Verkenning van de milieueffecten van lokale productie en distributie van voedsel in Almere : energieverbruik, emissie van broeikasgassen en voedselkilometers

Een van de toekomstige ontwikkelingsgebieden, Almere Oosterwold, is ongeveer 4.000 ha groot. De landbouw in het toekomstige Almere Oosterwold wordt door Almere gezien als een potentiële drager van de duurzaamheidprincipes van de stad. De leidende vraag is in welke mate de landbouw in Almere Oosterwold kan bijdragen aan een duurzame voedselvoorziening van toekomstig Almere. Uitgangspunt hierbij is dat Almere Oosterwold in 20% van de voedselbehoefte van toekomstig Almere met ca. 350.000 inwoners voorziet. Drie toekomst scenario’s voor lokale voedselproductie in Almere zijn doorgerekend. Het doel was om te bepalen in hoeverre 20% van de totale voedselbehoefte regionaal geproduceerd kan worden. Vervolgens is berekend wat deze lokale productie kan bijdragen aan de reductie van voedselkilometers, broeikasgasemissie en het gebruik van fossiele brandstof

Indirect energiegebruik en broeikasgassenuitstoot van huishouden : informatie en aanbevelingen voor gemeenten : planstudie Innovatieprogramma Klimaatneutrale Steden voor Amsterdam, Lochem en Wageningen

Bijna 70% van het energiegebruik van huishoudens wordt op een indirecte wijze geconsumeerd. Het wordt niet rechtstreeks betrokken van het energiebedrijf of het benzinestation, maar zit 'verborgen' in de aangeschafte producten en diensten. Dit rapport gaat over dat verborgen, indirecte energiegebruik van met name voeding en bouw en beschrijft de resultaten van een planstudie naar indirect energiegebruik en broeikasgassenuitstoot van huishoudens. De planstudie is uitgevoerd in opdracht van de gemeenten Amsterdam, Lochem en Wageningen

Autoantibodies against type I IFNs in patients with life-threatening COVID-19

Interindividual clinical variability in the course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is vast. We report that at least 101 of 987 patients with life-threatening coronavirus disease 2019 (COVID-19) pneumonia had neutralizing immunoglobulin G (IgG) autoantibodies (auto-Abs) against interferon-w (IFN-w) (13 patients), against the 13 types of IFN-a (36), or against both (52) at the onset of critical disease; a few also had auto-Abs against the other three type I IFNs. The auto-Abs neutralize the ability of the corresponding type I IFNs to block SARS-CoV-2 infection in vitro. These auto-Abs were not found in 663 individuals with asymptomatic or mild SARS-CoV-2 infection and were present in only 4 of 1227 healthy individuals. Patients with auto-Abs were aged 25 to 87 years and 95 of the 101 were men. A B cell autoimmune phenocopy of inborn errors of type I IFN immunity accounts for life-threatening COVID-19 pneumonia in at least 2.6% of women and 12.5% of men

Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19

Background: We previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15–20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in ~ 80% of cases. Methods: We report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded. Results: No gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5–528.7, P = 1.1 × 10−4) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR = 3.70[95%CI 1.3–8.2], P = 2.1 × 10−4). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR = 19.65[95%CI 2.1–2635.4], P = 3.4 × 10−3), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR = 4.40[9%CI 2.3–8.4], P = 7.7 × 10−8). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD] = 43.3 [20.3] years) than the other patients (56.0 [17.3] years; P = 1.68 × 10−5). Conclusions: Rare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old

Mapping the human genetic architecture of COVID-19

The genetic make-up of an individual contributes to the susceptibility and response to viral infection. Although environmental, clinical and social factors have a role in the chance of exposure to SARS-CoV-2 and the severity of COVID-19(1,2), host genetics may also be important. Identifying host-specific genetic factors may reveal biological mechanisms of therapeutic relevance and clarify causal relationships of modifiable environmental risk factors for SARS-CoV-2 infection and outcomes. We formed a global network of researchers to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity. Here we describe the results of three genome-wide association meta-analyses that consist of up to 49,562 patients with COVID-19 from 46 studies across19 countries. We report 13 genome-wide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19. Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases(3-7). They also represent potentially actionable mechanisms in response to infection. Mendelian randomization analyses support a causal role for smoking and body-mass index for severe COVID-19 although not for type II diabetes. The identification of novel host genetic factors associated with COVID-19 was made possible by the community of human genetics researchers coming together to prioritize the sharing of data, results, resources and analytical frameworks. This working model of international collaboration underscores what is possible for future genetic discoveries in emerging pandemics, or indeed for any complex human disease.Radiolog

Focus group study on mechanical in- exsufflation in invasively ventilated intensive care patients

Introduction: Few data described practicalities of using mechanical insufflation-exsufflation (MI-E) for invasively ventilated ICU patients and evidence for benefit of their use is lacking. Aim and objective: To identify barriers and facilitators to use MI-E devices in invasively ventilated ICU patients, and to explore reasons for their use in various patient indications. Methods: Four focus group discussions; 3 national (Netherlands) and 1 with international representation, each with a purposeful interprofessional sample of a maximum 10 participants with experience in using MI-E in invasively ventilated ICU patients. We developed a semi-structured interview guide informed by the Theoretical Domain Framework. An observer was present in each session. Sessions were audio recorded and transcribed verbatim. Data were analysed using content analysis. Results: Barriers for MI-E use were lack of evidence and lack of expertise in MI-E, as well as lack of device availability within the ICU. Facilitators were experience with MI-E and perceived clinical improvement in patients with MI-E use. Common reasons to start using MI-E were difficult weaning, recurrent atelectasis and pneumonia. Main contraindications were, bullous emphysema, ARDS, high PEEP, hemodynamic instability, recent pneumothorax. There was substantial variability on used technical settings of MI-E in invasively ventilated patients. Conclusions: Key barriers and facilitators to MI-E were lack of evidence, available expertise and perceived clinical improvement. Variability on technical settings likely reflect lack of evidence. Future studies should focus on settings, safety and feasibility of MI-E in invasively ventilated patients before studies on effect can be conducted

Airway care interventions and prone positioning in critically ill patients

This thesis bundles a collection of studies of (1) airway care interventions in ventilated critically ill patients in general, and (2) prone positioning in intensive care unit (ICU) patients with acute hypoxemic respiratory failure due to coronavirus disease 2019 (COVID–19). Invasively ventilated critically ill patients frequently undergo airway care interventions, like ‘endotracheal suctioning’, ‘manual hyperinflation’, ‘nebulizations’ and ‘mechanical insufflation-exsufflation’. All airway care interventions have in common that they are meant to prevent mucus accumulation in the airways, thereby possibly preventing complications. Evidence for benefit from airway care interventions in invasively ventilated critically ill patients, however, is surprisingly absent. Indications for their use vary and clinical mucus classifications do not seem to correlate with rheological properties. There is a wide variety in how these interventions are applied in daily ICU practice. Prone positioning can improve oxygenation. Before the COVID–19 pandemic, prone positioning was recommended to be used only in invasively ventilated patients with moderate to severe ARDS. During the pandemic, prone positioning started to become one of the most frequently used rescue therapies for hypoxemia patients with COVID–19 ARDS. Moreover, prone positioning was increasingly used in patients that are not intubated

Airway care interventions and prone positioning in critically ill patients

This thesis bundles a collection of studies of (1) airway care interventions in ventilated critically ill patients in general, and (2) prone positioning in intensive care unit (ICU) patients with acute hypoxemic respiratory failure due to coronavirus disease 2019 (COVID–19). Invasively ventilated critically ill patients frequently undergo airway care interventions, like ‘endotracheal suctioning’, ‘manual hyperinflation’, ‘nebulizations’ and ‘mechanical insufflation-exsufflation’. All airway care interventions have in common that they are meant to prevent mucus accumulation in the airways, thereby possibly preventing complications. Evidence for benefit from airway care interventions in invasively ventilated critically ill patients, however, is surprisingly absent. Indications for their use vary and clinical mucus classifications do not seem to correlate with rheological properties. There is a wide variety in how these interventions are applied in daily ICU practice. Prone positioning can improve oxygenation. Before the COVID–19 pandemic, prone positioning was recommended to be used only in invasively ventilated patients with moderate to severe ARDS. During the pandemic, prone positioning started to become one of the most frequently used rescue therapies for hypoxemia patients with COVID–19 ARDS. Moreover, prone positioning was increasingly used in patients that are not intubated