High-pressure lattice dynamics in wurtzite and rocksalt indium nitride investigated by means of Raman spectroscopy

We present an experimental and theoretical lattice-dynamical study of InN at high hydrostatic pressures. We perform Raman scattering measurements on five InN epilayers, with different residual strain and free electron concentrations. The experimental results are analyzed in terms of ab initio lattice-dynamical calculations on both wurtzite InN (w-InN) and rocksalt InN (rs-InN) as a function of pressure. Experimental and theoretical pressure coefficients of the optical modes in w-InN are compared, and the role of residual strain on the measured pressure coefficients is analyzed. In the case of the LO band, we analyze and discuss its pressure behavior considering the double-resonance mechanism responsible for the selective excitation of LO phonons with large wave vectors in w-InN. The pressure behavior of the L− coupled mode observed in a heavily doped n-type sample allows us to estimate the pressure dependence of the electron effective mass in w-InN. The results thus obtained are in good agreement with k⋅p theory. The wurtzite-to-rocksalt phase transition on the upstroke cycle and the rocksalt-to-wurtzite backtransition on the downstroke cycle are investigated, and the Raman spectra of both phases are interpreted in terms of DFT lattice-dynamical calculations. ©2013 American Physical SocietyWork was supported by the Spanish Ministerio de Economia y Competitividad through Projects MAT2010-16116, MAT2010-21270-C04-04 and MALTA Consolider Ingenio 2010 (CSD2007-00045).Ibánez, J.; Oliva, R.; Manjón Herrera, FJ.; Segura, A.; Yamaguchi, T.; Nanishi, Y.; Cuscó, R.... (2013). High-pressure lattice dynamics in wurtzite and rocksalt indium nitride investigated by means of Raman spectroscopy. Physical Review B. 88:115202-1-115202-13. https://doi.org/10.1103/PhysRevB.88.115202S115202-1115202-1388Wu, J. (2009). When group-III nitrides go infrared: New properties and perspectives. Journal of Applied Physics, 106(1), 011101. doi:10.1063/1.3155798Pinquier, C., Demangeot, F., Frandon, J., Pomeroy, J. W., Kuball, M., Hubel, H., … Gil, B. (2004). Raman scattering in hexagonal InN under high pressure. Physical Review B, 70(11). doi:10.1103/physrevb.70.113202Pinquier, C., Demangeot, F., Frandon, J., Chervin, J.-C., Polian, A., Couzinet, B., … Maleyre, B. (2006). Raman scattering study of wurtzite and rocksalt InN under high pressure. Physical Review B, 73(11). doi:10.1103/physrevb.73.115211Yao, L. D., Luo, S. D., Shen, X., You, S. J., Yang, L. X., Zhang, S. J., … Xie, S. S. (2010). Structural stability and Raman scattering of InN nanowires under high pressure. Journal of Materials Research, 25(12), 2330-2335. doi:10.1557/jmr.2010.0290Ibáñez, J., Manjón, F. J., Segura, A., Oliva, R., Cuscó, R., Vilaplana, R., … Artús, L. (2011). High-pressure Raman scattering in wurtzite indium nitride. 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High-pressure behavior of the bond-bending mode of AIN. Journal of Experimental and Theoretical Physics, 98(5), 981-985. doi:10.1134/1.1767565Ibáñez, J., Segura, A., García-Domene, B., Oliva, R., Manjón, F. J., Yamaguchi, T., … Artús, L. (2012). High-pressure optical absorption in InN: Electron density dependence in the wurtzite phase and reevaluation of the indirect band gap of rocksalt InN. Physical Review B, 86(3). doi:10.1103/physrevb.86.035210Serrano, J., Romero, A. H., Manjón, F. J., Lauck, R., Cardona, M., & Rubio, A. (2004). Pressure dependence of the lattice dynamics of ZnO: Anab initioapproach. Physical Review B, 69(9). doi:10.1103/physrevb.69.094306Cuscó, R., Ibáñez, J., Domenech-Amador, N., Artús, L., Zúñiga-Pérez, J., & Muñoz-Sanjosé, V. (2010). Raman scattering of cadmium oxide epilayers grown by metal-organic vapor phase epitaxy. Journal of Applied Physics, 107(6), 063519. doi:10.1063/1.3357377Cuscó, R., Alarcón-Lladó, E., Ibáñez, J., Yamaguchi, T., Nanishi, Y., & Artús, L. (2009). Raman scattering study of background electron density in InN: a hydrodynamical approach to the LO-phonon–plasmon coupled modes. Journal of Physics: Condensed Matter, 21(41), 415801. doi:10.1088/0953-8984/21/41/415801Cuscó, R., Ibáñez, J., Alarcón-Lladó, E., Artús, L., Yamaguchi, T., & Nanishi, Y. (2009). Photoexcited carriers and surface recombination velocity in InN epilayers: A Raman scattering study. Physical Review B, 80(15). doi:10.1103/physrevb.80.155204Wang, X., Che, S.-B., Ishitani, Y., & Yoshikawa, A. (2006). Experimental determination of strain-free Raman frequencies and deformation potentials for the E2 high and A1(LO) modes in hexagonal InN. Applied Physics Letters, 89(17), 171907. doi:10.1063/1.2364884Perlin, P., Jauberthie-Carillon, C., Itie, J. P., San Miguel, A., Grzegory, I., & Polian, A. (1992). 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Mortalidad de los hombres y las mujeres de 20 a 64 años. Medellín, 1994-2003.

"El presente documento pretende caracterizar la mortalidad de la población adulta de 20 a 64 años residente en la ciudad de Medellín, entre los años 1994 a 2003, según causa de muerte y sexo.

Mortalidad de los hombres y las mujeres de 20 a 64 años. Medellín, 1994-2003

Objetivo: caracterizar la mortalidad de la población adulta de 20 a 64 años residente en la ciudad de Medellín, entre los años 1994 a 2003, según causa de muerte y sexo. Materiales y métodos: estudio descriptivo longitudinal retrospectivo de las principales causas de muerte de los adultos de Medellín; con fuente de información secundaria de los certificados de defunción registrados por el Departamento Administrativo Nacional de Estadísticas DANE en la década 1994-2003. Resultados: durante los diez años de estudio, entre las primeras causas de muerte se evidenció que las agresiones cobraron el mayor número de víctimas, especialmente los causados por ataques con armas de fuego y explosivos y con instrumentos cortantes y punzantes, en los hombres y mujeres entre 20 y 44 años. El infarto agudo del miocardio para los hombres y mujeres entre los 45 y 64 años de edad ocasionó un gran número de muertes en este grupo poblacional. A pesar de no presentarse el Síndrome de Inmunodeficiencia Adquirida entre las primeras causas se muerte, sí se manifestó durante los últimos años de estudio en hombres y mujeres con edades de 20 a 44 años; para las mujeres ocupó la quinta causa durante 1998 y 1999 y para los hombres la tercera causa durante los últimos tres años 1997, 1998 y 1999. Conclusiones: las causas de fallecimiento de los hombres adultos de 20 a 64 años residentes en Medellín, ocurridas en la década 1994-2003, estuvieron origen en una causa externa y en enfermedades del sistema circulatorio; las defunciones de las mujeres en este mismo rango de edad fueron originadas por tumores o neoplasias y en enfermedades del sistema circulatorio, mostrando el mayor riesgo al que están expuestos los hombres de morir por causa violenta inflingida o autoinflingida que las mujeres (OR=7,73) y las mujeres presentan un riesgo mayor que los hombres de morir a causa de tumor o neoplasia (OR=4,66). AbstractTarget: to characterize the mortality of the adult population from 20 to 64 years old, resident in the city of Medellín, between the year 1994 to 2003, according to the cause of death and sex, Materials and methods; descriptive longitudinal retrospective study of the main causes of death of the adults of Medellín; with source of secondary information from the certificates of death registered by the Administrative National Department of Statistics in the decade 1994-2003. Results: During ten years of study, among the first causes of death it was shown that the aggressions resulted in the biggest number of victims, especially the ones caused by attacks with firearms and explosives and with cutting and pointed instruments, in men and women between 20 and 44 years. The acute infarct of the myocardium for men and women between 45 and 64 years of age caused a large number of deaths in this opulation group. In spite of the fact that deaths resulting from the Acquired Immunodeficiency Syndrome was not among the first causes of death, the Syndrome appeared during the last years of study in men and women with ages from 20 to 44 years. For the women it occupied the fifth cause during 1998 and 1999 and for the men the third cause during the last three years 1997, 1998 and 1999. Conclusions: The causes of death of adult men from 20 to 64 years old, resident ofMedellín, that took place in the decade 1994-2003, were the result of an external cause and of illnesses of the circulatory system. The deaths of women in the same group of age were caused by tumors or neoplasias and by illnesses of the circulatory system. This shows the biggest risk to which the men are exposed of dying as result of violent cause, both received o self-inflicted in comparison with women (OR=7,73), and women have a higher risk than men of dying from tumor or neoplasia (OR=4,66).Key words: Mortality, cause of death, Medellín

Characterization of service times and of women with breast cancer who attended in a hospital, 2005-2009

ABSTRACT: To characterize the clinical and sociodemographic profiles of women with breast cancer treated at the Oncology Unit of the Federico Lleras Acosta Hospital in Ibagué, Colombia between 2005 and 2009, and to identify service times. Methodology: a retrospective descriptive study in which 308 records were selected. Variables were collected using an instrument developed by the authors. The statistical analysis was conducted using the SPSS software. Results: the predominant age group was 45 to 64 years old. Additionally, 57.8% of these women were married. Similarly, most of them were from urban areas. The average age of menarche was 13 years. Half of the participants had been pregnant at least 3 times, and most of them were in the postmenopausal stage of their lives. The most frequent histological type was the infiltrating ductal one, as well as stage IIIB. The predominant surgical choices were modified radical mastectomy, pre- and post-operative chemotherapy, and postoperative radiotherapy. As for service times, there were delays in the admission to the oncology unit and treatment initiation. Conclusion: there was a low rate of carcinoma in situ and a high proportion of stage IV carcinoma in comparison to other studies from developed countries. The high rates of abandonment in post treatment follow-up, the shortcomings in case monitoring, and the findings concerning service times suggest the need for institutional corrective measures in order to improve the quality of the healthcare service in breast cancer patients.RESUMEN: Caracterizar el perfil sociodemográfico y clínico de mujeres con cáncer de mama tratadas en la Unidad Oncológica del Hospital Federico Lleras Acosta de Ibagué entre 2005 y 2009, e identificar tiempos de atención. Metodología: estudio descriptivo retrospectivo con selección de 308 historias clínicas, recolección de variables en un instrumento elaborado y análisis estadístico con el programa spss. Resultados: predominante el grupo de 45 a 64 años, casadas, provenientes de zonas urbanas, edad promedio de menarquia de 13 años, al menos 3 gestas y postmenopáusicas. El tipo histológico canalicular infiltrante fue el más frecuente, así como el estadio IIIB. La mastectomía radical modificada fue la elección quirúrgica predominante, al igual que la quimioterapia pre y postoperatoria y la radioterapia postoperatoria. En los tiempos de atención se evidenciaron demoras en el ingreso e inicio del tratamiento. Conclusión: un bajo porcentaje de carcinoma in situ y mayor proporción de estadio IV respecto a países desarrollados. Una alta proporción de abandono en controles postratamiento y fallas en seguimiento de casos, así como los hallazgos en tiempos de atención plantean la necesidad de correctivos institucionales para mejorar la calidad del servicio de salud en cáncer de mama

Neuroprotective Actions of Estradiol and Novel Estrogen Analogs in Ischemia: Translational Implications

This review highlights our investigations into the neuroprotective efficacy of estradiol and other estrogenic agents in a clinically relevant animal model of transient global ischemia, which causes selective, delayed death of hippocampal CA1 neurons and associated cognitive deficits. We find that estradiol rescues a significant number of CA1 pyramidal neurons that would otherwise die in response to global ischemia, and this is true when hormone is provided as a long-term pretreatment at physiological doses or as an acute treatment at the time of reperfusion. In addition to enhancing neuronal survival, both forms of estradiol treatment induce measurable cognitive benefit in young animals. Moreover, estradiol and estrogen analogs that do not bind classical nuclear estrogen receptors retain their neuroprotective efficacy in middle-aged females deprived of ovarian hormones for a prolonged duration (8 weeks). Thus, non-feminizing estrogens may represent a new therapeutic approach for treating the neuronal damage associated with global ischemia

Nuclear translocation of glutaminase GLS2 in human cancer cells associates with proliferation arrest and differentiation

Glutaminase (GA) catalyzes the first step in mitochondrial glutaminolysis playing a key role in cancer metabolic reprogramming. Humans express two types of GA isoforms: GLS and GLS2. GLS isozymes have been consistently related to cell proliferation, but the role of GLS2 in cancer remains poorly understood. GLS2 is repressed in many tumor cells and a better understanding of its function in tumorigenesis may further the development of new therapeutic approaches. We analyzed GLS2 expression in HCC, GBM and neuroblastoma cells, as well as in monkey COS-7 cells. We studied GLS2 expression after induction of differentiation with phorbol ester (PMA) and transduction with the full-length cDNA of GLS2. In parallel, we investigated cell cycle progression and levels of p53, p21 and c-Myc proteins. Using the baculovirus system, human GLS2 protein was overexpressed, purified and analyzed for posttranslational modifications employing a proteomics LC-MS/MS platform. We have demonstrated a dual targeting of GLS2 in human cancer cells. Immunocytochemistry and subcellular fractionation gave consistent results demonstrating nuclear and mitochondrial locations, with the latter being predominant. Nuclear targeting was confirmed in cancer cells overexpressing c-Myc- and GFP-tagged GLS2 proteins. We assessed the subnuclear location finding a widespread distribution of GLS2 in the nucleoplasm without clear overlapping with specific nuclear substructures. GLS2 expression and nuclear accrual notably increased by treatment of SH-SY5Y cells with PMA and it correlated with cell cycle arrest at G2/M, upregulation of tumor suppressor p53 and p21 protein. A similar response was obtained by overexpression of GLS2 in T98G glioma cells, including downregulation of oncogene c-Myc. Furthermore, human GLS2 was identified as being hypusinated by MS analysis, a posttranslational modification which may be relevant for its nuclear targeting and/or function. Our studies provide evidence for a tumor suppressor role of GLS2 in certain types of cancer. The data imply that GLS2 can be regarded as a highly mobile and multilocalizing protein translocated to both mitochondria and nuclei. Upregulation of GLS2 in cancer cells induced an antiproliferative response with cell cycle arrest at the G2/M phase

Real-Time PCR Improves Helicobacter pylori Detection in Patients with Peptic Ulcer Bleeding

Background and aims: Histological and rapid urease tests to detect H. pylori in biopsy specimens obtained during peptic ulcer bleeding episodes (PUB) often produce false-negative results. We aimed to examine whether immunohistochemistry and real-time PCR can improve the sensitivity of these biopsies. Patients and Methods: We selected 52 histology-negative formalin-fixed paraffin-embedded biopsy specimens obtained during PUB episodes. Additional tests showed 10 were true negatives and 42 were false negatives. We also selected 17 histology-positive biopsy specimens obtained during PUB to use as controls. We performed immunohistochemistry staining and real-time PCR for 16S rRNA, ureA, and 23S rRNA for H. pylori genes on all specimens. Results: All controls were positive for H. pylori on all PCR assays and immunohistochemical staining. Regarding the 52 initially negative biopsies, all PCR tests were significantly more sensitive than immunohistochemical staining (p<0.01). Sensitivity and specificity were 55% and 80% for 16S rRNA PCR, 43% and 90% for ureA PCR, 41% and 80% for 23S rRNA PCR, and 7% and 100% for immunohistochemical staining, respectively. Combined analysis of PCR assays for two genes were significantly more sensitive than ureA or 23S rRNA PCR tests alone (p<0.05) and marginally better than 16S rRNA PCR alone. The best combination was 16S rRNA+ureA, with a sensitivity of 64% and a specificity of 80%. Conclusions: Real-time PCR improves the detection of H. pylori infection in histology-negative formalin-fixed paraffin-embedded biopsy samples obtained during PUB episodes. The low reported prevalence of H. pylori in PUB may be due to the failure of conventional tests to detect infection

Safety and efficacy of GABAA α5 antagonist S44819 in patients with ischaemic stroke: a multicentre, double-blind, randomised, placebo-controlled trial

Background: S44819, a selective GABAA α5 receptor antagonist, reduces tonic post-ischaemic inhibition of the peri-infarct cortex. S44819 improved stroke recovery in rodents and increased cortical excitability in a transcranial magnetic stimulation study in healthy volunteers. The Randomized Efficacy and Safety Trial of Oral GABAA α5 antagonist S44819 after Recent ischemic Event (RESTORE BRAIN) aimed to evaluate the safety and efficacy of S44819 for enhancing clinical recovery of patients with ischaemic stroke. Methods: RESTORE BRAIN was an international, randomised, double-blind, parallel-group, placebo-controlled, multicentre phase 2 trial that evaluated the safety and efficacy of oral S44189 in patients with recent ischaemic stroke. The study was done in specialised stroke units in 92 actively recruiting centres in 14 countries: ten were European countries (Belgium, Czech Republic, France, Germany, Hungary, Italy, Netherlands, Poland, Spain, and the UK) and four were non-European countries (Australia, Brazil, Canada, and South Korea). Patients aged 18–85 years with acute ischaemic stroke involving cerebral cortex (National Institute of Health Stroke Scale [NIHSS] score 7–20) without previous disability were eligible for inclusion. Participants were randomly assigned to receive 150 mg S44819 twice a day, 300 mg S44819 twice a day, or placebo twice a day by a balanced, non-adaptive randomisation method with a 1:1:1 ratio. Treatment randomisation and allocation were centralised via the interactive web response system using computer-generated random sequences with a block size of 3. Blinding of treatment was achieved by identical appearance and taste of all sachets. Patients, investigators and individuals involved in the analysis of the trial were masked to group assignment. The primary endpoint was the modified Rankin Scale (mRS) score 90 days from onset of treatment, evaluated by shift analysis (predefined main analysis) or by dichotomised analyses using 0–1 versus 2–6 and 0–2 versus 3–6 cutoffs (predefined secondary analysis). Secondary endpoints were the effects of S44819 on the NIHSS and Montreal Cognitive Assessment (MoCA) scores, time needed to complete parts A and B of the Trail Making Test, and the Barthel index. Efficacy analyses were done on all patients who received at least one dose of treatment and had at least one mRS score taken after day 5 (specifically, on or after day 30). Safety was compared across treatment groups for all patients who received at least one dose of treatment. The study was registered at ClinicalTrials.gov, NCT02877615. Findings: Between Dec 19, 2016, and Nov 16, 2018, 585 patients were enrolled in the study. Of these, 197 (34%) were randomly assigned to receive 150 mg S44819 twice a day, 195 (33%) to receive 300 mg S44819 twice a day, and 193 (33%) to receive placebo twice a day. 189 (96%) of 197 patients in the 150 mg S44819 group, 188 (96%) of 195 patients in the 300 mg S44819 group, and 191 (99%) patients in the placebo group received at least one dose of treatment and had at least one mRS score taken after day 5, and were included in efficacy analyses. 195 (99%) of 197 patients in the 150 mg S44819 group, 194 (99%) of 195 patients in the 300 mg S44819 group, and 193 (100%) patients in the placebo group received at least one dose of treatment, and were included in safety analyses. The primary endpoint of mRS at day 90 did not differ between each of the two S44819 groups and the placebo group (OR 0·91 [95% CI 0·64–1·31]; p=0·80 for 150 mg S44819 compared with placebo and OR 1·17 [95% CI 0·81–1·67]; p=0·80 for 300 mg S44819 compared with placebo). Likewise, dichotomised mRS scores at day 90 (mRS 0–2 vs 3–6 or mRS 0–1 vs 2–6) did not differ between groups. Secondary endpoints did not reveal any significant group differences. The median NIHSS score at day 90 did not differ between groups (4 [IQR 2–8] in 150 mg S44819 group, 4 [2–7] in 300 mg S44819 group, and 4 [2–6] in placebo group), nor did the number of patients at day 90 with an NIHSS score of up to 5 (95 [61%] of 156 in 150 mg S44819 group, 106 [66%] of 161 in 300 mg S44819 group, and 104 [66%] of 157 in placebo group) versus more than 5 (61 [39%] in 150 mg S44819 group, 55 [34%] in 300 mg S44819 group, and 53 [34%] in placebo group). Likewise, the median MoCA score (22·0 [IQR 17·0–26·0] in 150 mg S44819 group, 23·0 [19·0–26·5] in 300 mg S44819 group, and 22·0 [17·0–26·0] in placebo group), time needed to complete parts A (50 s [IQR 42–68] in 150 mg S44819 group, 49 s [36–63] in 300 mg S44819 group, and 50 s [38–68] in placebo group) and B (107 s [81–144] in 150 mg S44819 group, 121 s [76–159] in 300 mg S44819 group, and 130 s [86–175] in placebo group) of the Trail Making Test, and the Barthel index (90 [IQR 60–100] in 150 mg S44819 group, 90 [70–100] in 300 mg S44819 group, and 90 [70–100] in placebo group) were similar in all groups. Number and type of adverse events were similar between the three groups. There were no drug-related adverse events and no drug-related deaths. Interpretation: There was no evidence that S44819 improved clinical outcome in patients after ischaemic stroke, and thus S44819 cannot be recommended for stroke therapy. The concept of tonic inhibition after stroke should be re-evaluated in humans. Funding: Servier

Deep-sequencing reveals broad subtype-specific HCV resistance mutations associated with treatment failure

A percentage of hepatitis C virus (HCV)-infected patients fail direct acting antiviral (DAA)-based treatment regimens, often because of drug resistance-associated substitutions (RAS). The aim of this study was to characterize the resistance profile of a large cohort of patients failing DAA-based treatments, and investigate the relationship between HCV subtype and failure, as an aid to optimizing management of these patients. A new, standardized HCV-RAS testing protocol based on deep sequencing was designed and applied to 220 previously subtyped samples from patients failing DAA treatment, collected in 39 Spanish hospitals. The majority had received DAA-based interferon (IFN) a-free regimens; 79% had failed sofosbuvir-containing therapy. Genomic regions encoding the nonstructural protein (NS) 3, NS5A, and NS5B (DAA target regions) were analyzed using subtype-specific primers. Viral subtype distribution was as follows: genotype (G) 1, 62.7%; G3a, 21.4%; G4d, 12.3%; G2, 1.8%; and mixed infections 1.8%. Overall, 88.6% of patients carried at least 1 RAS, and 19% carried RAS at frequencies below 20% in the mutant spectrum. There were no differences in RAS selection between treatments with and without ribavirin. Regardless of the treatment received, each HCV subtype showed specific types of RAS. Of note, no RAS were detected in the target proteins of 18.6% of patients failing treatment, and 30.4% of patients had RAS in proteins that were not targets of the inhibitors they received. HCV patients failing DAA therapy showed a high diversity of RAS. Ribavirin use did not influence the type or number of RAS at failure. The subtype-specific pattern of RAS emergence underscores the importance of accurate HCV subtyping. The frequency of “extra-target” RAS suggests the need for RAS screening in all three DAA target regions

Brand-specific estimates of influenza vaccine effectiveness for the 2021–2022 season in Europe: results from the DRIVE multi-stakeholder study platform

IntroductionDevelopment of Robust and Innovative Vaccine Effectiveness (DRIVE) was a European public-private partnership (PPP) that aimed to provide annual, brand-specific estimates of influenza vaccine effectiveness (IVE) for regulatory and public health purposes. DRIVE was launched in 2017 under the umbrella of the Innovative Medicines Initiative (IMI) and conducted IVE studies from its pilot season in 2017-2018 to its final season in 2021-2022. MethodsIn 2021-2022, DRIVE conducted four primary care-based test-negative design (TND) studies (Austria, Italy, Iceland, and England; involving &gt;1,000 general practitioners), nine hospital-based TND studies (France, Iceland, Italy, Romania, and Spain, for a total of 21 hospitals), and one population-based cohort study in Finland. In the TND studies, patients with influenza-like illness (primary care) or severe acute respiratory infection (hospital) were enrolled, and laboratory tested for influenza using RT-PCR. Study contributor-specific IVE was calculated using logistic regression, adjusting for age, sex, and calendar time, and pooled by meta-analysis. ResultsIn 2021-2022, pooled confounder-adjusted influenza vaccine effectiveness (IVE) estimates against laboratory-confirmed influenza (LCI) overall and per type and subtype/lineage was produced, albeit with wide confidence intervals (CI). The limited circulation of influenza in Europe did not allow the network to reach the optimal sample size to produce precise IVE estimates for all the brands included. The most significant IVE estimates were 76% (95% CI 23%-93%) for any vaccine and 81% (22%-95%) for Vaxigrip Tetra in adults &amp; GE;65 years old and 64% (25%-83%) for Fluenz Tetra in children (TND primary care setting), 85% (12%-97%) for any vaccine in adults 18-64 years (TND hospital setting), and 38% (1%-62%) in children 6 months-6 years (population-based cohort, mixed setting). DiscussionOver five seasons, DRIVE collected data on &gt;35,000 patients, more than 60 variables, and 13 influenza vaccines. DRIVE demonstrated that estimating brand-specific IVE across Europe is possible, but achieving sufficient sample size to obtain precise estimates for all relevant stratifications remains a challenge. Finally, DRIVE's network of study contributors and lessons learned have greatly contributed to the development of the COVID-19 vaccine effectiveness platform COVIDRIVE