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Determining feasibility and tolerability of large volume viscous subcutaneous injection may enable optimized, intuitive delivery system design. A translational early feasibility clinical study examined large volume subcutaneous injection viability, tolerability, acceptability, tissue effects and depot location for ~1, 8, and 20 cP injections at volumes up to 10 ml in the abdomen and 5 ml in the thigh in 32 healthy adult subjects. A commercial syringe pump system delivered 192 randomized, constant rate (20 µl/s) injections (6/subject) with in‐line injection pressure captured versus time. Deposition location was qualified via ultrasound. Tissue effects and pain tolerability were monitored through 2 hours post‐injection with corresponding Likert acceptability questionnaires administered through 72 hours. All injection conditions were feasible and well‐tolerated with ≥79.3% favorable subject responses for injection site appearance and sensation immediately post‐injection, increasing to ≥96.8% at 24 hours. Mean subject pain measured via 100 mm visual analog scale increased at needle insertion (6.9 mm, SD 10.8), peaked during injection (26.9 mm, SD 21.7) and diminished within 10 minutes post‐removal (1.9 mm, SD 4.2). Immediate injection site wheal (90.9%) and erythema (92.6%) formation was observed with progressive although incomplete resolution through 2 hours (44.6% and 11.4% remaining, respectively). Wheal resolution occurred more rapidly at lower viscosities. Most subjects (64.5%) had no preference between abdomen and thigh. Correlations between tissue effects, injection pressure and pain were weak (Pearson’s rho ± 0–0.4). The large volume injections tested, 1–20 cP viscosities up to 10 ml in the abdomen and 5 ml in the thigh, are feasible with good subject acceptability and rapid resolution of tissue effects and pain.

User experience was compared between a new pre-fillable 2.25 mL glass syringe equipped with an ultra-thin-wall (UTW) 8 mm staked needle and a marketed BD Neopak™ syringe equipped with a special-thin-wall (STW) 12.7 mm staked needle.Participants simulated subcutaneous injections with both syringes alone (formative Human Factors study) and in combination with a needlestick-prevention device (validation Human Factors study).Usability results of both studies showed higher success rates for delivering the full dose of 2 mL viscous solution (30 cP) with the 8mmUTW syringe than with the 12.7mmSTW one (63% vs. 42% in the formative study). The use of the 8mmUTW syringe demonstrated also better ease of use and acceptance results and 72% of formative study participants preferred this new syringe over the current one when delivering the viscous solution. Using a shorter needle also showed a benefit in decreasing the injection-related anxiety. Besides, in the case of a non-recommended injection technique, the calculated risk of accidental intramuscular injection is reduced by 2 to 13 times with the 8mmUTW syringe.Altogether, the results obtained demonstrated an improvement of the user experience with this new syringe compared to the current one in the manual delivery of 2 mL viscous solutions.

Background: This study undertook to assess usability, 24-h glycemic profiles, and safety of an investigational basal/bolus insulin delivery device (IDD) providing rapid-acting or regular human insulin (RHI) for people with type 2 diabetes (T2D) transitioning from multiple daily insulin injections (MDIs). Methods: This prospective, single-center, open-label two-period study enrolled adults with T2D and glycated hemoglobin (HbA1c) 7%–11% (53–97 mmol/M). Participants continued the usual MDI therapy during a 2- to 3-day in-clinic MDI period and then within 7 days were switched to the IDD, using current insulin dose, for a 6-day in-clinic IDD period, with blinded continuous glucose monitoring throughout the in-clinic periods. Results: We enrolled 21 participants (mean ± standard deviation age 57 ± 8 years; HbA1c 8.2% ± 0.9% [66 ± 9.8 mmol/M]) using U-100 insulin lispro (n = 11) or who switched to U-100 RHI (n = 10). Glycemic measures improved from the MDI to IDD period, including fasting blood glucose (BG), 141.2 ± 38.3 mg/dL (7.8 ± 2.1 mmol/L) versus 121.2 ± 35.0 mg/dL (6.7 ± 1.9 mmol/L; P = 0.002), respectively; 24-h mean BG, 137.0 ± 20.5 mg/dL (7.6 ± 1.1 mmol/L) versus 125.0 ± 16.5 mg/dL (6.9 ± 0.9 mmol/L; P = 0.004); and time in range (at 70–180 mg/dL; 3.9–10 mmol/L), 81.0% ± 14.4% versus 87.5% ± 10.6% (P = 0.008). No significant differences between MDIs and IDD use were recorded for time

OBJECTIVE Approximately 200 million people worldwide use injectable therapies as part of diabetes management. There appears to be a significant gap between insulin injection technique recommendations and injection practice for many. We aimed to develop and validate a novel, brief, self-administered injection technique assessment questionnaire. RESEARCH DESIGN AND METHODS An iterative codesign process was conducted. Focus groups and interviews with adults (or parents of children) with type 1 or type 2 diabetes and health care providers (HCPs) elicited views and refined the tool for broader distribution to the target audience. Questions addressed ease of understanding; relevance; included items and potential missing questions; feelings about diabetes; and any discomfort or judgment felt when completing the tool. A user guide was developed with cognitive interviewing performed to ensure relevance, acceptability, readability, and understanding. Statistical analyses included propensity score matching to identify a subset of the Worldwide Injection Technique Questionnaire with similar characteristics. Boruta feature selection, Cramér’s V, and multiple correspondence analysis were conducted. RESULTS HCPs and 16 people with diabetes participated in the initial focus groups and interviews. Questions were reported as clinically relevant, simple to complete, “about the right length,” relevant, and easy to understand. A total of 267 participants completed the survey reviewing the questionnaire. A further 16 participants underwent cognitive interviews. The complete resource was then reviewed by another 23 people with diabetes as a final check for completeness and usability. Statistical analyses demonstrated high validity and reliability. CONCLUSION This novel resource is clinically relevant, acceptable, and easy to use as both a clinical tool and a self-assessment tool for people using injectable therapies for diabetes.

Background and Aim: The efficacy of insulin and other injectable therapies depends on injection technique. To develop and validate a brief self-administered injection technique assessment questionnaire. Methods: The questionnaire was developed using an iterative process with people with diabetes (PWD) and healthcare professionals (HCP). Focus groups and 1:1 interviews were held with adults with T1D, T2D and HCPs separately to elicit views and refine the tool ready for broader distribution to target audience. Questions addressed ease of understanding, relevance, included questions and potential missing questions, feelings about diabetes and any discomfort or judgement felt. A user guide was developed with cognitive interviewing performed to ensure relevance, acceptability and understanding by potential users. Multiple Component Analysis assessed relationships between questions after extensive descriptive statistical analysis. Propensity score matching compared the questionnaire to the ITQ WW. Results: Five HCPs and 16 PWD participated in the initial focus groups and interviews. Questions were reported to be clinically relevant by HCPs and simple to complete. PWD reported the 9-item questionnaire to be ’about the right length’, with questions relevant and the user guide easy to read and interpret. 268 participants completed the survey reviewing the questionnaire and provided feedback. A further 16 participants (10 HCPs and 6 PWD) took part in the cognitive interviews. The complete resource was finally reviewed by a further 23 PWD as a check of completeness and usability. Statistical analyses showed the questionnaire to depict similar trends to those assessed in the detailed questionnaire (ITQ WW), confirming the validity of this new questionnaire as a shorter, more straightforward tool. Conclusions: The novel, brief questionnaire and user guide are clinically relevant, acceptable and easy to use both as a clinical resource and a self-assessment tool for people using injectable therapies. Disclosure K.D. Barnard: Advisory Panel; Self; Roche Diabetes Care, Sanofi-Aventis. Research Support; Self; BD, Novo Nordisk A/S, Roche Diabetes Care. E.T. Mahoney: Employee; Self; Becton, Dickinson and Company. D. Morel: Employee; Self; Becton, Dickinson and Company. S. Glezer: Employee; Self; Becton, Dickinson and Company. Employee; Spouse/Partner; Pfizer Inc. Stock/Shareholder; Self; Sanofi. Stock/Shareholder; Spouse/Partner; Sanofi. Funding BD

Pembrolizumab is an FDA-approved immune-checkpoint (IC) inhibitor that targets programmed cell death protein PD-1, and recent phase III trials have demonstrated its superiority over chemotherapy in the treatment of patients with advanced non-small cell lung cancer (NSCLC). Eligibility for treatment with Pembrolizumab is based on demonstration of PD-L1 expression on tumoral cells using the approved companion test 22C3 PharmDx (Dako). Access to the drug depends on a tumor proportion score (TPS) expressing the PD-L1 protein above predetermined cutoffs. The scoring interpretation guide requires a minimum of 100 viable cells to be considered adequate for evaluation. Recent studies have questioned the adequacy of the sampling process when small biopsies are utilized. To further explore this concern, the viable tumor area of 426 consecutive NSCLC biopsies and surgical excisions submitted for PD-L1 assessment was measured and recorded with corresponding PD-L1 expression. About 14.6% of all biopsies measured

A new automated MYC IHC classifier based on bivariate logistic regression is presented. The predictor relies on image analysis developed with the open-source ImageJ platform. From a histologic section immunostained for MYC protein, 2 dimensionless quantitative variables are extracted: (a) relative distance between nuclei positive for MYC IHC based on euclidean minimum spanning tree graph and (b) coefficient of variation of the MYC IHC stain intensity among MYC IHC-positive nuclei. Distance between positive nuclei is suggested to inversely correlate MYC gene rearrangement status, whereas coefficient of variation is suggested to inversely correlate physiological regulation of MYC protein expression. The bivariate classifier was compared with 2 other MYC IHC classifiers (based on percentage of MYC IHC positive nuclei), all tested on 113 lymphomas including mostly diffuse large B-cell lymphomas with known MYC fluorescent in situ hybridization (FISH) status. The bivariate classifier strongly outperformed the “percentage of MYC IHC-positive nuclei” methods to predict MYC+ FISH status with 100% sensitivity (95% confidence interval, 94-100) associated with 80% specificity. The test is rapidly performed and might at a minimum provide primary IHC screening for MYC gene rearrangement status in diffuse large B-cell lymphomas. Furthermore, as this bivariate classifier actually predicts “permanent overexpressed MYC protein status,” it might identify nontranslocation-related chromosomal anomalies missed by FISH.

Background: Lipohypertrophy (LH) is highly prevalent and is potentially harmful to insulin-injecting patients. Methods: In this study, we assessed the impact of injection technique (IT) education, including use of a 4-mm pen needle on insulin-treated patients with clinically observed LH in a randomized, controlled, prospective multicenter study in France with follow-up of 6 months. Intensive education and between-visit reinforcement were given to the intervention group. Control patients received similar messages at study outset. Results: A total of 123 patients were recruited (age 52.1 ± 15.7 years; men 70.7%; body mass index >30 kg/m2: 34.2%; type 1: 53.7%; years with diabetes mellitus: 18.1 ± 10.5), of which 109 patients were included in the final analysis. The intervention group (n = 53) showed a significant decrease of total daily dose of insulin (average at baseline: 54.1 IU) at 3 months (T-3) and 6 months (T-6), reaching just over 5 IU versus baseline (P = 0.035). Corresponding, although not significant, decreases occurred in controls (n = 56); between-group differences were not significant. There were significant decreases in HbA1c (up to 0.5%) at T-3 and T-6 in both groups, with no significant differences between groups. A significant number of intervention patients improved their IT habits; about half achieved ideal IT habits by T-3 versus a quarter of control patients. By T-6, 2/3 of intervention patients achieved either ideal or acceptable IT habits, while only 1/3 of control patients did. Conclusions: Our intervention was effective in both study arms, however, to a greater degree and more rapidly in the intervention group. Widespread application of this intervention could be highly cost-effective.

Background: Limited published data exists quantifying the influence of human factors (HF) and pen needle (PN) design on delivery outcomes of pen injection systems. This preclinical in vivo study examines the impact of PN hub design and applied force against the skin during injection on needle penetration depth (NPD). Method: To precisely locate injection depth, PN injections (20 µl; 2 IU, U-100 volume equivalent) of iodinated contrast agent were administered to the flank of Yorkshire swine across a range of clinically relevant application forces against the skin (0.25, 0.75, 1.25, and 2.0 lbf). The NPD, representing in vivo needle tip depth in SC tissue, from four 32 G × 4 mm PN devices (BD Nano™ 2nd Gen and three commercial posted-hub PN devices; n = 75/device/force, 1200 total) was measured by fluoroscopic imaging of the resulting depot. Results: The reengineered hub design more closely achieved the 4 mm target NPD with significantly less variability ( P = .006) than commercial posted-hub PN devices across the range of applied injection forces. Calculations of IM (intramuscular) injection risk completed through in silico probability model, using NPD and average human tissue thickness measurements, displayed a commensurate reduction (~2-8x) compared to conventional PN hub designs. Conclusions: Quantifiable differences in injection depth were observed between identical labeled length PN devices indicating that hub design features, coupled with aspects of variable injection technique, may influence injection depth accuracy and consistency. The reengineered hub design may reduce the impact of unintended individual technique differences by improving target injection depth consistency and reducing IM injection potential.

From February 1, 2014, through June 30, 2015, 13,289 insulin-injecting patients from 423 centers in 42 countries took part in one of the largest surveys ever performed in diabetes. The goal was to assess patient characteristics, as well as historical and practical aspects of their injection technique. Results show that 4- and 8-mm needle lengths are each used by nearly 30% of patients and 5- and 6-mm needles each by approximately 20%. Higher consumption of insulin (as measured by total daily dose) is associated with having lipohypertrophy (LH), injecting into LH, leakage from the injection site, and failing to reconstitute cloudy insulin. Glycated hemoglobin values are, on average, 0.5% higher in patients with LH and are significantly higher with incorrect rotation of sites and with needle reuse. Glycated hemoglobin values are lower in patients who distribute their injections over larger injection areas and whose sites are inspected routinely. The frequencies of unexpected hypoglycemia and glucose variability are significantly higher in those with LH, those injecting into LH, those who incorrectly rotate sites, and those who reuse needles. Needles associated with diabetes treatment are the most commonly used medical sharps in the world. However, correct disposal of sharps after use is critically suboptimal. Many used sharps end up in public trash and constitute a major accidental needlestick risk. Use of these data should stimulate renewed interest in and commitment to optimizing injection practices in patients with diabetes.

Background Automated infusion devices captures actual infused medication administration data in real-time. Vancomycin use is now recommended to be driven by AUC (area under the curve) dosing. We evaluated automated infusion device data to depict vancomycin administration practices in acute care hospitals. Figure 1. Distribution of vancomycin infusion dosing Figure 2. Distribution of time intervals between each vancomycin infusion session (mostly around 8 or 12 hours) Methods We analyzed archived vancomycin infusion data from 2,417 patients captured by automated infusion systems from 3 acute care hospitals. The infusion device informatics software recorded a variety of events during infusion – starting and stopping times, alarms and alerts, vancomycin dose, and other forms of timestamped usage information. We evaluated infusion session duration and dosing, using data-driven clustering algorithms. Results A total of 13,339 vancomycin infusion sessions from 2,417 unique adult patients were analyzed. Approximately 26.1% of patients had just one infusion of vancomycin. For the rest of the patients, the median number of infusion sessions per patient was 4; the interquartile range was 3 and 8. The most common dose was 1.0 gram (53.7%) or 1.5 gram (24.6%) (see Figure 1). The distribution of infusion session duration (hours) was 4.2% (≤1.0 hh); 40.1% (1.01–1.5 hh); 29.1% (1.51–2.0 hh); and 26.6% (>2.0 hh). The dosing frequency was 39.5% (q8 hh), 42.9% (q12 hh), 11.1% (q24 hh), and 6.5% (>q24 hh) (Figure 2), demonstrating clinical interpretability. Conclusion A considerable number of patients received just one vancomycin infusion during their hospital stay, suggesting a potential overuse of empiric vancomycin. The majority of infusion doses were between 1 to 1.5 grams and most infusion sessions were administered every 8 or 12 hours. The actual infusion duration for each dose often exceeds the prescribed 1- or 2-hour infusion orders, which may be due to known instances of infusion interruptions due to patient movement, procedures or IV access compromise. The data generated by infusion devices can augment insights on actual antimicrobial administration practices and duration. As vancomycin AUC dosing becomes more prevalent, real world infusion data may aid timely data-driven antimicrobial stewardship and patient safety interventions for vancomycin and other AUC dosed drugs. Disclosures Cynthia Yamaga, PharmD, BD (Employee) David L. Bostick, PhD, Becton, Dickinson and Co. (Employee) Ying P. Tabak, PhD, Becton, Dickinson and Co. (Employee) Ann Liu-Ferrara, PhD, Becton, Dickinson and Co. (Employee) Didier Morel, PhD, Becton, Dickinson and Co. (Employee) Kalvin Yu, MD, Becton, Dickinson and Company (Employee)GlaxoSmithKline plc. (Other Financial or Material Support, Funding)

Background Large scale research on antimicrobial usage in real-world populations traditionally does not consist of infusion data. With automation, detailed infusion events are captured in device systems, providing opportunities to harness them for patient safety studies. However, due to the unstructured nature of infusion data, the scale-up of data ingestion, cleansing, and processing is challenging. Figure 1. Illustration of dosing complexity Methods We applied algorithmic techniques to quantitate and visualize vancomycin administration data captured in real-time by automated infusion devices from 3 acute care hospitals. The device data included timestamped infusion events – infusion started, paused, restarted, alarmed, and stopped. We used time density-based segmentation algorithms to depict infusion sessions as bursts of event activity. We examined clinical interpretability of the cluster-defined sessions in defining infusion events, dosing intensity, and duration. Results The algorithms identified 13,339 vancomycin infusion sessions from 2,417 unique patients (mean = 5.5 sessions per patient). Clustering captured vancomycin infusion sessions consistently with correct event labels in >98% of cases. It disentangled ambiguity associated with unexpected events (e.g. multiple stopped/started events within a single infusion session). Segmentation of vancomycin infusion events on an example patient timeline is illustrated in Figure 1. The median duration of infusion sessions was 1.55 (1st, 3rd quartiles: 1.14, 2.02) hours, demonstrating clinical plausibility. Conclusion Passively captured vancomycin administration data from automated infusion device systems provide ramifications for real-time bed-side patient care practice. With large volume of data, temporal event segmentation can be an efficient approach to generate clinically interpretable insights. This method scales up accuracy and consistency in handling longitudinal dosing data. It can enable real-time population surveillance and patient-specific clinical decision support for large patient populations. Better understanding of infusion data may also have implications for vancomycin pharmacokinetic dosing. Disclosures David L. Bostick, PhD, Becton, Dickinson and Co. (Employee) Kalvin Yu, MD, Becton, Dickinson and Company (Employee)GlaxoSmithKline plc. (Other Financial or Material Support, Funding) Cynthia Yamaga, PharmD, BD (Employee) Ann Liu-Ferrara, PhD, Becton, Dickinson and Co. (Employee) Didier Morel, PhD, Becton, Dickinson and Co. (Employee) Ying P. Tabak, PhD, Becton, Dickinson and Co. (Employee)

All parenteral delivery systems require a device/tissue site interface, where design, human factors, and tissue biomechanics impact successful function for consistent, reliable delivery. Limited published data exists quantifying these factors and their interaction effects on delivery success. This in vivo study examines pen needle (PN) hub design and skin application force impacts on needle penetration depth (NPD). PN injections (2µl contrast agent) were administered to Yorkshire swine flanks at clinically measured skin application forces (0.25, 0.75, 1.25 and 2.0 lbf). In vivo NPD from four 32G x 4mm PN devices (investigational BD Nano™ PRO and three commercial PN devices; n=75/device/force, 1200 total) were measured by fluoroscopic imaging. The BD Nano™ PRO more closely achieved the 4mm target NPD with significantly less variability (p Quantifiable differences observed between PN devices indicate that design features, coupled with aspects of variable use, influence injection consistency. The BD Nano™ PRO design may reduce impact of unintended individual injection technique differences and IM injection potential, which could decrease insulin absorption variability leading to more consistent glycemic control. Disclosure C. Rini: Employee; Self; Becton, Dickinson and Company. B.C. Roberts: Employee; Self; Becton, Dickinson and Company. D. Morel: Employee; Self; Becton, Dickinson and Company. R. Klug: None. B.L. Selvage: None. R.J. Pettis: Employee; Self; Becton, Dickinson and Company. Stock/Shareholder; Self; Becton, Dickinson and Company. Research Support; Self; JDRF. Board Member; Self; JDRF.

Objective: Accuracy is recognized as an important attribute of continuous glucose monitors (CGMs). The objective of this research was to understand if improvements in CGM accuracy impact clinical outcomes in patients with T1DM or T2DM. Research Design and Methods: A review of literature published from January 1999 to June 2017 was conducted using Medline. Articles were included if they reported desired outcome measures of clinical efficacy (HbA1c reduction, time-in-range [TIR], hypoglycemia detection or reduction) regardless of patient diabetes type. Simple linear and multiple regressions were utilized to evaluate the relationship between mean absolute relative difference (MARD) and measures of efficacy. Results: The literature search yielded 574 results from which 20 articles met the inclusion criteria. MARD for commercialized CGM devices improved, on average, 0.75% per year (R2=0.87, p Conclusion: CGM accuracy correlates with an increased detection of hypoglycemic events, but not with HbA1c reduction. Disclosure C.J. Koziel: None. D. Bialonczyk: Employee; Self; Becton, Dickinson and Company. D. Morel: Employee; Self; Becton, Dickinson and Company. J. Petisce: None. D. Saliu: Employee; Self; Becton, Dickinson and Company.

Background Automation in microbiology laboratories impacts management, workflow, productivity and quality. Further improvements will be driven by the development of intelligent image analysis allowing automated detection of microbial growth, release of sterile samples, identification and quantification of bacterial colonies and reading of AST disk diffusion assays. We investigated the potential benefit of intelligent imaging analysis by developing algorithms allowing automated detection, semi-quantification and identification of bacterial colonies. Methods Defined monomicrobial and clinical urine samples were inoculated by the BD Kiestra™ InoqulA™ BT module. Image acquisition of plates was performed with the BD Kiestra™ ImagA BT digital imaging module using the BD Kiestra™ Optis™ imaging software. The algorithms were developed and trained using defined data sets and their performance evaluated on both defined and clinical samples. Results The detection algorithms exhibited 97.1% sensitivity and 93.6% specificity for microbial growth detection. Moreover, quantification accuracy of 80.2% and of 98.6% when accepting a 1 log tolerance was obtained with both defined monomicrobial and clinical urine samples, despite the presence of multiple species in the clinical samples. Automated identification accuracy of microbial colonies growing on chromogenic agar from defined isolates or clinical urine samples ranged from 98.3% to 99.7%, depending on the bacterial species tested. Conclusion The development of intelligent algorithm represents a major innovation that has the potential to significantly increase laboratory quality and productivity while reducing turn-around-times. Further development and validation with larger numbers of defined and clinical samples should be performed before transferring intelligent imaging analysis into diagnostic laboratories.

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International audience; Tissue microarrays (TMAs) make possible the screening of hundreds of different tumour samples for the expression of a specific protein. Automatic features extraction procedures lead to a series of covariates corresponding to the averaged stained scores. In this article, we model the random geometry of TMA cores using voronoi tesselations. This formalism enables the computation of indices of spatial correlation of stained scores using both classical and novel approaches. The potential of these spatial statistics to correctly discriminate between diseased and non-diseased cases is evaluated through the analysis of a TMA containing samples of breast carcinoma data. The results indicate a significant improvement in the breast cancer prognosis.

Despite the recent progress in the description of the molecular mechanisms of proliferation and differentiation controls in vitro, the regulation of the homeostasis of normal stratified epithelia remains unclear in vivo. Computer simulation represents a powerful tool to investigate the complex field of cell proliferation regulation networks. It provides huge computation capabilities to test, in a dynamic in silico context, hypotheses about the many pathways and feedback loops involved in cell growth and proliferation controls.

Qu’est-ce que l’ethique, et serait-elle « fonctionnelle » ? L’article interroge les limites des « bonnes intentions », en termes d’incidence relationnelle ; en ce sens, elles ne vaudraient que comprises et partagees. Mais l’attitude ethique ne s’exprime pas en fonction d’une reciprocite attendue, meme si l’on ne peut qu’en esperer une harmonie interpersonnelle. Celle-ci etant incertaine, c’est alors qu’il faut se preparer a etre moins decu ; c’est de lucidite et de sens des responsabilites dont il s’agit. Il est dans cet article question de notre rapport au reel.

A direct and easy chlorination of substituted isoprenoid derivatives in a hydrocarbon solvent affords allylic chlorides via an ene-type reaction. These mild conditions tolerate various functional groups and this procedure is very convenient for an industrial process.

The copper (I) catalysed substitution of allylic chlorides by alk-1-ynes leads to the synthesis of new terpene derivatives. An efficient synthesis of phytone is described.

Quel sens y aurait-il a pretendre que « l’ecole d’educateurs est une ecole de gauche » ? Il faut admettre la possible diversite des ideologies de chacun, comme il faut egalement distinguer endoctrinement et formation professionnelle.Cela dit, il est un cadre ethique dans lequel une relative pluralite de positionnements politiques est certes possible ; cadre auquel nous sommes tenus, qu’on le veuille ou non. Ce systeme de valeurs est celui des Droits de l’homme, sorte de religion civile contemporaine. On n’echappe donc pas a une formation qui comporte une forte dimension ideologique. On peut alors « travailler » la contradiction entre liberte de penser et cadre ideologique oblige.

The reaction of a hydroxylated base with 3-chloro-2-methyl-6-methylene 1,7-octadiene in the presence of a palladium complex and a quaternary ammonium salt gives a novel tetraene : 2-methyl-6-methylene-1,3E,7-octatriene, which is a new C 10 terpene synthon. A novel access to pseudo-ionone is also described.

The palladium-catalysed addition of allylic chlorides to carbonucleophiles leads to the formation of new terpene derivatives. A facile and economical route of phytone is described.

The reaction of β-ketoesters, β-diketones and β-sulfonylketones with N-halosuccinimides in the presence of a base gives α-halo-carbonyl and α-halo-sulfonyl derivatives by a one-pot halo-deacylation reaction. A facile synthesis of pseudo-ionone is described.

The water-soluble composition rhodium/tris (sodium 3-sulfophenyl) phosphine (TPPTS) selectively catalyses the condensation of isoprene with active methylene compounds. An efficient synthesis of isofeprazone is described.

Soluble polymers and crosslinked resins containing difluoroacetic side- groups were used as supports for h3-allyl nickel and molybdenum complexes. Both types of anchored complexes in themselves are effective catalysts for the stereospecific polymerization of 1,3 butadiene, while the nickel complex, activated by reaction with aluminium cocatalysts, catalyzes olefin and diolefin hydrogenation and propylene dimerization.