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Introduction Nintedanib can inhibit processes involved in the progression of fibrosis and can reduce the decline in forced vital capacity in patients with idiopathic pulmonary fibrosis (IPF) and fibrotic-interstitial lung disease (fibrotic-ILDs). Although the adverse events associated with nintedanib in IPF patients are well known, its safety in other fibrotic-ILD patients remained unclear. Methods We searched PubMed, EMBASE, Cochrane CENTRAL and Cochrane CDSR for randomized controlled studies which compared nintedanib with a placebo in ILD patients. We estimated pooled odds ratios (ORs) and 95% confidence intervals (CIs) for adverse events using the DerSimonian–Laird random-effects model. Results Six studies with a total of 2,583 patients were included in the meta-analysis. The pooled estimates showed that patients treated with nintedanib had a significantly higher likelihood of having any adverse events (OR = 2.39; 95% CI = 1.71–3.36) or adverse events leading to treatment discontinuation (OR = 1.73; 95% CI = 1.34–2.25). However, they had trend to lower likelihood of having fatal adverse events (OR = 0.69; 95% CI = 0.41–1.14) compared with the placebo group. Use of nintedanib was positively associated with diarrhea (OR = 5.96; 95% CI = 4.35–8.16), nausea (OR = 3.00; 95% CI = 1.93–4.66), vomiting (OR = 3.22; 95% CI = 2.17–4.76) and weight loss (OR = 3.38; 95% CI = 1.1.76–6.47). Whereas, patients treated with nintedanib were less likely to have a cough (OR = 0.73; 95% CI = 0.56–0.96) and dyspnea (OR = 0.70; 95% CI = 0.53–0.94). Conclusions Compared to a placebo, nintedanib was associated with a higher risk of adverse events, especially for diarrhea, nausea, vomiting and weight loss, but it was also associated with a lower risk of cough and dyspnea in IPF and fibrotic-ILD patients.

Drug inventory management is an important part of hospital management. The large amounts of drug data in hospitals bring challenges to optimizing the setting values for the safety stock and the maximum inventory of each drug. This study combined a two-stage clustering method with an inventory policy (s, S) and established a simulation optimization model for the case hospital’s outpatient pharmacy. This research used the simulation optimization software Arena OptQuest, developed by Rockwell Automation Inc (Rockwell Automation, Coraopolis, PA, USA), in order to determine the minimum and maximum values (s, S) of the best stock amounts for each drug under the considerations of cost and related inventory constraints. The research results showed that the minimum and maximum inventory settings for each drug in the simulation model were better than those set by the case outpatient pharmacy system. The average inventory cost was reduced by 55%, while the average inventory volume was reduced by 68%. The proposed method can improve management efficiency and inventory costs of hospital pharmacies without affecting patient services and increasing the inventory turnover rate of the drugs.

The Arctic is a vital component of the global climate, and its rapid environmental evolution is an important element of climate change around the world. To detect and diagnose the changes occurring to the coupled Arctic climate system, a state-of-the-art synthesis for assessment and monitoring is imperative. This paper presents the Arctic System Reanalysis, version 2 (ASRv2), a multiagency, university-led retrospective analysis (reanalysis) of the greater Arctic region using blends of the polar-optimized version of the Weather Research and Forecasting (Polar WRF) Model and WRF three-dimensional variational data assimilated observations for a comprehensive integration of the regional climate of the Arctic for 2000–12. New features in ASRv2 compared to version 1 (ASRv1) include 1) higher-resolution depiction in space (15-km horizontal resolution), 2) updated model physics including subgrid-scale cloud fraction interaction with radiation, and 3) a dual outer-loop routine for more accurate data assimilation. ASRv2 surface and pressure-level products are available at 3-hourly and monthly mean time scales at the National Center for Atmospheric Research (NCAR). Analysis of ASRv2 reveals superior reproduction of near-surface and tropospheric variables. Broadscale analysis of forecast precipitation and site-specific comparisons of downward radiative fluxes demonstrate significant improvement over ASRv1. The high-resolution topography and land surface, including weekly updated vegetation and realistic sea ice fraction, sea ice thickness, and snow-cover depth on sea ice, resolve finescale processes such as topographically forced winds. Thus, ASRv2 permits a reconstruction of the rapid change in the Arctic since the beginning of the twenty-first century–complementing global reanalyses. ASRv2 products will be useful for environmental models, verification of regional processes, or siting of future observation networks.

The Gridpoint Statistical Interpolation three-dimensional variational data assimilation (DA) system coupled with the Weather Research and Forecasting/Chemistry (WRF/Chem) model was utilized to improve aerosol forecasts and study aerosol direct and semi-direct radiative feedbacks during a US wild fire event. Assimilation of MODIS total 550 nm aerosol optical depth (AOD) retrievals clearly improved WRF/Chem forecasts of surface PM2.5 and organic carbon (OC) compared to the corresponding forecasts without aerosol data assimilation. The scattering aerosols in the fire downwind region typically cooled layers both above and below the aerosol layer and suppressed convection and clouds, which led to an average of 2% precipitation decrease during the fire week. This study demonstrated that, even with no input of fire emissions, AOD DA improved the aerosol forecasts and allowed a more realistic model simulation of aerosol radiative effects.

Objectives We investigated whether chronological changes in portal flow and clinical factors play a role in the liver regeneration (LR) process after right donor-hepatectomy. Materials and methods Participants in this prospective study comprised 58 donors who underwent right donor-hepatectomy during the period February 2014 to February 2015 at a single medical institution. LR was estimated using two equations: remnant left liver (RLL) growth (%) and liver volumetric recovery (LVR) (%). Donors were classified into an excellent regeneration (ER) group or a moderate regeneration (MR) group based on how their LR on postoperative day 7 compared to the median value. Results Multivariate analysis revealed that low residual liver volume (OR = .569, 95% CI: .367– .882) and high portal venous velocity in the immediate postoperative period (OR = 1.220, 95% CI: 1.001–1.488) were significant predictors of LR using the RLL growth equation; high portal venous velocity in the immediate postoperative period (OR = 1.325, 95% CI: 1.081–1.622) was a significant predictor of LR using the LVR equation. Based on the two equations, long-term LR was significantly greater in the ER group than in the MR group (p < .001). Conclusion Portal venous velocity in the immediate postoperative period was an important factor in LR. The critical time for short-term LR is postoperative day 7; it is associated with long-term LR in donor-hepatectomy.

Our goal was to evaluate the predictors of coagulopathic hemorrhage after living-donor liver transplant.We retrospectively evaluated 161 patients who had undergone living-donor liver transplant from July 2005 to April 2014 at a single medical institution. Of these patients, 32 developed hemorrhage after transplant. Patients were separated into those with coagulopathy-related hemorrhage (n=15) or noncoagulopathy-related hemorrhage (n=17) based on the results of computed tomography images. Predictors of hemorrhage after living-donor liver transplant evaluated in this study included preoperative, perioperative, and posttransplant factors and hemodynamic status.Patients who developed coagulopathy-related hemorrhage had significantly lower pretransplant platelet counts (P = .040), a longer cold-ischemia time (P = .045), more blood loss (P = .040), and earlier onset of hemorrhage (P = .048) than patients who had noncoagulopathy-related hemorrhage after transplant. Results of the generalized estimating equation analysis showed that heart rate and central venous pressure differed significantly between the 2 groups of patients. Heart rates increased significantly during hemorrhage (P.010). Central venous pressure was higher in the coagulopathic group (P = .005) than in the noncoagulopathic group.Lower pretransplant platelet counts, longer cold ischemia time, more blood loss, earlier onset of hemorrhage, and higher central venous pressure level are indicators of coagulopathic hemorrhage after living-donor liver transplant.

Total 550 nm aerosol optical depth, surface fine particulate matter (PM2.5), and meteorological observations were assimilated with continuously cycling three-dimensional variational (3DVAR), ensemble square root Kalman filter (EnSRF), and hybrid variational-ensemble data assimilation systems. The hybrid system's background error covariances (BECs) were a blend of those in 3DVAR and produced by the cycling EnSRF system, and the 3DVAR, EnSRF, and hybrid systems differed almost exclusively by their BECs. New analyses were produced every 6 h between 0000 UTC 1 June and 1800 UTC 14 July 2010 over a domain encompassing the contiguous United States (CONUS) and adjacent areas. Additionally, a control experiment that only assimilated meteorological observations was performed. Each 1800 UTC analysis initialized a 48 h Weather Research and Forecasting with Chemistry model forecast. These forecasts were evaluated with a focus on air quality prediction. The ensemble aerosol spread was generally insufficient, particularly over the western CONUS. However, despite the suboptimal ensemble spread, the hybrid system performed quite well and usually produced the best aerosol forecasts. Additionally, both the 3DVAR- and EnSRF-initialized forecasts typically outperformed the control. These results are encouraging and suggest the resiliency of the hybrid method. Improved aerosol ensembles should translate into even better future hybrid forecasts.

[1] The capability of assimilating surface PM10 (particulate matter with diameters less than 10 µm) observations has been developed within the National Centers for Environmental Prediction Gridpoint Statistical Interpolation three-dimensional variational (3DVAR) data assimilation (DA) system. It provides aerosol analyses for the Goddard Chemistry Aerosol Radiation and Transport aerosol scheme within the Weather Research and Forecasting/Chemistry model. Control and assimilation experiments were performed for June 2011 over China to explore in detail the impact of assimilating surface PM10. In the assimilation experiment, analyses were produced every 6 h to adjust the mass concentrations of different aerosol species. The statistical results from two parallel experiments demonstrate that the assimilation of surface PM10 observations can significantly reduce the uncertainty of initial aerosol fields and effectively improve the subsequent aerosol forecasts for at least 12 h. However, the benefit from the assimilation of PM10 diminishes rapidly with forecast range. Process analysis for PM10 formation indicates that the rapidly diminishing DA impact on aerosol forecasts, especially in early forecast hours, was dominated by vertical mixing with an additional contribution from advection. Both processes were mainly related to unbalanced aerosol fields in the horizontal and vertical after assimilating surface observations. These findings illustrate the importance of adjusting aerosol emission rates and the initial aerosol vertical profile.

Background Donor safety and preservation of donor health after living liver donation are of paramount importance. Diarrhea has a significant influence on gastrointestinal quality of life among donors who have undergone living donor hepatectomy. Thus, we aimed to investigate predictors of diarrhea after hepatectomy and its impact on gastrointestinal quality of life in living donors. Methods We retrospectively examined the medical records of 204 living liver donors who underwent hepatectomy during the period January 2010 to June 2013 at a single medical center. Diarrhea was defined as the passing of three or more liquid stools per day. The Chinese version of the Gastrointestinal Quality of Life Index (GIQLI) was used to assess the influence of diarrhea on quality of life in donors. Results During the study period, diarrhea was diagnosed in 62 (30.3%) of the 204 donors and the duration of diarrhea in the majority of them (n = 46, 74%) was

Data assimilation is the process by which observations are combined with short-range NWP model output to produce an analysis of the state of the atmosphere at a specified time. Since its inception in the late 1990s, the multiagency Weather Research and Forecasting (WRF) model effort has had a strong data assimilation component, dedicating two working groups to the subject. This article documents the history of the WRF data assimilation effort, and discusses the challenges associated with balancing academic, research, and operational data assimilation requirements in the context of the WRF effort to date. The WRF Model's Community Variational/Ensemble Data Assimilation System (WRFDA) has evolved over the past 10 years, and has resulted in over 30 refereed publications to date, as well as implementation in a wide range of real-time and operational NWP systems. This paper provides an overview of the scientific capabilities of WRFDA, and together with results from sample operation implementations at the U.S. ...

Background: The standardized mortality rate of type 2 diabetes is higher in Taiwan than that in other developed countries. In Taiwan, the diabetes mortality rate in Chiayi County is the highest nationwide. Purpose: This study was designed to explore the health status (to measure six physiological indicators), the health-related behaviors, and the associated factors among type 2 diabetes sufferers living in rural communities. Methods: Researchers used a cross-sectional, correlation design and conducted the study at nine local health districts in Chiayi County, Taiwan. A total of 387 participants previously diagnosed with type 2 diabetes were randomly selected and invited to join in the program. Results: Fifty-nine percent of participants were women; their mean age was 68.7 years, and their mean duration with diabetes was 7.9 years. Most were treated at local health centers and took oral medications (90.7%). More than 40% did not exercise regularly and 33.9% did not practice diet control. Results found a higher percentage of abnormal health indicators in terms of participant body mass index, waist circumference, HbA1C, and peripheral neurovascular function. After controlling for potential confounding factors, researchers found smaller waist circumference, participating in community support groups, better foot self-care capability, and frequent exercise to be associated with better health indicators. Diabetes duration, lower education, and being of male gender were found to be negatively associated with health status. Conclusions/Implications for Practice: This study found that rural residents with diabetes do not adequately control their diabetes and exhibit inadequate health-related behavior. Joining community support groups, increasing exercise frequencies, and improving foot self-care capabilities should be employed in nursing strategies and health policies for diabetes control-especially for those who have less formal education or are male.

The Weather Research and Forecasting (WRF) model–based variational data assimilation system (WRF-Var) has been extended from three- to four-dimensional variational data assimilation (WRF 4D-Var) to meet the increasing demand for improving initial model states in multiscale numerical simulations and forecasts. The initial goals of this development include operational applications and support to the research community. The formulation of WRF 4D-Var is described in this paper. WRF 4D-Var uses the WRF model as a constraint to impose a dynamic balance on the assimilation. It is shown to implicitly evolve the background error covariance and to produce the flow-dependent nature of the analysis increments. Preliminary results from real-data 4D-Var experiments in a quasi-operational setting are presented and the potential of WRF 4D-Var in research and operational applications are demonstrated. A wider distribution of the system to the research community will further develop its capabilities and to encourage testing under different weather conditions and model configurations.

Intensive nutritional support can reduce the catabolic response, improve protein synthesis, and promote liver regeneration. This study examined whether postoperative peripheral parenteral nutrition may improve recovery and reduce the length of hospital stay in right lobe liver donors.In this retrospective study, we enrolled liver donors with residual liver volume50%. Donors were classified into 2 groups: donors who received (n = 44) or did not receive (n = 40) postoperative peripheral parenteral nutrition. Liver function tests included alanine aminotransferase and total bilirubin levels, and postoperative complications included pleural effusion, atelectasis, and wound complications. Hospital length of stay was included as a potential risk factor for the evaluation of the effect of postoperative peripheral parenteral nutrition on recovery of right lobe liver donors.Male sex (β, 22.04; 95% confidence interval: 6.22 - 37.86) was a significant predictor of changes in postoperative alanine aminotransferase level. Male sex (β, 0.045; 95% confidence interval: 0.16 - 37.86) and receipt of peripheral parenteral nutrition (β, -0.045; 95% confidence interval: -0.72 - 0.17) were significant predictors of changes in total bilirubin level. Postoperative atelectasis (P.001), pleural effusion (P.011), and total complications (P = .015) had significantly lower incidence in the peripheral parenteral nutrition than control group. Multivariate logistic regression showed that recipients of peripheral parenteral nutrition (odds ratio, 0.161; 95% confidence interval: 0.043 - 0.598) and age (odds ratio, 0.870; 95% confidence interval: 0.782 - 0.968) were significant preoperative risk factors for postoperative complications.Postoperative peripheral parenteral nutrition is associated with a lower incidence of pleural effusion and atelectasis, a more rapid recovery of hyperbilirubinemia, and shorter length of stay in right lobe liver donors.

Donor safety and preservation of donor health after living liver donation are of paramount importance. In addition, the preoperative mental state of a donor is an important factor in determining the psychological impact of donor hepatectomy. Thus, we aimed to explore the mental health status of living liver donors after hepatectomy. We enrolled 60 donors who were scheduled to undergo living donor hepatectomy during the period January 2014 to March 2015 at a single medical center. Mental health status was measured before and 3 months after surgery using 3 self-report questionnaires, namely the Center for Epidemiologic Studies Depression Scale (CES-D) to assess depressive symptoms, the World Health Organization Quality of Life (WHOQOL-BREF) questionnaire to measure quality of life, and the Chinese Health Questionnaire (CHQ) to screen for minor psychiatric disorders. A comparison of the pre- and postdonation CES-D scores revealed a significant reduction in depressive symptoms after surgery (P = .031). There were significant improvements in the physical health domain (P = .031), the psychological health domain (P = .005), the social relationships domain (P = .005), and the environmental health domain (P = .010) of the WHOQOL-BREF. There were no significant changes in CHQ scores after donor hepatectomy (P = .136). All donors reported that they would donate again if required. Approximately one-third (33.3%) of donors experienced more pain than they had anticipated in the immediate postoperative period, and 20.0% of donors had complications after donor hepatectomy. Donor mental health status tended to improve as donors regained physical function during the 1st 3 months of recovery. Long-term monitoring of living donors’ mental health is needed to minimize the adverse psychological outcomes of living liver donation.

Ursolic acid (UA) is a pentacyclic triterpene acid that is present in a wide variety of medicinal herbs and edible plants. This study investigated the effect of UA on apoptosis and proliferation of hepatocellular carcinoma SK-Hep-1 cells. After treatment of SK-Hep-1 cells with different concentrations of UA, we observed that cell viability was reduced in a dose- and time-dependent manner. Furthermore, there was a dose-dependent increase in the percentage of cells in the sub-G1 and G2/M phases, with cells treated with 60 μM showing the highest percentages of cells in those phases. UA-induced chromatin condensation of nuclei was observed by using DAPI staining. The western blot results revealed that exposure to UA was associated with decreased expression of the anti-apoptotic proteins Mcl-1, Bcl-xL, Bcl-2, and TCTP and increased expression of apoptosis-related proteins TNF-α, Fas, FADD, Bax, cleaved caspase-3, caspase-8, caspase-9, and PARP. Immunocytochemistry staining showed that treatment with UA resulted in increased expression of caspase-3. Moreover, exposure to UA resulted in the inhibition of the PI3K/Akt and p38 MAPK signaling pathways. These findings suggest that UA inhibits the proliferation of SK-Hep-1 cells and induces apoptosis.

[1] Assimilation of the Moderate Resolution Imaging Spectroradiometer (MODIS) total aerosol optical depth (AOD) retrieval products (at 550 nm wavelength) from both Terra and Aqua satellites have been developed within the National Centers for Environmental Prediction (NCEP) Gridpoint Statistical Interpolation (GSI) three-dimensional variational (3DVAR) data assimilation system. This newly developed algorithm allows, in a one-step procedure, the analysis of 3-D mass concentration of 14 aerosol variables from the Goddard Chemistry Aerosol Radiation and Transport (GOCART) module. The Community Radiative Transfer Model (CRTM) was extended to calculate AOD using GOCART aerosol variables as input. Both the AOD forward model and corresponding Jacobian model were developed within the CRTM and used in the 3DVAR minimization algorithm to compute the AOD cost function and its gradient with respect to 3-D aerosol mass concentration. The impact of MODIS AOD data assimilation was demonstrated by application to a dust storm from 17 to 24 March 2010 over East Asia. The aerosol analyses initialized Weather Research and Forecasting/Chemistry (WRF/Chem) model forecasts. Results indicate that assimilating MODIS AOD substantially improves aerosol analyses and subsequent forecasts when compared to MODIS AOD, independent AOD observations from the Aerosol Robotic Network (AERONET) and Cloud-Aerosol Lidar with Orthogonal Polarization (CALIOP) instrument, and surface PM10 (particulate matter with diameters less than 10 μm) observations. The newly developed AOD data assimilation system can serve as a tool to improve simulations of dust storms and general air quality analyses and forecasts.

Summary Objective To explore the perceptions of group music therapy among elderly nursing home residents in Taiwan. Methods Focus group methodology was used to explore the perceptions of elderly participants about their experience of group music therapy. Verbatim transcripts of audiotaped interviews were analysed by content analysis. Results In total, 3 focus groups were held with 17 wheelchair-bound elderly residents. Analysis of participants’ perceptions of group music therapy revealed two major themes: (1) strength derived from the group dynamic and (2) enhanced quality of life. The first theme included three subthemes: (1) sense of energy, (2) distraction from suffering, and (3) confirmation as a person. The second major theme included four subthemes: (1) variety added to life, (2) motivation to exercise, (3) learning positive behaviour, and (4) greater life satisfaction. Conclusion Elderly, wheelchair-bound residents of a nursing home in Taiwan positively viewed their experiences with our group music therapy programme, particularly its active component. The findings of this study suggest that healthcare providers should consider integrating group music therapy into their programmes for elderly nursing home residents and design the therapy to add variety to their life, give them a sense of autonomy by having them choose their preferred musical activities, and improve their cognitive function.

Steganographic technology acts as the important role which defends information security in the network. The information could be hidden in multimedia object. Even if transmitted in an unsafe channel, the information is invisible by human visual system to maintain security. This paper presents a reversible palette image steganography based on de-clustering and predictive coding. The information is embedded into the image during compression encoding. It does not only solve problems encountered in interception and theft over Internet. The proposed method reforms the drawback of distortion of other schemes. When retrieving the information from stego-image, the original image also can be recovered. The proposed method is robust and useful for keeping transmission secure.

[1] This paper reports the first effort on real-time ensemble predictions of precipitation during the 2000–2002 Mei-Yu seasons (May to June) over the Taiwan area. Six members were included, each using the fifth-generation Pennsylvania State University-National Center for Atmospheric Research Mesoscale Model (MM5) nesting down to 15-km grid size, with different combinations of cumulus and microphysics parameterizations. Rainfall forecasts were evaluated with the equitable threat score (ETS) and bias score (BS). On the basis of verifications on 15-km grid points over three Mei-Yu seasons, it was found that no one member persistently had the least root mean square error of 12–24 hours and 24–36 hours accumulated rainfalls. For rainfall occurrence, most members had better predictions over the northeastern mountainous area, the northwestern coastal plain, the central mountain slope, the southwestern coastal plan, and the southwestern mountainous area. These regions also corresponded to areas of more accumulated rainfalls during three Mei-Yu seasons. An ensemble prediction, using a multiple linear regression (MLR) method which performed a least-square fit between the predicted and observed rainfalls in postseason analysis, had the best ETS and BS skill. The MLR ensemble forecast outperformed the average forecast (for all six members), the average forecasts of cumulus (four-member) and microphysics (three-member) ensembles, and also a high-resolution (5-km) forecast; however, a high-resolution forecast still had better skill for heavy rainfall events. The MLR ensemble forecast, using the weightings determined from previous Mei-Yu seasons, still had similar ETS trend to that with weightings determined by current-year Mei-Yu season, albeit with less skill.

1. The present study was carried out to identify the specific protein kinase C (PKC) isoform involved in regulatory volume decrease (RVD) responses, and to investigate the signal transduction pathways underlying the activation of volume-sensitive chloride channels in human cervical cancer HT-3 cells. The role of Ca2+ in RVD and in the activation of chloride currents was also studied. 2. The time course of RVDs was prolonged by microinjection of PKC-alpha antibody but not by PKC-beta or PKC-gamma antibody, and also by exposure to Ca2+-free medium, in particular when combined with microinjection of EDTA. Immunofluorescence staining showed that hypotonic superfusion evoked the translocation of PKC-alpha to the cell membrane, whereas PKC-beta or PKC-gamma remained unaffected. The translocation of PKC-alpha was observed a few minutes after hypotonic stress, reaching peak intensity at 30 min, and returned to the cytoplasm 60 min after hypotonic exposure. Western blot analyses showed an increased PKC-alpha level in terms of intensity and phosphorylation in the cell membrane, while neither PKC-beta nor PKC-gamma was activated upon hyposmotic challenge. 3. Whole-cell patch-clamp studies demonstrated that neomycin and PKC blockers such as staurosporine and H7 inhibited volume-sensitive chloride currents. The inhibitory effect of neomycin on chloride currents can be reversed by the PKC activator phorbol 12-myristate, 13-acetate (PMA). Moreover, the PKC inhibitor and PKC-alpha antibody, but not PKC-beta or PKC-gamma antibody, significantly attenuated the chloride currents. The activation of volume-sensitive chloride currents were insensitive to the changes of intracellular Ca2+ but required the presence of extracellular Ca2+. 4. Our results suggest the involvement of PKC-alpha and extracellular Ca2+ in RVD responses and the activation of volume-sensitive chloride channels in HT-3 cells.