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Background Comparison of two recommended European Pharmacopoeia 9th Ed methods of sterility assay (membrane filtration versus direct seeding (DS)) highlights an important difference of sensitivity threshold. This threshold by membrane filtration method is at least lower or equal to 0. 14UFC/mL. Purpose The aim of the study is to determine the sensitivity threshold of the DS method. This method is currently used in our Hospital Pharmacy Unit (HPU) for binary parenteral nutrition (PN) bags. Material and methods For this study, four bags of 30 mL, with a representative composition to those produced each day were each sown by a calibrated strain Bioball® 30 UFC (Candida albicans, Bacillus subtilis, Staphylococcus aureus, Pseudomonas aeruginosa) in order to obtain a concentration of 1UFC/mL. Then, four levels of dilution were carried out from each PN bag: 0.8 UFC/mL, 0.6 UFC/mL, 0.4 UFC/mL, 0.2 UFC/mL. For each level of dilution, 5 × 1 mL of each bag were taken in order to sow five cultures media, sabouraud dextrose agar slope (biomerieux) or Brain-Heart Infusion Broth (BHIB – comic) according to the strain. Culture media BHIB were incubated for 3 days at 37°C, then 11 days at 22°C, while the culture media sabouraud were incubated for 14 days at 22°C. Results After 14 days of incubation, for each strain tested, there were between 0 and 4 growths according to the dilution’s level. No concentration made it possible to have 100% of positivity, so sensitivity’s threshold is thus higher than 1UFC/mL. Compared to membrane filtration, the detection’s threshold by DS is at least seven times superior. Conclusion Even if this study did not estimate with precision a sensitivity threshold for the DS method, it has highlighted the limits for sterility assay of binary parenteral nutrition bags. So it possible to confirm the superiority of the membrane filtration method. Tests with higher micro-organisms’ concentrations in binary PN bags are planned to establish with precision the minimal detection threshold. No conflict of interest

Background Since the March 2015 directive publication of the country’s health department, parenteral nutrition (PN) must be produced by hospital pharmacists, under pharmaceutical responsibility. How to manage closing periods of the hospital pharmacy unit (HPU) to manufacture individualised formulation of paediatric PN (IFPN) for newborns. Purpose Summarise the state of management of HPU closure for IFPN through a survey of hospitals in the country in 2017. Material and methods A survey with oriented questions according to answers was developed. This form was sent by email to the hospital pharmacist. After general questions (Healthcare Establishment (HE) type: General Hospital Centre (GHC) or University Hospital Centre (UHC), maternity level (classed 1 to 3 in our country)), the first part approaches alternative solutions in case of no production during the HPU closing period. Then, the second part, for IFPN production, which answers different questions concerning formulation validation, production and controls. Results Nineteen received responses were studied. For HE type: 17 UHC (89.5%) and two GHC (10.5%), all had a maternity (whose 95% with neonatal intensive care unit, level 3 (n=18)). Twelve of 17 pharmacists (65%) report no IFPN during the closing period. A major alternative solution is IFPN, which wereproduced before the closure period (e.g. on Friday). While 16% (n=2) of HE reported using only IFPN, 83.3% (n=10) use IFPN and standardised PN (SPN) and 25% (n=3) associated IFPN, SPN, and industrial PN (with or without supplementation). For other HE (35%, n=7) with PN activity on the weekend, 57.1% (n=4) produces IFPN at HPU and 42.9% (n=3) in the paediatric care unit. Only IFPN which were produced at HPU are formulations checked by a pharmacist. Then, for controls, everybody declared a double visual control during production, 71% realised analytics assays (mainly Na and K), 40% performed microbiologic assay and 60% (n=4) labelling check and mirage. Pharmaceutical liberation is reported on 80%. Conclusion These results based on statements remain to be analysed cautiously but the trend is no production of IFPN on the weekend. In case of preparations, controls on final product allows the provision of a quality product for newborns. Compliance with the directive remains difficult, perhaps a consensus around SPN with paediatric physicians will make it possible to avoid PN production activity outside the opening period of HPU. References and/or Acknowledgements Pharmacists who had completed survey. No conflict of interest

Background Following the obtaining of the Temporary Recommendation for Use (RTU) in 2015, Hospital Pharmacy Unit (HPU) manufactured syringes of Avastin ® (bevacizumab) for treatment of age-related macular degeneration (AMD). Financial interest is significant, as cost of Avastin ® is definitely lower than current drugs used for the same disease, and whose similar effectiveness has been demonstrated by several bibliographical studies. Purpose The aim of the study is to determine the economic impact of this manufacturing of syringes by the HPU, from September 2016 to September 2017. Material and methods Avastin 2.5 mg/0.1 mL syringes manufacturing requires material resources (isolator, syringes, needles, caps, flask of Avastin ® 100 mg/4 mL) and staff (pharmacy technicians). Cost calculation of annual production made it possible to estimate the benefits obtained using manufacturated syringes by the ophthalmology care unit in our hospital and by other healthcare establishments (HE). A comparison with the estimated cost of using the Lucentis ® (ranibizumab) drug, which has Medicinal Market Authorisation (MMA) in this therapeutic indication, was carried out. Results The HPU produced 39 batches yearly, in 1010 syringes, for a total cost of €15 251. Finally, 17.8% of syringes are used by the hospital and are refunded by social security (€100), and 39.8% of syringes are sold at other HE. Total annual gain is €14,648, while use of Lucentis ® would allow an annual earning of €8451. Despite the losses (42.4%) due to a short expiry date, manufacturing Avastin ® syringes compared with Lucentis ® generates a higher gain, nearly €6,197€. Conclusion With current consumption, this study shows that manufacturing of Avastin ® syringes is financially promising in the treatment of AMD for our HPU, compared to the use of Lucentis ® . Nevertheless, to optimise the profitability of Avastin syringes’ production, it would be interesting to correlate sessions’ productions with requests, thus improving production scheduling to decrease losses and increase earnings. No conflict of interest

Localizada sobre una zona plantar, la queratodermia dinamica difiere de los queratomas puntuales ligados al apoyo, al roce articular o a presiones indeterminadas. Durante la marcha, las celulas queratinociticas se enmaranan, se deslizan las unas sobre las otras, forman columnas que se inclinan hacia uno u otro lado, pero permanecen en conjunto. La union dermoepidermica conecta la dermis con la epidermis y facilita su flexibilidad durante el paso. Las lineas de Langer, o dermatoglifos, marcan el anclaje epidermico a lo largo de lineas paralelas, hundidas, que resisten las tracciones de la epidermis, lo que explica el pliegue de las capas superficiales entre las lineas de Langer, el revestimiento epidermico. El mecanismo continua en tres etapas: primero una cresta gruesa y seca, a continuacion el espolon y, a nivel del corion, el banderin o la lengueta. Se observa el banderin sobre todo en los dedos en supra o infraductus, la lengueta bajo la arcada anterior de un pie cavo y el espolon a nivel del reborde posterior del talon. La piel plantar presenta los efectos del cambio del eje corporal en la estatica del pie, produciendo una rotacion dermoepidermica alrededor del eje de una articulacion. El callo dinamico, sintesis puntual del conjunto, presenta un eje oblicuo.

Background To improve medicinal treatment management, we decided to review prescriptions in a long term care unit (LTCU), because elderly patients are at higher risk of adverse drugs events. Firstly, they benefit from entrance medicines reconciliation (MedRec) but this can be very difficult with poor efficiency. Indeed, for these patients, questioning is difficult and their pharmacist or general practitioner are not informative because multiple hospitalisations results in loss of medical information. Secondly, it was decided to start periodical medication reviews (MedRev) in association with a physician/pharmacist to evaluate the efficiency of therapeutic medications. Purpose The aim of this study was to evaluate the efficiency of this new activity and physician acceptation to improve appreciation of MedRev. Material and methods Only patients in the LTCU were selected; MedRev is performed quarterly for each department. The LTCU covers 4 departments. Recorded information was ATC class, and type and number of pharmaceutical interventions (PI). Three tools were used: PAPA Guide, Laroche and STOPP/START lists. Results 2 departments benefited from this MedRev (34 patients). The average number of PI per patient was 1.3, with 47% acceptance rate. PI performed concerned mainly drugs of N ATC class (64%, nervous system medicines) and then drugs of A ATC class (28%, digestive system medicines). These PI were dose reduction in 58% and discontinuation in 38%. Whereas 60% of PI offering dose reduction were accepted, only 20% of PI regarding discontinuation were accepted. For medicines ATC A, 67% of the IP were accepted and only 41% of IP regarding ATC N drugs were followed. Conclusion It seems necessary to continue this work, which allows the creation of close links with doctors to discuss and optimise each prescription. High level of physician approbation shows the interest in the MedRev. It also helps pharmacists to improve their impact as members of the patient care team. References and/or acknowledgements Physician of LTCU. No conflict of interest

Background The development of experimental medicine (EM) for clinical trials is a tedious but lucrative activity for hospital pharmacies. This activity requires the compounding of poorly described compounds with often unfavourable biopharmaceutical characteristics. National competent authorities (NCA) now require a high level of proof to approve such preparations. To evaluate (i) safety of use and (ii) potential efficiency of EM, in vitro characterisation of tissular bioavailability can be performed on devices called diffusion cells. Purpose Available diffusion cells are research devices that are not well adapted to the context of HP. We developed and validated a new, easy to use, inexpensive and versatile diffusion cell called VitroPharma, meant to obtain permeation and penetration data across a wild range of biological or artificial membranes. Material and methods VitroPharma was developed in collaboration with a local plasturgist. A validation study using caffeine and testosterone as model compounds, covering (i) infinite and finite donor conditions, (ii) artificial and biological membranes and (iii) different types of liquid and semi-solid receptor fluids was performed. VitroPharma was compared with a widely used diffusion cell reference (ie, Franz cell). Results Permeation results in both cells were fitted to a mathematical model following Fick’s laws of diffusion. Permeability characteristics given by the model were compared using a non-parametric test. VitroPharma was found to be equivalent to the Franz cell under harmonised experimental conditions. Furthermore, VitroPharma enabled the determination of tissular penetration kinetics which in return enabled prefiguration of EM medicine active ingredient exposure and safety profile in future clinical trials. Such data will be presented to the NCA in the EM pharmaceutical dossier to apply for approval. Conclusion VitroPharma was adapted to EM development. Furthermore, it can be used in quality control hospital preparations containing BSC class III and IV compounds and in other assessments where penetration and permeation data in a biological or artificial (ie, gloves, conditioning device) membrane are required in hospital pharmacies. No conflict of interest

Background Enzyme replacement therapy with SUCRAID offers a pharmacologic alternative to sucrose free diets to treat symptoms in congenital sucrase–isomaltase deficiency (CSID). But a resent shortage leaves patients without any treatment. Invertase, like Kerry’s BIOINVERT 200 solution, is an enzyme widely used in confectionery production (E1103). It also hydrolyses sucrose to give glucose and fructose. It may be an interesting substitute for SUCRAID. However, this food grade solution needs pharmaceutical qualification. Purpose To propose a method of pharmaceutical qualification of BIOINVERT 200 based on our experience, and to evaluate its specifications as a substitute for SUCRAID. Material and methods Several characteristics were tested or measured, such as density (calculated by weighing), pH, osmolality (measurement by freezing point), enzyme activity (dosage with Sigma-Aldrich MAK118 set), residual solvent (search by gas chromatography coupled with flame ionisation detector), sterility test (by liquid cultures) and abnormal toxicity (tested on mice according to the European Pharmacopoeia). Results The results obtained are shown in the table. Conclusion Because of high osmolality, BIOINVERT, like SUCRAID, has to be diluted 10 times before use. The enzyme activity is lower than Kerry’s specifications (11 020–13 340 IU/mL at 55°C). It is also lower than SUCRAID (8500 IU/mL). For pharmaceutical qualification, heavy metals research is required. Then, the clinical effectiveness of BIOINVERT 200 could be tested. References and/or acknowledgements The association ‘La vie sans sucre’ and Dr Melanie Bonnet for her time and the loan of the microplate reader. No conflict of interest

International audience; The microstructure and hardness evolution of three alloys based on the system Cu–Ti–Sn, rich in copper, have been investigated (CuTi2 wt.%Sn2.75 wt.%, CuTi3 wt.%Sn2.75 wt.% and CuTi4 wt.%Sn2.75 wt.%). They are characterised by the presence of the ternary eutectic intermetallic CuTi3Sn5 in the as cast state. Suitable thermomechanical treatments cannot dissolve this phase. The effect of a variation in Ti content during ageing was studied by microstructure observations (S.E.M.), chemical analysis (W.D.S.), D.T.A, X.R.D. and hardness testing (Vickers). The low hardness obtained led to consider a chromium addition in CuTi4 wt.%Sn2.7 5wt.%. As for last materials, the microstructure of this alloy is related to its Vickers hardness.

International audience

A monoclonal antibody was obtained from BALB/c mice immunized with Penicillium frequentans mycelium. The specificity of the antibody was evaluated by enzyme-linked immunosorbent and indirect immunofluorescence assays against the same mycelium. This IgM antibody cross-reacted with various strains of the Penicillium and Aspergillus genera. By indirect immunofluorescence assays, the antibody was able to stain about 10% of Penicillium and Aspergillus conidia, but major part of conidia did not absorb the fluorescence-labeled antibody before swelling. During germination of P. frequentans conidia, the germ tube wall which constitutes a continuation of an inner wall layer was also stained. During germination of P. griseofulvum, the protrusion of the germ tube wall was not always recognized by the antibody because the germ tube wall was constituted by a continuation of an outer spore wall layer. The study of the staining patterns of the spores and the protrusions suggests that the antibody specifically recognizes an antigen of the inner spore wall layer. The monoclonal antibody reacts with extracellular galactomannans produced by genera Aspergillus and Penicillium but is not directed against beta-(1,5)-linked galactofuranose units.

Enzyme-linked immunosorbent assay (Elisa) and immunofluorescence have been used to detect species of Penicillium, Aspergillus and other moulds. Thirteen species of Penicillium subgenera Aspergilloides, Furcatum and Penicillium and five species of Aspergillus were tested for their immunological reaction with monoclonal antibodies directed to P. glabrum (Wehmer) Westling, A.versicolor (Vuill.) Tiraboschi, Geotrichum candidum Link and Mucor racemosus Fres. Cross reactions showed that monoclonal antibodies directed to M. racemosus, G. candidum and A.versicolor are specific. Similar reactions with monoclonal antibodies from P. glabrum or A.versicolor show that one antigenic determinant is shared by all species of moulds tested. Other monoclonal antibodies show that at least one epitope is shared by Penicillium and Aspergillus but not other genera listed above. At least one epitope is shared by all Penicillium subgen. Aspergilloides and Aspergillus, and at least one by all tested species of subgen. Aspergilloides. With the monoclonals tested, no distinction was found between subgen. Furcatum and subgen. Penicillium. Antigenicity appears to correlate well with morphological data. Elisa tests are faster than microscopical or biological examination. The method seems appropriate for defining precise relationships between taxa.

The palaeobotanical record of early Palaeolithic sites from Western Europe indicates that hominins settled in different kinds of environments. During the "Mid-Pleistocene Transition (MPT)", from about 1 to 0.6 Ma, the transition from 41-ka to 100-ka dominant climatic oscillations, occurring within a long-term cooling trend, was associated with an aridity crisis which strongly modified the ecosystems. Starting from the MPT the more favorable climate of central and southern Italy provided propitious environmental conditions for long-term human occupations even during the glacial times. In fact, the human strategy of territory occupation was certainly driven by the availabilities of resources. Prehistoric sites such as Notarchirico (ca. 680–600 ka), La Pineta (ca. 600–620 ka), Gaudo San Nicola (ca. 380–350 ka) or Ceprano (ca. 345–355 ka) testify to a preferential occupation of the central and southern Apennines valleys during interglacial phases, while later interglacial occupations were oriented towards the coastal plains, as attested by the numerous settlements of the Roma basin (ca. 300 ka). Faunal remains indicate that human subsistence behaviors benefited of a diversity of exploitable ecosystems, from semi-open to closed environments. In central and southern Italy, several palynological records have already illustrated the regional and local scale vegetation dynamic trends. During the Middle Pleistocene climate cycles, mixed mesophytic forests developed during the interglacial periods and withdrew in response to increasing aridity during the glacial episodes. New pollen data from the Boiano basin (Molise, Italy), attest to the evolution of vegetation and climate between OIS 13 and 9 (ca. 500 to 300 ka). In this basin, the persistence of high edaphic humidity, even during the glacial phases, could have favored the establishment of a refuge area for the arboreal flora and provided subsistence resources for the animal and hominin communities during the Middle Pleistocene. This could have constrained human groups to migrate into such a propitious area. Regarding to the local climate evolution during the glacial episodes, the supposed displacement from these sites could be linked to the environmental dynamics solely due to the aridity increase rather than directly to the global climate changes.