bluuebunny/crossref_metadata_2025_split huggingface dataset:
Footnotes to Kraepelin: Changes in the classification of mood disorders with DSM-5
Authors: Kalk Nicola J. , Young Allan H. 
Published: May 2017

SummaryReliable diagnosis of mood disorders continues to pose a challenge. This is surprising because they have been recognised clinically since classical times. Mood disorders are also common: major depressive disorder affects nearly 300 million people worldwide and bipolar affective disorder nearly 60 million and they are a major cause of disability. Nonetheless, the reliability trials of the updated Diagnostic and Statistical Manual, Fifth Edition (DSM-5) found that the reliability of the diagnosis of major depressive disorder was in the 'questionable' range. Although the reliability of the diagnosis of bipolar I disorder in the same trials was 'good', the sample size of the individuals recruited to validate bipolar II disorder was insufficient to confirm reliability. As the epidemiological prevalences of bipolar I and bipolar II disorders are the same, this alone implies problems in its recognition. Here, we critically evaluate the most recent iteration of DSM mood disorder diagnoses in a historical light and set out the implications for clinical practice and research.
Somatic genomic landscape of over 15,000 patients with advanced-stage cancer from clinical next-generation sequencing analysis of circulating tumor DNA.
Authors: Zill Oliver A. , Mortimer Stefanie , Banks Kimberly C. , Nagy Rebecca J , Chudova Darya , Jackson Coyt , Baca Arthur , Ye Joseph Z. , Lanman Richard Burnham , Talasaz AmirAli , Eltoukhy Helmy , Kurzrock Razelle 
Published: May 2017

LBA11501 Background: Next-generation sequencing (NGS) of circulating tumor DNA (ctDNA) enables non-invasive profiling of solid tumor cancers. Liquid biopsy studies to date have been limited to modest-size cohorts and case studies. Methods: Somatic genomic profiles of over 15,000 patients with advanced-stage clinical cancer were determined by a highly accurate, deep-coverage (15,000x) ctDNA NGS test targeting 70 genes (Guardant360). Frequencies of somatic ctDNA alterations per gene were compared to those previously described in tissue sequencing projects (e.g., TCGA). Accuracy of ctDNA sequencing (PPV) was assessed by comparing with matched tissue tests for 386 patients. Results: The cohort consisted of lung (37%), breast (14%), colorectal (10%) and other cancers (38%), with ctDNA clinical sensitivity of 86%, 83%, 85%, and 78%, respectively. Cancer-type-specific frequencies and mutual exclusivity patterns among major driver alterations largely recapitulated those seen in tissue sequencing studies. Mutation frequencies per codon correlated well between ctDNA and published tissue data, both for commonly altered tumor suppressors and for oncogenes (Pearson correlations: TP53, r = 0.94; KRAS, r = 0.99; PIK3CA, r = 0.99). The overall accuracy of ctDNA sequencing in comparison with matched tissue tests was 87% (336/386). The accuracy increased to 98% when blood and tumor were collected less than six months apart. Four distinct classes of clinical outcome benefits have been observed by liquid biopsy: 1) actionable mutations in cases with tissue QNS ( ALK fusion, or EGFR or BRAF activating mutations in lung; ERBB2 amp in gastric), 2) actionable resistance mutations at time of progression ( MET amp or EGFRT790M in lung), 3) evolution of sensitivity upon progression ( ERBB2-amplified metastatic breast cancer with triple negative primary), 4) under-genotyped tumors ( BRAFV600E or ERBB2indel in lung). Conclusions: Somatic alteration patterns in ctDNA samples largely agree with tissue alteration patterns, with the exception of resistance mutations. Clinical outcome benefits have been observed for patients treated based on ctDNA findings.
Disparities in cancer risk management among BRCA carriers across a diverse sample of young black, Hispanic, and non-Hispanic white breast cancer survivors.
Authors: Pal Tuya , Cragun Deborah , Lewis Courtney , Bonner Devon , Camperlengo Lucia P , Vadaparampil Susan Thomas 
Published: May 2017

LBA1504 Background: Rates of risk-reducing bilateral mastectomy (RRM) or risk-reducing prophylactic oophorectomy (RRSO) among BRCA carriers are based on studies of non-Hispanic whites (NHW), with little known among blacks or Hispanics. Methods: A population-based sample of NHW, black, and Hispanic women diagnosed with invasive BC < age 50 in 2009-12 were recruited through the Florida State Cancer Registry and completed a baseline survey. Among the subset of BRCA carriers, we compared risk management for: 1) ovarian cancer (OC) through RRSO; and 2) BC through RRM or MRI screening, by calculating percentages and conducting logistic regression to control for other variables. Results: Of 1570 participants, 884 reported BRCA testing. Of the 91 BRCA carriers, 1) RRSO was 71% (36/51) among NHW, 32% (9/28) among blacks, and 83% (10/12) among Hispanics; 2) either breast MRI or RRM was 98% (50/51) among NHW, 85.7% (24/28) among blacks, and 100% (12/12) among Hispanics. BC risk management modality differed across groups, with lower rates of RRM among blacks (67%) compared to Hispanics (83%) and NHW (94%). After controlling for age at enrollment, time since diagnosis, income, family history of BC, family history of OC and private insurance at diagnosis: 1) Hispanics and NHW were significantly more likely than blacks to have RRSO (p = 0.01 and 0.02 respectively); and 2) NHW were also significantly more likely than blacks to have RRM (p = 0.03), although Hispanic race approached statistical significance (p = 0.10). Conclusions: The racial disparities in uptake of RRSO observed among blacks is particularly concerning given that RRSO is strongly recommended as the main OC prevention option due to the absence of effective OC early detection methods. The benefit from genetic testing comes from uptake of cancer risk management options, rather from testing itself. Future studies are needed to better understand and develop methods to improve cancer risk management practices across all populations.
Anti-CD19 chimeric antigen receptor T cells preceded by low-dose chemotherapy to induce remissions of advanced lymphoma.
Authors: Kochenderfer James , Somerville Robert , Lu Tangying , Shi Victoria , Yang James C. , Sherry Richard , Klebanoff Christopher , Kammula Udai S. , Goff Stephanie L. , Bot Adrian , Rossi John , Sherman Marika , Perez Arianne , Xue Allen , Feldman Tatyana A. , Friedberg Jonathan W. , Roschewski Mark J. , Feldman Steven , McIntyre Lori , Rosenberg Steven A. 
Published: May 2017

LBA3010 Background: T cells genetically-modified to express chimeric antigen receptors (CARs) targeting CD19 have potent activity against a variety of B-cell malignancies. Chemotherapy is administered prior to CAR T cells because depletion of recipient leukocytes enhances the anti-malignancy efficacy of adoptively-transferred T cells; an increase in serum interleukin (IL)-15 is one mechanism for this enhancement. Previously, we (Kochenderfer et al. Journal of Clinical Oncology, 2015) and others have reported patients treated with high-dose chemotherapy prior to anti-CD19 CAR T-cell infusions. This report describes treatment of 22 patients with low-dose conditioning chemotherapy followed by infusion of anti-CD19 CAR T-cells. Methods: Eighteen of 22 treated patients received 300 mg/m2 of cyclophosphamide (cy) daily for 3 days; 4 patients received 500 mg/m2 of cy on the same schedule. All patients received fludarabine 30 mg/m2daily for 3 days on the same days as cy. Patients received a single dose of CAR T cells 2 days after completion of chemotherapy. Blood CAR T cells and serum cytokines were analyzed in all patients. Results: Nineteen patients with various subtypes of diffuse large B-cell lymphoma (DLBCL) had the following responses: 8 CR, 5 PR, 2 SD, and 4 PD. One patient with mantle cell lymphoma obtained a CR. Two patients with follicular lymphoma both obtained CRs. Durations of response currently range from 1 to 20 months; 10 remissions are ongoing. All but 4 patients had either chemotherapy-refractory lymphoma or lymphoma that had relapsed after autologous stem cell transplant. The most prominent toxicities were various neurological toxicities. Other toxicities included fever and hypotension. The median peak blood CAR+ cell level was 47/μL (range 4-1217/μL). Patients obtaining CRs or PRs had higher peak blood CAR+ cell levels than patients experiencing SD or PD. The mean serum IL-15 level was 4 pg/mL before the conditioning chemotherapy and 32 pg/mL after chemotherapy (P < 0.0001). Conclusions: Anti-CD19 CAR T cells can induce remissions of advanced B-cell lymphoma when administered after low-dose chemotherapy. In the near future, CAR T cells will likely be a standard therapy for lymphoma. Clinical trial information: NCT00924326.
Atezolizumab (atezo) as first-line (1L) therapy in cisplatin-ineligible locally advanced/metastatic urothelial carcinoma (mUC): Primary analysis of IMvigor210 cohort 1.
Authors: Balar Arjun Vasant , Galsky Matt D. , Loriot Yohann , Dawson Nancy Ann , Necchi Andrea , Srinivas Sandy , Joseph Richard Wayne , Vaishampayan Ulka N. , Sridhar Srikala S. , Quinn David I. , Drakaki Alexandra , Duran Ignacio , Rosenberg Jonathan E. , Powles Thomas , Hoffman-Censits Jean H. , Cui Na , Mariathasan Sanjeev , Thastrom Ann Christine , Abidoye Oyewale O. , Bajorin Dean F. 
Published: May 2017

LBA4500 Background: Cisplatin-based chemo is a standard 1L treatment (tx) for mUC and the only tx that prolongs OS; however, age or comorbidities render many pts ineligible, and 30-50% receive no tx. Atezo (MPDL3280A) is active and well tolerated in platinum-treated mUC, justifying testing atezo as 1L tx in cisplatin-ineligible pts. Methods: Pts were chemo naive in the metastatic setting and cisplatin ineligible (renal [GFR > 30 but < 60 mL/min]/hearing impairment, ≥ G2 peripheral neuropathy [PN] or ≥ ECOG PS2). Atezo 1200 mg was given IV q3w until PD (RECIST v1.1). Centrally assessed PD-L1 on tumor infiltrating immune cells (IC; SP142 IHC assay) was scored IC2/3, 1 or 0. The primary efficacy endpoint was confirmed ORR assessed per RECIST v1.1 (central independent review facility) using a data cutoff of Sep 14, 2015. Results: 119 efficacy/safety-evaluable pts of any PD-L1 IC had a median age of 73 y: 21% ≥ 80 y. 18% had prior systemic tx (21% [neo]adjuvant); 10% had radiotherapy. 66% had visceral mets. 71% had CrCl < 60 mL/min; 13% had hearing loss ≥ 25 dB; 6% had prior PN ≥ G2; 20% had ECOG PS2. ORR was 19% (95% CI 13-28; 5% CR), and responses occurred in all IC subgroups (Table; includes DCR/PFS/OS) and in pts with poor prognostic factors. 22/23 responses were ongoing with mDOR not reached. Median follow-up was 8.5 mo (range 0.2-14.3); median tx duration was 15 wk. Atezo was generally well tolerated. Tx-related all-G and G3-4 AEs were seen in 64% and 12% of pts, respectively. Related all-G AEs ≥ 10% included fatigue, pruritus, diarrhea. 1 G5 related AE occurred (sepsis). 3% had a G3-4 immune-mediated AE. Conclusions: Atezo has clinically meaningful activity in 1L cisplatin-ineligible mUC pts, and preliminary OS is encouraging. The durable nature of response and favorable AE profile makes this an attractive alternative to chemo. NCT02108652. Clinical trial information: NCT02108652. [Table: see text]
Patient-reported outcomes from MA.17R: A randomized trial of extending adjuvant letrozole for 5 years after completing an initial 5 years of aromatase inhibitor therapy alone or preceded by tamoxifen in postmenopausal women with early-stage breast cancer.
Authors: Lemieux Julie , Goss Paul E. , Parulekar Wendy R. , Ingle James N. , Pritchard Kathleen I. , Robert Nicholas J. , Muss Hyman , Gralow Julie , Strasser-Weippl Kathrin , Brundage Michael Donald , Whelan Kate , Tu Dongsheng , Whelan Timothy Joseph 
Published: May 2017

LBA506 Background: MA.17R is a Canadian Cancer Trials Group (CCTG) led phase III randomized controlled trial comparing letrozole to placebo after 5 years of aromatase inhibitor (AI) as adjuvant therapy for hormone-receptor positive breast cancer. The primary endpoint was disease-free survival. Quality of life (QOL) was a secondary endpoint. Methods: QOL was measured with the SF-36 (2 summary scores and 8 domains) and menopause-specific QOL (MENQOL) (4 symptom domains) at baseline and every 12 months (mo) up to 60 mo. QOL assessment was mandatory for CCTG centres but optional to centres in other groups. Mean change scores from baseline were calculated at 12 and 36 mo. Between-arm differences were assessed with the Wilcoxon test. Results: 1918 patients were randomized and 1428 patients completed the baseline QOL assessment. Compliance with QOL measures was over 85%. Baseline summary scores for SF-36 physical (PCS, 47.5 for letrozole and 47.9 for placebo) and mental (MCS, 55.5 for letrozole and 54.8 for placebo) were close to population norms (50). No differences were seen between groups in mean change scores for the SF-36 PCS and MCS and the other 8 QOL domains. Patients randomized to letrozole reported worse vasomotor symptoms (12 mo p = 0.02, 36 mo p = 0.03) and worse sexual functioning (12 mo p = 0.01, 36 mo p = 0.01). Further analyses with follow up to 60 months will be presented. Conclusions: No differences were seen in overall QOL measured by the SF 36 summary measures between letrozole and placebo groups. Differences existed for vasomotor symptoms and sexual functioning which were worse in the letrozole group and attributed to improvements in mean scores seen for women randomized to placebo. The data indicate that continuation of AI therapy after 5 years prior treatment is not associated with a deterioration of overall QOL. Treatment related vasomotor and sexual functioning alterations occur with ongoing treatment. Clinical trial information: NCT00754845.
Therapy of relapsed/refractory metastatic triple-negative breast cancer (mTNBC) with an anti-Trop-2-SN-38 antibody-drug conjugate (ADC), sacituzumab govitecan (IMMU-132): Phase II results.
Authors: Bardia Aditya , Diamond Jennifer Robinson , Messersmith Wells A. , Mayer Ingrid A. , Isakoff Steven J. , Abramson Vandana Gupta , Berlin Jordan , Starodub Alexander , O'Shaughnessy Joyce , Kalinsky Kevin , Moroose Rebecca L. , Shah Nikita C. , Juric Dejan , Shapiro Geoffrey , Guarino Michael J. , Ocean Allyson J. , Wilhelm Francois , Sharkey Robert M. , Goldenberg David M. , Vahdat Linda T. 
Published: May 2017

LBA509 Notice of Retraction: “Therapy of relapsed/refractory metastatic triple-negative breast cancer (mTNBC) with an anti-Trop-2-SN-38 antibody-drug conjugate (ADC), sacituzumab govitecan (IMMU-132): Phase II results.” ASCO's Confidentiality Policy requires that abstracts be considered confidential and embargoed from the time of submission until the findings have been publicly released in conjunction with the ASCO Annual Meeting. Abstract LBA509, published in the 2016 ASCO Annual Meeting Proceedings Part II, violated this policy and was retracted from publication and presentation at the 2016 ASCO Annual Meeting.
Exploration of the ASCO and ESMO Value Frameworks for Antineoplastic Drugs
Authors: Becker Daniel J. , Lin Daniel , Lee Steve , Levy Benjamin P. , Makarov Danil V. , Gold Heather T. , Sherman Scott 
Published: May 2017

Purpose: In 2015, both ASCO and the European Society for Medical Oncology (ESMO) proposed frameworks to quantify the benefit of antineoplastic drugs in the face of rising costs. We applied these frameworks to drugs approved by the US Food and Drug Administration over the past 12 years and examined relationships between costs and benefits. Methods: We searched FDA.gov for drugs that received initial approval for solid tumors from 2004 to 2015 and calculated the ASCO Net Health Benefit version 2016 (NHB16) and 2015 (NHB15) and the ESMO Magnitude of Clinical Benefit Scale scores for each drug. We calculated descriptive statistics and explored correlations and associations among benefit scores, cost, and independent variables. Results: We identified 55 drug approvals supported by phase II (18.2%) and III (81.8%) trials, with primary outcomes of overall survival (36.4%), progression-free survival (43.6%), or response rate (20.0%). No significant association was found between NHB16 and year of approval ( P = .81), organ system ( P = .20), or trial comparator arm ( P = .17), but trials with progression-free survival outcomes were associated with higher scores ( P = .007). Both NHB15 and Magnitude of Clinical Benefit Scale scores were approximately normally distributed, but only a moderate correlation existed between them ( r = 0.40, P = .006). No correlation between benefit score and cost (NHB16, r = 0.19; ESMO, r = −0.07) was found. Before 2010, two (15.3%) of 13 approved drugs exceeded $500/NHB point × month compared with 10 (25.0%) of 40 drugs subsequently approved. Conclusion: Our analysis of the ASCO and ESMO value frameworks illuminates the heterogeneous benefit of new medications and highlights challenges in constructing a unified concept of drug value. Drug benefit does not correlate with cost, and the number of high cost/benefit outliers has increased.
Relationship between Crystal Structures and Thermoluminescence Spectra of Gamma-Irradiated Shells of Shellfish Measured with a Multichannel Fourier-Transform Luminescence Spectrometer
Authors: Shonaka Moe , Ishii Hiroshi , Hironiwa Takayuki , Akai Nobuyuki , Nakata Munetaka 
Published: May 2017

Abstract
Thermoluminescence spectra of gamma-irradiated shells of oysters, scallops, mussels, littleneck clams, and freshwater clams are measured with a multichannel Fourier-transform luminescence spectrometer. Oysters, scallops, and mussels isothermally heated at 200 °C show strong luminescence due to the electronic transition of Mn2+, which is included as an impurity in shells and excited to a metastable state by gamma-ray irradiation. Littleneck clams and freshwater clams show very weak thermoluminescence under the same experimental conditions and show strong thermoluminescence owing to phase transition when they are heated at 450 °C before gamma-ray irradiation. The phase transition of the crystal structures from aragonite to calcite is monitored by infrared spectroscopy.
Measuring and Understanding Brand Value in a Dynamic Model of Brand Management
Authors: Borkovsky Ron N. , Goldfarb Avi , Haviv Avery M. , Moorthy Sridhar 
Published: May 2017

We develop a structural model of brand management to estimate the value of a brand to a firm. In our framework, a brand’s value is the expected net present value of future cash flows accruing to a firm due to its brand. Our brand value measure recognizes that a firm can change its brand equity by investing in advertising. We estimate quarterly brand values in the stacked chips category for the period 2001–2006 and explore how those values change over time. Comparing our brand value measure to its static counterpart, we find that a static measure, which ignores advertising and its ability to affect brand equity dynamics, yields brand values that are artificially high and that fluctuate too much over time. We also explore how changing the ability to build and sustain brand equity affects brand value. At our estimated parameterization, if brand equity were to depreciate more slowly, or if advertising were more effective at building brand equity, then brand value would increase. However, counterintuitively, we find that when the effectiveness of advertising is sufficiently high, increasing the rate at which brand equity depreciates can increase the value of a firm’s brand, even as it reduces the value of the firm overall.Data and the online appendix are available at https://doi.org/10.1287/mksc.2016.1020 .
An Experimental Investigation of Managing Quality Through Monetary and Relational Incentives
Authors: Davis Andrew M. , Hyndman Kyle 
Published: May 2017

We investigate the efficacy of monetary and relational incentives for managing the quality of a product in a two-tier supply chain. In our setting, a retailer offers a supplier contract terms for a product, where the product can be low or high quality. The supplier can choose to exert high effort, which is costly but guarantees high quality, or low effort, which does not assure high quality with certainty. We compare how monetary incentives, such as a bonus that is paid to the supplier when high quality is received by the retailer, and relational incentives, such as the two parties engaging in a long-term relationship where there is the threat of punishment, affect overall quality and supply chain efficiency. Two of our primary results suggest that (1) relational incentives improve both quality and supply chain efficiency, regardless of whether a monetary incentive is present, and (2) when relational incentives are present, the impact of adding monetary incentives is nonmonotonic: less efficient monetary incentives appear to crowd out the benefits of relational incentives leading even to a reduction in supply chain efficiency, whereas more efficient monetary incentives actually complement relational incentives and lead to significant increases in both quality and supply chain efficiency. We then proceed by demonstrating that a behavioral model of fairness can organize the data quite well. Data are available at https://doi.org/10.1287/mnsc.2016.2716 . This paper was accepted by Serguei Netessine, operations management.
Diabetes series, 6. Prevention and management of diabetic foot problems
Authors: Nazarko Linda 
Published: May 2017

Diabetes mellitus (DM) increases the risk of foot problems and the person with diabetes is at risk of major complications, including ulcers and amputations. A person with DM is 30 times more likely to require an amputation than a person without diabetes ( Khanolkar et al, 2008 ). Every day, 20 people with diabetes have a lower limb amputation ( Public Health England, 2016 ). Simple interventions such as smoking cessation, inspecting feet daily, seeking help if there are any concerns and wearing suitable footwear can reduce the risk of ulcers and amputations and improve quality of life. This article aims to educate the healthcare assistant on the reasons why people with diabetes develop foot ulcers and to enable the healthcare assistant to provide appropriate care and support to people with diabetes.
Nursing students' experiences of mentorship in their final placement
Authors: Thomson Robert , Docherty Angie , Duffy Raymond 
Published: May 2017

Aim: The aim of this study was to explore final-year students' experiences of the mentorship role in their final placement and, in particular, to establish their expectations of the mentorship role, as well as their support and supervision needs. Method: Seven final-placement students were recruited from one Scottish university, using purposive sampling. Heideggerian phenomenology was chosen as the underpinning philosophical approach because of its emphasis on the ‘lived experience’. Data were generated using unstructured interviews and analysed using a modified version of Colaizzi's procedural steps. Results: Five themes emerged from the data: ‘being more independent’, ‘support’, ‘belongingness’, ‘feedback’ and ‘anticipatory anxiety’. Discussion: Participants who had a positive experience of mentorship were exposed to a ‘good’ learning environment. As a result, they felt supported, received adequate opportunities to practise management skills, had a sense of ‘belonging’ within the nursing team and had regular feedback. Those who had a negative experience complained of not getting the opportunity to develop essential management skills and being dismissed for trying to be proactive. In addition, feedback was reported to be lacking. This experience resulted in reduced confidence levels, which left them feeling unprepared for the transition to registered nurse. Conclusion: The clinical learning environment itself and support from the mentor are key factors that influence student preparation for registration. Without this level of support, students may be left feeling unprepared to deal with the transition.