Estimation and Projection of Indicence and Prevalence Based on Doubly Truncated Data with Application to Pharmacoepidemiological Databases

Incidences of disease are of primary interest in any epidemiological analysis of disease spread in general populations. Ordinary estimates obtained from follow-up of an initially non-diseased cohort are costly, and so such estimates are not routinely available. In contrast, routine registers exist for many diseases with data on all detected cases within a given calendar time period, but lacking information on non-diseased. In the present work we show how this type of data supplemented with data on the past birth process can be analyzed to yield age specific incidence estimates as well as lifetime prevalence. A non-parametric model is studied with emphasis on the required assumptions, and a brief outlook on the analysis of the non-stationary case with calendar trends in age-specific incidence is given. The developed methods are applied to case cohort data on treatment with anti-diabetic medications and projections are provided for both diabetes incidence and prevalence. As projection of diabetes prevalence requires estimation of the distribution of disease durations, two novel approaches for this estimation is studied, a parametric and a non-parametric, respectively

Batch fluidized bed study of the interaction between alkali impurities and braunite oxygen carrier in chemical looping combustion

Chemical looping combustion (CLC) is a novel technology for heat and power generation with low-penalty CO2 capture. Using biomass in CLC (bio-CLC), negative CO2 emission can be attained. Alkali (mainly K and Na) in biomass can be problematic in bio-CLC, as it can interact with the oxygen carrier bed. The current work used charcoal and four charcoal samples impregnated with K2CO3, Na2CO3, KCl and NaCl, respectively, to study alkali interaction with a low-alkali braunite manganese ore oxygen carrier. The experiments were successfully carried out at 950\ub0C in a quartz batch fluidized-bed reactor. For each alkali-fuel sample, more than 30 cycles of redox were performed. Using the solid fuel impregnated with K2CO3, Na2CO3, KCl and NaCl, char gasification was improved by a factor of 10, 8, 4 and 3 as compared to the non-impregnated fuel. Partial-defluidization of the braunite particles was found with all the alkali-fuels, although the extent differed, e.g. K2CO3 and KCl resulted in earlier onset of partial defluidization than Na2CO3 and NaCl. Hard agglomeration was never observed, while soft partial agglomeration was seen. Accumulation of K, Si, and Ca in agglomerates and particle boundary was found after cycles with K2CO3- and KCl-charcoal, while Na, Si and Ca was found after the Na2CO3- and NaCl-charcoal cycles. The mechanism of agglomeration formation seems different for these alkali-charcoals. For K2CO3- and KCl-charcoal, it seems the potassium reacted with Fe and Mn in the braunite, forming low-melting point components and thus led to agglomeration. In the case of Na2CO3- and NaCl-charcoal, direct reaction with the braunite was not seen, and it seems as if other reactive species combined were formed, which acted as a binder between particles to form agglomerates. In addition, after cycles with the K2CO3- and Na2CO3- charcoals, 80% K and 40% Na were retained in the oxygen carrier particles. After the use with all the alkalis, the braunite reactivity with CH4, CO and H2 was similar to the fresh particles. It is clear that alkali species could react with the braunite oxygen carriers, and this could affect reactivity and fluidization tendency in the long run. Still, only soft agglomerates and partial defluidization were found, which may not be the case in a real CLC system operating at higher fluidizing velocities

Study of the interaction between a Mn ore and alkali chlorides in chemical looping combustion

Chemical looping combustion (CLC) is a novel technology for heat and power generation with inherent CO2 capture. Using biomass in CLC (bio-CLC), negative CO2 emissions can be attained. Biomass usually contains high content of alkalis (mainly K and Na) which can be problematic in the process, such as potential alkali-bed interaction, and this is the focus of current work. This work uses charcoal with and without the impregnation with alkali chlorides, KCl and NaCl. The results are compared to previous data from samples impregnated with K2CO3 and Na2CO3. A low-alkali braunite manganese ore is used as bed material to study the oxygen carrier interaction with the alkalis in cyclic experiments at 950 \ub0C in a quartz batch fluidized-bed reactor. As compared to charcoal without alkali impregnation, the impregnation with KCl, NaCl, K2CO3, and Na2CO3 can improve the rate of gasification by a factor of 4, 3, 10, 8, respectively. Partial-defluidization of the braunite particles was found with all the alkali-fuels, although the extent differed, e.g., K2CO3 and KCl resulted in earlier onset of defluidization than Na2CO3 and NaCl. Further, indications of partial defluidization were earlier and more permanent with the carbonates than the chlorides. Partial agglomeration with soft agglomerates of the bed was observed, while hard agglomerations were never seen. Accumulation of K, Na, Si, and Ca was found in the agglomerates after cycles with K2CO3-charcoal and Na2CO3-charcoal, while little K and Na was detected in the bridges between particles after the KCl and NaCl cycles. A significant fraction of the alkali added was found in the oxygen carrier, with 80% or more being retained for the Na salts, and around 40% for the K salts. There was no clear difference between chlorides and carbonates with respect to retention. The fresh and used braunite have very similar reactivity with CH4 and H2, whereas some decrease in reactivity is noticed with CO

Biogas upgrading through calcium looping: Experimental validation and study of CO2 capture

The calcium looping technology is one of the most promising technologies for capturing and storing CO2. This technology has been evaluated with a variety of sorbents and conditions in previous works, but the inlet CO2-ladden gas has typically been a flue gas from combustion, which typically has a composition of 10–20% CO2 and 80–90% N2. On the other side, the performance of the calcium looping process for CO2 capture of other gases (i.e., biogas or gases resulting from hydrothermal carbonization) remains largely unstudied. In this work, this knowledge gap is assessed through evaluating the performance of the calcium looping process for biogas (synthesized as 40% CO2, 60% CH4) in terms of carbonation conversion. This experimental study investigates the impact of: (1) using an inlet gas composition representative for biogas instead of combustion flue gas; (2) different biogas compositions; (3) the carbonation temperature; (4) the cooling-down and heating-up of the sorbent material between the reactor and ambient temperatures within cycles; (5) the atmosphere composition during calcination; and (6) the solids particle size. The main result obtained is that the overall CO2-capture performance of calcium looping improves when using biogas as inlet CO2-ladden gas, in comparison with combustion flue gas. One main contribution to this improved performance is shown to be the presence of secondary reactions (i.e., dry reforming, methanation). The impact of the CH4 to CO2 ratio tested is not remarkable, showing that the potentialities of the process in this aspect can be adapted to several biogas producing feedstocks

Oxygen Carrier and Alkali Interaction in Chemical Looping Combustion: Case Study Using a Braunite Mn Ore and Charcoal Impregnated with K2CO3or Na2CO3

Alkali is a problematic component in biomass and may create various operation issues in normal combustion as well as chemical looping combustion using biomass fuels (bio-CLC). To investigate the interaction of alkali with an oxygen carrier, a methodology has been developed where alkali salts are added with impregnated charcoal particles. This work studies the effect of K2CO3 and Na2CO3 on the fluidization/agglomeration behavior and reactivity as well as the interaction of a braunite manganese ore oxygen carrier with K and Na in a batch fluidized bed reactor. Charcoal impregnated with K2CO3 (K-charcoal) and charcoal impregnated with Na2CO3 (Na-charcoal) were used as solid fuels in the reduction step of the simulated CLC cycles. CH4 and syngas (50% CO + 50% H2) were periodically used to evaluate the reactivity of braunite before and after solid fuel experiments. In total, more than 50 cycles were performed for both K-charcoal series and Na-charcoal series tests, while some additional cycles with non-impregnated charcoal were conducted and considered as a reference. Partial agglomeration and partial defluidization were found after cycles with K-charcoal and Na-charcoal, and the use of K-charcoal tends to lead to the partial agglomeration/defluidization faster than the use of Na-charcoal. K, Na, Si, and Ca were found at a higher concentration on the surface of the agglomerated particles and can be assumed to be responsible for the partial agglomeration. The partial agglomeration with K-charcoal happened likely as a result of surface melting of the braunite particles, whereas the formation of the low-melting-point Na-Si-Ca system could be responsible for agglomeration in the Na-charcoal experiments. The concentration of K and Na in the braunite bed was found to increase during cycles with the alkali charcoals. In total, the added masses of K and Na were 0.8 and 1.2% of the bed, and around 40 and 80% of added K and Na were found, respectively, in the used oxygen carrier particles. Although partial agglomeration and accumulation were observed in the presence of these alkalis, the reactivity of used braunite was scarcely changed in comparison to the fresh sample

Determining breast cancer histological grade from RNA-sequencing data

BACKGROUND: The histologic grade (HG) of breast cancer is an established prognostic factor. The grade is usually reported on a scale ranging from 1 to 3, where grade 3 tumours are the most aggressive. However, grade 2 is associated with an intermediate risk of recurrence, and carries limited information for clinical decision-making. Patients classified as grade 2 are at risk of both under- and over-treatment. METHODS: RNA-sequencing analysis was conducted in a cohort of 275 women diagnosed with invasive breast cancer. Multivariate prediction models were developed to classify tumours into high and low transcriptomic grade (TG) based on gene- and isoform-level expression data from RNA-sequencing. HG2 tumours were reclassified according to the prediction model and a recurrence-free survival analysis was performed by the multivariate Cox proportional hazards regression model to assess to what extent the TG model could be used to stratify patients. The prediction model was validated in N=487 breast cancer cases from the The Cancer Genome Atlas (TCGA) data set. Differentially expressed genes and isoforms associated with HGs were analysed using linear models. RESULTS: The classification of grade 1 and grade 3 tumours based on RNA-sequencing data achieved high accuracy (area under the receiver operating characteristic curve = 0.97). The association between recurrence-free survival rate and HGs was confirmed in the study population (hazard ratio of grade 3 versus 1 was 2.62 with 95 % confidence interval = 1.04-6.61). The TG model enabled us to reclassify grade 2 tumours as high TG and low TG gene or isoform grade. The risk of recurrence in the high TG group of grade 2 tumours was higher than in low TG group (hazard ratio = 2.43, 95 % confidence interval = 1.13-5.20). We found 8200 genes and 13,809 isoforms that were differentially expressed between HG1 and HG3 breast cancer tumours. CONCLUSIONS: Gene- and isoform-level expression data from RNA-sequencing could be utilised to differentiate HG1 and HG3 tumours with high accuracy. We identified a large number of novel genes and isoforms associated with HG. Grade 2 tumours could be reclassified as high and low TG, which has the potential to reduce over- and under-treatment if implemented clinically.NonePublishe

Effect of the Mass Conversion Degree of an Oxygen Carrier on Char Conversion and Its Implication for Chemical Looping Gasification

Chemical looping gasification (CLG) is an emerging process that aims to produce valuable chemical feedstocks. The key operational requirement of CLG is to limit the oxygen transfer from the air reactor (AR) to the fuel reactor (FR). This can be accomplished by partially oxidizing the oxygen carrier in the AR, which may lead to a higher reduction degree of the oxygen carrier under the fuel conversion. A highly reduced oxygen carrier may experience multiple issues, such as agglomeration and defluidization. Given such an interest, this study examined how the variation of the mass conversion degree of ilmenite may affect the conversion of pine forest residue char in a fluidized bed batch reactor. Ilmenite was pre-reduced using diluted CO and then underwent the char conversion at 850, 900, 950, and 975 degrees C. Our investigations showed that the activation energy of the char conversion was between 194 and 256 kJ/mol, depending upon the mass conversion degree of ilmenite. Furthermore, the hydrogen partial pressure in the particle bed increased as the oxygen carrier mass conversion degree decreased, which was accompanied by a lower reaction rate and a higher reduction potential. Such a hydrogen inhibition effect was confirmed in the experiments; therefore, the change in the mass conversion degree indirectly affected the char conversion. Langmuir-Hinshelwood mechanism models used to evaluate the char conversion were validated. On the basis of the physical observation and characterizations, the use of ilmenite in CLG with biomass char as fuel will likely not suffer from major agglomeration or fluidization issues

Multi-parameter immune profiling of peripheral blood mononuclear cells by multiplexed single-cell mass cytometry in patients with early multiple sclerosis

Multiple sclerosis (MS) is an inflammatory demyelinating and neurodegenerative disease of the central nervous system (CNS). Studies in rodent models demonstrated an association of CNS-infiltrating monocyte-derived macrophages with disease severity. However, little is known about humans. Here, we performed an exploratory analysis of peripheral blood mononuclear cells (PBMCs) isolated from healthy controls and drug-naïve patients with early MS using multiplexed single-cell mass cytometry and algorithm-based data analysis. Two antibody panels comprising a total of 64 antibodies were designed to comprehensively analyse diverse immune cell populations, with particular emphasis on monocytes. PBMC composition and marker expression were overall similar between the groups. However, an increased abundance of CCR7+ and IL-6+ T cells was detected in early MS-PBMCs, whereas NFAT1hiT-bethiCD4+ T cells were decreased. Similarly, we detected changes in the subset composition of the CCR7+ and MIPβhi HLA-DR+ lymphocyte compartment. Only mild alterations were detected in monocytes/myeloid cells of patients with early MS, namely a decreased abundance of CD141hiIRF8hiCXCR3+CD68- dendritic cells. Unlike in Crohn's disease, no significant differences were found in the monocyte fraction of patients with early MS compared to healthy controls. This study provides a valuable resource for future studies designed to characterise and target diverse PBMC subsets in MS

Modelling of gas conversion with an analytical reactor model for biomass chemical looping combustion (bio-CLC) of solid fuels

Manganese ores are promising oxygen carriers for chemical looping combustion (CLC), due to their high reactivity with combustible gases. In this work, a manganese ore called EB (Elwaleed B, originating from Egypt) is studied for its reaction rate with CH4, CO and H2 and the data are used in an analytically solved reactor model. The reactivity of fresh and three used EB samples from previous operation in a 10 kWth pilot was examined in a batch fluidized bed reactor with CH4 and syngas (50%CO + 50%H2). In comparison with other manganese ores, the EB ore has a lower rate of reaction with CH4, while showing a significantly higher reactivity with syngas. Nevertheless, this manganese ore always presents a better conversion of CH4 and syngas than the benchmark ilmenite. Mass-based reaction rate constants were obtained using a pseudo first-order reaction mechanism: 1.1\ub710-4 m3/(kg\ub7s) for CH4, 6.6\ub710-3 m3/(kg\ub7s) for CO and 7.5\ub710-3 m3/(kg\ub7s) for H2. These rate constants were used in an analytical reactor model to further investigate results from previous operation in the 10 kWth unit. According to the analytical model, in the 10 kWth operation, 98% of the char in the biomass fuels was gasified before leaving the fuel reactor, while the char gasification products (CO and H2) have a 90% contact efficiency with the bed material. On the contrary, the volatiles have a much lower contact efficiency with the oxygen carrier bed, i.e. 20%, leading to low conversion of volatiles released. Thus, the results emphasize the importance of improving the contact between volatiles and bed material in order to promote combustion performance in the CLC process

Immune cell profiling reveals natural killer and T cell subpopulations to be associated with atopic dermatitis severity

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by a genetically determined impaired epidermal barrier function and predisposition to develop other atopic comorbidities.The role of adaptive and innate immunity, in particular IL- 4 and IL- 13 and T lymphocyte populations in AD pathogenesis are established, but the exact cellular mechanisms are not fully understood. At least partially, this is attributed to technical limitations of flow cytometry, that is, limited channels and signal spillover. Mass cytometry overcomes these limitations and allows advanced bioinformatic methods. An unbiased comprehensive analysis of the total peripheral immune cell pool in AD is not available