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As marine traffic increases globally, ship strikes have emerged as a primary threat to many baleen whale populations. Here we predict ship-strike rates for fin whales Balaenoptera physalus and humpback whales Megaptera novaeangliae in the central territorial waters of the Gitga’at First Nation (British Columbia, Canada), which face increases in existing marine traffic as well as new liquified natural gas (LNG) shipping in the next decade. To do so, we utilized Automatic Identification System (AIS) databases, line-transect surveys, shore-based monitoring, whale-borne tags, aerial drone-based focal follows, and iterative simulations. We predict that by 2030, whale encounters will triple for most vessel types, but the change is most extreme for large ships (length >180 m) in prime whale habitat, in which co-occurrences will increase 30-fold. Ship-strike mortalities are projected to increase in the next decade by 2.3× for fin whales and 3.9× for humpback whales, to 2 and 18 deaths yr-1, respectively. These unsustainable losses will likely deplete both species in the coastal region of BC. Models indicate that the largest single source of mortality risk in 2030 will be from the LNG Canada project. Of the mitigation options we evaluated, a 10 knot speed ceiling for all large ships is potentially effective, but the best measure for guaranteed mitigation would be seasonal restrictions on LNG traffic. While certain data gaps remain, particularly with respect to humpback whales, our predictions indicate that shipping trends within Gitga’at waters will impact whale populations at regional levels. We provide our analysis in the R package ‘shipstrike’.

PURPOSE: To investigate implicit bias (IB) in the peer review process across ASCO and Conquer Cancer Foundation and to propose potential mitigation strategies. MATERIALS AND METHODS: We, ASCO Working Group on Implicit Bias, selected four data sources: (1) literature search [(a) defining IB in peer review, (b) evidence of IB in peer review, and (c) strategies to mitigate IB]; (2) created and analyzed an ASCO database for sex, race, and institutional affiliation regarding peer review success; (3) constructed and conducted qualitative interviews of key stakeholders within the ASCO board, publications, and grants committee, on experience with IB within ASCO; and (4) constructed, delivered, and analyzed results of member survey on perception of IB within ASCO. RESULTS: Historically uncommon, PubMed articles on IB in peer review subsequently increased exponentially in the past 2 decades. Qualitative interviews of ASCO key stakeholders reveal that system changes and IB training were priorities. The committee member survey reported that their peer review decisions could be affected by IB and that mitigating IB should be a priority. Most reported having never been trained on IB. Available data from ASCO database support stakeholder findings, suggesting that there exists a disproportionate representation of males and better-known institutions among both reviewer positions and awardees. Ethnicity/race data were insufficiently reported. Limited data on interventions/strategies to mitigate IB in the peer-reviewed literature suggest that there are feasible processes for grants, program committees, and journals. CONCLUSION: Limited data reveal that the peer review process at ASCO is not exempt from IB and suggest association with sex and institutional affiliation. Working Group on Implicit Bias recommends three actions to mitigate IB within peer review: (1) create awareness and a culture of inclusivity, (2) create systems to reduce IB, and (3) collect data for ongoing analysis.

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Women with triple negative breast cancer (TNBC) have a high prevalence of BRCA1 mutations, and current clinical guidelines recommend genetic testing for patients with TNBC aged ≤60 years. However, studies supporting this recommendation have included few older women with TNBC. Methods Genetic testing results from women aged >60 years with TNBC enrolled in the Clinical Cancer Genomics Community Research Network (CCGCRN) registry were included in this analysis. Prevalence of breast cancer-associated pathogenic variants (PVs) was compared across age groups. Results We identified 151 women with TNBC aged >60 years (median 65 years; SD 5.3). Of these, 130 (86%) underwent genetic testing, and a breast cancer–associated PV was identified in 16 (12.3%; 95% CI 7–19): BRCA1 (n = 6), BRCA2 (n = 5), PALB2 (n = 2), ATM (n = 1) and RAD51C (n = 2). We found no differences in the proportion of patients with close blood relatives with breast (≤50 years) or ovarian cancer (any age) between PV carriers (37.5%) and non-carriers (34.2%) (p = 0.79). Among PV's carriers, the proportion of older women with a BRCA1 PV was lower when compared to younger women (37.5% vs 77.2%; p Conclusion Breast cancer-associated PVs were found in an important proportion of women aged >60 years with TNBC undergoing genetic testing, including greater representation of BRCA2. These results suggest that older women with TNBC should be offered genetic testing, and that their exclusion based on chronologic age alone may not be appropriate.

The Askaryan Radio Array (ARA) is a ground-based radio detector at the South Pole designed to capture Askaryan emission from ultra-high energy neutrinos interacting within the Antarctic ice. The newest ARA station has been equipped with a phased array trigger, in which radio signals in multiple antennas are summed in predetermined directions prior to the trigger. In this way, impulsive signals add coherently, while noise likely does not, allowing the trigger threshold to be lower than a traditional ARA station. Early results on just a fraction of available data from this new system prove the feasibility of a low-threshold analysis.

The Askaryan Radio Array (ARA) is an ultra-high energy (UHE) neutrino ($E_{\nu}$ > $10^{17}$ eV) detector at South Pole. ARA aims to utilize radio signals detected from UHE neutrino interactions in the glacial ice to infer properties about the interaction vertex as well as the incident neutrino. To retrieve these properties from experiment data, the first step is to extract timing, amplitude and frequency information from waveforms of different antennas buried in the deep ice. These features can then be utilized in a neural network to reconstruct the neutrino interaction vertex position, incoming neutrino direction and shower energy. So far, vertex can be reconstructed through interferometry while neutrino reconstruction is still under investigation. Here I will present a solution based on multi-task deep neural networks which can perform reconstruction of both vertex and incoming neutrinos with a reasonable precision. After training, this solution is capable of rapid reconstructions (e.g. 0.1 ms/event compared to 10000 ms/event in a conventional routine) useful for trigger and filter decisions, and can be easily generalized to different station configurations for both design and analysis purposes.

BACKGROUND/OBJECTIVES Women diagnosed with breast cancer (BC) at an older age are less likely to undergo genetic cancer risk assessment and genetic testing since the guidelines and referrals are biased toward earlier age at diagnosis. Thus, we determined the prevalence and type of pathogenic cancer predisposition variants among women with a history of BC diagnosed at the age of 65 years or older vs younger than 65 years. DESIGN Prospective registration cohort. SETTING The Clinical Cancer Genomics Community Research Network, including 40 community-based clinics in the United States and 5 in Latin America. PARTICIPANTS Women with BC and genetic testing results. MEASUREMENTS Sociodemographic characteristics, clinical variables, and genetic profiles were compared between women aged 65 years and older and those younger than 65 years at BC diagnosis. RESULTS Among 588 women diagnosed with BC and aged 65 years and older and 9412 diagnosed at younger than 65 years, BC-associated pathogenic variants (PVs) were detected in 5.6% of those aged 65 years and older (n = 33) and 14.2% of those younger than 65 years (n = 1340) (P

Introduction/Purpose Flow-diverting stents (FDS) are effective in treating complex intracranial aneurysms including posterior communicating artery (PCoA) aneurysms. However, some studies have suggested a decrease in efficacy of FDS in treating PCoA aneurysms associated with a fetal PCoA (FPCoA), postulating that the increased flow through the FPCoA prevents endothelialization of the FDS required for aneurysm occlusion. Others have expressed concern that treating FPCoA aneurysms using FDS could result in posterior circulation ischemia from reducing blood flow through the FPCoA. We therefore reviewed our institutional experience using FDS as a stand-alone intervention to treat complex FPCoA aneurysms. Material/Methods We performed a retrospective analysis of our endovascular database from 1/2012 to 12/2018 to identify patients with FPCoA aneurysms treated using a FDS as the standalone intervention. We identified aneurysms where the FPCoA vessel originated from the neck or dome of the aneurysm and who were therefore not appropriate candidates for standard coil embolization. We extracted demographic, clinical, treatment, and radiographic data. We considered a FPCoA as any PCoA with a caliber larger than the visualized P1 segment of the posterior cerebral artery. Results We performed stand-alone, single-device, FDS treatments for 16 PCoA aneurysms associated with FPCoA vessels that originated from either the neck or dome of the aneurysm. Ten of these 16 aneurysms were previously treated (6 coiled, 3 clipped, and 2 multiple open/endovascular interventions) and the FDS was used to treat a recurrence/residual. Seven were previously ruptured. For all cases, we carefully sized the device to ensure excellent wall apposition and focused on device expansion into the neck of the aneurysm to optimize flow-diversion. Using this technique, we achieved an excellent angiographic result in 12 of the 16 cases (75%), with complete obliteration of the aneurysm in 10 cases (62.5%) and near complete obliteration with only trace filling of a neochannel at the aneurysm base in 2 (12.5%). In the remaining 4 (25%) cases, in whom follow-up is ongoing, we observed significant, progressive aneurysm occlusion with marked flow stagnation within the remaining aneurysm. No cases have necessitated additional treatment. We assessed FPCoA patency on follow-up angiography in all patients and observed complete patency in 9, present but decreased flow in 4, markedly diminished flow in 2, and FPCoA occlusion in 1 patient. In all 7 cases with decreased FPCoA flow, we noted co-incident increased P1 flow. No patient exhibited symptoms attributable to posterior circulation ischemia. No procedural complications were encountered and all patients remained neurologically stable following treatment. Mean clinical and angiographic follow-up was 19.9 months. Conclusion FDS can be a safe and effective treatment option for PCoA aneurysms despite the presence of a FPCoA and can result in satisfactory occlusion rates without posterior circulation ischemia. The deployment technique of maximizing device expansion across the neck of the aneurysm may contribute to successful outcomes. Treatment using a FDS may be of particular utility for complex FPCoA aneurysms where – because of their morphology, relation to the FPCoA vessel, or prior treatments attempted –the ability for standard coiling or microsurgical treatment is limited. Disclosures J. Baranoski: None. S. Merrill: None. B. Hendricks: None. J. Catapano: None. T. Cole: None. N. Majmundar: None. D. Wilkinson: None. F. Albuquerque: None. A. Ducruet: None.

Introduction/Purpose Historically, spinal dural arteriovenous fistulas (SDAVFs) have been treated with intradural ligation of the draining vein. While endovascular embolization can achieve durable occlusion in a subset of these patients, recent studies have demonstrated a superiority of microsurgical ligation. However, given that spinal angiography is essential in the workup of suspected SDAVFs, we and others have demonstrated the utility of an ‘endovascular-first’ approach to SDAVFs. One limiting factor to the success of endovascular therapies has been the reliability of casting and occluding the draining vein using Onyx. In contrast, we have observed that n-butyl-2-cyanoacrylate (nBCA) glue can readily penetrate and cast the fistula and vein. We therefore sought to compare the efficacy of nBCA and Onyx embolization in the treatment of SDAVFs. Material and Methods We performed a retrospective analysis of our endovascular database from 4/2007 to 4/2019 to identify patients treated for SDAVFs. We extracted demographic, clinical, treatment, and radiographic information data. We considered a ‘durable cure’ of the SDAVF to include complete obliteration of the fistula following endovascular treatment, demonstrated clinical improvement, and follow-up radiographic studies demonstrating improvement of spinal cord edema and flow voids on MRI/MRA and/or persistent obliteration on follow-up angiograms. We compared our results using Onyx and nBCA embolysate. Results We performed 40 endovascular treatments for SDAVFs in 38 patients. The embolysates utilized were Onyx without any other embolysate (22), NBCA without any other liquid embolysate (16), and a combination of nBCA and Onyx (2). For the 22 treatments in which Onyx was the only embolysate used, endovascular treatment resulted in a durable cure in 11 cases (50%) (mean follow-up 20.8 months). For 10 of these 22 (45.5%), a complete obliteration of the fistula with casting of the vein was not achieved and these patients were referred for microsurgical ligation. For 1 of these 22 treatments, a complete obliteration of the fistula was noted on immediate post-procedure angiography. However, 4.2 months after treatment, he was found to have a recurrence. For the 16 treatments in which nBCA was the only liquid embolysate used, endovascular treatment resulted in a complete obliteration of the fistula following treatment in all 16 (100%) patients. None of these patients underwent subsequent microsurgical treatment. Follow-up data were available for 13 of these patients (81.3%). Of these 13, all (100%) achieved a durable cure (mean follow-up 19.6 months) without clinical or radiographic recurrence. A durable cure was achieved more frequently in patients treated with nBCA (100%) relative to those treated with Onyx only (50%) (p Conclusion NBCA embolization of SDAVFs is superior to Onyx embolization. NBCA embolization is safe and effective for a subset of SDAVFs with results in this population comparable to microsurgical ligation. Disclosures J. Baranoski: None. J. Catapano: None. T. Cole: None. N. Majmundar: None. B. Hendricks: None. D. Wilkinson: None. A. See: None. D. Cavalcanti: None. B. Flores: None. A. Ducruet: None. F. Albuquerque: None.

Purpose Bevacizumab improves progression-free survival but not overall survival in patients with metastatic breast cancer. E5103 tested the effect of bevacizumab in the adjuvant setting in patients with human epidermal growth factor receptor 2–negative disease. Patients and Methods Patients were assigned 1:2:2 to receive placebo with doxorubicin and cyclophosphamide (AC) followed by weekly paclitaxel (arm A), bevacizumab only during AC and paclitaxel (arm B), or bevacizumab during AC and paclitaxel followed by bevacizumab monotherapy for 10 cycles (arm C). Random assignment was stratified and bevacizumab dose adjusted for choice of AC schedule. Radiation and hormonal therapy were administered concurrently with bevacizumab in arm C. The primary end point was invasive disease–free survival (IDFS). Results Four thousand nine hundred ninety-four patients were enrolled. Median age was 52 years; 64% of patients were estrogen receptor positive, 27% were lymph node negative, and 78% received dose-dense AC. Chemotherapy-associated adverse events including myelosuppression and neuropathy were similar across all arms. Grade ≥ 3 hypertension was more common in bevacizumab-treated patients, but thrombosis, proteinuria, and hemorrhage were not. The cumulative incidence of clinical congestive heart failure at 15 months was 1.0%, 1.9%, and 3.0% in arms A, B, and C, respectively. Bevacizumab exposure was less than anticipated, with approximately 24% of patients in arm B and approximately 55% of patients in arm C discontinuing bevacizumab before completing planned therapy. Five-year IDFS was 77% (95% CI, 71% to 81%) in arm A, 76% (95% CI, 72% to 80%) in arm B, and 80% (95% CI, 77% to 83%) in arm C. Conclusion Incorporation of bevacizumab into sequential anthracycline- and taxane-containing adjuvant therapy does not improve IDFS or overall survival in patients with high-risk human epidermal growth factor receptor 2–negative breast cancer. Longer duration bevacizumab therapy is unlikely to be feasible given the high rate of early discontinuation.

259 Background: In April 2021, it was found that 35% of our breast cancer patients seen in the breast surgery and medical oncology clinics had no financial coverage leading to significant financial toxicity at Parkland Memorial Hospital, a safety net hospital for Dallas county in Texas. In addition, only 8% of all our breast cancer patients were financially screened in April 2021. We aimed to increase pre-visit phone calls to financially screen patients within a week of their subsequent visit with a provider from a baseline rate of 8% to 20% for all breast cancer patients in hopes of capturing more unfunded patients and providing appropriate resources. Methods: We used the Institute for Health Improvement (IHI) model as our quality improvement framework. Based on our fish bone and pareto chart analysis, it was discovered that the lack of consistent financial screening was likely due to lack of standardized training across our ancillary staff, lack of standardized processes for financial screening, and lack of education of both providers and patients regarding the financial coverage process. To address these issues, we created a standardized process of financial screening called “pre-visit planning (PVP)” involving a telephone call by our schedulers to breast oncology patients within 1 week of their next visit. Screening included checking financial application status and educating patients on methods of application submission including epic my-chart enrollment. Screening also included checking financial coverage status and if unfunded, a referral to a financial counselor was made. Formal training of staff was performed with mock trial phone calls. We initiated implementation in the breast surgery clinic initially with plans to expand to the medical oncology clinic. Results: At baseline, in April 2021, 300 patients were seen in the breast surgery clinic of which 19 were financially screened (6.3%). Implementation of PVP for all patients in the breast surgery clinic began in May 2021 with data representing 2 weeks of financial screening by our staff. Total number of patients seen over the span of 2 weeks in the breast surgery clinic was 165 of which 59 were financially screened making up 36% of patients. In addition, 8 patients in the breast surgery clinic were screened by a financial counselor increasing the rate of financial screening to 40.6%. Conclusions: We successfully implemented PVP to better assist our patients in several ways including updating their financial coverage, educating them on the financial process, as well as referring them to a financial counselor for additional aid. Increased follow up time is needed to assess the downstream effects of PVP such as increase in financial counselor visits and decrease in unfunded patients.

Summary Background CLEOPATRA was a phase 3 study comparing the efficacy and safety of pertuzumab, trastuzumab, and docetaxel with placebo, trastuzumab, and docetaxel in patients with HER2-positive metastatic breast cancer. In the primary analysis and subsequent reports, progression-free and overall survival were significantly improved in the pertuzumab group compared with the placebo group. Here, we report the end-of-study analysis of CLEOPATRA. Methods This was a double-blind, randomised, placebo-controlled, phase 3 trial that was done at 204 centres in 25 countries. Eligible patients were 18 years or older, had HER2-positive, metastatic breast cancer, had not received previous chemotherapy or biological treatment for their metastatic disease, and had an Eastern Cooperative Oncology Group performance status of 0 or 1. All study drugs were given intravenously, every 3 weeks. Patients were assigned to receive either pertuzumab or placebo at a loading dose of 840 mg, and 420 mg thereafter; plus trastuzumab at 8 mg/kg loading dose and 6 mg/kg thereafter; and docetaxel at 75 mg/m2, escalating to 100 mg/m2 if tolerated. Pertuzumab or placebo and trastuzumab were given until disease progression; docetaxel was given for six cycles, or longer at the investigators’ discretion. Randomisation (1:1) was done by use of an interactive voice-response system and was stratified by geographical region (Asia, Europe, North America, or South America) and previous treatment (previous adjuvant or neoadjuvant chemotherapy vs none). The primary endpoint was independent review facility-assessed progression-free survival, which has been reported previously. Since the confirmatory overall survival analysis had also occurred before this prespecified end-of-study analysis, analyses presented here are descriptive. Overall survival analyses were based on the intention-to-treat population with crossover patients analysed in the placebo group; analyses were not adjusted for crossover to the pertuzumab group and are likely to be conservative. Safety analyses were based on treatment received; crossover patients were counted in the placebo group up to the day before first pertuzumab dose. This trial is registered with ClinicalTrials.gov , number NCT00567190 . Findings Between Feb 12, 2008, and July 7, 2010, 1196 patients were assessed for eligibility, of whom 808 were enrolled and randomly assigned. 402 patients were assigned to receive docetaxel plus trastuzumab plus pertuzumab, and 406 patients were assigned to receive docetaxel plus trastuzumab plus placebo. Clinical cutoff for this analysis was Nov 23, 2018. Between July 2012 and clinical cutoff, 50 patients crossed from the placebo to the pertuzumab group. Median follow-up was 99·9 months in the pertuzumab group (IQR 92·9–106·4) and 98·7 months (90·9–105·7) in the placebo group. Median overall survival was 57·1 months (95% CI 50–72) in the pertuzumab group and 40·8 months (36–48) in the placebo group (hazard ratio 0·69, 95% CI 0·58–0·82); 8-year landmark overall survival rates were 37% (95% CI 31–42) in the pertuzumab group and 23% (19–28) in the placebo group. The most common grade 3–4 adverse event was neutropenia (200 [49%] of 408 patients in the pertuzumab group, 183 [46%] of 396 patients in the placebo group). Five (1%) of 408 patients in the pertuzumab group and six (2%) of 396 patients in the placebo group had treatment-related deaths. One new serious adverse event suggestive of congestive heart failure (pertuzumab group) and one new symptomatic left ventricular systolic dysfunction (post-crossover) occurred since the previous analysis. Interpretation Our analysis shows that the previously observed improvements in overall survival with pertuzumab, trastuzumab, and docetaxel versus placebo, trastuzumab, and docetaxel were maintained after a median of more than 8 years of follow-up. The long-term safety and cardiac safety profiles of pertuzumab, trastuzumab, and docetaxel were maintained in the overall safety population and within crossover patients. HER2-targeted therapy has changed the natural history of HER2-positive metastatic breast cancer, with the dual blockade of pertuzumab and trastuzumab, with docetaxel, demonstrating an 8-year landmark overall survival rate of 37%. Funding F Hoffmann-La Roche and Genentech.

3569 Background: Previous studies have shown that CCNE2 expression is higher in patients’ cancers resistant to CDK4/6 inhibitors. Increased expression of CCNE2, MTDH, or TSPYL5, genes contained within the 70-gene risk of distant recurrence signature (70GS), has also been implicated in breast oncogenesis, poor prognosis, and chemoresistance. These genes are located on chromosome region 8q22.1, one of the most recurrently amplified regions out of all 70GS genes in breast tumors (Fatima et al. 2017). MYC, located on 8q24, is overexpressed in 40% of all breast cancers (BC). Here we examined the expression of CCNE2, MTDH, and TSPYL5 in relation to 70GS risk and the 80-gene molecular subtype signature (80GS), and their correlation with MYC expression in early stage BC patients. Methods: CCNE2, MTDH, TSPYL5, and MYC mRNA expression was measured in 5022 BC samples sent to Agendia (Irvine, CA) for 70GS and 80GS testing, which included FFPE microarray full-transcriptome data. 70GS was used to stratify patients into Ultra Low Risk (UL), Low Risk (LR), High Risk (HR), and Ultra High Risk (UH). Both 70GS and 80GS were used to classify patient samples into Luminal A, Luminal B, HER2, or Basal type. Wilcoxon rank sum test was used to assess expression differences. Results: The expression of CCNE2, MTDH, and TSPYL5 significantly correlated with each other and was higher in HR patients compared to LR patients (p < 0.001) and higher in UH patients compared to HR patients (p < 0.001). Expression of these genes was highest in Basal type tumors, 83% of which were UH, followed by Luminal B type tumors, and lowest in Luminal A type tumors. CCNE2 and MYC expression was elevated in LR compared to UL patients (p < 0.001 and p = 0.0043). There was no difference in MYC expression between HR vs. LR or UH vs. HR. Lastly, there was no association between the expression of 8q22.1 genes and MYC in any 70GS subgroup. Conclusions: Within the 70GS, CCNE2, MTDH, and TSPYL5 have similar expression patterns and when overexpressed may identify an UH cohort of BC. This observation, in addition to their physical proximity at 8q22.1 suggests a possible amplicon in this region. The highest expression of CCNE2, MTDH, and TSPYL5 associated with UH patients and is concordant with previous studies that support the role of these genes in BC metastasis. Furthermore, this analysis suggests MYC may not stratify patients based on metastatic potential. These data may be clinically relevant for stratifying patients in ongoing clinical trials evaluating response and resistance to targeted therapies in early stage BC.

This paper provides empirical evidence on the performance effects and choice of appointments of supply chain and operations management executives (SCOMEs). The analysis is based on a sample of 681 SCOME appointments that were publicly announced during the 2000–2011 period. We find that the stock market reaction is positive on the day of the announcement. Categorizing the SCOME appointments as new or old and insider or outsider, we find that the market reaction for newly created SCOME positions is positive. The market also reacts more positively when a SCOME is an outsider rather than an insider. The strongest positive reaction is observed when outsiders are hired for newly created SCOME positions. We find evidence of both poor stock price performance and poor operating performance in the period preceding the appointment of new SCOMEs. New SCOME appointments are not followed by an immediate improvement in stock price and operating performance. However, there is no further decline in performance, suggesting that the decline observed in the preappointment period does not continue after the new SCOME is appointed. We also find that the likelihood of a SCOME being an outsider is greater for firms that are smaller, operate in more concentrated industries, and have experienced poor prior performance. This paper was accepted by Serguei Netessine, operations management.

Purpose To update the ASCO/Oncology Nursing Society (ONS) Chemotherapy Administration Safety Standards and to highlight standards for pediatric oncology. Methods The ASCO/ONS Chemotherapy Administration Safety Standards were first published in 2009 and updated in 2011 to include inpatient settings. A subsequent 2013 revision expanded the standards to include the safe administration and management of oral chemotherapy. A joint ASCO/ONS workshop with stakeholder participation, including that of the Association of Pediatric Hematology Oncology Nurses and American Society of Pediatric Hematology/Oncology, was held on May 12, 2015, to review the 2013 standards. An extensive literature search was subsequently conducted, and public comments on the revised draft standards were solicited. Results The updated 2016 standards presented here include clarification and expansion of existing standards to include pediatric oncology and to introduce new standards: most notably, two-person verification of chemotherapy preparation processes, administration of vinca alkaloids via minibags in facilities in which intrathecal medications are administered, and labeling of medications dispensed from the health care setting to be taken by the patient at home. The standards were reordered and renumbered to align with the sequential processes of chemotherapy prescription, preparation, and administration. Several standards were separated into their respective components for clarity and to facilitate measurement of adherence to a standard. Conclusion As oncology practice has changed, so have chemotherapy administration safety standards. Advances in technology, cancer treatment, and education and training have prompted the need for periodic review and revision of the standards. Additional information is available at http://www.asco.org/chemo-standards .

Problem definition: This paper provides empirical evidence on the effect of the 2011 Great East Japan Earthquake (GEJE) on the financial performance of firms. Academic/practical relevance: The GEJE was characterized as the most significant disruption ever for global supply chains. In its aftermath, there was a great deal of debate about the risks and vulnerabilities of global supply chains, and there were calls to redesign and restructure supply chains. Methodology: We empirically estimate the effect of the GEJE on the stock prices of firms. Our analyses are based on a global sample of 470 firms collected from articles and announcements in the business press that identify affected firms, as well as 382 firms that are not mentioned in the business press but are in industries potentially subject to contagion or competitive effects. Results: We estimate that firms experiencing supply chain disruptions as a result of the GEJE lost on average 5.21% of their shareholder value during the one-month period after the GEJE. For Japanese firms, the effect was much more severe with an average 9.32% loss in shareholder value. Non-Japanese firms averaged a 3.73% loss in shareholder value. We also find that upstream and downstream supply chain propagation effects from the GEJE are negative, and the contagion effect on firms related to the nuclear industry is very negative. For firms in the rebuilding industries or competitors to firms affected by the GEJE, the competitive effect from the GEJE is positive. Managerial implications: The loss suffered by both Japanese firms and non-Japanese firms experiencing supply chain disruptions as a result of the GEJE is economically significant. Although the loss is more severe for firms whose operations were directly affected by the GEJE, it is also significant for firms who experienced indirect effects from their upstream and downstream supply chain partners, further confirming the importance of supply chain risk mitigation strategies.

Most cancer quality measures focus on individual cancers, assess specific providers, and evaluate processes of care. Although important, these efforts are not sufficient. A more comprehensive measure set is needed to address gaps in care, focus on patients rather than providers, and assess the cross-cutting aspects of care that are relevant to all patients with cancer throughout the trajectory of their illness.With the long-term goal of developing a more comprehensive oncology measure set, the American Society of Clinical Oncology (ASCO) organized a collaborative measure summit that used an iterative consensus approach to identify priorities for the development of new cancer quality measures. The summit, which included professional societies and patient/consumer advocacy organizations, was held during the ASCO Quality Care Symposium in December 2012.This effort, which brought together 12 diverse stakeholders, identified 10 high-priority topics for cancer quality measure development that cross-cut cancer diagnoses and care settings and addressed patient-centered concerns. Topics of particular interest included planning and counseling before therapy, interdisciplinary and multidisciplinary coordinated care, comprehensive symptom assessment, patient experience of care, and use of palliative care and hospice services.This is an important first step in the development of patient-centered, cross-cutting cancer quality measures. Addressing the high-priority topics identified by this effort will help fill the gaps left by existing cancer quality measures, including care coordination and transitions, quality of life, safety, experience of care, and outcomes. More work will be needed to specify, implement, and validate measures based on these topics.

1509 Background: Clonal hematopoiesis (CH) in myeloid related-genes is associated with development of primary and secondary leukemia and atherosclerotic disease, as well as, decreased overall survival. Identification of factors beyond age and cytotoxic exposures that predispose to CH may be useful to both recognize individuals at increased risk for CH and to better understand how CH develops. We have previously shown that germline mutations in the DNA repair gene ATM may predispose to CH. We hypothesized here that heterozygous ATM germline mutation carriers would have higher rates of CH in myeloid genes compared to controls. Methods: Germline DNA samples from 34 heterozygous ATM germline mutation carriers (cases) and 22 controls without ATM germline mutations were sequenced on an Illumina 2500 using a custom 79-gene-myeloid-CH-coding-exon-amplicon-based Qiaseq panel. Read depth averaged 130x. Pathogenic and likely pathogenic CH variants (PV) above an allele fraction of 2% were used for analyses. Cases and controls were compared using a rank-sum test. Results: Cases had a higher median age (56 years, range 30-82) than controls (48 years, range 5-72). Cases and controls were similar in solid tumor cancer history and known exposure to cancer cytotoxic therapy; 73.5% vs 86.4%, and 18.1 vs 20.6%, respectively. The number of CH PV was similarly associated with age in both cases and controls (cor = 0.31, p = 0.01). Cases displayed more CH PVs than controls (total 62 vs 3 PVs, median 2 PVs vs 0, p = 10-6). Of note, cases frequently had a concomitant second (n = 10; 29% of cases) or third (n = 4; 11.8% of cases) unique ATM CH PV, whereas no ATM CH PVs were seen in controls. Even after excluding ATM CH PVs, CH PVs were more frequent in cases (p = 0.00003). After ATM CH PVs, the most frequent CH PVs in cases were in NF1 (5 PVs), BCORL1 (4 PVs), and DMNT3A (4 PVs). Conclusions: Our study supports ATM as a strong predisposition locus for myeloid gene CH. CH in ATM germline mutation carriers frequently involved unique low allele fraction PVs in ATM, suggesting ATM germline PVs are driving production of likely bi-allelic ATM inactivation in white blood cells, or complete ATM loss. Complete ATM loss may be a nidus particularly for lymphocytic leukemia, as bi-allelic ATM inactivation is a frequent somatic finding.

In this small breast cancer-dedicated solo practice, a retrospective medical record review disclosed the following: significant rate of chemotherapy-related nausea and vomiting and discordance between patient-reported compliance with prescribed antiemetics and medical record documentation of compliance. As part of the curriculum for the American Society of Clinical Oncology (ASCO) Quality Training Program, a quality improvement project was developed to improve adherence to oral antiemetics in our patients with breast cancer receiving highly emetogenic chemotherapy.The following steps were undertaken in plan-do-study-act cycles to improve adherence: enhanced patient education at time of chemotherapy consent, implementation of standardized in-person or e-mail contact with our patients receiving chemotherapy, and improvement of our electronic health record documentation of adherence to oral antiemetics. A run chart was generated to analyze our data.After our interventions, the percentage of patients who took their antiemetics as prescribed rose from a baseline of 49% to 79%.Significant improvement in adherence to oral antiemetics among patients with breast cancer receiving chemotherapy was achieved and sustained in this small-practice setting using the framework provided by participation in the ASCO Quality Training Program.

We consider whether and how firms improve their financial reporting credibility following a restatement by comparing two alternative views. The compliance view predicts that firms simply correct errors to comply with regulations; the signaling view predicts that improvements are broader to allow firms to signal higher reporting quality and thereby reduce information uncertainty. We find that accrual quality improves significantly following the restatement and that this improvement is observed for both earnings and non-earnings error restatements. We also find that the extent of real earnings� management decreases significantly. Further, we find that improvements in accrual quality are higher for firms with CEO turnover and higher incentives to improve, but lower for firms switching to an auditor of lower quality. Collectively, our findings suggest that firms signal improved reporting credibility following a restatement through higher accruals quality and lower real earnings management.

A supply chain management (SCM) system comprises many subsystems, including forecasting, order management, supplier management, procurement, production planning and control, warehousing and distribution, and product development. Demand�supply mismatches (DSMs) could indicate that some or all of these subsystems are not working as expected, creating uncertainties about the overall capabilities and effectiveness of the SCM system, which can increase firm risk. This article documents the effect of DSMs on firm risk as measured by equity volatility. Our sample consists of three different types of DSMs announced by publicly traded firms: production disruptions, excess inventory, and product introduction delays. We find that all three types of DSMs result in equity volatility increases. Over a 2-year period around the announcement date, we observe mean abnormal equity volatility increases of 5.62% for production disruptions, 11.19% for excess inventory, and 6.28% for product introduction delays. Volatility increases associated with excess inventory are significantly higher than the increases associated with production disruptions and product introduction delays. Across all three types of DSMs, volatility changes are positively correlated with changes in information asymmetry. The results provide some support that volatility changes are also correlated with changes in financial and operating leverage.

Over 19% of the US population resides in rural areas, where studies of disease risk and disease outcomes are difficult to assess due to smaller populations and lower incidence. While some studies suggest rural disparities for different chronic diseases, the data are inconsistent across geography and definitions of rurality. We reviewed the literature to examine if local variations in population genomic diversity may plausibly explain inconsistencies in estimating disease risk. Many rural communities were founded over 150 years ago by small groups of ethnically and ancestrally similar families. These have since endured relative geographical isolation, similar to groups in other industrialized nations, perhaps resulting in founder effects impacting local disease susceptibility. Studies in Europe and Asia have found that observably different phenotypes may appear in isolated communities within 100 years, and that genomic variation can significantly vary over small geographical scales. Epidemiological studies utilizing common “rural” definitions may miss significant disease differences due to assumptions of risk homogeneity and misinterpretation of administrative definitions of rurality. Local genomic heterogeneity should be an important aspect of chronic disease epidemiology in rural areas, and it is important to consider for designing studies and interpreting results, enabling a better understanding of the heritable components of complex diseases.

Article, Background Multiple recent genome-wide association studies (GWAS) have identified a single nucleotide polymorphism (SNP), rs10771399, at 12p11 that is associated with breast cancer risk. Method We performed a fine-scale mapping study of a 700 kb region including 441 genotyped and more than 1300 imputed genetic variants in 48,155 cases and 43,612 controls of European descent, 6269 cases and 6624 controls of East Asian descent and 1116 cases and 932 controls of African descent in the Breast Cancer Association Consortium (BCAC; http://bcac.ccge.medschl.cam.ac.uk/), and in 15,252 BRCA1 mutation carriers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Stepwise regression analyses were performed to identify independent association signals. Data from the Encyclopedia of DNA Elements project (ENCODE) and the Cancer Genome Atlas (TCGA) were used for functional annotation. Results Analysis of data from European descendants found evidence for four independent association signals at 12p11, represented by rs7297051 (odds ratio (OR) = 1.09, 95 % confidence interval (CI) = 1.06–1.12; P = 3 × 10-9), rs805510 (OR = 1.08, 95 % CI = 1.04–1.12, P = 2 × 10-5), and rs1871152 (OR = 1.04, 95 % CI = 1.02–1.06; P = 2 × 10-4) identified in the general populations, and rs113824616 (P = 7 × 10-5) identified in the meta-analysis of BCAC ER-negative cases and BRCA1 mutation carriers. SNPs rs7297051, rs805510 and rs113824616 were also associated with breast cancer risk at P, published version, peerReviewed

Our study investigates the adoption of the Balanced Scorecard (BSC) as a strategic planning system. We empirically examine the firm-level factors—business-level strategy, firm size, environmental uncertainty, investment in intangible assets, and prior performance— that are posited to differentiate BSC adopters from nonadopters. Drawing on a sample of Canadian firms and utilizing both survey and archival data, we find that BSC adopters (a) are more likely to follow a Prospector or Analyzer business strategy, (b) are significantly larger, (c) exhibit significantly higher environmental uncertainty than nonadopters, and (d) have weaker prior performance. Copyright © 2011 ASAC. Published by John Wiley & Sons, Ltd. Resume Cette etude enquete sur l'adoption d'un systeme de planification strategique : le tableau de bord equilibre (BSC). Elle examine empiriquement les facteurs qui, au niveau de l'entreprise, differencieraient celles qui adoptent le BSC de celles qui ne l'adoptent pas. Ces facteurs sont : la strategie au niveau de l'entreprise, la taille de l'entreprise, l'incertitude environnementale, l'investissement dans les actifs incorporels et la performance anterieure. En s'appuyant sur un echantillon de firmes canadiennes et en utilisant aussi bien les enquetes que les donnees d'archives, l'etude revele que les entreprises qui adoptent le BSC (a) sont plus enclines a adopter une strategie d'affaires Prospectrice ou Analyste (b) sont beaucoup plus grandes en taille (c) presentent une incertitude environnementale nettement plus elevee et (d) ont une performance anterieure plus faible. Copyright © 2011 ASAC. Published by John Wiley & Sons, Ltd.

Aim The aim of this study was to assess the oncological and postoperative outcomes of laparoscopic colorectal cancer surgery in obese patients. Method All obese (BMI > 30) patients who underwent laparoscopic colorectal cancer surgery from January 2005 to January 2008 were compared with nonobese patients undergoing similar surgery. We recorded patient demographics, intra-operative details and postoperative morbidity and mortality. Results Sixty-two obese and 172 nonobese patients underwent laparoscopic colorectal cancer resection. Both groups were well matched for demographic parameters. Overall mean operating times were not significantly different. Conversion to open surgery was more likely in obese patients. In particular, for rectal cancers, the conversion rate was 44% in the obese group compared with 17% in the nonobese group (P

This paper investigates the long-term stock price effects and equity risk effects of supply chain disruptions based on a sample of 827 disruption announcements made during 1989–2000. Stock price effects are examined starting one year before through two years after the disruption announcement date. Over this time period the average abnormal stock returns of firms that experienced disruptions is nearly –40%. Much of this underperformance is observed in the year before the announcement, the day of the announcement, and the year after the announcement. Furthermore, the evidence indicates that firms do not quickly recover from the negative effects of disruptions. The equity risk of the firm also increases significantly around the announcement date. The equity risk in the year after the announcement is 13.50% higher when compared to the equity risk in the year before the announcement.

This paper documents that excess inventory announcements, an indication of demand-supply mismatch, are associated with an economically and statistically significant negative stock market reaction. The results are based on a sample of 276 excess inventory announcements made during 1990–2002. Over a two-day period (the day of the announcement and the day before the announcement) the mean (median) stock market reaction ranges from −6.79% to −6.93% (−4.51% to −4.79%), depending on the benchmark used to estimate the market reaction. The percent of sample firms that experience negative market reaction ranges from 73% to 74%. When excess inventory is at the announcing firm's customers, the market reaction is more negative than when the excess inventory is at the announcing firm. The stock market reaction is less negative for excess inventory announcements made by larger firms but is more negative for firms with higher growth prospects and with higher debt-equity ratios.

This paper empirically examines whether operational slack, business diversification, geographic diversification, and vertical relatedness influence the stock market reaction to supply chain disruptions. The results are based on a sample of 307 supply chain disruptions announced by publicly traded firms during 1987–1998. Our analysis shows that firms with more slack in their supply chain experience less negative stock market reaction. The extent of business diversification has no significant effect on the stock market reaction. Firms that are more geographically diversified experience a more negative stock market reaction. We find that firms with a high degree of vertical relatedness experience a less negative stock market reaction. These results have important implications on how firms design and operate their supply chains to mitigate the negative effect of supply chain disruptions.

This paper estimates the shareholder wealth affects of supply chain disruptions. The results are based on a sample of 838 disruption announcements made during 1989–2001. Shareholder wealth affects are estimated by computing the abnormal stock returns (actual returns adjusted for industry and market-wide influences) around the date when information about disruptions is publicly announced. Supply chain disruption announcements are associated with an abnormal decrease in shareholder value of 10.28%. We find that larger firms experience a less negative market reaction, and firms with higher growth prospects experience a more negative reaction. We also provide descriptive results on how sources of responsibility and reasons for disruptions affect shareholder wealth.

We report O2/Ar ratios (a constraint on net community production) and the triple isotopic composition of dissolved O2 (a constraint on gross primary production) in samples collected from the surface mixed layer on 23 Southern Ocean transits. Samples were collected at 1–2° meridional resolution during the austral summer. Methodological limitations notwithstanding, the results constrain the net/gross production ratio, net O2 production, and gross O2 production at unprecedented resolution throughout the Southern Ocean mixed layer. Gross O2 production rates inferred from the oxygen triple isotopes are greater than production rates calculated from a model based on remotely sensed chlorophyll. This result agrees with previous 18O and 14C incubations along 170°W. O2/Ar ratios exceeding saturation are consistently observed within the Subantarctic and Polar Frontal Zones south of New Zealand and Australia, showing that a net autotrophic community predominates during austral summer. Lower O2/Ar values are observed within the Drake Passage and Antarctic Zone, suggesting unresolved influences of low net community production, net heterotrophy, and upwelling of O2-undersaturated waters. In autotrophic waters of the austral summer mixed layer, ratios of net community production/gross O2 production scatter about 0.13, corresponding to f ratios of ∼0.25. Net community/gross O2 production ratios show no meridional gradient across the Antarctic Circumpolar Current, suggesting that an approximately constant fraction of gross primary productivity is regenerated or exported. Our calculated net O2 production rates are in satisfactory agreement with comparable published estimates. Net and gross O2 production rates are highest in the Subantarctic and decline to the south, paralleling the well-known trend of chlorophyll a concentrations. In an analysis of variance of net O2 production and gross O2 production with other environmental variables, the strongest correlations are between net O2 production and sea surface temperature (SST) (direct correlation), climatological [NO3−] (inverse correlation), and estimates of primary productivity derived from a remote sensing (direct correlation). These trends are as expected if aerosol iron input is the most important influence on production. They are unexpected if upwelling-derived SiO2 and iron are the leading influence or if lower SSTs promote greater export in this region.