Exome Sequencing Identifies Susceptibility Loci for Sarcoidosis Prognosis

Many sarcoidosis-associating immunological genes have been shown to be shared between other immune-mediated diseases. In Finnish sarcoidosis patients, good prognosis subjects more commonly have HLA-DRB1*03:01 and/or HLA-DRB1*04:01-DPB1*04:01 haplotype, but no marker for persistent disease have been found. The objective was to further pinpoint genetic differences between prognosis subgroups in relation to the HLA markers. Whole-exome sequencing was conducted for 72 patients selected based on disease activity (resolved disease, n = 36; persistent disease, n = 36). Both groups were further divided by the HLA markers (one/both markers, n = 18; neither of the markers, n = 18). The Finnish exome data from the Genome Aggregation Database was used as a control population in the WES sample. Statistical analyses included single-variant analysis for common variants and gene level analysis for rare variants. We attempted to replicate associated variants in 181 Finnish sarcoidosis patients and 150 controls. An association was found in chromosome 1p36.21 (AADACL3 and C1orf158), which has recently been associated with sarcoidosis in another WES study. In our study, variations in these genes were associated with resolved disease (AADACL3, p = 0.0001 and p = 0.0003; C1orf158, p = 7.03E-05). Another interesting chromosomal region also peaked, Leucocyte Receptor Complex in 19q13.42, but the association diminished in the replication sample. In conclusion, this WES study supports the previously found association in the region 1p36.21. Furthermore, a novel to sarcoidosis region was found, but additional studies are warranted to verify this association.Peer reviewe

Which fractures are imaged with Ground Penetrating Radar? Results from an experiment in the Äspö Hardrock Laboratory, Sweden

Identifying fractures in the subsurface is crucial for many geomechanical and hydrogeological applications. Here, we assess the ability of the Ground Penetrating Radar (GPR) method to image open fractures with sub-mm apertures in the context of future deep disposal of radioactive waste. GPR experiments were conducted in a tunnel located 410 m below sea level within the Äspö Hard Rock Laboratory (Sweden) using 3-D surface-based acquisitions (3.4 m × 19 m) with 160 MHz, 450 MHz and 750 MHz antennas. The nature of 17 identified GPR reflections was analyzed by means of three new boreholes (BH1-BH3; 9–9.5 m deep). Out of 21 injection and outflow tests in packed-off 1-m sections, only five provided responses above the detection threshold with the maximum transmissivity reaching 7.0 × 10−10 m2/s. Most GPR reflections are situated in these permeable regions and their characteristics agree well with core and Optical Televiewer data. A 3-D statistical fracture model deduced from fracture traces on neighboring tunnel walls show that the GPR data mainly identify fractures with dips between 0 and 25°. Since the GPR data are mostly sensitive to open fractures, we deduce that the surface GPR method can identify 80% of open sub-horizontal fractures. We also find that the scaling of GPR fractures in the range of 1–10 m2 agrees well with the statistical model distribution indicating that fracture lengths are preserved by the GPR imaging (no measurement bias). Our results suggests that surface-GPR carries the resolution needed to identify the most permeable sub-horizontal fractures even in very low-permeability formations, thereby, suggesting that surface-GPR could play an important role in geotechnical workflows, for instance, for industrial-scale siting of waste canisters below tunnel floors in nuclear waste repositories

Inhaler Competence and Patient Satisfaction with Easyhaler: Results of Two Real-Life Multicentre Studies in Asthma and COPD.

OBJECTIVE: The aim of this study was to investigate patients' inhaler competence and satisfaction with the Easyhaler(R) dry powder inhaler. DESIGN: Two open, uncontrolled, non-randomised studies. SETTING: Real life based on patients attending 56 respiratory clinics in Hungary. PARTICIPANTS: Patients with asthma or chronic obstructive pulmonary disease (COPD) (n = 1016). INTERVENTION: In a 3-month study, adult patients (age range 18-88 years; n = 797) received twice-daily inhalations of formoterol via Easyhaler(R), and in a consequential study (from one visit to another, with 3-12 months in-between) children and adolescents (age range 4-17 years; n = 219) received salbutamol via Easyhaler(R) as needed. MAIN OUTCOME MEASURES: Control of six Easyhaler(R) handling steps and patients' satisfaction with Easyhaler(R) based on questionnaires. RESULTS: Correct performances (minimum and maximum of the six steps) were noticed after one demonstration in 92-98 % of the adults, 87-99 % of the elderly, 81-96 % of the children and 83-99 % of the adolescents. These figures had markedly increased at the last visit. Repeat instructions were necessary in 26 % of the cases. Investigators found Easyhaler(R) easy to teach in 87 % of the patients and difficult in only 0.5 %. Patients found Easyhaler(R) easy to learn and use, and the patients' (and parents') satisfaction with the inhaler was very high. Lung function values [forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), peak expiratory flow (PEF)] improved statistically significantly during the studies, indicating good inhaler competence and treatment adherence. CONCLUSION: Investigators found Easyhaler(R) easy to teach and patients found it easy to use, and their satisfaction with the device was high

Scaling of fractured rock flow. Proposition of indicators for selection of DFN based flow models

International audienceThe objective of the paper is to better understand and quantify the flow structure in fractured rocks from flow logs, and to propose relevant indicators for validating, calibrating or even rejecting hydrogeological models. We first studied what the inflow distribution tells us about the permeability structure from a series of analyses: distribution of transmissivities as a function of depth, proportion of flowing sections as a function of section scale, and scaling of the arithmetically-averaged and geometrically-averaged permeability. We then define three indicators that describe few fundamental characteristics of the flow/permeability, whatever the scale: a percolation scale , the way permeability increases with scale above , and the variability of permeability. A 4th indicator on the representative elemental volume could in principle be defined but the data show that this volume/scale is beyond the 300 m investigated. We tested a series of numerical models built in three steps: the geo-DFN based on the observed fracture network, the open-DFN which is the part of the geo-DFN where fractures are open, and a transmissivity model applying on each fracture of the open-DFN (Discrete Fracture Network). The analysis of the models showed that the percolation scale is controlled by the open-DFN structure and that the percolation scale can be predicted from a scale analysis of the percolation parameter (basically, the third moment of the fracture size distribution that provides a measure of the network connectivity). The way permeability increases with scale above the percolation threshold is controlled by the transmissivity model and in particular by the dependence of the fracture transmissivity on either the orientation of the fractures via a stress-controlled transmissivity or their size or both. The comparison with data on the first two indicators shows that a model that matches the characteristics of the geo-DFN with an open fraction of 15% as measured adequately fits the data provided that the large fractures remain open and that the fracture transmissivity model is well selected. Most of the other models show unacceptable differences with data but other models or model combinations has still to be explored before rejecting them. The third indicator on model variability is still problematic since the natural data show a higher variability than the models but the open fraction is also much more variable in the data than in the models

Data evaluation and numerical modeling of hydrological interactions between active layer, lake and talik in a permafrost catchment, Western Greenland

SummaryThis study investigates annual water balance conditions and their spatiotemporal variability under a wide variety of atmospheric driving conditions in the periglacial permafrost catchment of Two Boat Lake in Western Greenland. The study uses and combines a comprehensive hydrological multi-parameter dataset measured at the site with site conceptualization and numerical model development, application and testing. The model result reproduces measured lake and groundwater levels, as well as observations made by time-lapse cameras. The results highlights the importance of numerical modeling that takes into account and combines evapotranspiration with other surface and subsurface hydrological processes at various depths, in order to quantitatively understand and represent the dynamics and complexity of the interactions between meteorology, active layer hydrology, lakes, and unfrozen groundwater below permafrost in periglacial catchments. Regarding these interactions, the water flow between the studied lake and a through talik within and beneath it is found to be small compared to other water balance components. The modeling results show that recharge and discharge conditions in the talik can shift in time, while the lake and active layer conditions in the studied catchment are independent of catchment-external landscape features, such as the unfrozen groundwater system below the permafrost and the nearby continental-scale ice sheet

The Finnish experience to save asthma costs by improving care in 1987-2013

The Finnish National Asthma Program 1994-2004 markedly improved asthma care in the 1990s. We evaluated the changes in costs during 26 years from 1987 to 2013. Direct and indirect costs were calculated by using data from national registries. Costs from both the societal and patient perspectives were included. The costs were based on patients with persistent, physician-diagnosed asthma verified by lung function measurements. We constructed minimum and maximum scenarios to assess the effect of improved asthma care on total costs. The number of patients with persistent asthma in the national drug reimbursement register increased from 83,000 to 247,583. Improved asthma control reduced health care use and disability, resulting in major cost savings. Despite a 3-fold increase in patients, the total costs decreased by 14%, from (SIC)222 million to (SIC)191 million. Costs for medication and primary care visits increased, but overall annual costs per patient decreased by 72%, from (SIC)2656 to (SIC)749. The theoretical total cost savings for 2013, comparing actual with predicted costs, were between (SIC)120 and (SIC)475 million, depending on the scenario used. The Finnish Asthma Program resulted in significant cost savings at both the societal and patient levels during a 26-year period.Peer reviewe

Microtomography-based Inter-Granular Network for the simulation of radionuclide diffusion and sorption in a granitic rock

Field investigation studies, conducted in the context of safety analyses of deep geological repositories for nuclear waste, have pointed out that in fractured crystalline rocks sorbing radionuclides can diffuse surprisingly long distances deep into the intact rock matrix; i.e. much longer distances than those predicted by reactive transport models based on a homogeneous description of the properties of the rock matrix. Here, we focus on cesium diffusion and use detailed micro characterisation data, based on micro computed tomography, along with a grain-scale Inter-Granular Network model, to offer a plausible explanation for the anomalously long cesium penetration profiles observed in these in-situ experiments. The sparse distribution of chemically reactive grains (i.e. grains belonging to sorbing mineral phases) is shown to have a strong control on the diffusive patterns of sorbing radionuclides. The computed penetration profiles of cesium agree well with an analytical model based on two parallel diffusive pathways. This agreement, along with visual inspection of the spatial distribution of cesium concentration, indicates that for sorbing radionuclides the medium indeed behaves as a composite system, with most of the mass being retained close to the injection boundary and a non-negligible part diffusing faster along preferential diffusive pathways.Peer reviewe

北海道とフィンランドのサルコイドーシス : 比較研究の結果

Two comparative Finnish-Japanese sarcoidosis studies were carried out. One study compared the frequencies of sarcoidosis in 1984 in Hokkaido and Finland. We found a significantly and approximately four times higher prevalence and incidence of sarcoidosis in Finland than in Hok kaido ; prevalence 28.2/100,000 in Finland and 7.2/100,000 in Hokkaido ; incidence ll.4/100,000 in Fin land and 2.8/100,000 in Hokkaido, The other study compared the clinical picture and prognosis of sarcoidosis in two large hospital series ; 686 patients in Sapporo and 571 patients in Mjolbolsta, Fin land. The sex ratio was the same with a slight female predominance in both hospitals. The Japanese patients were younger at the time of diagnosis (mean age 30 years in Sapporo compared with 42 years in Mjolbolsta), although 50% of the patients in both series had been detected via rou tine health screening procedures. Among the symptomatic patients the mode of presentation of the disease varied considerably with eye symptoms as the dominating in Sapporo, but with respiratory symptoms and Lofgren\u27s syndrome in Finland. Stage I disease was more frequent in Sapporo, (57% of the patients compared with 48% in Finland) whereas more Finnish patients had parenchymal lesions. Extrapulmonary manifestations of sarcoidosis were more often diagnosed in Sapporo ; main ly because of the eye lesions. The prognosis of pulmonary sarcoidosis in Finland was significantly less favourable than the prognosis of the Japanese patients