Pharmacokinetic adaptation of 5-fluorouracil: where are we and where are we going?

International audienc

Interface Dipole : Effects on Threshold Voltage and Mobility for both Amorphous and Poly-crystalline Organic Field Effect Transistors

We report a detailed comparison on the role of a self-assembled monolayer (SAM) of dipolar molecules on the threshold voltage and charge carrier mobility of organic field-effect transistor (OFET) made of both amorphous and polycrystalline organic semiconductors. We show that the same relationship between the threshold voltage and the dipole-induced charges in the SAM holds when both types of devices are fabricated on strictly identical base substrates. Charge carrier mobilities, almost constant for amorphous OFET, are not affected by the dipole in the SAMs, while for polycrystalline OFET (pentacene) the large variation of charge carrier mobilities is related to change in the organic film structure (mostly grain size).Comment: Full paper and supporting informatio

Donald Trump’s use of Twitter during his campaign ahead of the US presidential election of 2016 – why Trump’s tweets are emotionally effective

This paper shows how Donald Trump uses Twitter to spread emotions, more specifi cally fear and anger. Noteworthy is the fact that Trump’s discourse is not primarily emotional. Although anger may sound legitimate, fear is viewed as an emotion one should be ashamed of. Rather than verbalising these emotions, discrediting his opponents – i.e. other candidates and journalists – and legitimising his own discourse for the sake of moral values are the hallmarks of Trump’s rhetoric. By presenting the future as precarious and uncertain, he stands as the only one able to make America powerful and infl uential (again). He adopts the stance of a victim, which is amplifi ed by the impact that social networks have on communities in terms of affi liation

Beyond aspect: will be -ing and shall be -ing

This article discusses the synchronic status and diachronic development of will be -ing and shall be -ing (as in I’ll be leaving at noon).2 Although available since at least Middle English, the constructions did not establish a significant foothold in standard English until the twentieth century. Both types are also more prevalent in British English (BrE) than American English (AmE). We argue that in present-day usage will/shall be -ing are aspectually underspecified: instances that clearly construe a situation as future-in-progress are in the minority. Similarly, although volition-neutrality has been identified as a key feature of will/shall be -ing, it is important to take account of other, generally richer meanings and associations, notably ‘future-as-matter-of-course’ (Leech 2004), ‘already-decided future’ (Huddleston & Pullum et al. 2002) and non-agentivity. Like volition-neutrality, these characteristics appear to be relevant not only in contemporary use, but also in their historical expansion. We show that the construction has evolved from progressive aspect towards more subjectivised evidential meaning

Higher gait variability is associated with decreased parietal gray matter volume among healthy older adults

The objectives of this study were to examine the association of stride time variability (STV) with gray and white matter volumes in healthy older adults, and to determine the specific location of any parenchymal loss associated with higher STV. A total of 71 participants (mean age 69.0 +/- 0.8 years; 59.7 % female) were included in this study. All participants had a 1.0 Tesla 3D T1-weighted MRI of the brain to measure gray and white matter volumes. STV was measured at steady-state self-selected walking speed using an electronic footswitch system. We found an association between higher STV and lower gray matter volume in the right parietal lobe (e.g., angular gyrus, Brodmann area 39, cluster corrected pFWE = 0.035). There were no significant associations between STV and higher gray matter volume or change in white matter volume. To the best of our knowledge this study is the first to identify a significant association of higher STV with lower right parietal gray matter volume in healthy older adults

Individual Fluorouracil Dose Adjustment in FOLFOX Based on Pharmacokinetic Follow-Up Compared With Conventional Body-Area-Surface Dosing: A Phase II, Proof-of-Concept Study

BackgroundTo compare the efficacy and safety of pharmacokinetically (PK) guided fluorouracil (5-FU) dose adjustment vs. standard body-surface-area (BSA) dosing in a FOLFOX (folinic acid, fluorouracil, oxaliplatin) regimen in metastatic colorectal cancer (mCRC). Patients And Methods A total of 118 patients with mCRC were administered individually determined PK-adjusted 5-FU in first-line FOLFOX chemotherapy. The comparison arm consisted of 39 patients, and these patients were also treated with FOLFOX with 5-FU by BSA. For the PK-adjusted arm 5-FU was monitored during infusion, and the dose for the next cycle was based on a dose-adjustment chart to achieve a therapeutic area under curve range (5-FUODPM Protocol). Results The objective response rate was 69.7% in the PK-adjusted arm, and median overall survival and median progression-free survival were 28 and 16 months, respectively. In the traditional patients who received BSA dosage, objective response rate was 46%, and overall survival and progression-free survival were 22 and 10 months, respectively. Grade 3/4 toxicity was 1.7% for diarrhea, 0.8% for mucositis, and 18% for neutropenia in the dose-monitored group; they were 12%, 15%, and 25%, respectively, in the BSA group. Conclusions Efficacy and tolerability of PK-adjusted FOLFOX dosing was much higher than traditional BSA dosing in agreement with previous reports for 5-FU monotherapy PK-adjusted dosing. Analysis of these results suggests that PK-guided 5-FU therapy offers added value to combination therapy for mCRC

Growth of one-dimensional Si/SiGe heterostructures by thermal CVD

4 pagesInternational audienceThe first results on a simple new process for the direct fabrication of one-dimensional superlattices using common CVD chambers are presented. The experiments were carried out in a 200 mm industrial Centura reactor (Applied Materials). Low dimensionality and superlattices allow a significant increase in the figure of merit of thermoelectrics by controlling the transport of phonons and electrons. The monocrystalline nanowires produced according to this process are both one-dimensional and present heterostructures, with very thin layers (40 nm) of Si and SiGe. Concentrations up to 30 at.% Ge were obtained in the SiGe parts. Complementary techniques including transmission electronic microscopy (TEM), selected area electron diffraction (SAED), energy dispersive x-ray spectroscopy (EDS), scanning transmission electron microscopy (STEM) in bright field and high angle annular dark field (HAADF STEM), and energy-filtered transmission electron microscopy (EF-TEM) were used to characterize the nanoheterostructures

In Vitro Stability of Low-Concentration Ziconotide Alone or in Admixtures in Intrathecal Pumps

ObjectivesZiconotide is often administered in combination with other analgesics via an intrathecal pump. Studies have established that ziconotide is stable when delivered alone in high concentrations. No stability data are available, however, for ziconotide given in low concentrations and/or with other analgesics as usually occurs in clinical oncology practice. The objective of this study was to assess the in vitro stability of ziconotide alone and combined with other analgesics in intrathecal pumps at 37°C, as well as in syringes at 5°C, to evaluate conditions for storing and transporting preparations. Materials and Methods Various ziconotide concentrations (0.1, 0.25, 0.5, and 0.75 μg/mL) were combined with an admixture of ropivacaine (7.5 mg/mL), morphine (7.5 mg/mL), and clonidine (15 μg/mL) in 20-mL intrathecal pumps at 37°C and in syringes at 5°C. Solutions of ziconotide alone in concentrations of 0.25, 0.5, 0.75, and 1 μg/mL were introduced into pumps at 37°C and syringes at 5°C. Assays were performed using ultra high pressure liquid chromatography. Results In admixtures, mean ziconotide concentrations decreased linearly to 53.4% (±3.33%) of baseline after 35 days. When ziconotide was introduced alone in pumps at 37°C, the residual concentration on day 31 was 35.54% (±0.04%) with 0.25 μg/mL, 39.37% (±0.15%) with 0.5 μg/mL, and 44.49% (±0.18%) with 1 μg/mL. Ziconotide alone or combined with the other analgesics was stable in syringes stored at 5°C. The preparations complied with the prescriptions, with a mean error of less than 10%, except with the lowest ziconotide concentration (0.1 μg/mL). Conclusions At the low ziconotide concentrations studied, the degradation of ziconotide admixed with other drugs was linear and only weakly influenced by the baseline concentration. Linear regression with intrapolation to 30 days showed that the degradation of ziconotide admixed with other drugs was consistent with previously published data

Water reservoirs, irrigation and sedimentation in Central Asia: a first-cut assessment for Uzbekistan

International audienceWater reservoirs play an important role in areas with limited and erratic precipitation where water is stored and re-distributed later for different purposes. Irrigation is primarily a major water consumer in arid countries of Central Asia for the economic development, employment and food security of the region. The major rivers of Central Asia (e.g., Amu Darya, Syr Darya, and Zerafshan) are turbid watercourses. Sedimentation reduces the main reservoir asset i.e., its volume capacity. In addition, vast territories of the region's countries have been transformed for agriculture to grow water intensive crops such as cotton, rice and wheat during the Soviet Union that dramatically accelerated soil erosion by water and wind. Thus, many man-made water reservoirs are affected by high sedimentation rates. Moreover, uneven spatial and temporal water resources and a Soviet-inherited unified hydraulic infrastructure have raised transboundary reservoir management issues over water resources allocation among the countries in the region such as Kyrgyzstan, Tajikistan, Kazakhstan, Uzbekistan and Turkmenistan. The rivers such as Syr Darya and Amu Darya are already regulated by more than 78 and 94 %, respectively and attempts for new reservoir projects upstream raises increased concerns of the downstream countries (e.g., the Rogun hydropower station in Tajikistan and the Toktogul reservoir in Kyrgyzstan). For instance, the uncoordinated use of reservoirs has caused the Arnasai lake problem in Uzbekistan with environmental, material damage and social unrest. The aim of this paper is first to review the present conditions and the role of man-made water reservoirs for irrigation in Central Asia with special focus on Uzbekistan, second to document past and current reservoir sedimentation conditions in Uzbekistan and third to discuss research carried out by Soviet and present-time local research community in the domain of erosion and sedimentation in the region

Air Masses Origin and Isotopic Tracers: A Study Case of the Oceanic and Mediterranean Rainfall Southwest of France

Aquifers recharge mainly by local rainfall, which depend on the air mass humidity and orographic lifting, causing rain. The stable isotopes of the water molecule, i.e., oxygen-18 and deuterium, are useful tracers to determine the water source origin. Moreover, the calculation of the deuterium excess enables one to differentiate between the air masses from the Atlantic Ocean or the Mediterranean Sea. A transect from one coast to the other one and going through the city of Toulouse have been made to sample the groundwater and determine their isotopic characteristic. A monthly rainfall sampling has also been done over one year, close to the city Toulouse, to see how the d-excess values range over the season. The discussion replaces these results in available isotopic data