52 9 years In all children, the all-seeing needle was safely int

52.9 years. In all children, the all-seeing needle was safely introduced into the abdominal cavity under direct vision. Then, CO2 pneumoperitoneum was succesfully performed. The mean time for optical puncture was calculated as 1.1 Selleckchem Small molecule library +/- 0.8 minutes. No complication was encountered during the introduction

of the needle, creation of the pneumoperitoneum, and placement of the trocars. Conclusions: The all-seeing needle appears to be beneficial in safe entry and for creating pneumoperitoneum in laparoscopic pediatric urology cases. It eliminates the disadvantages of the Veress needle, which is blunt insertion, and may possibly prevent complications.”
“Fibromyalgia is a chronic pain disorder that is characterized by diffuse musculoskeletal pain and sensitivity to mechanical stimulation. In this pilot clinical trial,

we tested the effectiveness of low-dose naltrexone in treating the symptoms of fibromyalgia.

Participants HIF-1 pathway completed a single-blind, crossover trial with the following time line: baseline (2 weeks), placebo (2 weeks), drug (8 weeks), and washout (2 weeks).

Ten women meeting criteria for fibromyalgia and not taking an opioid medication.

Naltrexone, in addition to antagonizing opioid receptors on neurons, also inhibits microglia activity in the central nervous system. At low doses (4.5 mg), naltrexone may inhibit the activity of microglia and reverse central and peripheral inflammation.

Participants completed reports of symptom severity everyday,

using a handheld computer. In addition, participants visited the lab every 2 weeks for tests of mechanical, heat, and cold pain sensitivity.

Low-dose naltrexone reduced fibromyalgia symptoms in the entire cohort, with a greater than 30% reduction of symptoms over placebo. In TPX-0005 inhibitor addition, laboratory visits showed that mechanical and heat pain thresholds were improved by the drug. Side effects (including insomnia and vivid dreams) were rare, and described as minor and transient. Baseline erythrocyte sedimentation rate predicted over 80% of the variance in drug response. Individuals with higher sedimentation rates (indicating general inflammatory processes) had the greatest reduction of symptoms in response to low-dose naltrexone.

We conclude that low-dose naltrexone may be an effective, highly tolerable, and inexpensive treatment for fibromyalgia.”
“Although tractography can noninvasively map axonal pathways, current approaches are typically incomplete or computationally intensive. Fast, complete maps may serve as a useful clinical tool for assessing neurological disorders stemming from pathological anatomical connections such as epilepsy. We re-frame tractography in terms of logic and conditional probabilities. The formalism inherently includes global constraints and can compute connections between any two arbitrary regions of the brain.

Samples were taken right after spiking and during viral inactivat

Samples were taken right after spiking and during viral inactivation treatment by 1% TnBP-1% Triton X-45 at

31 degrees C. DENV-1 infectivity was assessed on Vero E6 cells by a focus-forming assay (FFA). Culture medium and complement-inactivated plasma were used as experimental controls. Experiments were done in duplicate. Results DENV-1 infectivity was 7.5 log in spiked plasma and 7.1 and 7.3 log in spiked cryoprecipitate. There was no loss of DENV-1 infectivity in the spiked materials, nor in the controls not subjected to S/D treatment. No infectivity was found in plasma and cryoprecipitate subjected to S/D treatment at the first time-point evaluated (10 min). Conclusion DENV-1 was strongly inactivated in plasma and cryoprecipitate, respectively, within 10 min of 1% TnBP/1% Triton X-45 treatment Selleckchem VX-680 at 31 degrees C. These data provide

a reassurance of the safety of such S/D-treated plasma and cryoprecipitate with regard to the risk of transmission of all DENV serotypes and other flaviviruses.”
“A best evidence topic was written according to a structured protocol. The question addressed was whether harvesting the saphenous vein (SV) as a conduit for coronary artery bypass grafting (CABG) using a no-touch technique would result in better patency rates. This technique involves the harvest of the SV with a pedicle of peri-vascular tissue left intact and the avoidance of distension of the vein prior to anastomosis. Proteasome cleavage XMU-MP-1 A total of 405 papers

were found using the reported searches of which eight represented the best evidence to answer the clinical question. The authors, date, journal, study type, population, main outcome measures and results are tabulated. The studies found analysed the ultrastructural and mechanical properties of the endothelium and vessel walls of the two harvesting techniques; the protein and enzymatic expression and activity observed; the early atherosclerotic changes detected; and the overall patency of the grafts during short- and long-term angiographical follow-up. Three small prospectively randomised studies compared the patency of grafts harvested using the two techniques and found significant improvements in graft patency using the no-touch harvesting technique in comparison to both the conventional technique and more importantly comparable to the left internal thoracic artery (LITA) patency. The most favourable difference was that of graft patency after 8.5 years of follow-up [90% vs. 76% (P=0.01), LITA patency 90%], and incidence of graft stenosis [11% vs. 25% (P=0.006)]. These findings were supported by the demonstrated improvements in the cellular integrity of the vessels and the reduction in the mechanisms leading to graft failure seen in the no-touch harvested SV grafts.

Postoperative follow-up of patients operated on with

this

Postoperative follow-up of patients operated on with

this modified technique indicates that the technique is feasible and safe, with no apparent this website damage to the ovary. (C) 2009, Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.”
“Objective: There is growing evidence on the usefulness of biomarkers in the early detection of preterm infants at risk for brain damage. However, among different tools Activin A, S100B protein and adrenomedullin assessment offer the possibility to investigate brain/multiorgan function and development. This could be especially useful in perinatal medicine that requires even more non-invasive techniques in order to fulfill the minimal handling in diagnostic and therapeutic strategy performance. Materials and methods: The concept of Unconventional Biological Fluid (UBF: urine and saliva) is becoming even stronger and regards the assessment in non-invasive biological fluids of biochemical markers involved in the cascade of events leading to brain damage. Results: Activin A, S100B protein

Transmembrane Transporters inhibitor and adrenomedullin in UBF were increased in preterm newborns developing brain damage and/or ominous outcome. Conclusions: The present manuscript offers an update on the usefulness of Activin A, S100B protein an adrenomedullin in UBF as brain damage markers. The findings open a new cue on the use of these markers in daily neonatal intensive care unit (NICU) activities.”
“Objectives:

To review the current status of lupus registries, highlight the importance and evolution of registries in clinical see more lupus research, discuss substantial advances in the understanding of lupus through the use of registries, and discuss the future role of registries in terms of opportunities and challenges.

Methods: The literature reviewed originated from the PubMed database and was limited to adult disease in articles published before June 01, 2008. Keywords used in the PubMed search included the following terms: systemic lupus erythematosus, registry, cohort, and database. All articles were sorted and analyzed according to a template devised by the authors describing the different types of registries.

Results: The most important features of a lupus registry are that they contain a large number of subjects and reflect a relatively real world environment for lupus patients. Data obtained from the lupus registries are essential for planning, designing, and conducting clinical lupus studies, especially those difficult, inappropriate, or even unethical to study in randomized controlled trials. Up to now, some well-conducted registries have received recognition for their contributions to lupus research through their focus on different goals: epidemiology, genetics, ethnic diversity, clinical features, or outcomes.

The ZBTSC technique is characterized by an increased sensitivity

The ZBTSC technique is characterized by an increased sensitivity with respect to a standard TSC analysis. Due to the absence of the thermally activated background current, new TSC peaks have been observed in both HPHT and pCVD diamond films, related to shallow activation energies usually obscured by the emission of the dominant impurities. The ZBTSC peaks are explained in terms HDAC inhibitor of defect discharge

in the nonequilibrium potential distribution created by a nonuniform traps filling at the metal-diamond junctions. The electric field due to the charged defects has been estimated in a quasizero bias TSC experiment by applying an external bias. (C) 2009 American Institute of Physics. [DOI: 10.1063/1.3126704]“
“Neonatal seizures are one of the most common neurological disorders in infants. However, the optimal treatment strategy for neonatal seizures Autophagy signaling inhibitor remains controversial and there is little data regarding current treatment of neonatal seizures. In this study we describe the current treatment of neonatal seizures and variation in practice among 31 pediatric hospitals in the United States. We retrospectively identified 6099 infants

hospitalized in the first month of life in one of 31 pediatric hospitals participating in the Pediatric Health Information System, with a discharge diagnosis of seizure. As expected, most treated infants received phenobarbital. However, there was significant interhospital variability for all treatments studied including any antiepileptic drug treatment, phenytoin treatment, antiepileptic drug treatment through discharge, number of antiepileptic drugs used, and treatment with pyridoxine (P < .001). These findings highlight the need for rigorous controlled outcome studies to determine optimal therapy for neonatal seizures and devise treatment standards.”
“The signs of metabolic syndrome following chronic excessive macronutrient intake include body weight gain, excess visceral

adipose deposition, hyperglycaemia, glucose and insulin BV-6 Apoptosis inhibitor intolerances, hypertension, dyslipidaemia, endothelial damage, cardiovascular hypertrophy, inflammation, ventricular contractile dysfunction, fibrosis, and fatty liver disease. Recent studies show increased activity of soluble epoxide hydrolase (sEH) during obesity and metabolic dysfunction. We have tested whether sEH inhibition has therapeutic potential in a rat model of diet-induced metabolic syndrome. In these high-carbohydrate, high-fat-fed rats, chronic oral treatment with trans-4-[4-(3-adamantan-1-ylureido)-cyclohexyloxy]-benzoic acid (t-AUCB), a potent sEH inhibitor, alleviated the signs of metabolic syndrome in vivo including glucose, insulin, and lipid abnormalities, changes in pancreatic structure, increased systolic blood pressure, cardiovascular structural and functional abnormalities, and structural and functional changes in the liver.

The potential of the Dy3+: YAG transparent ceramics for yellow or

The potential of the Dy3+: YAG transparent ceramics for yellow or blue laser emission is discussed. (C) 2011 American Institute of Physics. [doi:10.1063/1.3656718]“
“We studied the kinetics and mechanism of the charge-transfer polymerization of methyl Pitavastatin manufacturer methacrylate (MMA) initiated with n-butyl amine (BA) and carbon tetrachloride (CCl4) catalyzed by palladium dichloride (PdCl2 or PdII) in a dimethyl sulfoxide medium by using a dilatometric technique at 60 degrees

C. The rate of polymerization (Rp) was a function of [MMA], [BA], [CCl4], and [PdII]. The kinetic data indicated a mechanism involving the possible participation of the charge-transfer complex formed between the BAPdII complex and CCl4 or monomer in the polymerization of MMA. In the absence of either CCl4 or BA, no polymerization of MMA was observed under these experimental conditions. Rp was inhibited by hydroquinone; this suggested a free-radical initiation. (C) 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012″
“Background: Several techniques for liver resection have been developed. We compared radiofrequency-assisted (RF) and clamp-crush CUDC-907 inhibitor (CC) liver resection (LR) in terms of blood loss,

operating time and short-term outcomes in primary and metastatic tumour resection.

Methods: From 2002 to 2007, 196 consecutive patients with primary or metastatic hepatic tumours underwent RF-LR (n = 109; group 1) or CC-LR (n = 87; group 2) in our unit. Primary endpoints were intraoperative blood loss (and blood transfusion requirements) and total operative time. Secondary endpoints included postoperative complications, mortality and intensive care unit (ICU) and hospital stay. Data were collected retrospectively on all patients with primary or secondary liver lesions.

Results: Blood loss was similar (P = 0.09) between the two groups of patients with the exception of high MELD score

(> 9) cirrhotic patients, in whom blood loss was lower when RF-LR was used (P < 0.001). Total operative time and transection time were shorter in the CC-LR group (P = 0.04 and P = 0.01, respectively), except for high MELD score (> 9) cirrhotic patients, in whom total operation and transection times were shorter when RF-LR was used (P = 0.04). Rates of bile leak and abdominal abscess formation were higher Selleckchem Savolitinib after RF-LR (P = 0.04 for both).

Conclusions: Clamp-crush LR is reliable and results in the same amount of blood loss and a shorter operating time compared with RF-LR. Radiofrequency-assisted LR is a unique, simple and safe method of resection, which may be indicated in cirrhotic patients with high MELD scores.”
“Acinetobacter baumannii is an opportunistic Gram-negative pathogen with increasing relevance in a variety of hospital-acquired infections especially among intensive care unit patients. Resistance to antimicrobial agents is the main reason for A. baumannii spread. A.

Radical scavenging and metal chelating assays were based on the m

Radical scavenging and metal chelating assays were based on the measurement of 1,1-diphenyl-2-picrylhydrazyl (DPPH) and ferrozine absorbance at 517 and 562 nm, respectively. Mushrooms total phenolic and flavonoid contents were determined by spectrophotometric methods. Antimicrobial activity was measured using Kirby-Bauer Susceptibility

Test. Cytotoxicity was assessed using brine shrimp toxicity assay.

Results: Total phenolic and flavonoid contents ranged from 0.90 – 6.03 mg GAE per g of dry sample and 0.17 – 6.95 mg QE per g of dry sample, respectively. A. polytricha demonstrated the strongest radical scavenging and metal chelating activities. Moderate antimicrobial activity was found for extracts of both P. florida and A. polytricha. Cytotoxicity LD50 ranged from 46.9 – 115.8 mu g/ml.

Conclusion: Rabusertib mouse The results suggest that A. polytricha is a suitable candidate for chemoprevention and would safe for use in large doses.”
“Hypothesis: NF2 gene alterations may have a clinical impact in non-NF2 vestibular schwannomas (VSs).

Background: It has been suggested that NF2 mutations might correlate with clinical expression of VS in NF2 patients. The aim of this study was to analyze the impact of genetic alterations in the NF2 gene on epidemiologic, clinical, and radiologic features of patients with sporadic VS. The association between cigarette consumption and the molecular genetic findings was also studied.

Methods: The study group

consisted of 51 patients who underwent surgery Erastin for removal of vestibular schwannoma in our institution between January 2006 and December 2010. Five highly polymorphic microsatellite DNA markers were used to observe the frequency PD98059 of loss

of heterozygosity (LOH) in chromosome 22. The NF2 gene mutations were detected using polymerase chain reaction amplification and denaturing high-performance liquid chromatography analysis (PCR/dHPLC), and direct sequencing of NF2. Multiplex ligation-dependent probe amplification (MLPA) of the NF2 gene was also performed.

Results: An NF2 mutation was identified in 49%, 22q LOH in 57%, and MLPA alterations in 13.7% of the cases. One mutational hit was present in 27%, and 2 hits were present in 45% of the tumors. No association was found between the type of NF2 mutation and relevant clinical parameters. The presence of NF2 mutations detected by PCR/dHPLC was associated with no complaint of hearing loss at the time of diagnosis (p = 0.023), with subjective aural fullness (p = 0.022) and with an absence of tumor involvement of the internal auditory canal (p = 0.029). Patients with NF2 mutations had lower mean corrected PTA thresholds compared with those with no NF2 mutation (p = 0.037). Inactivation of the NF2 gene by mutation, MLPA, or LOH was more frequent in smokers when compared with never smokers (p = 0.048).

Conclusion: NF2 mutations may play a role in the pathophysiology of hearing loss as well as in the pattern of growth of VS.

066) Median OS was significantly longer in patients negative for

066). Median OS was significantly longer in patients negative for TRAP1 than those positive for TRAP1(p=0.023). Patients negative for ERCC1 expression also had a better OS than those positive for ERCC1 (p=0.021). The median OS was 30.9 months for patients negative for TRAP1 and ERCC1 compared to 13.2 months for those positive for TRAP1 and/or positive DMH1 chemical structure for ERCC1 expression (p=0.006). The combination of TRAP1 and ERCC1 expression was significantly associated with the response to chemotherapy (p=0.046) and independently predicted median OS in multivariate analysis (hazard ratio, 2.98; 95% confidence interval, 1.18 to 7.49).

Conclusion The present study demonstrates that the combination of TRAP1 and ERCC1

expression predicts the survival of metastatic CRC patients who were treated with oxaliplatin/5-fluorouracil.”
“Prangos pabularia Lindl. (Apiaceae) is a widespread perennial herb distributed from Russia to Iran, Turkey, India, Central Asia and Caucasian. It has been used in folk medicine from ancient times as a diuretic agent www.selleckchem.com/products/17-DMAG,Hydrochloride-Salt.html and a treatment for leukoplakia, digestive disorders, healing scars and stopping bleeding. In the present study, the composition of the essential oils isolated from leaves, fruits and umbels of this plant was analyzed using GC-MS. The results showed that the leaves’

oil was dominated by sesquiterpene derivatives with spathulenol (16.09%) and alpha-bisabolol (14.30%) as major components. The fruits and umbels oil were characterized by monoterpenes comprised of alpha-pinene (33.87, 21.46%)

as the main compound. The essential oil of the plant leaves exhibited high allelopathic activity.”
“Purpose Cancer-related inflammation affects many aspects of malignancy. We confirm the effects of early postoperative systemic inflammation on cancer prognosis.

Materials and Methods Selleck Momelotinib Six hundred consecutive patients underwent surgery for colorectal cancer from 2006 to 2009. Measurements of white blood cells, neutrophils, lymphocytes, monocytes, and platelet counts were performed preoperatively, daily until the fourth postoperative day, and subsequently every two days. Patients were divided into three groups based on the days spent on the leukocyte count to drop below 10,000/mm(3) after surgery.

Results Preoperative white blood cell (WBC) counts correlated with stage of disease. In univariate survival analyses, tumor, node, metastasis (TNM) stage, and monocyte count were associated with cancer-free survival. In addition, cancer-free survival outcomes were worse in patients who required more than four days for the normalization of WBC count. A TNM stage greater than II and the neutrophil lymphocyte ratio were associated with the duration of overall survival. In a multivariate analysis of these significant variables, TNM stage, an interval longer than four days for normalization of WBC counts and monocyte count independently associated with cancer-free survival.

He used to tailor his prescriptions and frequency of controls to

He used to tailor his prescriptions and frequency of controls to each patient and phase of the disease, thus anticipating the tailored therapies and the patient empowerment presently considered as fundamental in chronic diseases. Furthermore, he suggested that physicians should

work outside the hospital in small coordinated teams, in which volunteers, dietitians and laboratory technicians would play a crucial role. Patient-centered care and the importance of nonmedical team members are clear from the first lines of his book. As far as we know, he was the first physician to stress the role of volunteers in CKD, DMXAA solubility dmso anticipating by decades nonprofit organizations such as the National Kidney Foundation.”
“Background: Missing outcome data are very

common in smoking cessation trials. It is often assumed that all such missing data are from participants who have been unsuccessful in giving up smoking (“”missing=smoking”"). Here we use data from a recent Internet based smoking cessation trial in order to investigate which of a set of a priori chosen baseline variables are predictive of missingness, and the evidence for and against the “”missing=smoking”" assumption.

Methods: We use a selection model, which models the probability that the outcome is observed given the outcome and other variables. The selection model includes Wnt signaling a parameter for which zero indicates that the data are Missing at Random (MAR) and large values indicate “”missing=smoking”". We examine the evidence for the predictive power of baseline variables in the context of a sensitivity analysis. We use data on the selleck chemicals number and type of attempts made to obtain outcome data in

order to estimate the association between smoking status and the missing data indicator.

Results: We apply our methods to the iQuit smoking cessation trial data. From the sensitivity analysis, we obtain strong evidence that older participants are more likely to provide outcome data. The model for the number and type of attempts to obtain outcome data confirms that age is a good predictor of missing data. There is weak evidence from this model that participants who have successfully given up smoking are more likely to provide outcome data but this evidence does not support the “”missing=smoking”" assumption. The probability that participants with missing outcome data are not smoking at the end of the trial is estimated to be between 0.14 and 0.19.

Conclusions: Those conducting smoking cessation trials, and wishing to perform an analysis that assumes the data are MAR, should collect and incorporate baseline variables into their models that are thought to be good predictors of missing data in order to make this assumption more plausible.

Consequently, transient epileptic amnesia may be readily misdiagn

Consequently, transient epileptic amnesia may be readily misdiagnosed as a nonepileptic memory dysfunction in older individuals. When appropriately recognized, it has been described as a treatment-responsive syndrome amenable to antiepileptic drugs. We describe a patient Selonsertib mouse with drug-resistant transient epileptic amnesia treated with unilateral temporal lobectomy. Prolonged postictal slowing in the mesial temporal structures was evident on invasive electroencephalography 5 hours after the occurrence of a brief focal seizure. These findings support the theory of a Todd phenomenon as the underlying pathophysiological mechanism in transient epileptic amnesia.

(C) 2010 Elsevier Inc. All rights reserved.”
“Bulgaria had been free from brucellosis since 1958, but during 2005-2007, a reemergence of human and animal disease was recorded. The reemergence of this zoonosis in the country highlights the importance of maintaining an active surveillance system for infectious diseases that will require full cooperation between public health and veterinary authorities.”
“Study Design. Cross sectional.

Objective.

This study presents the factor analysis of the Spinal Appearance Questionnaire (SAQ) and its psychometric properties.

Summary of Background Data. Although the SAQ has been administered to a large sample of patients with adolescent idiopathic scoliosis (AIS) treated surgically, its psychometric properties have not been fully evaluated. This study presents the factor analysis and scoring of the SAQ and evaluates its psychometric properties.

Methods. S63845 supplier The SAQ and selleck the Scoliosis Research Society-22 (SRS-22) were administered to AIS patients who were being observed, braced or scheduled for surgery. Standard demographic data and radiographic measures including Lenke type and curve magnitude were also collected.

Results. Of the 1802

patients, 83% were female; with a mean age of 14.8 years and mean initial Cobb angle of 55.degrees (range, 0 degrees 123 degrees). From the 32 items of the SAQ, 15 loaded on two factors with consistent and significant correlations across all Lenke types. There is an Appearance (items 1-10) and an Expectations factor (items 12-15). Responses are summed giving a range of 5 to 50 for the Appearance domain and 5 to 20 for the Expectations domain. The Cronbach’s alpha was 0.88 for both domains and Total score with a test-retest reliability of 0.81 for Appearance and 0.91 for Expectations. Correlations with major curve magnitude were higher for the SAQ Appearance and SAQ Total scores compared to correlations between the SRS Appearance and SRS Total scores. The SAQ and SRS-22 Scores were statistically significantly different in patients who were scheduled for surgery compared to those who were observed or braced.

Conclusion.

A comparison of the layer thicknesses with drug release measureme

A comparison of the layer thicknesses with drug release measurements reveals that capsules with the thinnest shellac layers provide the best entrapment. Additional squeezing experiments show that the shellac layer makes the capsules also mechanically more stable.”
“The most severe forms of xerostomia and salivary gland dysfunction, as well as a severely reduced quality of life, are seen in Sjogren syndrome (SS) and after radiotherapy for head and neck cancer. For both

conditions, no effective regenerative therapies yet exist. Thus, the aim Screening Library in vitro of this article was to assess, through systematic review, the potential benefit of mesenchymal stem cell (MSC) therapy in radiation-induced and SS-related salivary gland dysfunction and xerostomia. We searched PubMed/MEDLINE, selleck chemicals Embase, Web of Science, the Cochrane Database of Systematic Reviews, the World Health Organization Clinical Trials Registry Platform,

and Google Scholar. We identified 6 separate study comparisons eligible for inclusion. Owing to the limited number of studies, we conclude that more randomized, adequately powered clinical trials are needed to validate the potential beneficial effect of MSCs on salivary gland dysfunction and xerostomia. Nonetheless, the preliminary studies identified in the present review were encouraging for further research.”
“Purpose Adult hepatoblastoma is rare and the prognosis is extremely poor. Although surgery offers the only chance for cure, it often recurs even after complete resection. To date, no therapeutic strategy has been established.

We report here a rare case of adult hepatoblastoma successfully MK-4827 cost treated with multimodal treatment.

Methods A 25-year-old female who had been suffering from right hypochondriac pain was referred to our hospital. Preoperative diagnosis was adult hepatoblastoma. Huge liver tumor was initially deemed unresectable. An intensive chemotherapy including arterial chemoinfusion using interventional radiological technique resulted in a remarkable tumor reduction. Furthermore, lung metastasis that had later appeared was completely treated with additional chemotherapy. Then she underwent curative surgery at 8 months after initial treatment.

Results The pathological diagnosis was well-differentiated hepatoblastoma. The postoperative course was uneventful and she received short-course adjuvant chemotherapy. She survived for over 4 years after diagnosis.

Conclusions To our knowledge, this is the first report demonstrating long-term survival of a patient with initially unresectable adult hepatoblastoma. Our new therapeutic strategy may provide new insights into the treatment of this fatal disease.”
“Various techniques for the correction of sagittal craniosynostosis have been described in the literature. Nevertheless, there is a lack of consensus regarding surgical procedure and timing, although a long-term anthropometric analysis may shed light on this controversy.