Results: Four hundred sixty-nine RCTs proved eligible: 219 in hig

Results: Four hundred sixty-nine RCTs proved eligible: 219 in higher and 250 in lower impact journals. RCTs in higher vs. lower impact journals had larger sample sizes (median, 285 vs. 39), were more likely to receive industry funding

(53% vs. 28%), declare concealment of allocation (66% vs. 36%), declare blinding of health care providers (53% vs. 41%) and outcome adjudicators (72% vs. 54%), report a patient-important primary outcome (69% vs. 50%), report subgroup analyses (64% vs. 26%), prespecify subgroup hypotheses (42% vs. 20%), and report a test for interaction AZD8931 manufacturer (54% vs. 27%); P < 0.05 for all differences.

Conclusion: RCTs published in higher impact journals were more likely to report methodological Ricolinostat safeguards against bias and patient-important outcomes than those published in lower impact journals. However, sufficient limitations remain such that publication in a higher impact journal does not ensure low risk of bias. (C) 2013 Elsevier Inc. All rights reserved.”
“A chest roentgenogram of a 75-year-old immunocompetent woman showed disseminated micronodular densities in bilateral lung fields. Subsequent high-resolution computed tomography (CT) confirmed centrilobular micronodular densities associated with bronchial wall thickening and bronchiectatic changes. CT imaging also revealed volume loss with bronchiectatic changes in both the right middle lobe and the left lingular segment. Cytology specimens

were then obtained through bronchial brushing and washes. Smears from right B2 and B4 revealed filamentous gram-positive, branched bacteria embedded among many neutrophils. Nocardia transvalensis was cultured from the bronchial wash, and no mycobacteria

were identified. To our knowledge, this is the first report of a Nocardia transvalensis selleck compound pulmonary infection in an immunocompetent patient, and also the first detailed description of a Nocardia transvalensis pulmonary infection in Japan. Moreover, the radiographic and CT findings in this patient were quite similar to those seen in patients with nontuberculous mycobacterial pulmonary infections, a pattern not previously reported in patients with Nocardia pulmonary infections.”
“The lignocellulosic biomass of plant cell wall is a source of sugar that can be used for second generation of bioethanol. The technology used for converting the fermentable sugar in the cell wall into bioethanol involves a pretreatment step that helps to decrease the recalcitrance of biomass to deconstruction. Atomic force microscopy (AFM), due to its ability to generate high resolution images with negligible sample preparation, is a powerful tool for studying biological samples on a nanometer scale. In this work, we elucidated the microfibrillar arrangement of the sugarcane cell wall and analyzed the effect of a thermochemical pretreatment at the nanoscale level using AFM images. Initially, we isolated the sugarcane cell wall to improve the AFM analysis.


“Surgical technique and perioperative management in rectal


“Surgical technique and perioperative management in rectal cancer surgery have been substantially improved and standardized during the CX-6258 molecular weight last decades. However, anastomotic leakage following low anterior resection still is a significant problem. Based on animal experimental data of

improved healing of compression anastomosis, we hypothesized that a compression anastomotic device might improve healing rates of the highest-risk anastomoses.

All low anterior resections for rectal cancer performed or directly supervised by the senior author between January 2004 and June 2012 were analyzed. Only patients with a stapled or compression anastomosis located within 6 cm from the anal verge were included. Until December

2008, circular staplers were employed, while since January 2009, a novel compression anastomotic device was used for rectal reconstruction exclusively.

Out of 197 patients operated for rectal cancer, a total of 96 (34 females, 35.4 %) fulfilled inclusion criteria. Fifty-eight (60.4 %) were reconstructed with buy Volasertib circular staplers and 38 (39.6 %) using a compression anastomotic device. Significantly, more laparoscopic procedures were recorded in the compression anastomosis group, but distribution of gender, age, body mass index, American Society of Anaesthesiologists score, rate of preoperative radiotherapy, tumor staging, or stoma diversion rate were similar. Anastomotic leakage was observed in seven cases (7/58, 12.1 %) in the stapled and twice (2/38, 5.3 %) in the compression anastomosis group (p = 0.26).

In this series, rectal reconstruction following low anterior resection using a novel compression anastomotic device was safe and (at least)

equally effective compared to traditional circular staplers concerning leak rate.”
“The aims of this work are obtaining and evaluating paracetamol oral suspension 32 mg/mL by qualitative and quantitative planning of the ingredients. The observations of the physical-chemical formulations were based in comparison with the specifications of paracetamol solution contained in the Brazilian Pharmacopoeia and editing with some analysis on the same reference drug (Tylenol (R) child 4SC-202 in vitro 32 mg/mL). We sought to develop a low cost and good quality formulation, acceptable to the children’s market, since the suspension dosage form is characterized by disguising the unpleasant taste of drugs. The chosen formulation showed good rheology properties, excellent sensory and values of pH, viscosity, density and content within the pharmacopoeia specifications. We obtained a satisfactory formulation, with smaller amount of excipients in relation to the reference product, which can be used by diabetics and is compatible with the official specifications, with respect to physical-chemical tests performed.


“Objective: Lower serum total prostate-specific


“Objective: Lower serum total prostate-specific this website antigen (PSA) levels (tPSA) have been reported in obese men. It has not been confirmed if this association truly exists

in all ethnic groups. Thus, we evaluated the relationship between tPSA and obesity among Nigerian men. Methods: Men aged years with tPSA <20 ng/ml and no known prostatic disease were involved. Obesity was defined using the body mass index (BMI) and waist to hip ratio (WHR). Multivariate linear regression was used to investigate the relationship between tPSA and either BMI or WHR. The odds of having abnormal tPSA were estimated using logistic regression. Results: A total of 3,191 men participated, and 3,049(95.6%) were eligible for analysis. A BMI >= 25.0 and a WHR >= 0.9 were found in 47.7 and 64.6%, respectively. tPSA was significantly associated with age (p < 0.001) and digital rectal examination status (p < 0.001). Multivariate linear regression analysis showed no relationship between tPSA and obesity (BMI, p = 0.581; WHR, p = 0.160). Adjusting for age and digital rectal examination status, logistic regression showed no significantly observable trend of having a tPSA level greater than thresholds for men with a BMI >= 25 or a WHR >= 0.9 when compared with normal BMI or WHR, respectively. Z-VAD-FMK cost Conclusion:

Although overweight and obesity were common among healthy Nigerian men, there was no associated tendency towards lower serum tPSA. Copyright

(C) 2012 S. Karger AG, Basel”
“We investigate the mechanisms involved in the long-term antihypertensive effect of a polyphenol-rich cocoa powder, named CocoanOX (R) (CCX), in spontaneously hypertensive rats (SHR). We have carried out two different batches of experiments. For the first batch of experiments, forty selleck kinase inhibitor 3 week-old male SHR were randomly divided with ad libitum intake into four groups of 10 animals, that respectively received the following drinking fluids up to the 20th week of life (treatment period): tap water (control), CCX 100 mg/kg/day, CCX 200 mg/kg/day and CCX 400 mg/kg/day. Five 20 week-old rats of each group were sacrificed by decapitation. From the 20th to 24th week of life all the remaining animals were given tap water (follow-up period), and all of them were sacrificed at the end of the follow-up period. Plasma malondialdehyde (MDA), reduced glutathione in the liver, plasma and aorta angiotensin converting enzyme (ACE) activity and plasma angiotensin II were determined in all the sacrificed SHR that were included in this batch of experiments. Plasma MDA decreased and liver reduced glutathione increased in the 20 week-old CCX treated SHR. These effects were not observed in the rats that were sacrificed after the follow-up period.

In this review, we focus on findings from

In this review, we focus on findings from LDK378 in vitro the recent literature in which specific modulatory effects of MSCs on one or more individual effector

T-cell subsets and T(reg) phenotypes have been examined in vitro, in relevant animal models of in vivo immunological disease, and in human subjects. We conclude that MSCs have the potential to directly or indirectly inhibit disease-associated Th1, Th2, and Th17 cells as well as cytotoxic T lymphocytes but that many key questions regarding the potency, specificity, mechanistic basis, and predictable therapeutic value of these modulatory effects remain unanswered.”
“Optical properties of conjugated copolymer incorporating thienylene-dioctyloxyphenyle-thienylene and bipyridine units prepared by Stille coupling reactions in the ground and lowest singlet selleckchem excited states were calculated with Time Dependent Density Functional Theory (TD-DFT), CIS/3-21G*, and semiempirical (ZINDO) methods. The complementarities and the good agreement between theoretical and experimental results have permitted us to describe electronic structure and to predict a correlation between structure and properties of this new copolymer. Then, on

the basis of these results, we show that this copolymer could be exploited as an active layer in optoelectronic devices. (c) 2011 Wiley Periodicals, Inc. J Appl Polym Sci, selleck kinase inhibitor 2012″
“The combination of Dipyridamole and Aspirin and is widely used to

reduce thrombosis in patients with thrombotic diseases. A rapid, simple, precise and cost effective and reversed-phase high performance liquid chromatography (RP-HPLC) method has been developed and validated for the simultaneous determination of Aspirin and Dipyridamole in pharmaceutical formulations. Separation of both Aspirin and Dipyridamole was achieved within 5 min with required resolution, accuracy and precision thus enabling the utility of the method for routine analysis. Chromatographic separation was achieved on a waters symmetry C18 3.5 mu m, 50 x 4.6 mm using a mobile phase consisting of 0.1% ortho phosphoric acid and acetonitrile in the ratio of 75: 25 at a flow rate of 1.0 ml per minute. The detection was made at 227 nm and the retention time of Aspirin and Dipyridamole were1.5 and 2.8 minutes respectively. The method was found linear over the range of 4 to 80 mu g/ml for Dipyridamole and 0.5 to 10 mu g/ml for Aspirin.”
“Background: Treatment guidelines for dyslipidemic patients have focused on lipid levels and risk assessments. However, non-nolipidemic patients who have multiple risk factors for cardiovascular disease may also benefit from HMG-CoA reductase inhibitor (statin) therapy.

Objective: We examined the frequency of statin prescriptions in patients initiating antihypertensive drug treatment in a US managed-care setting.

Japan may have had the lowest case fatality rate for symptomatic

Japan may have had the lowest case fatality rate for symptomatic illness (<0.001%, Alvespimycin concentration 198/20.7 million) in the H1N1/09 pandemic because of the universal implementation of early treatment with NAI. A study of 1,000 children hospitalized because of a H1N1/09 infection revealed that NAIs, primarily oseltamivir, had been used to treat 984 (98.4%) of the 1,000 patients. In 88.9% of the patients, treatment with NAIs was initiated within 48 h after the onset of illness. In addition to oseltamivir and zanamivir, the newly approved inhalant drug, laninamivir, and the newly approved intravenous drug, peramivir, were used in Japan during the 2010-2011 season. Neuropsychiatric disorders that were suspected of being adverse reactions

to oseltamivir became a cause of concern in 2007. The Health, Labour and Welfare Ministry issued an emergency instruction to suspend the use of oseltamivir to treat patients between the ages of 10 and 19 years. However, according to the Vital Statistics data, the widespread use of oseltamivir has not caused an increase in deaths as a result of accidental falls or intentional jumps from buildings. Although oseltamivir is widely used in Japan, no outbreaks have been caused by oseltamivir-resistant viruses, and no serious illness caused by oseltamivir-resistant viruses has ever STI571 purchase been reported.”
“The development and implementation of strategies for CO2 mitigation are necessary to counteract

the greenhouse gas effect of carbon dioxide emissions. To demonstrate the possibility of simultaneously capturing CO2 and utilizing four-carbon compounds, an integrated system using CA and PEPCase was developed, which mimics an in vivo carbon dioxide concentration mechanism. We first cloned the PEPCase 1 gene of the marine diatom Phaeodactylum tricornutum and produced a recombinant PtPEPCase 1. The affinity column purified PtPEPCase 1 exhibited specific enzymatic activity (5.89 U/mg). When the simultaneous and coordinated reactions of CA from Dunaliella sp. and the PtPEPCase

1 occurred, more OAA was produced than when only PEPCase was present. Therefore, this integrated CA-PEPCase system can be used not only to capture CO2 but also for a new technology to produce value-added four-carbon platform chemicals.”
“A best evidence topic was written according to AG-14699 a structured protocol, asking ‘does surgery improve prognosis in patients with small-cell lung carcinoma (SCLC)?’ One hundred and thirteen papers were identified, of which the nine papers best able to answer the question were selected and the details of each tabulated. The prohibitive attitude of clinicians toward surgery in SCLC has prevailed since the 1960s, informed by a prospective randomized trial in which 144 patients were assigned to surgical treatment or to radical radiotherapy. Surgery conferred no survival benefit when compared with radical radiotherapy as assessed at 6 monthly intervals up to 10 years post-treatment.

4 billion people around the world,

or about 40% of the wo

4 billion people around the world,

or about 40% of the world’s population, depend on biomass fuels (wood, charcoal, dung, crop residue) to meet their energy needs for cooking and heating. The burden is especially high in Asia. Studies suggest that levels of pollutants including particulate matter <10 mu m and polycyclic AC220 cost aromatic hydrocarbons indoors in homes where biomass fuels are used far exceed levels recommended as safe. While in vitro and in vivo studies in animal models suggest that wood smoke emission extracts are mutagenic and carcinogenic, epidemiologic studies have been inconsistent. In this review, we discuss possible carcinogenic mechanisms of action of biomass fuel emissions, summarize the biological evidence for carcinogenesis, and review the epidemiologic evidence in humans of biomass fuel emissions as a risk factor for lung cancer. Finally, we highlight some issues relevant JQ-EZ-05 mouse for interpreting the epidemiologic evidence for the relationship between biomass fuel exposure and lung cancer: these include methodologic

considerations and recognition of possible effect modification by genetic susceptibility, smoking status, age of exposure and histologic type.”
“The lung begins as a simple outpouching of the foregut and develops by stages into a highly complex organ, the proper function of which is essential to life for terrestrial mammals. selleck Interruption of normal lung development can result in death or chronic disease. Conversely, repair after lung injury, as well as many acquired diseases, involves recapitulation, often aberrant, of developmental

pathways. The principal paradigms in lung development are branching morphogenesis and alveolar septation, but others, such as vasculogenesis, are critical. These are partially understood at the level of cellular differentiation and molecular signaling, but a true systems biology analysis of lung development and lung repair/regeneration, including bioinformatics analysis and integration of data from unbiased and complementary -omics level studies, is still lacking. The past decade has seen increasing numbers of genomic, proteomic, metabolomics, and epigenomic studies of lung development and lung remodeling. In many cases, these studies have confirmed the importance of pathways uncovered painstakingly through single-molecule approaches, but they have also uncovered novel and unexpected pathways and new paradigms such as noncoding RNA. Future studies will need to combine data from multiple repositories and apply novel mathematical and computational models in order to establish a systems-level understanding of this remarkable organ. WIREs Syst Biol Med 2013, 5:125133. doi: 10.1002/wsbm.1205 For further resources related to this article, please visit the WIREs website.

Results: 18 out of 1479 identified studies fulfilled the inclusio

Results: 18 out of 1479 identified studies fulfilled the inclusion criteria. 64 factors were identified and grouped according to the HBM into demographic and psychosocial characteristics, cues to action and perceived benefits versus perceived barriers. The belief that the medication is necessary and DMARD use prior to the use of anti-TNF had strong evidence for a positive association with adherence. There is limited evidence for positive associations between adherence and race other than White, general cognition, satisfactory contact with

the healthcare provider and the provision of adequate information from the healthcare provider. There is limited evidence for negative associations between adherence and having HMO insurance, weekly costs of TNF-I, having a busy GSK3326595 price lifestyle, receiving contradictory information or delivery of information in an insensitive manner by the rheumatologist. 18 factors PXD101 in vitro were unrelated to adherence.

Conclusions: The strongest relation with adherence is found to be prior use of DMARDs before using

anti-TNF and beliefs about the necessity of the medication. Because the last one is modifiable, this provides hope to improve adherence. (C) 2013 Elsevier Inc. All rights reserved.”
“The disease caused by cyprinid herpesvirus-3 (CyHV-3) severely impacts the natural freshwater ecosystem and damages carp and koi farming, however, the pathway of CyHV-3 transmission remains BLZ945 in vivo unclear. It is possible that the virus adheres to plankton, which then facilitate viral movement and transmission, and therefore, it is hypothesised that plankton are involved

in the disease dynamics. In this study, plankton were collected at eight sites in the Iba-naiko lagoon; we detected and quantified CyHV-3 DNA from plankton samples. The results of the correlation analysis showed a significant positive correlation between CyHV-3 copies and the number of Rotifera, suggesting that CyHV-3 binds to and/or is concentrated by Rotifera. Our results suggest that plankton affect viral ecology in the natural environment. (C) 2010 Elsevier Ltd. All rights reserved.”
“Magnetic nanoparticles (MNPs) used as heat sources for cancer thermotherapy have received much recent attention. While the mechanism for power dissipation in MNPs in a rf field is well understood, a challenge in moving to clinical trials is an inadequate understanding of the power dissipation in MNP-impregnated systems and the discrepancy between the predicted and observed heating rates in the same. Here we use the Rosensweig [J. Magn. Magn. Mater. 252, 370 (2002)] model for heat generation in a single MNP, considering immediate heating of the MNPs, and the double spherical-shell heat transfer equations developed by Andr et al. [J. Magn. Magn. Mater. 194, 197 (1999)] to model the heat distribution in and around a ferrofluid sample or a tumor impregnated with MNPs. We model the heat generated at the edge of a 2.

Furthermore, there is evidence that maternal obesity may also inc

Furthermore, there is evidence that maternal obesity may also increase the risk of obesity and diabetes in offspring. However, women with GDM possibly exhibit greater macrosomia than obese women. Obesity and diabetes in pregnancy have independent and additive effects on Selleck KPT-8602 obstetric complications, and both require proper management. Management of gestational diabetes mellitus and maternal obesity is essential for maternal and offspring’s good health. Increasing physical activity, preventing gestational weight gain, and having some qualitative nutritional habits may

be beneficial during both the pregnancy and offspring’s future life.”
“The levitation force and stability in a superconductor-magnet system with maglev geometry are studied as function of the critical-current density of the superconductor, from a IPI-145 purchase realistic model based on minimizing the magnetic

energy. Results show that although the force is an increasing function of the critical-current density J(c), an overhigh J(c) may result in instability. Therefore, the optimum critical-current density in the superconductor for a given levitation system should be an intermediate value which depends on the system dimensions and the magnetic field of the magnet.”
“BACKGROUND: The improved efficiency of steroid biotransformation using the biphasic system is generally attributed to the positive effect on the solubility of substrate in aqueous media. A promising alternative for the application of organic solvents in biphasic systems is the use of ionic liquids (ILs). This study aims to investigate the applicability of the biphasic ILs/water system for 11a hydroxylation of 16a, 17-epoxyprogesterone (HEP) by Aspergillus ochraceus. RESULTS: Of the

seven ILs tested, [C3mim][PF6] exhibited the best biocompatibility, with markedly improved biotransformation efficiency. In the [C3mim][PF6]-based biphasic system, substrate conversion reached 90% under the condition in which buffer pH, volume ratio of buffer to ILs, cell concentration, and substrate concentration buy Fosbretabulin were 4.8, 10/1, 165 g L-1 and 20 g L-1, respectively. This is more efficient than that of the monophasic aqueous system. The effects of the cations and anions of these ILs on the 11a hydroxylation of 16a, 17-epoxyprogesterone (HEP) by A. ochraceus is also discussed. CONCLUSION: The above results showed that IL/water biphasic system improved the efficiency of 11a hydroxylation of 16a, 17-epoxyprogesterone (HEP) by A. ochraceus, thus suggesting the potential industrial application of ILs-based biphasic systems for steroid biotransformation. (c) 2012 Society of Chemical Industry”
“There is a need to understand the separate or interdependent contributions of maternal prepregnancy BMI, gestational weight gain, glycaemic control, and macronutrient intake on the metabolic outcomes for the offspring.

Preliminary evidence suggests associations between TSH-receptor

Preliminary evidence suggests associations between TSH-receptor

variants and fasting glucose level, D1 variants and insulin-like ARN-509 Endocrinology & Hormones inhibitor growth factor I production, and D2 variants and hypertension, psychological well-being and response to T(3) or T(4) treatment. intriguingly, most of these associations are independent of serum thyroid hormone levels, which highlights the importance of local regulation of thyroid hormones in tissues. Future research might reveal novel roles for thyroid hormones in obesity, cardiovascular disease, osteoporosis and depression and could have implications for interpretation of thyroid function tests and individualization of thyroid hormone replacement therapy.”
“We investigated fluorescence from hemicyanine dye molecules in a liquid crystal (4,4′-n-pentylcyanobiphenyl) (5CB) medium at different temperatures. The fluorescence decay lifetime decreased monotonically irrespective of the thermodynamic phases of the host medium

as the temperature was increased. This behavior is due to an intramolecular motion of the dye promoted with the decrease in the viscosity of the medium facilitating a nonradiative decay of the excited dye molecules. By contrast, fluorescence intensity from the dyes in the nematic phase was about 3 times stronger than that in the crystalline or isotropic phase. This fluorescence enhancement in HM781-36B the nematic phase was found to be due to an anisotropic alignment of the dye molecules following the anisotropic alignment of the host liquid crystal medium along the pump-beam polarization direction. Selumetinib nmr This light-induced liquid crystal molecular alignment was markedly enhanced by the guest dyes preferentially excited along the pump-beam polarization direction. The orientational order parameter of the dyes in the liquid-crystalline phase deduced from fluorescence anisotropy measurement was similar to the known order parameter

of the liquid crystalline 5CB. (C) 2011 American Institute of Physics. [doi: 10.1063/1.3642960]“
“There are few dedicated pediatric neurophysiology services in Africa. Optimizing the efficiency of these units is essential for the large populations they serve. Two hundred eighty-seven electroencephalogram (EEG) studies, performed in a sub-Saharan neurophysiology unit, were analyzed for referral sources, appropriateness of referral, reporting consistency, and use in confirming epilepsy or a neurologic process. Pediatric neurologists requested 24% of the electroencephalogram studies and pediatricians 45%. Pediatric neurologists requested more appropriate referrals than pediatricians or nonspecialists. The electroencephalogram studies assisted management in 40% of cases. Electroencephalogram studies for nonepileptic indications, such as syncope, were highly predictable and typically normal. Education and training in the management of children with epilepsy could improve requesting practice and the subsequent usefulness of electroencephalograms in the diagnosis of epilepsy syndromes.

CONCLUSION: Factors related to patients’ intrinsic characteristic

CONCLUSION: Factors related to patients’ intrinsic characteristics and disease severity as Blebbistatin concentration well as the promptness of sepsis recognition are associated with early death among severe septic patients.”
“Objective: To determine the endotracheal tube (ETT) size and presence of subglottic narrowing in children less than 1 year old with Pierre Robin Sequence (PRS).

Materials

and methods: We performed a retrospective review from 2005 to 2009 of infants with PRS who underwent diagnostic laryngoscopy (DL) and intubation.

Results: Fifteen children with a median age of 25 days were reviewed. All patients, except one, were born full term. Subglottic narrowing was visualized in 5 patients (33%). 73% of all patients required an ETT size smaller than what is recommended by intubation guidelines in the literature in regards to normative data based on age and weight.

Conclusion: Infants with PRS may have a higher incidence of subglottic stenosis and require a smaller ETT compared to the normal population. This pilot study warrants a larger prospective investigation to validate these findings. (C) 2011 Elsevier Ireland Ltd. All rights reserved.”
“Sperm quality plays an important role in determining embryo development and intracytoplasmic sperm injection (ICSI) outcome. Selection

of competent sperm based on its ability to bind to hyaluronic acid (HA) has been suggested as one of the methods to assess sperm quality. The aim of the present study was to examine whether injection of HA bound sperm helps in improving selleck kinase inhibitor outcome in patients undergoing ICSI with unexplained infertility having normal semen parameters.

Patients with unexplained infertility having normal semen parameters in accordance with this website WHO 2010 criterion, undergoing their first IVF-ICSI cycle

were enrolled during the course of the study.156 patients were prospectively randomized after oocyte retrieval and were assigned to either the ICSI group, where sperm selection for injection was based on visual assessment, or the PICSI group, where sperm were selected based on their ability to bind to HA. Only fresh embryo transfers were included in the analysis.

There was no difference in the fertilization rates, number of top quality embryos and clinical pregnancy rates between the ICSI and PICSI groups (65.7 % vs 64.7 %; 45.8 % vs 43.6 % and 35 % vs 35.2 % respectively). However, a higher pregnancy loss rate was observed in the ICSI group (25 % vs 12 %; P = 0.227) as compared to the PICSI group, but the difference was not statistically significant. Implantation rates were 22.03 % and 18.84 % in the PICSI and ICSI groups respectively. There were 22 (31 %) live births in the PICSI group and 21(26.3 %) live births in the ICSI group.