Related to Anxiety: Arbitrarily Applicable Relational Responding and Experimental Psychopathology Research on Fear and Avoidance

Humans have an unparalleled ability to engage in arbitrarily applicable relational responding (AARR). One of the consequences of this ability to spontaneously combine and relate events from the past, present, and future may, in fact, be a propensity to suffer. For instance, maladaptive fear and avoidance of remote or derived threats may actually perpetuate anxiety. In this narrative review, we consider contemporary AARR research on fear and avoidance as it relates to anxiety. We first describe laboratory-based research on the emergent spread of fear- and avoidance-eliciting functions in humans. Next, we consider the validity of AARR research on fear and avoidance and address the therapeutic implications of the work. Finally, we outline challenges and opportunities for a greater synthesis between behavior analysis research on AARR and experimental psychopathology

<it>MDM2 </it>SNP309 promoter polymorphism and <it>p53 </it>mutations in urinary bladder carcinoma stage T1

<p>Abstract</p> <p>Background</p> <p>Urinary bladder carcinoma stage T1 is an unpredictable disease that in some cases has a good prognosis with only local or no recurrence, but in others can appear as a more aggressive tumor with progression to more advanced stages. The aim here was to investigate stage T1 tumors regarding <it>MDM2</it> promoter SNP309 polymorphism, mutations in the <it>p53</it> gene, and expression of p53 and p16 measured by immunohistochemistry, and subsequently relate these changes to tumor recurrence and progression. We examined a cohort of patients with primary stage T1 urothelial carcinoma of the bladder and their tumors.</p> <p>Methods</p> <p>After re-evaluation of the original slides and exclusions, the study population comprised 141 patients, all with primary stage T1 urothelial carcinoma of the bladder. The hospital records were screened for clinical parameters and information concerning presence of histologically proven recurrence and progression. The paraffin-embedded tumor material was evaluated by immunohistochemistry. Any mutations found in the <it>p53</it> gene were studied by single-strand conformation analysis and Sanger sequencing. The <it>MDM2</it> SNP309 polymorphism was investigated by pyrosequencing. Multivariate analyses concerning association with prognosis were performed, and Kaplan-Meier analysis was conducted for a combination of changes and time to progression.</p> <p>Results</p> <p>Of the 141 patients, 82 had at least one <it>MDM2</it> SNP309 G allele, and 53 had a mutation in the <it>p53</it> gene, but neither of those anomalies was associated with a worse prognosis. A mutation in the <it>p53</it> gene was associated with immunohistochemically visualized p53 protein expression at a cut-off value of 50%. In the group with <it>p53</it> mutation Kaplan-Meier analysis showed higher rate of progression and shorter time to progression in patients with immunohistochemically abnormal p16 expression compared to them with normal p16 expression (p = 0.038).</p> <p>Conclusions</p> <p><it>MDM2</it> SNP309 promoter polymorphism and mutations in <it>p53</it> were not associated with worse prognosis in this cohort of patients with primary stage T1 urinary bladder carcinoma. However, patients with abnormal p16 expression and a mutated <it>p53</it> gene had a higher rate of and a shorter time to progression, and <it>p53</it> gene mutation was associated with an abnormal immunohistochemistry for p53 at a cut-off of 50%.</p