Trans-Amazon Drilling Project (TADP): origins and evolution of the forests, climate, and hydrology of the South American tropics

This article presents the scientific rationale for an ambitious ICDP drilling project to continuously sample Late Cretaceous to modern sediment in four different sedimentary basins that transect the equatorial Amazon of Brazil, from the Andean foreland to the Atlantic Ocean. The goals of this project are to document the evolution of plant biodiversity in the Amazon forests and to relate biotic diversification to changes in the physical environment, including climate, tectonism, and the surface landscape. These goals require long sedimentary records from each of the major sedimentary basins across the heart of the Brazilian Amazon, which can only be obtained by drilling because of the scarcity of Cenozoic outcrops. The proposed drilling will provide the first long, nearly continuous regional records of the Cenozoic history of the forests, their plant diversity, and the associated changes in climate and environment. It also will address fundamental questions about landscape evolution, including the history of Andean uplift and erosion as recorded in Andean foreland basins and the development of west-to-east hydrologic continuity between the Andes, the Amazon lowlands, and the equatorial Atlantic. Because many modern rivers of the Amazon basin flow along the major axes of the old sedimentary basins, we plan to locate drill sites on the margin of large rivers and to access the targeted drill sites by navigation along these rivers

Expression of Xhdsi-1VOC, a novel member of the vicinal oxygen chelate (VOC) metalloenzyme superfamily, is up-regulated in leaves and roots during desiccation in the resurrection plant Xerophyta humilis (Bak) Dur and Schinz

The annotation of novel plant genes is frequently based on sequence and structural similarity to known protein motifs. Understanding the biological function of these genes is dependent on identifying conditions under which they are activated, however. The resurrection plant, Xerophyta humilis is a good model system for identifying and characterizing genes which are important for desiccation tolerance. Desiccation induced-1 (dsi-1VOC), a previously uncharacterized plant gene, is up-regulated during desiccation in leaves, roots, and seeds in X. humilis. The X. humilis desiccation induced-1 gene, Xhdsi-1VOC, shares structural homology with the vicinal oxygen chelate (VOC) metalloenzyme superfamily. Proteins in this superfamily share little sequence similarity, but are characterized by a common βαβββ structural fold. A number of plant orthologues of XhDsi-1VOC have been identified, including Arabidopsis thaliana At1g07645, which is currently annotated as a glyoxalase I-like gene, and many ESTs derived from seed cDNA libraries. Xhdsi-1VOC and its orthologues do not, however, contain the glutathione and zinc binding sites conserved in glyoxalase I genes. Furthermore, expression of Xhdsi-1VOC in yeast failed to rescue a yeast glyoxalase I mutant. Messenger RNA transcripts for At1g07645 accumulate during seed maturation, but are not induced by water loss, salt or mannitol stress in vegetative tissue in Arabidopsis. It is concluded that dsi-1VOC is a seed-specific gene in desiccation-sensitive plants that is activated by water loss in vegetative tissues in the resurrection plant X. humilis and plays an important role in allowing plant tissues to survive loss of 95% of their relative water content

Diet, physical exercise and cognitive behavioral training as a combined workplace based intervention to reduce body weight and increase physical capacity in health care workers - a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Health care workers comprise a high-risk workgroup with respect to deterioration and early retirement. There is high prevalence of obesity and many of the workers are overweight. Together, these factors play a significant role in the health-related problems within this sector. The present study evaluates the effects of the first 3-months of a cluster randomized controlled lifestyle intervention among health care workers. The intervention addresses body weight, general health variables, physical capacity and musculoskeletal pain.</p> <p>Methods</p> <p>98 female, overweight health care workers were cluster-randomized to an intervention group or a reference group. The intervention consisted of an individually dietary plan with an energy deficit of 1200 kcal/day (15 min/hour), strengthening exercises (15 min/hour) and cognitive behavioral training (30 min/hour) during working hours 1 hour/week. Leisure time aerobic fitness was planned for 2 hour/week. The reference group was offered monthly oral presentations. Body weight, BMI, body fat percentage (bioimpedance), waist circumference, blood pressure, musculoskeletal pain, maximal oxygen uptake (maximal bicycle test), and isometric maximal muscle strength of 3 body regions were measured before and after the intervention period.</p> <p>Results</p> <p>In an intention-to-treat analysis from pre to post tests, the intervention group significantly reduced body weight with 3.6 kg (p < 0.001), BMI from 30.5 to 29.2 (p < 0.001), body fat percentage from 40.9 to 39.3 (p < 0.001), waist circumference from 99.7 to 95.5 cm (p < 0.001) and blood pressure from 134/85 to 127/80 mmHg (p < 0.001), with significant difference between the intervention and control group (p < 0.001) on all measures. No effect of intervention was found in musculoskeletal pain, maximal oxygen uptake and muscle strength, but on aerobic fitness.</p> <p>Conclusion</p> <p>The significantly reduced body weight, body fat, waist circumference and blood pressure as well as increased aerobic fitness in the intervention group show the great potential of workplace health promotion among this high-risk workgroup. Long-term effects of the intervention remain to be investigated.</p> <p>Trial registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT01015716">NCT01015716</a></p

Creatine Fails to Augment the Benefits from Resistance Training in Patients with HIV Infection: A Randomized, Double-Blind, Placebo-Controlled Study

Progressive resistance exercise training (PRT) improves physical functioning in patients with HIV infection. Creatine supplementation can augment the benefits derived from training in athletes and improve muscle function in patients with muscle wasting. The objective of this study was to determine whether creatine supplementation augments the effects of PRT on muscle strength, energetics, and body composition in HIV-infected patients.This is a randomized, double blind, placebo-controlled, clinical research center-based, outpatient study in San Francisco. 40 HIV-positive men (20 creatine, 20 placebo) enrolled in a 14-week study. Subjects were randomly assigned to receive creatine monohydrate or placebo for 14 weeks. Treatment began with a loading dose of 20 g/day or an equivalent number of placebo capsules for 5 days, followed by maintenance dosing of 4.8 g/day or placebo. Beginning at week 2 and continuing to week 14, all subjects underwent thrice-weekly supervised resistance exercise while continuing on the assigned study medication (with repeated 6-week cycles of loading and maintenance). The main outcome measurements included muscle strength (one repetition maximum), energetics ((31)P magnetic resonance spectroscopy), composition and size (magnetic resonance imaging), as well as total body composition (dual-energy X-ray absorptiometry). Thirty-three subjects completed the study (17 creatine, 16 placebo). Strength increased in all 8 muscle groups studied following PRT, but this increase was not augmented by creatine supplementation (average increase 44 vs. 42%, difference 2%, 95% CI -9.5% to 13.9%) in creatine and placebo, respectively). There were no differences between groups in changes in muscle energetics. Thigh muscle cross-sectional area increased following resistance exercise, with no additive effect of creatine. Lean body mass (LBM) increased to a significantly greater extent with creatine. CONCLUSIONS / SIGNIFICANCE: Resistance exercise improved muscle size, strength and function in HIV-infected men. While creatine supplementation produced a greater increase in LBM, it did not augment the robust increase in strength derived from PRT.ClinicalTrials.gov NCT00484627

Long-Term Outcomes with Subcutaneous C1-Inhibitor Replacement Therapy for Prevention of Hereditary Angioedema Attacks

Background For the prevention of attacks of hereditary angioedema (HAE), the efficacy and safety of subcutaneous human C1-esterase inhibitor (C1-INH[SC]; HAEGARDA, CSL Behring) was established in the 16-week Clinical Study for Optimal Management of Preventing Angioedema with Low-Volume Subcutaneous C1-Inhibitor Replacement Therapy (COMPACT). Objective To assess the long-term safety, occurrence of angioedema attacks, and use of rescue medication with C1-INH(SC). Methods Open-label, randomized, parallel-arm extension of COMPACT across 11 countries. Patients with frequent angioedema attacks, either study treatment-naive or who had completed COMPACT, were randomly assigned (1:1) to 40 IU/kg or 60 IU/kg C1-INH(SC) twice per week, with conditional uptitration to optimize prophylaxis (ClinicalTrials.gov registration no. NCT02316353). Results A total of 126 patients with a monthly attack rate of 4.3 in 3 months before entry in COMPACT were enrolled and treated for a mean of 1.5 years; 44 patients (34.9%) had more than 2 years of exposure. Mean steady-state C1-INH functional activity increased to 66.6% with 60 IU/kg. Incidence of adverse events was low and similar in both dose groups (11.3 and 8.5 events per patient-year for 40 IU/kg and 60 IU/kg, respectively). For 40 IU/kg and 60 IU/kg, median annualized attack rates were 1.3 and 1.0, respectively, and median rescue medication use was 0.2 and 0.0 times per year, respectively. Of 23 patients receiving 60 IU/kg for more than 2 years, 19 (83%) were attack-free during months 25 to 30 of treatment. Conclusions In patients with frequent HAE attacks, long-term replacement therapy with C1-INH(SC) is safe and exhibits a substantial and sustained prophylactic effect, with the vast majority of patients becoming free from debilitating disease symptoms

Hemodynamic evaluation in patients with transposition of the great arteries after the arterial switch operation: 4D flow and 2D phase contrast cardiovascular magnetic resonance compared with Doppler echocardiography

Background: Peak velocity measurements are used to evaluate the significance of stenosis in patients with transposition of the great arteries after the arterial switch operation (TGA after ASO). 4D flow cardiovascular magnetic resonance (CMR) provides 3-directional velocity encoding and full volumetric coverage of the great arteries and may thus improve the hemodynamic evaluation in these patients. The aim of this study was to compare peak velocities measured by 4D flow CMR with 2D phase contrast (PC) CMR and the gold standard Doppler echocardiography (echo) in patients with TGA after ASO. Methods: Nineteen patients (mean age 13 +/- 9 years, range 1-25 years) with TGA after ASO who underwent 2D PC CMR and 4D flow CMR were included in this study. Peak velocities were measured with 4D flow CMR in the aorta and pulmonary arteries and compared to peak velocities measured with 2D PC CMR and Doppler echo. 2D PC CMR data were available in the ascending aorta, main, right and left pulmonary arteries (AAO/MPA/RPA/LPA) for 19/18/ 17/17 scans, respectively, and Doppler echo data were available for 13/9/6/6 scans, respectively. Peak velocities were measured with: 1) a single cross section for 2D PC CMR, 2) velocity maximum intensity projections (MIPs) for 4D flow CMR and 3) Doppler echo. Results: Significantly higher peak velocities were found with 4D flow CMR than 2D PC CMR in the AAO (p = 0.003), MPA (p = 0.002) and RPA (p = 0.005) but not in the LPA (p = 0.200). No difference in peak velocity was found between 4D flow CMR and Doppler echo (p > 0.46) or 2D PC CMR and echo (p > 0.11) for all analyzed vessel segments. Conclusions: 4D flow CMR evaluation of patients with TGA after ASO detected higher peak velocities than 2D PC CMR, indicating the potential of 4D flow CMR to provide improved stenosis assessment in these patients

Harmonization of Zika neutralization assays by using the WHO International Standard for anti-Zika virus antibody

During outbreaks of emerging viruses, such as the Zika outbreak in 2015–2016, speed and accuracy in detection of infection are critical factors to control the spread of the disease; often serological and diagnostic methods for emerging viruses are not well developed and validated. Thus, vaccines and treatments are difficult to evaluate due to the lack of comparable methods. In this study, we show how the 1st WHO International Standard for anti-Zika antibody was able to harmonize the neutralization titres of a panel of serological Zika-positive samples from laboratories worldwide. Expression of the titres in International Unit per millilitre reduced the inter-laboratory variance, allowing for greater comparability between laboratories. We advocate the use of the International Standard for anti-Zika virus antibodies for the calibration of neutralization assays to create a common language, which will permit a clear evaluation of the results of different clinical trials and expedite the vaccine/treatment development

Probing the viability of oxo-coupling pathways in iridium-catalyzed oxygen evolution

[Image: see text] A series of Cp*Ir(III) dimers have been synthesized to elucidate the mechanistic viability of radical oxo-coupling pathways in iridium-catalyzed O(2) evolution. The oxidative stability of the precursors toward nanoparticle formation and their oxygen evolution activity have been investigated and compared to suitable monomeric analogues. We found that precursors bearing monodentate NHC ligands degraded to form nanoparticles (NPs), and accordingly their O(2) evolution rates were not significantly influenced by their nuclearity or distance between the two metals in the dimeric precursors. A doubly chelating bis-pyridine–pyrazolide ligand provided an oxidation-resistant ligand framework that allowed a more meaningful comparison of catalytic performance of dimers with their corresponding monomers. With sodium periodate (NaIO(4)) as the oxidant, the dimers provided significantly lower O(2) evolution rates per [Ir] than the monomer, suggesting a negative interaction instead of cooperativity in the catalytic cycle. Electrochemical analysis of the dimers further substantiates the notion that no radical oxyl-coupling pathways are accessible. We thus conclude that the alternative path, nucleophilic attack of water on high-valent Ir-oxo species, may be the preferred mechanistic pathway of water oxidation with these catalysts, and bimolecular oxo-coupling is not a valid mechanistic alternative as in the related ruthenium chemistry, at least in the present system