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During endovascular aneurysm repair, commercial iliac branch devices (IBDs) have become an inescapable alternative for preserving antegrade internal iliac artery (IIA) blood flow. Due to the different morphological features of aneurysms, commercial IBDs may not be suitable for all patients. Reported experience with the implantation of the new surgeon-modified IBD (sm IBD) is limited. This investigation describes the indications, efficacy, and safety of the sm IBD.Data from consecutive elective implantations of IBDs in patients between March 2011 and May 2021 in a single center were incorporated. The sm IBDs were indicated in patients with common iliac artery aneurysms (CIAAs) and with a challenging anatomy and in those patients with or without abdominal aortic aneurysm (AAA).Fifteen patients (15 male, mean age 67.6±7.9 years) were included. Fifteen sm IBDs were implanted in one procedure (100%). Fourteen (93.3%) patients had simultaneous endovascular aneurysm repair (EVAR), and 1 (6.7%) patient previously had a bilateral CIAAs repair by EVAR. The mean CIA diameter was 36.6 ± 12.5 mm. Technical success was obtained in all patients (100%). The median operation time was 189.7 ± 78.6 min, with a median fluoroscopy time of 45.3 ± 15.9 min. Axillary artery access was used in 11 (73.3%) procedures. The mean total hospital stay was 5.6 ± 2.8 days, and the postoperative follow-up was 35.4 months (range 2-120). The estimated IIA bridge stent patency at 1 year after operation was 100%, and was 85.7%±13.2% at 5 years postoperatively. One (6.7%) IIA branch was occluded, and this patient remained asymptomatic. One patient (6.7%) needed reintervention, and another (6.7%) patient had type II leakage, which is currently under close surveillance.Using an IBD to maintain the pelvic blood flow is an effective and feasible intravas-cular technique, especially for patients with an abnormal iliac artery anatomy. This novel technique has similar midterm procedural success rate compared to the use of commercial IBDs. Therefore, these devices are more suitable for patients with certain anatomic challenges and can be used as an alternative treatment.

This article has been accepted for publication in IEEE/OSA Journal of Lightwave Technology. Citation information: DOI 10.1109/JLT.2022.3198649 Benefiting from the development of image sensors and the popularity of light-emitting diode (LED) lighting technology, visible light positioning (VLP) technology based on image sensors has ushered in vigorous development and broad prospects, which can provide low-cost and high-accuracy position service. However, the existing approaches require dense LEDs or sensors such as gyroscopes to assist positioning, which limits the area and lower the accuracy of positioning because of the errors from imperfect sensors. In this paper, we propose a simultaneous localization and calibration VLP method based on double coplanar circular LED lights aiming to get rid of the dependence on additional sensors and dense LED transmitters. By the pinhole camera model and the perspective projection of circle, our proposed method extends the available position area and relaxes the required quantity of LED to two. The experiment result showed that our system has a mean 3D positioning accuracy of 7.91cm, a mean angle error of less than 1.6°, and an average latency of 182ms on mobile devices.

BACKGROUND: The treatment strategy for patients with multiple infrapopliteal artery occlusions remains controversial. In this study, we investigated how anatomic factors affect the treatment effect of infrapopliteal artery intervention and identified suitable intervention strategies for patients with multiple infrapopliteal artery occlusions. METHODS: This was a prospective, single-center, observational cohort study. For each patient, the intrainterventional blood volume improvement of the dorsum and plantar surface was measured and classified into the direct perfused region (DR) or indirect perfused region (IR) on the basis of whether the supplying artery was revascularized. Digital subtraction angiography was performed to analyze how pedal arch patency affects blood communication between DR and IR. RESULTS: A total of 38 patients treated with infrapopliteal intervention at the Department of Vascular Surgery of Peking Union Medical College Hospital from November 2016 to November 2020 were considered for inclusion in this study. Finally, 26 patients were included in the analysis. In patients with type III pedal arch, blood volume improvements for DR and IR were 70.50 (17.50, 191.75) and 11.25 (−10.25, 50.25) mL/1,000 mL, respectively (P=0.018). No significant difference was found between DR and IR in patients with type I pedal arch (P=0.208) and type II pedal arch (P=0.110). CONCLUSIONS: Impaired pedal arch has an adverse impact on foot collateral circulation. Patients with these conditions are more suitable for direct revascularization than other patients. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03248323.

The NOAA-20 Ozone Mapping and Profiler Suite (OMPS) is the second OMPS flight unit in the US Joint Polar Satellite System (JPSS) program [1]. Flying on the NOAA-20 satellite, the OMPS extends the 40+-year total column ozone and ozone profile records to monitor ozone concentration in the Earth atmosphere. Recent studies have been conducted over a wide range of radiometric calibration and geolocation calibration areas to improve the quality of OMPS sensor data records. This study covers several topics, including the removal of a solar intrusion signal during science data collection, reduction of solar activity impact resulting from solar activities, update of geolocation accuracy via refinement of the instrument CCD spatial registration, and minimization of a misalignment at the edges of the sensor spatial field of view during Earth view measurements. The objective of this study is to improve OMPS instrument performance to OMPS users' expectations, and to advance the OMPS calibration accuracy of sensor data records above current product requirements [2], [3]. The solar intrusion correction improved local radiance retrieval accuracy 4% for the Nadir Profiler sensor, during science observations in the Northern hemisphere where solar zenith angle ranges from $60^{\circ}$ to $88^{\circ}$ . Solar model improvements achieve up to 1% better fidelity in irradiance measurements during solar observations. The calibrated CCD spatial registration minimizes the misalignment in the Nadir Mapper sensor spatial field of view in both cross track and along track measurements, and refines the geolocation accuracy to less than 5 km for the sensor's geolocation products that have a nominal spatial resolution of 50 km x 17 km.

The identification of circulating tumor cells (CTCs) relies on epithelial tumor cell markers. In the present study, we aimed to determine whether cell-surface vimentin could be a biomarker to isolate CTCs in pancreatic ductal adenocarcinoma (PDAC). Vimentin was identified as highly expressed on the surface of mesenchymal-phenotype pancreatic tumor cells. Vimentin+ CTCs were detected in 76% of patients with PDAC (76/100) using CTCs enriched via a microfluidic assay. A cut-off value of two vimentin+ CTCs distinguished patients with PDAC from healthy individuals. Combined vimentin+ CTCs and Carbohydrate antigen 19-9 provided favorable diagnostic potency, with an area under the curve of 0.968. Vimentin+ CTCs counts correlated with the change in tumor burden for patients undergoing resection. Significantly reduced CTC counts were observed after chemotherapy in subjects that responded to treatment. Preoperatively higher CTCs counts correlated with shortened recurrence-free survival. Taken together, vimentin+ CTCs could be a reliable biomarker in pancreatic cancer. The enrichment of mesenchymal CTCs complements the strategy of capturing epithelial CTCs, allowing a more thorough interrogation of the biology and clinical significance of CTCs in PDAC.

Forkhead box-O1 (FOXO1) is a downstream target of AKT and plays crucial roles in cell cycle control, apoptosis, metabolism and adipocyte differentiation. It is thought that FOXO1 affects adipocyte differentiation by regulating lipogenesis and cell cycle. With the deepening in the understanding of this field, it is currently believed that FOXO1 translocation between nuclei and cytoplasm is involved in the regulation of FOXO1 activity, thus affecting adipocyte differentiation. Translocation of FOXO1 depends on its post-translational modifications and interactions with 14-3-3. Based on these modifications and interactions, FOXO1 could regulate lipogenesis through PPARγ and the adipocyte cell cycle through p21 and p27. In this review, we aim to provide a comprehensive FOXO1 regulation network in adipocyte differentiation by linking together distinct functions mentioned above to explain their effects on adipocyte differentiation and to emphasize the regulatory role of FOXO1. In addition, we also focus on the novel findings such as the use of miRNAs in FOXO1 regulation and highlight the improvable issues, such as RNA modifications, for future research in the field.

Developing feasible ways to achieve tunable gate-opening pressure (Pgo) while minimizing the side effects on the adsorption capacity and enthalpy is greatly desired for flexible MOFs. In this work, we focused on solving this issue by cobalt substitution. We showed the successful modulation of the energy required for the reversible transformation of a soft paddle-wheel so that the whole framework presented a substitution-dependent Pgo for CO2 adsorption.

Vascular remodeling is a pathological basis of various disorders. Therefore, it is necessary to understand the occurrence, prevention, and treatment of vascular remodeling. Krüppel-like factor 5 (KLF5) has been identified as a significant factor in cardiovascular diseases during the last two decades. This review provides a mechanism network of function and regulation of KLF5 in vascular remodeling based on newly published data and gives a summary of its potential therapeutic applications. KLF5 modulates numerous biological processes, which play essential parts in the development of vascular remodeling, such as cell proliferation, phenotype switch, extracellular matrix deposition, inflammation, and angiogenesis by altering downstream genes and signaling pathways. Considering its essential functions, KLF5 could be developed as a potent therapeutic target in vascular disorders.

The performance of on-orbit satellite microwave instrument noise equivalent differential temperature (NEDT) and Temperature Data Record (TDR) data is always critical for the broad user community in both environmental data record (EDR) product retrieval and numerical weather prediction applications. Based on intensive pre-launch and post-launch calibration studies [1]–[5], this study assesses the post-launch performance of Metop-C AMSU-A instrument noise and antenna temperature data since the launch. It also conducts the quality assessment of the AMSU-A data in comparison with radiative transfer model (RTM) simulations, legacy NOAA-18/19 and Metop-A/B AMSU-A observations, and NOAA-20 ATMS observations. Finally, this study addresses impact of polarization and wavelength inconsistency on AMSU-A antenna temperature differences against ATMS.

Background: Spontaneous isolated superior mesenteric artery dissection (SISMAD) is a rare vascular disorder and the treatment strategies remain controversial. This study aimed to compare outcomes of conservative and endovascular treatments in symptomatic patients with SISMAD. Methods: Forty-two consecutive SISMAD patients between October 2009 and May 2018 in a single center were enrolled in the study. Based on their symptoms, 15 had conservative treatment and 27 had endovascular treatment. The baseline characteristics, treatments, and follow-up results of the conservative group and endovascular group were analyzed. Results: The rate of symptom relief was 93.3% in the conservative group and 96.3% in the endovascular group, respectively. The procedure-related complications in the endovascular group included one case of pseudoaneurysm formation in the left brachial artery. During the follow-up period (median 28.5 months), a higher proportion of patients in the conservative group had symptom recurrence (42.9% in the conservative group versus 4.8% in the endovascular group, p < 0.001). Four patients in the conservative group and one patient in the endovascular group had additional endovascular intervention during follow-up. Compared with the conservative group, patients in the endovascular group had statistically significantly longer symptom-free survival ( p = 0.014) and a higher rate of superior mesenteric artery (SMA) remodeling ( p < 0.001). Conclusions: For symptomatic SISMAD, endovascularly treated patients had a lower rate of symptom recurrence and a higher rate of SMA remodeling in the long term. Endovascular treatment should be considered as the first-line treatment of SISMAD.

Epigallocatechin-3-gallate (EGCG) is a pivotal effective component of green tea. It is known that EGCG has antioxidant activity, anti-angiogenesis, anti-tumor, cardiovascular protection and blood lipid regulation functions. Forkhead box-O1 (FOXO1) is one of the downstream signals of protein kinase B (AKT) and takes part in adipogenesis. The purpose of this study is to investigate the effects of EGCG on adipose differentiation and the likely mechanisms. 3T3-L1 cells were induced by DMI for 2, 4, 6 and 8 days, respectively. During induction, the cells were treated with EGCG (5 μM, 10 μM, 50 μM and 100 μM) or DMSO for the first 2 days. In addition, another batch of 3T3-L1cells were treated with SC-3036 (PI3K activator, 10 µM), or LY294002 (PI3K inhibitor, 10 µM) alone or combined with EGCG (100 μM) for the indicated times. Medium glucose concentration, lipid accumulation, the levels of TNF-α, resistin, adiponectin and leptin and the expression of FOXO1, phosphorylated-FOXO1 (P-FOXO1), PPARγ, fatty acid synthase (FAS) were detected, respectively. The present study demonstrated that EGCG inhibited glucose uptake, lipid accumulation and adipokine secretion in a concentration-dependent manner during adipogenesis, which suggests that EGCG inhibits adipocyte's differentiation, maturation and functions. Moreover, EGCG also down-regulated the expression levels of PPARγ and P-FOXO1. Conversely, the PI3K activator reversed these changes caused by EGCG, suggesting that the inhibitory effects of EGCG may be mediated by PI3K-AKT-FOXO1 pathway to negatively regulate the expression of PPARγ. The findings will provide a solid foundation for EGCG to prevent and cure the obesity-associated diseases.

In order to decipher a complex biological process, tools are required to perturb the various players involved to gain information about the important parameters. Optogenetic modules are genetically encoded molecular reagents that, when expressed in cells, allow a specific biological process to be precisely controlled by light in a spatiotemporal manner [1]. Optogenetics thus offers cell biologists an unprecedented new way to perturb cellular activities. The application of optogenetic approaches in cellular biology and synthetic biology research has evolved tremendously in the last few years.

An updated version of the microwave-integrated retrieval system (MiRS) V11.2 was recently released. In addition to the previous capability to process multiple satellites/sensors, the new version has been extended to process global precipitation measurement (GPM) microwave imager (GMI) measurements. The main purpose of this study is to introduce MiRS GPM products and to evaluate rain rate, total precipitable water (TPW), and snow water equivalent (SWE) using various independent datasets. Rain rate evaluations were performed for January, April, July, and October 2015 which represents one full month in each season. TPW was evaluated on four days: 9 January, 1 April, 13 July, and 1 October, which represents one full day in each season. SWE was evaluated for a week in January 2015. Results show that MiRS performance is generally satisfactory in regards to both global/regional geographical distribution and quantified statistical/categorical scores. Histograms show that MiRS GPM rain rate estimates have the capability to reproduce moderate to heavy rain frequency distribution over land, and light rain distribution over ocean when compared with a ground-based reference. Evaluations of TPW show the best performance over ocean with the correlation coefficient, bias, and standard deviation of 0.99

Translocator protein (TSPO) is highly expressed in the cardiovascular system, exerting crucial effects on both myocardial damage and protection. However, the role and mechanism of TSPO in myocardial ischemia/reperfusion (I/R) injury remains elusive. In the current study, we subjected H9c2 cardiomyocytes to anoxia/reoxygenation (A/R) and knocked down TSPO expression by RNA interference to investigate the possible mechanism of TSPO on I/R injury. TSPO expression in cardiomyocytes was up-regulated when exposed to A/R, but normal in anoxic preconditioned (APC) cardiomyocytes. Moreover, A/R also led to an increase in reactive oxygen species (ROS), oxidative stress aggravation, mitochondrial membrane potential collapse, mitochondrial permeability transition pore (mPTP) opening, and cell apoptosis. However, these events were completely compensated by downregulating TSPO expression. TSPO-downregulated cardiomyocytes produced lesser lactate dehydrogenase (LDH) and creatine phosphokinase (CPK), and showed lesser cytosol malondialdehyde (MDA) accumulation than normal cells after A/R injury. On the other hand, the TSPO- downregulated cells showed higher activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), mitochondrial function stabilization, resulting in less cell apoptosis and damage in case of A/R condition. In conclusion, TSPO expression is up-regulated under A/R injury, whereas repression of TSPO improves the endurance of cardiomyocytes against A/R injury by reducing oxidative stress, mitochondrial damage and cell apoptosis.

This study carries out the calibration and validation of Antenna Temperature Data Record (TDR) and Brightness Temperature Sensor Data Record (SDR) data from the last National Oceanic and Atmospheric Administration (NOAA) Advanced Microwave Sounding Unit-A (AMSU-A) flown on the Meteorological Operational satellite programme (MetOp)-C satellite. The calibration comprises the selection of optimal space view positions for the instrument and the determination of coefficients in calibration equations from the Raw Data Record (RDR) to TDR and SDR. The validation covers the analyses of the instrument noise equivalent differential temperature (NEDT) performance and the TDR and SDR data quality from the launch until 15 November 2019. In particular, the Metop-C data quality is assessed by comparing to radiative transfer model simulations and observations from Metop-A/B AMSU-A, respectively. The results demonstrate that the on-orbit instrument NEDTs have been stable since launch and continue to meet the specifications at most channels except for channel 3, whose NEDT exceeds the specification after April 2019. The quality of the Metop-C AMSU-A data for all channels except channel 3 have been reliable since launch. The quality at channel 3 is degraded due to the noise exceeding the specification. Compared to its TDR data, the Metop-C AMSU-A SDR data exhibit a reduced and more symmetric scan angle-dependent bias against radiative transfer model simulations, demonstrating the great performance of the TDR to SDR conversion coefficients. Additionally, the Metop-C AMSU-A data quality agrees well with Metop-A/B AMSU-A data, with an averaged difference in the order of 0.3 K, which is confirmed based on Simultaneous Nadir Overpass (SNO) inter-sensor comparisons between Metop-A/B/C AMSU-A instruments via either NOAA-18 or NOAA-19 AMSU-A as a transfer.

Epithelial-mesenchymal transition (EMT) is one of the most important mechanisms in the initiation and promotion of cancer cell metastasis. The phosphoinositide 3-kinase (PI3K) signaling pathway has been demonstrated to be involved in TGF-β induced EMT, but the complicated TGF-β signaling network makes it challenging to dissect the important role of PI3K on regulation of EMT process. Here, we applied optogenetic controlled PI3K module (named ‘Opto-PI3K’), which based on CRY2 and the N-terminal of CIB1 (CIBN), to rapidly and reversibly control the endogenous PI3K activity in cancer cells with light. By precisely modulating the kinetics of PI3K activation, we found that E-cadherin is an important downstream target of PI3K signaling. Compared with TGF-β treatment, Opto-PI3K had more potent effect in down-regulation of E-cadherin expression, which was demonstrated to be regulated in a light dose-dependent manner. Surprisingly, sustained PI3K activation induced partial EMT state in A549 cells that is highly reversible. Furthermore, we demonstrated that Opto-PI3K only partially mimicked TGF-β effects on promotion of cell migration in vitro. These results reveal the importance of PI3K signaling in TGF-β induced EMT, suggesting other TGF-β regulated signaling pathways are necessary for the full and irreversible promotion of EMT in cancer cells. In addition, our study implicates the great promise of optogenetics in cancer research for mapping input-output relationships in oncogenic pathways.

The NOAA Microwave Integrated Retrieval System (MiRS) retrieves the atmospheric profiles of state variables (temperature, moisture, liquid cloud, hydrometeors, surface emissivity spectrum and skin temperature) simultaneously and coherently with one-dimension Variational (1DVar) method based on passive microwave radiance observation from multiple polar-orbiting operational satellites, including NOAA18, NOAA19, MetOp (A and B), DMSP (F16 and F18) and SNPP. In MiRS, the geophysical consistency between the retrieved state variables is obtained through the constraint from the state variable background covariance matrices, which define the variability of each state variable and the relationship between them. The current atmospheric covariance matrices were mainly built based on the ECMWF 60 layer sample data set (EC60). Because no rain data available in EC60, the MM5 model output rain was used as a substitute. Although MiRS performs well based on current matrices, obviously, there is room for improvement if the matrices could be rebuilt based more representative, higher resolution dataset, and most importantly, all variables are from one datasets, so the cross relationship between parameters could be properly represented. The ECMWF IFS-137 dataset (EC137) is the most recent ECMWF sample data set. Besides several major modifications and improvements in ECMWF forecasting system, comparing with EC60, the profiles in EC137 have more than doubled vertical resolution. The hydrometeor variables are included in EC137, rather than in EC60. With upgraded sampling method, the profiles in EC137 are more evenly distributed in both temporal and spatial domains. And the profile population in EC137 shows significant different statistic characters than its precedents. To generate the new matrices, EC137 data is interpolated from 137 layers to 100 layers. The variable units are transferred to be used for radiation transfer calculation and match with those used in MiRS. For example, the unit of rain and snow is transferred from mass flux (Kg/(m2*s)) to water content (Kg/m2) with the assumption of rain (snow) drop speed as 4.0 (1.0) m/s. Comparing the matrix based on EC137 and that of current MiRS, except the variation in details, there are two significant distinct features are noticeable. First, the snow variable becomes effective in EC137 matrix because the snow variable is provided in EC137 rather than in EC60 and MM5. Second, the covariance between rain and other variables becomes meaningful in EC137 matrix. In the old matrix, rain is not well correlated with other variables, as rain data is from MM5, but other parameters are from EC60, two unrelated datasets. All these differences imply different, most likely better performance of MiRS system if employing the background covariance matrices based on EC137. Tuning is conducted after implementation of the new EC137 matrices. And the impact of the new matrices is assessed by comparing the retrieval products based on the new and old matrices, and with colloated dropsonde, radiosonde and ECMWF analysis profiles.

Frame difference is most widely used in video detection, but the original frame difference is not accurate enough to segment the moving object in special scenes such as light changes suddenly or camera shakes slightly. In this paper, we propose a segmentation algorithm based on improved frame differences. In the algorithm, we first set the frame difference value k by the environment characteristics, and then we determine whether the image movement is a global movement by the dual-threshold. If the global movement is caused by the illumination variation, we calculate the changing rate of gray value to detect the moving object. If it is caused by the camera shaking, we find the main direction of the movement by comparing a point in the background with the eight neighborhood points in the current frame to detect the moving object. The simulation results show the effectiveness of the proposed algorithm.

Reanalyses, retrospectively analyzing observations over climatological time scales, represent a merger between satellite observations and models to provide globally continuous data and have improved over several generations. Balancing the earth’s global water and energy budgets has been a focus of research for more than two decades. Models tend to their own climate while remotely sensed observations have had varying degrees of uncertainty. This study evaluates the latest NASA reanalysis, the Modern Era Retrospective-Analysis for Research and Applications (MERRA), from a global water and energy cycles perspective, to place it in context of previous work and demonstrate the strengths and weaknesses. MERRA was configured to provide complete budgets in its output diagnostics, including the incremental analysis update (IAU), the term that represents the observations influence on the analyzed states, alongside the physical flux terms. Precipitation in reanalyses is typically sensitive to the observational analysis. For MERRA, the global mean precipitation bias and spatial variability are more comparable to merged satellite observations [the Global Precipitation and Climatology Project (GPCP) and Climate Prediction Center Merged Analysis of Precipitation (CMAP)] than previous generations of reanalyses. MERRA ocean evaporation also has a much lower value, which is comparable to independently derived estimate datasets. The global energy budget shows that MERRA cloud effects may be generally weak, leading to excess shortwave radiation reaching the ocean surface. Evaluating the MERRA time series of budget terms, a significant change occurs that does not appear to be represented in observations. In 1999, the global analysis increments of water vapor changes sign from negative to positive and primarily lead to more oceanic precipitation. This change is coincident with the beginning of Advanced Microwave Sounding Unit (AMSU) radiance assimilation. Previous and current reanalyses all exhibit some sensitivity to perturbations in the observation record, and this remains a significant research topic for reanalysis development. The effect of the changing observing system is evaluated for MERRA water and energy budget terms.

Like all reanalysis efforts, the Modern Era Retrospective-Analysis for Research and Applications (MERRA) must contend with an inhomogeneous observing network. Here the effects of the two most obvious observing system epoch changes, the Advanced Microwave Sounding Unit-A (AMSU-A) series in late 1998 and, to a lesser extent, the earlier advent of the Special Sensor Microwave Imager (SSM/I) in late 1987 are examined. These sensor changes affect model moisture and enthalpy increments and thus water and energy fluxes, since the latter result from model physics processes that respond sensitively to state variable forcing. Inclusion of the analysis increments in the MERRA dataset is a unique feature among reanalyses that facilitates understanding the relationships between analysis forcing and flux response. In stepwise fashion in time, the vertically integrated global-mean moisture increments change sign from drying to moistening and heating increments drop nearly 15 W m−2 over the 30 plus years of the assimilated products. Regression of flux quantities on an El Niño–Southern Oscillation sea surface temperature (SST) index analysis reveals that this mode of climate variability dominates interannual signals and its leading expression is minimally affected by satellite observing system changes. Conversely, precipitation patterns and other fluxes influenced by SST changes associated with Pacific decadal variability (PDV) are significantly distorted. Observing system changes also induce a nonstationary component to the annual cycle signals. Principal component regression is found useful for identifying artifacts produced by changes of satellite sensors and defining appropriate adjustments. After the adjustments are applied, the spurious flux trend components are greatly diminished. Time series of the adjusted precipitation and the Global Precipitation Climatology Project (GPCP) data compare favorably on a global basis. The adjustments also provide a much better depiction of precipitation spatial trends associated with PDV-like forcing. The utility as well as associated drawbacks of this statistical adjustment and the prospects for future improvements of the methodology are discussed.