110 research outputs found
Towards practical dynamic trust monitoring of containerized services in NFV infrastructure
Although Network Function Virtualization (NFV) and containerized services embedded therein are an already active research field while becoming increasingly widespread in practice (e.g., 5G networks), the trust and security challenges still deserve more attention. To tackle relevant issues for this aspect, our work deals with the question of whether and how the issue of trust assessment can be addressed in such infrastructures. Different trust models are reviewed, and the trust attributes used in the literature are analysed and evaluated. These parameters are subsequently included in a trust calculation framework for their confidence analysis. Finally, a Dynamic Trust Monitoring (DTM) solution, namely MicroDTM, that supervises the trustworthiness of containerized services in an NFV infrastructure is proposed. By collecting and processing the trust parameters, a containerized service environment is evaluated according to trustworthiness for different scenarios. In addition to performance analysis, improvements and extensions necessary to use the system in a practical environment are identified
Digitalisierung und Energiesystemtransformation : Chancen und Herausforderungen
Welche Rolle spielt die Digitalisierung mit der Vielzahl ihrer Methoden und Anwendungen für die Energiewende - also für die Transformation unseres Energiesystems im Sinne der vereinbarten Klimaschutzziele? Ist sie notwendige Voraussetzung für den Systemumbau und ermöglicht beispielsweise erst den Übergang auf ein nahezu vollständig erneuerbares Energiesystem (Enabler) oder ist sie lediglich ein nützliches, den Umbau beschleunigendes Hilfsmittel (Facilitator)? Welche Veränderungen sind durch die Ziele der Energiewende getrieben und welche durch die Verbreitung von Techniken der Digitalisierung? All dies waren Fragen, die im Rahmen der Jahrestagung 2018 des Forschungsverbunds Erneuerbare Energien unter dem Titel "Die Energiewende - smart und digital" behandelt wurden. Dieser einführende Beitrag versucht einige Anhaltspunkte zur Beantwortung dieser Fragen zu liefern und in das Thema einzuführen
Well-designed medical pictograms accelerate search
Two types of newly designed pharmaceutical pictograms (with and without context) were compared with an existing type of certified pictograms regarding their search efficiency. Each of the 30 participants had to search a total of 1'090 "fictitious" medical shelves for a certain box defined by the amount and type of medical instructions given (memory size) and presented among a variable number of other boxes (set size). The boxes contained the different types of pictograms mentioned above. Calculated factorial analyses on reaction time data, among others, showed that the two newly designed pictogram types make search more efficient compared to existing types of pictograms (i.e., flatter reaction time x set size slopes). Furthermore, regardless of the type of pictogram, this set size effect became more pronounced with larger memory sizes. Overall, the newly designed pictograms need fewer attentional resources and therefore might help to increase patient adherence
How Costly Is Hospital Quality? A Revealed-Preference Approach
Abstract We analyze the cost of quality improvement in hospitals, dealing with two challenges. Hospital quality is multidimensional and hard to measure, while unobserved productivity may in ‡uence quality supply. We infer the quality of hospitals in Los Angeles from patient choices. We then incorporate 'revealed quality' into a cost function, instrumenting with hospital demand. We …nd that revealed quality di¤erentiates hospitals, but is not strongly correlated with clinical quality. Revealed quality is quite costly, and tends to increase with hospital productivity. Thus, non-clinical aspects of the hospital experience (perhaps including patient amenities) play important roles in hospital demand, competition, and costs. We wish to than
Protein kinase C and cardiac dysfunction: a review
Heart failure (HF) is a physiological state in which cardiac output is insufficient to meet the needs of the body. It is a clinical syndrome characterized by impaired ability of the left ventricle to either fill or eject blood efficiently. HF is a disease of multiple aetiologies leading to progressive cardiac dysfunction and it is the leading cause of deaths in both developed and developing countries. HF is responsible for about 73,000 deaths in the UK each year. In the USA, HF affects 5.8 million people and 550,000 new cases are diagnosed annually. Cardiac remodelling (CD), which plays an important role in pathogenesis of HF, is viewed as stress response to an index event such as myocardial ischaemia or imposition of mechanical load leading to a series of structural and functional changes in the viable myocardium. Protein kinase C (PKC) isozymes are a family of serine/threonine kinases. PKC is a central enzyme in the regulation of growth, hypertrophy, and mediators of signal transduction pathways. In response to circulating hormones, activation of PKC triggers a multitude of intracellular events influencing multiple physiological processes in the heart, including heart rate, contraction, and relaxation. Recent research implicates PKC activation in the pathophysiology of a number of cardiovascular disease states. Few reports are available that examine PKC in normal and diseased human hearts. This review describes the structure, functions, and distribution of PKCs in the healthy and diseased heart with emphasis on the human heart and, also importantly, their regulation in heart failure
The genetic architecture of membranous nephropathy and its potential to improve non-invasive diagnosis
Membranous Nephropathy (MN) is a rare autoimmune cause of kidney failure. Here we report a genome-wide association study (GWAS) for primary MN in 3,782 cases and 9,038 controls of East Asian and European ancestries. We discover two previously unreported loci, NFKB1 (rs230540, OR = 1.25, P = 3.4 × 10-12) and IRF4 (rs9405192, OR = 1.29, P = 1.4 × 10-14), fine-map the PLA2R1 locus (rs17831251, OR = 2.25, P = 4.7 × 10-103) and report ancestry-specific effects of three classical HLA alleles: DRB1*1501 in East Asians (OR = 3.81, P = 2.0 × 10-49), DQA1*0501 in Europeans (OR = 2.88, P = 5.7 × 10-93), and DRB1*0301 in both ethnicities (OR = 3.50, P = 9.2 × 10-23 and OR = 3.39, P = 5.2 × 10-82, respectively). GWAS loci explain 32% of disease risk in East Asians and 25% in Europeans, and correctly re-classify 20-37% of the cases in validation cohorts that are antibody-negative by the serum anti-PLA2R ELISA diagnostic test. Our findings highlight an unusual genetic architecture of MN, with four loci and their interactions accounting for nearly one-third of the disease risk
Interactions between Type 1 Interferons and the Th17 Response in Tuberculosis: Lessons Learned from Autoimmune Diseases
textabstractThe classical paradigm of tuberculosis (TB) immunity, with a central protective role for Th1 responses and IFN-γ-stimulated cellular responses, has been challenged by unsatisfactory results of vaccine strategies aimed at enhancing Th1 immunity. Moreover, preclinical TB models have shown that increasing IFN-γ responses in the lungs is more damaging to the host than to the pathogen. Type 1 interferon signaling and altered Th17 responses have also been associated with active TB, but their functional roles in TB pathogenesis remain to be established. These two host responses have been studied in more detail in autoimmune diseases (AID) and show functional interactions that are of potential interest in TB immunity. In this review, we first identify the role of type 1 interferons and Th17 immunity in TB, followed by an overview of interactions between these responses observed in systemic AID. We discuss (i) the effects of GM-CSF-secreting Th17.1 cells and type 1 interferons on CCR2+ monocytes; (ii) convergence of IL-17 and type 1 interferon signaling on stimulating B-cell activating factor production and the central role of neutrophils in this process; and (iii) synergy between IL-17 and type 1 interferons in the generation and function of tertiary lymphoid structures and the associated follicular helper T-cell responses. Evaluation of these autoimmune-related pathways in TB pathogenesis provides a new perspective on recent developments in TB research
Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial
Background: Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes. Methods: We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18–85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR)25–75 mL/min per 1·73 m 2 of body surface area, and a urine albumin-to-creatinine ratio (UACR)of 300–5000 mg/g who had received maximum labelled or tolerated renin–angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0·75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders)were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0·75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for ≥30 days)or end-stage kidney disease (eGFR <15 mL/min per 1·73 m 2 sustained for ≥90 days, chronic dialysis for ≥90 days, kidney transplantation, or death from kidney failure)in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials.gov, number NCT01858532. Findings: Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325)or placebo group (n=1323). Median follow-up was 2·2 years (IQR 1·4–2·9). 79 (6·0%)of 1325 patients in the atrasentan group and 105 (7·9%)of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR]0·65 [95% CI 0·49–0·88]; p=0·0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3·5%)of 1325 patients in the atrasentan group and 34 (2·6%)of 1323 patients in the placebo group (HR 1·33 [95% CI 0·85–2·07]; p=0·208). 58 (4·4%)patients in the atrasentan group and 52 (3·9%)in the placebo group died (HR 1·09 [95% CI 0·75–1·59]; p=0·65). Interpretation: Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Funding: AbbVie
Globally consistent quantitative observations of planktonic ecosystems
In this paper we review the technologies available to make globally quantitative observations of particles in general—and plankton in particular—in the world oceans, and for sizes varying from sub-microns to centimeters. Some of these technologies have been available for years while others have only recently emerged. Use of these technologies is critical to improve understanding of the processes that control abundances, distributions and composition of plankton, provide data necessary to constrain and improve ecosystem and biogeochemical models, and forecast changes in marine ecosystems in light of climate change. In this paper we begin by providing the motivation for plankton observations, quantification and diversity qualification on a global scale. We then expand on the state-of-the-art, detailing a variety of relevant and (mostly) mature technologies and measurements, including bulk measurements of plankton, pigment composition, uses of genomic, optical and acoustical methods as well as analysis using particle counters, flow cytometers and quantitative imaging devices. We follow by highlighting the requirements necessary for a plankton observing system, the approach to achieve it and associated challenges. We conclude with ranked action-item recommendations for the next 10 years to move toward our vision of a holistic ocean-wide plankton observing system. Particularly, we suggest to begin with a demonstration project on a GO-SHIP line and/or a long-term observation site and expand from there, ensuring that issues associated with methods, observation tools, data analysis, quality assessment and curation are addressed early in the implementation. Global coordination is key for the success of this vision and will bring new insights on processes associated with nutrient regeneration, ocean production, fisheries and carbon sequestration
31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two
Background
The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd.
Methods
We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background.
Results
First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001).
Conclusions
In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival
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