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Background The prognosis of patients with diffusely infiltrating gliomas is dismal but varies greatly between individuals. While characterization of gliomas was primarily relied on typical histopathological features, specific molecular markers increasingly gained importance and play a key role in the recently published 5th edition of the World Health Organization (WHO) classification. Heme biosynthesis represents a crucial pathway due to its key role in oxygen transport, energy production or drug metabolism. Recently, we described a “heme biosynthesis mRNA expression signature” that correlates with histopathological glioma grades and patient survival. The aim of the current study was to correlate the heme biosynthesis mRNA expression signature with the most recent diagnostic molecular markers for glioma stratification. Material and Methods In this study, patient data were derived from the “The Cancer Genome Atlas” (TCGA) lower-grade glioma and glioblastoma cohorts. We identified diffusely infiltrating gliomas correlating molecular tumor diagnosis according to the most recent WHO classification with heme biosynthesis mRNA expression. The following molecular markers were analyzed: EGFR amplification, TERT promoter mutation, CDKN2A/B homozygous loss, concurrent chromosome 7 gain/10 loss, MGMT methylation, IDH mutation, ATRX loss, p53 mutation and 1p19q co-deletion. Subsequently, we calculated the heme biosynthesis mRNA expression signature and correlated this signature with distinct molecular glioma markers as well as the resulting molecular subgroups. Results A total of 649 patients with available data on up-to-date molecular markers and heme biosynthesis mRNA expression were included. According to analysis of individual molecular markers, we found a significantly higher heme biosynthesis mRNA expression signature in gliomas with IDH wildtype (p Conclusion Our data demonstrate a significant correlation between diagnostic molecular markers and heme biosynthesis regulation in diffusely infiltrating gliomas. Consequently, heme biosynthesis expression is a promising biomarker for glioma aggressiveness and might constitute a potential target for novel therapeutic approaches.

Background The prospects of a patient with suspected glioblastoma may rely heavily on the indication for surgical resection versus biopsy only. Biopsy percentages vary considerably across hospitals and guidelines for treatment of glioblastoma lack criteria for surgical decision-making. To identify patient and tumor characteristics associated with the decision to resect or biopsy a glioblastoma and to develop and validate a prediction model for decision support. Material and Methods Clinical data and pre-operative MRI scans were collected for adults who underwent first-time surgery for supratentorial glioblastoma from a registry-based cohort study of 12 hospitals from the Netherlands, Germany, France, Italy, and the United States between 1st of January 2007 and 31st of December 2011. The main outcome was the type of surgical procedure: surgical resection or biopsy only. Predictors were patient- and tumor-related characteristics. Radiological factors were extracted from MRI using an automated tumor segmentation method. A prediction model was constructed using multivariable logistic regression analysis. The model was cross-validated and externally validated with a leave-one-hospital-out approach. Results Out of 1053 patients treated for glioblastoma, 28% underwent biopsy only. Biopsy rates varied from 15-40% across hospitals. The prediction model showed excellent discrimination with an average area under the curve of 0.86. Of the patient-related characteristics, younger age was associated more with resection and Karnofsky Performance Score of 60 or less with biopsy. Of the tumor-related characteristics, a location in the right hemisphere, unifocality, no tumor midline crossing, and no involvement of the cortical spinal tract, were associated with resection, as well as a high expected resectability index, a location in the right occipital lobe, and a higher percentage of tumor in Schaefer’s dorsal or ventral attention, limbic, and default networks. External validation proved acceptable to outstanding discrimination with areas under the curve ranging between 0.79 and 0.92 for hospitals. Conclusion A prediction model is presented and validated to support the decision to resect or to biopsy a patient with a suspected supratentorial glioblastoma. In this prediction model, tumor-related characteristics were more informative than patient-related factors. This may support surgical decision-making for individual patients, or facilitate comparisons of patient cohorts between surgeons or institutions.

Differences in reaction time (RT) variability have been documented between children with and without Attention Deficit Hyperactivity Disorder (ADHD). Most previous research has utilized estimates of normal distributions to examine variability. Using a nontraditional approach, the present study evaluated RT distributions on the Conners' Continuous Performance Test in children and adolescents from the Multimodal Treatment Study of ADHD sample compared to a matched sample of normal controls (n = 65 pairs). The ex-Gaussian curve was used to model RT and RT variability. Children with ADHD demonstrated faster RT associated with the normal portion of the curve and a greater proportion of abnormally slow responses associated with the exponential portion of the curve. These results contradict previous interpretation that children with ADHD have slower than normal responding and demonstrate why slower RT is found when estimates of variability assume normal Gaussian distributions. Further, results of this study suggest that the greater number of abnormally long RTs of children with ADHD reflect attentional lapses on some but not all trials.

Background: Whilestudieshaveincreasinglyinvestigateddeficitsinreactiontime(RT)andRTvariabilityin children with attention deficit/hyperactivity disorder (ADHD), few studies have examined the effectsof stimulant medication on these important neuropsychological outcome measures. Methods: 316children who participated in the Multimodal Treatment Study of Children with ADHD (MTA) completedthe Conners’ Continuous Performance Test (CPT) at the 24-month assessment point. Outcomemeasures included standard CPT outcomes (e.g., errors of commission, mean hit reaction time (RT))and RT indicators derived from an Ex-Gaussian distributional model (i.e., mu, sigma, andtau). Results: Analyses revealed significant effects of medication across all neuropsychological out-come measures. Results on the Ex-Gaussian outcome measures revealed that stimulant medicationslows RT and reduces RT variability. Conclusions: This demonstrates the importance of includinganalytic strategies that can accurately model the actual distributional pattern, including the positiveskew. Further, the results of the study relate to several theoretical models of ADHD. Key-words: ADHD/ADD, go/no-go test, stimulants, reaction time, distributions, neuropsychology, phar-macology.A significant body of literature has documented thebehavioral benefits of stimulant medications inchildren with attention deficit/hyperactivity disorder(ADHD; Swanson et al., 1995). A majority of thesestudies have used behavioral indices such as parentand teacher rating scales and interviews to docu-ment medication effects. A minority of these studieshave utilized neuropsychological indices to assessmedication effects (see Denney & Rapport, 2001 forreview). The most commonly used neuropsycholo-gical tests across studies have been tests of attentionand inhibition. Stimulant medications appear to re-duce inhibition errors. Medication also appears tosignificantly quicken reaction time (RT) and reduceRT variability, especially on continuous performancetests (see Riccio, Reynolds, & Lowe, 2001 for review).RT variability and to a lesser extent mean RT areincreasingly becoming an area of focus in neuro-psychological studies comparing the performance ofpatients with ADHD to a control group. Significantand reliable differences in RT variability betweenADHD and normal control groups have been docu-mented on response inhibition tests (Conners, Ep-stein, Angold, & Klaric, 2003), discrimination tests(Leth-Steenson, Elbaz, & Douglas, 2000), and con-tinuous performance tests (Riccio et al., 2001). Fur-ther, Epstein et al. (2003) have shown that RTvariability demonstrated the strongest and most re-liable relationship to actual ADHD symptomatologycompared to other outcome measures on a com-monly used neuropsychological test, the Conners’CPT. The general pattern of RT differences has beenthat ADHD patients have slower and more variableRTs than normal controls (Riccio et al., 2001). Fur-ther, ADHD medications appear to accelerate meanRT and reduce RT variability (Riccio et al., 2001).Innovative new analytic techniques have beenintroduced to more accurately examine RT patternsamong ADHD patients. As pointed out by Castell-anos and Tannock (2002), the intra-individual vari-ability or moment by moment process of taskperformance in which individuals with ADHD

Abatacept (Orencia) is the first in a new class of biologics known as selective costimulation modulators. It inhibits full activation of T cells and interacts with other cell types to affect additional mediators of the inflammatory cascade. The clinical efficacy of abatacept in patients with active rheumatoid arthritis, despite prior treatment with methotrexate or anti-tumor necrosis factor-alpha (anti-TNFalpha) therapies, has been investigated in two randomized, double-blind, placebo-controlled, multicenter, phase III trials of 6 or 12 months' duration. In these trials, patients received intravenous abatacept (fixed-dose regimen based on bodyweight) or placebo in addition to background disease-modifying anti-rheumatic drugs (DMARDs) other than anti-TNFalpha therapies. Relative to placebo, abatacept significantly improved signs and symptoms of disease assessed using American College of Rheumatology (ACR) 20, 50, and 70 criteria and specific improvement in physical function as measured by the Health Assessment Questionnaire Disability Index at 6 months and significantly slowed structural damage progression in joints at 12 months. Improvements in ACR 20, 50, and 70 response rates were maintained at the final assessment in the 12-month trial. Abatacept infusions were generally well tolerated. Acute infusion-related reactions occurred in 9% of abatacept and 6% of placebo recipients in phase III trials. Integrated safety data from five clinical trials showed that serious adverse events were reported in 13.6% of abatacept and 12.3% of placebo recipients and the incidence of serious infections was 3.0% and 1.9%. Abatacept administered with background biologic DMARDs appears to be less well tolerated than abatacept plus background nonbiologic DMARDs.

There is overwhelming evidence of genetic influence on cognition. The effect is seen in general cognitive ability, as well as in specific cognitive domains. A conventional assessment approach using face-to-face paper and pencil testing is difficult for large-scale studies. Computerized neurocognitive testing is a suitable alternative. A total of 267 parent-child dyads were selected from a larger database of computerized neurocognitive test results. Correlations were determined between parent-child dyads, as well as matched parent-child dyads. Univariate regression analyses were estimated to determine the extent to which children's performance could be accounted for by that of their parents, compared with matched control parents. Multiple significant positive correlations in neurocognitive test performance were found in parent-child dyads. Parent performance accounted for a greater proportion of variability in every case. These findings indicated that a computerized neurocognitive battery is an effective tool for studying heritability in cognitive performance in a large sample.

A comprehensive, empirically based review of the published studies addressing neuropsychological performance in adults diagnosed with attention-deficit/hyperactivity disorder (ADHD) was conducted to identify patterns of performance deficits. Findings from 33 published studies were submitted to a meta-analytic procedure producing sample-size-weighted mean effect sizes across test measures. Results suggest that neuropsychological deficits are expressed in adults with ADHD across multiple domains of functioning, with notable impairments in attention, behavioral inhibition, and memory, whereas normal performance is noted in simple reaction time. Theoretical and developmental considerations are discussed, including the role of behavioral inhibition and working memory impairment. Future directions for research based on these findings are highlighted, including further exploration of specific impairments and an emphasis on particular tests and testing conditions.

UNLABELLED Abacavir is a carbocyclic 2'-deoxyguanosine nucleoside analogue. It is metabolised intracellularly to a 2'-deoxyguanosine nucleoside analogue which competitively inhibits HIV reverse transcriptase and terminates proviral DNA chain extension. In double-blind trials in antiretroviral therapy-experienced or -naive patients, reductions in HIV RNA levels were greater and more prolonged in patients receiving abacavir in combination with other antiretroviral drugs than in those receiving placebo in combination with the same agents. Furthermore, abacavir in combination with lamivudine and zidovudine reduced viral load to below detectable levels in a proportion of patients, and to a similar extent to the protease inhibitor indinavir in combination with lamivudine and zidovudine. Greatest viral load reductions were seen in antiretroviral therapy-naive patients. Preliminary results suggest that the viral suppression achieved with a protease inhibitor plus 2 nucleoside reverse transcriptase inhibitors (NRTIs) can be maintained as effectively with abacavir in combination with 2 NRTIs as it can be by continuing the protease inhibitor-containing treatment regimen. Initial virological data from studies of combination regimens including abacavir and protease inhibitors appear promising but larger controlled trials are required to confirm these observations. Nausea is the most frequently reported adverse event in patients receiving abacavir-containing combination therapy. Adverse events tend to be reported most frequently soon after starting treatment; the majority of events are mild or moderate in intensity and transient. Other adverse events reported in >5% of patients include vomiting, malaise and fatigue, headache, diarrhoea, sleep disorders, cough, anorexia and rash. A major cause of abacavir treatment discontinuation is the development of a hypersensitivity reaction which has been reported in 3 to 5% of patients. The reaction usually occurs within 6 weeks of commencing treatment, shows evidence of multiorgan system involvement and typically includes fever and/or rash. Symptoms resolve rapidly after discontinuation of treatment. Continuing treatment or rechallenge can result in more severe symptoms, life-threatening hypotension and even death. CONCLUSION Abacavir used in combination with other antiretroviral drugs effectively reduces viral load in both adults and children with HIV infection. Although these responses are greatest in individuals with little or no previous antiretroviral treatment, useful responses are still sometimes achieved in heavily pretreated individuals. Abacavir in combination with lamivudine and zidovudine provides a simple and convenient dosage regimen which is generally well tolerated, able to produce sustained suppression of viral replication and has the advantage of sparing other classes of antiretroviral drugs for subsequent use. This triple combination represents an alternative antiretroviral regimen for patients intolerant to protease inhibitors or those wishing to retain the option of protease inhibitors for later use. Further clinical studies are needed to define the activity of abacavir in combination with protease inhibitors and non-nucleoside reverse transcriptase inhibitors.

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This field was discovered in June, 1949, with the completion of the Houston Oil Company-American Republics Corporation's Nona Fletcher Mineral Company No. 1 through perforations from 7,058 to 7,066 feet in the lower Yegua. It is located on a relatively low-relief anticlinal fold on the downthrown side of a down-to-the-south regional fault, which has 100-200 feet of throw. As of October 1, 1951, two years and four months after the discovery well, there are 141 wells producing from eight reservoirs in the middle and lower Yegua sands. Total production has been 4,568,905 barrels of oil, 3,731,711 MCF of casinghead gas, 131,850 barrels of condensate, and 3,063,909 MCF of non-associated gas. End_of_Article - Last_Page 2625