“
“Background. Patients with a history of previous malignancy are often encountered in a discussion of https://www.selleckchem.com/products/shp099-dihydrochloride.html surgical resection of non-small-cell lung cancer (NSCLC). The outcome of patients with 2 or more previous cancers remains unknown.\n\nMethods. We performed a retrospective study including all patients undergoing resection for NSCLC from January 1980 to December

2009 at 2 French centers. We then compared the survival of patients without a history of another cancer (group 1), those with a history of a single malignancy (group 2), and those with a history of 2 or more previous malignancies (group 3).\n\nResults. There were 5,846 patients: 4,603 (78%) in group 1, 1,147 (20%) in group 2, and 96 (2%) in group 3. The proportion of patients included in group 3 increased from 0.3% to 3% over 3 decades. Compared with groups 1 and 2, group 3 was associated with older age, a larger proportion of women, earlier tumor stage, less induction therapy, and fewer pneumonectomies. Despite this, postoperative complications and mortality were similar in groups 2 and 3, and higher than in group 1. Five-year survival rates were 44.6%, 35.1%, and 23.6% in groups 1, 2, and 3, respectively (p < 0.000001 for comparison between 3 groups; p = 0.18 for comparison between groups 2 and 3). In multivariate analysis, male sex, higher T stage,

higher N stage, incomplete resection, and study group were significant predictors of adverse prognosis.\n\nConclusions. Despite earlier diagnosis and acceptable long-term survival, patients operated on for NSCLC after 2 or 3 previous malignancies INCB028050 manufacturer carried a worse prognosis than did those undergoing operation after 1 malignancy or if there was no previous diagnosis of cancer. (Ann Thorac Surg 2013;95:1000-5) (C) 2013 by The Society of Thoracic Surgeons”
“The success of helminth parasites is partly related to their ability to modulate host immune responses towards an anti-inflammatory/regulatory phenotype. This ability resides with the molecules contained in the secretome of various helminths that have been shown to interact with host immune

cells and influence their function. Consequently, there exists a unique opportunity to exploit these molecules for the prophylactic and learn more therapeutic treatment of human pro- and auto-inflammatory disorders (for example septic shock, transplant rejection and autoimmune disease). In this review, we describe the mechanisms used by the trematode parasite, Fasciola hepatica, to modulate the immune responses of its host and discuss the potent immune-modulatory effects of three individual molecules within the secretome; namely cathepsin L1, peroxiredoxin and helminth defence molecule. With a focus on the requirements from industry, we discuss the strategies by which these molecules may be clinically developed to control human immune responses in a way that is conducive to the prevention of immune-mediated diseases. Crown Copyright (C) 2012 Published by Elsevier Ltd.

“
“Various studies have shown that lycopene, a non-provitamin A carotenoid, exerts antioxidant, antimutagenic and anticarcinogenic activities in this website different in vitro and in vivo systems. However, the results concerning its chemopreventive potential on rat hepatocarcinogenesis are ambiguous. The aim of the present study was to investigate the

antigenotoxic and anticarcinogenic effects of dietary tomato oleoresin adjusted to lycopene concentration at 30, 100 or 300ppm (administered 2 weeks before and during or 8 weeks after carcinogen exposure) on liver of male Wistar rats treated with a single intraperitoneal dose of 20 or 100 mg/kg of diethylnitrosamine (DEN), respectively. The level of DNA damage in liver cells and the development of putative preneoplastic single hepatocytes, minifoci and foci of altered hepatocytes (FHA) positive for glutathione S-transferase (GST-P) were used as endpoints. Significant reduction of DNA damage was detected when the highest lycopene concentration was administered before and

during the DEN exposure (20 mg/kg). However, the results also showed that lycopene consumption did not reduce cell proliferation in normal hepatocytes or the growth of initiated hepatocytes into minifoci positive for GST-P during early regenerative response after 70% partial hepatectomy, or the number and area of GST-P positive FHA induced by DEN (100 mg/ kg) at the end of week 10. Taken together, the data suggest a chemopreventive effect of tomato oleoresin against DNA damage induced by DEN but no clear effectiveness in initiating or promoting phases of rat hepatocarcinogenesis. Autophagy inhibitor library (c) 2008 Elsevier GmbH. All rights reserved.”
“Sickle-cell disease is one of the most common severe monogenic disorders in the world. Haemoglobin polymerisation, leading to erythrocyte rigidity

and vaso-occlusion, is central to the pathophysiology of this disease, although the see more importance of chronic anaemia, haemolysis, and vasculopathy has been established. Clinical management is basic and few treatments have a robust evidence base. One of the main problems of sickle-cell disease in children is the development of cerebrovascular disease and cognitive impairment, and the role of blood transfusion and hydroxycarbamide for prevention of these complications is starting to be understood. Recurrent episodes of vaso-occlusion and inflammation result in progressive damage to most organs, including the brain, kidneys, lungs, bones, and cardiovascular system, which becomes apparent with increasing age. Most people with sickle-cell disease live in Africa, where little is known about this disease; however, we do know that the disorder follows a more severe clinical course in Africa than for the rest of the world and that infectious diseases have a role in causing this increased severity of sickle-cell disease.

85 95% CI 1.81-8.19). Multivariable Cox regression adjusting for all clinical covariates demonstrated an increased mortality risk (hazard ratio [HR] 1.40, 95% CI 1.00-1.97, p < 0.05) among heavy drinkers compared to nondrinkers but no delays in cART initiation (1.04 95% CI buy BMS-345541 0.81-1.34)\n\nConclusions: Among this cohort of HIV-infected women, heavy

alcohol consumption was independently associated with earlier death. Baseline factors associated with heavy alcohol use included tobacco use, hepatitis C, and illicit drug use. Alcohol is a modifiable risk factor for adverse HIV-related outcomes. Providers should consistently screen for alcohol consumption and refer HIV-infected women with heavy alcohol use for treatment.”
“This paper presents a novel adaptive reduced-rank multiple-input-multiple-output (MIMO) equalization scheme and algorithms based on alternating optimization design techniques for MIMO spatial multiplexing systems. The proposed

reduced-rank equalization structure consists of a joint iterative optimization of the following two equalization stages: 1) a transformation matrix that performs dimensionality reduction and 2) a reduced-rank estimator that retrieves the desired transmitted symbol. The proposed reduced-rank architecture is incorporated into an equalization structure that allows both decision feedback and linear schemes to mitigate the interantenna AZD0530 chemical structure (IAI) and inter-symbol interference (ISI). We develop alternating least squares (LS) expressions for the design of the transformation matrix and the reduced-rank estimator

along with computationally efficient alternating recursive least squares (RLS) click here adaptive estimation algorithms. We then present an algorithm that automatically adjusts the model order of the proposed scheme. An analysis of the LS algorithms is carried out along with sufficient conditions for convergence and a proof of convergence of the proposed algorithms to the reduced-rank Wiener filter. Simulations show that the proposed equalization algorithms outperform the existing reduced- and full-algorithms while requiring a comparable computational cost.”
“Introduction: Gliosarcoma is a rare neoplasm of the central nervous system, similar to glioblastoma multiforme. In contrast to glioblastoma, it is characterised by its propensity for extracranial metastasis (11% of the cases) due to its sarcomatous component. Intramedullary metastasis from primary gliosarcoma is extremely rare. Case report: A patient who had surgery for primary cerebral gliosarcoma developed paraparesis during the course of the disease. A magnetic resonance image showed an intramedullary spinal cord metastasis requiring surgical treatment. This article reviews the literature on intramedullary spinal cord metastasis from gliosarcoma, and highlights the characteristics, treatment and overall survival. Conclusions: Only 4 cases of intramedullary gliosarcoma metastasis are described in the literature.

Immunotherapy has a 20-year history in treatment of metastatic kidney cancer. High-dose interleukin-2 (IL-2) is administered in some countries, whereas low-dose IL-2 and interferon-alpha (IFN-alpha) are popular in Japan. Molecular-targeted drugs, including sunitinib, bevacizumab and sorafenib, are being used for previously untreated and refractory patients. Asian and non-Asian populations have shown large differences in the incidences of adverse events with sorafenib and sunitinib. Consensus Statement: Kidney cancer is relatively uncommon in Asia compared

with the West, but its incidence is increasing in more developed Asian nations. Guidelines from the National Comprehensive Cancer Network , etc., for treating metastatic renal VX-680 clinical trial cell carcinoma are based on Phase III clinical trials conducted primarily in Western patients. Targeted therapies are now becoming primary recommendations, but efficacy/toxicity data from Asian patients are lacking.

Some drugs cause adverse effects in Asians because their recommended dosages are optimal for Caucasians but may be too high for Asians. Further research is necessary to develop optimal treatment strategies for Asians.”
“Background\n\nRecent literature on the lack of efficiency and acceptability of publicly provided health services has led to an interest in the use of partnerships with the private sector to deliver public services.\n\nObjectives\n\nTo assess the effectiveness of contracting out healthcare services in BVD-523 LGX818 solubility dmso improving access to care in low and middle-income countries and, where possible, health outcomes.\n\nSearch strategy\n\nWe searched a wide range of international databases, including the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE, in addition to development studies and economic databases. We also searched the websites and online resources of numerous international agencies, organisations

and universities to find relevant grey literature. The original searches were conducted between November 2005 and April 2006. An updated search in MEDLINE was carried out in May 2009.\n\nSelection criteria\n\nContracting out health services is defined as the provision of healthcare services on behalf of the government by non-state providers. Studies had to include an objective measure of at least one of the following outcomes: health care utilisation, health expenditure, health outcomes or equity outcomes. Studies also needed to use one of the following study designs: randomised controlled trial, non-randomised controlled trial, interrupted time series analysis or controlled before and after study.

Unlike mammalian neurons, which depolarize almost completely during SD, locust neurons only partially depolarized. SD-like events in the locust CNS were suppressed by pharmacological inhibition of the nitric oxide/cyclic guanosine monophosphate/ protein kinase G (NO/cGMP/PKG) pathway and were exacerbated by its activation. Also, environmental stressors such as heat and anoxia increased production

of nitric oxide in the locust CNS. Finally, for the intact animal, manipulation of the pathway affected the speed of recovery from suffocation by immersion under water. We propose that SD-like events in locusts provide an adaptive mechanism BMS-777607 order for surviving extreme environmental conditions. The highly conserved nature of the NO/cGMP/PKG signaling pathway suggests that it may be involved in modulating SD in other organisms, including mammals.”
“A simulation formalism for the nonlinear response of vibrational excitons is presented and applied to the OH stretching

vibrations of neat Lazertinib research buy liquid H(2)O. The method employs numerical integration of the Schrodinger equation and allows explicit treatment of fluctuating transition frequencies, vibrational couplings, dipole moments, and the anharmonicities of all these quantities, as well as nonadiabatic effects. The split operator technique greatly increases computational feasibility and performance. The electrostatic map for the OH stretching vibrations in liquid water employed in our previous study [A. Paarmann , J. Chem. Phys. 128, 191103 (2008)] is presented. The two-dimensional spectra are in close

agreement with experiment. The fast 100 fs dynamics are primarily attributed to intramolecular mixing between states in the two-dimensional OH stretching potential. Small intermolecular couplings are sufficient to reproduce the experimental energy transfer time scales. Interference effects between Liouville pathways in excitonic systems and their impact on the analysis of the nonlinear response are discussed.”
“The mammalian sperm acrosome contains a large learn more number of hydrolytic enzymes. When the acrosomal reaction and fertilization occur, these enzymes are released in an orderly fashion, suggesting that the acrosomal matrix is highly organized. It was decided to determine the identity of the structural scaffold underlying the organization of the acrosome. In permeabilized acrosomes and in the Triton X-100 extracted acrosomal matrices from guinea pig sperm, we used indirect immunofluorescence, immunogold labeling, and Western blotting to identify F-actin, spectrin, myosin, calmodulin, and gelsolin. These proteins were detected in the acrosomal matrix for the first time. In noncapacitated, intact spermatozoa the addition of the F-actin monomerizing agent cytochalasin D resulted in loss of the acrosome, suggesting that F-actin is needed to preserve an intact acrosome.

Matrix metalloproteinases (MMPs), proteolytic

enzymes, modulate the turnover of numerous substrates, including cytokine precursors, growth factors, and ECM molecules. However, SN-38 concentration the roles of MMPs in the regulation of adult stem cells are poorly understood. In the present study, we utilize the Drosophila midgut, which is an excellent model system for studying stem cell biology, to show that Mmp1 is involved in the regulation of intestinal stem cells (ISCs). The results showed that Mmp1 is expressed in the adult midgut and that its expression increases with age and with exposure to oxidative stress. Mmp1 knockdown or Timp-overexpressing flies and flies heterozygous for a viable, hypomorphic Mmp1 allele increased ISC proliferation in the

gut, as shown by staining with an anti-phospho-histone H3 antibody and BrdU incorporation assays. Reduced Mmp1 levels induced intestinal hyperplasia, and the Mmp1depletion-induced ISC proliferation was rescued by the suppression of the EGFR signaling pathway, suggesting that Mmp1 regulates ISC proliferation through the EGFR signaling pathway. Furthermore, adult gut-specific knockdown and whole-animal heterozygotes of Mmp1 increased additively sensitivity to paraquat-induced oxidative stress and shortened lifespan. Our data see more suggest that Drosophila Mmp1 is involved in the regulation of ISC proliferation for maintenance of gut homeostasis. (C) 2012 Elsevier Inc. All rights reserved.”
“The importance of neutropenia as a predisposing factor for infection in patients with haematological

malignancies was not clearly appreciated until effective therapeutic agents became available. This led to the important advance of administering antibiotics promptly to GSK2126458 supplier neutropenic patients when they developed fever, before a diagnosis was established. Although some antibiotics available in the 1960s had activity against many pathogens in vitro, they were ineffective against infections in neutropenic patients. The development of methods to administer white blood cell transfusions along with antibiotics was beneficial to some patients. The development of new antibiotics was of critical importance, such as methicillin for treatment of Staphylococcus aureus and carbenicillin for Pseudomonas aeruginosa. Prevention of infection was attempted, using isolation rooms, air filtration and prophylactic antibiotics. All of these early efforts laid the foundations for the many important current investigations.”
“CD8(+) T cell responses to persistent infections caused by intracellular pathogens are dominated by resting T effectors and T effector memory cells, with little evidence suggesting that a T central memory (T(CM)) population is generated. Using a model of Trypanosoma cruzi infection, we demonstrate that in contrast to the T effector/T effector memory phenotype of the majority of T.

In addition, using the quantitative function of the technique, along with simulation tools, we determined the refractive index of a single tubulin microtubule to be n(tubu) = 2.36 +/- 0.6 at lambda= 527 nm.”
“Satisfaction with

care is important to both patients and to those who pay for it. The Net Promoter Score (NPS), widely used in the service industries, has been introduced into the NHS as the ‘friends and family test’; an overarching measure of patient satisfaction. It assesses the likelihood of the patient recommending the healthcare buy BMS-754807 received to another, and is seen as a discriminator of healthcare performance. We prospectively assessed 6186 individuals undergoing primary lower limb joint replacement at a single university hospital to determine the

Net Promoter Score for joint replacements and to evaluate which factors contributed to the response. Achieving pain relief (odds ratio (OR) 2.13, confidence interval (CI) 1.83 to 2.49), the meeting of pre-operative expectation (OR 2.57, CI 2.24 to 2.97), and the hospital experience (OR 2.33, CI 2.03 to 2.68) are the domains that explain whether a patient would recommend joint replacement services. These three factors, combined with the type of surgery undertaken (OR 2.31, CI 1.68 to 3.17), drove a predictive model that was able to explain 95% of the variation in the patient’s recommendation response. Though intuitively similar, this ‘recommendation’ metric was found to be materially

different to satisfaction responses. The difference between THR (NPS 71) and TKR (NPS 49) suggests that no overarching Cilengitide score for a department should be used without an adjustment for case mix. However, the Net Promoter Score does measure a further important dimension to our existing metrics: the patient experience of healthcare delivery.”
“Purpose: To measure radiation dose in a water-equivalent medium from very high-energy electron (VHEE) beams and make comparisons to Monte Carlo (MC) simulation results. Methods: Dose in a polystyrene phantom delivered by an experimental VHEE beam line was measured with GSK2245840 in vitro Gafchromic films for three 50 MeV and two 70 MeV Gaussian beams of 4.0-6.9 mm FWHM and compared to corresponding MC-simulated dose distributions. MC dose in the polystyrene phantom was calculated with the EGSnrc/BEAMnrc and DOSXYZnrc codes based on the experimental setup. Additionally, the effect of 2% beam energy measurement uncertainty and possible non-zero beam angular spread on MC dose distributions was evaluated. Results: MC simulated percentage depth dose (PDD) curves agreed with measurements within 4% for all beam sizes at both 50 and 70 MeV VHEE beams. Central axis PDD at 8 cm depth ranged from 14% to 19% for the 5.4-6.9 mm 50 MeV beams and it ranged from 14% to 18% for the 4.0-4.5 mm 70 MeV beams.

“
“Magnetic fields affect biological systems. However, this is the first study on the effects of permanent magnetic fields (MFs) on the micropropagation of two ornamental plants, Spathiphyllum cv. i.e ‘Merry’ and Cymbidium Music Hour ‘Maria’. Cymbidium and Spathiphyllum shoots cultured in the ‘Miracle Pack’A (R) culture system were exposed PXD101 to MFs of different intensities, polarities, and duration of exposure. The results show that by increasing intensity from 5 x 10(-6) Tesla (T) as the geo-magnetic field to 0.1, 0.15, and 0.2 T negatively

influenced height and fresh mass of roots of Cymbidium plants (except for 0.1 T-S and 0.2 T-N treatments), but had no significant effect on other plantlet parameters. Long-term exposure (1, 2, or 3 mo) of Cymbidium shoots MLN4924 datasheet to 0.15 T-MFs negatively influenced plant

height, positively affected the number of leaves (with the exception of 0.15 T-S-1 mo), and had no clear effect on other parameters compared to the control. MFs (0.1, 0.15, and 0.2 T), regardless of their polarity, increased chlorophyll content (SPAD value) and the number of leaves, but slightly decreased the dry mass of Spathiphyllum shoots. Different exposure duration to 0.15 T (i.e., 2, 4, or 8 wk) had no significant influence on Spathiphyllum plantlet development other than increasing the SPAD value. These two ornamentals could serve as model systems to study plant development, space production, yield maximization, and the development of new morphotypes essential for the floricultural market.”
“Objectives: Selleck Buparlisib To examine the effects of electroacupuncture stimulation on behavioral changes and neuronal nitric oxide synthase expression in the rat spinal cord after nerve injury.\n\nMethods: Under pentobarbital anesthesia, male Sprague-Dawley rats were subjected to neuropathic surgery by tightly ligating and cutting the left tibial and sural nerves.

Behavioral responses to mechanical stimulation were tested for 2 weeks post-operatively. At the end of behavioral testing, electroacupuncture stimulation was applied to ST36 (Choksamni) and SP9 (Eumleungcheon) acupoints. Immunocytochemical staining was performed to investigate changes in the expression of neuronal nitric oxide synthase-immunoreactive neurons in the L4-5 spinal cord.\n\nResults: Mechanical allodynia was observed by nerve injury. The mechanical allodynia was decreased after electroacupuncture stimulation. Neuronal nitric oxide synthase expression was also decreased in L4-5 spinal cord by electroacupuncture treatment.\n\nDiscussion: These results suggest that electroacupuncture relieves mechanical allodynia in the neuropathic rats possibly by the inhibition of neuronal nitric oxide synthase expression in the spinal cord.

We urge that cooperative conservation

initiatives be undertaken and support (e.g., capacity-building) be given by more developed countries in the region and beyond.”
“We investigated the association between CASP-9 polymorphisms and susceptibility to neoplasm. Fourteen studies with a total of 2733 neoplasm cases and 3352 healthy controls were included. Meta-analysis showed that the rs4645981*T allele and the rs4645981*T allele Metabolism inhibitor carrier were positively associated with neoplasm susceptibility [odds ratio (OR) = 1.43, 95% confidence interval (95%CI) = 1.12-1.81, P = 0.004; OR = 1.46, 95%CI = 1.10-1.93, P = 0.009, respectively]. However, the rs1052576*A allele, rs1052576* A carrier, rs2308941* T allele, and rs2308941*T carrier might decrease the risk of cancer (OR = 0.72, 95%CI

= 0.58-0.89, P = 0.003; OR = 0.76, 95%CI = 0.63-0.92, P = 0.004; OR = 0.20, 95%CI = 0.09-0.45, P smaller than 0.0001; OR = 0.21, 95%CI = 0.06-0.75, P = 0.02, MEK162 molecular weight respectively). There was no significant association between rs1263, rs1052571, rs2308950, rs4645978, rs4645980, rs4645982, and rs4646018 and cancer risk (all P bigger than 0.05). In conclusion, this meta-analysis suggests that CASP-9 gene polymorphisms are involved in the pathogenesis of various cancers. The rs4645981* T allele and the rs4645981*T allele carrier might increase the risk of cancer, but the rs1052576*A allele, rs1052576*A carrier, rs2308941*T allele, and rs2308941* T carrier might be protective.”
“SFB, a candidate gene for the pollen S gene, has been identified in several species of Prunus (Rosaceae). We isolated 5 new SFB alleles LDN-193189 solubility dmso from 6 Japanese apricot (Prunus mume) lines using a specific Prunus SFB primer pair (SFB-C1F and Pm-Vb), which was designed from conserved regions of Prunus SFB. The nucleotide sequences of these SFB genes were submitted to the GenBank database. The 5 new SFB alleles share typical structural features with SFB alleles from other Prunus species and were found to be polymorphic, with 67.08 to 96.91% amino acid identity. These new SFB alleles were specifically expressed

in the pollen. We conclude that the PmSFB alleles that we identified are the pollen S determinants of Japanese apricot; they have potential as a tool for studies of the mechanisms of pollen self-incompatibility.”
“Background: Hansenula polymorpha DL1 is a methylotrophic yeast, widely used in fundamental studies of methanol metabolism, peroxisome biogenesis and function, and also as a microbial cell factory for production of recombinant proteins and metabolic engineering towards the goal of high temperature ethanol production. Results: We have sequenced the 9 Mbp H. polymorpha DL1 genome and performed whole genome analysis for the H. polymorpha transcriptome obtained from both methanol- and glucose-grown cells. RNA-seq analysis revealed the complex and dynamic character of the H.

“
“Steel-concrete-steel (SCS) sandwich panels are an effective means for protecting personnel and infrastructure facilities from the effects of external blast and high-speed vehicle impact. In conventional SCS construction, the external steel plates

are connected to the concrete infill by welded shear stud connectors. This paper describes a programme of research in which the non-composite SCS panels with axially restrained connections were studied experimentally and numerically. High fidelity finite element models for axially restrained steel-concrete-steel panels subjected to Cediranib nmr impact loading conditions were developed using LS-DYNA. The simulation results were validated against the dynamic testing experimental results. The numerical models were able to predict the initial flexural response of the panels followed by the tensile membrane resistance at large deformation. It was GDC-0973 found that the strain rate effects of the materials and the concrete material model could have significant effect on the numerically predicted flexural strength and tensile membrane resistance of the panels. (C) 2012 Elsevier

Ltd. All rights reserved.”
“Tibial defect is generally caused by high-energy injury, tumor, osteomyelitis, development deformity and bone non-union after internal fixation. This study was to determine stability of tibial defect reconstruction with fibular graft (FG) of different lengths by single free vascularized 5-Fluoracil in vivo fibular graft (SFVFG) and double-barrel free vascularized fibular graft (DBFVFG). The left lower extremity of a male volunteer was scanned with computer tomography scanner. The contours of the tibia and fibula were extracted and the

geometry of both bones rebuilt. From this intact model, the models of tibial defect reconstruction with fibular graft and external fixation were developed. Inter-fragmentary motion (IFM) and Von Mises stress on the fibular bone flap, and the locations of maximum Von Mises stress were introduced to quantify the biomechanical environment. Under the condition of the same graft length, the Von Mises stress value in DBFVFG group was 1.37 to 1.77 times higher than that in SFVFG group. When the length of graft was greater than 15 cm in the SFVFG group, the IFM exceeded 1 mm, but the IFM of the graft in the DBFVFG group was always less than 1 mm. The maximum Von Mises stress of models was frequently located at the second or third pin-bone interface. Thus, external fixation can provide a stable biomechanical environment for the reconstruction of tibial defect by both SFVFG and DBFVFG. The second or third pin-bone interface requires intensive care and that in the reconstruction of tibial defect by SFVFG, the graft length should not exceed 15 cm.”
“Objectives and BackgroundRotational atherectomy (RA) is used as a debulking technique prior to stenting in some specialized cardiac centers for calcified coronary lesions amenable to percutaneous coronary intervention (PCI).