Editing Team: Markus Fiedler

and contributions of the FIA community on the important research topics that should be addressed for the Framework Programme 8 research programmes broadly grouped around three main concerns; economic and business interests; societal interests and challenges; technical disruptions and capabilities. The contents of this roadmap originate with the community of researchers working on all aspects of the Future Internet and meet to share and discuss ideas through the Future Internet Assembly through an open consultation of research projects who participate in FIA. This roadmap is primarily concerned with identifying research that can be carried out in the second half of this decade and which will have an impact in 2020 and beyond. By ‘impact ’ we mean will result in products, services, systems, capabilities, that come to market and are available and deployed in that timeframe The approach adopted in this report is to integrate contributions across the entire space of future Internet research with the aim of bringing out the vision for how and where the Internet will make a significant difference in the future and identifying the broad challenges and gaps, and identifying the solutions and research needs in the future. In this report we have summarised and grouped ideas with the aim of identifying the strong themes and consistent challenges that emerge looking acros

Study on the effectiveness of commercial anti‐islanding algorithms in the prospect of mass penetration of PVs in low‐voltage distribution networks

In the coming years, distribution grids will be progressively flooded by renewable energy sources (RES) that will be interconnected with the main grid through power electronic converters. Photovoltaics (PVs) are one of the most promising renewable technologies even for densely built-up areas where space problems are inevitable. The high penetration prospect of PV facilities on low-voltage distribution networks raises questions regarding the necessity of advanced functions that will enable electronically coupled RES to support the operation of distribution grids and to enhance their reliability. In this context, the objective of this study is to investigate the effectiveness of various islanding prevention measures installed in commercial PV inverters, when multiple inverters are operating in parallel with a low-voltage distribution network (LVDN). Extensive experiments were performed under various PV penetration levels, linear/non-linear load and over/under voltage and over/under frequency conditions, as well as for various values of total harmonic distortion of the mains voltage. Further to the primary statistical analysis, the results were analysed in depth by advanced mathematical methods such as box plot and cluster analysis. The findings of this study indicate that commercial anti-islanding techniques present a high probability of failure in the case of multiple PV units at the same point of common coupling, calling for new and more advanced algorithms.European Commission, H2020, 65411

Case Report Primary Amyloidosis Manifesting as Cholestatic Jaundice after Laparoscopic Cholecystectomy

A 71-year-old female patient with cholelithiasis who had undergone laparoscopic cholecystectomy was admitted with obstructive jaundice (total bilirubin ∼6 mg/dL) three months later. An ERCP was performed, in which a gallstone was found, followed by a sphincterotomy and cleansing of the bile duct. Due to deterioration of jaundice (>25 mg/dL), a new, unsuccessful ERCP and stent placement was carried out. Because of ongoing cardiac failure, she underwent an echocardiogram which revealed restrictive cardiomyopathy possibly due to amyloidosis. A liver biopsy was performed, which was positive for amyloid deposits in the liver, and the diagnosis was confirmed by the detection of monoclonal IgG protein in urine. The patient's jaundice gradually deteriorated and she died one week later from hepatic insufficiency

Cabbage and fermented vegetables : From death rate heterogeneity in countries to candidates for mitigation strategies of severe COVID-19

Large differences in COVID-19 death rates exist between countries and between regions of the same country. Some very low death rate countries such as Eastern Asia, Central Europe, or the Balkans have a common feature of eating large quantities of fermented foods. Although biases exist when examining ecological studies, fermented vegetables or cabbage have been associated with low death rates in European countries. SARS-CoV-2 binds to its receptor, the angiotensin-converting enzyme 2 (ACE2). As a result of SARS-CoV-2 binding, ACE2 downregulation enhances the angiotensin II receptor type 1 (AT(1)R) axis associated with oxidative stress. This leads to insulin resistance as well as lung and endothelial damage, two severe outcomes of COVID-19. The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is the most potent antioxidant in humans and can block in particular the AT(1)R axis. Cabbage contains precursors of sulforaphane, the most active natural activator of Nrf2. Fermented vegetables contain many lactobacilli, which are also potent Nrf2 activators. Three examples are: kimchi in Korea, westernized foods, and the slum paradox. It is proposed that fermented cabbage is a proof-of-concept of dietary manipulations that may enhance Nrf2-associated antioxidant effects, helpful in mitigating COVID-19 severity.Peer reviewe

Nrf2-interacting nutrients and COVID-19 : time for research to develop adaptation strategies

There are large between- and within-country variations in COVID-19 death rates. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented foods whose intake is associated with the activation of the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) anti-oxidant transcription factor. There are many Nrf2-interacting nutrients (berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) that all act similarly to reduce insulin resistance, endothelial damage, lung injury and cytokine storm. They also act on the same mechanisms (mTOR: Mammalian target of rapamycin, PPAR gamma:Peroxisome proliferator-activated receptor, NF kappa B: Nuclear factor kappa B, ERK: Extracellular signal-regulated kinases and eIF2 alpha:Elongation initiation factor 2 alpha). They may as a result be important in mitigating the severity of COVID-19, acting through the endoplasmic reticulum stress or ACE-Angiotensin-II-AT(1)R axis (AT(1)R) pathway. Many Nrf2-interacting nutrients are also interacting with TRPA1 and/or TRPV1. Interestingly, geographical areas with very low COVID-19 mortality are those with the lowest prevalence of obesity (Sub-Saharan Africa and Asia). It is tempting to propose that Nrf2-interacting foods and nutrients can re-balance insulin resistance and have a significant effect on COVID-19 severity. It is therefore possible that the intake of these foods may restore an optimal natural balance for the Nrf2 pathway and may be of interest in the mitigation of COVID-19 severity

Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely