Genotyping of circulating tumor DNA in cholangiocarcinoma reveals diagnostic and prognostic information

Diagnosis of Cholangiocarcinoma (CCA) is difficult, thus a noninvasive approach towards (i) assessing and (ii) monitoring the tumor-specific mutational profile is desirable to improve diagnosis and tailor treatment. Tumor tissue and corresponding ctDNA samples were collected from patients with CCA prior to and during chemotherapy and were subjected to deep sequencing of 15 genes frequently mutated in CCA. A set of ctDNA samples was also submitted for 710 gene oncopanel sequencing to identify progression signatures. The blood/tissue concordance was 74% overall and 92% for intrahepatic tumors only. Variant allele frequency (VAF) in ctDNA correlated with tumor load and in the group of intrahepatic CCA with PFS. 63% of therapy naive patients had their mutational profile changed during chemotherapy. A set of 76 potential progression driver genes was identified among 710 candidates. The molecular landscape of CCA is accessible via ctDNA. This could be helpful to facilitate diagnosis and personalize and adapt therapeutic strategies

The groupoid approach to Leavitt path algebras

When the theory of Leavitt path algebras was already quite advanced, it was discovered that some of the more difficult questions were susceptible to a new approach using topological groupoids. The main result that makes this possible is that the Leavitt path algebra of a graph is graded isomorphic to the Steinberg algebra of the graph’s boundary path groupoid. This expository paper has three parts: Part 1 is on the Steinberg algebra of a groupoid, Part 2 is on the path space and boundary path groupoid of a graph, and Part 3 is on the Leavitt path algebra of a graph. It is a self-contained reference on these topics, intended to be useful to beginners and experts alike. While revisiting the fundamentals, we prove some results in greater generality than can be found elsewhere, including the uniqueness theorems for Leavitt path algebras

Low level methylmercury exposure affects neuropsychological function in adults

BACKGROUND: The neurotoxic effects of methylmercury (MeHg) have been demonstrated in both human and animal studies. Both adult and fetal brains are susceptible to the effects of MeHg toxicity. However, the specific effects of adult exposures have been less well-documented than those of children with prenatal exposures. This is largely because few studies of MeHg exposures in adults have used sensitive neurological endpoints. The present study reports on the results of neuropsychological testing and hair mercury concentrations in adults (>17 yrs) living in fishing communities of Baixada Cuiabana (Mato Grosso) in the Pantanal region of Brazil. METHODS: A cross-sectional study was conducted in six villages on the Cuiaba River. Participants included 129 men and women older than 17 years of age. They were randomly selected in proportion to the age range and number of inhabitants in each village. Questionnaire information was collected on demographic variables, including education, occupation, and residence history. Mercury exposure was determined by analysis of hair using flameless atomic absorption spectrophotometry. The neurocognitive screening battery included tests from the Wechsler Memory Scale and the Wechsler Adult Intelligence Scale, Concentrated Attention Test of the Toulouse-Pierron Factorial Battery, the Manual Ability Subtests of the Tests of Mechanical Ability, and the Profile of Mood States. RESULTS: Mercury exposures in this population were associated with fish consumption. The hair mercury concentration in the 129 subjects ranged from 0.56 to 13.6 μg/g; the mean concentration was 4.2 ± 2.4 micrograms/g and the median was 3.7 μg/g. Hair mercury levels were associated with detectable alterations in performance on tests of fine motor speed and dexterity, and concentration. Some aspects of verbal learning and memory were also disrupted by mercury exposure. The magnitude of the effects increased with hair mercury concentration, consistent with a dose-dependent effect. CONCLUSIONS: This study suggests that adults exposed to MeHg may be at risk for deficits in neurocognitive function. The functions disrupted in adults, namely attention, fine-motor function and verbal memory, are similar to some of those previously reported in children with prenatal exposures

The role of anxiety in perceiving and realizing affordances

Three experiments were conducted to examine the role of anxiety in perceiving and realizing affordances in wall climbing. Identical traverses were situated high and low on a climbing wall to manipulate anxiety. In Experiment 1, participants judged their maximal overhead reachability and performed maximal reaches on the climbing wall. Anxiety was found to reduce both perceived and actual maximal reaching height. In Experiment 2, participants climbed from right to left and back again on the high and low traverses, which now entailed an abundance of holds. Consistent with the reduction of perceived and actual maximal reaching height found in Experiment 1, anxiety led to the use of more holds. Finally, in Experiment 3, points of light were sequentially projected around the participants while they were climbing to measure attention. As participants detected fewer lights in the high-anxiety condition, it was concluded that anxiety narrowed attention. In general, the results underscored that the actor's emotional state plays an important role in perceiving and realizing affordances and that the perception of affordances changes as the accompanying action capabilities change. Copyright © 2006, Lawrence Krlbaum Associates, Inc