Restricted single isocenter for multiple targets dynamic conformal arc (RSIMT DCA) technique for brain stereotactic radiosurgery (SRS) planning.

In stereotactic radiosurgery (SRS), the multiple isocenters for multiple targets dynamic conformal arc (MIMT DCA) technique is traditionally used to treat multiple brain metastases, with one isocenter for each target. The single isocenter for multiple targets (SIMT) technique has recently been adopted to reduce the treatment time at the cost of plan quality. The objective of this study was to develop a restricted single isocenter for multiple targets DCA (RSIMT DCA) technique that can significantly reduce the treatment time but still maintain similar plan quality as the MIMT DCA technique.Treating multiple brain metastases with a single isocenter poses a challenge to SRS planning using DCA beams that are intrinsically 3D and do not modulate the beam intensity to spare the normal tissue between targets. To address this obstacle, we have developed a RSIMT DCA technique and used it to treat SRS patients with multiple brain metastases since February 2015. This planning approach is similar to the SIMT technique except that the number of targets for each isocenter is restricted and the distance between the isocenter and target is limited. In this technique, the targets are first split into batches so that all targets in a batch are within a chosen distance (e.g., 7 cm) of each other. All targets in a batch are combined into one target and the geometric center of the combined target is the isocenter for the group of DCA beams associated with that batch. Each DCA group typically consists of 3-4 DCA beams to irradiate 1-3 targets. For each DCA beam, the collimator angle is adjusted to minimize the exposure of normal tissue between targets. The dose of each treatment group is normalized so that the maximal point dose to the combined target is 125% of the prescription dose, which is equivalent to normalize the prescription dose to 80% isodose line. If the maximal point dose of a target is 95% and V19Gy=100%) was achieved for all plans using either technique. Most PTVs have a maximal point dose between 24.9 and 25.1 Gy, with 2 PTVs between 24.5 and 24.9 Gy. Overall, the plan quality was slightly better for the MIMT DCA technique and the normalized difference was statistically significantly larger than 0 for all investigated dose quality indexes. The normalized difference of body mean dose and conformity index (CI) between the RSIMT and MIMT techniques was respectively 4.2% (p=0.002) and 9.4% (p=0.001), indicating similar plan quality globally and in the high dose area. The difference was more pronounced for the mid-to-low dose spillage with the ratios of V12Gy and V10Gy/VPTV being 13.9% (p=3.8×10-6) and 14.9% (p=1.3×10-5), respectively. The treatment time was reduced by 30%-50% with the RSIMT DCA technique.The RSIMT DCA technique can produce satisfactory SRS plans for treating multiple targets and can significantly reduce the treatment time

Outcome of acute type A aortic dissection: single-center experience from 1998 to 2007

Introduction. Acute aortic dissection (AAD) is a serious disease of the aorta with high mortality and morbidity, which requires emergency surgical treatment in order to close the site of the dissection and direct blood flow into the true lumen. Improve- ments in surgical technique have led to better management of patients with reduced operative mortality, although it still remains high. The aim of this study is to evaluate early and late outcomes of the surgical treatment of acute type A aortic dissection at the hospital of Lecce between 1998 and 2007. We also aim to establish a correlation between these outcomes and pre-operative conditions, surgical procedures and location of the site of the tear. Methods. From 1998 to 2007, 100 patients (69 males and 31 females, average age 62.2 ± 12.3 years, range 22-85 years) underwent surgery for acute AAD at the center. Surgical tech- niques included replacement of the ascending aorta (Asc Ao) with or without valve replacement (including five patients who underwent the Bentall/De Bono procedure) and replacement of the Asc Ao with or without arch or hemiarch replacement. Results. In-hospital mortality was 22%, with different results between surgery for replacement of the aorta and for aorta with valve replacement (respectively, 16% and 23%). Different mor- tality rates were found between the distal surgical treatments, with rates of 20.8% and 18.2% respectively between replace- ments of the Asc Ao and of Asc Ao with arch/hemiarch, although they were not statistically significant. A different mortality rate that was subject to the patient?s preoperative condition has also been found (33.3% of mortality in patients in unstable or high- risk condition vs 13.8% in patients in stable condition). The peak reached 43.5% mortality in patients taken to the operating room while in shock or cardiac tamponade. The location of the site of the tear is another factor that distinguishes mortality rates, which are 17.8% if localized at the proximal ascending aorta and 22.2% in the aortic arch. Assessment of the outcome (10 years after surgery), has shown that four patients died several years later but for reasons unrelated to the surgery. Conclusions. The surgery of dissection is still an intervention with a relatively high in-hospital mortality risk, and whose outcome, which has been steady in the last 20 years, can be predicted according to the preoperative condition of the patient. This underlines the need to reduce the time of diagnosis indicat- ing immediate surgical treatment

CPVMatch - Concentrating photovoltaic modules using advanced technologies and cells for highest efficiencies

This paper presents the project Concentrating Photovoltaic modules using advanced technologies and cells for highest efficiencies (CPVMatch), which is funded from the European Union’s Horizon 2020 research and innovation programme. V multi-junction solar cells and CPV modules. Concerning cells, novel wafer bonded four-junction solar cells made of GaInP/GaAs//GaInAs/Ge are optimized with the target of reaching 48% efficiency under concentration at the end of the project. Moreover, multi-junction solar cell technologies with advanced materials - like ternary IV element mixtures (i.e. SiGeSn) and nanostructured anti-reflective coatings - are investigated. Concerning CPV modules the project focuses on both Fresnel-based and mirror-based technologies with a target efficiency of 40% under high concentrations beyond 800x. Achromatic Fresnel lenses for improved light management without secondary optics are investigated. In addition, smart, mirror-based HCPV modules are developed, which include a new mirror-based design, the integration of high efficiency, low cost DC/DC converters and an intelligent tracking sensor (PSD sensor) at module level. A profound life-cycle and environmental assessment and the development of adapted characterization methods of new multi-junction cells and HCPV modules complete the work plan of CPVMatch

The risk of incident depression when assessed with the Lifestyle and Well-Being Index.

OBJECTIVES Novel findings indicate links between unhealthy lifestyles and depression based on active inflammatory processes. Thus, identifying participants with poor habits could reveal differences in trends of incident depression. This study aimed to examine the association between an objective lifestyle assessment, as measured by the Lifestyle and Well-Being Index (LWB-I), and incident depression in healthy participants of a Spanish cohort. STUDY DESIGN This was a longitudinal analysis of a subsample of 10,063 participants from the Seguimiento Universidad de Navarra cohort study. METHODS Group comparisons and Cox proportional hazard models were conducted using the LWB-I, which categorizes the sample into groups with healthy and unhealthy lifestyles and well-being. The main outcome was incident depression as well as secondary outcomes. RESULTS Those classified to the transition category of LWB-I were associated with a hazard ratio of 0.67 (95% confidence interval: 0.52-0.87), and those in the excellent category showed a hazard ratio of 0.44 (95% confidence interval: 0.33-0.58), which in both groups reflects a significantly lower risk of incident depression compared with the group including those classified in the poor LWB-I level. Moreover, the available sensitivity analyses concerning time of depression diagnosis or antidepressant treatment further supported the role of nutrition and physical activity on incident depression. Interestingly, throughout the follow-up, incident depression was inversely related to healthier daily habits as measured by the LWB-I. CONCLUSIONS A global assessment of lifestyles such as the LWB-I provides valuable insight into the complex relationship between lifestyle factors and their link to depression risk

The Multifaceted Function of Granzymes in Sepsis: Some Facts and a Lot to Discover

Sepsis is a serious global health problem. In addition to a high incidence, this syndrome has a high mortality and is responsible for huge health expenditure. The pathophysiology of sepsis is very complex and it is not well-understood yet. However, it is widely accepted that the initial phase of sepsis is characterized by a hyperinflammatory response while the late phase is characterized by immunosuppression and immune anergy, increasing the risk of secondary infections. Granzymes (Gzms) are a family of serine proteases classified according to their cleavage specificity. Traditionally, it was assumed that all Gzms acted as cytotoxic proteases. However, recent evidence suggests that GzmB is the one with the greatest cytotoxic capacity, while the cytotoxicity of others such as GzmA and GzmK is not clear. Recent studies have found that GzmA, GzmB, GzmK, and GzmM act as pro-inflammatory mediators. Specially, solid evidences show that GzmA and GzmK function as extracellular proteases that regulate the inflammatory response irrespectively of its ability to induce cell death. Indeed, studies in animal models indicate that GzmA is involved in the cytokine release syndrome characteristic of sepsis. Moreover, the GZM family also could regulate other biological processes involved in sepsis pathophysiology like the coagulation cascade, platelet function, endothelial barrier permeability, and, in addition, could be involved in the immunosuppressive stage of sepsis. In this review, we provide a comprehensive overview on the contribution of these novel functions of Gzms to sepsis and the new therapeutic opportunities emerging from targeting these proteases for the treatment of this serious health problem

Enhanced antitumoral activity of TLR7 agonists via activation of human endogenous retroviruses by HDAC inhibitors

In this work, we are reporting that “Shock and Kill”, a therapeutic approach designed to eliminate latent HIV from cell reservoirs, is extrapolatable to cancer therapy. This is based on the observation that malignant cells express a spectrum of human endogenous retroviral elements (HERVs) which can be transcriptionally boosted by HDAC inhibitors. The endoretroviral gene HERV-V2 codes for an envelope protein, which resembles syncytins. It is significantly overexpressed upon exposure to HDAC inhibitors and can be effectively targeted by simultaneous application of TLR7/8 agonists, triggering intrinsic apoptosis. We demonstrated that this synergistic cytotoxic effect was accompanied by the functional disruption of the TLR7/8-NFκB, Akt/PKB, and Ras-MEK-ERK signalling pathways. CRISPR/Cas9 ablation of TLR7 and HERV-V1/V2 curtailed apoptosis significantly, proving the pivotal role of these elements in driving cell death. The effectiveness of this new approach was confirmed in ovarian tumour xenograft studies, revealing a promising avenue for future cancer therapies

NGCPV: A new generation of concentrator photovoltaic cells, modules and systems

This work introduces the lines of research that the NGCPV project is pursuing and some of the first results obtained. Sponsored by the European Commission under the 7th Framework Program and NEDO (Japan) within the first collaborative call launched by both Bodies in the field of energy, NGCPV project aims at approaching the cost of the photovoltaic kWh to competitive prices in the framework of high concentration photovoltaics (CPV) by exploring the development and assessment of concentrator photovoltaic solar cells and modules, novel materials and new solar cell structures as well as methods and procedures to standardize measurement technology for concentrator photovoltaic cells and modules. More specific objectives we are facing are: (1) to manufacture a cell prototype with an efficiency of at least 45% and to undertake an experimental activity, (2) to manufacture a 35% module prototype and elaborate the roadmap towards the achievement of 40%, (3) to develop reliable characterization techniques for III-V materials and quantum structures, (4) to achieve and agreement within 5% in the characterization of CPV cells and modules in a round robin scheme, and (5) to evaluate the potential of new materials, devices technologies and quantum nanostructures to improve the efficiency of solar cells for CPV

Characterization of concentrator receivers by an appropriate solar tester: system development and measurement procedure

CIRCE system is appropriate to perform a quality control of receivers in production line before being installed in a CPV modul