BACKGROUND. The cytologic differentiation between neoplastic and reactive/reparative processes in the endoscopic ultrasound-guided fine-needle aspirations (EUS-FNA) of the pancreas can be difficult. Malignant transformation of the pancreatic ductal epithelium changes the expression of apomucins. The goal of the current study was to determine an optimal immunohistochemical panel of mucin (MUC) antibodies that would allow the cytomorphologic distinction of pancreatic ductal adenocarcinoma and its differentiation from reactive/reparative processes and inadvertently sampled gastric and duodenal mucosa. METHODS. Pancreatic EUS-FNA specimens performed on 351 patients were reviewed. Expression profiles of MUC1, 2, 5AC, and 6 were examined on 56 cell block sections and 26 follow-up pancreatectomy specimens. RESULTS. MUC1 and 6 expression was found in nonneoplastic pancreatic samples, whereas there was an absence of expression of MUC2 and 5AC. MUC2 was detected in mucosal goblets cells of the duodenum, MUC6 in Brunner glands, and MUC5AC in gastric foveolar cells. MUC5AC expression in differentiating ductal adenocarcinomas from benign conditions demonstrated better operating characteristics than either MUC1 or MUC6. The apomucin expression pattern both in cytology and follow-up surgical pathology specimens was similar. In surgical pathology specimens, the panel of 3 antibodies, MUC1+/MUC2-/MUC5AC+, was noted in 15 of 17 ductal carcinomas (88.2%). In nonneoplastic pancreatic tissue, the expression panel MUC1+/MUC2-/MUC5AC- was observed in 14 of 17 (82.4%) cases. In cytology specimens, the combination of MUC1+/MUC2-/MUC5AC+ was noted in 21 of 30 ductal carcinoma cases (70.0%), 3 of 6 atypical cases (50%), and 1 of 1 suspicious for malignancy cases (100%). The combination MUC1+/MUC2-/MUC5AC+ was not observed in any of the negative for malignancy or reactive cases (0 of 6). CONCLUSIONS. The most optimal panel for the diagnosis of ductal adenocarcinoma in both the EUS-FNA specimens is a panel including MUC1/MUC2/MUC5AC, whereas a panel of all 4 antibodies (MUC1, 2, 5AC, and 6) will in addition aid in differentiating inadvertently sampled normal/reactive duodenal and gastric epithelium from neoplastic pancreatic tissue.

Ongoing controversies regarding the clinical and nosological status of ADHD in adults emphasize the need for studies examining whether <i>DSM-IV</i> ADHD symptom dimensions and subtypes identified in research with children are valid for adults. Firm symptom criteria validated by data from adult samples have not been developed. Moreover, many clinic-referred adults present with attentional complaints and exhibit symptoms, neurocognitive weaknesses, and secondary problems similar to those seen in ADHD. However, data are mixed regarding the profile of neurocognitive deficits involved in adult expressions of ADHD, and it is unknown whether patterns of weakness in neurocognitive performance can be identified that reliably discriminate adults with ADHD from those with other neurobehavioral disorders (e.g., learning disabilities, LD). The purpose of this study was to further (a) evaluate the discriminant validity of <i>DSM-IV</i> ADHD in adults, (b) examine the nature and severity of neurocognitive deficits in adult ADHD, and (c) clarify the diagnostic utility of executive functioning measures among clinic-referred adults. Overall, results supported the discriminant validity of adult ADHD, but little support emerged for the existence of separate <i>DSM-IV</i> subtypes. Importantly, symptom ratings supported the existence of two broad symptom domains consistent with those delineated in <i>DSM-IV</i>. Moreover, principal components analysis of neuropsychological data identified three dimensions of neurocognitive executive functioning (EF; verbal working memory; sustained intention; and effortful learning) in which ADHD adults (n=35) performed significantly less well than those who received an LD diagnosis (n=24) or no diagnosis (n=21). Furthermore, composite scores in these EF domains generated correct classifications that were significantly better than chance when classifying adults that (a) did and did not meet criteria for ADHD, (b) met criteria for ADHD or LD, and (c) met criteria for ADHD or no clinical diagnosis. Classification results were robust when submitted to a jackknife (leave-one-out) validation procedure. Finally, results provided general support for the developmental lag hypothesis of frontal-subcortical functioning in ADHD when considered vis-à-vis child ADHD data, but findings also supported the notion that ADHD in adults is associated with continuing dysfunction in specific neuroanatomical pathways believed to subserve executive attentional functions (e.g., dorsolateral prefrontal-subcortical; anterior cingulate-subcortical; orbitofrontal-subcortical). / Ph. D.

The post-firing variability of fire-affected rock (FAR) recovered from a stone-cooking platform within a prehistoric stone grill was examined. This examination tested the physical properties of FAR recovered from site CA-SBR-3773, located the Crowder Canyon Archaeological District in San Bernardino County, California. There is a lack of archaeological research in this area of Southern California; however, this project established a fundamental perspective of thermal feature reuse and episodes of firing activity for prehistoric cooking features by examining the physical changes FAR experienced due to various heat exposures. Regional archaeologists often encounter these features as they speckle the landscape of upland desert regions in California. This research is an experimental project that compares the cultural stones’ properties to those of non-cultural origin, which have been fired various times during controlled replicative experimentation. The end comparison identifies the FARs’ change in physical conditions. Repeated exposure to high temperatures has a direct relationship to the stability and matrices of rock, in this particular case, schist (Yavuz et al. 2010). As the stone is repeatedly exposed to high temperatures, its durability and structural components begin to deteriorate. This deterioration can be measured and compared to pre-fired physical properties. One of these physical properties is the stones’ porosity, which is calculated using the measured absorption rate of stone before and after exposure to firing episodes. These firing episodes are meant to approximate the cultural use of these stones during prehistoric cooking episodes. The results of the experiment show that FAR may have some diagnostic capabilities to infer multiple firing episodes, confirm facility reuse, and support suggested mobility with respect to available resources and temporal episodes through accelerator mass spectrometry (AMS) dating and other analyses such as micro-botanical analysis.

Chronic pain in children and adolescents is common; approximately 5% of children and adolescents report chronic pain along with moderate to high pain-related disability. Chronic pain is a subjective experience and can best be explained by a bio-psycho-social approach, which suggests reciprocal relations between different levels of this multidimensional phenomenon. The different dimensions of chronic pain need to be considered for a comprehensive assessment. Due to the subjective nature of pain, the child’s self-report is usually considered the best available and most valid estimate of the pain experience. A reliable and multidimensional assessment is an indispensable requirement for treatment planning. To date, questionnaires in German language are available to assess a wide range of relevant parameters in pediatric chronic pain. However, so far, no validated self-report tool exists to assess sensory and affective pain perception in children. These two parameters are of relevance since they describe aspects of the biological as well as the psychological dimension of chronic pain. Furthermore, a comprehensive diagnostic approach combining parameters from the three dimensions of chronic pain does not yet exist for children and adolescents. Such a comprehensive approach could be used for sample descriptions and standardized comparisons across different populations; it could serve as an approach for treatment planning or to classify outcome. This doctoral thesis is aimed at further developing the available diagnostic measures for older children and adolescents with chronic pain based on the above mentioned gaps in pediatric pain assessment. Research was performed on three patient samples. Sample 1 includes data from a prospective assessment at the German Pediatric Pain Centre from August 2008 to March 2009 (N(1)=139). Sample 2 includes retrospective data from patients who were treated at the German Pediatric Pain Centre from July 2005 to June 2010 (N(2)=1242). Sample 3 consists of pediatric pain patients who started an intensive interdisciplinary inpatient treatment between November 2009 and July 2011 (N(3)=83). In a first study, a tool to assess sensory and affective pain perception, the Pain Perception Scale for Adolescents, was adapted and validated in an adolescent clinical sample (Sample 1). The Pain Perception Scale for Adolescents allows pain patients to provide a valid and reliable self-report of parameters for both the biological and psychological dimensions of pain. In a second study, this tool was applied to a further sample of adolescents with migraine and tension-type headache (subsample of Sample 2). It was demonstrated that, contrary to the official headache classification guidelines, the sensory pain perception in this sample did not differentiate between migraine and tension-type headache. To develop a multidimensional assessment approach, in a third study, an adult classification system (Chronic Pain Grading) was applied to a sample of pediatric pain patients (Sample 2). This approach proved useful as a valid measure for a brief operationalization of pain problem severity, including pain intensity and pain-related disability only, and as an outcome measure. However, it displayed major shortcomings with regards to treatment stratification. To further develop an approach for treatment stratification and treatment planning, a fourth study focused on developing a new multidimensional approach for subgroup classification (subsample of Sample 2). The stability of subgroups was demonstrated in a cross-validation with an independent sample (Sample 1). Furthermore, the identified subgroups displayed distinct treatment outcomes after a standardized treatment program (Sample 3). In conclusion, this doctoral thesis offers an addition to diagnostic measures for older children and adolescents with chronic pain by adding the Pain Perception Scale for Adolescents and by proving the validity of the Chronic Pain Grading for the application in this patient group. These tools allow a valid description of adolescents’ subjective pain experience. Results from this doctoral thesis also indicate that the findings from adults cannot be readily transferred to children and adolescents. The final output of this doctoral thesis is a bio-psycho-social classification approach that identifies subgroups of adolescents with chronic pain with treatment relevant differences. This is a first step toward the development of subgroup-specific treatment.