N-of-1 trials target actionable mutations, yet such approaches do not test genomically-informed therapies in patient tumor models prior to patient treatment. To address this, we developed patient-derived xenograft (PDX) models from fine needle aspiration (FNA) biopsies (FNA-PDX) obtained from primary pancreatic ductal adenocarcinoma (PDAC) at the time of diagnosis. Here, we characterize PDX models established from one primary and two metastatic sites of one patient. We identified an activating KRAS G12R mutation among other mutations in these models. In explant cells derived from these PDX tumor models with a KRAS G12R mutation, treatment with inhibitors of CDKs (including CDK9) reduced phosphorylation of a marker of CDK9 activity (phospho-RNAPII CTD Ser2/5) and reduced viability/growth of explant cells derived from PDAC PDX models. Similarly, a CDK inhibitor reduced phospho-RNAPII CTD Ser2/5, increased apoptosis, and inhibited tumor growth in FNA-PDX and patient-matched metastatic-PDX models. In summary, PDX models can be constructed from FNA biopsies of PDAC which in turn can enable genomic characterization and identification of potential therapies.
The purpose of this study was to characterize the operating characteristics of the Personality Assessment Inventory (PAI) validity scales in distinguishing simulators feigning symptoms of traumatic brain injury (TBI) while completing the PAI (n = 84) from a clinical sample of patients with TBI who achieved adequate scores on performance validity tests (n = 112). The simulators were divided into two groups: (a) Specific Simulators feigning cognitive and somatic symptoms only or (b) Global Simulators feigning cognitive, somatic, and psychiatric symptoms. The PAI overreporting scales were indeed sensitive to the simulation of TBI symptoms in this analogue design. However, these scales were less sensitive to the feigning of somatic and cognitive TBI symptoms than the feigning of a broad range of cognitive, somatic, and emotional symptoms often associated with TBI. The relationships of TBI simulation to consistency and underreporting scales are also explored.
Errorless learning (EL) procedures have been shown to be effective in teaching new information and new procedures to individuals with severe memory impairment. The published studies have been based on comparatively short-term interventions delivered to individuals with relatively circumscribed impairments. In this single case study, we explore the usefulness of errorless learning procedures used for seven years with an adult with profound and complicated memory and executive function impairments associated with three distinct aetiologies. In primary functional areas targeted by the intervention, outcome was documented by behavioural descriptions and a frequency rating scale. Caregiver burden was documented with qualitative descriptors. A financial cost-benefit analysis is also provided. In the absence of change in underlying neuropsychological impairments, DI's everyday functioning in critical areas improved substantially, with corresponding reduction in supports and improved quality of life. Caregiver burden was reduced to acceptable levels and cost-benefit analysis demonstrates substantial ongoing cost savings.
The purpose of this study was to characterize the relationship between verbal memory and depression scores on the Personality Assessment Inventory following traumatic brain injury. Depression was associated with diminished delayed recall and recognition on the California Verbal Learning Test-II (CVLT-II), even after controlling for a neuropsychological composite score and/or a measure of motivation (i.e., the TOMM). There was no relationship between depression and recall on Verbal Paired Associates or Logical Memory when controlling for the same covariates. The findings were most consistent with depressed subjects failing to utilize the semantic organization of the CVLT-II list to enhance their learning.
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