Evidences for a quasi 60-year North Atlantic Oscillation since 1700 and its meaning for global climate change

The North Atlantic Oscillation (NAO) obtained using instrumental and documentary proxy predictors from Eurasia is found to be characterized by a quasi 60-year dominant oscillation since 1650. This pattern emerges clearly once the NAO record is time integrated to stress its comparison with the temperature record. The integrated NAO (INAO) is found to well correlate with the length of the day (since 1650) and the global surface sea temperature record HadSST2 and HadSST3 (since 1850). These findings suggest that INAO can be used as a good proxy for global climate change, and that a 60-year cycle exists in the global climate since at least 1700. Finally, the INAO ~60-year oscillation well correlates with the ~60- year oscillations found in the historical European aurora record since 1700, which suggests that this 60-year dominant climatic cycle has a solar-astronomical origin

Comparison between superdarn flow vectors and equivalent ionospheric currents from ground magnetometer arrays

[1] Equivalent ionospheric currents obtained with the spherical elementary current systems (SECS) method and derived from nearly 100 ground magnetometers spread over North America and Greenland are compared with ionospheric flow vectors measured by the SuperDARN radars during both the summer and winter seasons. This comparison is done over a range of spatial separations, magnetic latitudes, magnetic local times, and auroral electrojet activity to investigate under what conditions the vectors are anti-parallel to one another. Our results show that in general the equivalent ionospheric currents are anti-parallel to the flows and the best results are achieved within the auroral oval during active geomagnetic conditions in the dawn, dusk and noon sectors in the northern hemisphere summer. These results indicate the best anti-parallel alignment occurs when the currents and flows are large and well defined. Factors that may influence the alignment include ionospheric conductivity gradients and quiet time backgrounds. Our results can be used to approximate the macroscopic ($1000 km) ionospheric convection patterns. The SECS maps represent a value-added product from the raw magnetometer database and can be used for contextual interpretation; they can help with our understanding of magnetosphere-ionosphere coupling mechanisms using ground arrays and the magnetospheric spacecraft data, and they can be used as input for other techniques

Radiosensitization by BRAF inhibitor therapy—mechanism and frequency of toxicity in melanoma patients

This study shows radiosensitization by BRAF inhibitors in clinical practice and ex vivo by fluorescence in situ hybridization of chromosomal breaks. Nevertheless, radiotherapy with concomitant BRAF inhibitor therapy is feasible with an acceptable increase in toxicity. Vemurafenib is a more potent radiosensitizer than dabrafenib in both the patient study and the ex vivo experiment

Quantification of structural uncertainty in climate data records from GPS radio occultation

Global Positioning System (GPS) radio occultation (RO) has provided continuous observations of the Earth's atmosphere since 2001 with global coverage, all-weather capability, and high accuracy and vertical resolution in the upper troposphere and lower stratosphere (UTLS). Precise time measurements enable long-term stability but careful processing is needed. Here we provide climate-oriented atmospheric scientists with multicenter-based results on the long-term stability of RO climatological fields for trend studies. We quantify the structural uncertainty of atmospheric trends estimated from the RO record, which arises from current processing schemes of six international RO processing centers, DMI Copenhagen, EUM Darmstadt, GFZ Potsdam, JPL Pasadena, UCAR Boulder, and WEGC Graz. Monthly-mean zonal-mean fields of bending angle, refractivity, dry pressure, dry geopotential height, and dry temperature from the CHAMP mission are compared for September 2001 to September 2008. We find that structural uncertainty is lowest in the tropics and mid-latitudes (50° S to 50° N) from 8 km to 25 km for all inspected RO variables. In this region, the structural uncertainty in trends over 7 yr is <0.03% for bending angle, refractivity, and pressure, <3 m for geopotential height of pressure levels, and <0.06 K for temperature; low enough for detecting a climate change signal within about a decade. Larger structural uncertainty above about 25 km and at high latitudes is attributable to differences in the processing schemes, which undergo continuous improvements. Though current use of RO for reliable climate trend assessment is bound to 50° S to 50° N, our results show that quality, consistency, and reproducibility are favorable in the UTLS for the establishment of a climate benchmark record

HIV-1 drug resistance mutations emerging on darunavir therapy in PI-naive and -experienced patients in the UK

\ua9 The Author 2016. Background: Darunavir is considered to have a high genetic barrier to resistance. Most darunavir-associated drug resistance mutations (DRMs) have been identified through correlation of baseline genotype with virological response in clinical trials. However, there is little information on DRMs that are directly selected by darunavir in clinical settings. Objectives: We examined darunavir DRMs emerging in clinical practice in the UK. Patients and methods: Baseline and post-exposure protease genotypes were compared for individuals in the UK Collaborative HIV Cohort Study who had received darunavir; analyses were stratified for PI history. A selection analysis was used to compare the evolution of subtype B proteases in darunavir recipients and matched PInaive controls. Results: Of 6918 people who had received darunavir, 386 had resistance tests pre- and post-exposure. Overall, 2.8% (11/386) of these participants developed emergent darunavir DRMs. The prevalence of baseline DRMs was 1.0% (2/198) among PI-naive participants and 13.8% (26/188) among PI-experienced participants. Emergent DRMs developed in 2.0% of the PI-naive group (4 mutations) and 3.7% of the PI-experienced group (12 mutations). Codon 77 was positively selected in the PI-naive darunavir cases, but not in the control group. Conclusions: Our findings suggest that although emergent darunavir resistance is rare, it may be more common among PI-experienced patients than those who are PI-naive. Further investigation is required to explore whether codon 77 is a novel site involved in darunavir susceptibility

Virological failure and development of new resistance mutations according to CD4 count at combination antiretroviral therapy initiation

Objectives: No randomized controlled trials have yet reported an individual patient benefit of initiating combination antiretroviral therapy (cART) at CD4 counts > 350 cells/μL. It is hypothesized that earlier initiation of cART in asymptomatic and otherwise healthy individuals may lead to poorer adherence and subsequently higher rates of resistance development. Methods: In a large cohort of HIV-positive individuals, we investigated the emergence of new resistance mutations upon virological treatment failure according to the CD4 count at the initiation of cART. Results: Of 7918 included individuals, 6514 (82.3%), 996 (12.6%) and 408 (5.2%) started cART with a CD4 count ≤ 350, 351-499 and ≥ 500 cells/μL, respectively. Virological rebound occurred while on cART in 488 (7.5%), 46 (4.6%) and 30 (7.4%) with a baseline CD4 count ≤ 350, 351-499 and ≥ 500 cells/μL, respectively. Only four (13.0%) individuals with a baseline CD4 count > 350 cells/μL in receipt of a resistance test at viral load rebound were found to have developed new resistance mutations. This compared to 107 (41.2%) of those with virological failure who had initiated cART with a CD4 count < 350 cells/μL. Conclusions: We found no evidence of increased rates of resistance development when cART was initiated at CD4 counts above 350 cells/μL. HIV Medicin

The enigma of in vivo oxidative stress assessment: isoprostanes as an emerging target

Oxidative stress is believed to be one of the major factors behind several acute and chronic diseases, and may also be associated with ageing. Excess formation of free radicals in miscellaneous body environment may originate from endogenous response to cell injury, but also from exposure to a number of exogenous toxins. When the antioxidant defence system is overwhelmed, this leads to cell damage. However, the measurement of free radicals or their endproducts is tricky, since these compounds are reactive and short lived, and have diverse characteristics. Specific evidence for the involvement of free radicals in pathological situations has been difficult to obtain, partly owing to shortcomings in earlier described methods for the measurement of oxidative stress. Isoprostanes, which are prostaglandin-like bioactive compounds synthesized in vivo from oxidation of arachidonic acid, independently of cyclooxygenases, are involved in many human diseases, and their measurement therefore offers a way to assess oxidative stress. Elevated levels of F2-isoprostanes have also been seen in the normal human pregnancy, but their physiological role has not yet been defined. Large amounts of bioactive F2-isoprostanes are excreted in the urine in normal basal situations, with a wide interindividual variation. Their exact role in the regulation of normal physiological functions, however, needs to be explored further. Current understanding suggests that measurement of F2-isoprostanes in body fluids provides a reliable analytical tool to study oxidative stress-related diseases and experimental inflammatory conditions, and also in the evaluation of various dietary antioxidants, as well as drugs with radical-scavenging properties. However, assessment of isoprostanes in plasma or urine does not necessarily reflect any specific tissue damage, nor does it provide information on the oxidation of lipids other than arachidonic acid