The rapid reduction in the cost of renewable energy has motivated the transition from carbon-intensive chemical manufacturing to renewable, electrified, and decarbonized technologies. Although ...electrified chemical manufacturing technologies differ greatly, the feasibility of each electrified approach is largely related to the energy efficiency and capital cost of the system. Here, we examine the feasibility of ammonia production systems driven by wind and photovoltaic energy. We identify the optimal regions where wind and photovoltaic electricity production may be able to meet the local demand for ammonia-based fertilizers and set technology targets for electrified ammonia production. To compete with the methane-fed Haber–Bosch process, electrified ammonia production must reach energy efficiencies of above 20% for high natural gas prices and 70% for low natural gas prices. To account for growing concerns regarding access to water, geospatial optimization considers water stress caused by new ammonia facilities, and recommendations ensure that the identified regions do not experience an increase in water stress. Reducing water stress by 99% increases costs by only 1.4%. Furthermore, a movement toward a more decentralized ammonia supply chain driven by wind and photovoltaic electricity can reduce the transportation distance for ammonia by up to 76% while increasing production costs by 18%.
Sarcoidosis is a multisystem chronic inflammatory disease of unknown etiology, characterized by non-caseating granulomas. Sarcoidosis has the potential to involve every tissue in the body, which ...mainly affect the lymphatic system and lungs; gastrointestinal system, and particularly the colon, is an extremely rare location. We report the case of a 64-year-old male with history of pulmonary and cutaneous sarcoidosis diagnosed with neoplasm in the hepatic flexure of the colon and a polyp with high-grade dysplasia in the transverse colon by colonoscopy after a positive fecal occult blood test. The case was presented to a multidisciplinary committee and it was decided to perform a total laparoscopic colectomy and ileorectal anastomosis with histopathological evidence of infiltrating adenocarcinoma and intestinal sarcoidosis with non-caseating granulomas in the appendix, terminal ileum, colon and locoregional lymph nodes. The relationship between colon cancer and sarcoidosis is controversial, with studies showing a possible increased risk of cancer in patients with sarcoidosis, relating it to the chronic proinflammatory state of the disease. In these cases, lymph node involvement is especially important when assessing tumor extension studies, and may lead to changes in staging and, as a consequence, in the therapeutic approach.
This paper analyzes the influence of large bank shareholders on the terms of bank loans for a sample of 12,045 loans to 3,290 borrowers from 45 countries over the period 2004–2013. We investigate the ...effects of bank control over bank loan terms during the global financial crisis, regardless of whether the bank shareholder is a lender or not. In line with a monitoring effect, the results suggest that firms with bank shareholders that are non‐lenders borrowed at lower interest rates and longer maturities during the period of crisis. However, borrowers paid higher spreads and were offered shorter maturities when they borrowed from banks that are also shareholders. This effect is consistent with banks obtaining private benefits as large shareholders as a consequence of the informational hold‐up problems affecting borrowers.
Sarcopenia and sarcopenic obesity have been associated with poor outcomes in unresectable pancreatic cancer (PC). Neoadjuvant treatment (NT) is used increasingly to improve resectability; however, ...its effects on fat and muscle body composition have not been characterized.
To evaluate whether NT affects muscle mass and adipose tissue in patients with borderline resectable PC (BRPC) and locally advanced PC (LAPC) and determine whether there were potential differences between patients who ultimately underwent resection and those who did not.
In this retrospective cohort study conducted at 4 academic medical centers, 193 patients with BRPC and LAPC undergoing surgical exploration after NT who had available computed tomographic scans (both at diagnosis and preoperatively) and confirmed pancreatic ductal adenocarcinoma were evaluated. The study was conducted from January 2013 to December 2015. Data analysis was performed from September 2016 to May 2017. Measurement of body compartments was evaluated with volume assessment software before and after NT. A radiologist blinded to the patient outcome assessed the areas of skeletal muscle, total adipose tissue, and visceral adipose tissue through a standardized protocol.
Receipt of NT.
Achievement of pancreatic resection at surgical exploration after the receipt of NT.
Of the 193 patients with complete radiologic imaging available after NT, 96 (49.7%) were women; mean (SD) age at diagnosis was 64 (11) years. Most patients received combined therapy with fluorouracil, irinotecan, oxaliplatin, leucovorin, and folic acid (124 64.2%) and 86 (44.6%) received chemoradiotherapy as well. The median interval between pre-NT and post-NT imaging was 6 months (interquartile range IQR, 4-7 months). All body compartments significantly changed. The adipose compound decreased (median total adipose tissue area from 284.0 cm2; IQR, 171.0-414.0 to 250.0 cm2; IQR, 139.0-363.0; P < .001; median visceral adipose tissue area from 115.2 cm2; IQR, 59.9-191.0 to 97.7 cm2; IQR, 48.0-149.0 cm2; P < .001), whereas the lean mass slightly improved (median skeletal muscle from 122.1 cm2; IQR, 99.3-142.0 to 123 cm2; IQR 104.8-152.5 cm2; P = .001). Surgical resection was achievable in 136 (70.5%) patients. Patients who underwent resection had experienced a 5.9% skeletal muscle area increase during NT treatment, whereas those who did not undergo resection had a 1.7% decrease (P < .001).
Patients with PC experience a significant loss of adipose tissue during neoadjuvant chemotherapy, but no muscle wasting. An increase in muscle tissue during NT is associated with resectability.
Positive allosteric modulation of α7 isoform of nicotinic acetylcholine receptors (α7‐nAChRs) is emerging as a promising therapeutic approach for central nervous system disorders such as ...schizophrenia or Alzheimer's disease. However, its effect on Ca2+ signaling and cell viability remains controversial. This study focuses on how the type II positive allosteric modulator (PAM II) PNU120596 affects intracellular Ca2+ signaling and cell viability. We used human SH‐SY5Y neuroblastoma cells overexpressing α7‐nAChRs (α7‐SH) and their control (C‐SH). We monitored cytoplasmic and endoplasmic reticulum (ER) Ca2+ with Fura‐2 and the genetically encoded cameleon targeting the ER, respectively. Nicotinic inward currents were measured using patch‐clamp techniques. Viability was assessed using methylthiazolyl blue tetrazolium bromide or propidium iodide staining. We observed that in the presence of a nicotinic agonist, PNU120596 (i) reduced viability of α7‐SH but not of C‐SH cells; (ii) significantly increased inward nicotinic currents and cytosolic Ca2+ concentration; (iii) released Ca2+ from the ER by a Ca2+‐induced Ca2+ release mechanism only in α7‐SH cells; (iv) was cytotoxic in rat organotypic hippocampal slice cultures; and, lastly, all these effects were prevented by selective blockade of α7‐nAChRs, ryanodine receptors, or IP3 receptors. In conclusion, positive allosteric modulation of α7‐nAChRs with the PAM II PNU120596 can lead to dysregulation of ER Ca2+, overloading of intracellular Ca2+, and neuronal cell death.
This study focuses on how the type II positive allosteric modulator PNU120596 (PAM II PNU12) affects intracellular Ca2+ signaling and cell viability. Using SH‐SY5Y neuroblastoma cells overexpressing α7‐nAChRs (α7‐SH) and their control (C‐SH), we find that PAM of α7‐nAChRs with PNU120596: (i) increases inward calcium current (ICa) and cytosolic Ca2+ concentration (Ca2+cyt); (ii) releases Ca2+ from the ER (Ca2+ER) by a Ca2+‐induced Ca2+ release mechanism; and (iv) reduces cell viability. These findings were corroborated in rat hippocampal organotypic cultures. Ca2+cyt, cytosolic Ca2+ concentration; Ca2+ER, endoplasmic reticulum Ca2+ concentration; α7 nAChR, α7 isoform of nicotinic acetylcholine receptors; α7‐SH, SH‐SY5Y stably overexpressing α7 nAChRs cells; C‐SH, control SH‐SY5Y cells; Nic, nicotine; PNU12, PNU120596.
This study focuses on how the type II positive allosteric modulator PNU120596 (PAM II PNU12) affects intracellular Ca2+ signaling and cell viability. Using SH‐SY5Y neuroblastoma cells overexpressing α7‐nAChRs (α7‐SH) and their control (C‐SH), we find that PAM of α7‐nAChRs with PNU120596: (i) increases inward calcium current (ICa) and cytosolic Ca2+ concentration (Ca2+cyt); (ii) releases Ca2+ from the ER (Ca2+ER) by a Ca2+‐induced Ca2+ release mechanism; and (iv) reduces cell viability. These findings were corroborated in rat hippocampal organotypic cultures. Ca2+cyt, cytosolic Ca2+ concentration; Ca2+ER, endoplasmic reticulum Ca2+ concentration; α7 nAChR, α7 isoform of nicotinic acetylcholine receptors; α7‐SH, SH‐SY5Y stably overexpressing α7 nAChRs cells; C‐SH, control SH‐SY5Y cells; Nic, nicotine; PNU12, PNU120596.
Background
Metabolic syndrome (MetS) is a constellation of risk factors increasingly present in the world’s population. People with this syndrome are at an increased risk of cardiovascular disease ...and type 2 diabetes mellitus. Moreover, evidence has shown that it affects different organs. MetS and its risk factors are independently associated with impaired lung function, which can be quantified through spirometric variables.
Objective
This study aims to determine whether a high number of MetS criteria is associated with increased lung function decline.
Methods
We conducted a descriptive cross-sectional study with a random sample of 1980 workers. Workers with acute respiratory pathology (eg, influenza), chronic respiratory pathology (eg, chronic bronchitis), or exposure to substances harmful to the lungs (eg, organic and inorganic dust) were not included. MetS was established based on harmonized criteria, and lung function was assessed according to spirometric variables. On the basis of these, classification into restrictive lung disease (RLD), obstructive lung disease, and mixed lung disease (MLD) was performed. In addition, the association between MetS and lung function was established based on analysis of covariance, linear trend analysis, and multiple linear regression.
Results
MetS was associated with worse lung function according to all the spirometric parameters analyzed (percentage of predicted forced expiratory volume in 1 second: mean 83, SD 13.8 vs mean 89.2, SD 12.8; P<.001 and percentage of predicted forced vital capacity: mean 85.9, SD 11.6 vs mean 92, SD 11.3; P<.001). Moreover, those diagnosed with MetS had a higher prevalence of lung dysfunction (41% vs 21.9%; P<.001), RLD (23.4% vs 11.2%; P<.001), and MLD (7.3% vs 2.2%; P<.001). Furthermore, an increasing number of MetS criteria was associated with a greater impairment of pulmonary mechanics (P<.001). Similarly, with an increasing number of MetS criteria, there was a significant linear trend (P<.001) in the growth of the prevalence ratio of RLD (0 criteria: 1, 1: 1.46, 2: 1.52, 3: 2.53, 4: 2.97, and 5: 5.34) and MLD (0 criteria: 1, 1: 2.68, 2: 6.18, 3: 9.69, and 4: 11.37). Regression analysis showed that the alteration of all MetS risk factors, adjusted for various explanatory variables, was significantly associated with a worsening of spirometric parameters, except for forced expiratory volume in 1 second/forced vital capacity.
Conclusions
The findings have shown that an increase in cardiometabolic risk factors is associated with a more significant worsening of spirometric variables and a higher prevalence of RLD and MLD. As spirometry could be a crucial tool for monitoring patients at risk of developing chronic pathologies, we conclude that this inexpensive and easily accessible test could help detect changes in lung function in patients with cardiometabolic disorders. This highlights the need to consider the importance of cardiometabolic health in lung function when formulating public health policies.
Nutritional supplementation with antioxidants and vitamins is widely recommended in the treatment of vascular disorders affecting the retina, although there is insufficient evidence on its ...effectiveness. The vitamin-like compound coenzyme Q10 (CoQ10) is a nutritional supplement of current interest to treat neurodegenerative diseases. Here, we report a retrospective clinical case series study of 48 patients diagnosed with retinal vascular diseases, including non-arteritic ischemic optic neuropathy (NAION), retinal artery occlusion (RAO), and homonymous hemianopia or quadrantanopia following stroke, treated with oral supplementation with CoQ10 (100 mg per day) and vitamins. Patient follow-up was performed using the Humphrey field analyzer and 30-2 testing algorithm to determine the visual field index (VFI) and progression rates. All treated patients showed positive VFI progression rates per year: +11.5 ± 15% for NAION patients (
= 18), +22 ± 17% for RAO patients (
= 7), +9.3 ± 10.5% for hemianopia/quadrantanopia patients (
= 10), and +11 ± 21% for patients with other conditions (
= 13). The interruption of CoQ10 supplementation in one patient resulted in a pronounced decrease of the VFI, which was partially recovered when treatment was restored. This study supports the role of CoQ10 as a nutritional therapeutic agent for vascular diseases affecting the retina. Owing to decreased VFI after interruption of CoQ10, its beneficial effects may be reversible.
Abstract
Objective
To assess the efficacy and safety of abatacept (ABA) in monotherapy (ABAMONO) vs combined ABA ABA plus MTX (ABAMTX) or ABA plus non-MTX conventional synthetic DMARDs (csDMARDs) ...(ABANON-MTX) in RA patients with interstitial lung disease (ILD) (RA-ILD).
Methods
This was a restrospective multicentre study of RA-ILD Caucasian patients treated with ABA. We analysed in the three groups (ABAMONO, ABAMTX, ABANON-MTX) the following outcome variables: (i) dyspnoea; (ii) forced vital capacity (FVC) and diffusion capacity of the lung for the carbon monoxide (DLCO); (iii) chest high-resolution CT (HRCT); (iv) DAS28-ESR; (v) CS-sparing effect; and (vi) ABA retention and side-effects. Differences between basal and final follow-up were evaluated. Multivariable linear regression was used to assess the differences between the three groups.
Results
We studied 263 RA-ILD patients (mean ± s.d. age 64.6 ± 10 years) ABAMONO (n = 111), ABAMTX (n = 46) and ABANON-MTX (n = 106). At baseline, ABAMONO patients were older (67 ± 10 years) and took higher prednisone dose 10 (interquartile range 5–15) mg/day. At that time, there were no statistically significant differences in sex, seropositivity, ILD patterns, FVC and DLCO, or disease duration. Following treatment, in all groups, most patients experienced stabilization or improvement in FVC, DLCO, dyspnoea and chest HRCT as well as improvement in DAS28-ESR. A statistically significant difference between basal and final follow-up was only found in CS-sparing effect in the group on combined ABA (ABAMTX or ABANON-MTX). However, in the multivariable analysis, there were no differences in any outcome variables between the three groups.
Conclusion
In Caucasian individuals with RA-ILD, ABA in monotherapy or combined with MTX or with other conventional-DMARDs seems to be equally effective and safe. However, a CS-sparing effect is only observed with combined ABA.
This paper analyses the influence of large controlling shareholders on the terms of bank loans for a sample of 984 loans to 261 non-financial Spanish public and private firms over the period ...2001-2017. The results show that the presence of large controlling shareholders increases the interest rate spread of bank loans only in public firms, whereas the influence is insignificant for private firms. Similarly, a less evenly balanced distribution of ownership among large shareholders is associated with higher loan spreads for public firms. Our results reveal that large controlling shareholders expropriate wealth from other investors in public firms, in line with the existence of lower benefits for borrowers due to having large controlling shareholders when they have other internal and external mechanisms of control.
El objetivo del presente trabajo consiste en analizar la influencia que los grandes accionistas tienen sobre las condiciones de los préstamos bancarios para una muestra compuesta por 984 préstamos realizados a 261 empresas cotizadas y no cotizadas españolas no financieras durante el periodo 2001-2017. Los resultados muestran que la presencia de grandes accionistas incrementa el tipo de interés pagado por los préstamos en el caso de las empresas cotizadas, mientras el efecto no es significativo para las empresas no cotizadas. De forma similar, una distribución de la propiedad menos equilibrada entre los grandes accionistas está asociada con un mayor tipo de interés pagado por las empresas cotizadas. Los resultados ponen de manifiesto que los grandes accionistas expropian riqueza de otros inversores en las empresas cotizadas, en línea con la existencia de menores beneficios para los prestatarios de la existencia de grandes accionistas cuando disponen de otros mecanismos, tanto internos como externos, de control.
Building Energy Models (BEMs) are a key element of the Energy Performance of Buildings Directive (EPBD), and they are at the basis of Energy Performance Certificates (EPCs). The main goal of BEMs is ...to provide information for building stakeholders; they can be a powerful market tool to increase demand for energy efficiency solutions in buildings without affecting the comfort of users, as well as providing other benefits. The next generation of BEMs should value buildings in a holistic and cost-effective manner across several complementary dimensions: envelope performances, system performances, and controlling the ability of buildings to offer flexible services to the grid by optimizing energy consumption, distributed generation, and storage. SABINA is a European project that aims to look for flexibility to the grid, targeting the most economic source possible: existing thermal inertia in buildings. In doing so, SABINA works with a new generation of BEMs that tend to mimic the thermal behavior of real buildings and therefore requires an accurate methodology to choose the model that complies with the requirements of the system. This paper details our novel extensive research on which statistical indices should be chosen in order to identify the best model offered by the calibration process developed by Fernandez et al. in a previous paper and therefore is a continuation of that work.
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