Drug-coated balloons to improve femoropopliteal artery patency: rationale and design of the LEVANT 2 trial

Background Atherosclerotic peripheral artery disease (PAD) is common and results in limitations in quality of life and potential progression to limb loss. Options for therapy include medical therapy, supervised exercise, surgical revascularization, and, more recently, endovascular therapies to restore arterial perfusion to the limb. Endovascular revascularization has evolved over the past 2 decades, from percutaneous transluminal angioplasty (PTA) to self-expanding stents, atherectomy, laser angioplasty, and drug-eluting stents. Despite impressive technologic advances, PTA remains the standard of care at many institutions and is the recommended primary treatment modality for femoral-popliteal PAD according to current American College of Cardiology Foundation/American Heart Association guidelines. However, restenosis after PTA is common. Therefore, a significant clinical need remains for a device that is able to achieve more durable patency than PTA but does not require a permanent implant. Drug-coated balloons (DCBs) have the potential to address this need. Several randomized controlled clinical trials of PTA balloons coated with different formulations of paclitaxel have been conducted in Europe (N Engl J Med 2008;358:689-699) (Circulation 2008;118:1358-1365) (Circ Cardiovasc Interv 2012;5:831-840) (JACC Cardiovas Interv 2014;7:10-19) and demonstrated more durable efficacy than PTA with comparable safety. These studies were limited by small sample sizes and powered solely for an angiographic primary end point. The pivotal LEVANT 2 trial was designed in collaboration with the US Food and Drug Administration to demonstrate safety and efficacy in a large population and to obtain US Food and Drug Administration approval. Methods A prospective, multicenter, single-blind trial comparing the Lutonix DCB (Bard Lutonix; New Hope, MN) versus PTA for treatment of femoropopliteal PAD (LEVANT 2) is the first US-based 2:1 randomized controlled trial of 476 patients with femoral-popliteal PAD designed to demonstrate superior efficacy and noninferior safety of a novel paclitaxel DCB compared with PTA. The primary efficacy end point is primary patency at 12 months. The primary safety end point is composite freedom at 12 months from perioperative death, index limb amputation, reintervention, and limb-related mortality. A series of important secondary end points include physical functioning, quality of life, revascularizations, and alternative measures of patency. To minimize bias potential for confounding variables, LEVANT 2 (1) excluded patients stented after predilation before randomization, (2) incorporated very stringent criteria for bailout stenting, (3) did not count bailout stenting as a target lesion revascularization or failure of any end point, (4) required a blinded clinician to perform clinical evaluations at follow-up, and (5) required clinical assessment before review of duplex ultrasound results. Conclusions LEVANT 2 represents the first US-inclusive multicenter, randomized controlled trial to assess the safety and efficacy of a novel DCB compared with PTA as primary therapy for symptomatic PAD on the background of standard medical therapy

Microfield Fluctuations and Spectral Line Shapes in Strongly Coupled Two-Component Plasmas

The spectral line shapes for hydrogen-like heavy ion emitters embedded in strongly correlated two-component electron-ion plasmas are investigated with numerical simulations. For that purpose the microfield fluctuations are calculated by molecular dynamics simulations where short range quantum effects are taken into account by using a regularized Coulomb potential for the electron-ion interaction. The microfield fluctuations are used as input in a numerical solution of the time-dependent Schroedinger equation for the radiating electron. In distinction to the standard impact and quasistatic approximations the method presented here allows to account for the correlations between plasma ions and electrons. The shapes of the Ly-alpha line in Al are investigated in the intermediate regime. The calculations are in good agreement with experiments on the Ly-alpha line in laser generated plasmas.Comment: 5 figure

Developing core sets for persons following amputation based on the International Classification of Functioning, Disability and Health as a way to specify functioning

Amputation is a common late stage sequel of peripheral vascular disease and diabetes or a sequel of accidental trauma, civil unrest and landmines. The functional impairments affect many facets of life including but not limited to: Mobility; activities of daily living; body image and sexuality. Classification, measurement and comparison of the consequences of amputations has been impeded by the limited availability of internationally, multiculturally standardized instruments in the amputee setting. The introduction of the International Classification of Functioning, Disability and Health (ICF) by the World Health Assembly in May 2001 provides a globally accepted framework and classification system to describe, assess and compare function and disability. In order to facilitate the use of the ICF in everyday clinical practice and research, ICF core sets have been developed that focus on specific aspects of function typically associated with a particular disability. The objective of this paper is to outline the development process for the ICF core sets for persons following amputation. The ICF core sets are designed to translate the benefits of the ICF into clinical routine. The ICF core sets will be defined at a Consensus conference which will integrate evidence from preparatory studies, namely: (a) a systematic literature review regarding the outcome measures of clinical trails and observational studies, (b) semi-structured patient interviews, (c) international experts participating in an internet-based survey, and (d) cross-sectional, multi-center studies for clinical applicability. To validate the ICF core sets field-testing will follow. Invitation for participation: The development of ICF Core Sets is an inclusive and open process. Anyone who wishes to actively participate in this process is invited to do so

Electron-Positron Pair Production in Relativistic Heavy Ion Collisions

In recent years, a large number of papers have appeared that dealt with \EPEM pair production in heavy ion collisions at high energies. To a large extent these studies were motivated by the existence of relativistic heavy ion accelerators all over the world. There pair production can be studied in so called ``ultra-peripheral collisions'', where the ions do not come close enough to interact strongly with each other. Various different methods have been used and it is the purpose of this review to present a unified picture of the present status of the field.Comment: 51 pages, 16 figures, submitted to Physics Report

ADRENARCHE DURING THE GREAT RECESSION AS AN ENVIRONMENTAL CHALLENGE TO PSYCHOSOCIAL DEVELOPMENT: AN EVOLUTIONARY-DEVELOPMENTAL PERSPECTIVE

Adrenarche is an important developmental period to consider in relation to both physical and psychosocial outcomes. The reorganization of the stress response system during adrenarche, understood as physiological adjustment to environments that may vary from safe and supportive to unsafe and unsupportive, not only results in specific physiological patterns of response to stress, but also leads to specific social, sexual, emotional, and parenting behavioral profiles. In this dissertation, I elaborated on the connections between adverse developmental contexts and the development of behavior problems in children and adolescents using the Adaptive Calibration Model of Stress Responsivity. I used the Great Recession of 2007-2009 as a natural window to examine how changes in economic circumstances-the introduction of economic adversity-can affect the life course, especially when experienced during adrenarche. I hypothesized that declining wealth in general and during adrenarche would not only predict behavior problems in adolescence, but it would also affect menarche and physical development, such that sexual maturation would be a mediator of wealth and psychosocial adjustment. To test these hypotheses, I used nationally representative panel data from the Panel Study of Income Dynamics and child-level information from the Child Development Supplement of the PSID. The final sample included 767 adolescents and their households. When compared with persistently low levels of wealth, declines in household wealth in a "middle class" were associated with behavioral problems among children who experienced the stressor during adrenarche, and with earlier pubertal timing among children who experienced the stressor in later childhood. The results' implications are discussed both in terms of their practical application to child welfare, their contribution to evolutionary-developmental theory, and their insights regarding wealth inequality in the United States.Doctor of Philosoph

Diagnoses and clinical features associated with high risk for unplanned readmission in vascular surgery. A cohort study

Background: Readmission rate is an established health quality indicator. Preventable readmissions bear an unnecessary, high cost on the healthcare system. An analysis performed by the National Centre for Health Outcomes Development (NCHOD) has demonstrated an increasing trend in emergency readmissions in the UK. Vascular surgery has been reported to have high readmission rates second only to congestive heart failure. This study aims to identify diagnoses and other clinical risk factors for high unplanned readmission rates. This may be the first step to sparing both the health care system and patients of unnecessary readmissions. Results: The overall 30 day readmission rate for Leeds Vascular Institute was 8.8%. The two diagnoses with the highest readmission rates were lower limb ischaemia and diabetic foot sepsis. The readmission rate for medical reasons was overwhelmingly higher than for surgical reasons (6.5% and 2.3% respectively). The most common medical diagnoses were renal disease and COPD. The majority of the patients readmitted under the care of vascular surgery required further surgical treatment. Conclusion: Vascular units should focus on holistic and multidisciplinary treatment of lower limb ischaemia and diabetic foot sepsis, in order to prevent readmissions. Furthermore, the early involvement and input of physicians in the treatment of vascular patients with renal disease and COPD may be appropriate

Experimental study and kinetic modeling of high temperature and pressure CO2 mineralization

The potential for in-situ CO2 sequestration was analyzed experimentally for one basaltic hyaloclastite sample from the Nesjavellir geothermal reservoir in Iceland and three metasedimentary rock samples from the Kızıldere geothermal field in Turkey. Based on batch reaction experiments, this paper demonstrates the interaction between a CO2 gas-charged fluid and rock samples from these reservoirs. The experiments were conducted at 260 °C and 0.8 MPa, and 105 °C and 17 MPa for the basaltic and metasedimentary rocks, respectively. The experimental results indicate that CO2 sequestration within the glassy basaltic rocks is hampered by zeolite, chlorite, and anhydrite, which compete with carbonate minerals to uptake divalent cations at the P-T conditions applied. In contrast, the carbonation process for the metasedimentary rocks is inhibited by their mineralogical composition. Generally, these rocks are less reactive and provide an insufficient supply of divalent cations. The batch reactor experiments were numerically simulated with the PHREEQC geochemical modeling program. The simulations indicate that CO2 sequestration is feasible at the tested P-T conditions, provided that silicate and SO4 mineralization is suppressed for the basaltic rocks and that there is an effective source of divalent cations for the metasedimentary rocks

Peripheral artery disease: how much inter-leg symmetry? A contrast-enhanced magnetic resonance angiography study

The aim of this observational retrospective study was to qualitatively and quantitatively evaluate the symmetry of atherosclerotic plaques in patients with peripheral artery disease (PAD) undergoing contrast-enhanced magnetic resonance angiography of lower limbs. We retrospectively evaluated the peripheral magnetic resonance angiography of 82 patients considering the iliac, femoral and tibial arteries. Stenosis was scored 0 (none), 1 (<50%), 2 (50%-74%), 3 (75%-99%), and 4 (occluded). Symmetry was quantified as the percentage of bilaterally-diseased arteries and using the inter-leg absolute score difference (0-4). Signs test and Cohen \u3ba were also calculated. Seventy-one (87%) patients had 651 bilaterally-diseased artery, and 168 (20%) of 820 artery pairs were bilaterally affected. At least 1 bilateral stenosis was observed from 11% (right internal iliac) to 73% (right superficial femoral). All 10 arteries showed symmetry, none of the inter-leg comparisons being significantly different (P 65 .100). Cohen \u3ba ranged from 0.208 (common femoral) to 0.533 (internal iliac). This study showed that PAD was symmetrically distributed between the 2 legs, with the internal iliac artery being the most symmetric segment. Symmetry of PAD was quantified in 20%

Linking geological and infrastructural requirements for large-scale underground hydrogen storage in Germany

Hydrogen storage might be key to the success of the hydrogen economy, and hence the energy transition in Germany. One option for cost-effective storage of large quantities of hydrogen is the geological subsurface. However, previous experience with underground hydrogen storage is restricted to salt caverns, which are limited in size and space. In contrast, pore storage facilities in aquifers -and/or depleted hydrocarbon reservoirs- could play a vital role in meeting base load needs due to their wide availability and large storage capacity, but experiences are limited to past operations with hydrogen-bearing town gas. To overcome this barrier, here we investigate hydrogen storage in porous storage systems in a two-step process: 1) First, we investigate positive and cautionary indicators for safe operations of hydrogen storage in pore storage systems. 2) Second, we estimate hydrogen storage capacities of pore storage systems in (current and decommissioned) underground natural gas storage systems and saline aquifers. Our systematic review highlights that optimal storage conditions in terms of energy content and hydrogen quality are found in sandstone reservoirs in absence of carbonate and iron bearing accessory minerals at a depth of approx. 1,100 m and a temperature of at least 40°C. Porosity and permeability of the reservoir formation should be at least 20% and 5 × 10−13 m2 (∼500 mD), respectively. In addition, the pH of the brine should fall below 6 and the salinity should exceed 100 mg/L. Based on these estimates, the total hydrogen storage capacity in underground natural gas storages is estimated to be up to 8 billion cubic meters or (0.72 Mt at STP) corresponding to 29 TWh of energy equivalent of hydrogen. Saline aquifers may offer additional storage capacities of 81.6–691.8 Mt of hydrogen, which amounts to 3.2 to 27.3 PWh of energy equivalent of hydrogen, the majority of which is located in the North German basin. Pore storage systems could therefore become a crucial element of the future German hydrogen infrastructure, especially in regions with large industrial hydrogen (storage) demand and likely hydrogen imports via pipelines and ships