Formes d'innovation des sous-traitants des filières automobile, plasturgie et microtechnique franc-comtoises

C es dernières années sont marquées par un essor important de la sous-traitance, de la co-traitance, des collaborations, des alliances entre les entreprises. " L'entreprise en réseau " est devenue la forme organisationnelle dominante, la mieux adaptée dans une économie fortement concurrentielle. Malgré cela, on sait peu de choses sur la façon dont les industries sous-traitantes régionales s'adaptent à l'évolution des marchés. Une enquête réalisée en 2008 par le laboratoire ThéMA/CEREQ dans le cadre d'une étude faite par la MSHE C.N. Ledoux pour le Secrétariat général aux affaires régionales de Franche-Comté apporte des éclairages intéressants

Quality in practice: integrating routine collection of patient language data into hospital practice

Quality problem Timely identification of patients' language needs can facilitate the provision of language-appropriate services and contribute to quality of care, clinical outcomes and patient satisfaction. Initial assessment At the University Hospitals of Geneva, Switzerland, timely organization of interpreter services was hindered by the lack of systematic patient language data collection. Choice of solution We explored the feasibility and acceptability of a procedure for collecting patient language data at the first point of contact, prior to its hospital-wide implementation. Implementation During a one-week period, receptionists and triage nurses in eight clinical services tested a new procedure for collecting patient language data. Patients were asked to identify their primary language and other languages they would be comfortable speaking with their doctor. Staff noted patients' answers on a paper form and provided informal feedback on their experience with the procedure. Evaluation Registration staff encountered few difficulties collecting patient language data and thought that the two questions could easily be incorporated into existing administrative routines. Following the pilot test, two language fields with scroll-down language menus were added to the electronic patient file, and the subsequent filling-in of these fields has been rapid and hospital wide. Lessons learned Our experience suggests that routine collection of patient language data at first point of contact is both feasible and acceptable and that involving staff in a pilot project may facilitate hospital-wide implementation. Future efforts should focus on exploring the sensitivity and specificity of the proposed questions, as well as the impact of data collection on interpreter us

Mental and physical health of Kosovar Albanians in their place of origin: a post-war 6-year follow-up study

Purpose: Long-term outcome of traumatic experiences among war-exposed civilians living in their home country has been seldom documented. The present study examined change in posttraumatic stress disorder (PTSD) frequency and perceived physical and mental health in a cohort of Kosovar Albanians over 6years (2001-2007). Methods: Of 996 Albanian Kosovar civilians included in the 2001 survey, 551 subjects (55.3%) were recalled and interviewed in 2007. Diagnoses of PTSD and major depressive episode were assessed using the Mini International Neuropsychiatric Interview. Subjective physical and mental health were investigated using the Medical Outcomes Study 36-Item Short-Form (SF-36). A list of traumatic events adapted from the Harvard Trauma Questionnaire and other stressful life events was also considered. Results: Posttraumatic stress disorder was significantly less frequent in 2007 than in 2001 (14.5% vs. 23.2%, p<0.001). For 18.0, 5.3 and 9.3% of participants, PTSD remitted, persisted and developed over the 6-year follow-up period, respectively. Ill health without having access to medical care and major changes in responsibilities at work were associated with both persistence and new occurrence of PTSD. While the SF-36 mental component summary score significantly improved (mean change +4.5, p<0.001), the physical component summary score did not change between 2001 and 2007, after adjustment for age (mean change −0.8, p=0.14). Conclusions: Results point at the importance of economic and health system reconstruction programs with respect to public health in post-conflict countrie

Colour variation in red grapevines (Vitis vinifera L.): genomic organisation, expression of flavonoid 3'-hydroxylase, flavonoid 3',5'-hydroxylase genes and related metabolite profiling of red cyanidin-/blue delphinidin-based anthocyanins in berry skin

BACKGROUND: Structural genes of the phenyl-propanoid pathway which encode flavonoid 3'- and 3',5'-hydroxylases (F3'H and F3'5'H) have long been invoked to explain the biosynthesis of cyanidin- and delphinidin-based anthocyanin pigments in the so-called red cultivars of grapevine. The relative proportion of the two types of anthocyanins is largely under genetic control and determines the colour variation among red/purple/blue berry grape varieties and their corresponding wines. RESULTS: Gene fragments of VvF3'H and VvF3'5'H, that were isolated from Vitis vinifera 'Cabernet Sauvignon' using degenerate primers designed on plant homologous genes, translated into 313 and 239 amino acid protein fragments, respectively, with up to 76% and 82% identity to plant CYP75 cytochrome P450 monooxygenases. Putative function was assigned on the basis of sequence homology, expression profiling and its correlation with metabolite accumulation at ten different ripening stages. At the onset of colour transition, transcriptional induction of VvF3'H and VvF3'5'H was temporally coordinated with the beginning of anthocyanin biosynthesis, the expression being 2-fold and 50-fold higher, respectively, in red berries versus green berries. The peak of VvF3'5'H expression was observed two weeks later concomitantly with the increase of the ratio of delphinidin-/cyanidin-derivatives. The analysis of structural genomics revealed that two copies of VvF3'H are physically linked on linkage group no. 17 and several copies of VvF3'5'H are tightly clustered and embedded into a segmental duplication on linkage group no. 6, unveiling a high complexity when compared to other plant flavonoid hydroxylase genes known so far, mostly in ornamentals. CONCLUSION: We have shown that genes encoding flavonoid 3'- and 3',5'-hydroxylases are expressed in any tissues of the grape plant that accumulate flavonoids and, particularly, in skin of ripening red berries that synthesise mostly anthocyanins. The correlation between transcript profiles and the kinetics of accumulation of red/cyanidin- and blue/delphinidin-based anthocyanins indicated that VvF3'H and VvF3'5'H expression is consistent with the chromatic evolution of ripening bunches. Local physical maps constructed around the VvF3'H and VvF3'5'H loci should help facilitate the identification of the regulatory elements of each isoform and the future manipulation of grapevine and wine colour through agronomical, environmental and biotechnological tools

A physical map of the heterozygous grapevine 'Cabernet Sauvignon' allows mapping candidate genes for disease resistance

<p>Abstract</p> <p>Background</p> <p>Whole-genome physical maps facilitate genome sequencing, sequence assembly, mapping of candidate genes, and the design of targeted genetic markers. An automated protocol was used to construct a <it>Vitis vinifera </it>'Cabernet Sauvignon' physical map. The quality of the result was addressed with regard to the effect of high heterozygosity on the accuracy of contig assembly. Its usefulness for the genome-wide mapping of genes for disease resistance, which is an important trait for grapevine, was then assessed.</p> <p>Results</p> <p>The physical map included 29,727 BAC clones assembled into 1,770 contigs, spanning 715,684 kbp, and corresponding to 1.5-fold the genome size. Map inflation was due to high heterozygosity, which caused either the separation of allelic BACs in two different contigs, or local mis-assembly in contigs containing BACs from the two haplotypes. Genetic markers anchored 395 contigs or 255,476 kbp to chromosomes. The fully automated assembly and anchorage procedures were validated by BAC-by-BAC blast of the end sequences against the grape genome sequence, unveiling 7.3% of chimerical contigs. The distribution across the physical map of candidate genes for non-host and host resistance, and for defence signalling pathways was then studied. NBS-LRR and RLK genes for host resistance were found in 424 contigs, 133 of them (32%) were assigned to chromosomes, on which they are mostly organised in clusters. Non-host and defence signalling genes were found in 99 contigs dispersed without a discernable pattern across the genome.</p> <p>Conclusion</p> <p>Despite some limitations that interfere with the correct assembly of heterozygous clones into contigs, the 'Cabernet Sauvignon' physical map is a useful and reliable intermediary step between a genetic map and the genome sequence. This tool was successfully exploited for a quick mapping of complex families of genes, and it strengthened previous clues of co-localisation of major NBS-LRR clusters and disease resistance <it>loci </it>in grapevine.</p

Effets induits des grandes infrastructures : synthèse de l'analyse bibliographique

Ce rapport constitue la synthèse de l'étude bibliographique réalisée dans le cadre de l'action du programme, menée sur trois ans, dont il est la première phase, et qui porte plus largement sur la problématique des effets induits des grandes infrastructures . L'analyse a été volontairement limitée à une cinquantaine de références centrées d'une part, sur les effets socio-économiques, il s'agit d'études réalisées en application de la loi d'orientation sur les transports intérieurs, et d'autre part, sur les infrastructures autoroutières et voies ferrées à grande vitesse. L'objectif de cette approche vise non seulement à dresser un état des lieux de la connaissance et des pratiques d'études sur le thème des effets induits, mais aussi, à repérer les marges de progrès et de renouvellements à la fois dans les concepts et les méthodes. En conséquence, le rapport est conçu selon deux parties : • la première consacrée à l'état des connaissances et des pratiques, notamment sur le concept d'effets induits et sur la mesure de ces effets, • la deuxième développée autour du constat que l'évolution de la représentation spatiale rend nécessaire le renouvellement des concepts et des pratiques

Long COVID and the cardiovascular system—elucidating causes and cellular mechanisms in order to develop targeted diagnostic and therapeutic strategies: a joint Scientific Statement of the ESC Working Groups on Cellular Biology of the Heart and Myocardial and Pericardial Diseases

Long COVID has become a world-wide, non-communicable epidemic, caused by long-lasting multiorgan symptoms that endure for weeks or months after SARS-CoV-2 infection has already subsided. This scientific document aims to provide insight into the possible causes and therapeutic options available for the cardiovascular manifestations of long COVID. In addition to chronic fatigue, which is a common symptom of long COVID, patients may present with chest pain, ECG abnormalities, postural orthostatic tachycardia, or newly developed supraventricular or ventricular arrhythmias. Imaging of the heart and vessels has provided evidence of chronic, post-infectious perimyocarditis with consequent left or right ventricular failure, arterial wall inflammation, or microthrombosis in certain patient populations. Better understanding of the underlying cellular and molecular mechanisms of long COVID will aid in the development of effective treatment strategies for its cardiovascular manifestations. A number of mechanisms have been proposed, including those involving direct effects on the myocardium, microthrombotic damage to vessels or endothelium, or persistent inflammation. Unfortunately, existing circulating biomarkers, coagulation, and inflammatory markers, are not highly predictive for either the presence or outcome of long COVID when measured 3 months after SARS-CoV-2 infection. Further studies are needed to understand underlying mechanisms, identify specific biomarkers, and guide future preventive strategies or treatments to address long COVID and its cardiovascular sequelae

Assessing the impact of diagenesis on foraminiferal geochemistry from a low latitude, shallow-water drift deposit

Due to their large heat and moisture storage capabilities, the tropics are fundamental in modulating both regional and global climate. Furthermore, their thermal response during past extreme warming periods, such as super interglacials, is not fully resolved. In this regard, we present high-resolution (analytical) foraminiferal geochemical (δ18O and Mg/Ca) records for the last 1800 kyr from the shallow (487 m) Inner Sea drift deposits of the Maldives archipelago in the equatorial Indian Ocean. Considering the diagenetic susceptibility of these proxies, in carbonate-rich environments, we assess the integrity of a suite of commonly used planktonic and benthic foraminifera geochemical datasets (Globigerinoides ruber (white), Globigerinita glutinata (with bulla), Pulleniatina obliquiloculata (with cortex) and Cibicides mabahethi) and their use for future paleoceanographic reconstructions. Using a combination of spot Secondary Ion Mass Spectrometer, Electron Probe Micro-Analyzer and Scanning Electron Microscope image data, it is evident that authigenic overgrowths are present on both the external and internal test (shell) surfaces, yet the degree down-core as well as the associated bias is shown to be variable across the investigated species and proxies. Given the elevated authigenic overgrowth Mg/Ca (∼12–22 mmol/mol) and δ18O values (closer to the benthic isotopic compositions) the whole-test planktonic G. ruber (w) geochemical records are notably impacted beyond ∼627.4 ka (24.7 mcd). Yet, considering the setting (i.e. bottom water location) for overgrowth formation, the benthic foraminifera δ18O record is markedly less impacted with only minor diagenetic bias beyond ∼790.0 ka (28.7 mcd). Even though only the top of the G. ruber (w) and C. mabahethi records (whole-test data) would be suitable for paleo-reconstructions of absolute values (i.e. sea surface temperature, salinity, seawater δ18O), the long-term cycles, while dampened, appear to be preserved. Furthermore, planktonic species with thicker-tests (i.e. P. obliquiloculata (w/c)) might be better suited, in comparison to thinner-test counter-parts (i.e. G. glutinata (w/b), G. ruber (w)), for traditional whole- test geochemical studies in shallow, carbonate-rich environments. A thicker test equates to a smaller overall bias from the authigenic overgrowth. Overall, if the diagenetic impact is constrained, as done in this study, these types of diagenetically altered geochemical records can still significantly contribute to studies relating to past tropical seawater temperatures, latitudinal scale ocean current shifts and South Asian Monsoon dynamics

Familial hypercholesterolaemia in children and adolescents from 48 countries: a cross-sectional study

Background: Approximately 450 000 children are born with familial hypercholesterolaemia worldwide every year, yet only 2·1% of adults with familial hypercholesterolaemia were diagnosed before age 18 years via current diagnostic approaches, which are derived from observations in adults. We aimed to characterise children and adolescents with heterozygous familial hypercholesterolaemia (HeFH) and understand current approaches to the identification and management of familial hypercholesterolaemia to inform future public health strategies. Methods: For this cross-sectional study, we assessed children and adolescents younger than 18 years with a clinical or genetic diagnosis of HeFH at the time of entry into the Familial Hypercholesterolaemia Studies Collaboration (FHSC) registry between Oct 1, 2015, and Jan 31, 2021. Data in the registry were collected from 55 regional or national registries in 48 countries. Diagnoses relying on self-reported history of familial hypercholesterolaemia and suspected secondary hypercholesterolaemia were excluded from the registry; people with untreated LDL cholesterol (LDL-C) of at least 13·0 mmol/L were excluded from this study. Data were assessed overall and by WHO region, World Bank country income status, age, diagnostic criteria, and index-case status. The main outcome of this study was to assess current identification and management of children and adolescents with familial hypercholesterolaemia. Findings: Of 63 093 individuals in the FHSC registry, 11 848 (18·8%) were children or adolescents younger than 18 years with HeFH and were included in this study; 5756 (50·2%) of 11 476 included individuals were female and 5720 (49·8%) were male. Sex data were missing for 372 (3·1%) of 11 848 individuals. Median age at registry entry was 9·6 years (IQR 5·8-13·2). 10 099 (89·9%) of 11 235 included individuals had a final genetically confirmed diagnosis of familial hypercholesterolaemia and 1136 (10·1%) had a clinical diagnosis. Genetically confirmed diagnosis data or clinical diagnosis data were missing for 613 (5·2%) of 11 848 individuals. Genetic diagnosis was more common in children and adolescents from high-income countries (9427 [92·4%] of 10 202) than in children and adolescents from non-high-income countries (199 [48·0%] of 415). 3414 (31·6%) of 10 804 children or adolescents were index cases. Familial-hypercholesterolaemia-related physical signs, cardiovascular risk factors, and cardiovascular disease were uncommon, but were more common in non-high-income countries. 7557 (72·4%) of 10 428 included children or adolescents were not taking lipid-lowering medication (LLM) and had a median LDL-C of 5·00 mmol/L (IQR 4·05-6·08). Compared with genetic diagnosis, the use of unadapted clinical criteria intended for use in adults and reliant on more extreme phenotypes could result in 50-75% of children and adolescents with familial hypercholesterolaemia not being identified. Interpretation: Clinical characteristics observed in adults with familial hypercholesterolaemia are uncommon in children and adolescents with familial hypercholesterolaemia, hence detection in this age group relies on measurement of LDL-C and genetic confirmation. Where genetic testing is unavailable, increased availability and use of LDL-C measurements in the first few years of life could help reduce the current gap between prevalence and detection, enabling increased use of combination LLM to reach recommended LDL-C targets early in life

Bevacizumab, Irinotecan, or Topotecan Added to Temozolomide for Children With Relapsed and Refractory Neuroblastoma: Results of the ITCC-SIOPEN BEACON-Neuroblastoma Trial

Purpose Outcomes for children with relapsed and refractory high-risk neuroblastoma (RR-HRNB) remain dismal. The BEACON Neuroblastoma trial (EudraCT 2012-000072-42) evaluated three backbone chemotherapy regimens and the addition of the antiangiogenic agent bevacizumab (B). Materials and Methods Patients age 1-21 years with RR-HRNB with adequate organ function and performance status were randomly assigned in a 3 × 2 factorial design to temozolomide (T), irinotecan-temozolomide (IT), or topotecan-temozolomide (TTo) with or without B. The primary end point was best overall response (complete or partial) rate (ORR) during the first six courses, by RECIST or International Neuroblastoma Response Criteria for patients with measurable or evaluable disease, respectively. Safety, progression-free survival (PFS), and overall survival (OS) time were secondary end points. Results One hundred sixty patients with RR-HRNB were included. For B random assignment (n = 160), the ORR was 26% (95% CI, 17 to 37) with B and 18% (95% CI, 10 to 28) without B (risk ratio [RR], 1.52 [95% CI, 0.83 to 2.77]; P = .17). Adjusted hazard ratio for PFS and OS were 0.89 (95% CI, 0.63 to 1.27) and 1.01 (95% CI, 0.70 to 1.45), respectively. For irinotecan ([I]; n = 121) and topotecan (n = 60) random assignments, RRs for ORR were 0.94 and 1.22, respectively. A potential interaction between I and B was identified. For patients in the bevacizumab-irinotecan-temozolomide (BIT) arm, the ORR was 23% (95% CI, 10 to 42), and the 1-year PFS estimate was 0.67 (95% CI, 0.47 to 0.80). Conclusion The addition of B met protocol-defined success criteria for ORR and appeared to improve PFS. Within this phase II trial, BIT showed signals of antitumor activity with acceptable tolerability. Future trials will confirm these results in the chemoimmunotherapy era