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Sökning: WFRF:(Boyd John)

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1.
  • Locke, Adam E, et al. (författare)
  • Genetic studies of body mass index yield new insights for obesity biology.
  • 2015
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 197-401
  • Tidskriftsartikel (refereegranskat)abstract
    • Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.
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2.
  • Sumaila, U. Rashid, et al. (författare)
  • WTO must ban harmful fisheries subsidies
  • 2021
  • Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 374:6567, s. 544-544
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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3.
  • Alimena, Juliette, et al. (författare)
  • Searching for long-lived particles beyond the Standard Model at the Large Hadron Collider
  • 2020
  • Ingår i: Journal of Physics G. - : IOP Publishing. - 0954-3899 .- 1361-6471. ; 47:9
  • Tidskriftsartikel (refereegranskat)abstract
    • Particles beyond the Standard Model (SM) can generically have lifetimes that are long compared to SM particles at the weak scale. When produced at experiments such as the Large Hadron Collider (LHC) at CERN, these long-lived particles (LLPs) can decay far from the interaction vertex of the primary proton-proton collision. Such LLP signatures are distinct from those of promptly decaying particles that are targeted by the majority of searches for new physics at the LHC, often requiring customized techniques to identify, for example, significantly displaced decay vertices, tracks with atypical properties, and short track segments. Given their non-standard nature, a comprehensive overview of LLP signatures at the LHC is beneficial to ensure that possible avenues of the discovery of new physics are not overlooked. Here we report on the joint work of a community of theorists and experimentalists with the ATLAS, CMS, and LHCb experiments-as well as those working on dedicated experiments such as MoEDAL, milliQan, MATHUSLA, CODEX-b, and FASER-to survey the current state of LLP searches at the LHC, and to chart a path for the development of LLP searches into the future, both in the upcoming Run 3 and at the high-luminosity LHC. The work is organized around the current and future potential capabilities of LHC experiments to generally discover new LLPs, and takes a signature-based approach to surveying classes of models that give rise to LLPs rather than emphasizing any particular theory motivation. We develop a set of simplified models; assess the coverage of current searches; document known, often unexpected backgrounds; explore the capabilities of proposed detector upgrades; provide recommendations for the presentation of search results; and look towards the newest frontiers, namely high-multiplicity 'dark showers', highlighting opportunities for expanding the LHC reach for these signals.
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4.
  • Chan, Kai M. A., et al. (författare)
  • Levers and leverage points for pathways to sustainability
  • 2020
  • Ingår i: People and Nature. - : Wiley. - 2575-8314. ; 2:3, s. 693-717
  • Tidskriftsartikel (refereegranskat)abstract
    • 1. Humanity is on a deeply unsustainable trajectory. We are exceeding planetary boundaries and unlikely to meet many international sustainable development goals and global environmental targets. Until recently, there was no broadly accepted framework of interventions that could ignite the transformations needed to achieve these desired targets and goals.2. As a component of the IPBES Global Assessment, we conducted an iterative expert deliberation process with an extensive review of scenarios and pathways to sustainability, including the broader literature on indirect drivers, social change and sustainability transformation. We asked, what are the most important elements of pathways to sustainability?3. Applying a social-ecological systems lens, we identified eight priority points for intervention (leverage points) and five overarching strategic actions and priority interventions (levers), which appear to be key to societal transformation. The eight leverage points are: (1) Visions of a good life, (2) Total consumption and waste, (3) Latent values of responsibility, (4) Inequalities, (5) Justice and inclusion in conservation, (6) Externalities from trade and other telecouplings, (7) Responsible technology, innovation and investment, and (8) Education and knowledge generation and sharing. The five intertwined levers can be applied across the eight leverage points and more broadly. These include: (A) Incentives and capacity building, (B) Coordination across sectors and jurisdictions, (C) Pre-emptive action, (D) Adaptive decision-making and (E) Environmental law and implementation. The levers and leverage points are all non-substitutable, and each enables others, likely leading to synergistic benefits.4. Transformative change towards sustainable pathways requires more than a simple scaling-up of sustainability initiatives-it entails addressing these levers and leverage points to change the fabric of legal, political, economic and other social systems. These levers and leverage points build upon those approved within the Global Assessment's Summary for Policymakers, with the aim of enabling leaders in government, business, civil society and academia to spark transformative changes towards a more just and sustainable world.
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5.
  • Elks, Cathy E, et al. (författare)
  • Thirty new loci for age at menarche identified by a meta-analysis of genome-wide association studies
  • 2010
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:12, s. 1077-85
  • Tidskriftsartikel (refereegranskat)abstract
    • To identify loci for age at menarche, we performed a meta-analysis of 32 genome-wide association studies in 87,802 women of European descent, with replication in up to 14,731 women. In addition to the known loci at LIN28B (P = 5.4 × 10⁻⁶⁰) and 9q31.2 (P = 2.2 × 10⁻³³), we identified 30 new menarche loci (all P < 5 × 10⁻⁸) and found suggestive evidence for a further 10 loci (P < 1.9 × 10⁻⁶). The new loci included four previously associated with body mass index (in or near FTO, SEC16B, TRA2B and TMEM18), three in or near other genes implicated in energy homeostasis (BSX, CRTC1 and MCHR2) and three in or near genes implicated in hormonal regulation (INHBA, PCSK2 and RXRG). Ingenuity and gene-set enrichment pathway analyses identified coenzyme A and fatty acid biosynthesis as biological processes related to menarche timing.
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6.
  • Iveson, Timothy J., et al. (författare)
  • 3 versus 6 months of adjuvant oxaliplatin-fluoropyrimidine combination therapy for colorectal cancer (SCOT) : an international, randomised, phase 3, non-inferiority trial
  • 2018
  • Ingår i: The Lancet Oncology. - : ELSEVIER SCIENCE INC. - 1470-2045 .- 1474-5488. ; 19:4, s. 562-578
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: 6 months of oxaliplatin-containing chemotherapy is usually given as adjuvant treatment for stage 3 colorectal cancer. We investigated whether 3 months of oxaliplatin-containing chemotherapy would be non-inferior to the usual 6 months of treatment.Methods: The SCOT study was an international, randomised, phase 3, non-inferiority trial done at 244 centres. Patients aged 18 years or older with high-risk stage II and stage III colorectal cancer underwent central randomisation with minimisation for centre, choice of regimen, sex, disease site, N stage, T stage, and the starting dose of capecitabine. Patients were assigned (1: 1) to receive 3 months or 6 months of adjuvant oxaliplatin-containing chemotherapy. The chemotherapy regimens could consist of CAPOX (capecitabine and oxaliplatin) or FOLFOX (bolus and infused fluorouracil with oxaliplatin). The regimen was selected before randomisation in accordance with choices of the patient and treating physician. The primary study endpoint was disease-free survival and the non-inferiority margin was a hazard ratio of 1.13. The primary analysis was done in the intention-to-treat population and safety was assessed in patients who started study treatment. This trial is registered with ISRCTN, number ISRCTN59757862, and follow-up is continuing.Findings: 6088 patients underwent randomisation between March 27, 2008, and Nov 29, 2013. The intended treatment was FOLFOX in 1981 patients and CAPOX in 4107 patients. 3044 patients were assigned to 3 month group and 3044 were assigned to 6 month group. Nine patients in the 3 month group and 14 patients in the 6 month group did not consent for their data to be used, leaving 3035 patients in the 3 month group and 3030 patients in the 6 month group for the intention-to-treat analyses. At the cutoff date for analysis, there had been 1482 disease-free survival events, with 740 in the 3 month group and 742 in the 6 month group. 3 year disease-free survival was 76.7% (95% CI 75.1-78.2) for the 3 month group and 77.1% (75.6-78.6) for the 6 month group, giving a hazard ratio of 1.006 (0.909-1.114, test for non-inferiority p=0.012), significantly below the non-inferiority margin. Peripheral neuropathy of grade 2 or worse was more common in the 6 month group (237 [58%] of 409 patients for the subset with safety data) than in the 3 month group (103 [25%] of 420) and was long-lasting and associated with worse quality of life. 1098 serious adverse events were reported (492 reports in the 3 month group and 606 reports in the 6 month group) and 32 treatment-related deaths occurred (16 in each group).Interpretation: In the whole study population, 3 months of oxaliplatin-containing adjuvant chemotherapy was non-inferior to 6 months of the same therapy for patients with high-risk stage II and stage III colorectal cancer and was associated with reduced toxicity and improved quality of life. Despite the fact the study was underpowered, these data suggest that a shorter duration leads to similar survival outcomes with better quality of life and thus might represent a new standard of care.
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7.
  • Robles-Zurita, Jose, et al. (författare)
  • SCOT : a comparison of cost-effectiveness from a large randomised phase III trial of two durations of adjuvant Oxaliplatin combination chemotherapy for colorectal cancer
  • 2018
  • Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 119:11, s. 1332-1338
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The Short Course Oncology Therapy (SCOT) study is an international, multicentre, non-inferiority randomised controlled trial assessing the efficacy, toxicity, and cost-effectiveness of 3 months (3 M) versus the usually given 6 months (6 M) of adjuvant chemotherapy in colorectal cancer.METHODS: In total, 6088 patients with fully resected high-risk stage II or stage III colorectal cancer were randomised and followed up for 3-8 years. The within-trial cost-effectiveness analysis from a UK health-care perspective is presented using the resource use data, quality of life (EQ-5D-3L), time on treatment (ToT), disease-free survival after treatment (DFS) and overall survival (OS) data. Quality-adjusted partitioned survival analysis and Kaplan-Meier Sample Average Estimator estimated QALYs and costs. Probabilistic sensitivity and subgroup analysis was undertaken.RESULTS: The 3M arm is less costly (-4881; pound 95% CI: -6269; pound -3492) pound and entails (non-significant) QALY gains (0.08; 95% CI: -0.086; 0.230) due to a better significant quality of life. The net monetary benefit was significantly higher in 3M under a wide range of monetary values of a QALY. The subgroup analysis found similar results for patients in the CAPOX regimen. However, for the FOLFOX regimen, 3M had lower QALYs than 6M (not statistically significant).CONCLUSIONS: Overall, 3M dominates 6M with no significant detrimental impact on QALYs. The results provide the economic case that a 3M treatment strategy should be considered a new standard of care.
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8.
  • Glasbey, JC, et al. (författare)
  • 2021
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9.
  • 2021
  • swepub:Mat__t
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10.
  • 2021
  • swepub:Mat__t
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11.
  • Kanai, M, et al. (författare)
  • 2023
  • swepub:Mat__t
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13.
  • Agarwal, Girish, et al. (författare)
  • Light, the universe and everything-12 Herculean tasks for quantum cowboys and black diamond skiers
  • 2018
  • Ingår i: Journal of Modern Optics. - : Informa UK Limited. - 0950-0340 .- 1362-3044. ; 65:11, s. 1261-1308
  • Tidskriftsartikel (refereegranskat)abstract
    • The Winter Colloquium on the Physics of Quantum Electronics (PQE) has been a seminal force in quantum optics and related areas since 1971. It is rather mind-boggling to recognize how the concepts presented at these conferences have transformed scientific understanding and human society. In January 2017, the participants of PQE were asked to consider the equally important prospects for the future, and to formulate a set of questions representing some of the greatest aspirations in this broad field. The result is this multi-authored paper, in which many of the world's leading experts address the following fundamental questions: (1) What is the future of gravitational wave astronomy? (2) Are there new quantum phases of matter away from equilibrium that can be found and exploited - such as the time crystal? (3) Quantum theory in uncharted territory: What can we learn? (4) What are the ultimate limits for laser photon energies? (5) What are the ultimate limits to temporal, spatial and optical resolution? (6) What novel roles will atoms play in technology? (7) What applications lie ahead for nitrogen-vacancy centres in diamond? (8) What is the future of quantum coherence, squeezing and entanglement for enhanced super-resolution and sensing? (9) How can we solve (some of) humanity's biggest problems through new quantum technologies? (10) What new understanding of materials and biological molecules will result from their dynamical characterization with free-electron lasers? (11) What new technologies and fundamental discoveries might quantum optics achieve by the end of this century? (12) What novel topological structures can be created and employed in quantum optics?
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14.
  • Anchordoqui, Luis A., et al. (författare)
  • The Forward Physics Facility : Sites, experiments, and physics potential
  • 2022
  • Ingår i: Physics reports. - : Elsevier. - 0370-1573 .- 1873-6270. ; 968, s. 1-50
  • Tidskriftsartikel (refereegranskat)abstract
    • The Forward Physics Facility (FPF) is a proposal to create a cavern with the space and infrastructure to support a suite of far-forward experiments at the Large Hadron Collider during the High Luminosity era. Located along the beam collision axis and shielded from the interaction point by at least 100 m of concrete and rock, the FPF will house experiments that will detect particles outside the acceptance of the existing large LHC experiments and will observe rare and exotic processes in an extremely low-background environment. In this work, we summarize the current status of plans for the FPF, including recent progress in civil engineering in identifying promising sites for the FPF and the experiments currently envisioned to realize the FPF's physics potential. We then review the many Standard Model and new physics topics that will be advanced by the FPF, including searches for long-lived particles, probes of dark matter and dark sectors, high-statistics studies of TeV neutrinos of all three flavors, aspects of perturbative and non-perturbative QCD, and high-energy astroparticle physics.
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15.
  • Bentzer, Peter, et al. (författare)
  • Heparin-binding protein is important for vascular leak in sepsis
  • 2016
  • Ingår i: Intensive Care Medicine Experimental. - : Springer Science and Business Media LLC. - 2197-425X. ; 4:1
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Elevated plasma levels of heparin-binding protein (HBP) are associated with risk of organ dysfunction and mortality in sepsis, but little is known about causality and mechanisms of action of HBP. The objective of the present study was to test the hypothesis that HBP is a key mediator of the increased endothelial permeability observed in sepsis and to test potential treatments that inhibit HBP-induced increases in permeability.METHODS: Association between HBP at admission with clinical signs of increased permeability was investigated in 341 patients with septic shock. Mechanisms of action and potential treatment strategies were investigated in cultured human endothelial cells and in mice.RESULTS: Following adjustment for comorbidities and Acute Physiology and Chronic Health Evaluation (APACHE) II, plasma HBP concentrations were weakly associated with fluid overload during the first 4 days of septic shock and the degree of hypoxemia (PaO2/FiO2) as measures of increased systemic and lung permeability, respectively. In mice, intravenous injection of recombinant human HBP induced a lung injury similar to that observed after lipopolysaccharide injection. HBP increased permeability of vascular endothelial cell monolayers in vitro, and enzymatic removal of luminal cell surface glycosaminoglycans (GAGs) using heparinase III and chondroitinase ABC abolished this effect. Similarly, unfractionated heparins and low molecular weight heparins counteracted permeability increased by HBP in vitro. Intracellular, selective inhibition of protein kinase C (PKC) and Rho-kinase pathways reversed HBP-mediated permeability effects.CONCLUSIONS: HBP is a potential mediator of sepsis-induced acute lung injury through enhanced endothelial permeability. HBP increases permeability through an interaction with luminal GAGs and activation of the PKC and Rho-kinase pathways. Heparins are potential inhibitors of HBP-induced increases in permeability.
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16.
  • Bentzer, Peter, et al. (författare)
  • Plasma cytokine levels predict response to corticosteroids in septic shock
  • 2016
  • Ingår i: Intensive Care Medicine. - : Springer Science and Business Media LLC. - 0342-4642 .- 1432-1238. ; 42:12, s. 1970-1979
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: To investigate if plasma cytokine concentrations predict a beneficial response to corticosteroid treatment in septic shock patients. Methods: A cohort of septic shock patients in whom a panel of 39 cytokines had been measured at baseline (n = 363) was included. Patients who received corticosteroids were propensity score matched to non-corticosteroid-treated patients. An optimal threshold to identify responders to corticosteroid treatment for each cytokine was defined as the concentration above which the odds ratio for 28-day survival between corticosteroid- and non-corticosteroid-treated patients was highest. Results: Propensity score matching partitioned 165 patients into 61 sets; each set contained matched corticosteroid- and non-corticosteroid-treated patients. For 13 plasma cytokines threshold concentrations were found where the odds ratio for survival between corticosteroid- and non-corticosteroid-treated patients was significant (P <0.05). CD40 ligand was associated with the highest odds ratio and identified 21 % of the patients in the propensity score matched cohort as responders to corticosteroid treatment. Combinations of triplets of cytokines with a significant odds ratio, using the thresholds identified above, were tested to find a higher proportion of responders. IL3, IL6, and CCL4 identified 50 % of the patients in the propensity score matched cohort as responders to corticosteroid treatment. The odds ratio for 28-day survival was 19 (95 % CI 3.5–140, P = 0.02) with a concentration above threshold for a least one of these cytokines. Conclusion: Plasma concentration of selected cytokines is a potential predictive biomarker to identify septic shock patients that may benefit from treatment with corticosteroids.
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17.
  • Bentzer, Peter, et al. (författare)
  • Will this hemodynamically unstable patient respond to a bolus of intravenous fluids?
  • 2016
  • Ingår i: JAMA: The Journal of the American Medical Association. - : American Medical Association (AMA). - 0098-7484. ; 316:12, s. 1298-1309
  • Tidskriftsartikel (refereegranskat)abstract
    • IMPORTANCE Fluid overload occurring as a consequence of overly aggressive fluid resuscitation may adversely affect outcome in hemodynamically unstable critically ill patients. Therefore, following the initial fluid resuscitation, it is important to identify which patients will benefit from further fluid administration. OBJECTIVE To identify predictors of fluid responsiveness in hemodynamically unstable patients with signs of inadequate organ perfusion. DATA SOURCES AND STUDY SELECTION Search of MEDLINE and EMBASE (1966 to June 2016) and reference lists from retrieved articles, previous reviews, and physical examination textbooks for studies that evaluated the diagnostic accuracy of tests to predict fluid responsiveness in hemodynamically unstable adult patients who were defined as having refractory hypotension, signs of organ hypoperfusion, or both. Fluid responsiveness was defined as an increase in cardiac output following intravenous fluid administration. DATA EXTRACTION Two authors independently abstracted data (sensitivity, specificity, and likelihood ratios [LRs]) and assessed methodological quality. A bivariate mixed-effects binary regression model was used to pool the sensitivities, specificities, and LRs across studies. RESULTS A total of 50 studies (N = 2260 patients) were analyzed. In all studies, indices were measured before assessment of fluid responsiveness. The mean prevalence of fluid responsiveness was 50% (95%CI, 42%-56%). Findings on physical examination were not predictive of fluid responsiveness with LRs and 95%CIs for each finding crossing 1.0. A low central venous pressure (CVP) (mean threshold 8mmHg) was associated with fluid responsiveness (positive LR, 2.6 [95%CI, 1.4-4.6]; pooled specificity, 76%), but a CVP greater than the threshold made fluid responsiveness less likely (negative LR, 0.50 [95%CI, 0.39-0.65]; pooled sensitivity, 62%). Respiratory variation in vena cava diameter measured by ultrasound (distensibility index >15%) predicted fluid responsiveness in a subgroup of patients without spontaneous respiratory efforts (positive LR, 5.3 [95%CI, 1.1-27]; pooled specificity, 85%). Patients with less vena cava distensibility were not as likely to be fluid responsive (negative LR, 0.27 [95%CI, 0.08-0.87]; pooled sensitivity, 77%). Augmentation of cardiac output or related parameters following passive leg raising predicted fluid responsiveness (positive LR, 11 [95%CI, 7.6-17]; pooled specificity, 92%). Conversely, the lack of an increase in cardiac output with passive leg raising identified patients unlikely to be fluid responsive (negative LR, 0.13 [95%CI, 0.07-0.22]; pooled sensitivity, 88%). CONCLUSIONS AND RELEVANCE Passive leg raising followed by measurement of cardiac output or related parameters may be the most useful test for predicting fluid responsiveness in hemodynamically unstable adults. The usefulness of respiratory variation in the vena cava requires confirmatory studies.
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18.
  • Bombarda, F., et al. (författare)
  • Runaway electron beam control
  • 2019
  • Ingår i: Plasma Physics and Controlled Fusion. - : IOP Publishing. - 1361-6587 .- 0741-3335. ; 61:1
  • Tidskriftsartikel (refereegranskat)
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19.
  • Boucher, L. M., et al. (författare)
  • Expanding conceptualizations of harm reduction: results from a qualitative community-based participatory research study with people who inject drugs
  • 2017
  • Ingår i: Harm Reduction Journal. - : Springer Science and Business Media LLC. - 1477-7517. ; 14
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The perspectives of people who use drugs are critical in understanding why people choose to reduce harm in relation to drug use, what practices are considered or preferred in conceptualizations of harm reduction, and which environmental factors interfere with or support the use of harm reduction strategies. This study explores how people who inject drugs (PWID) think about harm reduction and considers the critical imperative of equity in health and social services delivery for this community. Methods: This community-based participatory research study was conducted in a Canadian urban centre. Using a peer-based recruitment and interviewing strategy, semi-structured qualitative interviews were conducted by and with PWID. The Vidaview Life Story Board, an innovative tool where interviewers and participant co-construct a visual "life-scape" using a board, markers, and customized picture magnets, was used to facilitate the interviews. The topics explored included injection drug use and harm reduction histories, facilitators and barriers to using harm reduction strategies, and suggestions for improving services and supports. Results: Twenty-three interviews with PWID (14 men and 9 women) were analysed, with a median age of 50. Results highlighted an expanded conceptualization of harm reduction from the perspectives of PWID, including motivations for adopting harm reduction strategies and a description of harm reduction practices that went beyond conventional health-focused concerns. The most common personal practices that PWID used included working toward moderation, employing various cognitive strategies, and engaging in community activities. The importance of social or peer support and improving self-efficacy was also evident. Further, there was a call for less rigid eligibility criteria and procedures in health and social services, and the need to more adequately address the stigmatization of drug users. Conclusions: These findings demonstrated that PWID incorporate many personal harm reduction practices in their daily lives to improve their well-being, and these practices highlight the importance of agency, self-care, and community building. Health and social services are needed to better support these practices because the many socio-structural barriers this community faces often interfere with harm reduction efforts. Finally, "one size does not fit all" when it comes to harm reduction, and more personalized or de-medicalized conceptualizations are recommended.
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20.
  • Cardone, Monica, et al. (författare)
  • The novel ETS factor TEL2 cooperates with Myc in B lymphomagenesis.
  • 2005
  • Ingår i: Mol Cell Biol. - 0270-7306. ; 25:6, s. 2395-405
  • Tidskriftsartikel (refereegranskat)abstract
    • The human ETS family gene TEL2/ETV7 is highly homologous to TEL1/ETV6, a frequent target of chromosome translocations in human leukemia and specific solid tumors. Here we report that TEL2 augments the proliferation and survival of normal mouse B cells and dramatically accelerates lymphoma development in Emu-Myc transgenic mice. Nonetheless, inactivation of the p53 pathway was a hallmark of all TEL2/Emu-Myc lymphomas, indicating that TEL2 expression alone is insufficient to bypass this apoptotic checkpoint. Although TEL2 is infrequently up-regulated in human sporadic Burkitt's lymphoma, analysis of pediatric B-cell acute lymphocytic leukemia (B-ALL) samples showed increased coexpression of TEL2 and MYC and/or MYCN in over one-third of B-ALL patients. Therefore, TEL2 and MYC also appear to cooperate in provoking a cadre of human B-cell malignancies.
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21.
  • Carleo, Ilaria, et al. (författare)
  • The Multiplanet System TOI-421*
  • 2020
  • Ingår i: Astronomical Journal. - : American Astronomical Society. - 1538-3881 .- 0004-6256. ; 160:3
  • Tidskriftsartikel (refereegranskat)abstract
    • We report the discovery of a warm Neptune and a hot sub-Neptune transiting TOI-421 (BD-14 1137, TIC 94986319), a bright (V = 9.9) G9 dwarf star in a visual binary system observed by the Transiting Exoplanet Survey Satellite (TESS) space mission in Sectors 5 and 6. We performed ground-based follow-up observations-comprised of Las Cumbres Observatory Global Telescope transit photometry, NIRC2 adaptive optics imaging, and FIbre-fed Echelle Spectrograph, CORALIE, High Accuracy Radial velocity Planet Searcher, High Resolution echelle Spectrometer, and Planet Finder Spectrograph high-precision Doppler measurements-and confirmed the planetary nature of the 16 day transiting candidate announced by the TESS team. We discovered an additional radial velocity signal with a period of five days induced by the presence of a second planet in the system, which we also found to transit its host star. We found that the inner mini-Neptune, TOI-421 b, has an orbital period of P-b = 5.19672 +/- 0.00049 days, a mass of M-b = 7.17 +/- 0.66 M-circle plus, and a radius of R-b = R-circle plus, whereas the outer warm Neptune, TOI-421 c, has a period of P-c = 16.06819 +/- 0.00035 days, a mass of M-c = 16.42(-1.04)(+1.06)M(circle plus), a radius of R-c = 5.09(-0.15)(+0.16)R(circle plus), and a density of rho(c) = 0.685(-0.072)(+0.080) cm(-3). With its characteristics, the outer planet (rho(c) = 0.685(-0.0072)(+0.080) cm(-3)) is placed in the intriguing class of the super-puffy mini-Neptunes. TOI-421 b and TOI-421 c are found to be well-suited for atmospheric characterization. Our atmospheric simulations predict significant Ly alpha transit absorption, due to strong hydrogen escape in both planets, as well as the presence of detectable CH4 in the atmosphere of TOI-421 c if equilibrium chemistry is assumed.
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22.
  • Duncanson, Laura, et al. (författare)
  • Aboveground biomass density models for NASA's Global Ecosystem Dynamics Investigation (GEDI) lidar mission
  • 2022
  • Ingår i: Remote Sensing of Environment. - : Elsevier BV. - 0034-4257 .- 1879-0704. ; 270
  • Tidskriftsartikel (refereegranskat)abstract
    • NASA's Global Ecosystem Dynamics Investigation (GEDI) is collecting spaceborne full waveform lidar data with a primary science goal of producing accurate estimates of forest aboveground biomass density (AGBD). This paper presents the development of the models used to create GEDI's footprint-level (~25 m) AGBD (GEDI04_A) product, including a description of the datasets used and the procedure for final model selection. The data used to fit our models are from a compilation of globally distributed spatially and temporally coincident field and airborne lidar datasets, whereby we simulated GEDI-like waveforms from airborne lidar to build a calibration database. We used this database to expand the geographic extent of past waveform lidar studies, and divided the globe into four broad strata by Plant Functional Type (PFT) and six geographic regions. GEDI's waveform-to-biomass models take the form of parametric Ordinary Least Squares (OLS) models with simulated Relative Height (RH) metrics as predictor variables. From an exhaustive set of candidate models, we selected the best input predictor variables, and data transformations for each geographic stratum in the GEDI domain to produce a set of comprehensive predictive footprint-level models. We found that model selection frequently favored combinations of RH metrics at the 98th, 90th, 50th, and 10th height above ground-level percentiles (RH98, RH90, RH50, and RH10, respectively), but that inclusion of lower RH metrics (e.g. RH10) did not markedly improve model performance. Second, forced inclusion of RH98 in all models was important and did not degrade model performance, and the best performing models were parsimonious, typically having only 1-3 predictors. Third, stratification by geographic domain (PFT, geographic region) improved model performance in comparison to global models without stratification. Fourth, for the vast majority of strata, the best performing models were fit using square root transformation of field AGBD and/or height metrics. There was considerable variability in model performance across geographic strata, and areas with sparse training data and/or high AGBD values had the poorest performance. These models are used to produce global predictions of AGBD, but will be improved in the future as more and better training data become available.
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23.
  • Elmsheuser, Johannes, et al. (författare)
  • Evolution of the ATLAS analysis model for Run-3 and prospects for HL-LHC
  • 2020
  • Ingår i: 24TH INTERNATIONAL CONFERENCE ON COMPUTING IN HIGH ENERGY AND NUCLEAR PHYSICS (CHEP 2019). - : EDP Sciences.
  • Konferensbidrag (refereegranskat)abstract
    • With an increased dataset obtained during the Run-2 of the LHC at CERN, the even larger forthcoming Run-3 data and the expected increase of the dataset by more than one order of magnitude for the HL-LHC, the ATLAS experiment is reaching the limits of the current data production model in terms of disk storage resources. The anticipated availability of an improved fast simulation will enable ATLAS to produce significantly larger Monte Carlo samples with the available CPU, which will then be limited by insufficient disk resources. The ATLAS Analysis Model Study Group for Run-3 was setup at the end of Run-2. Its tasks have been to analyse the efficiency and suitability of the current analysis model and to propose significant improvements. The group has considered options allowing ATLAS to save, for the same sample of data and simulated events, at least 30% disk space overall, and has given recommendations on how significantly larger savings could be realised for the HL-LHC. Furthermore, suggestions were made to harmonise the current stage of analysis across the collaboration. The group has now completed its work: key recommendations will be the new small sized analysis formats DAOD_PHYS and DAOD_PHYSLITE and the increased usage of a tape carousel mode in the centralised production of these formats. This proceeding reviews the recommended ATLAS analysis model for Run-3 and the status of its implementation. It also provides an outlook to the HL-LHC analysis.
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24.
  • Fisher, Jane, et al. (författare)
  • Heparin-Binding Protein (HBP) : A Causative Marker and Potential Target for Heparin Treatment of Human Sepsis-Induced Acute Kidney Injury
  • 2017
  • Ingår i: Shock. - 1540-0514. ; 48:3, s. 313-320
  • Tidskriftsartikel (refereegranskat)abstract
    • RATIONALE: Sepsis-induced acute kidney injury (AKI) is a common condition with high morbidity and mortality. Neutrophil-derived heparin-binding protein (HBP) induces vascular leakage and is a promising biomarker of sepsis-induced organ dysfunction. It remains unknown if HBP is prognostic of AKI in septic shock and if HBP could play a role in the pathophysiology of sepsis-induced AKI.OBJECTIVES: To determine the association of plasma HBP levels with development of AKI, investigate the role of HBP in the pathophysiology of sepsis-induced AKI, and test the effect of blocking HBP using heparin derivatives.METHODS: In 296 septic shock patients from the randomized multicenter Vasopressin and Septic Shock Trial (VASST) plasma HBP levels were associated with development of AKI and need for renal replacement therapy (RRT). Human renal tubular cells were exposed to recombinant HBP to evaluate inflammation and heparin derivatives were used to abrogate these effects. Finally, mice were exposed to HBP with and without heparin derivatives and the kidneys examined for signs of inflammation.FINDINGS: Plasma HBP levels were significantly higher in patients with AKI and those requiring RRT. HBP levels identified patients with moderate AKI with an area under curve (AUC) of 0.85. HBP increased IL-6 production in renal tubular epithelial cells. Different heparin derivatives abrogated the HBP-induced increased inflammatory response in vitro and in vivo.CONCLUSION: Elevated plasma HBP is associated with development of sepsis-induced AKI and HBP is involved in its pathophysiology. Our studies suggest that heparin(s) could be tested for efficacy and safety of prevention of sepsis-induced AKI.
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25.
  • Fisher, Jane, et al. (författare)
  • Is heparin-binding protein inhibition a mechanism of albumin's efficacy in human septic shock?
  • 2018
  • Ingår i: Critical Care Medicine. - 0090-3493. ; 46:5, s. 364-374
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: Our objectives were to determine first whether albumin prevents heparin-binding protein-induced increased endothelial cell permeability and renal cell inflammation and second, whether a plasma heparin-binding protein-to-albumin ratio predicts risk of acute kidney injury, fluid balance, and plasma cytokine levels in septic shock. Design: In vitro human endothelial and renal cell model and observation cohort of septic shock. Settings: Research laboratory and multicenter clinical trial (Vasopressin and Septic Shock Trial). Patients: Adult septic shock (norepinephrine dose > 5 μg/min for > 6 hr). Interventions: In vitro: heparin-binding protein (or thrombin) was added with or without albumin to 1) human endothelial cell monolayers to assess permeability and 2) to human renal tubular epithelial cells to assess inflammation. Measurements and Main Results: Transendothelial electrical resistance - a marker of permeability - of human endothelial cells was measured using a voltohmmeter. We measured plasma heparin-binding protein-to-albumin ratio and a panel of cytokines in septic shock patients (n = 330) to define an heparin-binding protein-to-albumin ratio that predicts risk of acute kidney injury. Albumin inhibited heparin-binding protein (and thrombin-induced) increased endothelial cell permeability at a threshold concentration of 20-30 g/L but increased renal tubular cell interleukin-6 release. Patients who developed or had worsened acute kidney injury had significantly higher heparin-binding protein-to-albumin ratio (1.6 vs 0.89; p < 0.001) and heparin-binding protein (38.2 vs 20.8 ng/mL; p < 0.001) than patients without acute kidney injury. The highest heparin-binding protein-to-albumin ratio (> 3.05), heparin-binding protein quartiles (> 69.8), and heparin-binding protein > 30 ng/mL were significantly associated with development or worsening of acute kidney injury (p < 0.001) in unadjusted and adjusted analyses and were robust to sensitivity analyses for death as a competing outcome. Heparin-binding protein and heparin-binding protein-to-albumin ratio were directly associated with positive fluid balance (p < 0.001) and with key inflammatory cytokines. Increasing quartiles of heparin-binding protein-to-albumin ratio and heparin-binding protein (but not albumin) were highly significantly associated with days alive and free of acute kidney injury and renal replacement therapy (p < 0.001), vasopressors (p < 0.001), ventilation (p < 0.001), and with 28-day mortality. Conclusions: Albumin inhibits heparin-binding protein-induced increased human endothelial cell permeability and heparin-binding protein greater than 30 ng/mL and heparin-binding protein-to-albumin ratio greater than 3.01 - but not serum albumin - identified patients at increased risk for acute kidney injury in septic shock.
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26.
  • Genga, Kelly Roveran, et al. (författare)
  • Impact of PCSK9 loss-of-function genotype on 1-year mortality and recurrent infection in sepsis survivors
  • 2018
  • Ingår i: EBioMedicine. - : Elsevier BV. - 2352-3964. ; 38, s. 257-264
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Reduced activity of proprotein convertase subtilisin/kexin type 9 (PCSK9) has been associated with decreased short-term death in patients with septic shock. Whether PCSK9 genotype influences long-term outcomes in sepsis survivors is unknown. Methods: We evaluated the impact of PCSK9 loss-of-function (LOF) genotype on both 1-year mortality and infection-related readmission (IRR) after an index sepsis admission. The Derivation cohort included 342 patients who survived 28 days after a sepsis admission in a tertiary hospital (Vancouver/Canada, 2004–2014), while an independent Validation cohort included 1079 septic shock patients admitted at the same hospital (2000–2006). All patients were genotyped for three common missense PCSK9 LOF variants rs11591147, rs11583680, rs562556 and were classified in 3 groups: Wildtype, single PCSK9 LOF, and multiple PCSK9 LOF, according to the number of LOF alleles per patient. We also performed a meta-analysis using both cohorts to investigate the effects of PCSK9 genotype on 90-day survival. Findings: In the Derivation cohort, patients carrying multiple PCSK9 LOF alleles showed lower risk for the composite outcome 1-year death or IRR (HR: 0.40, P = 0.006), accelerated reduction on neutrophil counts (P = 0.010), and decreased levels of PCSK9 (P = 0.037) compared with WT/single LOF groups. Our meta-analysis revealed that the presence of multiple LOF alleles was associated with lower 90-day mortality risk (OR = 0.69, P = 0.020). Interpretation: The presence of multiple PCSK9 LOF alleles decreased the risk of 1-year death or IRR in sepsis survivors. Biological measures suggest this may be related to an enhanced resolution of the initial infection. Funding: Canadian Institutes of Health Research (PJT-156056).
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27.
  • Gerdts, Eva, et al. (författare)
  • Impact of baseline severity of aortic valve stenosis on effect of intensive lipid lowering therapy (from the SEAS study)
  • 2010
  • Ingår i: American Journal of Cardiology. - : Elsevier. - 0002-9149 .- 1879-1913. ; 106:11, s. 1634-1639
  • Tidskriftsartikel (refereegranskat)abstract
    • Retrospective studies have suggested a beneficial effect of lipid-lowering treatment on the progression of aortic stenosis (AS) in milder stages of the disease. In the randomized, placebo-controlled Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study, 4.3 years of combined treatment with simvastatin 40 mg and ezetimibe 10 mg did not reduce aortic valve events (AVEs), while ischemic cardiovascular events (ICEs) were significantly reduced in the overall study population. However, the impact of baseline AS severity on treatment effect has not been reported. Baseline and outcomes data in 1,763 SEAS patients (mean age 67 years, 39% women) were used. The study population was divided into tertiles of baseline peak aortic jet velocity (tertile 1: <= 2.8 m/s; tertile 2: >2.8 to 3.3 m/s; tertile 3: >3.3 m/s). Treatment effect and interaction were tested in Cox regression analyses. The rates of AVEs and ICEs increased with increasing baseline severity of AS. In Cox regression analyses, higher baseline peak aortic jet velocity predicted higher rates of AVEs and ICEs in all tertiles (all p values <0.05) and in the total study population (p <0.001). Simvastatin-ezetimibe treatment was not associated with a statistically significant reduction in AVEs in any individual tertile. A significant quantitative interaction between the severity of AS and simvastatin-ezetimibe treatment effect was demonstrated for ICEs (p <0.05) but not for AVEs (p = 0.10). In conclusion, the SEAS study results demonstrate a strong relation between baseline the severity of AS and the rate of cardiovascular events but no significant effect of lipid-lowering treatment on AVEs, even in the group with the mildest AS.
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28.
  • Hanna, Catherine R., et al. (författare)
  • Three Versus Six Months of Adjuvant Doublet Chemotherapy for Patients With Colorectal Cancer : A Multi-Country Cost-Effectiveness and Budget Impact Analysis
  • 2021
  • Ingår i: Clinical colorectal cancer. - : Elsevier. - 1533-0028. ; 20:3, s. 236-244
  • Tidskriftsartikel (refereegranskat)abstract
    • This study widens the transferability of cost-utility results from the SCOT trial showing that administering 3 months of adjuvant, oxaliplatin-based chemotherapy is cost-effective and cost saving compared to 6 months from the perspective of all countries recruited to SCOT. The impact on healthcare budgets if the findings are implemented as predicted will amount to savings of at least US$150 million over 5 years. Background: The Short Course Oncology Treatment (SCOT) trial demonstrated non-inferiority, less toxicity, and cost-effectiveness from a UK perspective of 3 versus 6 months of oxaliplatin-based chemotherapy for patients with colorectal cancer. This study assessed the cost-effectiveness of shorter treatment and the budget impact of implementing trial findings from the perspectives of all countries recruited to SCOT: Australia, Denmark, New Zealand, Spain, Sweden, and the United Kingdom. Patients and Methods: Individual cost-utility analyses were performed from the perspective of each country. Resource, quality of life, and survival estimates from the SCOT trial (N = 6065) were used. Probabilistic sensitivity analysis and subgroup analyses were undertaken. Using undiscounted costs from these cost-utility analyses, the impact on country-specific healthcare budgets of implementing the SCOT trial findings was calculated over a 5-year period. The currency used was US dollars (US$), and 2019 was the base year. One-way and scenario sensitivity analysis addressed uncertainty within the budget impact analysis. Results: Three months of treatment were cost saving and cost-effective compared to 6 months from the perspective of all countries. The incremental net monetary benefit per patient ranged from US$8972 (Spain) to US$13,884 (Denmark). The healthcare budget impact over 5 years for the base-case scenario ranged from US$3.6 million (New Zealand) to US$61.4 million (UK) and totaled over US$150 million across all countries. Conclusion: This study has widened the transferability of results from the SCOT trial, showing that shorter treatment is cost-effective from a multi-country perspective. The vast savings from implementation could fully justify the investment in conducting the SCOT trial.
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29.
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30.
  • Kahn, Fredrik, et al. (författare)
  • Heparin-Binding Protein As A Prognostic Biomarker of Sepsis and Disease Severity at The Emergency Department
  • 2019
  • Ingår i: Shock. - 1540-0514. ; 52:6, s. 135-135
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: Rapid and early detection of patients at risk to develop sepsis remains demanding. Heparin-binding protein (HBP) has previously demonstrated good prognostic properties in detecting organ dysfunction among patients with suspected infections. This study aimed to evaluate the plasma-levels of HBP as a prognostic biomarker for infection-induced organ dysfunction among patients seeking medical attention at the emergency department.DESIGN: Prospective, international multicenter, convenience sample study SETTING:: Four general emergency departments at academic centers in Sweden, Switzerland and Canada.PATIENTS: All emergency encounters among adults where one of the following criteria were fulfilled: a) respiratory rate >25 breaths per minute; b) heart rate >120 beats per minute; c) altered mental status; d) systolic blood pressure <100 mm Hg; e) oxygen saturation <90% without oxygen; f) oxygen saturation <93% with oxygen; g) reported oxygen saturation <90%.INTERVENTION: None MEASUREMENTS AND MAIN RESULTS:: A total of 524 ED patients were prospectively enrolled, of these 236 (45%) were eventually adjudicated to have a non-infectious disease. Three hundred forty-seven patients (66%) had or developed organ dysfunction within 72 hours, 54 patients (10%) were admitted to an intensive care unit (ICU), and 23 patients (4%) died within 72 hours. For the primary outcome, detection of infected-related organ dysfunction within 72 hours, the AUC for HBP was 0.73 (95% C.I. 0.68-0.78) among all patients and 0.82 (95% C.I. 0.76-0.87) among patients confidently adjudicated to either infection or no infection. Against the secondary outcome, infection leading to admittance to the ICU, death or a persistent high SOFA-score due to an infection (SOFA-score ≥5 at 12-24 hours) HBP had an AUC of 0.87 (95% C.I. 0.79-0.95) among all patients and 0.88 (95% C.I. 0.77-0.99) among patients confidently adjudicated to either infection or non-infection.CONCLUSIONS: Among patients at the emergency department, HBP demonstrated good prognostic and discriminatory properties in detecting the most severely ill patients with infection.
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31.
  • Keller, Ulrich B, et al. (författare)
  • Myc targets Cks1 to provoke the suppression of p27Kip1, proliferation and lymphomagenesis.
  • 2007
  • Ingår i: EMBO J. - 0261-4189. ; 26:10, s. 2562-74
  • Tidskriftsartikel (refereegranskat)abstract
    • Reduced levels of the cyclin-dependent kinase inhibitor p27(Kip1) connote poor prognosis in cancer. In human Burkitt lymphoma and in precancerous B cells and lymphomas arising in Emu-Myc transgenic mice, p27(Kip1) expression is markedly reduced. We show that the transcription of the Cks1 component of the SCF(Skp2) complex that is necessary for p27(Kip1) ubiquitylation and degradation is induced by Myc. Further, Cks1 expression is elevated in precancerous Emu-Myc B cells, and high levels of Cks1 are also a hallmark of Emu-Myc lymphoma and of human Burkitt lymphoma. Finally, loss of Cks1 in Emu-Myc B cells elevates p27(Kip1) levels, reduces proliferation and markedly delays lymphoma development and dissemination of disease. Therefore, Myc suppresses p27(Kip1) expression, accelerates cell proliferation and promotes tumorigenesis at least in part through its ability to selectively induce Cks1.
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32.
  • Lang, Anthony E, et al. (författare)
  • Integrated Safety of Levodopa-Carbidopa Intestinal Gel From Prospective Clinical Trials.
  • 2016
  • Ingår i: Movement Disorders. - : Wiley. - 0885-3185 .- 1531-8257. ; 31:4, s. 538-546
  • Tidskriftsartikel (refereegranskat)abstract
    • Continuous administration of levodopa-carbidopa intestinal gel (carbidopa-levodopa enteral suspension) through a percutaneous endoscopic gastrojejunostomy is a treatment option for advanced Parkinson disease (PD) patients with motor fluctuations resistant to standard oral medications. Safety data from 4 prospective studies were integrated to assess the safety of this therapy.
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33.
  • Lindén-Søndersø, Anja, et al. (författare)
  • Survey of non-resuscitation fluids administered during septic shock : a multicenter prospective observational study
  • 2019
  • Ingår i: Annals of Intensive Care. - : Springer Science and Business Media LLC. - 2110-5820. ; 9
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The indication, composition and timing of administration of non-resuscitation fluid in septic shock have so far received little attention and accordingly the potential to reduce this source of fluid is unknown. The objective of the study was to quantify and characterize non-resuscitation fluid administered to patients with septic shock.METHODS: This prospective observational study was performed in eight intensive care units in Sweden and Canada during 4 months in 2018. Adult patients with septic shock within 24 h of admission to the intensive care unit were eligible for inclusion. Non-resuscitation fluids were defined as fluids other than colloids, blood products and crystalloids at a rate ≥ 5 ml/kg/h. Indication, volume and type of fluid were recorded during the first 5 days after admission. A maximum of 30 patients could be included per centre. To estimate the potential to reduce administration of non-resuscitation fluid, a pragmatic "restrictive" protocol for administration of non-resuscitation fluids was devised based on the most restrictive practice already in place for non-resuscitation fluids at any of the participating centres. Data are presented as median (interquartile range [IQR]).RESULTS: A total of 200 patients were included in the study and the 30-day mortality was 35%. Patients received a total of 7870 (4060-12,340) ml of non-resuscitation fluids and 2820 (1430-4580) of resuscitation fluids during the observation period. Median volumes of non-resuscitation and resuscitation fluids were similar at day 1 (1620 [710-2320] and 1590 [520-3000]) ml, respectively) and non-resuscitation fluids represented the largest source of fluid from day 2 and onwards after admission to the ICU. Vehicles for drugs such as vasoactive drugs and antibiotics constituted the largest fraction of non-resuscitation fluids (2400 [1270-4030] ml) during the 5-day observation period. Modelling suggested that volume of non-resuscitation fluids could be reduced by 2840 (1270-4900) ml during the first 5 days of admission to the ICU, mainly through reducing maintenance fluids.CONCLUSIONS: Non-resuscitation fluids constitute the major fraction of fluids administered in the ICU to patients suffering from septic shock and may represent the largest modifiable target to reduce fluid overload.
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34.
  • Linder, Adam, et al. (författare)
  • Heparin-Binding Protein Measurement Improves the Prediction of Severe Infection With Organ Dysfunction in the Emergency Department
  • 2015
  • Ingår i: Critical Care Medicine. - : LIPPINCOTT WILLIAMS and WILKINS. - 0090-3493 .- 1530-0293. ; 43:11, s. 2378-2386
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: Early identification of patients with infection and at risk of developing severe disease with organ dysfunction remains a difficult challenge. We aimed to evaluate and validate the heparin-binding protein, a neutrophil-derived mediator of vascular leakage, as a prognostic biomarker for risk of progression to severe sepsis with circulatory failure in a multicenter setting. Design: A prospective international multicenter cohort study. Setting: Seven different emergency departments in Sweden, Canada, and the United States. Patients: Adult patients with a suspected infection and at least one of three clinical systemic inflammatory response syndrome criteria (excluding leukocyte count). Intervention: None. Measurements and Main Results: Plasma levels of heparin-binding protein, procalcitonin, C-reactive protein, lactate, and leukocyte count were determined at admission and 12-24 hours after admission in 759 emergency department patients with suspected infection. Patients were defined depending on the presence of infection and organ dysfunction. Plasma samples from 104 emergency department patients with suspected sepsis collected at an independent center were used to validate the results. Of the 674 patients diagnosed with an infection, 487 did not have organ dysfunction at enrollment. Of these 487 patients, 141 (29%) developed organ dysfunction within the 72-hour study period; 78.0% of the latter patients had an elevated plasma heparin-binding protein level (greater than 30 ng/mL) prior to development of organ dysfunction (median, 10.5 hr). Compared with other biomarkers, heparin-binding protein was the best predictor of progression to organ dysfunction (area under the receiver operating characteristic curve = 0.80). The performance of heparin-binding protein was confirmed in the validation cohort. Conclusion: In patients presenting at the emergency department, heparin-binding protein is an early indicator of infection-related organ dysfunction and a strong predictor of disease progression to severe sepsis within 72 hours.
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35.
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36.
  • Linder, Adam, et al. (författare)
  • Short-term organ dysfunction is associated with long-term (10-Yr) mortality of septic shock
  • 2016
  • Ingår i: Critical Care Medicine. - 0090-3493. ; 44:8, s. 728-736
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: As mortality of septic shock decreases, new therapies focus on improving short-term organ dysfunction. However, it is not known whether short-term organ dysfunction is associated with long-term mortality of septic shock. Design: Retrospective single-center. Setting: Mixed medical-surgical ICU. Patients: One thousand three hundred and thirty-one patients with septic shock were included from 2000-2004. To remove the bias of 28-day nonsurvivors' obvious association with long-term mortality, we determined the associations of days alive and free of ventilation, vasopressors and renal replacement therapy in 28-day and 1-year survivors with 1-, 5- and 10-year mortality in unadjusted analyses and analyses adjusted for age, gender, Acute Physiology and Chronic Health Evaluation II and presence of chronic comorbidities. Interventions: None. Measurements and Main Results: Days alive and free of ventilation, vasopressors, and renal replacement therapy were highly significantly associated with 1-, 5-, and 10-year mortality (p <0.0001). In 28-day survivors, using Bonferroni-corrected multiple logistic regression, days alive and free of ventilation (p <0.0001, p = 0.0002, and p = 0.001), vasopressors (p <0.0001, p <0.0001, and p = 0.0004), and renal replacement therapy (p = 0.0008, p = 0.0008, and p = 0.0002) were associated with increased 1-, 5-, and 10-year mortality, respectively. In 1-year survivors, none of the acute organ support and dysfunction measures were associated with 5- and 10-year mortality. Conclusions: Days alive and free of ventilation, vasopressors, and renal replacement therapy in septic shock in 28-day survivors was associated with 1-, 5-, and 10-year mortality. These associations are nullified in 1-year survivors in whom none of the acute organ support measures were associated with 5- and 10-year mortality. This suggests that therapies that decrease short-term organ dysfunction could also improve long-term outcomes of 28-day survivors of septic shock.
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37.
  • Linder, Adam, et al. (författare)
  • Small Acute Increases in Serum Creatinine Are Associated with Decreased Long-Term Survival in the Critically Ill
  • 2014
  • Ingår i: American Journal of Respiratory and Critical Care Medicine. - 1535-4970. ; 189:9, s. 1075-1081
  • Tidskriftsartikel (refereegranskat)abstract
    • Rationale: Long-term outcomes after acute kidney injury (AKI) are poorly described. Objectives: We hypothesized that one single episode of minimal (stage 1) AKI is associated with reduced long-term survival compared with no AKI after recovery from critical illness. Methods: A prospective cohort of 2,010 intensive care unit (ICU) patients admitted to the ICU between years 2000 and 2009 at a provincial tertiary care hospital. Development of AKI was determined according to the KDIGO classification and mortality up to 10 years after ICU admission was recorded. Measurements and Main Results: Of the 1,844 eligible patients, 18.4% had AKI stage 1, 12.1% had stage 2, 26.5% had stage 3, and 43.0% had no AKI. The 28-day, 1-year, 5-year, and 10-year survival rates were 67.1%, 51.8%, 44.1%, and 36.3% in patients with mild AKI, which was significantly worse compared with the critically ill patients with no AKI at any time (P < 0.01). The unadjusted 10-year mortality hazard ratio was 1.53 (95% confidence interval, 1.2-2.0) for 28-day survivors with stage 1 AKE compared with critically ill patients with no AKI. Adjusted 10-year mortality risk was 1.26 (1.0-1.6). After propensity matching stage 1 AKI with no AKE patients, mild AKE was still significantly associated with decreased 10-year survival (P =0.036). Conclusions: Patients with one episode of mild AKI have significantly lower long-term survival rates than critically ill patients with no AKI. Close medical follow-up of these patients may be warranted and mechanistic research is required to understand how AKI influences long-term events.
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38.
  • Linder, Adam, et al. (författare)
  • The specific organism : Not bacterial gram type: Drives the inflammatory response in septic shock
  • 2020
  • Ingår i: Journal of Innate Immunity. - : S. Karger AG. - 1662-811X .- 1662-8128. ; 12:2, s. 182-190
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and Hypothesis: The inflammatory response was targeted by unsuccessful therapies but ignored pathogen. We hypothesized that the inflammatory response differs according to organism in human septic shock. Materials and Methods: We measured 39 cytokines at baseline and 24 h in patients (n = 363) in the Vasopressin and Septic Shock Trial (VASST). We compared cytokine profiles (cytokine functional class) at baseline and at 24 h by organism and used hierarchical clustering to classify cytokines according to 28-day outcomes. Results: In 363 patients, 88 and 176 patients had at least 1 species isolated from blood and other sites, respectively. Cytokine levels differed significantly according to organism: Neisseria meningitidis and Streptococcus pneumoniae had the highest (baseline and at 24 h), while Enterococcus faecalis (blood) had the lowest mean cytokine levels. N. meningitidis and Klebsiella pneumoniae had significantly higher cytokine levels at baseline versus 24 h (p = 0.01 and 0.02, respectively); E. faecalis had significantly higher cytokine levels at 24 h versus baseline. Hierarchical clustering heat maps showed that pathogens elicited similar cytokine responses not related to the functional cytokine class. Conclusion: The organism type induces different cytokine profiles in septic shock. Specific gram-positive and gram-negative pathogens stimulated similar plasma cytokine-level patterns.
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39.
  • Mellhammar, Lisa, et al. (författare)
  • NEWS2 is Superior to qSOFA in Detecting Sepsis with Organ Dysfunction in the Emergency Department
  • 2019
  • Ingår i: Journal of Clinical Medicine. - : MDPI AG. - 2077-0383. ; 8:8
  • Tidskriftsartikel (refereegranskat)abstract
    • Early administration of antibiotics is associated with better survival in sepsis, thus screening and early detection for sepsis is of clinical importance. Current risk stratification scores used for bedside detection of sepsis, for example Quick Sequential Organ Failure Assessment (qSOFA) and National Early Warning Score 2 (NEWS2), are primarily validated for death and intensive care. The primary aim of this study was to compare the diagnostic accuracy of qSOFA and NEWS2 for a composite outcome of sepsis with organ dysfunction, infection-related mortality within <72 h, or intensive care due to an infection. Retrospective analysis of data from two prospective, observational, multicentre, convenience trials of sepsis biomarkers at emergency departments were performed. Cohort A consisted of 526 patients with a diagnosed infection, 288 with the composite outcome. Cohort B consisted of 645 patients, of whom 269 had a diagnosed infection and 191 experienced the composite outcome. In Cohort A and B, NEWS2 had significantly higher area under receiver operating characteristic curve (AUC), 0.80 (95% CI 0.75-0.83) and 0.70 (95% CI 0.65-0.74), than qSOFA, AUC 0.70 (95% CI 0.66-0.75) and 0.62 (95% CI 0.57-0.67) p < 0.01 and, p = 0.02, respectively for the composite outcome. NEWS2 was superior to qSOFA for screening for sepsis with organ dysfunction, infection-related mortality or intensive care due to an infection both among infected patients and among undifferentiated patients at emergency departments.
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40.
  • Mellhammar, Lisa, et al. (författare)
  • Scores for sepsis detection and risk stratification – construction of a novel score using a statistical approach and validation of RETTS
  • 2020
  • Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 15:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Background To allow early identification of patients at risk of sepsis in the emergency department (ED), a variety of risk stratification scores and/or triage systems are used. The first aim of this study was to develop a risk stratification score for sepsis based upon vital signs and biomarkers using a statistical approach. Second, we aimed to validate the Rapid Emergency Triage and Treatment System (RETTS) for sepsis. RETTS combines vital signs with symptoms for risk stratification. Methods We retrospectively analysed data from two prospective, observational, multicentre cohorts of patients from studies of biomarkers in ED. A candidate risk stratification score called Sepsis Heparin-binding protein-based Early Warning Score (SHEWS) was constructed using the Least Absolute Shrinkage and Selector Operator (LASSO) method. SHEWS and RETTS were compared to National Early Warning Score 2 (NEWS2) for infection-related organ dysfunction, intensive care or death within the first 72h after admission (i.e. sepsis). Results 506 patients with a diagnosed infection constituted cohort A, in which SHEWS was derived and RETTS was validated. 435 patients constituted cohort B of whom 184 had a diagnosed infection where both scores were validated. In both cohorts (A and B), AUC for infection-related organ dysfunction, intensive care or death was higher for NEWS2, 0.80 (95% CI 0.76–0.84) and 0.69 (95% CI 0.63–0.74), than RETTS, 0.74 (95% CI 0.70–0.79) and 0.55 (95% CI 0.49–0.60), p = 0.05 and p <0.01, respectively. SHEWS had the highest AUC, 0.73 (95% CI 0.68–0.79) p = 0.32 in cohort B. Conclusions Even with a statistical approach, we could not construct better risk stratification scores for sepsis than NEWS2. RETTS was inferior to NEWS2 for screening for sepsis.
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41.
  • Morel, Alexandra C., et al. (författare)
  • Carbon dynamics, net primary productivity and human-appropriated net primary productivity across a forest–cocoa farm landscape in West Africa
  • 2019
  • Ingår i: Global Change Biology. - : Wiley. - 1354-1013 .- 1365-2486. ; 25:8, s. 2661-2677
  • Tidskriftsartikel (refereegranskat)abstract
    • Terrestrial net primary productivity (NPP) is an important metric of ecosystem functioning; however, there are little empirical data on the NPP of human-modified ecosystems, particularly smallholder, perennial crops like cocoa (Theobroma cacao), which are extensive across the tropics. Human-appropriated NPP (HANPP) is a measure of the proportion of a natural system's NPP that has either been reduced through land-use change or harvested directly and, previously, has been calculated to estimate the scale of the human impact on the biosphere. Additionally, human modification can create shifts in NPP allocation and decomposition, with concomitant impacts on the carbon cycle. This study presents the results of 3 years of intensive monitoring of forest and smallholder cocoa farms across disturbance, management intensity, distance from forest and farm age gradients. We measured among the highest reported NPP values in tropical forest, 17.57 ± 2.1 and 17.7 ± 1.6 Mg C ha−1 year−1 for intact and logged forest, respectively; however, the average NPP of cocoa farms was still higher, 18.8 ± 2.5 Mg C ha−1 year−1, which we found was driven by cocoa pod production. We found a dramatic shift in litterfall residence times, where cocoa leaves decomposed more slowly than forest leaves and shade tree litterfall decomposed considerably faster, indicating significant changes in rates of nutrient cycling. The average HANPP value for all cocoa farms was 2.1 ± 1.1 Mg C ha−1 year−1; however, depending on the density of shade trees, it ranged from −4.6 to 5.2 Mg C ha−1 year−1. Therefore, rather than being related to cocoa yield, HANPP was reduced by maintaining higher shade levels. Across our monitored farms, 18.9% of farm NPP was harvested (i.e., whole cocoa pods) and only 1.1% (i.e., cocoa beans) was removed from the system, suggesting that the scale of HANPP in smallholder cocoa agroforestry systems is relatively small.
  •  
42.
  • Morel, Alexandra C., et al. (författare)
  • Landscape and management influences on smallholder agroforestry yields show shifts during a climate shock
  • 2024
  • Ingår i: Agriculture, Ecosystems and Environment. - 0167-8809. ; 366
  • Tidskriftsartikel (refereegranskat)abstract
    • Sustaining yields for smallholder perennial agriculture under a rapidly changing climate regime may require consideration of landscape features and on-farm management decisions in tandem. Optimising landscape and management may not be possible for maximising yields in any one year but maintaining heterogeneous landscapes could be an important climate adaptation strategy. In this study, we observed elevation, forest patch and shade management gradients affecting smallholder coffee (Coffea arabica) yields in a ‘normal’ year versus the 2015/16 El Niño. We generally found a benefit to yields from having leguminous shade trees and low canopy openness, while maintaining diverse shade or varying canopy openness had more complex influences during a climate shock. The two years of observed climate shock were dominated by either drought or high temperatures, with yield responses generally negative. Climate projections for East Africa predict more erratic rainfall and higher temperatures, which will disproportionately impact smallholder farmers.
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43.
  • Morel, Alexandra C., et al. (författare)
  • The Ecological Limits of Poverty Alleviation in an African Forest-Agriculture Landscape
  • 2019
  • Ingår i: Frontiers in Sustainable Food Systems. - : Frontiers Media SA. - 2571-581X. ; 3
  • Tidskriftsartikel (refereegranskat)abstract
    • Cocoa yields in Ghana remain low. This has variously been attributed to low rates of fertilizer application, pollinator limitation, and particularly dry growing conditions. In this paper we use an African forest-agriculture landscape dominated by cocoa (Theobroma cacao) to develop an ecological production function, allowing us to identify key ecological and management limits acting on cocoa yields simultaneously. These included more consistent application of fertilizers inter-annually, distributing rotting biomass throughout the farm and reducing the incidence of capsid attacks. By relaxing these limits, we estimate plausible increases in yields and, by extension, farm incomes. Our analysis reveals that resulting increases in cocoa yields requiring both ecological and intensive management interventions could be significant (113 ± 60%); however, benefits are disproportionately realized by the wealthiest households. We found that wealthier households benefited proportionally more from ecological intensification methods (e.g., leaving more rotting biomass in their farms) and the poorest households benefited proportionally more from capital-intensive intensification methods (e.g., pesticide and fertilizer applications). We treated poverty as multi-dimensional, and show that only certain dimensions of poverty (school attendance, assets, and food security) are significantly related to cocoa incomes, while several other dimensions (access to clean water, sanitation and electricity, and infant mortality) are not. We explore how increased household cocoa incomes could impact different dimensions of poverty. Our findings suggest, that if all households adopted the optimal level of each of these management options, and in so doing had similar poverty profiles to those households already managing optimally, we would see the community-averaged probability: a child of a household misses school decrease from 47 to 31%, a household would be able to acquire assets increase from 40 to 59% and a household would have access to an adequate amount of food increase from 62 to 79%.
  •  
44.
  • Morel, Alexandra C., et al. (författare)
  • The structures underpinning vulnerability : Examining landscape-society interactions in a smallholder coffee agroforestry system
  • 2019
  • Ingår i: Environmental Research Letters. - : IOP Publishing. - 1748-9326. ; 14:7
  • Tidskriftsartikel (refereegranskat)abstract
    • Smallholder farmers dependent on rain-fed agriculture are particularly vulnerable to extreme climate events and, therefore, it is necessary to identify adaptive measures that would increase farmer resilience to these shocks. The management options in a low-input system, like forest coffee (Coffea arabica), are limited and there are several factors out of farmers' control driving their vulnerability to changing climatic conditions. These can relate to social structures and landscape factors, which can interact to reduce farmers' adaptive capacity, creating a state of contextual vulnerability. We explored the potential synergies of this interaction across elevation, patch area and shade management gradients for smallholder coffee farms around the UNESCO Yayu Coffee Forest Biosphere Reserve in Ethiopia before, during and immediately following the 2015/16 El Niño. We documented a dramatic collapse in coffee yields across all farms, resulting in coffee incomes 29.5% ±18.0% and 19.5% ±10.0% of 2014 incomes in 2015 and 2016, respectively. We identified farms at elevations between 1500 and 1600 m with canopy openness between 40% and 45% as being consistently low yielding over our study period. We found these farmers had the highest rates of income diversification and, therefore, were already exhibiting adaptive capacity. Farmers with the largest income losses were spatially concentrated between 1600 and 1700 m, located in larger patch areas with lower canopy openness. Farmers at this elevation have access to poor infrastructure, restrictions on shade management and reported higher dependence on income from coffee, indicating an interaction of biotic and social factors exacerbating their vulnerability. Unfortunately, due to a nationally declared state of emergency, we were unable to survey farmers on the adaptive measures they undertook; therefore, we are limited in assessing their resilience. However, we do show the importance of considering both biotically and socially-mediated influences for assessing smallholder vulnerability, particularly barriers to diversifying incomes.
  •  
45.
  • Morrison, John C., et al. (författare)
  • Numerical methods for solving the Hartree-Fock equations of diatomic molecules I.
  • 2009
  • Ingår i: Communications in Computational Physics. - 1815-2406 .- 1991-7120. ; 5:5, s. 959-985
  • Tidskriftsartikel (refereegranskat)abstract
    • The theory of domain decomposition is described and used to divide the variable domain of a diatomic molecule into separate regions which are solved independently. This approach makes it possible to use fast Krylov methods in the broad interior of the region while using explicit methods such as Gaussian elimination on the boundaries. As is demonstrated by solving a number of model problems, these methods enable one to obtain solutions of the relevant partial differential equations and eigenvalue equations accurate to six significant figures with a small amount of computational time. Since the numerical approach described in this article decomposes the variable space into separate regions where the equations are solved independently, our approach is very well-suited to parallel computing and offers the long term possibility of studying complex molecules by dividing them into smaller fragments that are calculated separately.
  •  
46.
  • Murray, Alison E., et al. (författare)
  • Roadmap for naming uncultivated Archaea and Bacteria
  • 2020
  • Ingår i: Nature Microbiology. - : NATURE PUBLISHING GROUP. - 2058-5276. ; 5:8, s. 987-994
  • Tidskriftsartikel (refereegranskat)abstract
    • The assembly of single-amplified genomes (SAGs) and metagenome-assembled genomes (MAGs) has led to a surge in genome-based discoveries of members affiliated with Archaea and Bacteria, bringing with it a need to develop guidelines for nomenclature of uncultivated microorganisms. The International Code of Nomenclature of Prokaryotes (ICNP) only recognizes cultures as 'type material', thereby preventing the naming of uncultivated organisms. In this Consensus Statement, we propose two potential paths to solve this nomenclatural conundrum. One option is the adoption of previously proposed modifications to the ICNP to recognize DNA sequences as acceptable type material; the other option creates a nomenclatural code for uncultivated Archaea and Bacteria that could eventually be merged with the ICNP in the future. Regardless of the path taken, we believe that action is needed now within the scientific community to develop consistent rules for nomenclature of uncultivated taxa in order to provide clarity and stability, and to effectively communicate microbial diversity. In this Consensus Statement, the authors discuss the issue of naming uncultivated prokaryotic microorganisms, which currently do not have a formal nomenclature system due to a lack of type material or cultured representatives, and propose two recommendations including the recognition of DNA sequences as type material.
  •  
47.
  • Nilsson, Jonas A, et al. (författare)
  • Id2 is dispensable for myc-induced lymphomagenesis.
  • 2004
  • Ingår i: Cancer Res. - 0008-5472. ; 64:20, s. 7296-301
  • Tidskriftsartikel (refereegranskat)abstract
    • The Emu-Myc transgenic mouse appears to be an accurate model of human Burkitt's lymphoma that bears MYC/Immunoglobulin gene translocations. Id2, a negative regulator of basic helix-loop-helix transcription factors, has also been proposed as a Myc target gene that drives the proliferative response of Myc by binding to and overriding the checkpoint functions of the retinoblastoma tumor suppressor protein. Targeted deletion of Id2 in mice results in defects in B-cell development and prevents the development of peripheral lymphoid nodes. In precancerous B cells and lymphomas that arise in Emu-Myc transgenic mice and in Burkitt's lymphomas, Id2 is overexpressed, suggesting that it plays a regulatory role in lymphoma development. Surprisingly, despite these connections, Emu-Myc mice lacking Id2 succumb to lethal B-cell lymphoma at rates comparable with wild-type Emu-Myc transgenics. Furthermore, precancerous splenic B cells lacking Id2 do not exhibit any significant defects in Myc-induced target gene transactivation and proliferation. However, due to their lack of secondary lymph nodes, Emu-Myc mice lacking Id2 rather succumb to disseminated lymphoma with an associated leukemia, with pronounced infiltrates of the bone marrow and other major organs. Collectively these findings argue that targeting Id2 functions may be ineffective in preventing Myc-associated malignancies.
  •  
48.
  • Palmer, Victoria J., et al. (författare)
  • The Participatory Zeitgeist : An explanatory theoretical model of change in an era of coproduction and codesign in healthcare improvement
  • 2019
  • Ingår i: Medical Humanities. - : BMJ Publishing Group Ltd. - 1468-215X .- 1473-4265. ; 45:3, s. 247-257
  • Tidskriftsartikel (refereegranskat)abstract
    • Healthcare systems redesign and service improvement approaches are adopting participatory tools, techniques and mindsets. Participatory methods increasingly used in healthcare improvement coalesce around the concept of coproduction, and related practices of cocreation, codesign and coinnovation. These participatory methods have become the new Zeitgeist - the spirit of our times in quality improvement. The rationale for this new spirit of participation relates to voice and engagement (those with lived experience should be engaged in processes of development, redesign and improvements), empowerment (engagement in codesign and coproduction has positive individual and societal benefits) and advancement (quality of life and other health outcomes and experiences of services for everyone involved should improve as a result). This paper introduces Mental Health Experience Co-design (MH ECO), a peer designed and led adapted form of Experience-based Co-design (EBCD) developed in Australia. MH ECO is said to facilitate empowerment, foster trust, develop autonomy, self-determination and choice for people living with mental illnesses and their carers, including staff at mental health services. Little information exists about the underlying mechanisms of change; the entities, processes and structures that underpin MH ECO and similar EBCD studies. To address this, we identified eight possible mechanisms from an assessment of the activities and outcomes of MH ECO and a review of existing published evaluations. The eight mechanisms, recognition, dialogue, cooperation, accountability, mobilisation, enactment, creativity and attainment, are discussed within an 'explanatory theoretical model of change' that details these and ideal relational transitions that might be observed or not with MH ECO or other EBCD studies. We critically appraise the sociocultural and political movement in coproduction and draw on interdisciplinary theories from the humanities - narrative theory, dialogical ethics, cooperative and empowerment theory. The model advances theoretical thinking in coproduction beyond motivations and towards identifying underlying processes and entities that might impact on process and outcome. Trial registration number: The Australian and New Zealand Clinical Trials Registry, ACTRN12614000457640 (results). 
  •  
49.
  • Stephens, Philip, et al. (författare)
  • Capital and income breeding: the role of food supply.
  • 2014
  • Ingår i: Ecology. - : Wiley. - 0012-9658. ; 95:4, s. 882-896
  • Tidskriftsartikel (refereegranskat)abstract
    • An aspect of life history that has seen increasing attention in recent years is that of strategies for financing the costs of offspring production. These strategies are often described by a continuum ranging from capital breeding, in which costs are met purely from endogenous reserves, to income breeding, in which costs are met purely from concurrent intake. A variety of factors that might drive strategies towards a given point on the capital-income continuum has been reviewed, and assessed using analytical models. However, aspects of food supply, including seasonality and unpredictability, have often been cited as important drivers of capital and income breeding but are difficult to assess using analytical models. Consequently, we used dynamic programming to assess the role of the food supply in shaping offspring provisioning strategies. Our model is parameterized for a pinniped (one taxon remarkable for the range of offspring strategies that it illustrates). We show that increased food availability, increased seasonality and, to a lesser extent, increased unpredictability can all favor the emergence of capital breeding. In terms of the conversion of energy into offspring growth, the shorter periods of care associated with capital breeding are considerably more energetically efficient than income breeding, because shorter periods of care are associated with a higher ratio of energy put into offspring growth, to energy spent on parent and offspring maintenance metabolism. Moreover, no clear costs are currently associated with capital accumulation in pinnipeds. This contrasts with general assumptions about endotherms, which suggest that income breeding will usually be preferred. Our model emphasizes the role of seasonally high abundances of food in enabling mothers to pursue an energetically efficient capital breeding strategy. We discuss the importance of offspring development for dictating strategies for financing offspring production.
  •  
50.
  • Timmis, Kenneth, et al. (författare)
  • A concept for international societally relevant microbiology education and microbiology knowledge promulgation in society
  • 2024
  • Ingår i: Microbial Biotechnology. - 1751-7907. ; 17:5
  • Tidskriftsartikel (refereegranskat)abstract
    • EXECUTIVE SUMMARY: Microbes are all pervasive in their distribution and influence on the functioning and well-being of humans, life in general and the planet. Microbially-based technologies contribute hugely to the supply of important goods and services we depend upon, such as the provision of food, medicines and clean water. They also offer mechanisms and strategies to mitigate and solve a wide range of problems and crises facing humanity at all levels, including those encapsulated in the sustainable development goals (SDGs) formulated by the United Nations. For example, microbial technologies can contribute in multiple ways to decarbonisation and hence confronting global warming, provide sanitation and clean water to the billions of people lacking them, improve soil fertility and hence food production and develop vaccines and other medicines to reduce and in some cases eliminate deadly infections. They are the foundation of biotechnology, an increasingly important and growing business sector and source of employment, and the centre of the bioeconomy, Green Deal, etc. But, because microbes are largely invisible, they are not familiar to most people, so opportunities they offer to effectively prevent and solve problems are often missed by decision-makers, with the negative consequences this entrains. To correct this lack of vital knowledge, the International Microbiology Literacy Initiative-the IMiLI-is recruiting from the global microbiology community and making freely available, teaching resources for a curriculum in societally relevant microbiology that can be used at all levels of learning. Its goal is the development of a society that is literate in relevant microbiology and, as a consequence, able to take full advantage of the potential of microbes and minimise the consequences of their negative activities. In addition to teaching about microbes, almost every lesson discusses the influence they have on sustainability and the SDGs and their ability to solve pressing problems of societal inequalities. The curriculum thus teaches about sustainability, societal needs and global citizenship. The lessons also reveal the impacts microbes and their activities have on our daily lives at the personal, family, community, national and global levels and their relevance for decisions at all levels. And, because effective, evidence-based decisions require not only relevant information but also critical and systems thinking, the resources also teach about these key generic aspects of deliberation. The IMiLI teaching resources are learner-centric, not academic microbiology-centric and deal with the microbiology of everyday issues. These span topics as diverse as owning and caring for a companion animal, the vast range of everyday foods that are produced via microbial processes, impressive geological formations created by microbes, childhood illnesses and how they are managed and how to reduce waste and pollution. They also leverage the exceptional excitement of exploration and discovery that typifies much progress in microbiology to capture the interest, inspire and motivate educators and learners alike. The IMiLI is establishing Regional Centres to translate the teaching resources into regional languages and adapt them to regional cultures, and to promote their use and assist educators employing them. Two of these are now operational. The Regional Centres constitute the interface between resource creators and educators-learners. As such, they will collect and analyse feedback from the end-users and transmit this to the resource creators so that teaching materials can be improved and refined, and new resources added in response to demand: educators and learners will thereby be directly involved in evolution of the teaching resources. The interactions between educators-learners and resource creators mediated by the Regional Centres will establish dynamic and synergistic relationships-a global societally relevant microbiology education ecosystem-in which creators also become learners, teaching resources are optimised and all players/stakeholders are empowered and their motivation increased. The IMiLI concept thus embraces the principle of teaching societally relevant microbiology embedded in the wider context of societal, biosphere and planetary needs, inequalities, the range of crises that confront us and the need for improved decisioning, which should ultimately lead to better citizenship and a humanity that is more sustainable and resilient.ABSTRACT: The biosphere of planet Earth is a microbial world: a vast reactor of countless microbially driven chemical transformations and energy transfers that push and pull many planetary geochemical processes, including the cycling of the elements of life, mitigate or amplify climate change (e.g., Nature Reviews Microbiology, 2019, 17, 569) and impact the well-being and activities of all organisms, including humans. Microbes are both our ancestors and creators of the planetary chemistry that allowed us to evolve (e.g., Life's engines: How microbes made earth habitable, 2023). To understand how the biosphere functions, how humans can influence its development and live more sustainably with the other organisms sharing it, we need to understand the microbes. In a recent editorial (Environmental Microbiology, 2019, 21, 1513), we advocated for improved microbiology literacy in society. Our concept of microbiology literacy is not based on knowledge of the academic subject of microbiology, with its multitude of component topics, plus the growing number of additional topics from other disciplines that become vitally important elements of current microbiology. Rather it is focused on microbial activities that impact us-individuals/communities/nations/the human world-and the biosphere and that are key to reaching informed decisions on a multitude of issues that regularly confront us, ranging from personal issues to crises of global importance. In other words, it is knowledge and understanding essential for adulthood and the transition to it, knowledge and understanding that must be acquired early in life in school. The 2019 Editorial marked the launch of the International Microbiology Literacy Initiative, the IMiLI. HERE, WE PRESENT: our concept of how microbiology literacy may be achieved and the rationale underpinning it; the type of teaching resources being created to realise the concept and the framing of microbial activities treated in these resources in the context of sustainability, societal needs and responsibilities and decision-making; and the key role of Regional Centres that will translate the teaching resources into local languages, adapt them according to local cultural needs, interface with regional educators and develop and serve as hubs of microbiology literacy education networks. The topics featuring in teaching resources are learner-centric and have been selected for their inherent relevance, interest and ability to excite and engage. Importantly, the resources coherently integrate and emphasise the overarching issues of sustainability, stewardship and critical thinking and the pervasive interdependencies of processes. More broadly, the concept emphasises how the multifarious applications of microbial activities can be leveraged to promote human/animal, plant, environmental and planetary health, improve social equity, alleviate humanitarian deficits and causes of conflicts among peoples and increase understanding between peoples (Microbial Biotechnology, 2023, 16(6), 1091-1111). Importantly, although the primary target of the freely available (CC BY-NC 4.0) IMiLI teaching resources is schoolchildren and their educators, they and the teaching philosophy are intended for all ages, abilities and cultural spectra of learners worldwide: in university education, lifelong learning, curiosity-driven, web-based knowledge acquisition and public outreach. The IMiLI teaching resources aim to promote development of a global microbiology education ecosystem that democratises microbiology knowledge.
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