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This paper investigates how carbon taxes affect emissions by examining British Columbia's revenue-neutral carbon tax in the manufacturing sector. We theoretically demonstrate that carbon taxes can achieve emission reductions while increasing production. Recycling carbon tax revenues to lower corporate income tax rates encourages investments, allowing plants to emit less per unit of output. Using detailed confidential plant-level data, we evaluate this theoretical prediction by exploiting the treatment intensity through plants' emission intensity. We find that the carbon tax lowers emissions by 4 percent. Furthermore, we find that the policy had a positive output effect and negative emission intensity effect, suggesting that the carbon tax encouraged plants to produce more with less energy. We provide initial evidence showing how a revenue-neutral carbon tax may achieve emission reductions while stimulating the economy.

This paper investigates the employment impacts of British Columbia’s revenue neutral carbon tax. Using the synthetic control method with firm-level data, we find considerable heterogeneity in employment responses to the policy. We show that firm size matters. In particular, the carbon tax had a negative impact on large emission-intensive firms, but simultaneous tax cuts and transfers increased the purchasing power of low income households, substantially benefiting small businesses in the service sector and food/clothing manufacturing. Furthermore, we find that aggregate employment was not adversely affected by the policy. Our results provide additional insight for the “job-shifting hypothesis” of revenue neutral carbon taxes.

We compare the employment effect of the British Columbia carbon tax using two empirical methods: a reduced-form econometric model and counterfactual simulations conducted using an applied g...

To evaluate the usefulness of deep learning image reconstruction (DLIR) to improve the image quality of dual-energy computed tomography (DECT) of the abdomen, compared to hybrid iterative reconstruction (IR).This study included 40 patients who underwent contrast-enhanced DECT of the abdomen. Virtual monochromatic 40-, 50-, and 70-keV and iodine density images were reconstructed using three reconstruction algorithms, including hybrid IR (ASiR-V50%) and DLIR (TrueFidelity) at medium- and high-strength level (DLIR-M and DLIR-H, respectively). The standard deviation of attenuation in liver parenchyma was measured as image noise. The contrast-to-noise ratio (CNR) for the portal vein on portal venous phase CT was calculated. The vessel conspicuity and overall image quality were graded on a 5-point scale ranging from 1 (poor) to 5 (excellent). The comparative scale of lesion conspicuity in 47 abdominal solid lesions was evaluated on a 5-point scale ranging from 0 (best) to -4 (markedly inferior).The image noise of virtual monochromatic 40-, 50 -, and 70-keV and iodine density images was significantly decreased by DLIR compared to hybrid IR (p 0.0001). The CNR was significantly higher in DLIR-H and DLIR-M than in hybrid IR (p 0.0001). The vessel conspicuity and overall image quality scores were also significantly greater in DLIR-H and DLIR-M than in hybrid IR (p 0.05). The lesion conspicuity scores for DLIR-M and DLIR-H were significantly higher than those for hybrid IR in the virtual monochromatic image of all energy levels (p ≤ 0.001).DLIR improves vessel conspicuity, CNR, and lesion conspicuity of virtual monochromatic and iodine density images in abdominal contrast-enhanced DECT, compared to hybrid IR.• Deep learning image reconstruction (DLIR) is useful for reducing image noise and improving the CNR of visual monochromatic 40-, 50-, and 70-keV images in dual-energy CT. • DLIR can improve lesion conspicuity of abdominal solid lesions on virtual monochromatic images compared to hybrid iterative reconstruction. • DLIR can also be applied to iodine density maps and significantly improves their image quality.

We retrospectively investigated the success rate of pulmonary arteriovenous separation in a single-phase computed tomography (CT) protocol using the estimated time of arrival (ETA) method. A total of 223 patients who underwent a single-phase CT protocol using the ETA method for pulmonary arteriovenous separation were included in the analysis. Dual source CT (SOMATOM Force, SIEMENS) was used for imaging. The tube voltage was 80 kVp, and the scan mode was turbo flash spiral mode. CT values of main pulmonary artery (MPA), peripheral pulmonary artery (pPA), peripheral pulmonary vein (pPV), left atrium (LA), ascending aorta (AAo) and descending aorta (DAo) were measured. When the difference in CT values on the central side was 100 Hounsfield unit (HU) or more, it was judged that the separation was successful. The mean CT values were 671.9±154 HU for MPA, 424.4±81.2 HU for LA, 551.1±142.6 HU for pPA, 351.6±94.0 HU for pPV, 362.2±75.8 HU for AAo, and 282.7±83.7 HU for DAo. The mean difference in CT values of the pulmonary artery and vein was 247.5±138.9 HU on the central side and 199.5±133.0 HU on the peripheral side. There were 90.1% of cases where the difference in CT values on the central side was 100 HU or more. In addition, a strong positive correlation (r=0.849, p

Whether inflammatory biomarkers including procalcitonin (PCT) and C-reactive protein (CRP) are useful for predicting prognosis in nursing and healthcare-associated pneumonia (NHCAP) is unknown. The aim of the present study was to investigate the utility of serial PCT and CRP measurements for predicting prognosis and treatment efficacy for hospitalized NHCAP patients.This prospective, observational, cohort study enrolled consecutive NHCAP patients hospitalized at Kurashiki Central Hospital from October 2010 to September 2017. PCT and CRP were measured twice, once on admission and again within 48-72 h after admission. The primary outcome was 30-day all-cause mortality, and the secondary outcome was initial treatment failure.A total of 299 patients were included. The 30-day mortality rate was 8.4% (25/299), and the initial treatment failure rate was 15.4% (46/299). On multivariate analysis, performance status [odds ratio (OR) (95% confidence interval (CI)): 2.25 (1.34-3.77), P = 0.002], temperature [OR (95%CI): 0.53 (0.32-0.88), P = 0.02], heart rate [OR (95%CI): 1.03 (1.01-1.06), P = 0.007], albumin [OR (95%CI): 0.42 (0.18-0.95), P = 0.04], and blood urea nitrogen [OR (95%CI): 1.02 (1.00-1.05), P = 0.04] were significant prognostic factors, and CRP D3 [OR (95%CI): 1.07 (1.02-1.11), P = 0.003] and PSI [OR (95%CI): 1.01 (1.00-1.02), P = 0.01] were the predictors of initial treatment failure. Consecutive measurements of PCT and CRP were not significant predictors of 30-day mortality.Inflammatory biomarkers including PCT and CRP were not useful for predicting prognosis and treatment efficacy in NHCAP patients. We should carefully evaluate the patients' vital signs and comorbidities when managing NHCAP patients.

Introduction Whether the sensitivity of the BinaxNOW Streptococcus pneumoniae urinary antigen test kit (BinaxNOW), adjusted by some variables including vital signs, laboratory examinations and pneumonia severity, has been decreasing is unknown. The aim of the present study was to investigate whether BinaxNOW sensitivity has decreased recently and to identify the predictors of the BinaxNOW result, including the time trend. Methods This prospective cohort study enrolled consecutive patients with pneumococcal community-acquired pneumonia who were hospitalised at Kurashiki Central Hospital from January 2001 to December 2015. Pneumococcal community-acquired pneumonia was defined as positive blood or pleural effusion or sputum culture results. To evaluate the effect of the time trend for the sensitivity of BinaxNOW, time series regression analysis was performed. In addition, predictors of the BinaxNOW result were examined by multivariable analysis using variables such as sex, vital signs, blood tests such as C-reactive protein, albumin, blood urea nitrogen, creatinine, white blood cell count, haematocrit and platelets, antibiotic pre-treatment, bacteraemia, and pneumonia severity, in addition to time trend and seasonality. Results A total of 446 patients were included. BinaxNOW sensitivity showed a significant, gradual decrease from 2001 (81.3%) to 2015 (48.7%). On multivariable analysis [odds ratio (95% confidence interval)], bacteraemia [2.516 (1.387–4.561), P = 0.002] was a predictor of a positive BinaxNOW result, whereas male sex [0.467 (0.296–0.736), P = 0.001], white blood cell count [0.959 (0.930–0.989), P = 0.008] and the time trend per year [0.900 (0.859–0.943), P

Background: Japan experienced a heavy rainfall event from June 28 to July 8, 2018, and many casualties were caused by both heavy rainfall and flooding. Few studies have investigated patients’ characteristics and causative pathogens of community-acquired pneumonia before and after heavy rainfall events. The aim of the present study was to evaluate the causative pathogens and clinical characteristics of hospitalised patients with community-acquired pneumonia before and after the heavy rainfall event using prospective cohort data.Methods: The study was divided into two periods: July to November 2013-2017 (pre heavy rainfall) and July to November 2018 (post heavy rainfall). The patients’ clinical characteristic and causative pathogens before and after the heavy rainfall were investigated. Regarding the causative pathogens, precipitation and seasonal patterns were adjusted.Results: There were no significant differences in the number and clinical characteristics of patients pre and post heavy rainfall. However, the frequency of Legionella pneumonia was significantly higher after than before the heavy rainfall event (8.9% vs 3.0%, P = 0.02) and remained significant after adjusting for precipitation and season. Three of 7 Legionella pneumonia patients engaged in reconstruction work and 2 Legionella pneumonia patients had soil exposure.Conclusions: An increased risk of Legionella pneumonia after not only rainfall and serious flooding, but also following recovery work or soil exposure should be considered. Trial registration: A prospective epidemiological study for patients with pneumonia in a single center in Japan, UMIN000004353. Registered 7 October 2010, https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000005195

To evaluate the usefulness of the deep learning image reconstruction (DLIR) to enhance the image quality of abdominal CT, compared to iterative reconstruction technique. Pre and post-contrast abdominal CT images in 50 patients were reconstructed with 2 different algorithms: hybrid iterative reconstruction (hybrid IR: ASiR-V 50%) and DLIR (TrueFidelity). Standard deviation of attenuation in normal liver parenchyma was measured as the image noise on pre and post-contrast CT. The contrast-to-noise ratio (CNR) for the aorta, and the signal-to-noise ratio (SNR) of the liver were calculated on post-contrast CT. The overall image quality was graded on a 5-point scale ranging from 1 (poor) to 5 (excellent). The image noise was significantly decreased by DLIR compared to hybrid-IR [hybrid IR, median 8.3 Hounsfield unit (HU) (interquartile range (IQR) 7.6–9.2 HU); DLIR, median 5.2 HU (IQR 4.6–5.8), P

Background: Previous studies reported that β-lactam and macrolide combination therapy significantly improved outcomes for patients with severe community-acquired pneumonia hospitalized in the intensive care unit (ICU) compared with a non-macrolide regimen. However, whether β-lactam and macrolide therapy truly reduces mortality is controversial, because no randomized, controlled trials have been conducted. The aim of the present study was to evaluate the usefulness of β-lactam and macrolide combination therapy for severe community-acquired pneumonia patients hospitalized in the ICU compared with a non-macrolide β-lactam-containing regimen.Methods: A prospective, observational, cohort study of hospitalized pneumonia patients was performed. Hospitalized severe community-acquired pneumonia patients admitted to the ICU within 24 hours between October 2010 and October 2017 were included for analysis. The primary outcome was 30-day mortality, and secondary outcomes were 14-day mortality and ICU mortality. Inverse probability of treatment weighting analysis as a propensity score analysis was used to reduce biases, including six covariates: age, sex, C-reactive protein, albumin, Pneumonia Severity Index score, and APACHE II score.Results: A total of 78 patients were included. There were 48 patients in the non-macrolide-containing β-lactam therapy group, including β-lactam monotherapy and β-lactam and non-macrolide-containing combination therapy, and 30 patients in the macrolide combination therapy group. β-lactam and macrolide combination therapy significantly decreased 30-day mortality (16.7% vs. 43.8%; P=0.015) and 14-day mortality (6.7% vs. 31.3%; P=0.020), but not ICU mortality (10% vs 27.1%, P=0.08) compared with non-macrolide-containing β-lactam therapy. After adjusting by inverse probability of treatment weighting, macrolide combination therapy also decreased 30-day mortality (odds ratio, 0.29; 95%CI, 0.09-0.96; P=0.04) and 14-day mortality (odds ratio, 0.19; 95%CI, 0.04-0.92; P=0.04), but not ICU mortality (odds ratio, 0.34; 95%CI, 0.08-1.36; P=0.13).Conclusions: Combination therapy with β-lactam and macrolides significantly improved the prognosis of severe community-acquired pneumonia patients hospitalized in the ICU compared with a non-macrolide-containing β-lactam regimen on propensity score analysis.Trial registration: UMIN Clinical Trials Registry, UMIN000004353. Registered on 7 October 2010

Introduction and Objectives: Disease Probability Measure (DPM) is a useful image assessment tool for gas-trapping and emphysema using inspiratory and expiratory computed tomography (CT) data for chronic obstructive pulmonary disease (COPD). We hypothesized that the cluster analysis using DPM parameters could help to understand the relationship between the pathological changes of the lungs and other parameters in COPD. Methods: A total of 131 COPD patients were enrolled. Forced oscillation technique (FOT), spirometry and inspiratory and expiratory CT scans were conducted. Using CT data, the percentage of low attenuation voxels (LAV%) and the square root of airway wall area of the hypothetical airway with an internal perimeter of 10 mm (√Aaw at Pi10) were quantitatively evaluated. DPM analysis was performed and hierarchical cluster analysis was applied. The COPD patients were classified into five imaging clusters using DPM parameters; DPMNormal, DPMGasTrap and DPMEmphy. The clusters were named as follows; Normal (NL), Normal-GasTrap (NL-GT), GasTrap (GT), GasTrap-Emphysema (GT-EM) and Emphysema (EM). Results: FEV1%predicted and respiratory reactance at 5Hz (X5) were gradually decreased in the order of the NL, NL-GT, GT, GT-EM, and EM. LAV% was significantly higher in the GT-EM than in the NL, NL-GT and GT. LAV% was also significantly higher in the EM than in the GT-EM. Four clusters other than the NL showed significantly higher values of √Aaw at Pi10 than the NL cluster but there were no significant differences among the four clusters. Conclusions: The five DPM clusters could reflect the pathophysiological changes in COPD.

This paper examines the employment impact of British Columbia's revenue-neutral carbon tax implemented in 2008. While all industries appear to benefit from the redistributed tax revenues, the most carbon-intensive and trade-sensitive industries see employment fall with the tax, while clean service industries see employment rise. By aggregating across industries I find the BC carbon tax generated, on average, a small but statistically significant 0.74 percent annual increases in employment over the 2007–2013 period. This paper provides initial evidence showing how a revenue-neutral carbon tax may not adversely affect employment.

Whether macrolide combination therapy reduces the mortality of patients with severe community-acquired pneumonia (CAP) hospitalized in the non-intensive care unit (ICU) remains unclear. Therefore, we investigated the efficacy of adding azithromycin to β-lactam antibiotics for such patients. This prospective cohort study enrolled consecutive patients with CAP hospitalized in the non-ICU between October 2010 and November 2016. The 30-day mortality between β-lactam and azithromycin combination therapy and β-lactam monotherapy was compared in patients classified as mild to moderate and severe according to the CURB-65, Pneumonia Severity Index (PSI), and Infectious Diseases Society of America (IDSA)/American Thoracic Society (ATS) criteria. Inverse probability of treatment weighting (IPTW) analysis was used to reduce biases. Based on the CURB-65 and PSI, combination therapy did not significantly reduce the 30-day mortality in either group (179 patients in the combination group, 952 in the monotherapy group). However, based on the IDSA/ATS criteria, combination therapy significantly reduced the 30-day mortality in patients with severe (odds ratio [OR] 0.12, 95% confidence interval [CI] 0.007–0.57), but not non-severe pneumonia (OR 1.85, 95% CI 0.51–5.40); these results were similar after IPTW analysis. Azithromycin combination therapy significantly reduced the mortality of patients with severe CAP who met the IDSA/ATS criteria.

The usefulness of existing pneumonia severity indices for predicting mortality in nursing and healthcare-associated pneumonia (NHCAP) is unclear. This study compared the usefulness of existing pneumonia severity indices for predicting mortality in NHCAP and community-acquired pneumonia (CAP). Consecutive hospitalized pneumonia patients including NHCAP and CAP patients were prospectively enrolled between October 2010 and November 2017. Admission pneumonia severity was assessed using CURB-65, Pneumonia Severity Index (PSI), A-DROP, Infectious Diseases Society of America (IDSA)/American Thoracic Society (ATS) severe pneumonia criteria, and I-ROAD. The primary outcome was 30-day mortality. The discriminatory ability of each severity index was evaluated by receiver operating characteristic curve analysis. Overall, 828 patients had NHCAP, and 1330 patients had CAP. Thirty-day mortality was 12.8% and 5.6% in NHCAP and CAP patients, respectively. The area under the curve of PSI (0.717, 95% confidence interval 0.673–0.761) was the highest among all pneumonia severity indices, with significant differences compared with CURB-65 (0.651, 95% confidence interval 0.598–0.705, P = 0.02) and IDSA/ATS severe pneumonia criteria (0.659, 95% confidence interval 0.612–0.707, P = 0.03). The predictive abilities for 30-day mortality of the pneumonia severity indices, excluding PSI and I-ROAD, were significantly inferior for NHCAP than for CAP. PSI may be the most useful pneumonia severity score for predicting mortality in NHCAP. However, the predictive ability for mortality of each pneumonia severity score was worse for NHCAP than for CAP; therefore, the prognostic factors in NHCAP need to be identified for better management of NHCAP patients.

The aim of the present study was to investigate the predictors of targeted therapy (TT) for pneumococcal community-acquired pneumonia (PCAP) with a positive urinary antigen test (UAT) and compare the outcomes with those of nontargeted therapy. This prospective cohort study enrolled consecutive PCAP patients with a positive UAT who were hospitalized at Kurashiki Central Hospital from October 2010 to November 2019. A total of 286 patients were included. Of them, 56 patients (19.6%) were included in the TT group. On multivariate analysis, identification of Gram-positive diplococci by Gram stain (OR [95% CI]: 2.46 [1.32-4.63]) was a positive predictor, whereas aspiration pneumonia (0.17 [0.03-0.59]) and CURB-65 score (0.59 [0.42-0.81]) were negative predictors of TT. Initial treatment failure and 30-day mortality were not significantly different. The UAT is not used enough for TT, and TT for PCAP did not have worse outcomes.

This study aimed to investigate the usefulness of procalcitonin-guided therapy in hospitalized community-acquired pneumonia patients to reduce antibiotic duration and costs without worsening prognosis.352 hospitalized community-acquired pneumonia patients in an observational cohort study in which procalcitonin was measured three times serially, on admission (Day 1) and 2-3 days (Day 3) and 6-8 days (Day 7) after admission, between October 2010 and February 2016 were reviewed retrospectively. Antibiotics could be stopped if Day 7 procalcitonin was0.25 ng mLUsing theoretical procalcitonin guidance, antibiotic duration could be reduced from 12.6 to 8.6 days (P 0.001), while costs could be reduced from 45,833 to 38,952 yen (P = 0.005). Among the patients in whom theoretical procalcitonin guidance could be adopted, recurrence rates (5.6% vs. 8.1%, P = 0.15) and mortality rates (0% vs. 5.1%, P = 0.07) did not worsen between the group having the same antibiotic durations as with theoretical procalcitonin guidance in actual practice (N = 71) and the group having durations more than 2 days longer in actual practice than in theoretical procalcitonin guidance (N = 198). There was no significant difference in pneumonia severity using A-DROP, CURB-65, and PSI between two groups.Procalcitonin-guided therapy may be useful in hospitalized community-acquired pneumonia patients to reduce antibiotic duration and costs without worsening the prognosis.

This study investigated the pore distributions in water-saturated Ca-montmorillonite using 1H nuclear magnetic resonance (NMR) measurements for various dry densities (0.8–1.6 g/cm 3 ) and porewater salinity conditions (deionized water, 0.1 and 1 M CaCl2) at a temperature range of 233–303 K. The volume fractions of the interlayer pore and the non-interlayer pore in the compacted Ca-montmorillonite were quantified by NMR relaxometry. At a lower Ca-montmorillonite density (0.8 g/cm 3 ), the volume fraction of the 3-HL-dominated interlayer pore was close to 20%, while that of the non-interlayer pore was higher ( > 80%) than that in Na-montmorillonite. For the higher density (1.4 g/cm 3 ), the volume fraction of the interlayer pore in both Ca- and Na-montmorillonite seemed to be more than 90% close to the total porosity. This comparison showed that the main factor affecting the pore distribution in the compacted Ca- and Na-montmorillonite is density. Meanwhile, the effect of the porewater salinity is relatively smaller. The effect of the interlayer cations is also relatively smaller at the higher density. The established method based on NMR relaxometry is expected to provide structural parameters for a realistic modeling of mass transport in water-saturated compacted clay.

Background Empyema is an important and serious disease with high morbidity and mortality worldwide. However, the bacteriology and prognostic factors of empyema remain poorly understood, and data on the relationships among these parameters are scant. Methods We retrospectively analyzed a prospectively collected database of patients with empyema admitted to Kurashiki Central Hospital, Japan, between May 2007 and September 2015. Only patients who had positive results on pleural fluid bacterial culture were included. We collected patient characteristics, bacteriology findings, treatments, and outcomes, and we assessed the prognostic factors for in-hospital mortality. Results We included 71 patients in this study. The most commonly isolated bacteria were members of the Streptococcus anginosus group (37%), followed by anaerobes (30%). In-hospital mortality was 11%. On multivariate analysis, polymicrobial empyema (odds ratio [OR], 8.25; 95% confidence interval [CI], 1.08–62.90) and RAPID (renal, age, purulence, infection source, and dietary factors) score (OR, 6.89; 95% CI, 1.73–27.40) were significant risk factors for in-hospital mortality. The most common etiology of polymicrobial empyema was a combination of the members of the S. anginosus group and anaerobes, but no relationship was observed between the combination of microorganisms and outcomes. Although no significant difference was observed in treatment between the survivor and non-survivor groups, all patients who underwent surgery survived. Conclusions Members of the S. anginosus group and anaerobes were frequent pathogens in empyema, and polymicrobial etiology was independently associated with mortality in addition to the RAPID score. Surgery may be one option for preventing mortality.

Disorders of the fractality of an airway tree and a vessel tree have been studied in pulmonary diseases. Here we successfully applied Mishima's D to the bronchial minimal inner cross-sectional area (iCSA) measured in multidetector computed tomography (MDCT) images of chronic obstructive pulmonary disease (COPD) and non-COPD smokers (n = 162), by defining D in the following formula: logN(≥X) = -D × logX + c, where X is a certain iCSA value, N(≥X) is the number of airway branches having iCSA greater than or equal to X, and c is a constant. Mathematically, this D of iCSA was associated with the expected reduction ratio of iCSA at bifurcations, which can be estimated by 2-1/D. This D of iCSA also correlated weakly with the box-counting fractal dimension and Weibel's reduction ratio over airway generations, which indicated that the airway tree was not a perfect fractal object and that the branch bifurcation was asymmetric. The D of iCSA showed positive correlations with lung function measurements of airflow limitation in study participants. In addition, D of iCSA representing the periphery showed an association with future body mass index reduction, most likely as an indicator of energy efficacy for breathing as predicted by Hess-Murray's law. D of iCSA may be helpful to understanding the pathogenesis of obstructive lung diseases.NEW & NOTEWORTHY An airway tree is a fractal object. We showed that the distribution of minimal inner cross-sectional area (iCSA) of airway branches can be expressed by a fractal index, D, of minimal iCSA. This D was correlated with airflow limitation and future body mass index reduction in chronic obstructive pulmonary disease patients, as predicted by Hess-Murray's law.

The restlessness of young children often causes motion artifacts on CT images. We devised a new animation projector system (CT Theater) that enables a child to view an animation during a pediatric head CT examination. The purpose of this study is to assess the usefulness on a children of a video viewed during a head CT scan. Children of 3-10 years old who underwent head CT (SOMATOM Definition Flash, SOMATOM Force; Siemens) were analyzed for a period from 6 months before, to 6 months after, introduction of the projector system (before: n=46, after: n=29). Mobile projector (MP-CL1; Sony) connected with tablet device (iPad; Apple) was put on the CT table near the child's head. An animation was projected on the child's line of sight inside the gantry. The animation is projected on the line of sight of the child such that the projector moves with the child on the table. The number of requests for use made by children was 28/29 (96.6%). The presence of images without motion artifacts decreased significantly after introduction (before/after introduction: 84.8% vs 100%, p=0.03). The overall examination success rate tended to increase after introduction (84.8% vs 92.9%, p=0.26). The overall examination time was significantly reduced (92.4±42.4 s vs 65.1±47.3 s, p

Recent studies have suggested a possible involvement of abnormal tau in some retinal degenerative diseases. The common view in these studies is that these retinal diseases share the mechanism of tau-mediated degenerative diseases in brain and that information about these brain diseases may be directly applied to explain these retinal diseases. Here we collectively examine this view by revealing three basic characteristics of tau in the rod outer segment (ROS) of bovine retinal photoreceptors, i.e., its isoforms, its phosphorylation mode and its interaction with microtubules, and by comparing them with those of brain tau. We find that ROS contains at least four isoforms: three are identical to those in brain and one is unique in ROS. All ROS isoforms, like brain isoforms, are modified with multiple phosphate molecules; however, ROS isoforms show their own specific phosphorylation pattern, and these phosphorylation patterns appear not to be identical to those of brain tau. Interestingly, some ROS isoforms, under the normal conditions, are phosphorylated at the sites identical to those in Alzheimer's patient isoforms. Surprisingly, a large portion of ROS isoforms tightly associates with a membranous component(s) other than microtubules, and this association is independent of their phosphorylation states. These observations strongly suggest that tau plays various roles in ROS and that some of these functions may not be comparable to those of brain tau. We believe that knowledge about tau in the entire retinal network and/or its individual cells are also essential for elucidation of tau-mediated retinal diseases, if any.

Extracorporeal membrane oxygenation (ECMO) is widely used for circulatory support in pediatric cardiac patients with low cardiac output and hypoxemia. We retrospectively evaluated the efficacy of ECMO support for respiratory and heart failure in infants and children. From April 2002 to February 2011, 14 patients aged 19 days to 20 years old (average 44 months), with body weight 2.6 kg to 71 kg (median 14.1 kg), underwent ECMO support for failing cardiac function, hypoxemia, and low cardiac output syndrome. In 12 patients, ECMO was introduced after operation for congenital heart disease (four with complete repair including Fontan circulation, and eight with palliative repair). In one patient, ECMO was introduced after partial pulmonary resection for congenital cystic adenomatoid malformation because of respiratory failure. ECMO was introduced in a patient with severe heart failure caused by fulminant myocarditis. Patients' demographics, duration of extracorporeal membrane oxygenation, additional support, and outcomes were analyzed. Ten patients (71%) were successfully weaned from ECMO, and eight patients (57%) were discharged from the hospital. The mean duration of ECMO support was 332 h (range 11-2030 h). Although management of the ECMO circuit, including anticoagulation (activated clotting time: 150-250), was conducted following the institutional practice guidelines, it was difficult to control the bleeding. Seven patients required renal replacement therapy during ECMO support using peritoneal dialysis or continuous hemodiafiltration. Five patients had additional operative procedures: systemic-pulmonary shunt in two, bidirectional Glenn takedown with right modified Blalock-Taussig shunt, total cavopulmonary connection takedown, and redo ECMO in one patient each. The patient who had the longest ECMO support for respiratory failure due to acute respiratory distress syndrome after lung surgery was successfully weaned from ECMO because high-frequency oscillation (HFO) improved respiratory function. ECMO for heart and respiratory failure in infants and children is effective and allows time for recovery of cardiac dysfunction and acute hypoxic insult. The long-term ECMO support for over 2000 h was very rare, but it was possible to wean this patient from ECMO using HFO.

The effect of cabin pressure change on the respiratory system during flight is well documented in the literature, but how the change in atmospheric pressure affects ventricular assist device (VAD) output flow has not been studied yet. The purpose of our study was to evaluate the change in VAD output using a mock circulatory system in a low-pressure chamber mimicking high altitude. Changes in output and driving pressure were measured during decompression from 1.0 to 0.7 atm and pressurization from 0.7 to 1.0 atm. Two driving systems were evaluated: the VCT system and the Mobart system. In the VCT system, output and driving pressure remained the same during decompression and pressurization. In the Mobart system, the output decreased as the atmospheric pressure dropped and recovered during pressurization. The lowest output was observed at 0.7 atm, which was 80% of the baseline driven by the Mobart system. Under a practical cabin pressure of 0.8 atm, the output driven by the Mobart system was 90% of the baseline. In the Mobart system, the output decreased as the atmospheric pressure dropped, and recovered during pressurization. However, the decrease in output was slight. In an environment where the atmospheric pressure changes, it is necessary to monitor the diaphragmatic motion of the blood pump and the driving air pressure, and to adjust the systolic:diastolic ratio as well as the positive and negative pressures in a VAD system.

Retinal photoreceptor phosphodiesterase (PDE6), a key enzyme for phototransduction, consists of a catalytic subunit complex (Pαβ) and two inhibitory subunits (Pγs). Pαβ has two noncatalytic cGMP-binding sites. Here, using bovine PDE preparations, we show the role of these cGMP-binding sites in PDE regulation. Pαβγγ and its transducin-activated form, Pαβγ, contain two and one cGMP, respectively. Only Pαβγ shows [3H]cGMP binding with a Kd∼ 50 nm and Pγ inhibits the [3H]cGMP binding. Binding of cGMP to Pαβγ is suppressed during its formation, implying that cGMP binding is not involved in Pαβγγ activation. Once bound to Pαβγ, [3H]cGMP is not dissociated even in the presence of a 1000-fold excess of unlabeled cGMP, binding of cGMP changes the apparent Stokes’ radius of Pαβγ, and the amount of [3H]cGMP-bound Pαβγ trapped by a filter is spontaneously increased during its incubation. These results suggest that Pαβγ slowly changes its conformation after cGMP binding, i.e. after formation of Pαβγ containing two cGMPs. Binding of Pγ greatly shortens the time to detect the increase in the filter-trapped level of [3H]cGMP-bound Pαβγ, but alters neither the level nor its Stokes’ radius. These results suggest that Pγ accelerates the conformational change, but does not add another change. These observations are consistent with the view that Pαβγ changes its conformation during its deactivation and that the binding of cGMP and Pγ is crucial for this change. These observations also imply that Pαβγγ changes its conformation during its activation and that release of Pγ and cGMP is essential for this change. Structured digital abstract • PDE6 alpha , PDE6 beta and PDE6 gamma physically interact by molecular sieving (View interaction)

The psychological effects of surgery have received little attention in patients with lung cancer, so it is unclear how much psychological support is required by these patients. This study was done to assess the mental state of patients with lung cancer before and after surgery and to determine their need for psychological care.A group of 165 patients with lung cancer scheduled for surgical treatment were included in this study. They were asked to complete the Profile of Mood States questionnaire before surgery and on discharge after completion of treatment. The data on mood from the questionnaires were analyzed.Tension-anxiety improved significantly after surgery, whereas the fatigue score increased significantly. The scores for depression-dejection and confusion were elevated before surgery and were unchanged afterward.Patients with lung cancer were depressed before surgery and remained depressed after their operations, although postoperative tension-anxiety diminished. These results indicate that lung cancer patients need psychological support to alleviate depression during the perioperative period.

Background: This study endeavored to clarify the location, frequency, and prognostic value of metastatic lymph nodes in the mediastinum among patients with left upper lung cancer who underwent complete dissection of the superior mediastinal lymph node through a median sternotomy. Methods: Forty-four patients with left upper lobe cancer underwent extended radical mediastinal nodal dissection (ERD), all of whom were analyzed in this retrospective study. The group comprised 12 females and 32 males, with ages ranging from 28 to 70 years (median age, 60 years). Mediastinal nodal status was assessed according to the systems of Mountain/Dresler 7 and Naruke 8. The clinicopathological records of each patient were examined for prognostic factors, including age, sex, histology, tumor size, c-N number, preoperative serum CEA level, metastatic stations and distribution of metastatic nodes according to Naruke’s system 8. The superior mediastinal lymph nodes which cannotbedissectedthrougha leftthoracotomy(bilateral#1and#2,#3,right#3a,andright#4accordingtoNaruke’smap8 weredefinedasextrasuperior mediastinal nodes for left lung cancer (ESMD). Results: Fourteen patients had one or more metastases to mediastinal lymph nodes, among whom the most common metastatic station was the aortic nodes: 71.4% had metastasis to #5 or #6 (57.1% to #5 and 50% to #6). The next mostcommonmetastatic station wasthe left tracheobronchialnodes (42.8%).Metastasis to the ESMDoccurredin 7 of the 44study subjects (16%), representing a 50% rate of occurrence (7/14) among those with mediastinal nodal involvement. Univariate analysis found that CN factor and aortic nodal involvement (#5, #6) were significant predictive factors for ESMD metastasis. Multivariate analysis determined that only aortic nodal involvement was significant (p = 0.008). Furthermore, ESMD metastasis was rare (5.8%) in the absence of aortic node metastasis. The overall survival rate at 5 years was 50% among the patients without ESMD metastasis. However, the survival rate was 32% at 3 years and 0% at 5 years among the seven patients with ESMD metastasis. Conclusions: The aortic lymph node is the most common site of metastasis from left upper lobe cancer. Multivariate analysis demonstrated that aortic nodal involvement was a significant predictive factor for ESMD metastasis. Based upon the rates of metastasis and the post-operative prognosis in our study patients, dissection of aortic nodes and left tracheobronchial nodes may be important for patients with left upper lobe cancer. Whether ESMD dissection has a beneficial effect on prognosis remains controversial.

We have recently shown that activation of retinal guanylate cyclase (retGC) by GC-activating proteins (GCAPs) is much stronger than that previously reported and that preincubation of photoreceptor outer segment homogenates with ATP or its analogue, adenylyl imidodiphosphate (AMP-PNP), is required for the strong activation [Yamazaki, A., Yu, H., Yamazaki, M., Honkawa, H., Matsuura, I., Usukura, J., and Yamazaki, R. K. (2003) J. Biol. Chem. 278, 33150-33160]. Here we show that illuminated rhodopsin is essential for development of the AMP-PNP incubation effect. This was demonstrated by illumination of dark homogenates and treatments of illuminated homogenates with 11-cis-retinal and hydroxylamine prior to the AMP-PNP incubation and by measurement of the GCAP2 concentration required for 50% activation. We also found that the AMP-PNP incubation effect was not altered by addition of guanosine 5'-O-(3-thiotriphosphate), indicating that transducin activation is not required. It is concluded that illuminated rhodopsin is involved in retGC activation in two ways: to initiate the ATP incubation effect for preparation of retGC activation as shown here and to reduce the Ca 2+ concentrations through cGMP phosphodiesterase activation as already known. These two signal pathways may be activated in a parallel and perhaps proportional manner and finally converge for strong activation of retGC by Ca 2+ -free GCAPs.

ATP bound to retinal guanylate cyclase (retGC)/membranes prior to the assay (pre-binding effect) and during the assay (direct effect) further enhances retGC activity stimulated by GC-activating proteins (GCAPs). Here we investigate differences between these two effects. We found that the pre-binding effect, but not the direct effect, was absent in membranes pre-washed with Mg(2+)-free hypotonic buffers, that the pre-binding effect, but not the direct effect, was strictly limited to GCAP-stimulated retGC activity, and that these two effects were independent and additive rather than being synergistic. Pre-incubation with amiloride enhanced GCAP2-activated retGC activity in a manner similar to that by ATP pre-binding; however, amiloride did not directly stimulate the retGC activity. These results indicate that these two effects are mechanistically different. Levels of retGC activation by these effects and conditions required for these effects indicate that only the mechanism involving ATP pre-binding is physiologically relevant to retGC activation.

Background: Right upper lobectomy with right cervical and bilateral mediastinal lymph node dissection via a median approach was performed for non-small cell lung cancer. Methods: From 1995 to 2003, 48 patients aged ≤ 70 years underwent resection of cancer in the right upper lobe, including 26 with N0, four with N1 and 18 with N2 disease. Results: Metastases to the right cervical, highest mediastinal, pretracheal and bilateral tracheobronchial lymph nodes were frequent. There were no operative or hospital deaths. Preoperative accuracy of N-factor diagnosis was only 35.4%. The overall 5-year survival rate was 58.8%. The rate for C-N2 disease (n = 18) was 42.6%, and the rate for p-N2 disease (n = 7) and p-N3 disease (n = 13) was 57.1% and 0%, respectively, using the Kaplan−Meier method. Conclusions: Patients without N3 disease have a good prognosis, and extended and systematic radical lymphadenectomy via median sternotomy improves the staging, and possibly the prognosis of pure N2 disease.

Objective: We worked to devise a new way to prevent postoperative persistent air leaks in high-risk pulmonary surgery patients. Methods: From November 1993 to June 2002, 60 patients with difficult to control intraoperative pulmonary air leakage were treated using bioabsorbable polyglycolide felt patches soaked in fibrin glue to cover the leakage site. Results: After application, the felt patch adhered tightly to the lung surface without peeling off, enabling good leakage closure with only 2 ml of fibrin glue used. Air leakage was controlled successfully in 52 (86.7%) of the 60. Four of the 8 patients in whom this method failed to stop air leakage also developed mild pyothorax, with 2 requiring a second operation by video-assisted thoracic surgery. Leakage was eventually controlled in all patients, with no postoperative deaths relating to air leakage. Conclusions: Fibrin-glue-soaked bioabsorbable felt patches effectively seal intraoperative intractable air leaks. Felt patch use may increase the risk of postoperative infection. It should be considered for use on patients with fistulas that cannot be controlled by direct closure or otherwise intraoperatively and who may potentially develop uncontrollable air leakage postoperatively.

Retinal cGMP phosphodiesterase (PDE6) is a key enzyme in vertebrate phototransduction. Rod PDE contains two homologous catalytic subunits (Pαβ) and two identical regulatory subunits (Pγ). Biochemical studies have shown that amphibian Pαβ has high affinity, cGMP-specific, non-catalytic binding sites and that Pγ stimulates cGMP binding to these sites. Here we show by molecular cloning that each catalytic subunit in amphibian PDE, as in its mammalian counterpart, contains two homologous tandem GAF domains in its N-terminal region. In Pγ-depleted membrane-bound PDE (20–40% Pγ still present), a single type of cGMP-binding site with a relatively low affinity (K d ∼ 100 nm) was observed, and addition of Pγ increased both the affinity for cGMP and the level of cGMP binding. We also show that mutations of amino acid residues in four different sites in Pγ reduced its ability to stimulate cGMP binding. Among these, the site involved in Pγ phosphorylation by Cdk5 (positions 20–23) had the largest effect on cGMP binding. However, except for the C terminus, these sites were not involved in Pγ inhibition of the cGMP hydrolytic activity of Pαβ. In addition, the Pγ concentration required for 50% stimulation of cGMP binding was much greater than that required for 50% inhibition of cGMP hydrolysis. These results suggest that the Pαβ heterodimer contains two spatially and functionally distinct types of Pγ-binding sites: one for inhibition of cGMP hydrolytic activity and the second for activation of cGMP binding to GAF domains. We propose a model for the Pαβ-Pγ interaction in which Pγ, by binding to one of the two sites in Pαβ, may preferentially act either as an inhibitor of catalytic activity or as an activator of cGMP binding to GAF domains in frog PDE.