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Context: Palonosetron (PALO) is one of the two active components of NEPA, the fixed-combination antiemetic comprising netupitant (oral)/fosnetupitant (IV) and PALO. To increase the convenience of NEPA administration, especially for patients with swallowing difficulties, an IV NEPA formulation has been developed, where PALO is administered as a 30-minute infusion instead of the approved 30-second bolus.Objectives: To determine the efficacy and safety of the PALO component used in IV NEPA.Methods: Noninferiority, double-blind, and randomized Phase 3 trial in chemotherapy-naive adult patients with cancer requiring highly emetogenic chemotherapy. Patients were randomized to receive a single dose of PALO 0.25 mg administered IV either as a 30-minute infusion or as a 30-second bolus before highly emetogenic chemotherapy. The primary objective was to demonstrate noninferiority of the 30-minute infusion vs. 30-second bolus in terms of complete response (CR; no emesis and no rescue medication) in the acute phase. Secondary efficacy endpoints were CR in the delayed and overall phases and no emesis and no rescue medication in all phases. Safety was a secondary endpoint.Results: Overall, 440 patients received study treatment. In the infusion group, 186 (82.7%) patients reported CR in the acute phase vs. 186 (86.5%) patients in the bolus group, demonstrating the noninferiority of PALO infusion vs. bolus (P < 0.001). Secondary endpoints showed similar results between the two treatment groups.Conclusion: PALO 0.25-mg 30-minute IV infusion was noninferior to 30-second IV bolus in terms of CR rate in the acute phase. These results support the use of PALO 0.25 mg as a component of IV NEPA. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Fuel management projects on national forests typically have multiple objectives. • Project performance must account for uncertainty in wildfire occurrence. • Performance can be measured by fire-treatment interactions over time. • Wildfire stochasticity limits the potential for fire-treatment interactions. • Spatial prioritization based on burn probability had the highest performance. Abstract Predicting the efficacy of fuel treatments aimed at reducing high severity fire in dry-mixed conifer forests in the western US is a challenging problem that has been addressed in a variety of ways using both field observations and wildfire simulation models. One way to describe the efficacy of fuel treatments is to quantify how often wildfires are expected to intersect areas prioritized for treatment. In real landscapes treatments are static, restricted to a small portion of the landscape and against a background of stochastic fire and dynamic vegetation, thus the likelihood of fire encountering a treatment during the period treatments remain effective is small. In this paper we simulate a wide range of different treatment prioritization schemes using the forest landscape simulation model Envision to examine 50 years of fire-treatment interactions and forest succession. We first reviewed 47 fuel management projects in Oregon, USA to build prioritization schemes that addressed different fuel management objectives. We then simulated different priority schemes in the 18 planning areas of the Deschutes National Forest in central Oregon and measured potential fire-treatment interactions over time. Simulated annual area burned was used to calculate the success odds for each priority scheme and planning area. Out of the ten metrics considered only three had higher success odds than a random prioritization of planning areas. Spatial allocation of projects based on burn probability and transmitted wildfire had the highest success odds among the tested metrics. However, success odds declined sharply as desired success levels increased suggesting that fuel management goals need to be tempered to consider the stochastic nature of wildfire. Meeting long-term multiple management goals over time can benefit from consideration of short- and long-term tradeoffs from different treatment prioritization schemes. Our work contributes towards a better framing of both management and public expectations regarding the performance of fuel treatments programs. [ABSTRACT FROM AUTHOR]

Background: NEPA, an oral fixed combination of the NK1RA netupitant (300 mg) and clinically/pharmacologically distinct 5-HT3RA palonosetron (PALO, 0.50 mg), is the first fixed antiemetic combination to have been approved. A single oral NEPA capsule plus dexamethasone (DEX) given before anthracycline-cyclophosphamide (AC) and non-AC highly emetogenic chemotherapy (HEC) showed superior prevention of chemotherapy-induced nausea and vomiting (CINV) over PALO plus DEX for 5 days postchemotherapy. The safety of NEPA was well-established in the phase II/III clinical program in 1169 NEPA-treated patients. An intravenous (i.v.) formulation of the NEPA combination (fosnetupitant 235 mg plus PALO 0.25 mg) has been developed. Patients and methods: This randomized, multinational, double-blind, stratified (by sex and country) phase III study (NCT02517021) in chemotherapy-naïve patients with solid tumors assessed the safety of a single dose of i.v. NEPA infused over 30 min before initial and repeated cycles of HEC. Patients received either i.v. NEPA or oral NEPA, both with oral DEX on days 1-4. Safety was assessed primarily by treatment-emergent adverse events (AEs) and electrocardiograms. Results: A total of 404 patients completed 1312 cycles. The incidence and type of treatment-emergent AEs were similar for both treatment groups with the majority of AEs as mild/moderate in intensity. There was no increased incidence of AEs in subsequent cycles in either group. The incidence of treatment-related AEs was similar and relatively low in both groups (12.8% i.v. NEPA and 11.4% oral NEPA during the entire study), with constipation being the most common (6.4% i.v. NEPA, 6.0% oral NEPA). No serious treatment-related AEs occurred in either group. No infusion site or anaphylactic reactions related to i.v. NEPA occurred. No clinically relevant changes in QTc and no cardiac safety concerns were observed. Conclusions: Intravenous NEPA was well-tolerated with a similar safety profile to oral NEPA in patients with various solid tumors receiving HEC. [ABSTRACT FROM AUTHOR]

Background: Co-administration of multiple antiemetics that inhibit several molecular pathways involved in emesis is required to optimize chemotherapy-induced nausea and vomiting (CINV) control in patients receiving highly emetogenic chemotherapy (HEC). NEPA, a fixed combination of a highly selective NK1 receptor antagonist, netupitant (300 mg), and the pharmacologically distinct 5-HT3RA, palonosetron (PALO 0.50 mg), has shown superior CINV prevention compared with PALO in cisplatin and anthracycline/cyclophosphamide-based settings. This study is the first head-to-head comparison of NEPA versus an aprepitant (APR)/granisetron (GRAN) regimen. Patients and methods: This randomized, double-blind phase III study conducted in Asia was designed with the primary objective to demonstrate non-inferiority of a single oral dose of NEPA compared with a 3-day oral APR/GRAN regimen in chemotherapy-naïve patients receiving cisplatin-based HEC. All patients also received oral dexamethasone (DEX) on days 1-4. The primary efficacy endpoint was complete response (CR: no emesis/no rescue medication) during the overall (0-120 h) phase. Non-inferiority was defined as a lower 95% CI greater than the non-inferiority margin set at -10%. Secondary efficacy endpoints included no emesis, no rescue medication, and no significant nausea (NSN). Results: Treatment groups were comparable for the 828 patients analyzed: predominantly male (71%); mean age 54.5 years; ECOG 0-1 (98%); lung cancer (58%). NEPA demonstrated non-inferiority to APR/GRAN for overall CR [NEPA 73.8% versus APR/GRAN 72.4%, 95% CI (-4.5%, 7.5%)]. No emesis [NEPA 75.0% versus APR/GRAN 74.0%, 95% CI (-4.8%, 6.9%)] and NSN rates [NEPA 75.7% versus APR/GRAN 70.4%, 95% CI (-0.6%, 11.4%)] were similar between groups, but significantly more NEPA patients did not take rescue medication [NEPA 96.6% versus APR/GRAN 93.5%, 95% CI (0.2%, 6.1%)]. NEPA was well tolerated with a similar safety profile to APR/GRAN. Conclusions: In this first study comparing NK1RA regimens and DEX, NEPA administered only on day 1 was non-inferior to a 3-day oral APR/GRAN regimen in preventing CINV associated with HEC. [ABSTRACT FROM AUTHOR]

Objectives Breast cancer (BC) patients represent a high-risk population for experiencing chemotherapy-induced nausea and vomiting (CINV), since they frequently receive highly emetogenic anthracycline-cyclophosphamide–based (AC) chemotherapy, and are often female and young, two predisposing risk factors for CINV. Guidelines recommend the combination of a neurokinin-1 receptor antagonist (NK 1 RA), 5-hydroxytryptamine-3 RA (5-HT 3 RA), and dexamethasone (DEX) for CINV prophylaxis in AC-treated patients. This post-hoc analysis evaluated the efficacy of NEPA, a fixed combination of netupitant (NETU [NK 1 RA]) and palonosetron (PALO [5-HT 3 RA]) in BC patients from two phase III studies. Methods Overall, 1460 BC patients received AC (Study 1) or non-AC (Study 2) therapy over 6060 cycles. Randomized patients received DEX with either NEPA or oral PALO (Study 1), or NEPA or aprepitant+oral PALO (Study 2) before chemotherapy. Results In AC-receiving patients, overall complete response (CR) rates with NEPA+DEX were statistically significantly higher than oral PALO+DEX rates (cycles 1–4: 73.9% vs 65.9%, 80.0% vs 66.0%, 83.6% vs 69.9%, 83.6% vs 74.4%, respectively). Overall, no significant nausea (NSN) rates were also superior with NEPA+DEX vs oral PALO+DEX (respectively, 74.2%–79.9% vs 68.5%–74.9%). A greater proportion of NEPA+DEX patients experienced “no-impact-on-daily-life” due to CINV (78.4% vs 71.4%) in cycle 1. In non-AC–receiving patients, prophylaxis with NEPA+DEX resulted in high CR and NSN rates across 1–4 chemotherapy cycles; no formal comparison with the control arm was performed. Conclusion NEPA+DEX administered as a single dose is an effective option for preventing CINV in BC patients receiving AC and non-AC, across multiple chemotherapy cycles. Clinical trials registration numbers Study 1 : NCT01339260 , Study 2: NCT01376297 . [ABSTRACT FROM AUTHOR]

Objectives Prevention of chemotherapy-induced nausea and vomiting is critical in older patients with cancer. NEPA is an oral fixed combination of netupitant 300 mg, a new NK 1 receptor antagonist (RA), and palonosetron 0.5 mg, a pharmacologically distinct 5-HT 3 RA. This retrospective analysis evaluated the efficacy and safety of NEPA in older patients. Methods Patients aged ≥ 65 and ≥ 70 years from one phase II and two phase III trials were considered. Chemotherapy-naive patients with malignant tumors were treated with anthracycline–cyclophosphamide (AC), non-AC-based moderately emetogenic chemotherapy (non-AC MEC), or highly emetogenic chemotherapy (HEC). Following single-dose NEPA, patients received oral dexamethasone on day 1 (AC and non-AC MEC) or days 1–4 (HEC). Efficacy was evaluated through complete response (CR) in cycle 1. Safety was evaluated by AEs and ECGs. Data were summarized by descriptive statistics. Results Overall, 214 patients were ≥ 65 years and 80 were ≥ 70 years. A higher CR was observed in older patients versus the total population; in the acute phase > 90% of patients ≥ 65 years experienced CR. Efficacy was maintained over multiple cycles of chemotherapy. No significant nausea rates were generally higher in the older patients versus total population. Similar rates of AEs in the first treatment cycle were reported for patients ≥ 65 years, ≥ 70 years, and total population (72.9% vs 67.5% vs 70.0%, respectively). No cardiac safety concerns were raised. Conclusion NEPA is highly effective in older patients receiving MEC or HEC regimens. NEPA is also well tolerated, demonstrating suitability for use in older patients who may have comorbidities. [ABSTRACT FROM AUTHOR]

As the unequal impacts of environmental harms and climate change have become apparent, environmental justice (EJ) is an increasingly salient matter in US environmental policy and impact assessments. The EJ impacts of important infrastructural decisions and investments are most often analyzed in environmental impact statements required by the National Environmental Policy Act (NEPA)—a globally influential piece of legislation—with significant discretion given to organizations on how to conduct these analyses. There is little systematic understanding of how these analyses are conducted and what the findings of these analyses tend to be. In this paper, we analyze a decade's worth of EJ analyses that appear in environmental impact statements conducted in the state of Arizona in the US as a first attempt to fill this gap in understanding. We find that throughout EJ analyses 11 different demographic indicators, ten different community boundaries, and eight different population thresholds are used with considerable variation to identify EJ communities. The variation in how these criteria are applied points to an inconsistent definition of an EJ community throughout the federal government. Still, analyses consistently do not find negative EJ impacts to be likely. While NEPA has promoted positive environmental outcomes in the past, it may currently be failing to do this for EJ. We highlight possible flaws in EJ analysis methods and shortcomings of the NEPA process itself that may cumulatively obstruct meaningful EJ consideration. With the widespread influence of NEPA on environmental impact assesment approaches globally, our findings raise questions that EJ analyses in environmental impact assesments outside the US could suffer from the same methodological shortcomings we identify. • The US federal government expressed environmental justice (EJ) goals in the Justice40 Initiative. • EJ impacts are most often analyzed in NEPA-required environmental impact statements; little is known about these analyses. • The federal government lacks a consistent understanding of identifying EJ communities or impacts. • EJ analyses may fail to identify EJ communities or impacts by using inappropriate analysis methods. • Our findings are relevant to global EJ-focused environmental impact analyses, given the widespread influence NEPA. [ABSTRACT FROM AUTHOR]

Pending either legislative action or formal agency guidance, utilization of the Social Cost of Carbon in analyses of energy development projects on federal land under the National Environmental Policy Act (NEPA) is not required. However, current trends indicate that future NEPA documentation of proposed energy projects on federal land will likely address and discuss project impacts on climate change using increasingly quantitative metrics. Accordingly, parties should be prepared to offer substantive comments on the suitability and accuracy of quantitative analyses of the impacts associated with greenhouse gas emissions and offer suggestions for meaningful mitigation measures to reduce such estimates. [ABSTRACT FROM AUTHOR]

The National Environmental Policy Act (NEPA) provides a regulatory decision-making process that requires U.S. federal agencies to assess the purpose and socio-environmental impacts of a proposed action before deciding to move forward with that action. The multiplicity of NEPA objectives, the complex tradeoffs embedded in the Environmental Impact Assessment (EIA), and the difficulties in accessing data have presented challenges for evaluating NEPA performance. Researchers have responded with a growing array of performance dimensions and specialized measurement approaches. In this paper, we advance a performance framework for EIAs that integrates several of these dimensions and provides a conceptually coherent approach to procedural and substantive performance. The framework articulates three procedural elements (use of science and analysis, nature of public participation, and management of EIA processes); and three substantive elements (quality of both the NEPA review and action decision, and both the accountability and efficiency of the NEPA review decision). Each element is further elaborated by specific functions with specific variables as a basis for future performance measurements. We use two hypothetical use cases, drawn from public land management and federal highway planning, to illustrate how the performance concepts from the framework can be operationalized and measured. • Since its inception 50 years ago in the US, performance measurement of Environmental Impact Assessments (EIAs) has been frustrated by the multiplicity of NEPA objectives and its inherent tradeoffs. • In this paper, we advance a conceptual framework for evaluating both procedural and substantive performance of EIAs that provides conceptual clarity and the basis for operationalizing measurement. • We use two hypothetical cases, from public land management and federal highway planning, to illustrate how the framework's performance concepts can be used to measure and evaluate EIAs. [ABSTRACT FROM AUTHOR]

Many patients undergoing moderately or highly emetogenic chemotherapy experience chemotherapy-induced nausea/vomiting (CINV) and report reduced daily functioning, despite prophylaxis with antiemetic drugs. While modern antiemetics have largely alleviated acute emesis, management of nausea and delayed emesis remains particularly challenging. We briefly review the pathophysiologic mechanisms of CINV and the clinical impact of current antiemetics, i.e., the serotonin subtype 3 (5-HT3) receptor antagonists (RAs) and neurokinin-1 (NK1)RAs, before summarizing recent data from clinical trials of new agents. The new antiemetics reviewed include the two most recently approved drugs, the NK1RA rolapitant and the fixed-dose combination product, NEPA, which is composed of the NK1RA netupitant and the 5-HT3RA palonosetron. Phase 3 studies demonstrate improved control of CINV in the delayed and overall phases when rolapitant is added to a standard 5-HT3RA regimen. Phase 2 and phase 3 clinical trials with NEPA demonstrate improved control of CINV in the acute, delayed, and overall phases vs. 5-HT3RA regimens. These data suggest that delayed emesis can be substantially reduced via combined 5-HT3 and NK1 receptor neurotransmitter pathway inhibition. [ABSTRACT FROM AUTHOR]

Ecologists and economists have promoted the concept of ecosystem services as a means of assisting environmental decision-making. Currently, several U.S. federal agencies and international institutions are incorporating the ecosystem services approach into their decision-making processes. Since 1999, the concept has been included in guidance documents for environmental impact assessments under the U.S. National Environmental Policy Act (NEPA). More recently, the U.S. Forest Service approved a Planning Rule to include ecosystem services in Forest Plans. However, some people already describe the U.S. Forest Service NEPA process as cumbersome, which might be compounded by adding new layers of analysis. To assess the potential of incorporating ecosystem services into land management decisions, we surveyed over 500 U.S. Forest Service professionals about incorporating ecosystem services in environmental impact analysis processes. Our goal was to determine (a) whether and how the ecosystem services concept is currently used in Forest Service NEPA analyses, (b) staff perceptions about how influential NEPA guidance documents are, and (c) whether respondents think that the ecosystem services concept is useful in NEPA processes (and more broadly in environmental decision-making). Forty-one percent of respondents were unfamiliar with ecosystem services, but a majority of the respondents thought that ecosystem services could be helpful in the NEPA process. Opinions were divided about whether or not ecosystem services would improve communication with stakeholders. One finding with potentially broad implications for executive branch policy-making is that survey results indicate that U.S. Forest Service staff found Environmental Protection Agency and Council on Environmental Quality guidance documents less influential than internal Forest Service directives. At the same time, the guidance documents that include ecosystem services language were the least influential among the guidance documents listed in the survey. Applying the results as a case study to advance ecosystem services scholarship, we suggest clarification of the ecosystem services framework, metrics, and guidance. [ABSTRACT FROM AUTHOR]

The prevention of chemotherapy-induced nausea and vomiting (CINV) has been revolutionized over the past 25 years. Guideline-based treatment means that vomiting can be prevented in the majority, but not in all patients. Therefore, antiemetic research continues with the goal of optimizing CINV control for all patients. This comprehensive review summarizes the research efforts in this field over the past few years. Emerging from this research are two new antiemetic agents, netupitant/ palonosetron, the first antiemetic combination agent and rolapitant, a new NK1RA. In addition, studies have evaluated the benefits of olanzapine and ginger, explored optimal combinations of agents for delayed CINV prevention, confirmed that dexamethasone-sparing regimens are effective, and demonstrated the value of NK1RAs in high-dose chemotherapy settings as well as with certain moderately emetogenic chemotherapies such as carboplatin. Research has also validated the correlation between antiemetic guideline adherence and improved CINV control. Finally, regulatory authorities have utilized extreme caution in retiring some 5-HT3RAs or decreasing their maximum dose. [ABSTRACT FROM AUTHOR]

NEPA is an oral single, fixed-dose combination of netupitant, a new highly selective NK1 RA and palonosetron (PALO), a pharmacologically/clinically distinct 5-HT3 RA. It delivers antiemetic guideline-recommended prophylaxis by targeting two critical molecular pathways associated with chemotherapy-induced nausea/vomiting. This Phase III study demonstrated the superiority of NEPA compared with PALO.Background Antiemetic guidelines recommend co-administration of agents that target multiple molecular pathways involved in emesis to maximize prevention and control of chemotherapy-induced nausea and vomiting (CINV). NEPA is a new oral fixed-dose combination of 300 mg netupitant, a highly selective NK1 receptor antagonist (RA) and 0.50 mg palonosetron (PALO), a pharmacologically and clinically distinct 5-HT3 RA, which targets dual antiemetic pathways. Patients and methods This multinational, randomized, double-blind, parallel group phase III study (NCT01339260) in 1455 chemotherapy-naïve patients receiving moderately emetogenic (anthracycline–cyclophosphamide) chemotherapy evaluated the efficacy and safety of a single oral dose of NEPA versus a single oral dose (0.50 mg) of PALO. All patients also received oral dexamethasone (DEX) on day 1 only (12 mg in the NEPA arm and 20 mg in the PALO arm). The primary efficacy end point was complete response (CR: no emesis, no rescue medication) during the delayed (25–120 h) phase in cycle 1. Results The percentage of patients with CR during the delayed phase was significantly higher in the NEPA group compared with the PALO group (76.9% versus 69.5%; P = 0.001), as were the percentages in the overall (0–120 h) (74.3% versus 66.6%; P = 0.001) and acute (0–24 h) (88.4% versus 85.0%; P = 0.047) phases. NEPA was also superior to PALO during the delayed and overall phases for all secondary efficacy end points of no emesis, no significant nausea and complete protection (CR plus no significant nausea). NEPA was well tolerated with a similar safety profile as PALO. Conclusions NEPA plus a single dose of DEX was superior to PALO plus DEX in preventing CINV following moderately emetogenic chemotherapy in acute, delayed and overall phases of observation. As a fixed-dose antiemetic drug combination, NEPA along with a single dose of DEX on day 1 offers guideline-based prophylaxis with a convenient, single-day treatment. [ABSTRACT FROM AUTHOR]

This study was designed to determine the appropriate clinical dose of netupitant (NETU), a new NK1 receptor antagonist (RA), to combine with the 5-HT3 RA, palonosetron (PALO) in a fixed-dose antiemetic combination (NEPA). All NEPA doses provided superior prevention of chemotherapy-induced nausea and vomiting compared with PALO, with NEPA300 (300mg NETU + 0.50 mg PALO) being the best dose studied.Background NEPA is a novel oral fixed-dose combination of netupitant (NETU), a new highly selective neurokinin-1 (NK1) receptor antagonist (RA) and palonosetron (PALO), a pharmacologically and clinically distinct 5-hydroxytryptamine type 3 (5-HT3) RA. This study was designed to determine the appropriate clinical dose of NETU to combine with PALO for evaluation in the phase 3 NEPA program. Patients and methods This randomized, double-blind, parallel group study in 694 chemotherapy naïve patients undergoing cisplatin-based chemotherapy for solid tumors compared three different oral doses of NETU (100, 200, and 300 mg) + PALO 0.50 mg with oral PALO 0.50 mg, all given on day 1. A standard 3-day aprepitant (APR) + IV ondansetron (OND) 32 mg regimen was included as an exploratory arm. All patients received oral dexamethasone on days 1–4. The primary efficacy endpoint was complete response (CR: no emesis, no rescue medication) during the overall (0–120 h) phase. Results All NEPA doses showed superior overall CR rates compared with PALO (87.4%, 87.6%, and 89.6% for NEPA100, NEPA200, and NEPA300, respectively versus 76.5% PALO; P < 0.050) with the highest NEPA300 dose studied showing an incremental benefit over lower NEPA doses for all efficacy endpoints. NEPA300 was significantly more effective than PALO and numerically better than APR + OND for all secondary efficacy endpoints of no emesis, no significant nausea, and complete protection (CR plus no significant nausea) rates during the acute (0–24 h), delayed (25–120 h), and overall phases. Adverse events were comparable across groups with no dose response. The percent of patients developing electrocardiogram changes was also comparable. Conclusions Each NEPA dose provided superior prevention of chemotherapy-induced nausea and vomiting (CINV) compared with PALO following highly emetogenic chemotherapy; however, NEPA300 was the best dose studied, with an advantage over lower doses for all efficacy endpoints. The combination of NETU and PALO was well tolerated with a similar safety profile to PALO and APR + OND. [ABSTRACT FROM AUTHOR]

In this multinational, phase III study, the safety and efficacy of NEPA, a convenient, fixed-dose antiemetic combination of netupitant, a highly selective NK1 receptor antagonist (RA), and palonosetron, a distinct 5-HT3 RA, were evaluated over multiple cycles of highly and moderately emetogenic chemotherapy. NEPA was shown to be safe, well tolerated and highly effective over 1961 chemotherapy cycles.Background Safe, effective and convenient antiemetic regimens that preserve benefit over repeated cycles are needed for optimal supportive care during cancer treatment. NEPA, an oral fixed-dose combination of netupitant, a highly selective NK1 receptor antagonist (RA), and palonosetron (PALO), a distinct 5-HT3 RA, was shown to be superior to PALO in preventing chemotherapy-induced nausea and vomiting after a single cycle of highly (HEC) or moderately (MEC) emetogenic chemotherapy in recent trials. This study was designed primarily to assess the safety but also to evaluate the efficacy of NEPA over multiple cycles of HEC and MEC. Patients and methods This multinational, double-blind, randomized phase III study (NCT01376297) in 413 chemotherapy-naïve patients evaluated a single oral dose of NEPA (NETU 300 mg + PALO 0.50 mg) given on day 1 with oral dexamethasone (DEX). An oral 3-day aprepitant (APR) regimen + PALO + DEX was included as a control (3:1 NEPA:APR randomization). In HEC, DEX was administered on days 1–4 and in MEC on day 1. Safety was assessed primarily by adverse events (AEs), including cardiac AEs; efficacy by complete response (CR: no emesis, no rescue). Results Patients completed 1961 total chemotherapy cycles (76% MEC, 24% HEC) with 75% completing ≥4 cycles. The incidence/type of AEs was comparable for both groups. Most frequent NEPA-related AEs included constipation (3.6%) and headache (1.0%); there was no indication of increasing AEs over multiple cycles. The majority of AEs were mild/moderate and there were no cardiac safety concerns based on AEs and electrocardiograms. The overall (0–120 h) CR rates in cycle 1 were 81% and 76% for NEPA and APR + PALO, respectively, and antiemetic efficacy was maintained over repeated cycles. Conclusions NEPA, a convenient single oral dose antiemetic targeting dual pathways, was safe, well tolerated and highly effective over multiple cycles of HEC/MEC. [ABSTRACT FROM AUTHOR]

Abstract: Robust scientific information is essential to proper leasing decisions in offshore waters of the United States. This information develops the necessary understanding of the environment required to protect ecosystems during sustainable energy development offshore. Collection of existing scientific information can be a laborious and time-consuming process. In an effort to collate and evaluate scientific information in a more effective and timely manner, the Bureau of Ocean Energy Management (BOEM) created a system that would improve the speed with which environmental research is performed while maintaining scientific defensibility of the resulting decisions. The EcoSpatial Information Database (ESID, pronounced “ee-sid”), available at http://esid.boem.gov, makes relevant scientific literature and ecological data for the Outer Continental Shelf (OCS) of the U.S. Atlantic Coast readily accessible via advanced location and content data searches. A unique search protocol was developed to identify and scientifically screen thousands of scientific articles and environmental reports to identify scientific datasets in the disciplines of marine geology, water quality, pelagic ecology, and benthic ecology. A prioritization process culled the results to a total of 3108 resources spanning the years of 1884 to 2010. These resources were then geospatially referenced and incorporated into the ESID. A web-based Geographic Information System (GIS), hosted in the Amazon Elastic Compute Cloud (EC2), was developed to provide broad access to the data and supporting documents. The cloud-based ESID Web Application allows users to search by content and location, view citations and abstracts, export bibliographic entries and view and download documents. The system is designed to support virtually unlimited geographic and subject matter expansion and will streamline BOEM's efforts to produce the required National Environmental Policy Act documents in a more efficient manner. [Copyright &y& Elsevier]

Abstract: Traditional mechanisms for public participation in environmental impact assessment under U.S. federal law have been criticized as ineffective and unable to resolve conflict. As these mechanisms are modified and new approaches developed, we argue that participation should be designed and evaluated not only on practical grounds of cost-effectiveness and efficiency, but also on ethical grounds based on democratic ideals. In this paper, we review and synthesize modern democratic theory to develop and justify four ethical principles for public participation: equal opportunity to participate, equal access to information, genuine deliberation, and shared commitment. We then explore several tensions that are inherent in applying these ethical principles to public participation in EIA. We next examine traditional NEPA processes and newer collaborative approaches in light of these principles. Finally, we explore the circumstances that argue for more in-depth participatory processes. While improved EIA participatory processes do not guarantee improved outcomes in environmental management, processes informed by these four ethical principles derived from democratic theory may lead to increased public engagement and satisfaction with government agency decisions. [Copyright &y& Elsevier]

Abstract: Cumulative effects analysis (CEA) allows natural resource managers to understand the status of resources in historical context, learn from past management actions, and adapt future activities accordingly. U.S. federal agencies are required to complete CEA as part of environmental impact assessment under the National Environmental Policy Act (NEPA). Past research on CEA as part of NEPA has identified significant deficiencies in CEA practice, suggested methodologies for handling difficult aspects of CEA, and analyzed the rise in litigation over CEA in U.S. courts. This article provides a review of the literature and legal standards related to CEA as it is done under NEPA and then examines current practice on a U.S. National Forest, utilizing qualitative methods in order to provide a detailed understanding of current approaches to CEA. Research objectives were to understand current practice, investigate ongoing challenges, and identify impediments to improvement. Methods included a systematic review of a set of NEPA documents and semi-structured interviews with practitioners, scientists, and members of the public. Findings indicate that the primary challenges associated with CEA include: issues of both geographic and temporal scale of analysis, confusion over the purpose of the requirement, the lack of monitoring data, and problems coordinating and disseminating data. Improved monitoring strategies and programmatic analyses could support improved CEA practice. [Copyright &y& Elsevier]

Abstract: Evaluating and comparing development alternatives with regard to sustainability is an important goal for comprehensive project appraisal. In the United States, this component has been largely missing from standard environmental impact assessment practice. Cumulative effects assessment provides a way to appraise the sustainability of project alternatives in terms of their probable contributions to long-term trends affecting the condition of valued environmental components. Sustainability metrics and predictors are being developed as criteria for rating systems and evaluation processes that are applied to community planning, building design, and transportation infrastructure. Increasing interest in adaptive management is also providing cost-effective solutions to optimizing safety and function throughout the long-term operation of a facility or infrastructure. Recent federal legislation is making it easier to integrate sustainability features into development alternatives through early, community-based planning. [Copyright &y& Elsevier]

Abstract: Health has always had a place in wider impact assessment activities, from the earliest days of the National Environmental Policy Act in the United States. However, early thinking tended to focus on health protection and environmental health issues, especially in relation to the effects of pollution. The adoption of wider models of health was reflected in impact assessment circles from the early 1990s, with particular emphasis on an integrated approach to impact assessment, especially at the project level, which would see health impact assessment benefiting from working with other forms of impact assessment, such as social and ecological. Yet twenty years later, integration still seems a distant prospect in many countries. In this paper I examine the case for integrating health considerations within the wider IA process, discuss some of the problems that have historically restricted progress towards this end, and explore the degree to which impact assessment practitioners have been successful in seeking to improve the consideration of health in IA. In New Zealand, project-level impact assessment is based on an integrated model under the Resource Management Act. In addition, HIA was recognised in the early 1990s as a valuable addition to the toolkit for project assessment. Since then policy-level HIA has grown supported by extensive capacity building. If health is being integrated into wider impact assessment, it should be happening in New Zealand where so many enabling conditions are met. Three major project proposals from New Zealand are examined, to characterise the broad trends in HIA development in New Zealand in the last ten years and to assess the degree to which health concerns are being reflected in wider impact assessments. The findings are discussed in the context of the issues outlined in the early part of the paper. [Copyright &y& Elsevier]

Since the creation of the National Environmental Policy Act in 1970, the United States has required the Environmental Protection Agency (EPA) to rate draft environmental statements (DEISs) for both information adequacy and the impact of the preferred alternative on the environment. In a previous study by Tzoumis and Finegold (2000), these ratings were found to be declining from 1970 to 1997. This current study investigates if that trend continued from 1998 to 2004. In addition, the top producing agencies (the Forest Service, the Federal Highway Administration, Army Corp of Engineers, and the Bureau of Land Management) are compared for the achievement of DEIS ratings. The results show that when the ratings are disaggregated for these agencies, the results indicate that there continues to be weak performance. The DEISs continue to have insufficient and sometimes inadequate information. Agencies continue to propose projects that have environmental concerns and sometimes objections. The agencies have some similarities in not being able to achieve the highest ratings on a consistent basis over time. However, more disturbing is the profile of agencies that have episodic peaks of achieving the lowest ratings. Conclusions and recommendations are focused on the agencies who submit that DEISs and EPA. One major conclusion is to better track the ratings and make them collectively available for the public. Agencies are encouraged to develop a best management practice in preparing DEISs to promote agency learning. [Copyright &y& Elsevier]

Abstract: The “International Principles for Social Impact Assessment” and the “Principles and Guidelines for Social Impact Assessment in the USA”, both developed under the auspices of the International Association for Impact Assessment and published in 2003, are compared. Major differences in the definition and approach to social impact assessment (SIA) are identified. The US Principles and Guidelines is shown to be positivist/technocratic while the International Principles is identified as being democratic, participatory and constructivist. Deficiencies in both documents are identified. The field of SIA is changing to go beyond the prevention of negative impacts, to include issues of building social capital, capacity building, good governance, community engagement and social inclusion. [Copyright &y& Elsevier]

Abstract: The National Environmental Policy Act (NEPA) mandates that the U.S. Forest Service (USFS) conduct an Environmental Impact Assessment (EIA) as its fire management policy evolves to cope with a legacy of over 100 years of fire suppression on national forest lands and an increasing occurrence of uncharacteristically large, intense wildfires. This paper argues that integration of a risk assessment approach into the EIA is a logical extension of the EIA process and provides a more robust method for assessing comparative risks of proposed alternatives, and integrating ecological risks with economic and social cost-benefit analyses. Risk assessment is the process of estimating the likelihood and magnitude of the occurrence of an unwanted, adverse effect. It begins with a well-defined problem formulation step that ensures involvement of stakeholders, uses available or newly developed scientific information to ascribe probabilities to the likelihood of fire initiation under various forest management practices, and describes or quantifies the magnitude of effects associated with fires of various frequencies and intensities. The risk characterization step provides comprehensive statements of risk, including assertions about uncertainty, and communicates results in a clear and intelligible manner to resource managers and interested stakeholders. Risk assessment uses probabilistic modeling to incorporate environmental stochasticity and experimental uncertainty, and incorporates spatial attributes, simultaneous multiple risks, comparative analyses of different risks, socioeconomic concerns, and ecological effects into the analysis. Placed within the EIA process, risk assessment provides a robust framework for reaching agreement on risks of uncharacteristic wildfires under a variety of proposed management scenarios. [Copyright &y& Elsevier]

• An NK 1 RA, 5-HT 3 RA, and dexamethasone are recommended to prevent CINV in patients at high emetic risk. • IV NEPA is an innovative fixed combination antiemetic, comprised of the NK 1 RA, fosnetupitant, and 5-HT 3 RA, palonosetron. • IV NEPA has had no associated injection-site or hypersensitivity reactions. • This paper presents the efficacy of IV NEPA relative to oral NEPA and also to historical data for other NK 1 RA regimens. This paper presents an overview of the efficacy of intravenous (IV) NEPA (fixed combination of the NK 1 RA, fosnetupitant, and 5-HT 3 RA, palonosetron) relative to oral NEPA and also to historical data for other NK 1 RA regimens. Data is compiled from 5 pivotal NEPA studies in adult chemotherapy-naïve patients with solid tumors undergoing either cisplatin- or anthracycline cyclophosphamide (AC)-based chemotherapy. Additionally, data was reviewed from 10 pivotal Phase 3 studies utilizing other NK 1 RA regimens approved for clinical use. The overall (0−120 h) complete response (no emesis, no rescue use), no emesis, and no significant nausea rates for IV NEPA were similar to that of oral NEPA and were consistently numerically higher than historical NK 1 RA regimens. As a single-dose prophylactic antiemetic combination given with dexamethasone, IV NEPA is a highly effective and convenient guideline-compliant antiemetic agent which may offer a safety benefit over other IV NK 1 RA regimens due to its lack of associated hypersensitivity and injection-site reactions. [ABSTRACT FROM AUTHOR]