4,153 research outputs found
Cytotoxics compounded sterile preparation control by HPLC during a 16-month assessment in a French university hospital: importance of the mixing bags step
The Centralized Chemotherapy Reconstitution Unit (CCRU) of Paul Brousse Hospital Pharmacy Department assessed the reliability of its Cytotoxics Compounded Sterile Products (CCSP) preparation method in order to improve its CCSP quality assurance system. Five cytotoxic drugs — gemcitabine, 5-fluorouracil, docetaxel, paclitaxel, and oxaliplatin — were assayed by high performance liquid chromatography (HPLC) to determine CCSP concentration. During the observation period, 23,892 CCSP were prepared. Overall, 12,964 preparations contained one of the five analyzed drugs; 7382 (56.9%) out of 12,964 CCSP were analyzed by HPLC; 646 (8.8%) out of 7382 concentrations were outside ± 20% of the prescribed dose; 544 (84.2%) out of 646 were post-administration results and could not be verified. Out of 102 (15.8%) pre-administration results that were re-tested after re-shaking, 94 (92.2%) were found to be acceptable upon re-testing, and 8 (7.8%) were confirmed to be unacceptable and needed to be re-compounded. The 8.8% of tested CCSP were outside ± 20% of the prescribed dose, but extrapolating the results on re-tested CCSP, we can say that our CCSP preparation is reliable with an estimation of only 0.7% of 7382 CCSP analyzed, confirmed as being ± 20% outside the prescribed dose. Nevertheless, this ± 20% magnitude of error should be reduced. Based on pre-administration results, the primary cause of concentration errors appeared to be insufficient mixing of the finished product. Most CCSP dosages occurred after it had been administered, the organization should, therefore, be improved to include testing all CCSP prior to administration. Pharmaceutical companies should endeavor to manufacture compounded injectible drugs in a ‘ready to use’ form and provide vehicles in accurate volumes in order to improve compounding precision
Effective action and the quantum equation of motion
We carefully analyse the use of the effective action in dynamical problems,
in particular the conditions under which the equation \frac{\delta \Ga}
{\delta \phi}=0 can be used as a quantum equation of motion, and the relation
between the asymptotic states involved in the definition of \Ga and the
initial state of the system. By considering the quantum mechanical example of a
double-well potential, where we can get exact results for the time evolution of
the system, we show that an approximation to the effective potential in the
quantum equation of motion that correctly describes the dynamical evolution of
the system is obtained with the help of the wilsonian RG equation (already at
the lowest order of the derivative expansion), while the commonly used one-loop
effective potential fails to reproduce the exact results.Comment: 28 pages, 13 figures. Revised version to appear in The European
Physical Journal
Eutectic Colony Formation: A Stability Analysis
Experiments have widely shown that a steady-state lamellar eutectic
solidification front is destabilized on a scale much larger than the lamellar
spacing by the rejection of a dilute ternary impurity and forms two-phase cells
commonly referred to as `eutectic colonies'. We extend the stability analysis
of Datye and Langer for a binary eutectic to include the effect of a ternary
impurity. We find that the expressions for the critical onset velocity and
morphological instability wavelength are analogous to those for the classic
Mullins-Sekerka instability of a monophase planar interface, albeit with an
effective surface tension that depends on the geometry of the lamellar
interface and, non-trivially, on interlamellar diffusion. A qualitatively new
aspect of this instability is the occurence of oscillatory modes due to the
interplay between the destabilizing effect of the ternary impurity and the
dynamical feedback of the local change in lamellar spacing on the front motion.
In a transient regime, these modes lead to the formation of large scale
oscillatory microstructures for which there is recent experimental evidence in
a transparent organic system. Moreover, it is shown that the eutectic front
dynamics on a scale larger than the lamellar spacing can be formulated as an
effective monophase interface free boundary problem with a modified
Gibbs-Thomson condition that is coupled to a slow evolution equation for the
lamellar spacing. This formulation provides additional physical insights into
the nature of the instability and a simple means to calculate an approximate
stability spectrum. Finally, we investigate the influence of the ternary
impurity on a short wavelength oscillatory instability that is already present
at off-eutectic compositions in binary eutectics.Comment: 26 pages RevTex, 14 figures (28 EPS files); some minor changes;
references adde
Changing concepts in plant hormone action
Summary: A plant hormone is not, in the classic animal sense, a chemical synthesized in one organ, transported to a second organ to exert a chemical action to control a physiological event. Any phytohormone can be synthesized everywhere and can influence different growth and development processes at different places. The concept of physiological activity under hormonal control cannot be dissociated from changes in concentrations at the site of action, from spatial differences and changes in the tissue's sensitivity to the compound, from its transport and its metabolism, from balances and interactions with the other phytohormones, or in their metabolic relationships, and in their signaling pathways as well. Secondary messengers are also involved. Hormonal involvement in physiological processes can appear through several distinct manifestations (as environmental sensors, homeostatic regulators and spatio-temporal synchronizers, resource allocators, biotime adjusters, etc.), dependent on or integrated with the primary biochemical pathways. The time has also passed for the hypothesized ‘specific' developmental hormones, rhizocaline, canlocaline, and florigen: root, stem, and flower formation result from a sequential control of specific events at the right places through a coordinated control by electrical signals, the known phytohormones and nonspecific molecules of primary and secondary metabolism, and involve both cytoplasmic and apoplastic compartments. These contemporary views are examined in this revie
Sources and sinks separating domains of left- and right-traveling waves: Experiment versus amplitude equations
In many pattern forming systems that exhibit traveling waves, sources and
sinks occur which separate patches of oppositely traveling waves. We show that
simple qualitative features of their dynamics can be compared to predictions
from coupled amplitude equations. In heated wire convection experiments, we
find a discrepancy between the observed multiplicity of sources and theoretical
predictions. The expression for the observed motion of sinks is incompatible
with any amplitude equation description.Comment: 4 pages, RevTeX, 3 figur
De novo variants disturbing the transactivation capacity of POU3F3 cause a characteristic neurodevelopmental disorder
POU3F3, also referred to as Brain-1, is a well-known transcription factor involved in the development of the central nervous system, but it has not previously been associated with a neurodevelopmental disorder. Here, we report the identification of 19 individuals with heterozygous POU3F3 disruptions, most of which are de novo variants. All individuals had developmental delays and/or intellectual disability and impairments in speech and language skills. Thirteen individuals had characteristic low-set, prominent, and/or cupped ears. Brain abnormalities were observed in seven of eleven MRI reports. POU3F3 is an intronless gene, insensitive to nonsense-mediated decay, and 13 individuals carried protein-truncating variants. All truncating variants that we tested in cellular models led to aberrant subcellular localization of the encoded protein. Luciferase assays demonstrated negative effects of these alleles on transcriptional activation of a reporter with a FOXP2-derived binding motif. In addition to the loss-of-function variants, five individuals had missense variants that clustered at specific positions within the functional domains, and one small in-frame deletion was identified. Two missense variants showed reduced transactivation capacity in our assays, whereas one variant displayed gain-of-function effects, suggesting a distinct pathophysiological mechanism. In bioluminescence resonance energy transfer (BRET) interaction assays, all the truncated POU3F3 versions that we tested had significantly impaired dimerization capacities, whereas all missense variants showed unaffected dimerization with wild-type POU3F3. Taken together, our identification and functional cell-based analyses of pathogenic variants in POU3F3, coupled with a clinical characterization, implicate disruptions of this gene in a characteristic neurodevelopmental disorder
The impact of population-based faecal occult blood test screening on colorectal cancer mortality:a matched cohort study
BACKGROUND: Randomised trials show reduced colorectal cancer (CRC) mortality with faecal occult blood testing (FOBT). This outcome is now examined in a routine, population-based, screening programme. METHODS: Three biennial rounds of the UK CRC screening pilot were completed in Scotland (2000–2007) before the roll out of a national programme. All residents (50–69 years) in the three pilot Health Boards were invited for screening. They received a FOBT test by post to complete at home and return for analysis. Positive tests were followed up with colonoscopy. Controls, selected from non-pilot Health Boards, were matched by age, gender, and deprivation and assigned the invitation date of matched invitee. Follow-up was from invitation date to 31 December 2009 or date of death if earlier. RESULTS: There were 379 655 people in each group (median age 55.6 years, 51.6% male). Participation was 60.6%. There were 961 (0.25%) CRC deaths in invitees, 1056 (0.28%) in controls, rate ratio (RR) 0.90 (95% confidence interval (CI) 0.83–0.99) overall and 0.73 (95% CI 0.65–0.82) for participants. Non-participants had increased CRC mortality compared with controls, RR 1.21 (95% CI 1.06–1.38). CONCLUSION: There was a 10% relative reduction in CRC mortality in a routine screening programme, rising to 27% in participants
Paving the way toward autonomous shipping development for European Waters – The AUTOSHIP project
New developments in maritime industry include the design and operation of autonomous ships. The AUTOSHIP project is one initiative promoting the use of autonomous ships in European waters focusing on two specific use cases, a Short Sea Shipping (SSS) cargo vessel and an Inland Waterways (IWW) barge. The AUTOSHIP objectives include thorough regulatory, societal, financial, safety and security analyses for the two investigated use cases as well as the development of a novel framework and methods for the design of autonomous vessels. This objective is achieved with the support of a number of activities, including supply chain, regulatory, risk and gaps analyses. Some results and findings from these activities are presented in this paper. The results demonstrate that the supply chain analysis is important to understand the complex relationships between different partners and phases for the effective design of maritime autonomous systems. Furthermore, a number of regulatory gaps needs to be addressed for the wider adoption of the AUTOSHIP use cases. There is a number of essential hazards associated with each of the two use cases; measures to mitigate these hazards are presented
Non-Arrhenius Behavior of Secondary Relaxation in Supercooled Liquids
Dielectric relaxation spectroscopy (1 Hz - 20 GHz) has been performed on
supercooled glass-formers from the temperature of glass transition (T_g) up to
that of melting. Precise measurements particularly in the frequencies of
MHz-order have revealed that the temperature dependences of secondary
beta-relaxation times deviate from the Arrhenius relation in well above T_g.
Consequently, our results indicate that the beta-process merges into the
primary alpha-mode around the melting temperature, and not at the dynamical
transition point T which is approximately equal to 1.2 T_g.Comment: 4 pages, 4 figures, revtex
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