/or the rodent strain selected; (iii) the optimization of each in vitro assay for a given species should be a major objective rather than the search of an hypothetical trans-species consensual model-system, as the organization of the testis is intrinsically different between mammalian species; (iv) due to the uncertainty existing on the internal exposure of the human fetal testis to BPA, and the insufficient number of epidemiological studies on the endocrine disruptive effects of BPA, caution should be taken in the extrapolation of our present results to the human reproductive health after fetal exposure to BPA.

CONTEXT:An association between an adjuvanted (AS03) A/H1N1 pandemic vaccine and narcolepsy has been reported in Europe. OBJECTIVE:To assess narcolepsy risk following administration of a similar vaccine in Quebec. DESIGN:Retrospective population-based study. SETTING:Neurologists and lung specialists in the province were invited to report narcolepsy cases to a single reference centre. POPULATION:Patients were interviewed by two sleep experts and standard diagnostic tests were performed. Immunization status was verified in the provincial pandemic influenza vaccination registry. MAIN OUTCOME MEASURES:Confirmed narcolepsy with or without cataplexy with onset of excessive daytime sleepiness between January 1st, 2009, and December 31st, 2010. Relative risks (RRs) were calculated using a Poisson model in a cohort analysis, by a self-controlled case series (SCCS) and a case-control method. RESULTS:A total of 24 cases were included and overall incidence rate was 1.5 per million person-years. A cluster of 7 cases was observed among vaccinated persons in the winter 2009-2010. In the primary cohort analysis, 16-week post-vaccination RR was 4.32 (95% CI: 1.50-11.12). RR was 2.07 (0.70-6.17) in the SCCS, and 1.48 (0.37-7.03) using the case-control method. Estimates were lower when observation was restricted to the period of pandemic influenza circulation, and tended to be higher in persons

BACKGROUND: A chickenpox vaccine was recently licensed in Canada. Because this vaccine has caused some controversy within the health care profession, studies among Quebec parents and vaccine providers were carried out, surveying their opinions concerning chickenpox vaccination.

BACKGROUND: In order to inform meningococcal disease prevention strategies, we analysed the epidemiology of invasive meningococcal disease (IMD) in the province of Quebec, Canada, 10 years before and 10 years after the introduction of serogroup C conjugate vaccination. METHODOLOGY: IMD cases reported to the provincial notifiable disease registry in 1991-2011 and isolates submitted for laboratory surveillance in 1997-2011 were analysed. Serogrouping, PCR testing and assignment of isolates to sequence types (ST) by using multilocus sequence typing (MLST) were performed. RESULTS: Yearly overall IMD incidence rates ranged from 2.2-2.3/100,000 in 1991-1992 to 0.49/100,000 in 1999-2000, increasing to 1.04/100,000 in 2011. Among the 945 IMD cases identified by laboratory surveillance in 1997-2011, 68%, 20%, 8%, and 3% were due to serogroups B, C, Y, and W135, respectively. Serogroup C IMD almost disappeared following the implementation of universal childhood immunization with monovalent C conjugate vaccines in 2002. Serogroup B has been responsible for 88% of all IMD cases and 61% of all IMD deaths over the last 3 years. The number and proportion of ST-269 clonal complex has been steadily increasing among the identified clonal complexes of serogroup B IMD since its first identification in 2003, representing 65% of serogroup B IMD in 2011. This clonal complex was first introduced in adolescent and young adults, then spread to other age groups. CONCLUSION: Important changes in the epidemiology of IMD have been observed in Quebec during the last two decades. Serogroup C has been virtually eliminated. In recent years, most cases have been caused by the serogroup B ST-269 clonal complex. Although overall burden of IMD is low, the use of a vaccine with potential broad-spectrum coverage could further reduce the burden of disease. Acceptability, feasibility and cost-effectiveness studies coupled with ongoing clinical and molecular surveillance are necessary in guiding public policy decisions.

To identify recent trends in invasive meningococcal diseases (IMD) in Quebec, Canada, with a focus on MenY cases and MenY strains. IMD cases and MenY strains from January 1, 2015 to August 11, 2023 were analyzed for clonal analysis and prediction of susceptibility to MenB vaccines. MenY strains of ST-23 CC from Quebec were analyzed with global MenY strains by core-genomic multi-locus sequence typing (cg-MLST). Since 2015 the serogroup distribution of IMD in Quebec has shifted from predominantly MenB to mainly MenY, with most (80.9 %) of the latter belonging to ST-23 CC. The median age of MenY cases due to ST-23 CC were statistically younger than MenY cases due to non-ST-23 CC. MenY of ST-23 CC showed genetic diversity and the major genetic cluster were similar to the Swedish Y1 strain. The increase in invasive MenY disease in Quebec was due to a sub-clade of Lineage 23.1 which caused an elevated proportion of severe disease in young adults. The increase in invasive MenY disease in Quebec, Canada was driven by the expansion of a sub-clade of Lineage 23.1 in young adults. Currently available quadrivalent A,C,W,Y-conjugate meningococcal vaccines were predicted to provide protection against these strains. • Since 2015 IMD cases in Quebec has shifted from largely MenB to predominantly MenY. • Increase in MenY was due to the ST-23 clonal complex causing IMD in young people. • cg-MLST of Quebec ST-23 CC MenY revealed three distinct clades. • Quebec ST-23 CC MenY were related to international MenY Lineages. • A sub-clade of Lineage 23.1 caused MenY disease in young adults with severe disease. [ABSTRACT FROM AUTHOR]

Abstract Background Vaccine coverage (VC) at a given age is a widely-used indicator for measuring the performance of vaccination programs. However, there is increasing data suggesting that measuring delays in administering vaccines complements the measure of VC. Providing feedback to vaccinators is recognized as an effective strategy for improving vaccine coverage, but its implementation has not been widely documented in Canada. The objective of this study was to evaluate the feasibility of providing personalized feedback to vaccinators and its impact on vaccination delays (VD). Methods In April and May 2008, a one-hour personalized feedback session was provided to health professionals in vaccinating medical clinics in the Quebec City region. VD for vaccines administered at two and twelve months of age were presented. Data from the regional vaccination registry were analysed for participating clinics. Two 12-month periods before and after the intervention were compared, namely from April 1st, 2007 to March 31st, 2008 and from June 1st, 2008 to May 31st, 2009. Results Ten medical clinics out of the twelve approached (83%), representing more than 2500 vaccinated children, participated in the project. Preparing and conducting the feedback involved 20 hours of work and expenses of $1000 per clinic. Based on a delay of one month, 94% of first doses of DTaP-Polio-Hib and 77% of meningococcal vaccine doses respected the vaccination schedule both before and after the intervention. Following the feedback, respect of the vaccination schedule increased for vaccines planned at 12 months for the four clinics that had modified their vaccination practices related to multiple injections (depending on the clinic, VD decreased by 24.4%, 32.0%, 40.2% and 44.6% respectively, p < 0.001 for all comparisons). Conclusions The present study shows that it is feasible to provide personalized feedback to vaccinating clinics. While it may have encouraged positive changes in practice concerning multiple injections, this intervention on its own did not impact vaccination delays of the clinics visited. It is possible that feedback integrated into other types of effective interventions and sustained over time may have more impact on VD.

Abstract: Seabirds are increasingly threatened worldwide, with population declines for many species that are faster than in any other group of birds. Here the Important Bird Area (IBA) criteria recommended by BirdLife International were applied to a large tracking dataset collected from a range of seabirds, to identify areas of importance at an ocean basin scale. Key areas were identified using tracks obtained from both the breeding and non-breeding periods of 10 species that have different habitat requirements. These species range in their IUCN threat status from Least Concern to Critically Endangered. An evaluation of spatial overlap between the key areas for these species and the jurisdiction of Regional Fisheries Management Organisations (RFMOs), national Exclusive Economic Zones (EEZs) and other stakeholder bodies highlighted the major importance of the French EEZs (around Crozet, Kerguelen and Amsterdam Islands) for seabird conservation. The majority of the candidate marine IBAs that were identified were located in the High Seas, where Marine Protected Areas cannot easily be designated under existing international agreements, except in the Commission for the Conservation of Antarctic Marine Living Resources Convention Area. In the short term, it seems that only fisheries regulations (through international agreements) can bring about efficient protection for seabirds in the High Seas. The BirdLife IBA approach, although sensitive to heterogeneity in the data (species selected, inclusion of different life stages, years etc.), proved valuable for selecting important areas corresponding to large-scale oceanographic structures that are considered to be key foraging habitats for many species. [Copyright &y& Elsevier]

The Japanese Tower dates from 1904 and was designed by the French architect Alexandre Marcel at the request of King Leopold II of Belgium. The Tower is a timber building constructed by European craftsmen. The remarkable interior decoration consists of European materials and elements shipped from Japan. A rich variety of decoration techniques and materials were found during recent preliminary research into the architectural paintwork. The major challenge facing the researchers was the identification and differentiation of Japanese and European interventions on the interior decoration. The rediscovery and research of the sumptuous interior decoration of the Japanese Tower, including the many items brought from Japan, provides a unique insight into Meiji era Japonisme in Europe and cultural relations between Europe and Japan at the turn of the twentieth century. [ABSTRACT FROM AUTHOR]

Background: Composite Y-grafts, using the left internal thoracic artery as the inflow, allow a more efficient use of conduits without the need to touch a diseased ascending aorta. Among other conduits, the saphenous vein graft may be an alternative to the radial artery in elderly patients. Patients and Methods: We evaluated the hemodynamic characteristics of 17 composite Y-grafts made with the left internal thoracic artery anastomosed to the left anterior descending coronary artery in all cases and with either the free right internal thoracic artery (RITA group, n = 10) or a saphenous vein graft (SVG group, n = 7) implanted proximally to the left internal thoracic artery and distally to the circumflex territory 6 months after the operation. Results: At baseline, the pressure gradient measured with a 0.014-inch pressure wire was minimal between the aorta and the internal thoracic artery stem (2 ± 1 mm Hg), the internal thoracic artery and left anterior descending (4 ± 2 mm Hg), the internal thoracic artery and left circumflex (3 ± 1 mm Hg), and the saphenous vein graft and left circumflex (2 ± 2 mm Hg). During hyperemia induced by adenosine, the pressure gradient increased significantly to 6 ± 2 mm Hg in the internal thoracic artery stem, 9 ± 4 mm Hg in the internal thoracic artery and left anterior descending artery, 9 ± 3 mm Hg in the internal thoracic artery and left circumflex, and 7 ± 4 mm Hg in the saphenous vein graft and left circumflex. Fractional flow reserve was 0.94 ± 0.02 in internal thoracic artery stem, 0.90 ± 0.04 mm Hg in the internal thoracic artery and left anterior descending, 0.91 ± 0.03 mm Hg in the internal thoracic artery and left circumflex, and 0.92 ± 0.06 mm Hg in the saphenous vein graft and left circumflex. No difference between the two types of composite Y-grafts was observed for pressure gradients or fractional flow reserve measured in internal thoracic artery stem or in distal branches. Conclusions: Composite Y-grafts with saphenous vein or right internal thoracic arteries allow similar and adequate reperfusion of the left system with minimal resistance to maximal flow and an even distribution of flow in both distal branches. [Copyright &y& Elsevier]