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Campylobacter is a leading causing of bacterial foodborne and zoonotic illnesses in the USA. Pulsed-field gene electrophoresis (PFGE) and 7-gene multilocus sequence typing (MLST) have been historically used to differentiate sporadic from outbreak Campylobacter isolates. Whole genome sequencing (WGS) has been shown to provide superior resolution and concordance with epidemiological data when compared with PFGE and 7-gene MLST during outbreak investigations. In this study, we evaluated epidemiological concordance for high-quality SNP (hqSNP), core genome (cg)MLST and whole genome (wg)MLST to cluster or differentiate outbreak-associated and sporadic Campylobacter jejuni and Campylobacter coli isolates. Phylogenetic hqSNP, cgMLST and wgMLST analyses were also compared using Baker’s gamma index (BGI) and cophenetic correlation coefficients. Pairwise distances comparing all three analysis methods were compared using linear regression models. Our results showed that 68/73 sporadic C. jejuni and C. coli isolates were differentiated from outbreak-associated isolates using all three methods. There was a high correlation between cgMLST and wgMLST analyses of the isolates; the BGI, cophenetic correlation coefficient, linear regression model R 2 and Pearson correlation coefficients were >0.90. The correlation was sometimes lower comparing hqSNP analysis to the MLST-based methods; the linear regression model R 2 and Pearson correlation coefficients were between 0.60 and 0.86, and the BGI and cophenetic correlation coefficient were between 0.63 and 0.86 for some outbreak isolates. We demonstrated that C. jejuni and C. coli isolates clustered in concordance with epidemiological data using WGS-based analysis methods. Discrepancies between allele and SNP-based approaches may reflect the differences between how genomic variation (SNPs and indels) are captured between the two methods. Since cgMLST examines allele differences in genes that are common in most isolates being compared, it is well suited to surveillance: searching large genomic databases for similar isolates is easily and efficiently done using allelic profiles. On the other hand, use of an hqSNP approach is much more computer intensive and not scalable to large sets of genomes. If further resolution between potential outbreak isolates is needed, wgMLST or hqSNP analysis can be used.

Supplemental material, sj-docx-1-opp-10.1177_10781552231168951 for New-onset persistent hyperglycemia with initiation of brentuximab treatment by Joseph Quintas, Kelley B Mowatt, Jamie A Mullally and Amir Steinberg in Journal of Oncology Pharmacy Practice

Supplemental material, sj-docx-1-opp-10.1177_10781552231168951 for New-onset persistent hyperglycemia with initiation of brentuximab treatment by Joseph Quintas, Kelley B Mowatt, Jamie A Mullally and Amir Steinberg in Journal of Oncology Pharmacy Practice

Oxybenzones like benzophenone-3 (BP3) are ultraviolet (UV) filters widely used in personal care products such as sunscreens. BP3 is currently receiving a great deal of attention because many of its properties, including high water solubility and potential to bioaccumulate, enable it to have damaging effects on aquatic ecosystems. One of these effects, the induction of coral bleaching, has led Hawaii to ban all sunscreens containing BP3. BP3 also appears to have endocrine-disrupting properties and has been found to affect animal physiology. However, behavioural consequences of BP3 exposure have yet to be thoroughly characterized. In the present study, we investigated the effects of BP3 on boldness, courtship and aggression in male Siamese fighting fish, Betta splendens, as little is known about the effects that BP3 has on fish social behaviour. To accomplish this, we assigned males to a treatment group (control, low, medium or high BP3 concentration) and completed individual (empty tank, novel environment and shoal) and social (courtship and aggression) behavioural assays before and after a 28-day exposure period. BP3 influenced the expression of social behaviours, with individual boldness generally unaffected. Changes in shoaling occurred regardless of BP3 concentration, while BP3-associated decreases in courtship and aggression were concentration dependent. Abnormal social behaviour may impede successful mating and alter territorial dynamics, with potentially heightened effects in species already experiencing other anthropogenic stressors.

There is growing concern about radiation exposure from nuclear myocardial perfusion imaging (MPI), particularly among younger patients who are more prone to develop untoward effects of ionizing radiation, and hence US and European professional society guidelines recommend age as a consideration in weighing radiation risk from MPI. We aimed to determine how patient radiation doses from MPI vary across age groups in a large contemporary international cohort.Data were collected as part of a global cross-sectional study of centers performing MPI coordinated by the International Atomic Energy Agency (IAEA). Sites provided information on each MPI study completed during a single week in March-April 2013. We compared across age groups laboratory adherence to pre-specified radiation-related best practices, radiation effective dose (ED; a whole-body measure reflecting the amount of radiation to each organ and its relative sensitivity to radiation's deleterious effects), and the proportion of patients with ED ≤ 9 mSv, a target level specified in guidelines.Among 7911 patients undergoing MPI in 308 laboratories in 65 countries, mean ED was 10.0 ± 4.5 mSv with slightly higher exposure among younger age groups (trend p value 0.001). There was no difference in the proportion of patients with ED ≤ 9 mSv across age groups, or in adherence to best practices based on the median age of patients in a laboratory.In contemporary nuclear cardiology practice, the age of the patient appears not to impact protocol selection and radiation dose, contrary to professional society guidelines.

Brentuximab is a CD-30-directed antibody-drug conjugate. The addition of brentuximab vedotin (BV) to adriamycin, vinblastine, and dacarbazine (AVD) has become a standard-of-care approach for advanced stage Hodgkin Lymphoma. BV has well known toxicities including peripheral neuropathy and infusion reactions. One emerging toxicity that is beginning to be recognized is new-onset hyperglycemia and diabetes mellitus. This case describes a rare presentation of new-onset diabetes mellitus one month after initiation of BV+AVD therapy in a patient with Hodgkin Lymphoma. A 41 year old previously healthy woman presented initially with complaints of chest and back pain. Cardiac etiology was ruled out, and lymphadenopathy was noted on chest imaging. Subsequent pathologic report from a robotic-assisted excision of a mediastinal mass and level five lymph node revealed Classical Hodgkin Lymphoma, nodular sclerosis type. Her baseline Hba1c was 5.8% at time of diagnosis. BV+AVD therapy was initiated about five weeks later. Six weeks after initiating treatment, she was admitted for abdominal pain secondary to constipation, at which time her blood glucose was noted to be 357 mg/dL. A repeated Hba1c was 8.1%. She required rapid acting insulin, and her glucoses ranged from 132-263 mg/dL. After discharge, a fasting glucose of over 250 mg/dL deemed her ineligible to have a PET/CT performed to assess disease status after completing cycle 2. She was referred urgently to the endocrinology clinic. She had been receiving dexamethasone 12mg every two weeks in conjunction with her chemotherapy, as well as additional lower doses for chemotherapy induced nausea. Thus, there was some thought she could have steroid-induced diabetes mellitus. However, her last dose of dexamethasone was given more than ten days prior to her most recent FSBG reading of 220 mg/dL, so steroid-induced diabetes was deemed less likely. The more likely etiology considered was BV-induced hyperglycemia. The patient was started on basal insulin, a DPP4i, and a meglitinide analog. Since initiation of this therapy, her glucose levels are now better controlled with readings consistently under 200 mg/dL. Furthermore, her lymphoma is in remission after three cycles of BV+AVD therapy, with a plan to complete six cycles. For many years, the standard of Hodgkin Lymphoma treatment consisted of adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD). In 2017, the results of the ECHELON-1 phase 3 clinical trial demonstrated that a regimen with BV in conjunction with adriamycin, vinblastine, and dacarbazine (BV+AVD) has superior modified progression-free survival for patients with stage III/IV classical Hodgkin Lymphoma when compared to ABVD (Connors, NEJM, Jan, 2018). In a subsequent 3-year follow up study published in Blood, the authors demonstrated superior 3-year PFS for BV+AVD relative to ABVD. While BV has been a preferred treatment option to bleomycin, and one that avoids the dreaded complication of pulmonary fibrosis, we are learning more about other emerging toxicities related to its use. When the drug was first approved in 2011 for use in relapsed/refractory Hodgkin Lymphoma, the toxicity of hyperglycemia was not noted in the side effect profile. As the drug has now been in use for ten years, emerging data on other toxicities have been noted in trials and reported to the manufacturer. Hyperglycemia is a listed adverse effect in the prescribing label with an incidence of up to 8% of patients experiencing any grade hyperglycemia, and 6% experiencing Grade 3 or 4 hyperglycemia. The pathophysiology of hyperglycemia with BV administration is currently unclear. Interestingly, there is a paucity of literature describing this toxicity of the drug, and most incidence reports may be related to clinical trial data or post-approval reporting. An extensive literature search revealed only one other case report of new onset diabetes mellitus in patients receiving BV (Chiang, AACE, 2020). The authors suggest a general decrease in immune surveillance while on the drug leading to autoimmune conditions. Regardless of the mechanism of action, the above case report demonstrates a need to monitor blood glucose levels carefully during the initiation of BV therapy, especially in those individuals who have risk factors such as obesity or pre-diabetes mellitus. Future studies may further address the mechanism of hyperglycemia from BV and if the resultant diabetes is reversible. Disclosures No relevant conflicts of interest to declare.

Recognising social partners allows individuals to establish social networks with one another, informs mating decisions, and decreases energy expenditure. Studies rarely examine if females have this ability outside of mate choice. Additionally, it is unknown if familiarity differs when females encounter females versus males. Female Siamese fighting fish were placed into one of six treatment groups that differed based on the sex of the interactant (female or male) and experience (familiar, unfamiliar or no previous exposure). In both female–female and female–male interactions, less behaviour was performed towards familiar individuals. However, the degree to which familiarity had an effect differed depending on the sex of the interactant and the behaviour measured. Familiarity may serve an important function if it increases an individual’s ability to remember the outcome of prior encounters and use this information in later encounters with the same individual. To fully understand social dynamics, both sexes must be examined.

In the midst of the current changes in family structure, increasing school violence, and children spending more time socializing with media than with people, developing social skills in young children have been a continual challenge. Additionally, children who have experienced trauma, have ADHD or Autism, or have a challenging home environment, also struggle to relate to others in healthy ways. The language of young children is play. Throughout history, children have learned social norms, roles, as well as social skills through play. This article will review the Play is Hard Work social skills group for four to six-year-old children. This group utilizes games and playful interaction to allow children to connect with each other in meaningful ways. Children are intentionally given opportunities to dysregulate their emotions so that they may then be taught skills to regulate them. Some of the therapeutic interventions drawn upon include: Trust Based Relational Intervention (TBRI), child centered play therapy, Theraplay, and adventure-based counseling. The ultimate goal of this play group is to help children enter the classroom with the skills needed to be more productive and successful, as well as having the skills they need to become fully integrated into their family life. Children become connected and successful by using the learned skills of self-regulation, problem solving, sharing, teamwork, giving and receiving care, perspective taking, negotiation, and showing respect. The content and theoretical practices used in the social skills group are discussed.

Components of boldness, such as activity level and locomotion, influence an individual's ability to avoid predators and acquire resources, generating fitness consequences. The presence of endocrine disrupting chemicals (EDCs) in the aquatic environment may affect fitness by changing morphology or altering behaviors like courtship and exploration. Most research on EDC-generated behavioral effects has focused on estrogen mimics and reproductive endpoints. Far fewer studies have examined the effects of other types of EDCs or measured non-reproductive behaviors. EDCs with antiandrogenic properties are present in waterways yet we know little about their effects on exposed individuals although they may produce effects similar to those caused by estrogen mimics because they act on the same hormonal pathway. To examine the effects of antiandrogens on boldness, this study exposed male Siamese fighting fish, Betta splendens, to a high or low dose of one of two antiandrogens, vinclozolin or flutamide, and observed behavior in three boldness assays, both before and after exposure. Overall, antiandrogen exposure increased boldness behavior, especially following exposure to the higher dose. Whether or not antiandrogen exposure influenced boldness, as well as the nature and intensity of the effect, was assay-dependent. This demonstrates the importance of studying EDC effects in a range of contexts and, at least within this species, suggests that antiandrogenic compounds may generate distinct physiological effects in different situations. How and why the behavioral effects differ from those caused by exposure to an estrogen mimic, as well as the potential consequences of increased activity levels, are discussed. Exposure to an antiandrogen, regardless of dose, produced elevated activity levels and altered shoaling and exploration in male Siamese fighting fish. These modifications may have fitness consequences.

This article identifies six characteristics in families that are subject to changing during crisis situations: (a) roles, (b) boundaries, (c) communication, (d) rules/processes, (e) goals, and (f) values. Understanding changes in these characteristics provides valuable information for helping crisis counselors assist families cope with and resolve the crisis. Identification of these characteristics is a step toward development of a theoretical model for helping families in crisis.

We evaluated the efficacy and safety of capecitabine and temozolomide (CAPTEM) in patients with metastatic neuroendocrine tumors (NETs) to the liver. This regimen was based on our studies with carcinoid cell lines that showed synergistic cytotoxicity with sequence-specific dosing of 5-fluorouracil preceding temozolomide (TMZ).A retrospective review was conducted of 18 patients with NETs metastatic to the liver who had failed 60 mg/month of Sandostatin LAR™ (100%), chemotherapy (61%), and hepatic chemoembolization (50%). Patients received capecitabine at 600 mg/m(2) orally twice daily on days 1-14 (maximum 1,000 mg orally twice daily) and TMZ 150-200 mg/m(2) divided into two doses daily on days 10-14 of a 28-day cycle. Imaging was performed every 2 cycles, and serum tumor markers were measured every cycle.Using RECIST parameters, 1 patient (5.5%) with midgut carcinoid achieved a surgically proven complete pathological response (CR), 10 patients (55.5%) achieved a partial response (PR), and 4 patients (22.2%) had stable disease (SD). Total response rate was 61%, and clinical benefit (responders and SD) was 83.2%. Of four carcinoid cases treated with CAPTEM, there was 1 CR, 1 PR, 1 SD, and 1 progressive disease. Median progression-free survival was 14.0 months (11.3-18.0 months). Median overall survival from diagnosis of liver metastases was 83 months (28-140 months). The only grade 3 toxicity was thrombocytopenia (11%). There were no grade 4 toxicities, hospitalizations, opportunistic infections, febrile neutropenias, or deaths.CAPTEM is highly active, well tolerated and may prolong survival in patients with well-differentiated, metastatic NET who have progressed on previous therapies.

Background: Neuroendocrine tumors are uncommon tumors that are histopathologically and biologically heterogeneous and include the multiple endocrine neoplasia (MEN) 1 and 2 syndromes. The morbidity of MEN-1 and MEN-2 is often due to the symptomatology of the endocrine hormones produced, and the mortality mainly occurs from hepatic dysfunction incurred by liver metastases. At present, there is essentially no effective cure once the tumor has metastasized to the liver. Patient: We present a patient with progressive, metastatic MEN-1 with the classic ‘3 P’s’ triad of neuroendocrine tumor of the pancreas, parathyroid adenoma and a pituitary adenoma. Results: After progression on high-dose Sandostatin LAR (60 mg/month) and multiple surgeries, the patient had a partial response (40% decrease) to a novel regimen of capecitabine and temozolomide (CAPTEM) and progression-free survival of 18 months. He had minor grade 1 toxicities and no grade 2, 3 or 4 toxicities. Discussion: The history and treatment options for MEN-1/2 cancers are reviewed, as well as the data behind our novel regimen, CAPTEM. Conclusion: The CAPTEM regimen is a tolerable, safe, easy to administer oral regimen with possible efficacy for MEN-1 tumors.

Summary Background: Continuous peripheral nerve blocks (CPNBs) are increasingly used to control postoperative and chronic pain. At our pediatric oncology institution, the duration of CPNBs is often prolonged. The risk of catheter-associated infection with prolonged CPNBs has not been previously investigated. Aim: We analyzed the incidence of CPNB-related infection and its relation to catheter duration, catheter site, intensive care stay, and antibiotic coverage. Methods: All CPNBs placed at our institution between August 1, 2005 and October 31, 2010 were studied. Primary diagnosis and the site, indication, duration, and infectious adverse effects of CPNBs were obtained from our Pain Service QI database. Patients’ age and sex, antibiotic administration, and number of days in intensive care were collected from patients’ medical records. Results: The use of 179 catheters in 116 patients was evaluated. Mean age at CPNB placement was 15.1 years (median, 14.7; range, 0.4–26.9). The most frequent indication for CPNB was surgery (89.4%), most commonly orthopedic (78.8%). Mean CPNB duration was 7.2 days (median, 5.0; range, 1–81 days). Two cases (1.12%) of CPNBs developed signs of infection, both associated with femoral catheters. The infections were mild and necessitated catheter removal at days 10 and 13, respectively. Conclusion: Nerve block catheter-associated infections are infrequent at our institution despite prolonged CPNB use. Both patients with infection had femoral catheters and prolonged catheter (≥10 days) use.

Comparison of Latin American (LA) nuclear cardiology (NC) practice with that in the rest of the world (RoW) will identify areas for improvement and lead to educational activities to reduce radiation exposure from NC. INCAPS collected data on all SPECT and PET procedures performed during a single week in March-April 2013 in 36 laboratories in 10 LA countries (n = 1139), and 272 laboratories in 55 countries in RoW (n = 6772). Eight “best practices” were identified a priori and a radiation-related Quality Index (QI) was devised indicating the number used. Mean radiation effective dose (ED) in LA was higher than in RoW (11.8 vs 9.1 mSv, p

Aims To characterize patient radiation doses from nuclear myocardial perfusion imaging (MPI) and the use of radiation-optimizing 'best practices' worldwide, and to evaluate the relationship between laboratory use of best practices and patient radiation dose. Methods and results We conducted an observational cross-sectional study of protocols used for all 7911 MPI studies performed in 308 nuclear cardiology laboratories in 65 countries for a single week in March-April 2013. Eight 'best practices' relating to radiation exposure were identified a priori by an expert committee, and a radiation-related quality index (QI) devised indicating the number of best practices used by a laboratory. Patient radiation effective dose (ED) ranged between 0.8 and 35.6 mSv (median 10.0 mSv). Average laboratory ED ranged from 2.2 to 24.4 mSv (median 10.4 mSv); only 91 (30%) laboratories achieved the median ED

The juvenile of Utterbackia imbecillis has recently become an important toxicity test organism. However, in temperate climates, gravid U. imbecillis are not readily available during many months of the year, especially if shoreline collection methods are used. This shortage of gravid mussels presents a logistical problem for use of juvenile U. imbecillis as toxicity test organisms. Therefore, this study was designed to test the feasibility of delaying and manipulating glochidial maturation in the laboratory through temperature control, because temperature changes seem to cue the maturation of glochidia in gravid mussels in the natural environment. The objectives of this study were to determine whether glochidial maturation can be stalled by holding adult mussels at cold temperatures, to determine if glochidial maturation could be cued by increasing water temperature at the time juveniles are needed for toxicity testing, and to predict the time required for cold-stored mussels to become gravid (time-to-gravid). Results of this study suggest that glochidial maturation can be stalled by holding mussels at winter temperature. Furthermore, glochidial maturation can later be cued by increasing the water temperature. Additionally, a survival analysis method is suitable for estimating the time-to-gravid for cold-stored mussels. These results should be useful for researchers requiring year-round availability of U. imbecillis for toxicity testing.

The Department of Mathematical Sciences at the United States Military Academy is prepared to lead the young minds of America into the 21st century with a bold and innovative curriculum coupled with student and faculty growth models and interdisciplinary lively applications. In 1990, the mathematics department began its first iteration of their “7 into 4” core curriculum. Each year improvements have been incorporated into the core mathematics program. In 1992, interdisciplinary applications appeared in the core program as an opportunity to communicate and work with the academic disciplines. Our core curriculum is tied together both vertically and horizontally with threads. These threads tie together both the content within each course as well as among all the courses. Student attitudes are measured through course surveys as we attempt to develop “life long learners”. Student performance is measured or calibrated throughout their four years.

BACKGROUND: This study assessed the co-occurrence of cognitive problems and difficult temperament characteristics in children aged 3 to 5 years exhibiting aggressive behavior. METHODS: Thirty-one children with high ratings on the Aggressive Behavior subscale of the Achenbach Child Behavior Checklist or Teacher Report Form were recruited from a school district-based clinic. Cognitive ability and temperament were assessed with the Differential Ability Scales and the Carey Temperament Scales Behavioral Styles Questionnaire, respectively. Cluster analysis was applied to these variables. RESULTS: Three prominent groups of children sharing cognitive and temperament characteristics emerged. The first, comprising 41.9% of the sample, demonstrated low adaptability, low persistence, high activity, negative mood, and low rhythmicity, along with borderline-deficient cognitive scores. The second (38.7%) demonstrated low adaptability, low persistence, high activity, and negative mood, along with average cognitive scores. The third (19.4%) demonstrated essentially midrange temperament characteristics and average cognitive scores. All 3 groups shared temperamental tendencies toward a higher threshold of response. Most children in the sample also had significant sleep disturbances (54.5%), other health problems (63.6%), and/or suspected developmental problems (54.5%). CONCLUSIONS: The widespread presence of sleep, health, cognitive, temperament, and developmental problems in this sample supports the involvement of medical and developmental health experts in teams evaluating young children who present with high levels of aggressive behavior. The diverse nature of cognitive-temperament profiles in this sample also suggests a need to assess cognitive ability and temperament in young, aggressive children to provide individualized interventions. Language: en

Health care institutions must use the principles of quality improvement to demonstrate appropriate assessment and effective management of pain. Here, we describe the quality improvement initiative implemented at our pediatric institution to improve the quality of pain management. We conducted chart audits for the previous 24 hours during which patients received inpatient care. Over six years, 2,478 charts were audited for 87 24-hour periods (average 1.2 days/month) to answer the following: (1) Was pain intensity assessed as per the institutional pain standard of care, (2) What proportion of audited inpatients had significant pain (>or=5/10), and (3) When significant pain (>or=5/10) occurred, was treatment effective (pain score

179 Background: We found in our lab that capecitabine (CAP), the prodrug of 5-FU, and temozolomide (TEM) were synergistic in inducing apoptosis in BON neuroendocrine tumor (NET) cell lines. We were the first to report in 2004 the use and mechanism of action of CAP and TEM (CAPTEM) in well differentiated NETs with promising results. Here we describe the interim analysis of an ongoing Phase II trial. Methods: 28 patients with metastatic well-moderately differentiated NET (ki-67 ≤20%) who had shown progression only on 60mg Sandostatin LAR (if octreotide scan positive) were treated with the following regimen: CAP 1,500mg/m2/day (PO divided BID, maximum 2,500 mg/day) on d1-14, and TEM 150-200mg/m2/day (PO divided BID, lower dose for patients who had prior chemotherapy or extensive radiation) on d10-14, with the next two weeks off, in a 28 day cycle. Primary objective was RR based upon RECIST, and secondary objectives included PFS, OS (from time of initiation of therapy), and toxicity evaluation. Other inclusion criteria were: age 20mo for all subtypes with 18/28 (64%) having progressed at this time. Twelve of 28 had died at this analysis with ongoing mOS of >25.3mo. The most common G3/4 toxicities were lymphopenia (32%), hyperglycemia (15%, unlikely related), thrombocytopenia (3%), and diarrhea (3%). No hospitalizations, opportunistic infections, or deaths occurred from CAPTEM. Conclusions: CAPTEM is an effective treatment for patients with progressive NET who failed high dose octreotide, with high PR and SD rates in carcinoids and insulinomas. The ongoing PFS in pancreatic NETs (>18.2 mo) is 150% greater than reported with everolimus and sutent. Clinical trial information: NCT00869050. [Table: see text]

274 Background: Chemoradiation (CRT) is used in unresectable pancreatic cancer (PC) to convert patients to a resectable state. Those who go to surgery can have a similar survival as those initially deemed resectable, with a mOS of 8.2-9 mo. We recently reported a prospective phase II trial of our synergistic regimen (GTX) for patients with metastatic PC with a mOS of 14.7 mo. Methods: 35 patients with ECOG PS 0-2 and completely unresectable advanced PC (localized to the pancreas, small bowel, stomach and/or encasing at least 2 vessels such as the SMA, CA, HA, PV, or SMV) were treated with GTX: Capecitabine (Xeloda) PO 1500mg/m2 divided into 2 doses daily on days 1-14, gemcitabine 750mg/m2 IV given over 75 min on days 4 & 11, docetaxel 30mg/m2 IV infusion over 30 minutes preceded by dexamethasone 10mg IV/PO on days 4 & 11, in a 21 day cycle. 3 cycles were given before evaluation. If eligible, a patient was allowed to proceed to surgery without radiation. Otherwise, starting on week 12, 5040 cGy of conformal radiation was given over 5-6 weeks (Mon-Fri) with weekly gemcitabine 250-300mg/m2 IV infusion over 30 min. No adjuvant treatment was given on protocol. Primary objective was conversion rate to operable status, and secondary objectives included RR (based upon RECIST), OS, and PFS. Results: Duration of neoadjuvant chemotherapy was 9 weeks and 0% showed POD during this time. 20 of 35 patients (57%) became eligible for surgery. Of all 35 patients, there was a 49% rate of negative margins at surgery (in 85% of those patients who underwent surgery). 23 patients (66%) underwent CRT, and 11 of them (48%) ultimately went to surgery and had clean margins. Median OS from initiation of chemotherapy for all patients was 17.4 mo and >22 mo if they went to surgery (20/35 pts, 1 alive). PFS of patients who underwent surgery was 13.2 mo. Grade 3/4 toxicities primarily included neutropenia (25%), leukopenia (11%), and diarrhea (6%). No deaths were attributed to GTX. Conclusions: Neoadjuvant GTX +/- radiation with gemcitabine can be used as an effective treatment for patients with truly unresectable PC. Clinical trial information: NCT00869258.

209 Background: We found that in pancreatic cancer (PC) cells, when gemcitabine, docetaxel, capecitabine (GTX) are given in a sequence and time specific manner, it 1) increased Bax, Bak, Fas and decreased Bcl-2 and Bcl-XL expression; 2) increased hENT-1 expression >8 fold, which increased intracellular gemcitabine accumulation by 220%; 3) specifically inhibited MEK to ERK phosphorylation (p-MEK) by >70%. Methods: From this pre-clinical data, we developed the GTX regimen utilizing: capecitabine 750 mg/m2/BID capped at 2500mg/day for days 1-14; on days 4 and 11 gemcitabine at 750mg/m2 given over 75mins (FDR), followed by docetaxel at 30mg/m2. Week 3 is off all drugs. Forty four patients with previously untreated metastatic PC were enrolled and followed until death. ECOG PS was: 0(2%), 1(63%), 2(35%), and median age was 60 (33-72). Over 85% of patients had >3 liver metastases. Results: Median response rate (RR) was 38% with 14% CR in metastatic or primary sites and 40% stable disease using RECIST 1.0 indices. Median PFS was 6.9 months and median OS was 14.5 months. After failing GTX, 80% of patients received our second line synergistic regimen called ICM (irinotecan 80mg/m2 and cisplatin 25mg/m2 on days 1 and 8, and mitomycin C 5mg/m2 on day 1 only, out of a 28 day cycle). The 6, 12, 18, 24, 30 and 36 month survival on GTX was 77, 59, 35, 16, 14 and 7%, respectively. Grade3/4 toxicities were: leukopenia (32%), neutropenia (29%), febrile neutropenia (3%), anemia (12%), thrombocytopenia (12%), diarrhea (5%), HFS (3%), fatigue (8%), and mucositis (8%). GTX inhibited MEK to ERK phosphorylation (P-MEK). We performed IHC (0-4+) for P-MEK in 16 patients and found high P-MEK (3-4+) correlated with an 85% RR while low P-MEK (0-1+) correlated with a 90% rate of PD to GTX. Conclusions: GTX is an effective regimen for metastatic PC with durable RR, PFS, OS rates, and acceptable toxicities. IHC for P-MEK seems to be a good biomarker to identify subsets of patients who will respond to GTX. GTX is a rationally designed regimen derived from lab studies. GTX increases pro-apoptotic and decreases anti-apoptotic proteins, inhibiting MEK to ERK in the MAPK pathway. Clinical trial information: NCT00996333.

308 Background: We have observed efficacy and tolerability of the CAPTEM regimen in pNET. We conducted a retrospective review of patients with liver metastasis from any NET, including carcinoid, who were treated with this regimen at our institution between 2002-2008. Methods: We identified patients with neuroendocrine tumors who demonstrated progressive liver metastasis while on treatment with long-acting octreotide (up to 60mg/month) and were then treated with CAPTEM as per our institutional protocol. Patients received capecitabine for 14 days at 1000mg PO bid with temozolomide at 150 or 200mg/m2 in bid dosing on days 10-14 of each 28 day cycle. All patients had contrast enhanced CT or MRI, response was assessed by a radiologist utilizing RECIST 1.0 criteria. Results: We identified 18 patients (50% female, median age- 55), 9 had pNET (2 functional, 7 non-functional), 2 had MEN1, 4 had carcinoid (1 functional), 2 with gastrinoma and 1 with glucagonoma. All patients had Ki-67

Prison sentences set by a paroling authority vary, as expected, with characteristics of the offenders. Is part of the variation in sentences, however, associated not with the offenders but with the persons responsible for the decisions? Comparisons of sentences set by various parole board members may be misleading if differences in the types of offenders con cerned are not taken into account. If an experimental study of the question with adequate controls for "types of offenders" is not feasible, statistical controls might be substituted. The purpose of this paper is to illustrate a method for com paring decisions by parole board members. Study of the sentences of 2,053 men paroled in one year, analyzed according to six parole board members who participated in the hearing, demon strated the need for the study suggested. The groups of offenders were not directly comparable. When relevant characteristics of the offenders were taken into account, it was found that the decision-makers tended to make similar decisions.

This study compares two statistical techniques-multiple re gression and configural analysis—used in developing parole pre diction tables, according to their ability to (1) differentiate be tween offenders who violate parole and those who do not, (2) predict violators from among a new group of parolees, and (3) assist administrators and researchers. First, experience tables had to be developed and tested for prediction ability. Once their accuracy in predicting had been demonstrated, they could be used as base expectancies because they had the quality of being "expected." As such, they could be used as a yardstick to evaluate correctional programs' ability to reduce these "expected" violation rates. The two methods were applied to the same body of data and the results were compared. The data consist of Wisconsin adult male offenders paroled in 1954-57 and in 1958-59. All were followed up for two years while they were on parole. The first group was used to develop the experience tables; the second group was used to test prediction ability. The tables were compared for accuracy in predicting through use of the Dc index and for accuracy in differentiating by the J index, measures developed by H. Richard John using Daniel Glaser's data gathered for federal parolees.

At the request of leading national parole organizations, the National Parole Institutes undertook a study to determine whether a useful information system describing the results of parole can be developed as a joint effort of paroling authori ties. A tentative model for uniform parole statistics was devised by representatives of twenty-nine parole agencies. The model was tested by eight agencies, which contributed data monthly, and was examined further by sixteen agencies. The result is a workable data collection system, a common vocabulary, and pro cedures for feedback to participating agencies. The data collected during the study demonstrate that com parisons of agency effectiveness must take into account differ ences in the kinds of offenders paroled. The study shows that the tentative model ultimately can pro vide a firm basis for meaningful analyses of parole experience based on uniform reporting from all our diverse parole systems. A three-year study has been initiated to develop the Uniform Parole Reporting System.