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Background and importance Despite a strict regulatory framework of clinical trials (CTs), few standardised tools are available. Our national survey conducted in 2020 demonstrated that all clinical research pharmacists (CRPs) have initiated a quality approach, which is however very heterogeneous and implemented more in university hospital centres and cancer centres, with a high activity level. New standardised tools for the investigational health products (IHPs) circuit would be of interest to 88/94 CRPs. The most useful tool was the self-assessment grid, according to 94% of CRPs. Thus we developed such a tool to manage specific risks of IHPs (complex protocols, assignment of treatment numbers, confusing packaging or labelling). Aim and objectives The aim of this work was create a standardised self-assessment grid to manage the specific risks of IHPs. Material and methods A pharmacy resident and two doctors of pharmacy of a regional working group defined a list of 66 evaluation criteria, mainly based on good clinical practices and on a professional guide of 2020 by the national university centre hospitals’ pharmacists commission. The criteria were divided into three main parts: general organisation and support functions; pharmaceutical management of CTs; and risk assessment and risk management. Then the grid was sent for validation to the 94 CRPs who had answered our national survey. The Delphi method was used and consensus among experts was defined by a satisfaction rate of >80% for relevance, clearness and accessibility. Results The first round of proofreading by 16 pharmacists led to a consensus of 85% (56/66) for the criteria, which were considered relevant, clear and assessable. This led to 36 modifications, 4 deletions and 2 additions of criteria. The second round by 8 pharmacists led to a consensus of 88% (60/68) for the criteria and resulted in 18 modifications and 2 deletions. There remained only one criterion considered irrelevant, which was deleted. These results led us to validate the final version of the grid, including 62 criteria. Conclusion and relevance This interactive tool will be disseminated in a free public online ‘CTs’ toolbox. It will provide a conformity score per process, allowing specific risks to be identified across the circuit of IHPs, by pharmacies in any healthcare facility, whatever the level of activity. References and/or acknowledgements Conflict of interest No conflict of interest

Surface mass balance (SMB) variations of the Greenland ice sheet (GrIS) have been identified as an important contributor to contemporary and projected global mean sea level variations, but their impact on the regional sea level change pattern is still poorly known. This study proposes estimates of GrIS SMB over 1900–2100 based on the output of 32 atmosphere–ocean general circulation models and Earth system models involved in phase 5 of the Climate Model Intercomparison Project (CMIP5). It is based on a downscaling technique calibrated against the Modèle Atmosphérique Régional (MAR) regional climate model and it provides an ensemble of 32 Greenland SMB estimates for each Greenland major drainage basin. Because the GrIS SMB does not respond uniformly to greenhouse gas (GHG) emissions, the southern part of the GrIS is more sensitive to climate warming. This study shows that this part should be in imbalance in the twenty-first century sooner than the northern part. This regional variability significantly affects the associated relative sea level pattern over the entire ocean and particularly along the U.S. East Coast and the northern coast of Europe. This highlights the necessity of taking into account GrIS regional SMB changes to evaluate accurately relative sea level changes in future projections.

Introduction et but de l’etude Le recours a la nutrition parenterale (NP) en oncologie doit repondre a certaines obligations (telles que la prescription, l’administration et les surveillances associees). Lors d’une precedente evaluation des pratiques professionnelles realisee avec l’INTERCLAN d’Auvergne, une forte demande de formation complementaire a pu etre mise en evidence au sujet de la NP de la part du personnel infirmier interroge. Materiel et methodes Dans un premier temps, nous avons elabore un questionnaire pour identifier les connaissances sur les bonnes pratiques de la NP chez l’adulte. Ce dernier a ete distribue au sein des principaux services prescripteurs du Centre Jean Perrin (centre de lutte contre le cancer) a Clermont-Ferrand: reanimation, chirurgie et oncologie. Le personnel a repondu a 21 items classes en cinq categories (prescription, preparation, administration, interactions et surveillances associees a une poche de NP). Dans un second temps, nous avons imagine un fascicule de poche reprenant ces bonnes pratiques. Resultats et analyse statistique A partir d’un effectif de 68 infirmiers, 22 questionnaires ont ete recueillis du 14 janvier au 28 fevrier 2019. Recommandations connues par la majorite des interroges Recommandations peu connues par la majorite des interroges Prescription d’une poche de NP Co-prescription d’une supplementation oligo-vitaminiques (100 %) Prescription d’une NP non recommandee pour une duree estimee inferieure a 7 jours (54 %) Preparation d’une poche de NP Duree de stabilite d’une poche de NP (86 %) Verification systematique de differents parametres avant administration, exemple: integrite de la poche et date de peremption (95 %) Administration d’une poche de NP Via une voie d’abord centrale (100 %) Utilisation de compresses avec antiseptique alcoolique (82 %) Debit maximal de perfusion de 2 mL/kg/h (59 %) Desinfection des mains avec solution hydroalcoolique (54 %) Interactions/Incompatibilites avec la poche de NP Aucun medicament ne doit etre ajoute directement dans la poche (63 %) Surveillances a effectuer lors d’une administration d’une poche de NP Temperature du patient (95 %) Poids du patient (50 %) Inspection du point d’entree (59 %) Conclusion La majorite des infirmier(e)s interroges sont globalement sensibilises aux risques lies a la prescription d’une NP. Il nous a semble important d’insister sur certains points pour la redaction du fascicule notamment: les precautions d’hygiene, la co-prescription systematique d’oligo-elements et vitamines, les modalites d’administration des medicaments lors d’une NP associee ainsi que la surveillance quotidienne du patient.

The rising of oral anticancer therapies let more and more patients to be cared at home and improve their quality of life. However the toxicities of these drugs and the distance with health professionals imply that the patient needs to be more autonomous with respect to his treatment. Patients through therapeutic education programs allows them to manage side effects, to be more observant and then to subsequently benefit from the treatment. We report here, oncology clinical pharmacists experiences in some health facilities in France, presented at the 1st day of clinical oncology pharmacy (December 2017, Marseille).

Summary Introduction In order to reduce outpatient-waiting delays in oncology departments, there has been development of new production processes. This study aimed to determine the impact of three different production organizations (nominative extemporaneous preparations, anticipated preparations, and non-nominative dose-banded preparations), with or without analytical control, on outpatient chemotherapy production times, in a French regional cancer center. Materials and methods For the three organizations, we measured the global and detailed production times of the preparations, during three distinct periods, and compared them. Results With an analytical control, anticipated nominative preparations and non-nominative dose-banded preparations reduced waiting delays by 29 and 19 minutes, respectively, compared to extemporaneous nominative preparations, and by 12 and 9 minutes, respectively, without analytical control. Discussion Anticipated nominative preparations and non-nominative dose standardized preparations allow reducing time dispensation, even with analytical control. Conclusion Implementing these new production processes could reduce outpatient-waiting delays in oncology departments.

Resume Introduction Afin de reduire le temps d’attente des patients des hopitaux de jour en oncologie, de nouveaux processus de preparation ont ete developpes. Cette etude compare les temps de dispensation de trois circuits de production (preparations magistrales du jour meme, preparations magistrales anticipees ou preparations hospitalieres a doses standardisees), avec ou sans controle analytique, au sein d’un centre de lutte contre le cancer. Materiel et methodes Au cours de trois periodes distinctes, les temps totaux de dispensation et les temps des etapes intermediaires ont ete mesures, puis compares entre eux. Resultats Les preparations magistrales anticipees et hospitalieres a doses standardisees permettent des gains de temps respectifs de 29 et 19 minutes avec un controle analytique, et de 12 et 9 minutes sans controle analytique, sur les preparations magistrales du jour meme. Discussion Les preparations magistrales et les preparations hospitalieres a doses standardisees reduisent le temps de dispensation, y compris en cas de controle analytique. Conclusion Ces nouveaux procedes de fabrication et de gestion de la production peuvent participer a la diminution du temps d’attente des patients en hopital de jour.

A novel method to produce spin-aligned rare-isotope (RI) beam has been developed, that is the two-step projectile fragmentation method with a technique of dispersion matching. The present method was verified in an experiment at the RIKEN RIBF, where an RI beam of 32Al with spin alignment of 8(1) % was successfully produced from a primary beam of 48Ca, with 33Al as an intermediate nucleus. Figure of merit of the present method was found to be improved by a factor larger than 50 compared with a conventional method employing single-step projectile fragmentation. ispartof: pages:47-51 ispartof: Hyperfine Interactions vol:220 issue:1 pages:47-51 ispartof: 4th Joint International Conference on Hyperfine Interactions / International Symposium on Nuclear Quadrupole Interactions (HFI/NQI) location:Beijing, China date:10 Sep - 14 Sep 2012 status: published

The electric quadrupole moment of the $_{13}^{33}\mathrm{Al}_{20}$ ground state, located at the border of the island of inversion, was obtained using continuous-beam $\ensuremath{\beta}$-detected nuclear quadrupole resonance ($\ensuremath{\beta}$-NQR). From the measured quadrupole coupling constant ${\ensuremath{\nu}}_{Q}=2.31(4)$ MHz in an $\ensuremath{\alpha}\ensuremath{-}{\mathrm{Al}}_{2}{\mathrm{O}}_{3}$ crystal, a precise value for the electric quadrupole moment is extracted: $\left|{Q}_{s}\left(^{33}\mathrm{Al}\right)\right|=141(3)$ mb. A comparison with large-scale shell model calculations shows that $^{33}\mathrm{Al}$ has at least 50% intruder configurations in the ground state wave function, favoring the excitation of two neutrons across the $N=20$ shell gap. $^{33}\mathrm{Al}$ therefore clearly marks the gradual transition north of the deformed Na and Mg nuclei towards the normal $Z\ensuremath{\ge}14$ isotopes.

The decays of two isomeric states in the neutron-rich nucleus $^{75}\mathrm{Cu}$ have been studied via delayed $\ensuremath{\gamma}$-ray spectroscopy. These states were populated by the fragmentation of a $60.4\phantom{\rule{4pt}{0ex}}A\phantom{\rule{0.16em}{0ex}}\mathrm{MeV} ^{86}\mathrm{Kr}$ primary beam, which impinged on a Be target at the LISE2k spectrometer of GANIL. Isomeric half-lives and branching ratios were measured, and a $\ensuremath{\gamma}\ensuremath{-}\ensuremath{\gamma}$ coincidence analysis performed. These have allowed a revised level scheme of $^{75}\mathrm{Cu}$ to be proposed. A comparison with large-scale shell-model calculations using different effective interactions and valence spaces shows the importance of proton excitations across the $Z=28$ shell gap for reproducing the energy spacing between the isomeric states. The coexisting collective and single-particle properties of the $(1/{2}^{\ensuremath{-}})$ and $(3/{2}^{\ensuremath{-}})$ states, respectively, are similar to those of the same states in the neighboring $^{69,71,73}\mathrm{Cu}$. The small energy spacings between the $(1/{2}^{\ensuremath{-}}), (3/{2}^{\ensuremath{-}})$, and $5/{2}^{\ensuremath{-}}$ states are responsible for the isomerism.

We report on a new measurement of the g factor of the (13/2(+)) isomeric state in the neutron-rich nucleus Cu-69. This study demonstrates the possibility of obtaining considerable nuclear spin alignment for multi-quasiparticle states in single-nucleon removal reactions. The time-dependent perturbed angular distribution (TDPAD) method was used to extract the gyromagnetic factor of the (13/2(+)) [T-1/2 = 351(14) ns] isomeric state of Cu-69. Its g factor was obtained as g(13/2(+)) = 0.248( 9). The experimentally observed spin alignment for the state of interest was deduced as A = -3.3(9)%.

Excited states of the neutron-rich nuclei (97,99)Rb were populated for the first time using the multistep Coulomb excitation of radioactive beams. Comparisons of the results with particle-rotor model calculations provide clear identification for the ground-state rotational band of (97)Rb as being built on the πg(9/2) [431] 3/2(+) Nilsson-model configuration. The ground-state excitation spectra of the Rb isotopes show a marked distinction between single-particle-like structures below N=60 and rotational bands above. The present study defines the limits of the deformed region around A∼100 and indicates that the deformation of (97)Rb is essentially the same as that observed well inside the deformed region. It further highlights the power of the Coulomb-excitation technique for obtaining spectroscopic information far from stability. The (99)Rb case demonstrates the challenges of studies with very short-lived postaccelerated radioactive beams.

Influence of stress on immunity and pathogenesis relates to corticotropic axis: hypothalamus-hypophysis-surrenals (HHS). Its over-stimulation due to traumas during early childhood or before birth seems to generate brain abnormalities such as reduction of hippocampus volume. More typical of adult age, hypothalamus-pineal gland axis (HP), responsible for melatonin production, may be impaired because of chronic stress, mainly through sleep disturbances or addictive behaviours. Old age has been reported to produce same impairments. Circadian cycle of melatonin is closely related to immune functions and its disturbance seems to induce, among populations undergoing frequent changes of life rhythm, a significant raise of cancer incidence: night shift workers, air pilots... Stress then seems enable to increase cancer risk through its negative impact on HHS and HP axis and therefore on immunity. Immunotherapy, which was an interesting solution considering this, has not yield yet expected results. Upstream, other ways have been successfully investigated in prospective randomised trials, such as psychotherapeutic treatments, with positive effects on cellular immunity and survival. The ability to condition immune responses in animals allows thinking that hypnotherapy could also be used along with standard treatments.

Resume La melatonine est une petite molecule lipophile, secretee essentiellement dans la glande pineale. La synthese de cette hormone suit un rythme circadien avec un pic vers les 2–3 heures du matin. La melatonine possede de nombreux recepteurs dans l'organisme ce qui lui confere des fonctions multiples telles que la resynchronisation des rythmes biologiques, l'induction du sommeil, la vasoregulation mais aussi l'immunomodulation. De nombreuses experiences realisees dans ce domaine ont permis de decouvrir differentes interactions entre la melatonine et le systeme immunitaire, et surtout le lien qui existe entre la melatonine et la lutte anticancereuse de l'organisme via le systeme immunitaire. Des essais de phase II chez l'homme rapportent une diminution de la thrombocytopenie, une amelioration du taux de certaines cytokines et une augmentation de la reponse objective chez des patients atteints de cancer. Afin de confirmer et d'approfondir ces resultats, nous nous proposons de realiser un essai de phase II randomise melatonine versus placebo chez des patientes atteintes de cancers du sein metastatiques apres deux lignes de traitement.

We report on a shell model study of ${}^{43}S$ and ${}^{44}S$. Quadrupole rotational invariants proposed by Kumar about 40 years ago allow us to estimate axial and triaxial deformation parameters from shell model calculations. Present results, showing the large impact of the triaxial degree of freedom on the low-lying structure of studied sulfur isotopes, resolve several inconsistencies in previous interpretations of experimental data. In ${}^{43}S$ the prolate ground-state band coexists with a triaxial band built on the 7/2${}_{1}^{\ensuremath{-}}$ isomer and an excited prolate structure built on the ${K}^{\ensuremath{\pi}}$ = 5/2${}^{\ensuremath{-}}$ deformed orbit originating from the $\ensuremath{\nu}{f}_{7/2}$ shell. In ${}^{44}S$ coexistence of two deformed bands built on mixed 0${}_{1,2}^{+}$ states is reported as well as a pseudo-$\ensuremath{\gamma}$-band and an excited triaxial structure for which a particle-hole neutron excitation couples to proton collectivity. Present results are in good global agreement with recent antisymmetrized molecular dynamics and beyond-mean-field calculations.

International audience; La démence à corps de Lewy (DCL) est la deuxième cause de démence dégénérative du sujet âgé, dans les grandes séries autopsiques. Dans la réalité quotidienne des centres mémoire pourtant, la DCL représente une faible proportion des diagnostics cliniques, avec une forte disparité entre les centres. Plusieurs raisons peuvent rendre compte de la faible sensibilité du diagnostic de DCL : l’imprécision et la subjectivité des critères diagnostiques existants ; la place insuffisante donnée à certains signes non-moteurs (troubles du comportement en sommeil paradoxal, dysautonomie) ; enfin et surtout l’association quasi constante de la pathologie de Lewy à une pathologie de type Alzheimer, qui domine rapidement le phénotype clinique. À l’heure de l’essor des thérapies ciblées contre les agrégats protéiques, de nouvelles échelles cliniques permettant d’appréhender la coexistence de la pathologie de Lewy dans la maladie d’Alzheimer sont plus que jamais nécessaires.

A method to produce spin-aligned rare isotope (RI) beams has been developed, where a scheme of twostep projectile fragmentation to produce the RI of interest with high spin alignment and a technique of momentum-dispersion matching are combined. Effectiveness of the present method was demonstrated in an experiment at the RIKEN RIBF, where an RI beam of 32Al with spin alignment of 8(1)% was successfully produced from a primary beam of 48Ca, via an intermediate RI of 33Al. Figure of merit of the present method was found to be more than 50 times greater than that of the conventional method employing single-step projectile fragmentation. ispartof: Nuclear Instruments & Methods in Physics Research B vol:317 pages:769-773 ispartof: location:JAPAN, RIKEN Nishina Ctr Accelerator Based Sci, Matsue status: published

Dementia with Lewy bodies (DLB) is the second cause of degenerative dementia in autopsy studies. In clinical pratice however, the prevalence of DLB is much lower with important intercenter variations. Among the reasons for this low sensitivity of DLB diagnosis are (1) the imprecision and subjectivity of the diagnostic criteria; (2) the underestimation of non-motor symptoms (REM-sleep behavior disorder, dysautonomia, anosmia); mostly (3) the nearly constant association of Lewy bodies with Alzheimer's disease pathology, which dominates the clinical phenotype. With the avenue of targeted therapies against the protein agregates, new clinical scales able to apprehend the coexistence of Lewy pathology in Alzheimer's disease are expected.

Drugs pharmacokinetic control is a usual practice in case of flat continuous infusions. It enables among others, to modulate delivered doses when drug concentrations in blood appear too high. With chronotherapy, this possibility becomes more difficult because of sinusoidal outflows of infusion. We propose here a method that enables this follow-up, established through the study of 21 metastatic colorectal cancer patients, treated with a chronomodulated infusion of high dose 5-fluoro-uracil (5-FU) and folinic acid. This pharmacokinetic follow-up permitted the modelisation of 5-FU clearance and the calculation of an index, which was, in our study, correlated to the treatment response and also to main encountered toxicities.

This work has been supported by BMBF 06BN109, GA of Czech Republic 202/040791, MICINN-FPA2009-13377, CM-HEPHACOSS2009/ESP-1473 (Spain), the EC through the Eurons project Contracts No. RII3-CT-3/2004-506065, No. OTKA K68801, and No. K100835, the Bolyai Foundation, and by Romanian ANCS, CNCS UEFISCDI, Project No. PN-II-RU-TE-2011- 3-0051. R. B., A. B., F. N., and F. R. acknowledge the IN2P3/ CNRS support

We report on the spectroscopic quadrupole moment measurement of the 7/2(1)(-) isomeric state in S-43(16)27 [E* = 320.5(5) keV, T-1/2 = 415(3) ns], using the time dependent perturbed angular distribution technique at the RIKEN RIBF facility. Our value, vertical bar Q(s) vertical bar = 23(3) efm(2), is larger than that expected for a single-particle state. Shell model calculations using the modern SDPF-U interaction for this mass region reproduce remarkably well the measured vertical bar Q(s) vertical bar, and show that non-negligible correlations drive the isomeric state away from a purely spherical shape.

The $g$ factor of the ${2}_{1}^{+}$ state of ${}^{168}$Hf was measured using the perturbed angular correlation technique in a static external magnetic field. The result, $g({2}_{1}^{+})=0.17(3)$, is discussed in relation to the systematics of the previously reported $g$ factors in the Hf isotopes and compared to the predictions of several models. An interesting outcome of the analysis presented in this paper has to do with the relatively small result for the $g$ factor. This indicates that in the Hf isotopes, a minimum in the $g$(${2}_{1}^{+}$) dependence on $N$ occurs at $N\ensuremath{\le}98$ and not at midshell, as expected from IBA-2 or large-scale shell-model calculations. The pairing plus quadrupole model of Kumar and Baranger predicts a minimum at $N=98$ and gives the best description of the experimental data. The present result clearly shows the importance of $g$-factor measurements in ``fine-tuning'' among different models.

Expérience GANIL/LISE3/EXOGAM; International audience; It is well known that the nuclear shell structure changes for the most exotic nuclei. One of the consequences ofthis phenomenon is the modification of the "classical" magic numbers, as experimentally observed at N = 20 and N = 28.Nevertheless, the mechanisms responsible for such changes are still under discussion and more experimental information isneeded to better constrain the theoretical models. In these proceedings, we report on the discovery and the experimental studyby precise spectroscopy experiments of the 0+2 state in 34Si and 44S. The 34Si is located between the magic spherical 36S andthe deformed 32Mg, member of the so-called island of inversion, whereas 44S is located between the magic spherical 48Caand the deformed 42Si. Therefore, the structure of these nuclei, and in particular the phenomenon of shape coexistence, isof crucial importance to understand how the intruder configurations progressively dominate the ground state structure of themost exotic nuclei at both N = 20 and N = 28.

We measured the lifetimes of the ${2}_{1,2}^{+}$ and ${4}_{1}^{+}$ states in ${}^{98}$Ru in order to reduce their uncertainties and resolve the discrepancies in the literature for the lifetime of the ${4}_{1}^{+}$ state. Coulomb excitation in inverse kinematics was used to populate excited states in ${}^{98}$Ru, and the recoil distance doppler shift (RDDS) method was employed using the nNew Yale plunger device (NYPD). This technique combined with inverse Coulomb excitation requires several corrections due to relativistic and deorientation effects but yields high precision lifetimes. The determined ${B}_{4/2}=B({4}_{1}^{+}\ensuremath{\rightarrow}{2}_{1}^{+})/B({2}_{1}^{+}\ensuremath{\rightarrow}{0}_{1}^{+})=1.86(16)$ agrees well with the vibrational limit. In order to analyze the data, a new method for the deorientation correction of RDDS data was developed using the perturbation of experimental angular correlations. The simultaneous measurement of deorientation and lifetime of a given state and its application are discussed. The method is suitable for radioactive beam experiments.

The degree of freedom of spin in quantum systems serves as an unparalleled laboratory where intriguing quantum physical properties can be observed, and the ability to control spin is a powerful tool in physics research. We propose a novel method for controlling spin in a system of rare isotopes which takes advantage of the mechanism of the projectile fragmentation reaction combined with the momentum-dispersion matching technique. The present method was verified in an experiment at the RIKEN RI Beam Factory, in which a degree of alignment of 8% was achieved for the spin of a rare isotope Al-32. The figure of merit for the present method was found to be greater than that of the conventional method by a factor of more than 50., Comment: 18 pages, 5 figures

International audience; To produce a radioactive-isotope (RI) beam with high spin alignment, we have developed a novel method, the two-step projectile-fragmentation (PF) method, that employs momentum-dispersion matching. An on-line experiment to produce 32Al from 48Ca via 33Al was performed at RIKEN RI Beam Factory. In the experiment, we succeeded in producing approximately 8% spin alignment in an RI beam of 32Al. In this paper, we focus on evaluating the magnitude of spin alignment realized in one-nucleon removal from 33Al

The 02+ state in Si34 has been populated at the GANIL-LISE3 facility through the β decay of a newly discovered 1 + isomer in Al34 of 26(1) ms half-life. The simultaneous detection of e +e - pairs allowed the determination of the excitation energy E(02+)=2719(3)keV and the half-life T 1/2=19.4(7)ns, from which an electric monopole strength of ρ2(E0)=13.0(0.9)×10 -3 was deduced. The 21+ state is observed to decay both to the 01+ ground state and to the newly observed 02+ state [via a 607(2) keV transition] with a ratio R(21+→01+/21+→02+)=1380(717). Gathering all information, a weak mixing with the 01+ and a large deformation parameter of β=0.29(4) are found for the 02+ state, in good agreement with shell model calculations using a new sdpf-u-mix interaction allowing np-nh excitations across the N=20 shell gap, This work has been supported by BMBF 06BN109, GA of Czech Republic 202/040791, MICINN-FPA2009-13377, CM-HEPHACOSS2009/ESP-1473 (Spain), the EC through the Eurons project Contracts No. RII3-CT-3/2004-506065, No. OTKA K68801, and No. K100835, the Bolyai Foundation, and by Romanian ANCS, CNCS UEFISCDI, Project No. PN-II-RU-TE-2011- 3-0051. R. B., A. B., F. N., and F. R. acknowledge the IN2P3/ CNRS support

A new plunger device for Recoil-Distance Doppler Shift and Time-Differential Recoil-In-Vacuum measurements has been developed at the CSNSM in collaboration with the IPN Orsay. It is conceived to be easily adapted to different experimental setups and facilities, in particular to the future radioactive beam facility Spiral2. An electronic feedback system keeping the distance between target and stopper foils constant, imperative for precision measurements of short lifetimes, was also developed. The plunger device was commissioned with an experiment performed at the IPN Orsay Tandem accelerator laboratory using the Orgam germanium detector array. Excited states in 76 Kr were populated using the reaction 45 Sc( 35 Cl,2p2n) 76 Kr. The lifetime τ of the 4 1 + state was determined to 4.3(6) ps, in accordance with previous measurement, confirming the functionality of the new plunger device. The commissioning experiment showed in particular that the electronic feed back system works as foreseen.

The compatibility and stability of continuously infused isosorbide dinitrate (ISDN) and heparin with medical plastics were investigated by simulating therapeutic conditions practiced in hospital. High-performance liquid chromatography (HPLC) with UV detection and C18 column was used to quantify the drugs. The results show that the compatibility of ISDN and heparin solutions with polypropylene syringesduring a 12 h continuous infusion is good. Preparing the syringes 8 h in advance does not alter the stability of the drugs, as long as the ISDN is not refrigerated (at + 4°C). The stability of ISDN with PVC/PE tubing (polyvinyl chloride on the outside and polyethylene inside) is also satisfactory irrespective of whether it is administered alone or mixed with heparin. The behaviour of heparin with the PVC/PE tubing is more difficult to interpret, since the variations in concentration near 10% of the initial concentration of heparin. ISDN and heparin both have a compatibility problem with PVC tubing. ISDN is rapidly fixed on PVC and then released: it is released earlier when it is administered with heparin in the tube. Some heparin is lost in the PVC tubing. This loss is relatively stable with time and is similar and independent of the type of infusion solvent, or whether heparin is used by itself or in combination with ISDN.

The quadrupole deformations for the low-lying states in the transitional nuclei 100,101Pd have been deduced through the measurement of their electric quadrupole transition probabilities using the Recoil Distance Doppler Shift Method. The nuclei were studied using a 268 MeV 80Se beam impinging on a thin, self-supporting 24Mg target. States in 100Pd and 101Pd populated by the four and three neutron evaporation channels respectively, with reaction gamma-rays detected using the SPEEDY gamma-ray detection array. The recoiling nuclei were stopped in a copper foil and gamma-ray coincidence data taken at 10 separate target-stopper distances between 35 μm and 750 μm. The mean-lifetimes for the lowest lying 2+ (in 100Pd) and 15/2- (in 101Pd) states were measured to be 13.3(9) ps and 10.8(8) ps respectively. These data are compared with predictions from nuclear Total Routhian Surface calculations, which are found to agree with the experimentally deduced values to within 10%.

Neurofilaments are neuronal intermediate filaments that play an important role in the growth and maintenance of large myelinated axons. Mammalian neurofilaments are composed of three polypeptide subunits, designed as NF-L, NF-M, and NF-H, all of which are phosphorylated. Here, we demonstrate by several criteria that neurofilament polypeptides are also modified by an abundant type of intracellular protein glycosylation in which single N-acetylglucosamine monosaccharides are O-glycosidically (O-GlcNAc) linked to serine or threonine residues. In purified neurofilament proteins, the O-GlcNAc modifications occur at a stoichiometry of approximately 0.1 and 0.15 mol of GlcNAc/mol of NF-L and NF-M, respectively. The predominant sites of O-GlcNAc attachment on NF-L and NF-M are identified using proteolysis, purification of the glycopeptides, and subsequent analysis by automated gas-phase sequencing, manual Edman degradation, and laser desorption mass spectrometry. For NF-L, both major sites of glycosylation (Thr21 and Ser27) are located at the NH2-terminal head domain. For NF-M, one major site (Thr48) lies within the NH2-terminal head domain, whereas the other (Thr431) is located at the tail domain. Deletions encompassing these sites have been shown previously to have a dominant detrimental effect upon neurofilament assembly, raising questions about the specific function(s) of the saccharide moieties at these sites. Specific identification of these O-GlcNAc attachment sites has set the stage for more detailed mutagenic analysis of O-GlcNAc functions on neurofilaments.

Ambiguities in amino acid sequences are a potential problem in X-ray crystallographic studies of proteins. Amino acid side chains often cannot be reliably identified from the electron density. Many protein crystal structures that are now being solved are simple variants of a known wild-type structure. Thus, cloning artifacts or other untoward events can readily lead to cases in which the proposed sequence is not correct. An example is presented showing that mass spectrometry provides an excellent tool for analyzing suspected errors. The X-ray crystal structure of an insertion mutant of Staphylococcal nuclease has been solved to 1.67 Å resolution and refined to a crystallographic R value of 0.170 [Keefe & Lattman (1992). In preparation]. A single residue has been inserted in the C-terminal α helix. The inserted amino acid was believed to be an alanine residue, but the final electron density maps strongly indicated that a glycine had been inserted instead. To confirm the observations from the X-ray data, matrix-assisted laser desorption mass spectrometry was employed to verify the glycine insertion. This mass spectrometric technique has sufficient mass accuracy to detect the methyl group that distinguishes glycine from alanine and can be extended to the more common situation in which crystallographic measurements suggest a problem with the sequence, but cannot pinpoint its location or nature.

Traditional herbal formulas used to treat inflammatory arthritis in China and India include Boswellia carterii or Boswellia serrata . They both contain boswellic acids (BAs) which have been shown to exhibit anti-inflammatory and antiarthritic properties. This study tests the hypothesis that mixtures of BAs derived from B. carterii have immunomodulatory properties. B. carterii plant resin obtained from China was prepared as an ethanol extract, and the presence of seven BAs was confirmed by column chromatography, high-performance liquid chromatography, and UV laser desorption/ionization tandem mass spectroscopy. The extract was then tested for its ability to alter in vitro production of TH1 cytokines (interleukin-2 [IL-2] and gamma interferon) and TH2 cytokines (IL-4 and IL-10) by murine splenocytes. Delivery of the resin extract using ethanol as a solvent resulted in significant cellular toxicity not seen with the addition of ethanol alone. By contrast, delivery of the resin extract using a sesame oil solvent resulted in a dose-dependent inhibition of TH1 cytokines coupled with a dose-dependent potentiation of TH2 cytokines. These results indicate that a purified mixture of BAs from B. carterii plant resin exhibits carrier-dependent immunomodulatory properties in vitro.

Influence of stress on immunity and pathogenesis relates to corticotropic axis: hypothalamus-hypophysis-surrenals (HHS). Its over-stimulation due to traumas during early childhood or before birth seems to generate brain abnormalities such as reduction of hippocampus volume. More typical of adult age, hypothalamus-pineal gland axis (HP), responsible for melatonin production, may be impaired because of chronic stress, mainly through sleep disturbances or addictive behaviours. Old age has been reported to produce same impairments. Circadian cycle of melatonin is closely related to immune functions and its disturbance seems to induce, among populations undergoing frequent changes of life rhythm, a significant raise of cancer incidence: night shift workers, air pilots... Stress then seems enable to increase cancer risk through its negative impact on HHS and HP axis and therefore on immunity. Immunotherapy, which was an interesting solution considering this, has not yield yet expected results. Upstream, other ways have been successfully investigated in prospective randomised trials, such as psychotherapeutic treatments, with positive effects on cellular immunity and survival. The ability to condition immune responses in animals allows thinking that hypnotherapy could also be used along with standard treatments.

Melatonin is a small lipophile molecule, essentially secreted by pineal gland. The synthesis of this hormone shows a circadian pattern with a peak around 2-3 hours am. Many melatonin receptors are found in the body, which explains its multiple functions as biological rhythms resynchronisation, sleep induction, vasoregulation and even immunomodulation. Many experiments realised in this field have permit to discover different interactions between melatonin and the immune system, and especially the link which exists between melatonin and the fight against cancer via the immune system. Phase II studies reported a decrease of thrombocytopenia, an increase of some cytokines rate and an increase of objective responses in cancer patients. In order to confirm these results and to lead further research, we propose to realise a phase II randomised study melatonin versus placebo in metastatic breast cancer patients after two lines of treatment.

Drugs pharmacokinetic control is a usual practice in case of flat continuous infusions. It enables among others, to modulate delivered doses when drug concentrations in blood appear too high. With chronotherapy, this possibility becomes more difficult because of sinusoidal outflows of infusion. We propose here a method that enables this follow-up, established through the study of 21 metastatic colorectal cancer patients, treated with a chronomodulated infusion of high dose 5-fluoro-uracil (5-FU) and folinic acid. This pharmacokinetic follow-up permitted the modelisation of 5-FU clearance and the calculation of an index, which was, in our study, correlated to the treatment response and also to main encountered toxicities.

Medical prescription of hematopoietic growth factors (HGF) was analysed in 19 anticancer french centers during 2 months. About 4% of anticancer chemotherapeutic cycles prescribed during this period were supported by HGF prescription. The mean duration of treatment was 8 days. Among the 755 collected prescriptions, two tumor localizations represented about 50% of the prescriptions: malignant non Hodgkin lymphomas and breast cancer. The other main localizations concerned adult or pediatric soft tissue sarcomas (18%), testicular cancer (7%) and gynecologic tumors (6%). The prescription for primary prophylaxis for febrile neutropenia remains the main use of HGF (44%). The respect of the guidelines established by the F|d|ration nationale des centres de lutte contre le cancer was analyzed. Overall, 66% of the prescriptions were in adequation with these guidelines. Whereas the consommation of HGF decreased in the 19 considered institutions, it did not reach a plateau and could decrease in institutions which are awaked to the international and national recommendations.