From downbuilding to contractional reactivation of salt-sediment systems: insights from analog modeling.

This work studies salt-detached fold-and-thrust belts involving minibasins by means of physical analogue modeling. The experimental set up consist of a series of minibasins and diapirs built by downbuilding into a regular polygonal framework. The minibasins-diapir framework were then submitted to contraction, and for some examples accompanied by different rates of syncontractional sedimentation. We aimed at evaluating the influence of an initial salt basin geometry (i.e. equal thickness vs. along-strike tapered) on the development of the salt-sediment system, and how this influences the geometries and kinematics of fold-and-thrust belts. We also tested how these are influenced by different syncontractional sedimentation rates. Results show that major differences on the early salt structures occur during downbuilding as a result of original salt budget (i.e. from pillows to diapirs), with a positive correlation between amount of original salt and salt structure development. Initial contractional deformation is localized on the weaker salt bodies, favoring salt extrusion. Shortening is then transferred forwards once vertical salt feeders are welded (i.e. secondary welds), while basal (primary) welds are sheared, rolled or delaminated. Changes on structural styles occur abruptly along-strike as controlled by degree of development of the precontractional salt structures. Relatively low syncontractional sedimentation rate delays forward propagation of deformation and promotes minibasins tilting. With larger sedimentation rates, a thicker cover inhibits minibasins deformation and secondary welding and, promotes a more coherent mechanical beam detached on the basal weld. Our modeling is compared to natural fold-and-thrust belts such as the Zagros and the European Alps

From salt‐bearing rifted margins to fold‐and‐thrust belts. Insights from analog modeling and northern calcareous alps case study

Analog modeling is used to study the role played by the inherited salt-sediment architecture of a salt-bearing rifted margin, developed by minibasin downbuilding and margin-scale gliding, and then incorporated into a fold-and-thrust belt system influenced by surface processes. Inherited salt bodies localize contractional deformation at different scales and the salt-sediment architecture determines structural styles of fold-and-thrust belts. In our analog models, a large-transport thrust detached along allochthonous model salt (silicone polymer) accumulated in a former distal raft system. And the squeezing of salt walls, together with the tilting of minibasins, accounted for most of the shortening in a salt wall-minibasin province. Shortening and surface processes promote the extrusion and erosion of about 75% of the original model salt. The role played by salt tectonics during the contraction of salt-bearing rifted margins could be underestimated because of the low salt-sediment ratio found in fold-and-thrust belts. Our modeling results are compared with and assist in the interpretation of a section along the Northern Calcareous Alps

Lawson criterion for ignition exceeded in an inertial fusion experiment

For more than half a century, researchers around the world have been engaged in attempts to achieve fusion ignition as a proof of principle of various fusion concepts. Following the Lawson criterion, an ignited plasma is one where the fusion heating power is high enough to overcome all the physical processes that cool the fusion plasma, creating a positive thermodynamic feedback loop with rapidly increasing temperature. In inertially confined fusion, ignition is a state where the fusion plasma can begin "burn propagation" into surrounding cold fuel, enabling the possibility of high energy gain. While "scientific breakeven" (i.e., unity target gain) has not yet been achieved (here target gain is 0.72, 1.37 MJ of fusion for 1.92 MJ of laser energy), this Letter reports the first controlled fusion experiment, using laser indirect drive, on the National Ignition Facility to produce capsule gain (here 5.8) and reach ignition by nine different formulations of the Lawson criterion

Circulating microRNAs in sera correlate with soluble biomarkers of immune activation but do not predict mortality in ART treated individuals with HIV-1 infection: A case control study

Introduction: The use of anti-retroviral therapy (ART) has dramatically reduced HIV-1 associated morbidity and mortality. However, HIV-1 infected individuals have increased rates of morbidity and mortality compared to the non-HIV-1 infected population and this appears to be related to end-organ diseases collectively referred to as Serious Non-AIDS Events (SNAEs). Circulating miRNAs are reported as promising biomarkers for a number of human disease conditions including those that constitute SNAEs. Our study sought to investigate the potential of selected miRNAs in predicting mortality in HIV-1 infected ART treated individuals. Materials and Methods: A set of miRNAs was chosen based on published associations with human disease conditions that constitute SNAEs. This case: control study compared 126 cases (individuals who died whilst on therapy), and 247 matched controls (individuals who remained alive). Cases and controls were ART treated participants of two pivotal HIV-1 trials. The relative abundance of each miRNA in serum was measured, by RTqPCR. Associations with mortality (all-cause, cardiovascular and malignancy) were assessed by logistic regression analysis. Correlations between miRNAs and CD4+ T cell count, hs-CRP, IL-6 and D-dimer were also assessed. Results: None of the selected miRNAs was associated with all-cause, cardiovascular or malignancy mortality. The levels of three miRNAs (miRs -21, -122 and -200a) correlated with IL-6 while miR-21 also correlated with D-dimer. Additionally, the abundance of miRs -31, -150 and -223, correlated with baseline CD4+ T cell count while the same three miRNAs plus miR- 145 correlated with nadir CD4+ T cell count. Discussion: No associations with mortality were found with any circulating miRNA studied. These results cast doubt onto the effectiveness of circulating miRNA as early predictors of mortality or the major underlying diseases that contribute to mortality in participants treated for HIV-1 infection

Development and Validation of a Risk Score for Chronic Kidney Disease in HIV Infection Using Prospective Cohort Data from the D:A:D Study

Ristola M. on työryhmien DAD Study Grp ; Royal Free Hosp Clin Cohort ; INSIGHT Study Grp ; SMART Study Grp ; ESPRIT Study Grp jäsen.Background Chronic kidney disease (CKD) is a major health issue for HIV-positive individuals, associated with increased morbidity and mortality. Development and implementation of a risk score model for CKD would allow comparison of the risks and benefits of adding potentially nephrotoxic antiretrovirals to a treatment regimen and would identify those at greatest risk of CKD. The aims of this study were to develop a simple, externally validated, and widely applicable long-term risk score model for CKD in HIV-positive individuals that can guide decision making in clinical practice. Methods and Findings A total of 17,954 HIV-positive individuals from the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study with >= 3 estimated glomerular filtration rate (eGFR) values after 1 January 2004 were included. Baseline was defined as the first eGFR > 60 ml/min/1.73 m2 after 1 January 2004; individuals with exposure to tenofovir, atazanavir, atazanavir/ritonavir, lopinavir/ritonavir, other boosted protease inhibitors before baseline were excluded. CKD was defined as confirmed (>3 mo apart) eGFR In the D:A:D study, 641 individuals developed CKD during 103,185 person-years of follow-up (PYFU; incidence 6.2/1,000 PYFU, 95% CI 5.7-6.7; median follow-up 6.1 y, range 0.3-9.1 y). Older age, intravenous drug use, hepatitis C coinfection, lower baseline eGFR, female gender, lower CD4 count nadir, hypertension, diabetes, and cardiovascular disease (CVD) predicted CKD. The adjusted incidence rate ratios of these nine categorical variables were scaled and summed to create the risk score. The median risk score at baseline was -2 (interquartile range -4 to 2). There was a 1: 393 chance of developing CKD in the next 5 y in the low risk group (risk score = 5, 505 events), respectively. Number needed to harm (NNTH) at 5 y when starting unboosted atazanavir or lopinavir/ritonavir among those with a low risk score was 1,702 (95% CI 1,166-3,367); NNTH was 202 (95% CI 159-278) and 21 (95% CI 19-23), respectively, for those with a medium and high risk score. NNTH was 739 (95% CI 506-1462), 88 (95% CI 69-121), and 9 (95% CI 8-10) for those with a low, medium, and high risk score, respectively, starting tenofovir, atazanavir/ritonavir, or another boosted protease inhibitor. The Royal Free Hospital Clinic Cohort included 2,548 individuals, of whom 94 individuals developed CKD (3.7%) during 18,376 PYFU (median follow-up 7.4 y, range 0.3-12.7 y). Of 2,013 individuals included from the SMART/ESPRIT control arms, 32 individuals developed CKD (1.6%) during 8,452 PYFU (median follow-up 4.1 y, range 0.6-8.1 y). External validation showed that the risk score predicted well in these cohorts. Limitations of this study included limited data on race and no information on proteinuria. Conclusions Both traditional and HIV-related risk factors were predictive of CKD. These factors were used to develop a risk score for CKD in HIV infection, externally validated, that has direct clinical relevance for patients and clinicians to weigh the benefits of certain antiretrovirals against the risk of CKD and to identify those at greatest risk of CKD.Peer reviewe

Structural styles in fold-and-thrust belts involving early salt structures: The Northern Calcareous Alps (Austria)

Shortened salt-withdrawal minibasins and associated salt welds are exposed in the Mesozoic strata of the Northern Calcareous Alps fold-and-thrust belt (Austria). Geological mapping and sequential restoration of a balanced cross section have indicated that these salt and salt-related structures developed during the postrift stage of the Neo-Tethys continental margin by evacuation and inflation/deflation of uppermost Permian to lowermost Triassic salt. Middle to Late Triassic minibasins were formed by down-building and downslope translation, flanked by megaflaps and salt walls. Salt and salt structures were rejuvenated by salt-wall fall and formation of bowl minibasins as a response to Penninic rifting since Rhaetian times. Complex structural styles, including younger-on-older contacts, tight folds, and kilometer-scale fully overturned panels resulted from the shortening of early salt structures upon the onset of Jurassic regional convergence. Salt tectonics can reconcile the stratigraphic development and internal structure of the long-debated Northern Calcareous Alps. Our work also provides a new line of research for understanding other fold-and-thrust belts developed from the Neo-Tethys continental margin (i.e., the Carpathian Mountains, the Southern Alps in Europe, the Dinaric Alps) and sets guidelines for other salt-influenced fold belts