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BACKGROUND: Grade 3 gastroenteropancreatic neuroendocrine neoplasms (G3 GEPNENs) are often aggressive, and the optimal treatment is unclear for this subgroup of neuroendocrine neoplasms (NENs). Temozolomide (TEM)-based regimens have been increasingly used to treat grade 1-2 NENs, but their efficacy in G3 NENs remains undetermined. We aimed to assess the clinical efficacy of TEM-containing regimens in advanced grade 3 GEPNENs. MATERIALS AND METHODS: A multicenter retrospective review (2008-2018) of patients with metastatic/unresectable G3 GEPNENs who received a TEM-containing regimen was undertaken within a North American partnership to pool data. The primary endpoint was time to treatment failure (TTF). Radiologic response was extracted from local reports. RESULTS: One hundred and thirty patients in six high-volume NEN centers were included (median age 55, 64% male, 18% functional, 67% pancreatic NEN). Forty-nine percent were well-differentiated, 35% poorly differentiated, and 15% unknown based on local pathology reports. The regimen used was capecitabine and temozolomide (CAPTEM) in 92% and TEM alone in 8%. Radiological response by local assessment was seen in 36% of patients. Median TTF was 3.6 months and median overall survival (OS) 19.2 months. Six percent of patients required discontinuation of therapy due to adverse events. TTF was longer in first-line treatment (7.8 months vs. 2.9 months; hazard ratio, 1.62; 95% confidence interval, 1.11-2.36; p = .015) and in patients with pancreatic NENs (panNENs) compared with gastrointestinal NENs (5.8 months vs 1.8 months; p = .04). The overall response rate was higher in the first-line setting (51% vs 29%; p = .02) and in panNEN (41% vs 23%; p = .04). CONCLUSION: This is the largest TEM treatment series in G3 NEN, involving collaboration of several major North American NEN centers as a partnership. Thirty-six percent of patients showed some degree of radiographic response, and treatment was generally well tolerated, although the median duration of response was short. Response rates and time to treatment failure were superior in the first-line setting. CAPTEM should be considered a viable treatment option in this setting. Further randomized trials are warranted. IMPLICATIONS FOR PRACTICE: Neuroendocrine neoplasms (NENs) are heterogeneous, and optimal treatment for aggressive grade 3 (G3) NENs remains undetermined. The capecitabine and temozolomide (CAPTEM) regimen has been used in low-grade pancreas NENs but there are few data for its safety and efficacy in the G3 setting. This article reports on the efficacy of temozolomide-containing regimens, particularly CAPTEM, in management of G3 NENs. The good tolerance and response rate show that CAPTEM should be considered a viable regimen in treatment of G3 NENs pending confirmatory prospective studies.

Duvelisib (IPI-145), an oral, dual inhibitor of phosphoinositide-3-kinase (PI3K)-δ and -γ, was evaluated in a Phase 1 study in advanced hematologic malignancies, which included expansion cohorts in relapsed/refractory (RR) chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) and treatment-naïve (TN) CLL. Per protocol, TN patients were at least 65 years old or had a del(17p)/TP53 mutation. Duvelisib was administered twice daily (BID) in 28-day cycles at doses of 8-75 mg in RR patients (n = 55) and 25 mg in TN patients (n = 18.) Diarrhea was the most common nonhematologic AE (TN 78%, RR 47%); transaminase elevations the most frequent lab-abnormality AE (TN 33.3%, RR 30.9%); and neutropenia the most common ≥grade 3 AE (RR 44%, TN 33%). The overall response rates were 56.4% for RR patients (1.8% CR, 54.5% PR) and 83.3% for TN patients (all PRs); median response duration was 21.0 months in RR patients but was not reached for TN patients. Based upon phase 1 efficacy, pharmacodynamics, and safety, duvelisib 25 mg BID was selected for further investigation in a phase 3 study in RR CLL/SLL.

The authors explore the use of metaphors as a training tool for beginning counselors for enhancing client case conceptualization, counselor-client relationships, and intervention strategies. The history of the use of metaphors in counseling, several definitions, and a case study are presented. The authors discuss intentional use of metaphors with students in training and with clients. How to introduce the use of metaphors into counselor training and practice is also included.

This study examined the relationship between level of depression and level of psychological abuse in women. In addition, the relationship between the use of self-report and measured report of psychological abuse within an intimate relationship was assessed. One hundred women were surveyed using the Psychological Maltreatment of Women Inventory (PMWI) and the Beck Depression Inventory (BDI). Results form the PMWI, the BDI and self-report measures were compared and analyzed. Statistical results indicated that a significant relationship existed between level of depression and level of psychological abuse. In addition, self-report was not predictive of psychological abuse as measured by the PMWI.

Adventure-based therapy has grown in both scope and popularity. These groups are frequently utilized in the treatment of adolescents with behavioral or substance abuse issues. Less evident is the use of this modality with other populations. Described here is a personal account of the author's participation in a wilderness-based group for women. Women of Courage is a course designed by Outward Bound specifically for women who self-describe as survivors of abuse. The program includes either a backpacking or canoeing component, a solo camping experience, and the opportunity to rock climb.

The authors studied the relationships between adult workers' spiritual well-being and job satisfaction. Two hundred participants completed 2 instruments: the Spiritual Well-Being Scale (C. W. Ellison & R. F. Paloutzian, 1982) and the Minnesota Satisfaction Questionnaire Short Form (D. J. Weiss, R. V. Dawis, G. W. England, & L. H. Lofquist, 1967). A bivariate correlational analysis showed spiritual well-being, religious well-being, and existential well-being to be positively related to job satisfaction for this sample. With a forced-entry multiple regression analysis, overall spiritual well-being was found to have a moderate influence, existential well-being had a much stronger influence, and religious well-being had a minimal influence all on, general job satisfaction. (Contains 3 tables.)

Describes the recent evolution of American University's internal newspaper, the "American Weekly," and how it strives to attain the sometimes conflicting ideals of supporting the university and providing independent press coverage. (EV)

Uranyl oxide hydrate minerals are common in the altered zones of U deposits and are expected to form where spent nuclear fuel is altered in an oxidizing environment. Consistent with all known uranyl oxide hydrate minerals, metaschoepite [[(U[O.sub.2]).sub.4]O[(OH).sub.6]] [([H.sub.2]O).sub.5], contains sheets of uranyl polyhedra with [H.sub.2]O groups located in the interlayer. Several crystals along the series from metaschoepite to Na-substituted metaschoepite (Na-MS), approximate formula Na[(U[O.sub.2]).sub.4][O.sub.2][(OH).sub.5] [([H.sub.2]O).sub.5], have been synthesized and their structures have been determined. Each contains sheets of uranyl pentagonal bipyramids that are topologically identical to those in metaschoepite, schoepite and fourmarierite. The sheets are electroneutral in metaschoepite, but substitution of O for OH located at the equatorial vertices of the uranyl polyhedra gives a charged sheet that is balanced by incorporation of Na in the interlayer. Synthesis of crystals of Na-MS from a solution containing ~500 ppm [Np.sup.5+], followed by analysis of the crystals using laser-ablation inductively coupled-plasma mass-spectroscopy, demonstrated that the crystals incorporate Np. This is in contrast to earlier studies that showed no incorporation of [Np.sup.5+] in synthetic metaschoepite (which has electroneutral sheets), and supports the hypothesis that [Np.sup.5+] incorporation is more likely in uranyl oxide hydrates with charged species in the interlayer. Keywords: Metaschoepite, uranyl, uranium, nuclear waste, geologic repository, crystal structure, neptunium