Expanded access to cancer treatments from conversion to neutropenia prophylaxis with biosimilar filgrastim-sndz

Aim: Biosimilar medicines offer significant cost-savings potential over their reference products, which can be re-allocated to provide access to other cancer treatments on a budget-neutral basis. Methods: Simulation study using cost data for the USA under consideration of several prophylaxis patterns. Results: Potential savings from conversion from reference filgrastim to biosimilar filgrastim-sndz are significant. These savings expand budget-neutral access to novel immunotherapies (obinutuzumab; pembrolizumab) or supportive care (filgrastim-sndz). Conclusion: The combination of biosimilar savings and expanded access increases the value of cancer care as the same supportive care is provided at lower cost, additional cancer care is enabled at no additional cost, and more patients will have access to cancer care.Sandoz Inc., Princeton, NJ, USAOpen access article.This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Reviews and syntheses: the GESAMP atmospheric iron deposition model intercomparison study

This work reports on the current status of the global modeling of iron (Fe) deposition fluxes and atmospheric concentrations and the analyses of the differences between models, as well as between models and observations. A total of four global 3-D chemistry transport (CTMs) and general circulation (GCMs) models participated in this intercomparison, in the framework of the United Nations Joint Group of Experts on the Scientific Aspects of Marine Environmental Protection (GESAMP) Working Group 38, The Atmospheric Input of Chemicals to the Ocean. The global total Fe (TFe) emission strength in the models is equal to  ∼ 72Tg Fe yr−1 (38–134Tg Fe yr−1) from mineral dust sources and around 2.1Tg Fe yr−1 (1.8–2.7Tg Fe yr−1) from combustion processes (the sum of anthropogenic combustion/biomass burning and wildfires). The mean global labile Fe (LFe) source strength in the models, considering both the primary emissions and the atmospheric processing, is calculated to be 0.7 (±0.3)Tg Fe yr−1, accounting for both mineral dust and combustion aerosols. The mean global deposition fluxes into the global ocean are estimated to be in the range of 10–30 and 0.2–0.4Tg Fe yr−1 for TFe and LFe, respectively, which roughly corresponds to a respective 15 and 0.3Tg Fe yr−1 for the multi-model ensemble model mean. The model intercomparison analysis indicates that the representation of the atmospheric Fe cycle varies among models, in terms of both the magnitude of natural and combustion Fe emissions as well as the complexity of atmospheric processing parameterizations of Fe-containing aerosols. The model comparison with aerosol Fe observations over oceanic regions indicates that most models overestimate surface level TFe mass concentrations near dust source regions and tend to underestimate the low concentrations observed in remote ocean regions. All models are able to simulate the tendency of higher Fe concentrations near and downwind from the dust source regions, with the mean normalized bias for the Northern Hemisphere ( ∼ 14), larger than that of the Southern Hemisphere ( ∼ 2.4) for the ensemble model mean. This model intercomparison and model–observation comparison study reveals two critical issues in LFe simulations that require further exploration: (1) the Fe-containing aerosol size distribution and (2) the relative contribution of dust and combustion sources of Fe to labile Fe in atmospheric aerosols over the remote oceanic regions

Pyrogenic iron: The missing link to high iron solubility in aerosols

Atmospheric deposition is a source of potentially bioavailable iron (Fe) and thus can partially control biological productivity in large parts of the ocean. However, the explanation of observed high aerosol Fe solubility compared to that in soil particles is still controversial, as several hypotheses have been proposed to explain this observation. Here, a statistical analysis of aerosol Fe solubility estimated from four models and observations compiled from multiple field campaigns suggests that pyrogenic aerosols are the main sources of aerosols with high Fe solubility at low concentration. Additionally, we find that field data over the Southern Ocean display a much wider range in aerosol Fe solubility compared to the models, which indicate an underestimation of labile Fe concentrations by a factor of 15. These findings suggest that pyrogenic Fe-containing aerosols are important sources of atmospheric bioavailable Fe to the open ocean and crucial for predicting anthropogenic perturbations to marine productivity

Assessing the application of miscible CO2 flooding in oil reservoirs: a case study from Pakistan

Miscible carbon dioxide (CO2) flooding has been recognized as a promising approach to enhance the recovery of oil reservoirs. However, depending on the injection strategy and rock/fluid characteristics, efficiency of the miscible CO2flooding varies from reservoir to reservoir. Although, many studies have been carried out to evaluate the performance of the miscible CO2flooding, a specific strategy which can be strictly followed for a hydrocarbon reservoir has not been established yet. The aim of this study is to assess one of Pakistan’s oil reservoirs for miscible CO2flooding by applying a modified screening criterion and numerical modeling. As such, the most recent miscible CO2screening criteria were modified, and a numerical modeling was applied on the prospective reservoir. Based on the results obtained, South oil reservoir (S3) is chosen for a detailed assessment of miscible CO2flooding. It was also found that implementation of CO2water-alternating gas (CO2-WAG) injection at early stages of production can increase the production life of the reservoir

Novel quantitative trait locus is mapped to chromosome 12p11 for left ventricular mass in Dominican families: the Family Study of Stroke Risk and Carotid Atherosclerosis

<p>Abstract</p> <p>Background</p> <p>Left ventricular mass (LVM) is an important risk factor for stroke and vascular disease. The genetic basis of LVM is unclear although a high heritability has been suggested. We sought to map quantitative trait loci (QTL) for LVM using large Dominican families.</p> <p>Methods</p> <p>Probands were selected from Dominican subjects of the population-based Northern Manhattan Study (NOMAS). LVM was measured by transthoracic echocardiography. A set of 405 microsatellite markers was used to screen the whole genome among 1360 subjects from 100 Dominican families who had complete phenotype data and DNA available. A polygenic covariate screening was run to identify the significant covariates. Variance components analysis was used to estimate heritability and to detect evidence for linkage, after adjusting for significant risk factors. Ordered-subset Analysis (OSA) was conducted to identify a more homogeneous subset for stratification analysis.</p> <p>Results</p> <p>LVM had a heritability of 0.58 in the studied population (p < 0.0001). The most significant evidence for linkage was found at chromosome 12p11 (MLOD = 3.11, empirical p = 0.0003) with peak marker at D12S1042. This linkage was significantly increased in a subset of families with the high average waist circumference (MLOD = 4.45, p = 0.0045 for increase in evidence for linkage).</p> <p>Conclusion</p> <p>We mapped a novel QTL near D12S1042 for LVM in Dominicans. Enhanced linkage evidence in families with larger waist circumference suggests that gene(s) residing within the QTL interact(s) with abdominal obesity to contribute to phenotypic variation of LVM. Suggestive evidence for linkage (LOD = 1.99) has been reported at the same peak marker for left ventricular geometry in a White population from the HyperGEN study, underscoring the importance of this QTL for left ventricular phenotype. Further fine mapping and validation studies are warranted to identify the underpinning genes.</p

Current cardiac imaging techniques for detection of left ventricular mass

Estimation of left ventricular (LV) mass has both prognostic and therapeutic value independent of traditional risk factors. Unfortunately, LV mass evaluation has been underestimated in clinical practice. Assessment of LV mass can be performed by a number of imaging modalities. Despite inherent limitations, conventional echocardiography has fundamentally been established as most widely used diagnostic tool. 3-dimensional echocardiography (3DE) is now feasible, fast and accurate for LV mass evaluation. 3DE is also superior to conventional echocardiography in terms of LV mass assessment, especially in patients with abnormal LV geometry. Cardiovascular magnetic resonance (CMR) and cardiovascular computed tomography (CCT) are currently performed for LV mass assessment and also do not depend on cardiac geometry and display 3-dimensional data, as well. Therefore, CMR is being increasingly employed and is at the present standard of reference in the clinical setting. Although each method demonstrates advantages over another, there are also disadvantages to receive attention. Diagnostic accuracy of methods will also be increased with the introduction of more advanced systems. It is also likely that in the coming years new and more accurate diagnostic tests will become available. In particular, CMR and CCT have been intersecting hot topic between cardiology and radiology clinics. Thus, good communication and collaboration between two specialties is required for selection of an appropriate test

Seasonal and longitudinal distributions of atmospheric water-soluble dicarboxylic acids, oxocarboxylic acids, and α-dicarbonyls over the North Pacific

In order to assess the seasonal variability of atmospheric abundances of dicarboxylic acids, oxocarboxylic acids, and -dicarbonyls over the North Pacific and Sea of Japan, aerosol samples were collected along the longitudinal transacts during six cruises between Canada and Japan. The back trajectory analyses indicate that aerosol samples collected in winter and spring are influenced by the East Asian outflow, whereas summer and fall samples are associated with the pristine maritime air masses. Molecular distributions of water-soluble organics in winter and spring samples show the predominance of oxalic acid (C-2) followed by succinic (C-4) and malonic acids (C-3). In contrast, summer and fall marine aerosols are characterized by the predominance of C-3 over C-4. Concentrations of dicarboxylic acids were higher over the Sea of Japan than the North Pacific. With a lack of continental outflow, higher concentrations during early summer are ascribed to atmospheric oxidation of organic precursors associated with high biological activity in the North Pacific. This interpretation is further supported by the high abundances of azelaic acid, which is a photochemical oxidation product of biogenic unsaturated fatty acids, over the Bering Sea in early summer when surface waters are characterized by high biological productivity. We found higher ratios of oxalic acid to pyruvic and glyoxylic acids (C-2/Pyr and C-2/C-2) and glyoxal and methylglyoxal (C-2/Gly and C-2/MeGly) in summer and fall than in winter and spring, suggesting a production of C-2 from the aqueous-phase oxidation of oceanic isoprene. In this study, dicarboxylic acids account for 0.7-38% of water-soluble organic carbon

Atmospheric outflow of nutrients to the Bay of Bengal: Impact of anthropogenic sources

The air–sea deposition of nutrients (N, P and Fe) to the oceanic regions located downwind of pollution sources in south and south-east Asia is gaining considerable attention in the present-day scenario of climate change. We report here a case study on the atmospheric outflow of nutrients from the Indo-Gangetic Plain (IGP) to the Bay of Bengal (BoB). Air mass back trajectories suggest conspicuous downwind transport of chemical constituents from the IGP to the BoB during the late NE-monsoon (January–April); thus, representing BoB as one of the unique oceanic regions influenced by anthropogenic sources over a short span of 3–4 months. During the course of this study (November '09–March '10), nutrient (NO₃⁻, NH₄⁺, N_Org, PO₄³⁻ and Fe_ws) concentrations in the atmospheric outflow show pronounced temporal variability. The inorganic nitrogen (NH₄⁺-N: &#8764;90% of N_Inorg) dominates the total soluble nitrogen (N_Tot). Although the contribution of organic nitrogen is not significant, the mass ratio of N_Org/N_Tot in the outflow varied from 0.07 to 0.40. The abundances of P_Inorg and Fe_ws varied from 0.4 to 4.8 nmol m⁻³ and 0.2 to 0.6 nmol m⁻³, respectively. The high abundance of K⁺ and significant (P-value &#60; 0.05) correlation with P_Inorg and Fe_ws suggest their significant contribution from biomass burning emissions (BBEs). The characteristic mass ratios of nutrients (N_Inorg/N_Tot: 0.92 &#177; 0.13, N_Org/N_Tot: 0.21 &#177; 0.11 and P_Inorg/nss-Ca²⁺: 0.35 &#177; 0.23) in the IGP-outflow show striking similarity with those reported over the BoB. These results have implications to further increase in the atmospheric deposition of nutrients and their impact on biogeochemistry of surface Bay of Bengal