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Plant epigenetic regulations are involved in transposable element silencing, developmental processes and responses to the environment1-7. They often involve modifications of DNA methylation, particularly through the DEMETER (DME) demethylase family and RNA-dependent DNA methylation (RdDM)8. Root nodules host rhizobia that can fix atmospheric nitrogen for the plant's benefit in nitrogen-poor soils. The development of indeterminate nodules, as in Medicago truncatula, involves successive waves of gene activation9-12, control of which raises interesting questions. Using laser capture microdissection (LCM) coupled to RNA-sequencing (SYMbiMICS data11), we previously identified 4,309 genes (termed NDD) activated in the nodule differentiation and nitrogen fixation zones, 36% of which belong to co-regulated genomic regions dubbed symbiotic islands13. We found MtDME to be upregulated in the differentiation zone and required for nodule development, and we identified 474 differentially methylated regions hypomethylated in the nodule by analysing ~2% of the genome4. Here, we coupled LCM and whole-genome bisulfite sequencing for a comprehensive view of DNA methylation, integrated with gene expression at the tissue level. Furthermore, using CRISPR-Cas9 mutagenesis of MtDRM2, we showed the importance of RdDM for CHH hypermethylation and nodule development. We thus proposed a model of DNA methylation dynamics during nodule development.
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Medicago truncatula , Nódulos Radiculares de Plantas , Desmetilação do DNA , Metilação de DNA , Regulação da Expressão Gênica de Plantas , Medicago truncatula/metabolismo , Nitrogênio/metabolismo , RNA/metabolismo , Nódulos Radiculares de Plantas/metabolismo , Simbiose/genéticaRESUMO
Draf III frontal sinusotomy is one of the most complex surgical procedures on the frontal sinus, designed to limit the risks of restenosis by ensuring unification of the two ostia and resection of the floor of the sinus. This procedure requires a good knowledge of anatomy and sufficient surgical expertise to avoid the risk of CSF leak and to limit the risk of restenosis. The surgeon can use various landmarks, consisting of foramina, bone grooves and arteries located on the anterior part of the cribriform plate to guide the procedure. The purpose of this technical note is to explain the use of these landmarks to ensure safe Draf III frontal sinusotomy via a medial approach.
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Seio Frontal , Artérias , Constrição Patológica , Endoscopia , Osso Etmoide , Seio Frontal/cirurgia , HumanosRESUMO
OBJECTIVES: Tumor mutation screening is standard of care for patients with stage IV NSCLC. Since a couple of years, widespread NGS approaches used in routine diagnostics to detect driver mutations such as EGFR, KRAS, BRAF or MET allows the identification of other alterations that could modulated the intensity or duration of response to targeted therapies. The prevalence of co-occurring alterations that could affect response or prognosis as not been largely analyzed in clinical settings and large cohorts of patients. Thanks to the IFCT program "Biomarkers France", a collection of samples and data at a nation-wide level was available to test the impact of co-mutations on first line EGFR TKI in patients with EGFR mutated cancers. MATERIALS AND METHODS: Targeted NGS was assessed on available (n = 208) samples using the Ion AmpliSeq™ Cancer Hotspot Panel v2 to screen for mutations in 50 different cancer genes. RESULTS: This study showed that PTEN inactivating mutations, ATM alterations, IDH1 mutations and complex EGFR mutations were predictors of short PFS in patients with a stage 4 lung adenocarcinoma receiving first line EGFR TKI and that PTEN, ATM, IDH1 and KRAS mutations as well as alterations in the MAPK pathway were related to shorter OS. CONCLUSION: These findings may lead to new treatment options in patients with unfavorable genotypes to optimize first line responses.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Inibidores de Proteínas Quinases , Proteínas Mutadas de Ataxia Telangiectasia , Biomarcadores , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Receptores ErbB/genética , França/epidemiologia , Humanos , Isocitrato Desidrogenase , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Mutação , PTEN Fosfo-Hidrolase , Inibidores de Proteínas Quinases/uso terapêuticoRESUMO
OBJECTIVE: Multi-centre study of the National French Registry (EPIIC) of patients with cochlear implants, focusing on infants who were operated-on under the age of 24 months between 2012 and 2016. PATIENTS AND METHODS: A total of 615 profoundly deaf infants, who received cochlear implants (CIs) before their second birthday, were included in the registry by different CI centers. Epidemiological, surgical, speech therapy and school, follow-up data were included in the registry, 12, 24, 36 and 48 months thereafter. The following parameters were studied: type of implantation (uni- or bilateral), complications, cause of deafness, category of auditory perception (CAP), Open-set word recognition score (OSW), speech intelligibility rating, lexical comprehension with EVIP (Peabody), communication mode and type of schooling. Bilateral simultaneous CI (BiCI) and unilateral CI (UniCI) groups were compared. RESULTS: There were 744 implantations. The explantation-reimplantation rate, within the four-year follow-up, was just 3.6%. Mean implantation age was 16.0 months, and similar in the two groups (BiCI/UniCI). A total of 51% of children had their first implant between 12 and 18 months, and 15% before 12 months. Implantation was unilateral in 52% of cases. Fifty-six percent of the bilateral procedures were sequential, with a mean delay of 16.8 months for the second implantation. The cause of deafness was unknown in 52% of cases. Of the 48% (297/615) of attributed cases, 32% had clear genetic causes. The remaining deafness was due to cytomegalovirus (CMV, 8%), inner-ear malformation (5%) and meningitis (3%). The main complications were from infections (47%) and internal device failure (25%). Four years post-operation, 84% of the UniCI and 75% of BiCl groups had a CAP≥5, and 83% of UniCl and 100% BiCI had OSW≥80%. Furthermore 74% of UniCI and 77% of BiCI communicated orally and 85% of UniCI and 90% of BiCI integrated into mainstream schooling. CONCLUSION: The French Registry of cochlear implants (EPIIC) is the only such national registry in the world. Our analysis illustrates the immediate benefits of, either single or double, cochlear implantation for language, perception skills and schooling.
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Percepção Auditiva , Linguagem Infantil , Implante Coclear/estatística & dados numéricos , Implantes Cocleares/estatística & dados numéricos , Surdez/reabilitação , Sistema de Registros/estatística & dados numéricos , Fatores Etários , Implante Coclear/efeitos adversos , Implante Coclear/métodos , Implantes Cocleares/efeitos adversos , Comunicação , Correção de Deficiência Auditiva/instrumentação , Correção de Deficiência Auditiva/estatística & dados numéricos , Surdez/etiologia , Remoção de Dispositivo/estatística & dados numéricos , Educação de Pessoas com Deficiência Auditiva/métodos , Educação de Pessoas com Deficiência Auditiva/estatística & dados numéricos , Seguimentos , França , Humanos , Lactente , Recém-Nascido , Inclusão Escolar/estatística & dados numéricos , Reoperação/estatística & dados numéricos , Instituições Acadêmicas , Inteligibilidade da Fala , Fonoterapia/estatística & dados numéricos , Fatores de TempoRESUMO
Cochlear and brainstem implants have been included on the list of reimbursable products (LPPR) in France since March of 2009. The implants were initially inscribed for 5 years, after which an application for renewal with the French National Commission for the Evaluation of Medical Devices and Health Technologies (Commission Nationale d'évaluation des dispositifs médicaux et des technologies de santé - CNEDiMTS) was required [Haute Autorité de santé, 2009]. Upon registration to the list of reimbursable products, the companies and the reference centers for cochlear and brainstem implants were asked to set up a post-registration registry called EPIIC. This article reports the evolution in the EPIIC registry of the general indicators for 5051 patients over the five years from 2012-2016.
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Implantes Auditivos de Tronco Encefálico/estatística & dados numéricos , Implantes Cocleares/estatística & dados numéricos , Sistema de Registros/estatística & dados numéricos , Comitês Consultivos/organização & administração , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Implantes Auditivos de Tronco Encefálico/economia , Implante Coclear/estatística & dados numéricos , Implantes Cocleares/economia , Segurança Computacional , Bases de Dados como Assunto , Aprovação de Equipamentos/legislação & jurisprudência , Remoção de Dispositivo/estatística & dados numéricos , França , Guias como Assunto/normas , Setor de Assistência à Saúde/economia , Setor de Assistência à Saúde/legislação & jurisprudência , Humanos , Lactente , Recém-Nascido , Reembolso de Seguro de Saúde , Controle de Qualidade , Padrões de Referência , Fatores de TempoRESUMO
This study aims to determine the frequency and causes of cochlear explants with re-implantation (ERI) after 5 years' follow up of the patients included in the French national EPIIC (étude post-inscription des implants cochléaires) registry tracking patients with cochlear implantation. This multicenter, descriptive prospective study was conducted on 5051 patients enrolled in the EPIIC database between January 2012 and December 2016. Ninety-five patients (1.9%) received a primary implant and an ERI during the study. Of these, four benefitted from two ERIs. The number of ERIs was significantly higher in the pediatric population than among adults. The explantation and reimplantation were performed simultaneously in 86% of cases. The reasons for explantation were: in 46.4% of cases linked to a malfunction of the implant, and in 39.3% of cases for medical or surgical reasons. The number of electrodes inserted was significantly higher after the ERI than after the first implantation. There was just one post-ERI infection for these 95 explanted and re-implanted patients. As well as explantation with reimplantation rarely being necessary, it generally presents no major surgical difficulty and in most cases it allows a better integration than in the first implantation.
Assuntos
Implante Coclear/estatística & dados numéricos , Implantes Cocleares/estatística & dados numéricos , Remoção de Dispositivo/estatística & dados numéricos , Sistema de Registros/estatística & dados numéricos , Reoperação/estatística & dados numéricos , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Implantes Cocleares/efeitos adversos , França , Humanos , Lactente , Pessoa de Meia-Idade , Estudos Prospectivos , Falha de Prótese , Reimplante/estatística & dados numéricos , Fatores de Tempo , Adulto JovemRESUMO
OBJECTIVES: The aim of this study was to evaluate peri- and post-operative complications related to cochlear implantations. We searched for risk factors predicting these complications and analyzed the complications in the youngest and most elderly. STUDY DESIGN: Retrospective analysis of cochlear implant patients. MATERIALS AND METHODS: All patients who underwent cochlear implantation in France between January 2012 and December 2016 were anonymized and registered in the EPIIC database. This population included 3483 adults and 2245 children. Their demographic and surgical data and their incidence of peri- or post-operative complications, including their severity, whether major or minor, were all indicated. RESULTS: The global complication rate was 6.84%. The risk of complication was higher in initial implantation versus reimplantation (P<0.0001). The risk was also higher for bilateral implantation versus unilateral (P<0.0001). Complications were more frequent for patients with cochlear malformation (P=0.002). There was no difference in complication rates across age groups; babies under 1 year old, and the elderly over 80 and even over 90, did not have more complications than the rest of the population. Patients treated in the daily care unit had no more complications than those who were hospitalized for one night or more (P=0.64). CONCLUSION: Cochlear implantation is a safe technique with a low incidence of complications. The absence of increased risk in patients at the extremes of the age spectrum justifies offering this solution to all, without age limitation.
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Implante Coclear/efeitos adversos , Perda Auditiva/reabilitação , Complicações Intraoperatórias/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Sistema de Registros/estatística & dados numéricos , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Cóclea/anormalidades , Implante Coclear/métodos , Hospital Dia/estatística & dados numéricos , França/epidemiologia , Perda Auditiva/etiologia , Hospitalização/estatística & dados numéricos , Humanos , Incidência , Lactente , Pessoa de Meia-Idade , Reoperação/efeitos adversos , Reoperação/estatística & dados numéricos , Estudos Retrospectivos , Fatores de Risco , Adulto JovemRESUMO
OBJECTIVE: Evaluate in France the outcomes of cochlear implantation outside the selection criteria, off-label. MATERIAL AND METHODS: This is a prospective cohort study including adults and children having received a cochlear implant (CI) in an off-label indication, that is outside the criteria established by the "Haute Autorité de santé (HAS)" in 2012. The data was collected from the "EPIIC" registry on recipients who received CIs in France between 2011 and 2014. Speech audiometry was performed at 60dB preimplantation and after one year of CI use, as well as an evaluation of the scores of the quality of life with the APHAB questionnaire, the scores for CAP and the professional/academic status in pre- and post-implantation conditions. Major and minor complications at surgery have been recorded. RESULTS: In total, 590 patients (447 adults and 143 children) with an off-label indication for CIs were included in this study from the EPIIC registry (11.7% of the whole cohort of EPIIC). For adults, the median percentage of comprehension using monosyllabic word lists was 41% in preimplantation condition versus 53% after one year of CI use (P<0.001) and 60% versus 71% in dissyllabic word lists (P<0.001). The CAP scores were 5 versus 6 in pre- and post-implantation conditions respectively (P<0.001) and the APHAB scores were statistically lower after implantation (P<0.001). In the children cohort, the median percentage of comprehension using monosyllabic word lists was 51% in preimplantation condition and 65% after CI (P<0.001), and 48% versus 82% (P<0.001) for dissyllabic word lists. The CAP scores were 5 versus 7 respectively in pre- and post-CI conditions (P<0.001). Thirty-two minor complications (5.4%) and 17 major complications (2.8%) were reported in our panel of off-label indication patients. CONCLUSION: These results suggest that a revision of the cochlear implantation candidacy criteria is necessary to allow more patients with severe or asymmetric hearing loss to benefit from a CI when there is an impact on quality of life despite the use of an optimal hearing aid.
Assuntos
Implante Auditivo de Tronco Encefálico/estatística & dados numéricos , Implante Coclear/estatística & dados numéricos , Implantes Cocleares/estatística & dados numéricos , Perda Auditiva/reabilitação , Seleção de Pacientes , Sistema de Registros/estatística & dados numéricos , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Audiometria da Fala/métodos , Criança , Pré-Escolar , Implante Coclear/efeitos adversos , Implantes Cocleares/efeitos adversos , Feminino , França/epidemiologia , Inquéritos Epidemiológicos , Humanos , Masculino , Pessoa de Meia-Idade , Uso Off-Label/estatística & dados numéricos , Complicações Pós-Operatórias/epidemiologia , Período Pós-Operatório , Cuidados Pré-Operatórios , Estudos Prospectivos , Qualidade de Vida , Adulto JovemRESUMO
OBJECTIVES: To analyze the performance of cochlear implants in French patients aged 65 and over, implanted between 2012 and 2016, using data from the French national registry for cochlear implants (EPIIC). MATERIALS AND METHODS: The French national registry incorporates patient data from before implantation and for three years after implantation, stratified in different age groups (18-39, 40-64years, 65-74years and>75years). Here, we assessed the latter two categories. Hearing was assessed using mono- and disyllabic words in a silent background. The Category of Auditory Performance (CAP) scale was also implemented and subjects took the Abbreviated Profile of Hearing Aid Benefit (Aphab) questionnaire. RESULTS: The population aged over 65 accounted for 38% (n=1193) of the 3178 adult implanted patients. The performance for mono- and disyllabic words in silence, the CAP scores and the APHAB questionnaire answers for ease of communication, background noise and reverberation were dramatically improved at one year post-implantation (P<0.0001 for each score) and remained stable between one and three years thereafter. The percentage improvement was similar across all age groups. The scores for loud-noise intolerance did not change after cochlear implantation in any age group. CONCLUSION: Cochlear implants improve hearing and communication in subjects aged 65 and over, with comparable efficiency to that achieved in younger subjects. Cochlear implantation should thus be proposed whenever hearing aids provide only limited benefit. However, between 2012 and 2016, cochlear implantation was given to less than 1% of the French population aged 65 and over with profound deafness.
Assuntos
Implante Coclear/estatística & dados numéricos , Implantes Cocleares/estatística & dados numéricos , Perda Auditiva/reabilitação , Sistema de Registros/estatística & dados numéricos , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Percepção Auditiva , Implante Coclear/métodos , Comunicação , Feminino , França , Inquéritos Epidemiológicos , Perda Auditiva/etiologia , Testes Auditivos/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Ruído/efeitos adversos , Estudos Retrospectivos , Fatores de Tempo , Adulto JovemRESUMO
OBJECTIVES: Assessment of the incidence and results of bilateral cochlear implantation in adults and children in France. MATERIALS AND METHODS: Multicenter retrospective study of data in the French national registry of cochlear implantations from January 1st 2012 to December 31st 2016. Functional results from CAP (Category of Auditory Performance) questionnaires and speech audiometry tests, with mono- and di-syllabic word-lists, were compared before and after implantation. Speech audiometry tests were carried out against a noisy background, except before simultaneous implantations. RESULTS: Nine hundred and forty two bilateral cochlear implantations were performed during this period, that is, 16.4% of all cochlear implantations. Five hundred and eighty eight bilateral implantations were performed sequentially. 59% of the bilateral implantations were performed in children. Bilateral implants significantly improved CAP scores in all cases (P<0.001). Auditory performance, with the two types of word-list, were significantly improved after simultaneous implantation (P<0.01). After sequential implantation, the speech discrimination score, already very good with the first implant, reached 63±26% [0-100] with monosyllabic word lists, and 72±28% [0-100] with dissyllabic words. There were more complications due to surgery in bilateral cases than in the entire population of cochlear recipients (9.1% vs 6.4%, P<0.02). CONCLUSION: Hearing is significantly improved by simultaneous cochlear implantation. For sequential implantation, at one year, when auditory results were already excellent from the first implant, in the bimodal condition CAP scores were significantly improved, although there was no further change in speech audiometry in noise.
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Implante Coclear/métodos , Implantes Cocleares/estatística & dados numéricos , Surdez/reabilitação , Sistema de Registros/estatística & dados numéricos , Adulto , Audiometria da Fala/métodos , Percepção Auditiva , Criança , Implante Coclear/efeitos adversos , Implante Coclear/estatística & dados numéricos , Surdez/etiologia , Feminino , França , Humanos , Masculino , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Testes de Discriminação da Fala/estatística & dados numéricosRESUMO
This study concerns the results of cochlear implantation in children and adults from French cochlear implantation centers, monitored at one, two and three years by the Cochlear Implant French Registry EPIIC. This multicenter study enrolled 2603 subjects (1667 adults and 936 children) implanted in one ear. The following parameters were studied: hearing overall performances, monosyllabic or dissyllabic word perception, speech intelligibility, self-assessment questionnaire of Cochlear Implant (CI) benefits (Abbreviated profile of Hearing aid Benefit); professional activity and schooling. This study confirms the ceiling effect in adults' performances after the 1st year and the progressive growth in children's performances. It also shows that the contralateral hearing aid enhances performances compared to the CI alone condition, in all follow-up sessions. The French register of CIs is the only worldwide register of systematic follow-up on a period of three years and more of all adults and children implanted in a country.
Assuntos
Implante Coclear/estatística & dados numéricos , Implantes Cocleares/estatística & dados numéricos , Surdez/reabilitação , Qualidade de Vida , Sistema de Registros/estatística & dados numéricos , Adolescente , Adulto , Fatores Etários , Percepção Auditiva , Criança , Pré-Escolar , Educação , Emprego , Seguimentos , França , Humanos , Lactente , Recém-Nascido , Autoavaliação (Psicologia) , Inteligibilidade da Fala , Inquéritos e Questionários , Fatores de Tempo , Resultado do TratamentoRESUMO
The noise from the flow around a circular cylinder in the critical regime is investigated by combining a compressible wall-resolved large eddy simulation and a Ffowcs Williams and Hawkings analogy on solid and porous surfaces. This simulation is validated by comparing several flow parameters with previous experimental and numerical data in the same flow regime. Significantly reduced drag and increased vortex shedding Strouhal number (0.33) are observed. Two slightly asymmetric laminar separation bubbles (LSBs) on the cylinder surface at about 100° are shown to trigger turbulence through Kelvin-Helmholtz (KH) shear-layer instability. The latter contributes to a narrowband hump in the wall-pressure fluctuations with a tone at a Strouhal number of 27, which can be as intense as the dominant vortex shedding tone. The ratio of the corresponding Strouhal numbers is consistent with the proposed variation with the Reynolds number by Prasad and Williamson [(1997). J. Fluid Mech. 333, 375-402]. The dominant far-field noise source is still the vortex shedding dipolar tone radiating mostly at 90°. Yet, two additional broadband noise sources are evidenced in the wake, one at low frequencies caused by the wake oscillation and another one at high frequencies caused by the KH instability mostly directly toward the LSB locations.
RESUMO
AIM: The sedentary lifestyle is defined by a lack of regular mobilizing activities in the activities of daily life. The purpose of this work was to gather data related to the potential link between urinary incontinence and sedentary lifestyle in women. METHOD: A literature review (Pubmed/MEDLINE databases) based on keywords: women; urinary incontinence; sedentary; sedentary behavior; sedentary lifestyle; physical activity; exercise; sport, over the period 2008-2018 was carried out. RESULTS: Five cross-sectional observational studies were analyzed. Overall, the data supported a link between sedentary behavior and urinary incontinence in women. Several potential confounding factors (age, body mass index, comorbidities, lower socio-familial support) have been identified in the literature. Pathophysiological mechanisms remain poorly established, potentially including metabolic factors, postural factors and muscle dysfunctions. Few articles respected the strict definition of sedentary lifestyle, and no prospective study investigating the causal link between meddle or long-term sedentary was highlighted. CONCLUSION: The limited data available in the literature suggests that sedentary lifestyle is a risk factor for female urinary incontinence. Many confounding factors have been identified, justifying further studies evaluating more specifically the causal link between sedentary lifestyle and urinary incontinence in women.
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Estilo de Vida , Comportamento Sedentário , Incontinência Urinária/epidemiologia , Estudos Transversais , Exercício Físico/fisiologia , Feminino , Humanos , Estudos Observacionais como Assunto/estatística & dados numéricos , Fatores de Risco , Fatores SexuaisRESUMO
BACKGROUND: In France, advance directives are favourably perceived by most of the population, although the drafting rate is low. This ambivalence is challenging because advance directives are meant to promote the autonomy and freedom of choice of patients. The purpose of this study was to analyse the content of advance directives written by patients suffering from malignant haemopathies to better understand how patients put them into practice. These could be relevant as early as the initial diagnosis of haematological malignancies because of the uncertain course of the disease. METHODS: This was a multicentre, qualitative, descriptive study. The advance directives written by patients with malignant haemopathies treated in one of the six French hospital departments were included in the study from 01/06/2008 to 15/04/2016. A thematic analysis of the advance directives was performed by two researchers: a senior haematologist and a research assistant. RESULTS: The median age of the patients was 69. Most were women (sex ratio: 0.59), living as a couple (57%), with lymphoid pathologies (66%), who were still alive two years after the instructions were written (63%) and had nominated a health care proxy (88.6%). Free texts (62.9%) were richer in content than pre-defined forms. The advance directives were used in three ways: for a purely legal purpose, to focus on medical treatments or actions, or to communicate a message to the family. Three main themes emerged: (1) refusal of medical treatment (100%), in which patients express refusal of life-sustaining care (97.1%). The actual treatments or the moment when they should be limited or stopped were not always mentioned in detail. (2) A desire for effective pain relief to avoid suffering (57.1%) and (3) messages for their family (34.3%), such as funeral arrangements (17.1%) and messages of love or trust (14.3%). CONCLUSIONS: Patients who write advance directives are not necessarily at the end of their lives. Their content mainly conveys treatment wishes, although patients also use them to pass on personal messages to their close family. This emerging role of advance directives to communicate messages within the family should be valued, even if it is not their original purpose.
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Diretivas Antecipadas/psicologia , Comportamento de Escolha , Família/psicologia , Adolescente , Adulto , Diretivas Antecipadas/legislação & jurisprudência , Diretivas Antecipadas/tendências , Idoso , Idoso de 80 Anos ou mais , Comunicação , Feminino , França , Hematologia/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Pesquisa Qualitativa , Estudos RetrospectivosRESUMO
BACKGROUND: EGFR mutations cause inconsistent response to EGFR tyrosine-kinase inhibitors (TKI). To better understand these features, we reviewed all cases of EGFR-mutated non-small-cell lung cancer collected in the Biomarkers France database. PATIENTS AND METHODS: Of 17 664 patients, 1837 (11%) with EGFR-mutated non-small-cell lung cancer were retrospectively analyzed for clinical and molecular characteristics. Results were correlated with survival and treatment response for the 848 stage IV patients. RESULTS: EGFR exon 18, 19, 20 and 21 mutations were found in 102 (5.5%), 931 (51%), 102 (5.5%) and 702 (38%) patients, respectively. Over 50% of exon 18 and 20 mutated patients were smokers. The median follow-up was 51.7 months. EGFR mutation type was prognostic of overall survival (OS) versus wild-type {exon 19: hazard ratio (HR)=0.51 [95% confidence interval (CI): 0.41-0.64], P < 0.0001; exon 21: HR = 0.76 (95% CI: 0.61-0.95), P = 0.002; exon 20: HR = 1.56 (95% CI: 1.02-2.38), P = 0.004}. EGFR mutation type was prognostic of progression-free survival versus wild-type [exon 19: HR = 0.62 (95% CI: 0.49-0.78), P < 0.0001; exon 20: HR = 1.46 (95% CI: 0.96-2.21), P = 0.07]. First-line treatment choice did not influence OS in multivariate analysis. First-line TKI predicted improved progression-free survival versus chemotherapy [HR = 0.67 (95% CI: 0.53-0.85), P = 0.001]. OS was longer for del19 versus L858R, which was associated with better OS compared with other exon 21 mutations, including L861Q. TKI improved survival in patients with exon 18 mutations, while chemotherapy was more beneficial for exon 20-mutated patients. CONCLUSION: EGFR mutation type can inform the most appropriate treatment. Therapeutic schedule had no impact on OS in our study, although TKI should be prescribed in first-line considering the risk of missing the opportunity to use this treatment.
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Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Receptores ErbB/genética , Neoplasias Pulmonares/patologia , Mutação , Inibidores de Proteínas Quinases/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Receptores ErbB/antagonistas & inibidores , Seguimentos , França , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Prognóstico , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
Tubulocystic renal cell carcinoma is a rare tumor with an indolent behavior in the majority of cases. In contrast, tubulocystic renal cell carcinoma with poorly differentiated foci has a bad prognosis with an aggressive and metastatic behavior. We present the case of a patient diagnosed with tubulocystic renal cell carcinoma with poorly differentiated foci.
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Carcinoma de Células Renais/patologia , Neoplasias Renais/patologia , Idoso , Humanos , MasculinoRESUMO
Voluntariness stands for one of the four pillars of ethics in blood donation; it is, however, more related to tradition than to legislation. Because it seems necessary to apply "marketing" techniques to blood collection in order to meet the needs in blood components, both in terms of quantity and quality, one wonders if this may be at the expense of this principle of voluntariness. This seminar-belonging actually to a series of seminars in Ethics in Transfusion Medicine-aimed at questioning the possible weakness of voluntariness in the field of blood donation. To achieve this goal, specialists of numerous disciplines in medical sciences, law and humanities gathered to discuss all related issues to voluntariness in blood donation.
Assuntos
Doadores de Sangue/ética , Medicina Transfusional/ética , Voluntários , Altruísmo , Atitude Frente a Saúde , Doadores de Sangue/legislação & jurisprudência , Doadores de Sangue/psicologia , Segurança do Sangue , Transfusão de Sangue/economia , Transfusão de Sangue/ética , Transfusão de Sangue/legislação & jurisprudência , Necessidades e Demandas de Serviços de Saúde , Humanos , Motivação , Comunicação Persuasiva , Poder Psicológico , Remuneração , Valores SociaisRESUMO
Eco-efficiency is a useful guide to dairy farm sustainability analysis aimed at increasing output (physical or value added) and minimizing environmental impacts (EIs). Widely used partial eco-efficiency ratios (EIs per some functional unit, e.g. kg milk) can be problematic because (i) substitution possibilities between EIs are ignored, (ii) multiple ratios can complicate decision making and (iii) EIs are not usually associated with just the functional unit in the ratio's denominator. The objective of this study was to demonstrate a 'global' eco-efficiency modelling framework dealing with issues (i) to (iii) by combining Life Cycle Analysis (LCA) data and the multiple-input, multiple-output production efficiency method Data Envelopment Analysis (DEA). With DEA each dairy farm's outputs and LCA-derived EIs are aggregated into a single, relative, bounded, dimensionless eco-efficiency score, thus overcoming issues (i) to (iii). A novelty of this study is that a model providing a number of additional desirable properties was employed, known as the Range Adjusted Measure (RAM) of inefficiency. These properties altogether make RAM advantageous over other DEA models and are as follows. First, RAM is able to simultaneously minimize EIs and maximize outputs. Second, it indicates which EIs and/or outputs contribute the most to a farm's eco-inefficiency. Third it can be used to rank farms in terms of eco-efficiency scores. Thus, non-parametric rank tests can be employed to test for significant differences in terms of eco-efficiency score ranks between different farm groups. An additional DEA methodology was employed to 'correct' the farms' eco-efficiency scores for inefficiencies attributed to managerial factors. By removing managerial inefficiencies it was possible to detect differences in eco-efficiency between farms solely attributed to uncontrollable factors such as region. Such analysis is lacking in previous dairy studies combining LCA with DEA. RAM and the 'corrective' methodology were demonstrated with LCA data from French specialized dairy farms grouped by region (West France, Continental France) and feeding strategy (regardless of region). Mean eco-efficiency score ranks were significantly higher for farms with 30% maize in the total forage area before correcting for managerial inefficiencies. Mean eco-efficiency score ranks were higher for West than Continental farms, but significantly higher only after correcting for managerial inefficiencies. These results helped identify the eco-efficiency potential of each region and feeding strategy and could therefore aid advisors and policy makers at farm or region/sector level. The proposed framework helped better measure and understand (dairy) farm eco-efficiency, both within and between different farm groups.
Assuntos
Indústria de Laticínios/métodos , Ecologia/métodos , Eficiência Organizacional/estatística & dados numéricos , Meio Ambiente , Fazendas/estatística & dados numéricos , Animais , Bovinos , Indústria de Laticínios/normas , Indústria de Laticínios/estatística & dados numéricos , Dieta/métodos , Dieta/estatística & dados numéricos , Dieta/veterinária , Ecologia/normas , Ecologia/estatística & dados numéricos , Eficiência Organizacional/normas , Fazendas/normas , Feminino , França , Leite , Modelos Teóricos , Estatística como AssuntoRESUMO
Landfill bioreactors are based on an acceleration of in-situ waste biodegradation by performing leachate recirculation. To quantify the water content and to evaluate the leachate injection system, in-situ methods are required to obtain spatially distributed information, usually electrical resistivity tomography (ERT). In a previous study, the MICS (multiple inversions and clustering strategy) methodology was proposed to improve the hydrodynamic interpretation of ERT results by a precise delimitation of the infiltration area. In this study, MICS was applied on two ERT time-lapse data sets recorded on different waste deposit cells in order to compare the hydrodynamic behaviour of leachate flow between the two cells. This comparison is based on an analysis of: (i) the volume of wetted waste assessed by MICS and the wetting rate, (ii) the infiltration shapes and (iii) the pore volume used by the leachate flow. This paper shows that leachate hydrodynamic behaviour is comparable from one waste deposit cell to another with: (i) a high leachate infiltration speed at the beginning of the infiltration, which decreases with time, (ii) a horizontal anisotropy of the leachate infiltration shape and (iii) a very small fraction of the pore volume used by the leachate flow. This hydrodynamic information derived from MICS results can be useful for subsurface flow modelling used to predict leachate flow at the landfill scale.