Energy Technology Roll-Out for Climate Change Mitigation: A Multi-Model Study for Latin America

AbstractIn this paper we investigate opportunities for energy technology deployment under climate change mitigation efforts in Latin America. Through several carbon tax and CO2 abatement scenarios until 2050 we analyze what resources and technologies, notably for electricity generation, could be cost-optimal in the energy sector to significantly reduce CO2 emissions in the region. By way of sensitivity test we perform a cross-model comparison study and inspect whether robust conclusions can be drawn across results from different models as well as different types of models (general versus partial equilibrium). Given the abundance of biomass resources in Latin America, they play a large role in energy supply in all scenarios we inspect. This is especially true for stringent climate policy scenarios, for instance because the use of biomass in power plants in combination with CCS can yield negative CO2 emissions. We find that hydropower, which today contributes about 800 TWh to overall power production in Latin America, could be significantly expanded to meet the climate policies we investigate, typically by about 50%, but potentially by as much as 75%. According to all models, electricity generation increases exponentially with a two- to three-fold expansion between 2010 and 2050. We find that in our climate policy scenarios renewable energy overall expands typically at double-digit growth rates annually, but there is substantial spread in model results for specific options such as wind and solar power: the climate policies that we simulate raise wind power in 2050 on average to half the production level that hydropower provides today, while they raise solar power to either a substantially higher or a much lower level than hydropower supplies at present, depending on which model is used. Also for CCS we observe large diversity in model outcomes, which reflects the uncertainties with regard to its future implementation potential as a result of the challenges this CO2 abatement technology experiences. The extent to which different mitigation options can be used in practice varies greatly between countries within Latin America, depending on factors such as resource potentials, economic performance, environmental impacts, and availability of technical expertise. We provide concise assessments of possible deployment opportunities for some low-carbon energy options, for the region at large and with occasional country-level detail in specific cases

Management of cerebral azole-resistant Aspergillus fumigatus infection : a role for intraventricular liposomal-amphotericin B

Objectives: In the pre-azole era, central nervous system (CNS) infections with Aspergillus had a dismal outcome. Survival improved with voriconazole but CNS infections caused by azole-resistant Aspergillus fumigatus preclude its use. Intravenous liposomal-amphotericin B (L-AmB) is the preferred treatment option for azole-resistant CNS infections but has suboptimal brain concentrations. Methods: We describe three patients with biopsy-proven CNS aspergillosis where intraventricular L-AmB was added to systemic therapy. Two patients with azole-resistant aspergillosis and one patient with azole-susceptible CNS aspergillosis were treated with intraventricular L-AmB at a dose of 1 mg weekly. Results: We describe three patients successfully treated with a combination of intravenous and intraventricular L-AmB. All three patients survived but one patient developed serious headaches, most likely not related to this treatment. Conclusions: Intraventricular L-AmB may have a role in the treatment of therapy-refractory CNS aspergillosis when added to systemic therapy. (C) 2020 The Author(s). Published by Elsevier Ltd on behalf of International Society for Antimicrobial Chemotherapy

Variant mapping using mass spectrometry–based proteotyping as a diagnostic tool in von Willebrand disease

Background: von Willebrand disease (VWD) is the most common inherited bleeding disorder, characterized by either partial or complete von Willebrand factor (VWF) deficiency or by the occurrence of VWF proteoforms of altered functionality. The gene encoding VWF is highly polymorphic, giving rise to a variety of proteoforms with varying plasma concentrations and clinical significance. Objectives: To address this complexity, we translated genomic variation in VWF to corresponding VWF proteoforms circulating in blood. Methods: VWF was characterized in VWD patients (n = 64) participating in the Willebrand in the Netherlands study by conventional laboratory testing, DNA sequencing and complementary discovery, and targeted mass spectrometry–based plasma proteomic strategies. Results: Unbiased plasma profiling combined with immune enrichment of VWF verified VWF and its binding partner factor VIII as key determinants of VWD and revealed a remarkable heterogeneity in VWF amino acid sequence coverage among patients. Subsequent VWF proteotyping enabled identification of both polymorphisms (eg, p.Thr789Ala, p.Gln852Arg, and p.Thr1381Ala), as well as pathogenic variants (n = 16) along with their corresponding canonical sequences. Targeted proteomics using stable isotope–labeled peptides confirmed unbiased proteotyping for 5 selected variants and suggested differential proteoform quantities in plasma. The variant-to-wild-type peptide ratio was determined in 6 type 2B patients heterozygous for p.Arg1306Trp, confirming the relatively low proteoform concentration of the pathogenic variant. The elevated VWF propeptide/VWF ratio indicated increased clearance of specific VWF proteoforms. Conclusion: This study highlights how VWF proteotyping from plasma could be the first step to bridge the gap between genotyping and functional testing in VWD.</p

Population Pharmacokinetics and Pharmacodynamics of Ciprofloxacin Prophylaxis in Pediatric Acute Lymphoblastic Leukemia Patients

Background: Ciprofloxacin is used as antimicrobial prophylaxis in pediatric acute lymphoblastic leukemia (ALL) to decrease infections with gram-negative bacteria. However, there are no clear guidelines concerning prophylactic dose. Aims: To determine the pharmacokinetics and pharmacodynamics (PKPD) of ciprofloxacin prophylaxis in a pediatric ALL population. The effect of patient characteristics and antileukemic treatment on ciprofloxacin exposure, the area under the concentration time curve over minimal inhibitory concentration (AUC24/MIC) ratios, and emergence of resistance were studied. Methods: A total of 615 samples from 129 children (0-18 years) with ALL were collected in a multicenter prospective study. A population pharmacokinetic model was developed. Microbiological cultures were collected prior to and during prophylaxis. An AUC24/MIC of ≥125 was defined as target ratio. Results: A 1-compartment model with zero-order absorption and allometric scaling best described the data. No significant (P <. 01) covariates remained after backward elimination and no effect of asparaginase or azoles were found. Ciprofloxacin AUC24 was 16.9 mg∗h/L in the prednisone prophase versus 29.3 mg∗h/L with concomitant chemotherapy. Overall, 100%, 81%, and 18% of patients at, respectively, MIC of 0.063, 0.125, and 0.25 mg/L achieved AUC24/MIC ≥ 125. In 13% of the patients, resistant bacteria were found during prophylactic treatment. Conclusion: Ciprofloxacin exposure shows an almost 2-fold change throughout the treatment of pediatric ALL. Depending on the appropriateness of 125 as target ratio, therapeutic drug monitoring or dose adjustments might be indicated for less susceptible bacteria starting from ≥ 0.125 mg/L to prevent the emergence of resistance and reach required targets for efficacy

Feasibility and reliability of PRISMA-Medical for specialty-based incident analysis

Aims and objectives: In this study, the feasibility and reliability of the Prevention Recovery Information System for Monitoring and Analysis (PRISMA)-Medical method for systematic, specialty-based analysis and classification of incidents in the neonatal intensive care unit (NICU) were determined. Methods: After the introduction of a Neonatology System for Analysis and Feedback on Medical Events (NEOSAFE) in eight tertiary care NICUs and one paediatric surgical ICU, PRISMA-Medical was started to be used to identify root causes of voluntary reported incidents by multidisciplinary unit patient safety committees. Committee members were PRISMA-trained and familiar with the department and its processes. In this study, the results of PRISMA-analysis of incidents reported during the first year are described. At t¿=¿3 months and t¿=¿12 months after introduction, test cases were performed to measure agreement at three levels of root cause classification using PRISMA-Medical. Inter-rater reliability was determined by calculating generalised ¿ values for each level of classification. Results: During the study period, 981 out of 1786 eligible incidents (55%) were analysed for underlying root causes. In total, 2313 root causes were identified and classified, giving an average of 2.4 root causes for every incident. Although substantial agreement (¿ 0.70–0.81) was reached at the main level of root cause classification of the test cases (discrimination between technical, organisational and human failure) and agreement among the committees at the second level (discrimination between skill-based, rule-based and knowledge-based errors) was acceptable (¿ 0.53–0.59), discrimination between rule-based errors (the third level of classification) was more difficult to assess (¿ 0.40–0.47). Conclusion: With some restraints, PRISMA-Medical proves to be both feasible and acceptably reliable to identify and classify multiple causes of medical events in the NICU

Evaluation of the pharmacokinetics of prednisolone in paediatric patients with acute lymphoblastic leukaemia treated according to Dutch Childhood Oncology Group protocols and its relation to treatment response

Glucocorticoids form the backbone of paediatric acute lymphoblastic leukaemia (ALL) treatment. Many studies have been performed on steroid resistance; however, few studies have addressed the relationship between dose, concentration and clinical response. The aim of the present study was to evaluate the pharmacokinetics of prednisolone in the treatment of paediatric ALL and the correlation with clinical parameters. A total of 1028 bound and unbound prednisolone plasma concentrations were available from 124 children (aged 0–18 years) with newly diagnosed ALL enrolled in the Dutch Childhood Oncology Group studies. A population pharmacokinetic model was developed and post hoc area under the curve (AUC) was tested against treatment outcome parameters. The pharmacokinetics of unbound prednisolone in plasma was best described with allometric scaling and saturable binding to proteins. Plasma protein binding decreased with age. The AUC of unbound prednisolone was not associated with any of the disease parameters or treatment outcomes. Unbound prednisolone plasma concentrations correlated with age. No effect of exposure on clinical treatment outcome parameters was observed and does not substantiate individualised dosing. Poor responders, high-risk and relapsed patients showed a trend towards lower exposure compared to good responders. However, the group of poor responders was small and requires further research.</p

Specialty-based, voluntary incident reporting in neonatal intensive care: description of 4846 incident reports

OBJECTIVES: To examine the characteristics of incidents reported after introduction of a voluntary, non-punitive incident reporting system for neonatal intensive care units (NICUs) in the Netherlands; and to investigate which types of reported incident pose the highest risk to patients in the NICU. DESIGN: Prospective multicentre survey. METHODS: Voluntary, non-punitive incident reporting was introduced in eight level III NICUs and one paediatric surgical ICU. An incident was defined as any unintended event which (could have) reduced the safety margin for the patient. Multidisciplinary, unit-based patient safety committees systematically collected and analysed incident reports, and assigned risk scores to each reported incident. Data were centrally collected for specialty-based analysis. This paper describes the characteristics of incidents reported during the first year. Bivariate logistic regression analysis was conducted to identify high-risk incident categories. RESULTS: There were 5225 incident reports on 3859 admissions, of which 4846 were eligible for analysis. Incidents with medication were most frequently reported (27%), followed by laboratory (10%) and enteral nutrition (8%). Severe harm was described in seven incident reports, and moderate harm in 63 incident reports. Incidents involving mechanical ventilation and blood products were most likely to be assigned high-risk scores, followed by those involving parenteral nutrition, intravascular lines and medication dosing errors. CONCLUSIONS: Incidents occur much more frequently in Dutch NICUs than has been previously observed, and their impact on patient morbidity is considerable. Reported incidents concerning mechanical ventilation, blood products, intravascular lines, parenteral nutrition and medication dosing errors pose the highest risk to patients in the NIC