Of the 14 patients with a thrombus located in the left ventricle,

Of the 14 patients with a thrombus located in the left ventricle, 12 (86%) presented with left ventricular motion abnormalities using conventional echocardiography, whereas wall motion abnormalities

click here were observed in all 14 patients (100%) using contrast agent. In these patients, 91 and 99% of left ventricular segments were well visualized using conventional and contrast echocardiography, respectively (p < 0.0001).\n\nConclusions. – Contrast echocardiography may be useful for the tissue characterization of intracardiac masses. (C) 2009 Elsevier Masson SAS. All rights reserved.”
“Objective: Smoking is a prominent risk factor for lung cancer. However, it is not an established prognostic factor for lung cancer in clinics. To date, no gene test is available for diagnostic screening of lung cancer risk or prognostication of clinical outcome in smokers. This study sought to identify a smoking associated gene signature in order to provide a more precise diagnosis and prognosis of lung cancer in smokers.\n\nMethods and materials: An implication network based methodology was used to identify

biomarkers by modeling crosstalk with major lung cancer signaling pathways. Specifically, the methodology contains the following steps: (1) identifying genes significantly associated with lung cancer survival; (2) selecting candidate genes which are differentially expressed in smokers versus non-smokers from the survival genes identified in Step 1; (3) from these candidate genes, constructing gene coexpression networks based on prediction Napabucasin ic50 logic for the smoker group and the non-smoker group, respectively; (4) identifying smoking-mediated differential components, i.e., the unique gene coexpression patterns specific to each group; and (5) from the differential components, identifying genes directly co-expressed with major lung cancer signaling hallmarks.\n\nResults: A smoking-associated 6-gene signature was identified for prognosis

of Vorinostat manufacturer lung cancer from a training cohort (n =256). The 6-gene signature could separate lung cancer patients into two risk groups with distinct post-operative survival (log-rank P < 0.04, Kaplan-Meier analyses) in three independent cohorts (n = 427). The expression-defined prognostic prediction is strongly related to smoking association and smoking cessation (P < 0.02; Pearson’s Chi-squared tests). The 6-gene signature is an accurate prognostic factor (hazard ratio = 1.89,95% Cl: [1.04, 3.431) compared to common clinical covariates in multivariate Cox analysis. The 6-gene signature also provides an accurate diagnosis of lung cancer with an overall accuracy of 73% in a cohort of smokers (n = 164). The coexpression patterns derived from the implication networks were validated with interactions reported in the literature retrieved with STRING8, Ingenuity Pathway Analysis, and Pathway Studio.\n\nConclusions: The pathway-based approach identified a smoking-associated 6-gene signature that predicts lung cancer risk and survival.

If preexposure prophylaxis is used, precautions similar to those

If preexposure prophylaxis is used, precautions similar to those in the current heterosexual

preexposure prophylaxis trials would be recommended, and the unknown risks of preexposure prophylaxis used during conception and early fetal development should be considered. Anecdotal reports suggest that oral preexposure prophylaxis use is already occurring. It is time to have open discussions of when and how preexposure prophylaxis might be indicated for HIV-discordant couples attempting conception.”
“Hippocampal neurons of neonatal rats were cultured in serum-free culture medium for 5 days in vitro, and treated Emricasan purchase with the Rho-kinase inducer lysophosphatidic acid. Atomic force microscopy revealed that the numbers of level-1, -2 and -3 neurites protruding from rat hippocampal neurons was significantly reduced. After treatment with the Rho

kinase inhibitor Y27632, a significant increase in the numbers of these neurites was observed. Our experimental findings indicate that the Rho-kinase pathway is closely associated with the neurites of hippocampal neurons.”
“ObjectiveRecent genome-wide association studies (GWAS) have identified 3 loci in or near PRDM16 (1p36.32, rs2651899), LRP1 (12q13.3, rs11172113) and TRPM8 (2q37.1, rs10166942) in the population-based Women’s Genome Health Study (WGHS) of migraine, and 2 loci in or near TRPM8 and LRP1 were repeated in European GWAS study. To evaluate whether

the same variants are related to migraine in Chinese population, we investigated migraine with aura (MA) CBL0137 cell line and migraine without aura (MO) patients of Chinese IPI-145 solubility dmso Han ethnicity in mainland China.\n\nMethodsA case-control study in a cohort of 207 migraine cases and 205 ethnically matched controls was conducted by using the dual-color fluorescence resonance energy transfer (FRET) probes analysis.\n\nResultsThe genotypes of all polymorphisms in 2 groups followed the Hardy-Weinberg equilibrium. We found significant differences in allele distribution of rs2651899 variant in PRDM16 between MO patients and control subjects (P=.049, OR=1.335, 95%CI 1.001-1.782), and there were no difference between MA patients and controls in the frequency of genotype and allele. Also, no significant differences in genotypic and allelic distributions between MA or MO patients and controls were observed in the polymorphisms of rs10166942 of TRPM8 and rs11172113 of LRP1, and there was no significant difference comparing male with female in all loci.\n\nConclusionOur data suggested that rs2651899 variant in PRDM16 plays a potential role in Chinese MO migraine susceptibility, and gender may not play a role.”
“Land use can alter the phosphorus (P) pool in soil. Understanding detailed P changes derived from different land uses is important for sustainable development of soil resources.

“The effects of aluminum (Al) exposure on reproductive fun

“The effects of aluminum (Al) exposure on reproductive functions of male rats were investigated. Forty male Wistar rats (4 weeks old) weighing 75-95 g were randomly divided into four groups and orally exposed to 0 (control group GC), 64.18 (low-dose group GL), 128.36 (middle-dose group GM), and 256.72 (high-dose group GH) mg/kg aluminum trichloride in drinking water for 120 days. The levels of testosterone (T), follicle-stimulating hormone (FSH), and luteinizing hormone (LH) were determined

by radioimmunoassay. The androgen receptor (AR) expressions in testes were detected selleck chemical respectively by immunohistochemistry and time quantitative PCR. Results showed that the levels of T and LH in GM and GH were lower than those in GC (P < 0.05), but there were no significant changes in FSH level in all Al-treated groups (P > 0.05). selleck chemicals AR protein expressions in GM and GH were lower than those in GC (P < 0.05), and

there was a dose-response relationship between Al-exposure doses and AR protein expressions. The levels of AR mRNA expressions were lower in all Al-treated groups than those of GC (P < 0.05). The results indicate that Al can cause endocrinal disorders and interfere with AR expression, which suppresses development and functional maintenance of the testes.”
“Background and Aim: To evaluate the prevalence and risk factors of gastroesophageal reflux disease (GERD) in a general population in Taiwan.\n\nMethods: A validated symptom questionnaire, the Chinese GERD questionnaire, was utilized to determine the prevalence of GERD within a community in Taiwan. A cut-off value for GERD diagnosis was a total score >= 12. Additionally,

demographic data, including sex, age, body mass index, and consumption of tobacco and alcohol, were recorded, and a logistic regression analysis was conducted to search the independent risk factors for the development of GERD in a general population.\n\nResults: In total, 1238 residents were recruited for this study. The monthly frequencies of heartburn, epigastric acidic discomfort, and acid regurgitation were 4.4%, 3.7%, and 2.9%, respectively. PXD101 The GERD prevalence was 25% in the community. The multivariate analysis showed that female sex and age of 40-49 years and 50-59 years were independent risk factors related to the development of GERD, with odd ratios of 1.71, 3.65, and 2.41, respectively (95% confidence intervals: 1.26-2.34, 1.62-8.21, and 1.11-2.54, respectively).\n\nConclusions: GERD has become a common disorder in the general population in Taiwan. Female sex and age of 40-49 years and 50-59 years are risk factors for the development of GERD within a community.”
“McArdle disease (MD) is a metabolic myopathy due to myophosphorylase deficiency.

VAP is the most frequent intensive-care-unit (ICU)-acquired infec

VAP is the most frequent intensive-care-unit (ICU)-acquired infection among patients receiving IMV. It contributes to an increase in hospital mortality, duration of MV and ICU

and length of hospital stay. Therefore, it worsens the condition of the critical patient and increases the total cost of hospitalization. The introduction of preventive measures has become imperative, to ensure control and to reduce the incidence of VAP. Preventive measures focus on modifiable risk factors, mediated by non-pharmacological and pharmacological evidence based strategies recommended by guidelines. These measures are intended to reduce the risk associated with endotracheal intubation and to prevent microaspiration of pathogens to the lower airways. (C) 2013 Sociedade Portuguesa de Pneumologia. Published by Lonafarnib nmr Elsevier Espana, S.L. All rights reserved.”
“Objective To evaluate whether hyperemesis gravidarum (HG) affects first-trimester maternal SU5402 serum PAPP-A and free beta-hCG levels.\n\nMethod An observational study was conducted in 115 cases of HG and 110 control pregnancies who attended the first-trimester prenatal screening program between January 2006 and July 2010.\n\nResults Maternal serum TSH levels were lower and free T4, and transaminases (ALT, AST) levels were higher in pregnancies complicated with HG compared with

controls (p < 0.05 for all). In HG cases, median values of maternal serum PAPP-A were significantly higher with respect to normal pregnancies (1.2 vs 1.0 MoM; p = 0.009). Similarly,

median values of free beta-hCG were 1.3 MoM in HG pregnancies and 1.0 MoM in controls 4SC-202 nmr (p = 0.006). Multivariate analysis revealed that PAPP-A and hCG were independently associated with HG after controlling for TSH, free T4, AST, and ALT.\n\nConclusion HG is associated with elevated levels of PAPP-A and free beta-hCG, and such changes are independent of serum indicators of thyroid and liver function. Copyright (C) 2011 John Wiley & Sons, Ltd.”
“Background: The way people use health technology assessment (HTA) terms varies considerably across Europe. Such variation can lead to misunderstandings when reading HTA reports from different contexts. This work is one of the outputs of the EUnetHTA Project and was undertaken between 2006 and 2008.\n\nObjectives: The aim of this study was to develop a glossary of HTA adaptation terms to help reduce the misunderstandings of terms used in HTA reports from contexts other than the reader’s own.\n\nMethods: Several HTA glossaries were examined to identify ways in which an additional glossary could offer readers something new and to identify adaptation terms for inclusion. Twenty-eight European HTA organizations provided terms for the glossary and drafted descriptions and examples of how each specific term was used in their particular setting.

The monomorphic type was the most common, with diffuse large B-ce

The monomorphic type was the most common, with diffuse large B-cell lymphoma as the origin. The most frequent presentation was fever. Four in five patients had Epstein-Barr related PTLD. All patients received various regimens FK228 in vitro of immunosuppression reduction (IR), with 4 converting CNI to mTOR inhibitor (imTOR). Subsequent treatment (when needed) was chemotherapy, radiotherapy, and surgery. The maximum follow-up time was 6.7 years, with a 50% mortality rate that occurred at a median time of 3.5 months (2 died with functioning kidney). All 4 patients who were in remission

at the end of follow-up had CNI conversion to imTOR, and none lost the allograft. Conclusions. Despite the small number of cases, our results confirm the high PTLD impact in overall and allograft survival. Our PTLD type distribution is in accord with the literature. First-line PTLD treatment is IR, but the best method is still unknown; our results may suggest a beneficial effect of CNI conversion to imTOR.”
“Cell-to-cell communication, or quorum sensing (QS), enables cell CA4P datasheet density-dependent regulation of bacterial gene expression which can be exploited for the autonomous-signal-guided expression of recombinant proteins (C. Y. Tsao, S. Hooshangi, H.

C. Wu, J. J. Valdes, and W. E. Bentley, Metab. Eng. 12:291-297, 2010). Earlier observations that the metabolic potential of Escherichia coli is conveyed via the QS signaling molecule autoinducer-2 (AI-2) suggested that the capacity for protein synthesis could also be affected by AI-2 signaling (M. P. DeLisa, J. J. Valdes, and W. E. Bentley, J. Bacteriol. 183:2918-2928, 2001). In this work, we found that simply adding conditioned medium containing high levels of GSK J4 concentration AI-2 at the same time as inducing the synthesis of recombinant proteins doubled the yield of active product. We have hypothesized that AI-2 signaling “conditions” cells as a natural consequence of cell-to-cell communication and that this could tweak the signal transduction

cascade to alter the protein synthesis landscape. We inserted luxS (AI-2 synthase) into vectors which cosynthesized proteins of interest (organophosphorus hydrolase [OPH], chloramphenicol acetyltransferase [CAT], or UV-variant green fluorescent protein [GFPuv]) and evaluated the protein expression in luxS-deficient hosts. In this way, we altered the level of luxS in the cells in order to “tune” the synthesis of AI-2. We found conditions in which the protein yield was dramatically increased. Further studies demonstrated coincident upregulation of the chaperone GroEL, which may have facilitated higher yields and is shown for the first time to be positively regulated at the posttranscriptional level by AI-2. This report is the first to demonstrate that the protein synthesis capacity of E. coli can be altered by rewiring quorum sensing circuitry.

One way analysis of variance (ANOVA) was used to test the null hy

One way analysis of variance (ANOVA) was used to test the null hypothesis. Results: Fifty patients (43) were found to be HIV positive and were put on HAART. The other 66 patients (57) were HIV negative. The sputum conversion rate for HIV positive TB patients after two months and five months was 88

and 94, respectively. The sputum conversion rate for HIV negative TB patients at two months and after five months was 92 and 97, respectively. However, there was no significant difference in the bacteriological outcome responses to TB chemotherapy between the two groups. Conclusion: The high sputum conversion rates in the two groups indicated good control and management of TB. Findings in this study indicated that delayed use of HAART during TB treatment leads to better outcome in TB treatment. CYT387 nmr SNX-5422 supplier The study recommends more concerted efforts to provide TB treatment to HIV positive TB patients in Kenya.”
“Objectives Poor understanding of drugs prescribed at the time of paediatric emergency department (PED) discharge has been described. The aim of this study was to determine parents’ and patients’ expectations regarding drug information. Methods A 7-week prospective study was conducted with

French-speaking families presenting to the PED of a Swiss university hospital. Standardised questionnaires, using categorical Likert scale (from 1=useless to 6=very useful) were filled in by parents or paediatric patients aged bigger

than = 12 years old. A general section (18 questions) focused on drug’s effect, administration, formulation, storage and costs. A specific additional section intended for patients aged bigger than = 12 years old concerned overdosing, drug and sport, alcohol or other medication. Results were expressed as mean +/- SD. Results Sixty-two questionnaires were collected (9 patients bigger than = 12 years). Information considered the most useful by parents were: delay between subsequent dose if no effect (5.4 +/- 0.9), regular or on demand posology (5.3 +/- 1.1), treatment discontinuation if child is improving (5.1 +/- 1.4), emergency symptoms which require medical care (5.1 +/- 1.4), administration with meals (5.1 +/- 1.3), drug effects (5.5 +/- 1.0), interactions (5.1 +/- 1.4). Information on drug formulations, storage, costs was evaluated as less useful. Patients bigger click here than = 12 years were more interested in drugs’ impact on sport capacities (5.2 +/- 1.6) and risks of overdosing (5.1 +/- 1.7). Information on drug interaction with alcohol was assessed as more useful than with acne treatment or contraceptives. Conclusions Potentially useful information is not included in the official drugs’ leaflets for patients. Missing information was prioritised based on parents’ expectations and will be included in preparation of patient-centred drug information cards to improve continuity of care after PED discharge.

Results: After adjusting for potential confounders, every one-poi

Results: After adjusting for potential confounders, every one-point decline in global cognitive function (odds ratio [OR]: 1.57 [1.21-2.03]), MMSE (OR: 1.07 [1.03-1.10]), Episodic Memory (OR: 1.46 [1.14-1.86]), and Perceptual Speed (OR: 1.05 [1.02-1.07]) scores were associated with increased risk for EM. Lowest tertiles in global cognitive function (OR: 2.71 [1.49-4.88]), MMSE (OR: 2.02 [1.07-3.80]), Episodic Memory (OR: 2.70 [1.41-5.16]), and

Perceptual Speed (OR: 4.41 [2.22-8.76]) scores were associated with increased risk for EM. Conclusion: Decline in global cognitive function, MMSE, and Perceptual Speed scores were associated with increased risk for EM.”
“The Bloom syndrome helicase, BLM, has numerous functions that prevent mitotic crossovers. PD-1/PD-L1 Inhibitor 3 We used unique features of Drosophila melanogaster to investigate origins and properties of mitotic crossovers that occur when BLM is absent. Induction of lesions Rabusertib nmr that block replication forks increased crossover frequencies, consistent with functions for BLM in responding to fork blockage. In contrast, treatment with hydroxyurea, which stalls forks, did not elevate crossovers, even though mutants lacking BLM are sensitive to killing by this agent. To learn about sources of spontaneous recombination, we mapped mitotic crossovers in mutants lacking BLM. In the male germline, irradiation-induced crossovers were distributed

randomly across the euchromatin, but spontaneous crossovers were nonrandom. We suggest that regions of the genome with a high frequency of mitotic crossovers may be analogous to common fragile sites in the human genome. Interestingly, in the male germline there is a paucity of crossovers in the interval that spans the pericentric heterochromatin, but in the female germline

this interval is more prone to crossing over. Finally, our system allowed us to recover pairs of reciprocal crossover chromosomes. Sequencing of these revealed the existence Panobinostat concentration of gene conversion tracts and did not provide any evidence for mutations associated with crossovers. These findings provide important new insights into sources and structures of mitotic crossovers and functions of BLM helicase.”
“A rapid and sensitive LC method was developed and validated for the determination of diastereomeric purity of tenofovir alafenamide (GS-7340). Baseline separation with resolution bigger than 2.8 was achieved within 17 min on a CHIRALPAK AD-3 (250 x 4.6 mm; particle size 3 mu m) column using n-hexane:2-propanol (60:40 v/v) as the mobile phase at a flow rate of 1 mL min(-1). The analytes were detected by UV absorbance at 260 nm. The effects of ethanol, 2-propanol, and temperature on diastereomeric selectivity and resolution of diastereomerism were evaluated. The method was extensively validated and proved to be robust. The recoveries were between 98.17 and 102.84 % with smaller than 1.93 % relative standard deviation. The limit of detection and limit of quantitation for GS-7339 were 0.77 and 2.

Both orders can explain

the RS reduction, but the octupol

Both orders can explain

the RS reduction, but the octupole order breaks the time reversal symmetry, in agreement with the ligand NMR measurements, while the quadrupole order does not. Consequently, the E-u octupole order is favorable for the HO of URu2Si2.”
“Radiation induced genomic instability is a well-studied phenomenon, the underlying mechanisms of which are poorly understood. Persistent oxidative stress, mitochondrial dysfunction, elevated cytokine levels and epigenetic changes are among the mechanisms invoked in the perpetuation of the phenotype. To determine whether epigenetic aberrations affect genomic instability we measured DNA methylation, mRNA and microRNA (miR) levels in well characterized chromosomally stable and unstable clonally expanded single cell survivors of irradiation. While no changes GSK1838705A in DNA methylation were observed for the gene promoters evaluated, increased LINE-1 methylation was observed for two unstable clones (LS12 and CS9) and decreased Alu element methylation was observed for the other two unstable clones (115 and Fe5.0-8). These relationships also manifested for mRNA and miR expression. mRNA identified for the LS12 and CS9 clones were most similar to each other (261 mRNA),

while the 115 and Fe5.0-8 clones were more similar to each other, and surprisingly also similar to the two stable clones, 114 and 118 (286 mRNA among these four clones). Pathway analysis showed enrichment for pathways involved in mitochondrial function and cellular redox, themes routinely invoked in JQ1 ic50 genomic instability. The commonalities between the two subgroups of clones were also observed for miR. The number of miR for which anti-correlated

mRNA were identified suggests that these miR exert functional effects in https://www.selleckchem.com/products/gant61.html each clone. The results demonstrate significant genetic and epigenetic changes in unstable cells, but similar changes are almost as equally common in chromosomally stable cells. Possible conclusions might be that the chromosomally stable clones have some other form of instability, or that some of the observed changes represent a sort of radiation signature and that other changes are related to genomic instability. Irrespective, these findings again suggest that a spectrum of changes both drive genomic instability and permit unstable cells to persist and proliferate.”
“In vivo the vasculature provides an effective delivery system for cellular nutrients; however, artificial scaffolds have no such mechanism, and the ensuing limitations in mass transfer result in limited regeneration. In these investigations, the regional mass transfer properties that occur through a model scaffold derived from the human umbilical vein (HUV) were assessed.

04 (0 86, 1 27), 1 13 (0 95, 1 36), 1 01 (0 86, 1 18), and 1 18 (

04 (0.86, 1.27), 1.13 (0.95, 1.36), 1.01 (0.86, 1.18), and 1.18 (0.89, 1.56), respectively (P for trend = 0.91). The RRs of CVD mortality across the same categories of coffee intake were 1, 0.99 (0.75, 1.31), 1.03 (0.80, 1.35), 0.97 (0.78, 1.21), and 1.25 (0.85, 1.84), respectively (P for trend = 0.76). Similarly, caffeine intake was not associated with total or CVD mortality. Finally, we observed no association of the most recent coffee and caffeine intakes with total and CVD mortality

in the subsequent buy Buparlisib 2 y.\n\nConclusion: Consumption of filtered caffeinated coffee was not associated with CVD or all-cause mortality in women with CVD. Am J Clin Nutr 2011;94:218-24.”
“Laparoscopic P5091 price sleeve gastrectomy (LSG) has become a common option in the management of morbid obesity. Although this procedure seems easier, many caveats remain, especially in terms of leakage. Other serious complications include strictures, bleeding, and gastroesophageal reflux disease (GERD). Strictures are related to operative technique but also to healed leaks and fistulas. To our knowledge, the literature reports on the physiopathology and management of strictures after LSG are scarce.\n\nA retrospective analysis of our

database provided a total of 16 patients who underwent laparoscopic surgery for the treatment of strictures. A comprehensive review of each case was done including their management.\n\nSixteen patients were treated laparoscopically for strictures. There were eight females (mean age, 40.6 years). Most common complaints were dysphagia (n = 14) and/or GERD (n = 8). Body Mass Dactolisib PI3K/Akt/mTOR inhibitor Index was 30.5 kg/m(2) +/- 9.3. Fourteen patients underwent a seromyotomy (SM) and two a wedge resection of the stenosis. After SM, morbidity

included five leaks on the short term and five reoperations in the long-term. Of the 16 patients, 12 were treated satisfactorily, three required endoscopies and one had minimal GERD symptoms.\n\nStrictures and stenosis can be managed by laparoscopic approach with acceptable results. SM can be useful but carries a high complication rate. Accurate technique with parsimonious use of coagulation and possibly with the systematic use of an omental patch might lead to better results. The wedge resection of the stomach including the stricture was performed successfully in two cases. In addition, wedge resection was used secondarily in two other cases to address a complication of the seromyotomy.”
“The authors adopted the angiographic osmotic blood-brain barrier opening method on pigs. During the angiography beside the previously experienced complications, new complications that unambiguously related to the BBB opening have not been occurred.

Results: Although the mRNA expression was significantly elevated

Results: Although the mRNA expression was significantly elevated in 46.6% of the examined tumor tissues; its expression was low in others (36.6%).

Moreover, there was only a marginal statistical difference MDV3100 concentration between the MTDH gene expression of all tumor specimens compared to their paired non-tumor ones and no statistically significant association with the grades and types of the tumors. Conclusion: Taken together, our results demonstrated that expression of MTDH at the transcriptional level may be increased in gastric cancer tissue samples but with considerable heterogeneity. Due to this, it may have the potential to be used as a target for diagnostic/therapeutic purposes only in a subset of patients.”

Keloids and hypertrophic scars are benign growths of dermal collagen that can cause physical and psychological (cosmetic) problems for patients.\n\nMethods. In this 12-week, double-blind, clinical trial, 40 patients were randomized into two study groups. Patients in group 1 were given intralesional triamcinolone acetonide (TAC), and patients in group 2 were given a combination of TAC and 5-fluorouracil (5-FU); both groups received injections at weekly intervals for 8 weeks. Lesions were assessed for erythema, pruritus, pliability, height, length and width.\n\nResults. Four patients in group 1 and three patients in group 2 failed to complete the study. At the 8-week and 12-week follow-up visits, both groups showed an acceptable improvement in nearly all parameters, Selleck Nutlin3 but phosphatase inhibitor these were more significant in the TAC + 5-FU group (P < 0.05 for all except pruritus and percentage of itch reduction). Good to excellent (> 50%) improvement were reported by 20% of the patients in group 1 and 55% of the patients in group 2, which was significantly

different (P = 0.02). Good to excellent responses was reported by trained observers as 15% in group 1 and 40% in group 2. Their difference was not significant (P = 0.08).\n\nConclusion. The overall efficacy of TAC + 5-FU was comparable with TAC, but the TAC + 5-FU combination was more acceptable to patients and produced better results.”
“Unlike many other areas of therapeutics, specific regulatory trial programmes are required to be undertaken in newly diagnosed epilepsy to support the licensing of novel antiepileptic drugs for use in drug-naive patients. To complicate matters further, American and European regulators have taken markedly different approaches to this issue, with the FDA requiring withdrawal to monotherapy data comparing more than one dose of newer agents with historical controls, whereas the EMA recommends undertaking randomised head-to-head studies versus an established comparator. The former studies are designed to show superiority compared to previously published data, whereas the latter will accept a non-inferiority (equivalence) outcome.