Exploring Short-Sea Shipping as an Alternative to Non-Bulk Freight Trucking in Southeastern MA

The Island of Martha’s Vineyard relies on the transport of goods and people via Steamship Authority Vessels operating from Woods Hole in Falmouth, MA. The purpose of this research project was to study the feasibility of expanding the waterborne distribution of non-bulk freight between mainland Massachusetts and the island of Martha’s Vineyard. The study focused on understanding the congestion and emissions impacts resulting from any change in port(s) of origin. Based on an analysis of information gathered from the Steamship Authority, interviews, document reviews, and the MOVES tool, this study concluded that (1) the Port of New Bedford is suited, based on location and existing infrastructure, to serve as an additional port for freight ferry service — though upgrades to existing infrastructure would be required, (2) impacts to traffic volume resulting from transporting some percentage of freight through an off-Cape port would be minimal, and (3) operating a freight ferry roughly three trips/day from New Bedford, as modeled in this analysis, would increase emissions as compared to the current scenario of all non-bulk freight passing through Woods Hole

Managing Journals by Committee

What do you do when your serials librarian retires and there is no option to hire a replacement? You form a committee. When the University of Cincinnati (UC) Health Sciences serials librarian retired in early 2010, budget cuts required that the position be eliminated from the personnel lines. While other aspects of her position could be redistributed, rather than reassign another librarian to manage the collection development tasks, the library director decided to pool the responsibilities for serials selection, faculty contact, subscription termination, and all other tasks relative to serials collection maintenance. With varying knowledge of journal management, the committee of five (the director, two information services librarians, one informationist, and a technical services librarian) has worked as a team through journal cancellations, continued format switches, and new acquisitions for 3 years. Over those 3 years, we have systematically addressed new requests, budget impact, journal usage, the balance between clinical versus research faculty requests, and a significant change in our user mix that continues to inform us that, no matter the number of journals in our collections, if the desired journal title is not among them, there are not enough journals. This paper will describe the myriad challenges, changes, and lessons learned plus our successes and a few missteps along the way during the last 3 years of managing the UC Health Sciences Library journal collection by committee

1 Examining the immune tumor microenvironment of endometrial cancer patients treated with pembrolizumab plus lenvatinib

Objectives: Our aim is to examine the immune microenvironment of endometrial cancer (EMCA) patients treated with pembrolizumab plus lenvatinib (P+L) that could contribute to increased time on treatment. This may help inform patient selection and identify new therapeutic targets among aggressive endometrial cancer subtypes. Methods: 229 endometrial cancer patients were analyzed using Next-Gen sequencing of the DNA (NextSeq, 592 genes or NovaSeq, WES) and RNA (NovaSeq, WTS) (Caris Life Sciences, Phoenix, AZ. Time on treatment (TOT) was obtained from insurance claims and Kaplan-Meier estimates were calculated for molecularly defined patient cohorts as the time of first to last treatment of P+L. Responders (R) and non-responders (NR) were defined by treatment for > or <6 months, respectively. Relative abundance of immune-cell infiltrates was calculated by Quantiseq. T-cell inflamed score was calculated from a 160 gene expression signature, and the interferon (IFN) score was calculated from an 18-gene signature. Statistical significance was calculated using Mann-Whitney U test. Results: The median TOT of P+L was 4.97 months for all EMCA patients treated with P+L (n=229). The mTOT for endometrioid EMCA patients (n=93) was 5.96 months compared to 3.49 mToT for serous EMCA (n=76) (HR: 0.543, 95% CI (0.395-0.746), p-value <0.001). Overall, all EMCA responders had higher median HLA class 2 gene expression (HLA-DQB2, 2.31-fold; HLA-DPB1, 1.42-fold; HLA-DQA1, 1.66-fold; HLA-DRB1, 1.40-fold; HLA-DPA1, 1.33-fold) and CD8+ T-cells (0.42% vs 0.06%) (p<0.05). Of endometrioid EMCA patients, responders had increased median HLA class 2 gene expression (HLA-DPB1, 2.059-fold; HLA-DQA1, 2.580-fold; HLA-DRB1, 1.568-fold; HLA-DPA1, 1.765-fold) (all p<0.05), but no significant differences in immune cell infiltrates or immune signatures. In serous EMCA, responders also had higher median HLA class 2 gene expression (HLA-DQB2, 4.30-fold; HLA-DPB1, 1.60-fold; HLA-DOB, 2.10-fold), CD8+ T cells, (1.41% vs 0.16%), IFN score (–0.0383 vs –0.265) and T-cell inflamed score (48 vs –67) (all p<0.05). Conclusions: Components of cytotoxic T-cell response in the TME including elevated IFN-γ and T-cell inflamed scores in conjunction with high expression of HLA class II was associated with longer time on treatment with P+L among serous endometrial cancers

Prognostic impact of adjuvant chemotherapy treatment intensity for ovarian cancer.

OBJECTIVE:We aimed to investigate the prognostic impact of duration of first-line chemotherapy administration in patients with epithelial ovarian cancer (EOC). METHODS:Chemotherapy records were abstracted from the electronic medical record. Patients with on-time completion (105 days) were compared to patients finishing early (4 weeks. For 222 women with stage IIIC/IV, stage-stratified estimates of progression-free survival (PFS) and overall survival (OS) were compared. A delay sub-study was performed with outliers removed. Each week of delay was correlated with the change in PFS and OS to identify time points associated with change in outcome. RESULTS:Most women had on-time completion of chemotherapy (23.6%) or a treatment delay of ≤4 weeks (21.8%); 21.6% of women experienced a delay longer than 4 weeks. R0 resection at initial debulking (OR = 1.99, 95%CI: 1.18-3.36, p = 0.010) and RECIST complete response (OR = 4.88, 95%CI: 2.47-10.63, p1 month delay had decreased median survival of 18.1 months (14.7-24.9 months), while women with short intervals survived 35.0 months (95%CI: 21.8-49.8 months). Short-term delays lead to progressively decreasing OS. This was significantly different from the on-schedule survival estimate after 6 weeks of delay. CONCLUSIONS:On-time completion of chemotherapy correlates with increased survival and higher complete response rates. Increasing delays in chemotherapy completion were associated with decreased survival

Prognostic value of miliary versus non-miliary sub-staging in advanced ovarian cancer

WOS: 000404945600010PubMed ID: 28495239Objective. The presence of miliary disease during initial ovarian cancer debulking may reflect a distinct mode of peritoneal spread independent from size-based tumor staging and may explain variation in response to treatment and survival outcomes. To infer the prevalence, presentation and clinical implications of miliary disease we reviewed existing surgical records. Methods. Reports were available for 1008 primary debulking surgeries for ovarian, primary peritoneal or fallopian tube cancer between 2001 and 2015 (685 reports from 2005 to 2015). Clinical outcome data was available for 938 patients. We analyzed a high-stage sub-cohort for survival (N = 436). Results. Most records were evaluable for miliary disease (761/938); for these, the miliary phenotype was highly prevalent (249/761, 32.7%) and often accompanied by ascites (185/249, 74%). While optimal debulking rates were unaffected by miliary disease, total resection (RO) rates were poorer. Liver, stomach, spleen or bladder appeared to be sporadically involved while the omentum, mesentery, bowel, peritoneum and diaphragm were affected simultaneously (Spearman rho > 0.5). Overall, miliary disease was associated with worse progression free survival, overall survival, and time from relapse to death independent of stage. Survival effects were particularly strong for Stage IV disease where median overall survival varied by over 30 months (log-rank p = 0.002). Conclusions. Miliary disease is an identifiable surgical phenotype reflecting a distinct clinical trajectory that adds prognostic information to standard disease burden-based staging. These findings should permit further retrospective investigation in a wider cohort and prompt the consideration of prospective structured operative reporting standards and treatment strategies. (C) 2017 The Authors. Published by Elsevier Inc.National Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [K01LM012100, T32CA108456, P30CA016056]; RPCI-UPCI Ovarian Cancer SPORE [P50CA159981-01A1]; Roswell Park Alliance Foundation; Roswell Park Cancer InstituteThis work was supported by the National Institutes of Health (K01LM012100, T32CA108456, P30CA016056), RPCI-UPCI Ovarian Cancer SPORE (P50CA159981-01A1) and the Roswell Park Alliance Foundation, Roswell Park Cancer Institute. The authors report no conflicts of interest

Treatment of ovarian cancer by targeting the tumor stem cell-associated carbohydrate antigen, Sialyl-Thomsen-nouveau

Recurrent ovarian cancer (OvCa) is thought to result in part from the inability to eliminate rare quiescent cancer stem cells (CSCs) that survive cytotoxic chemotherapy and drive tumor resurgence. The Sialyl-Thomsen-nouveau antigen (STn) is a carbohydrate moiety present on protein markers of CSCs in pancreatic, colon, and gastric malignancies. We have demonstrated that human OvCa cell lines contain varying levels of cells that independently express either STn or the ovarian CSC marker CD133. Here we determine co-expression of STn and CD133 in a subset of human OvCa cell lines. Analyses of colony and sphere forming capacity and of response to standard-of-care cytotoxic therapy suggest a subset of OvCa STn+ cells display some CSC features. The effect of the anti-STn antibody-drug conjugates (ADCs) S3F-CL-MMAE and 2G12-2B2-CL-MMAE on OvCa cell viability in vitro and in vivo was also assessed. Treatment with S3F-CL-MMAE reduced the viability of two of three OvCa cell lines in vitro and exposure to either S3F-CL-MMAE or 2G12-2B2-CL-MMAE reduced OVCAR3-derived xenograft volume in vivo, depleting STn+ tumor cells. In summary, STn+ cells demonstrate some stem-like properties and specific therapeutic targeting of STn in ovarian tumors may be an effective clinical strategy to eliminate both STn+ CSC and STn+ non-CSC populations

History of thyroid disease and survival of ovarian cancer patients: results from the Ovarian Cancer Association Consortium, a brief report

Background:Findings from in vitro studies suggest that increased exposure to thyroid hormones can influence progression of ovarian tumours. However, epidemiologic evidence on this topic is limited.Methods:We pooled data from 11 studies from the Ovarian Cancer Association Consortium. Using multivariate Cox proportional hazards models, we estimated associations between hyper-and hypothyroidism and medications prescribed for these conditions with 5-year all-cause survival among women diagnosed with invasive ovarian cancer.Results:Overall, there was a nonsignificant association with history of hyperthyroidism (n=160 cases) and mortality (HR=1.22; 95% CI=0.97-1.53). Furthermore, diagnosis of hyperthyroidism within the 5 years before ovarian cancer diagnosis was associated with an increased risk of death (HR=1.94; 95% CI=1.19-3.18). A more modest association was observed with history of hypothyroidism (n=624 cases) and mortality (HR=1.16; 95% CI=1.03-1.31). Neither duration of hypothyroidism nor use of thyroid medications was associated with survival.Conclusions:In this large study of women with ovarian cancer, we found that recent history of hyperthyroidism and overall history of hypothyroidism were associated with worse 5-year survival