Pharmacokinetic analysis of two different docetaxel dose levels in patients with non-small cell lung cancer treated with docetaxel as monotherapy or with concurrent radiotherapy

<p>Abstract</p> <p>Background</p> <p>Previous pharmacokinetic studies with docetaxel have mostly used 3-weekly (75 mg/m²and 100 mg/m²) or weekly regimens (35–40 mg/m²). The pharmacokinetics and radiosensitizing efficacy of weekly 20 mg/m²docetaxel, has however not been well characterized. We examined the pharmacokinetics of weekly docetaxel when administered with concurrent radiotherapy and compared the results with a 3-weekly 100 mg/m²regimen.</p> <p>Methods</p> <p>Thirty-four patients with non small cell lung cancer (NSCLC) were included in this study, 19 receiving 100 mg/m²docetaxel 3-weekly as single therapy, and 15 receiving 20 mg/m²docetaxel weekly with concurrent radiotherapy. A newly developed HPLC method was used for measuring docetaxel levels, capable of quantifying docetaxel in plasma down to the nanomolar level.</p> <p>Results</p> <p>The HPLC method showed detectable concentrations of docetaxel in plasma even after 72 hours. In the present study we have demonstrated that median docetaxel plasma levels of 3 nM can be obtained 72 hours after a dose of 20 mg/m².</p> <p>Conclusion</p> <p>The pharmacokinetics of docetaxel is characterized by great inter-individual variability and at some time points plasma concentrations for 20 mg/m²and 100 mg/m²docetaxel were overlapping. Extrapolation of these results indicates that radio sensitizing docetaxel concentrations may be present for as long as 1 week, thus supporting the use of 20 mg/m²weekly docetaxel.</p

Redox evolution of a degassing magma rising to the surface.

Volatiles carried by magmas, either dissolved or exsolved, have a fundamental effect on a variety of geological phenomena, such as magma dynamics1–5 and the composition of the Earth's atmosphere 6. In particular, the redox state of volcanic gases emanating at the Earth's surface is widely believed to mirror that of the magma source, and is thought to have exerted a first-order control on the secular evolution of atmospheric oxygen6,7. Oxygen fugacity (fO2 ) estimated from lava or related gas chemistry, however, may vary by as much as one log unit8–10, and the reason for such differences remains obscure. Here we use a coupled chemical–physical model of conduit flow to show that the redox state evolution of an ascending magma, and thus of its coexisting gas phase, is strongly dependent on both the composition and the amount of gas in the reservoir. Magmas with no sulphur show a systematic fO2 increase during ascent, by as much as 2 log units. Magmas with sulphur show also a change of redox state during ascent, but the direction of change depends on the initial fO2 in the reservoir. Our calculations closely reproduce the H2S/SO2 ratios of volcanic gases observed at convergent settings, yet the difference between fO2 in the reservoir and that at the exit of the volcanic conduit may be as much as 1.5 log units. Thus, the redox state of erupted magmas is not necessarily a good proxy of the redox state of the gases they emit. Our findings may require re-evaluation of models aimed at quantifying the role of magmatic volatiles in geological processes

The Adolescent Depression Rating Scale (ADRS): a validation study

BACKGROUND: To examine the psychometric properties of the Adolescent Depression Rating Scale (ADRS), a new measure was specifically designed to evaluate adolescent depression. METHODS: The 11-item clinician-report and 44-item self-report versions of the ADRS were developed from a qualitative phase involving interviews of experts and adolescents. These two instruments were then administered to 402 French speaking adolescents with and without depressive disorders. Item distribution, internal consistency, convergent validity, discriminant validity and factorial structure were assessed. RESULTS: After reduction procedures, a 10-item clinician version and a 10-item self-report version were obtained. The ADRS demonstrated good internal consistency (alpha Cronbach coefficient >.70). It also discriminated better between adolescents with and without depression than the Hamilton Depressive Rating Scale and the Beck Depression Inventory (BDI-13). CONCLUSION: The ADRS is a useful, short, clinician-report and self-report scale to evaluate adolescent depression. Further studies to replicate our findings and evaluate ADRS sensitivity to effects of treatment and psychometric properties in populations of adolescents with several psychiatric disorders are warranted

Complications after hip arthroplasty and the association with hospital procedure volume: A nationwide retrospective cohort study on 50,080 total hip replacements with a follow-up of 3 months after surgery

Background and purpose: It has been suggested that a higher procedure volume is associated with less complications af

Effect of high parity on occurrence of anemia in pregnancy: a cohort study

<p>Abstract</p> <p>Background</p> <p>Studies that explore the controversial association between parity and anaemia-in-pregnancy (AIP) were often hampered by not distinguishing incident cases caused by pregnancy from prevalent cases complicated by pregnancy. The authors' aim in conducting this study was to overcome this methodological concern.</p> <p>Methods</p> <p>A retrospective cohort study was conducted in Oman on 1939 pregnancies among 479 parous female participants with available pregnancy records in a community trial. We collected information from participants, the community trial, and health records of each pregnancy. Throughout the follow-up period, we enumerated 684 AIP cases of which 289 (42.2%) were incident cases. High parity (HP, ≥ 5 pregnancies) accounted for 48.7% of total pregnancies. Two sets of regression analyses were conducted: the first restricted to incident cases only, and the second inclusive of all cases. The relation with parity as a dichotomy and as multiple categories was examined for each set; multi-level logistic regression (MLLR) was employed to produce adjusted models.</p> <p>Results</p> <p>In the fully adjusted MLLR models that were restricted to incident cases, women with HP pregnancies had a higher risk of AIP compared to those who had had fewer pregnancies (Risk Ratio, RR = 2.92; 95% CI 2.02, 4.59); the AIP risk increased in a dose-response fashion over multiple categories of parity. In the fully adjusted MLLR models that included all cases, the association disappeared (RR = 1.11; 95% CI 0.91, 1.18) and the dose-response pattern flattened.</p> <p>Conclusions</p> <p>This study shows the importance of specifying which cases of AIP are incident and provides supportive evidence for a causal relation between parity and occurrence of incidental AIP.</p

Atmospheric oxygenation caused by a change in volcanic degassing pressure

International audienceThe Precambrian history of our planet is marked by two major events: a pulse of continental crust formation at the end of the Archaean eon and a weak oxygenation of the atmosphere (the Great Oxidation Event) that followed, at 2.45 billion years ago. This oxygenation has been linked to the emergence of oxygenic cyanobacteria1,2 and to changes in the compositions of volcanic gases3,4, but not to the composition of erupting lavas--geochemical constraints indicate that the oxidation state of basalts and their mantle sources has remained constant since 3.5 billion years ago5,6. Here we propose that a decrease in the average pressure of volcanic degassing changed the oxidation state of sulphur in volcanic gases, initiating themodern biogeochemical sulphur cycle and triggering atmospheric oxygenation. Using thermodynamic calculations simulating gas-melt equilibria in erupting magmas, we suggest that mostly submarine Archaean volcanoes produced gases with SO2/H2S,1 and low sulphur content. Emergence of the continents due to a global decrease in sea level and growth of the continental crust in the late Archaean then led to widespread subaerial volcanism, which in turn yielded gases much richer in sulphur and dominated bySO2. Dissolution of sulphur in sea water and the onset of sulphate reduction processes could then oxidize the atmosphere

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

Low and moderate, rather than high intensity strength exercise induces benefit regarding plasma lipid profile

<p>Abstract</p> <p>Background</p> <p>The effects of chronic aerobic exercise upon lipid profile has been previously demonstrated, but few studies showed this effect under resistance exercise conditions.</p> <p>Objective</p> <p>The aim of this study was to examine the effects of different resistance exercise loads on blood lipids.</p> <p>Methods</p> <p>Thirty healthy, untrained male volunteers were allocated randomly into four groups based at different percentages of one repetition maximum (1 RM); 50%-1 RM, 75%-1 RM, 90%-1 RM, and 110%-1 RM. The total volume (sets × reps × load) of the exercise was equalized. The lipid profile (Triglycerides [TG], HDL-cholesterol [HDL-c], LDL-cholesterol, and Total cholesterol) was determined at rest and after 1, 24, 48 and 72 h of resistance exercise.</p> <p>Results</p> <p>The 75%-1 RM group demonstrated greater TG reduction when compared to other groups (p < 0.05). Additionally, the 110%-1 RM group presented an increased TG concentration when compared to 50% and 75% groups (p = 0.01, p = 0.01, respectively). HDL-c concentration was significantly greater after resistance exercise in 50%-1 RM and 75%-1 RM when compared to 110%-1 RM group (p = 0.004 and p = 0.03, respectively). Accordingly, the 50%-1 RM group had greater HDL-c concentration than 110%-1 RM group after 48 h (p = 0.05) and 72 h (p = 0.004), respectively. Finally, The 50% group has showed lesser LDL-c concentration than 110% group after 24 h (p = 0.007). No significant difference was found in Total Cholesterol concentrations.</p> <p>Conclusion</p> <p>These results indicate that the acute resistance exercise may induce changes in lipid profile in a specific-intensity manner. Overall, low and moderate exercise intensities appear to be promoting more benefits on lipid profile than high intensity. Long term studies should confirm these findings.</p