19 research outputs found
Multiple Andreev Reflection and Giant Excess Noise in Diffusive Superconductor/Normal-Metal/Superconductor Junctions
We have studied superconductor/normal metal/superconductor (SNS) junctions
consisting of short Au or Cu wires between Nb or Al banks. The Nb based
junctions display inherent electron heating effects induced by the high thermal
resistance of the NS boundaries. The Al based junctions show in addition
subharmonic gap structures in the differential conductance dI/dV and a
pronounced peak in the excess noise at very low voltages V. We suggest that the
noise peak is caused by fluctuations of the supercurrent at the onset of
Josephson coupling between the superconducting banks. At intermediate
temperatures where the supercurrent is suppressed a noise contribution ~1/V
remains, which may be interpreted as shot noise originating from large multiple
charges.Comment: 7 pages, 7 figures, extended versio
Lowering water table reduces carbon sink strength and carbon stocks in northern peatlands
Peatlands at high latitudes have accumulated >400âPg carbon (C) because saturated soil and cold temperatures suppress C decomposition. This substantial amount of C in Arctic and Boreal peatlands is potentially subject to increased decomposition if the water table (WT) decreases due to climate change, including permafrost thaw-related drying. Here, we optimize a version of the Organizing Carbon and Hydrology In Dynamic Ecosystems model (ORCHIDEE-PCH4) using site-specific observations to investigate changes in CO2 and CH4 fluxes as well as C stock responses to an experimentally manipulated decrease of WT at six northern peatlands. The unmanipulated control peatlands, with the WT 2âkgâCâmâ2 over 100âyears when WT is lowered by 50âcm, while permafrost peatlands temporally switched from C sinks to sources. These results highlight that reductions in C storage capacity in response to drying of northern peatlands are offset in part by reduced CH4 emissions, thus slightly reducing the positive carbon climate feedbacks of peatlands under a warmer and drier future climate scenario
Tracking development assistance for health and for COVID-19 : a review of development assistance, government, out-of-pocket, and other private spending on health for 204 countries and territories, 1990-2050
Background The rapid spread of COVID-19 renewed the focus on how health systems across the globe are financed, especially during public health emergencies. Development assistance is an important source of health financing in many low-income countries, yet little is known about how much of this funding was disbursed for COVID-19. We aimed to put development assistance for health for COVID-19 in the context of broader trends in global health financing, and to estimate total health spending from 1995 to 2050 and development assistance for COVID-19 in 2020. Methods We estimated domestic health spending and development assistance for health to generate total health-sector spending estimates for 204 countries and territories. We leveraged data from the WHO Global Health Expenditure Database to produce estimates of domestic health spending. To generate estimates for development assistance for health, we relied on project-level disbursement data from the major international development agencies' online databases and annual financial statements and reports for information on income sources. To adjust our estimates for 2020 to include disbursements related to COVID-19, we extracted project data on commitments and disbursements from a broader set of databases (because not all of the data sources used to estimate the historical series extend to 2020), including the UN Office of Humanitarian Assistance Financial Tracking Service and the International Aid Transparency Initiative. We reported all the historic and future spending estimates in inflation-adjusted 2020 US per capita, purchasing-power parity-adjusted US8. 8 trillion (95% uncertainty interval [UI] 8.7-8.8) or 40.4 billion (0.5%, 95% UI 0.5-0.5) was development assistance for health provided to low-income and middle-income countries, which made up 24.6% (UI 24.0-25.1) of total spending in low-income countries. We estimate that 13.7 billion was targeted toward the COVID-19 health response. 1.4 billion was repurposed from existing health projects. 2.4 billion (17.9%) was for supply chain and logistics. Only 1519 (1448-1591) per person in 2050, although spending across countries is expected to remain varied. Interpretation Global health spending is expected to continue to grow, but remain unequally distributed between countries. We estimate that development organisations substantially increased the amount of development assistance for health provided in 2020. Continued efforts are needed to raise sufficient resources to mitigate the pandemic for the most vulnerable, and to help curtail the pandemic for all. Copyright (C) 2021 The Author(s). Published by Elsevier Ltd.Peer reviewe
LH pulsatile release patterns, follicular growth and function during repetitive periods of suckling and non-suckling in sows
This paper presents LH, estradiol, and cortisol in 12 sows that were separated from their piglets for 12 h a day, beginning around 2 w of lactation, until weaning (intermittent suckling, IS). To separate sows from their piglets, the sows either were moved to a different unit (total separation), or were only inhibited from suckling their piglets by a physical barrier (physical separation). Blood samples were frequently collected during 4.5 consecutive days. At the start of IS, four sows showed advanced follicle growth. In the eight remaining sows, total separation resulted in 4/4 sows ovulating, while physical separation resulted in 2/4 sows ovulating. Total and physical separation resulted in different LH secretion patterns. Total separation resulted in a lower amplitude of LH pulses than physical separation throughout the period of sampling (0.26 versus 0.53 ng/ml; P <0.01), and seemed to result in an escape from inhibition of LH secretion during suckling. Similarly, sows that ovulated had a lower amplitude of LH pulses (0.30 versus 0.54 ng/ml; P <0.05), and also showed a different effect of suckling on LH secretion than anovulatory sows. Total separation, in contrast to physical separation, consistently resulted in increased cortisol after separation (P <0.05). This contrast was not observed between ovulating and non-ovulating sows. We therefore conclude that IS results in an increased LH secretion. Inhibition of all contact between sows and piglets seems to result in a more sustained increase in LH secretion, which increases the chance of ovulation
Comparison of antipsychotic drug use among Dutch Youth before and after implementation of the Youth Act (2010â2019)
Objective: The Dutch law on youth care (the Youth Act) was implemented from 2015 onwards. One of the governmentâs aims by implementing this new policy was de-medicalization of youths by separating youth mental healthcare from the rest of the healthcare system. A previous study conducted by our research group showed that prevalence rates of antipsychotic drug prescriptions stabilized among Dutch youth in the period 2005â2015, just before the introduction of the Youth Act. In our study, we aimed to describe antipsychotic drug use among Dutch children aged 0â19Â years old before and after implementation of the Youth Act (2010â2019). Methods: We analyzed prescription data of 7405 youths aged 0â19Â years using antipsychotic drugs between 2010 and 2019, derived from a large Dutch community pharmacy-based prescription database (IADB.nl). Results: Prevalence rates of antipsychotic drug use per thousand youths decreased significantly in youths aged 7â12Â years old in 2019 compared to 2015 (7.9 vs 9.0 p < 0.05). By contrast, prevalence rates increased in adolescent females in 2019 compared to 2015 (11.8 vs 9.5 p < 0.05). Incidence rates increased significantly in adolescent youths in 2019 compared to 2015 (3.9 vs 3.0 p < 0.05), specifically among adolescent girls (4.2 per thousand in 2019 compared to 3.0 per thousand in 2015). Dosages in milligram declined for the most commonly prescribed antipsychotic drugs during the study period. The mean duration of antipsychotic drug use in the study period was 5.7 (95% CI 5.2â6.2) months. Conclusion: Despite the aim of the Youth Act to achieve de-medicalization of youths, no clear reduction was observed in prevalence rates of antipsychotic drugs or treatment duration in all subgroups. Prevalence rates even increased in adolescent females
Transferrin Saturation/Hepcidin Ratio Discriminates TMPRSS6-Related Iron Refractory Iron Deficiency Anemia from Patients with Multi-Causal Iron Deficiency Anemia
Pathogenic TMPRSS6 variants impairing matriptase-2 function result in inappropriately high hepcidin levels relative to body iron status, leading to iron refractory iron deficiency anemia (IRIDA). As diagnosing IRIDA can be challenging due to its genotypical and phenotypical heterogeneity, we assessed the transferrin saturation (TSAT)/hepcidin ratio to distinguish IRIDA from multi-causal iron deficiency anemia (IDA). We included 20 IRIDA patients from a registry for rare inherited iron disorders and then enrolled 39 controls with IDA due to other causes. Plasma hepcidin-25 levels were measured by standardized isotope dilution mass spectrometry. IDA controls had not received iron therapy in the last 3 months and C-reactive protein levels were <10.0 mg/L. IRIDA patients had significantly lower TSAT/hepcidin ratios compared to IDA controls, median 0.6%/nM (interquartile range, IQR, 0.4â1.1%/nM) and 16.7%/nM (IQR, 12.0â24.0%/nM), respectively. The area under the curve for the TSAT/hepcidin ratio was 1.000 with 100% sensitivity and specificity (95% confidence intervals 84â100% and 91â100%, respectively) at an optimal cut-off point of 5.6%/nM. The TSAT/hepcidin ratio shows excellent performance in discriminating IRIDA from TMPRSS6-unrelated IDA early in the diagnostic work-up of IDA provided that recent iron therapy and moderate-to-severe inflammation are absent. These observations warrant further exploration in a broader IDA population
Risperidone plasma concentrations are associated with side effects and effectiveness in children and adolescents with autism spectrum disorder
Aim: Risperidone is the most commonly prescribed antipsychotic drug to children and adolescents worldwide, but it is associated with serious side effects, including weight gain. This study assessed the relationship of risperidone and 9-hydroxyrisperidone trough concentrations, maximum concentrations and 24-hour area under the curves (AUCs) with body mass index (BMI) z-scores in children and adolescents with autism spectrum disorder (ASD) and behavioural problems. Secondary outcomes were metabolic, endocrine, extrapyramidal and cardiac side effects and effectiveness. Methods: Forty-two children and adolescents (32 males) aged 6-18 years were included in a 24-week prospective observational trial. Drug plasma concentrations, side effects and effectiveness were measured at several time points during follow-up. Relevant pharmacokinetic covariates, including medication adherence and CYP2D6, CYP3A4, CYP3A5 and P-glycoprotein (ABCB1) genotypes, were measured. Nonlinear mixed-effects modelling (NONMEMÂź) was used for a population pharmacokinetic analysis with 205 risperidone and 205 9-hydroxyrisperidone concentrations. Subsequently, model-based trough concentrations, maximum concentrations and 24-hour AUCs were analysed to predict outcomes using generalized and linear mixed-effects models. Results: A risperidone two-compartment model combined with a 9-hydroxyrisperidone one-compartment model best described the measured concentrations. Of all the pharmacokinetic parameters, higher risperidone sum trough concentrations best predicted higher BMI z-scores during follow-up (P <.001). Higher sum trough concentrations also predicted more sedation (P <.05), higher prolactin levels (P <.001) and more effectiveness measured with Aberrant Behavior Checklist irritability score (P <.01). Conclusion: Our results indicate a therapeutic window exists, which suggests that therapeutic drug monitoring of risperidone might increase safety and effectiveness in children and adolescents with ASD and behavioural problems