The private sector’s role in climate finance is increasingly subject to political and scientific debate. Yet there is poor empirical evidence of private engagement in adaptation and its potential ...contribution to the industrialised countries’ mobilisation of USD 100 billion of annual climate finance from 2020 onwards to support developing countries to address climate change. This paper analysed 101 case studies of private sector adaptation under the Private Sector Initiative (PSI) of the UNFCCC Nairobi work programme, and examined these against ten ‘adaptation finance criteria’ that were distilled from UN climate negotiation outcomes. Results show that private adaptation interventions complement public adaptation activities. Yet the ten adaptation finance criteria are not met, which demonstrates that the diplomatic UNFCCC conceptualisation of financing adaptation is dissonant from the private sector reality. For example, while the case studies’ investments are ‘new and additional’ to Official Development Assistance (ODA), their ‘predictability’ remains unclear. And despite some commitment for ‘up-scaling’, plans and associated costs for doing so remain undisclosed. Developed countries’ role in ‘mobilising’ private financial resources under the PSI seems limited. It is unrealistic to expect that the UNFCCC alters existing criteria to suit private initiatives, or that the private sector aligns its initiatives to meet existing criteria. This paper advocates monitoring and reporting only of those private investments that principally finance adaptation. This practical way forward would allow private finance to meet criteria such as predictability, transparency, and mobilisation, but would drastically reduce the amount of private investment that could contribute to reaching the USD 100 billion climate finance target.
The caliber of the retinal vessels has been shown to be associated with stroke events. However, the consistency and magnitude of association, and the changes in predicted risk independent of ...traditional risk factors, are unclear. To determine the association between retinal vessel caliber and the risk of stroke events, the investigators combined individual data from 20,798 people, who were free of stroke at baseline, in 6 cohort studies identified from a search of the Medline (National Library of Medicine, Bethesda, Maryland) and EMBASE (Elsevier B.V., Amsterdam, the Netherlands) databases. During follow-up of 5–12 years, 945 (4.5%) incident stroke events were recorded. Wider retinal venular caliber predicted stroke (pooled hazard ratio = 1.15, 95% confidence interval: 1.05, 1.25 per 20-μm increase in caliber), but the caliber of retinal arterioles was not associated with stroke (pooled hazard ratio = 1.00, 95% confidence interval: 0.92, 1.08). There was weak evidence of heterogeneity in the hazard ratio for retinal venular caliber, which may be attributable to differences in follow-up strategies across studies. Inclusion of retinal venular caliber in prediction models containing traditional stroke risk factors reassigned 10.1% of people at intermediate risk into different, mostly lower, risk categories.
The most recent updated classification of inborn errors of immunity/primary immunodeficiencies, compiled by the International Union of Immunological Societies Expert Committee, was published in ...January 2020. Within days of completing this report, it was already out of date, evidenced by the frequent publication of genetic variants proposed to cause novel inborn errors of immunity. As the next formal report from the IUIS Expert Committee will not be published until 2022, we felt it important to provide the community with a brief update of recent contributions to the field of inborn errors of immunity. Herein, we highlight studies that have identified 26 additional monogenic gene defects that reach the threshold to represent novel causes of immune defects.
Numerous pharmacogenetic clinical guidelines and recommendations have been published, but barriers have hindered the clinical implementation of pharmacogenetics. The Translational Pharmacogenetics ...Program (TPP) of the National Institutes of Health (NIH) Pharmacogenomics Research Network was established in 2011 to catalog and contribute to the development of pharmacogenetic implementations at eight US healthcare systems, with the goal to disseminate real‐world solutions for the barriers to clinical pharmacogenetic implementation. The TPP collected and normalized pharmacogenetic implementation metrics through June 2015, including gene–drug pairs implemented, interpretations of alleles and diplotypes, numbers of tests performed and actionable results, and workflow diagrams. TPP participant institutions developed diverse solutions to overcome many barriers, but the use of Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines provided some consistency among the institutions. The TPP also collected some pharmacogenetic implementation outcomes (scientific, educational, financial, and informatics), which may inform healthcare systems seeking to implement their own pharmacogenetic testing programs.
Daratumumab is an anti-CD38 monoclonal antibody with lytic activity against multiple myeloma (MM) cells, including ADCC (antibody-dependent cellular cytotoxicity) and CDC (complement-dependent ...cytotoxicity). Owing to a marked heterogeneity of response to daratumumab therapy in MM, we investigated determinants of the sensitivity of MM cells toward daratumumab-mediated ADCC and CDC. In bone marrow samples from 144 MM patients, we observed no difference in daratumumab-mediated lysis between newly diagnosed or relapsed/refractory patients. However, we discovered, next to an expected effect of effector (natural killer cells/monocytes) to target (MM cells) ratio on ADCC, a significant association between CD38 expression and daratumumab-mediated ADCC (127 patients), as well as CDC (56 patients). Similarly, experiments with isogenic MM cell lines expressing different levels of CD38 revealed that the level of CD38 expression is an important determinant of daratumumab-mediated ADCC and CDC. Importantly, all-trans retinoic acid (ATRA) increased CD38 expression levels but also reduced expression of the complement-inhibitory proteins CD55 and CD59 in both cell lines and primary MM samples. This resulted in a significant enhancement of the activity of daratumumab in vitro and in a humanized MM mouse model as well. Our results provide the preclinical rationale for further evaluation of daratumumab combined with ATRA in MM patients.
CYP2D6
and
CYP2C19
polymorphisms affect the exposure, efficacy and safety of tricyclic antidepressants (TCAs), with some drugs being affected by CYP2D6 only (e.g., nortriptyline and desipramine) and ...others by both polymorphic enzymes (e.g., amitriptyline, clomipramine, doxepin, imipramine, and trimipramine). Evidence is presented for
CYP2D6
and
CYP2C19
genotype-directed dosing of TCAs. This document is an update to the 2012 Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for
CYP2D6
and
CYP2C19
Genotypes and Dosing of Tricyclic Antidepressants.
The interfacial shear strength of carbon nanotube coated carbon fibers in epoxy was studied using the single-fiber composite fragmentation test. The carbon fibers were coated with carbon nanotubes ...(CNT) on the fiber surface using thermal chemical vapor deposition (CVD). The CVD process was adjusted to produce two CNT morphologies for the study: radially aligned and randomly oriented. The purpose of the CNT coating was to potentially produce a multifunctional structural composite. Results of the single-fiber fragmentation tests indicate an improvement in interfacial shear strength with the addition of a nanotube coating. This improvement can most likely be attributed to an increase in the interphase yield strength as well as an improvement in interfacial adhesion due to the presence of the nanotubes.
The Solar Wind Electrons Alphas and Protons experiment on the Parker Solar Probe (PSP) mission measures the three-dimensional electron velocity distribution function. We derive the parameters of the ...core, halo, and strahl populations utilizing a combination of fitting to model distributions and numerical integration for ∼100,000 electron distributions measured near the Sun on the first two PSP orbits, which reached heliocentric distances as small as ∼0.17 au. As expected, the electron core density and temperature increase with decreasing heliocentric distance, while the ratio of electron thermal pressure to magnetic pressure (βe) decreases. These quantities have radial scaling consistent with previous observations farther from the Sun, with superposed variations associated with different solar wind streams. The density in the strahl also increases; however, the density of the halo plateaus and even decreases at perihelion, leading to a large strahl/halo ratio near the Sun. As at greater heliocentric distances, the core has a sunward drift relative to the proton frame, which balances the current carried by the strahl, satisfying the zero-current condition necessary to maintain quasi-neutrality. Many characteristics of the electron distributions near perihelion have trends with solar wind flow speed, βe, and/or collisional age. Near the Sun, some trends not clearly seen at 1 au become apparent, including anticorrelations between wind speed and both electron temperature and heat flux. These trends help us understand the mechanisms that shape the solar wind electron distributions at an early stage of their evolution.
The global carbon budget 1959–2011 Le Quéré, C; Andres, R. J; Boden, T ...
Earth system science data,
05/2013, Letnik:
5, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Accurate assessments of anthropogenic carbon dioxide (CO sub(2)) emissions and their redistribution among the atmosphere, ocean, and terrestrial biosphere is important to better understand the global ...carbon cycle, support the climate policy process, and project future climate change. Present-day analysis requires the combination of a range of data, algorithms, statistics and model estimates and their interpretation by a broad scientific community. Here we describe datasets and a methodology developed by the global carbon cycle science community to quantify all major components of the global carbon budget, including their uncertainties. We discuss changes compared to previous estimates, consistency within and among components, and methodology and data limitations. CO sub(2) emissions from fossil fuel combustion and cement production (E sub(FF)) are based on energy statistics, while emissions from Land-Use Change (E sub(LUC)), including deforestation, are based on combined evidence from land cover change data, fire activity in regions undergoing deforestation, and models. The global atmospheric CO sub(2) concentration is measured directly and its rate of growth (G sub(ATM)) is computed from the concentration. The mean ocean CO sub(2) sink (S sub(OCEAN)) is based on observations from the 1990s, while the annual anomalies and trends are estimated with ocean models. Finally, the global residual terrestrial CO sub(2) sink (S sub(LAND)) is estimated by the difference of the other terms. For the last decade available (2002-2011), E sub(FF) was 8.3 plus or minus 0.4 PgC yr super(-1), E sub(LUC) 1.0 plus or minus 0.5 PgC yr super(-1), G sub(ATM) 4.3 plus or minus 0.1PgC yr super(-1), S sub(OCEAN) 2.5 plus or minus 0.5 PgC yr super(-1), and S sub(LAND) 2.6 plus or minus 0.8 PgC yr super(-1). For year 2011 alone, E sub(FF) was 9.5 plus or minus 0.5 PgC yr super(-1), 3.0 percent above 2010, reflecting a continued trend in these emissions; E sub(LUC) was 0.9 plus or minus 0.5 PgC yr super(-1), approximately constant throughout the decade; G sub(ATM) was 3.6 plus or minus 0.2 PgC yr super(-1), S sub(OCEAN) was 2.7 plus or minus 0.5 PgC yr super(-1), and S sub(LAND) was 4.1 plus or minus 0.9 PgC yr super(-1). G sub(ATM) was low in 2011 compared to the 2002-2011 average because of a high uptake by the land probably in response to natural climate variability associated to La Nina conditions in the Pacific Ocean. The global atmospheric CO sub(2) concentration reached 391.31 plus or minus 0.13 ppm at the end of year 2011. We estimate that E sub(FF) will have increased by 2.6% (1.9-3.5%) in 2012 based on projections of gross world product and recent changes in the carbon intensity of the economy. All uncertainties are reported as plus or minus 1 sigma (68% confidence assuming Gaussian error distributions that the real value lies within the given interval), reflecting the current capacity to characterise the annual estimates of each component of the global carbon budget. This paper is intended to provide a baseline to keep track of annual carbon budgets in the future. All data presented here can be downloaded from the Carbon Dioxide Information Analysis Center (doi:10.3334/CDIAC/GCP_V2013).
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