•End-user oriented approaches for artifact creation and modification are considered.•A systematic mapping study in the fields of EUD, EUP and EUSE is presented.•Trends and gaps emerged from the study ...are discussed.
End-User Development (EUD), End-Programming (EUP) and End-User Software Engineering (EUSE) are three related research fields that study methods and techniques for empowering end users to modify and create digital artifacts. This paper presents a systematic mapping study aimed at identifying and classifying scientific literature about EUD, EUP and EUSE in the time range January 2000–May 2017. We selected 165 papers found through a manual selection of papers from specific conferences, journal special issues, and books, integrated with an automatic search on the most important digital libraries. The answer to our research question was built through a classification of the selected papers on seven dimensions: type of approach, interaction technique, phase in which the approach is adopted, application domain, target use, class of users, and type of evaluation. Our findings suggest that EUD, EUP and EUSE are active research topics not only in Human–Computer Interaction, but also in other research communities. However, little cross-fertilization exists among the three themes, as well as unifying frameworks and approaches for guiding novice designers and practitioners. Other findings highlight trends and gaps related to the analysis’ dimensions, which have implications on the design of future tools and suggest open issues for further investigations.
The incidence of food allergy has increased dramatically in the last few decades in westernized developed countries. We propose that the Western lifestyle and diet promote innate danger signals and ...immune responses through production of “alarmins.” Alarmins are endogenous molecules secreted from cells undergoing nonprogrammed cell death that signal tissue and cell damage. High molecular group S (HMGB1) is a major alarmin that binds to the receptor for advanced glycation end-products (RAGE). Advanced glycation end-products (AGEs) are also present in foods. We propose the “false alarm” hypothesis, in which AGEs that are present in or formed from the food in our diet are predisposing to food allergy. The Western diet is high in AGEs, which are derived from cooked meat, oils, and cheese. AGEs are also formed in the presence of a high concentration of sugars. We propose that a diet high in AGEs and AGE-forming sugars results in misinterpretation of a threat from dietary allergens, promoting the development of food allergy. AGEs and other alarmins inadvertently prime innate signaling through multiple mechanisms, resulting in the development of allergic phenotypes. Current hypotheses and models of food allergy do not adequately explain the dramatic increase in food allergy in Western countries. Dietary AGEs and AGE-forming sugars might be the missing link, a hypothesis supported by a number of convincing epidemiologic and experimental observations, as discussed in this article.
Advanced glycation end products (AGEs), formed via the Maillard reaction (MR) during processing of foods, have been implicated in inflammatory and degenerative diseases in human beings. Cellular ...damage is primarily caused by AGE binding with the receptor for AGEs (RAGE) on cell membranes. An isoform of RAGE, soluble RAGE (sRAGE), acts as a decoy receptor binding circulating AGEs preventing cellular activation. Pet food manufacturing involves processing methods similar to human food processing that may increase dietary AGEs (dAGEs). We hypothesized that diet, plasma and urine AGEs, and serum sRAGE concentrations would differ between thermally processed diets. This study examined the association of four differently processed diets: ultra‐processed canned wet food (WF); ultra‐processed dry food (DF); moderately processed air‐dried food (ADF) and minimally processed mildly cooked food (MF) on total plasma levels of the AGEs, carboxymethyllysine (CML), carboxyethyllysine (CEL), methylglyoxal hydroimidazolone‐1, glyoxal hydroimidazolone‐1, argpyrimidine, urine CML, CEL and lysinoalanine, and serum sRAGE concentration. Ultra‐high‐performance liquid chromatography–tandem mass spectrometry was used to measure AGEs. sRAGE concentration was measured using a commercial canine‐specific enzyme‐linked immunosorbent assay kit. Total dAGEs (mg/100 kcal as fed) were higher in WF than in other diets. Plasma total AGEs (nM/50 μL) were significantly higher with WF, with no difference found between DF, ADF, and MF; however, ADF was significantly higher than MF. Urine CML (nmol AGEs/mmol creatinine) was significantly higher with DF than with WF and MF. There were no significant differences in total urine AGEs or serum sRAGE concentration between diets. In conclusion, different methods of processing pet foods are associated with varied quantities of AGEs influencing total plasma AGE concentration in healthy dogs. Serum sRAGE concentration did not vary across diets but differences in total AGE/sRAGE ratio were observed between MF and WF and, ADF and DF.
The US Food and Drug Administration currently accepts halving of glomerular filtration rate (GFR), assessed as doubling of serum creatinine level, as a surrogate end point for the development of ...kidney failure in clinical trials of kidney disease progression. A doubling of serum creatinine level generally is a late event in chronic kidney disease (CKD); thus, there is great interest in considering alternative end points for clinical trials to shorten their duration, reduce sample size, and extend their conduct to patients with earlier stages of CKD. However, the relationship between lesser declines in GFR and the subsequent development of kidney failure has not been well characterized. The National Kidney Foundation and Food and Drug Administration sponsored a scientific workshop to critically examine available data to determine whether alternative GFR-based end points have sufficiently strong relationships with important clinical outcomes of CKD to be used in clinical trials. Based on a series of meta-analyses of cohorts and clinical trials and simulations of trial designs and analytic methods, the workshop concluded that a confirmed decline in estimated GFR of 30% over 2 to 3 years may be an acceptable surrogate end point in some circumstances, but the pattern of treatment effects on GFR must be examined, specifically acute effects on estimated GFR. An estimated GFR decline of 40% may be more broadly acceptable than a 30% decline across a wider range of baseline GFRs and patterns of treatment effects on GFR. However, there are other circumstances in which these end points could lead to a reduction in statistical power or erroneous conclusions regarding benefits or harms of interventions. We encourage careful consideration of these alternative end points in the design of future clinical trials.
Distinct prognostic stages of advanced chronic liver disease (ACLD) are defined by severity of portal hypertension (PH) and the presence/absence of clinical complications. We characterised the degree ...of liver dysfunction, PH, and systemic inflammation across the distinct prognostic stages and assessed their relative impact on decompensation and mortality.
A single-centre, prospective cohort of ACLD patients undergoing hepatic venous pressure gradient (HVPG) measurement between 01/2017 and 08/2019 were classified into 6 prognostic stages: mild PH (HVPG 6–9 mmHg, S0), clinically significant PH (HVPG ≥10 mmHg without varices, S1), presence of varices (S2), history of variceal bleeding (S3), first non-bleeding decompensation (S4), and further decompensation (S5). The model for end-stage liver disease (MELD), C-reactive protein (CRP), and IL-6 levels were assessed in relation to their predictive value for decompensation and death.
Among 168 ACLD patients 78 had compensated (cACLD, S0 = 13; S1 = 21; S2 = 44) and 90 had decompensated (dACLD, S3 = 10; S4 = 58; S5 = 22) disease. MELD increased across all stages (p <0.001), whereas HVPG mostly increased within cACLD substages. Significant increases in CRP and IL-6 levels were only noted across dACLD substages. IL-6 was an independent predictor of decompensation at 1-year follow-up in cACLD (hazard ratio HR 1.06, 95% CI 1.01–1.10; p = 0.013). In dACLD patients, IL-6 levels predicted death/transplantation after 1-year of follow-up (HR 1.02, 95% CI 1.01–1.03; p = 0.004).
HVPG progression occurs mostly in cACLD patients, whereas systemic inflammation, as reflected by IL-6 levels, only increases substantially across dACLD stages. IL-6 levels correlate with the risk of first decompensation in cACLD and of death/transplantation in dACLD patients.
Patients with advanced chronic liver disease (ACLD; i.e. liver cirrhosis) have a certain risk of mortality according to their stage of disease. Progression of disease is greatly influenced by increased pressure in the portal venous system (i.e. portal hypertension) and occurrence of clinical complications (i.e. decompensation). Our study demonstrates that systemic inflammation markedly increases across highest disease stages, and the inflammation biomarker IL-6 in blood may specifically indicate risk of disease progression in patients with ACLD.
The study is registered at ClinicalTrials.gov (NCT03267615).
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•Progression of portal hypertension severity (reflected by HVPG) occurs mostly across compensated ACLD stages.•Systemic inflammation (reflected by CRP and IL-6 levels) substantially increases only across decompensated ACLD.•IL-6 levels are independent predictors of first decompensation in compensated ACLD and death/liver transplantation in decompensated ACLD.
Advanced glycation end-products (AGEs) constitute a non-homogenous, chemically diverse group of compounds formed either exogeneously or endogeneously on the course of various pathways in the human ...body. In general, they are formed non-enzymatically by condensation between carbonyl groups of reducing sugars and free amine groups of nucleic acids, proteins, or lipids, followed by further rearrangements yielding stable, irreversible end-products. In the last decades, AGEs have aroused the interest of the scientific community due to the increasing evidence of their involvement in many pathophysiological processes and diseases, such as diabetes, cancer, cardiovascular, neurodegenerative diseases, and even infection with the SARS-CoV-2 virus. They are recognized by several cellular receptors and trigger many signaling pathways related to inflammation and oxidative stress. Despite many experimental research outcomes published recently, the complexity of their engagement in human physiology and pathophysiological states requires further elucidation. This review focuses on the receptors of AGEs, especially on the structural aspects of receptor-ligand interaction, and the diseases in which AGEs are involved. It also aims to present AGE classification in subgroups and to describe the basic processes leading to both exogeneous and endogeneous AGE formation.
Network slicing has emerged as a promising networking paradigm to provide resources tailored for Industry 4.0 and diverse services in 5G networks. However, the increased network complexity poses a ...huge challenge in network management due to virtualized infrastructure and stringent quality-of-service requirements. Digital twin (DT) technology paves a way for achieving cost-efficient and performance-optimal management, through creating a virtual representation of slicing-enabled networks digitally to simulate its behaviors and predict the time-varying performance. In this article, a scalable DT of network slicing is developed, aiming to capture the intertwined relationships among slices and monitor the end-to-end (E2E) metrics of slices under diverse network environments. The proposed DT exploits the novel graph neural network model that can learn insights directly from slicing-enabled networks represented by non-Euclidean graph structures. Experimental results show that the DT can accurately mirror the network behaviour and predict E2E latency under various topologies and unseen environments.
Dying Green Vatovec, Christine
2023, 20230414, 2023-04-14
eBook
The slow violence being inflicted on our environment-through
everything from carbon emissions to plastic pollution-also
represents an impending public health catastrophe. Yet standard
health care ...practices are more concerned with short-term outcomes
than long-term sustainability. Every resource used to deliver
medical care, from IV tubes to antibiotics to electricity, has a
significant environmental impact. This raises an urgent ethical
dilemma: in striving to improve the health outcomes of individual
patients, are we damaging human health on a global scale? In
Dying Green , award-winning educator Christine Vatovec
offers an engaging study that asks us to consider the broader
environmental sustainability of health care. Through a comparative
analysis of the care provided to terminally ill patients in a
conventional cancer ward, a palliative care unit, and an acute-care
hospice facility, she shows how decisions made at a patient's
bedside govern the environmental footprint of the healthcare
industry. Likewise, Dying Green offers insights on the
many opportunities that exist for reducing the ecological impacts
of medical practices in general, while also enhancing care for the
dying in particular. By envisioning a more sustainable approach to
care, this book offers a way forward that is better for both
patients and the planet.
Recent temporal action detection models have focused on end-to-end trainable approaches to utilize the representational power of backbone networks. Despite the advantages of end-to-end trainable ...methods, these models still employ a small spatial resolution (e.g., 96 × 96) due to the inefficient trade-off between computational cost and spatial resolution. In this study, we argue that a simple pooling method (e.g., adaptive average pooling) acts as a bottleneck at the spatial aggregation part, restricting representational power. To address this issue, we propose a temporal-wise spatial attentive pooling (TSAP), which alleviates the bottleneck between the backbone and the detection head using a temporal-wise attention mechanism. Our approach mitigates the inefficient trade-off between spatial resolution and computational cost, thereby enhancing spatial scalability in temporal action detection. Moreover, TSAP is adaptable to previous end-to-end approaches by simply replacing the spatial pooling part. Our experiments demonstrated the essential role of spatial aggregation, and consistent improvements are observed by incorporating TSAP into previous end-to-end methods.
Direct‐acting antiviral (DAA) therapy, recently approved for patients with decompensated cirrhosis (DC) secondary to hepatitis C virus (HCV), is associated with improved hepatic function. We analyzed ...trends in liver transplant (LT) wait‐listing (WL) to explore potential impact of effective medical therapy on WL registration. This is a cohort study using the Scientific Registry of Transplant Recipients database from 2003 to 2015. A total of 47,591 adults wait‐listed for LT from HCV, hepatitis B virus (HBV), and nonalcoholic steatohepatitis (NASH) were identified. LT indication was defined as DC if the Model for End‐Stage Liver Disease (MELD) at WL was ≥15 or hepatocellular carcinoma (HCC). Era of listing was divided into interferon (IFN; 2003‐2010), protease inhibitor (PI; 2011‐2013), and direct‐acting antiviral (DAA; 2014‐2015). Annual standardized incidence rates of WL were analyzed using Poisson regression. Adjusted incidences of LT WL for DC in HCV patients decreased by 5% in the PI era (P = 0.004) and 32% in the DAA era (P < 0.001) compared to the IFN era. Listing for DC in HBV also decreased in the PI (–17%; P = 0.002) and DAA eras (–24%; P < 0.001). Conversely, WL for DC in NASH increased by 41% in the PI era (P < 0.001) and 81% in the DAA era (P < 0.001). WL for HCC in both the HCV and NASH populations increased in both the PI and DAA eras (P < 0.001 for all) whereas HCC WL in HBV remained stable (P > 0.05 for all). Conclusion: The rate of LT WL for HCV complicated by DC has decreased by over 30% in the era of DAA therapy. Further reductions in WL are anticipated with increased testing, linkage to care, and access to DAA therapy. (Hepatology 2017;65:804‐812).