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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]

Objective: Patients with gynecological cancers are at high risk for chemotherapy-induced nausea and vomiting (CINV) after platinum-based chemotherapy (CT). NEPA (300-mg netupitant, 0.50-mg palonosetron) is the first oral fixed-combination antiemetic. Pivotal trials demonstrated the superiority of oral NEPA over intravenous palonosetron in preventing CINV after highly emetogenic (anthracycline-cyclophosphamide–based [AC] and cisplatin-based [non-AC]) CT. This post hoc subset analysis considered patients with gynecological cancer receiving cisplatin- or carboplatin-based CT from 1 pivotal trial and from 1 multicycle safety trial to evaluate the efficacy of oral NEPA in preventing CINV. Methods: Single-dose NEPA was given before CT in combination with dexamethasone. The efficacy end points for the acute (0–24 hours), delayed (25–120 hours), and overall (0–120 hours) CINV phases after CT included complete response (CR; no emesis, no rescue medication) and no significant nausea (<25 mm on a 0- to 100-mm visual analog scale). Safety was also assessed. Results: For cisplatin-induced CINV, NEPA achieved high CR rates (acute phase: >90%; delayed, overall phases: ≥85%). For carboplatin-induced CINV, NEPA was also highly effective, with high acute, delayed, and overall CR rates (cycle 1: >75%; cycles 2–4: >95%). No significant nausea rates were more than 90% and more than 80% in the acute and delayed phases, respectively, for patients receiving cisplatin or carboplatin. NEPA was well tolerated. Conclusions: Results suggest that oral NEPA is effective and safe in preventing CINV in patients with gynecological cancers treated with cisplatin- or carboplatin-based CT. Single fixed-combination NEPA is a convenient option for CINV prevention in high-risk CINV patients. [ABSTRACT FROM AUTHOR]

Courts have experienced a dramatic rise in climate change claims initiated over the last ten years, yet few studies have empirically documented the outcomes of this litigation. To better understand the universe of climate change litigation, this research analyzed all cases filed under the National Environmental Policy Act (NEPA) through the lens of a legal case characteristic model and a politics of judicial choice model. Overall, courts have adhered to a legal model of decision-making with deference granted to federal defendants in the majority (54%) of cases. However, case outcomes did vary by characteristics including the jurisdictional location, the identity of the lead agency, and the type of NEPA analysis challenged. Although not statistically significant, district court judges appointed by Democratic Presidents tended to decide in favor of environmental plaintiffs more often than Republican appointees. [ABSTRACT FROM AUTHOR]

BACKGROUND: Prevention of chemotherapy-induced nausea and vomiting (CINV) can be improved with guideline-consistent use of antiemetics. However, adherence to antiemetic guidelines remains often insufficient. Therefore, new strategies that improve adherence are needed. OBJECTIVES: To review the latest antiemetic guideline recommendations and provide an update on the use of NEPA, a fixed combination antiemetic composed of the neurokinin-1 receptor antagonist (RA) netupitant and the 5-hydroxytryptamine-3 RA palonosetron (Akynzeo®). METHODS: Analysis of the literature was performed, including guidelines, published literature, congress data on NEPA, and relevant articles on CINV. FINDINGS: Increased knowledge about CINV treatment recommendations and new antiemetic agents allow nurses to promote individualized antiemetic prophylaxis and maximize supportive patient care. Nurses are in a unique position to promote guideline-consistent antiemetic prophylaxis and are central in the education of patients and caregivers. [ABSTRACT FROM AUTHOR]

Purpose: Patients receiving platinum-based chemotherapy are at high risk of chemotherapy-induced nausea and vomiting (CINV), a distressing side effect of treatment. This post-hoc subgroup analysis of two pivotal trials evaluated the efficacy of NEPA in preventing CINV in subsets of patients with lung cancer who received cisplatin or carboplatin.Methods: In each study, the efficacy endpoints complete response (CR; defined as no emetic episodes and no rescue medication) and no significant nausea (NSN; defined as a score of < 25 mm on a visual analog scale of 0-100 mm) during the acute (0-24 h), delayed (25-120 h), and overall (0-120 h) phases post-chemotherapy in cycle 1 (study 1) and cycles 1-4 (study 2) were assessed. Safety was evaluated by recording treatment-emergent adverse events (AEs) and treatment-related AEs.Results: NEPA treatment resulted in high CR rates across the acute, delayed, and overall phases (cisplatin: > 88% overall CR; carboplatin: > 75% overall CR), with higher CR rates for NEPA-treated patients than those receiving palonosetron; moreover, CR rates were sustained over multiple chemotherapy cycles (> 75%). High rates of NSN observed during cycle 1 (> 79%) were also maintained over multiple chemotherapy cycles. NEPA was well tolerated in all patients.Conclusions: NEPA appears to be effective and well tolerated in patients with lung cancer receiving platinum-based chemotherapy, across the acute, delayed, and overall phases and throughout multiple cycles. As a highly effective oral combination antiemetic agent administered as a single dose once per cycle, NEPA may offer a convenient, simplified prophylactic antiemetic. [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]

Conflicts surrounding the development of public lands are on the rise around the world. In the United States, where laws require federal agencies to conduct environmental and cultural impact assessments before approving or permitting development projects, conflicts still occur. This is especially true for projects that impact indigenous lands, resources, and communities, as the recent controversy surrounding Dakota Access Pipeline project so well illustrates. The purpose of this article is to highlight some of the problems I have encountered as an anthropologist conducting cultural impact assessments for federal agencies and for indigenous communities. Central among the problems encountered are the lack of awareness and appreciation for indigenous values by project proponents, agencies, and sometimes even the analysts hired to conduct the assessments. Recommendations for improving the quality of cultural impact assessments, which are based on the tenets of Action Anthropology, are explained. [ABSTRACT FROM AUTHOR]

Federal landholding agencies such as the Department of Defense (DoD) are actively seeking to diversify energy supplies and decrease fossil fuel reliance while increasing energy security and resilience. Within DoD, the Army’s Office of Energy Initiatives (OEI) works to achieve these goals by developing large-scale renewable and alternative energy projects on Army land through private sector financing. Proper implementation of the National Environmental Policy Act (NEPA) ensures renewable energy projects have a net positive impact on environmental health and sustainability. The Army’s experience conducting NEPA assessments for these projects provides a unique perspective on the effectiveness of the NEPA process, including challenges, best practices, and lessons learned that apply broadly to NEPA practitioners. This article illustrates specific examples through descriptions of NEPA assessments for three OEI projects at various stages of completion. [ABSTRACT FROM PUBLISHER]

With constantly improving cancer therapies, patient's quality of life, the management of potential side effects and treatment-related symptoms have also made considerable progress. Chemotherapy-induced nausea and vomiting (CINV) still constitutes a major problem for many patients. New developments in the field allow a more comfortable administration of guideline-based antiemetic therapy and may further improve the control of nausea. Therapeutic options for the cancer anorexia-cachexia syndrome (CACS), common in advanced cancers, are still limited and hampered by numerous side effects. Among these, targeting the ghrelin-receptor pathway could be a novel approach; however, data are still immature. [ABSTRACT FROM AUTHOR]

Developing efficient and effective tools for navigating the National Environmental Policy Act (NEPA) process is becoming increasingly important as Federal and State agencies have limited resources (staff and funding) and are required to review and process documents in an expedited fashion. To carry a project through the NEPA process, a skilled team with tools to streamline the interagency review process as well as community input process is highly beneficial. There are numerous approaches to streamlining the NEPA process. This article highlights two potential transformative tools. The tools have not been proven for NEPA application, but they have been successful in other industries. In Fall 2017, the Maryland Transit Administration (MTA) is launching a pilot study to test the tool’s effectiveness with respect to NEPA. The first tool is aDocument Management Systemfor agency coordination and comment periods to expedite the review and approval time. The second tool is the development of aVirtual NEPA GIS-Based Platformto reduce the number of pages in an Environmental Assessment (EA) and Environmental Impact Statement (EIS) document and improve the transparency of the NEPA process. Too often projects are delayed or over budget as a result of poor coordination processes and lack of transparency during the public review process. This article discusses the importance of and tools to improve project communication, both internally and externally, and the public involvement process. [ABSTRACT FROM AUTHOR]

Scleractinian, octocoral, and antipatharian corals have colonized many of the offshore oil and gas platforms in the northern Gulf of Mexico. We surveyed 25 offshore oil and gas platforms for these cnidarians. Few to no corals were detected on inshore, shallow-water structures at <25 m depth; however, the abundance of corals increased, ranging from 14 to 194/m, on platforms in waters deeper ≥25 m. The most common coral encountered were Tubastraea coccinea (Scleractinia) and Telesto spp. (Octocorallia). The data suggest that the offshore platforms located in waters of >25-30 m in the study area are often colonized by these corals. We recommend that structures located in deeper waters should be surveyed for coral and, if the populations are substantial, consider alternate uses for the retired platforms, and leaving them in place, when feasible. [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]

Purpose: Antiemetic guidelines recommend co-administration of targeted prophylactic medications inhibiting molecular pathways involved in emesis. NEPA is a fixed oral combination of a new NK1 receptor antagonist (RA), netupitant (NETU 300 mg), and palonosetron (PALO 0.50 mg), a pharmacologically distinct 5-HT3 RA. NEPA showed superior prevention of chemotherapy-induced nausea and vomiting (CINV) compared with oral PALO in a single chemotherapy cycle; maintenance of efficacy/safety over continuing cycles is the objective of this study.Methods: This study is a multinational, double-blind study comparing a single oral dose of NEPA vs oral PALO in chemotherapy-naïve patients receiving anthracycline/cyclophosphamide-based chemotherapy along with dexamethasone 12 mg (NEPA) or 20 mg (PALO) on day 1. The primary efficacy endpoint was delayed (25-120 h) complete response (CR: no emesis, no rescue medication) in cycle 1. Sustained efficacy was evaluated during the multicycle extension by calculating the proportion of patients with overall (0-120 h) CR in cycles 2-4 and by assessing the probability of sustained CR over multiple cycles.Results: Of 1455 patients randomized, 1286 (88 %) participated in the multiple-cycle extension for a total of 5969 cycles; 76 % completed ≥4 cycles. The proportion of patients with an overall CR was significantly greater for NEPA than oral PALO for cycles 1-4 (74.3 vs 66.6 %, 80.3 vs 66.7 %, 83.8 vs 70.3 %, and 83.8 vs 74.6 %, respectively; p ≤ 0.001 each cycle). The cumulative percentage of patients with a sustained CR over all 4 cycles was also greater for NEPA (p < 0.0001). NEPA was well tolerated over cycles.Conclusions: NEPA, a convenient, guideline-consistent, fixed antiemetic combination is effective and safe over multiple cycles of chemotherapy. [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]

After two draft documents and more than seven years, in the August 5, 2016 edition of the Federal Register, the White House Council on Environmental Quality (CEQ) published final guidance for federal agencies to incorporate greenhouse gas (GHG) emissions and climate change into National Environmental Policy Act (NEPA) reviews. Questions and legal opinions on the final guidance are plentiful. Is the final guidance consistent with existing case law, is it binding, will it adequately protect agencies and project proponents from litigation, or does it require agencies to force reductions on project proponents? Questions and opinions aside, this article focuses on the practical implications of the final guidance—how environmental professionals can prepare NEPA reviews that align with its spirit and intent, meaningfully assess potential impacts and compare alternatives, and maintain consistency with established GHG accounting principles. [ABSTRACT FROM PUBLISHER]

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]

Environmental impact assessment (EIA) procedures required in the United States and many other countries are often highlighted as a major hindrance to timely and efficient deployment of critical infrastructure projects. Under the U.S. National Environmental Policy Act, a more extensive environmental impact statement (EIS) review can take several more years and cost much more than a succinct environmental assessment (EA). This not only affects the project in question, but also likely informs how-or whether-additional projects are pursued. Thus, understanding key predictors of the EA versus EIS choice sheds light on supply-side considerations affecting infrastructure deficits. Using the case of NEPA reviews conducted for 244 transmission line projects between 2005 and 2018 by two U.S. federal agencies in the western United States, the Bureau of Land Management (BLM) and Department of Energy (DOE), this addresses the following question: What project features most predict whether EA or an EIS is used to assess a transmission line project? Drawing upon NEPA assessment guidance and agency NEPA records, we use a regression classification tree to analyze how protocols and project attributes relate to assessment choice. The result is essentially a null finding: transmission line length is by far the most important predictor of whether a project receives an extensive EIS or a shorter EA, with little predictive value provided by other attributes. While absolute project size undoubtedly influences impacts, the lack of further differentiation in what predicts use of EISs versus EAs suggests assessment does not simply respond to project details but also shapes proposal and design choices beforehand., (© 2022 Society for Risk Analysis.)

Purpose: Antiemetic guideline recommendations are inconsistent as to whether a neurokinin-1 receptor antagonist (NK1 RA) should be administered with a 5-hydroxytryptamine-3 (5HT3) RA + dexamethasone (DEX) in patients receiving carboplatin. Patients receiving cisplatin routinely receive an NK1 RA-containing regimen with a resulting 14-22 % benefit in no emesis rates over a 5-HT3 RA/DEX control. Recent studies suggest a similar benefit in patients receiving carboplatin. NEPA is the first fixed antiemetic combination agent and comprises the highly selective NK1 RA, netupitant, and pharmacologically distinct 5-HT3 RA, palonosetron (PALO). This paper presents the efficacy of NEPA in the subset of patients receiving carboplatin in a phase 3 trial (NCT01376297), in the context of aprepitant (APR) data in the carboplatin setting.Methods: One hundred ninety-six patients (47 % of all study patients: n = 145 NEPA + DEX; n = 51 APR + PALO + DEX) received carboplatin in a multinational, double-blind, randomized phase 3 study. Complete response (CR: no emesis/rescue) and no significant nausea (NSN: score ≤25 on 100 mm visual analog scale) rates were calculated.Results: Cycle 1-4 overall (0-120 h) CR rates were similar for NEPA (80, 91, 92, and 93 %) and APR (82, 88, 88, and 90 %). Overall NSN rates were also similar (NEPA 84-96 %; APR 82-90 %).Conclusions: Response rates for NEPA and APR regimens were similar and consistent with prior studies evaluating the contribution of adding NK1 RAs in patients receiving carboplatin. Considering such evidence, guideline groups/practitioners should consider giving a NK1 RA antiemetic triplet in patients receiving carboplatin. [ABSTRACT FROM AUTHOR]

According to the U.S. National Environmental Policy Act of 1969 (NEPA), federal action to manipulate habitat for species conservation requires an environmental impact statement, which should integrate natural, physical, economic, and social sciences in planning and decision making. Nonetheless, most impact assessments focus disproportionately on physical or ecological impacts rather than integrating ecological and socioeconomic components. We developed a participatory social-ecological impact assessment (SEIA) that addresses the requirements of NEPA and integrates social and ecological concepts for impact assessments. We cooperated with the Bureau of Land Management in Idaho, USA on a project designed to restore habitat for the Greater Sage-Grouse (Centrocercus urophasianus). We employed questionnaires, workshop dialogue, and participatory mapping exercises with stakeholders to identify potential environmental changes and subsequent impacts expected to result from the removal of western juniper (Juniperus occidentalis). Via questionnaires and workshop dialogue, stakeholders identified 46 environmental changes and associated positive or negative impacts to people and communities in Owyhee County, Idaho. Results of the participatory mapping exercises showed that the spatial distribution of social, economic, and ecological values throughout Owyhee County are highly associated with the two main watersheds, wilderness areas, and the historic town of Silver City. Altogether, the SEIA process revealed that perceptions of project scale varied among participants, highlighting the need for specificity about spatial and temporal scales. Overall, the SEIA generated substantial information concerning potential impacts associated with habitat treatments for Greater Sage-Grouse. The SEIA is transferable to other land management and conservation contexts because it supports holistic understanding and framing of connections between humans and ecosystems. By applying this SEIA framework, land managers and affected people have an opportunity to fulfill NEPA requirements and develop more comprehensive management plans that better reflect the linkages of social-ecological systems. [ABSTRACT FROM AUTHOR]

The combination of netupitant and palonosetron was approved by the Food and Drug Administration in October 2014 for the prevention of acute and delayed chemotherapy-induced nausea and vomiting associated with initial and repeat courses of moderately and highly emetogenic chemotherapy. Netupitant and palonosetron is available as a single capsule to be administered prior to each cycle of chemotherapy. The approval was based on phase II and III data in patients undergoing treatment with moderately and highly emetogenic chemotherapy. Netupitant and palonosetron’s benefits include a convenient dosage form, dual-targeted mechanism, and favorable side effect profile, while its main limitations are cost and potential logistical issues surrounding administration. More studies are needed to adequately determine its role in therapy as well as which patients will derive the most benefit from its use. [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]

A cumulative effect analysis (CEA) is a tool that can be utilized for the review of multiple anthropogenic projects or activities for the purposes of planning, regulation, conservation, or the general evaluation of environmental health. Such an assessment is problematic because spatially consistent and temporally repeated data informing the condition of a location are often not available. When such data can be identified, the potential response of that resource to additional impacts may be unpredictable. Despite these limitations, in many cases, it may be critical to identify those locations for further scrutiny which may be vulnerable to collective impacts from development or other environmental challenges. Here, we present an approach which considers the vulnerability of aquatic resources in relation to the anticipated effects of development-related activities that could be used to identify locations where the potential for cumulative effects is the greatest. This application considers CEA in the context of identifying where development-related activities of minimal impact may be viewed as relatively more substantial when viewed cumulatively. We identify HUC 8-level watersheds where the current resource condition and anticipated development-related activities may have greater potential to result in an impact on watershed condition (i.e., water quality, water quantity, and habitat value). The vulnerability of the watershed was estimated from the number, type, and location of a specific suite of reported activities. The existing condition of the watershed was measured as a function of existing assessments of resource conditions. The relationship between the vulnerability and the existing watershed condition was used to project future conditions and to identify watersheds that warrant further scrutiny. This is a unique approach to CEA which allows for transparent, repeatable identification of watersheds which may be adversely impacted by further activities or projects. [ABSTRACT FROM AUTHOR]

Antiemetic treatment compliance is important to prevent chemotherapy-induced nausea and vomiting, a feared chemotherapy side effect. NEPA, a new oral fixed combination of netupitant, a highly selective NK1 receptor antagonist (RA), and palonosetron, a second-generation 5-HT3 RA, targets dual antiemetic pathways with a single dose. This study investigated the effect of food intake and age on NEPA pharmacokinetics (PK) and safety. In this open-label, single-center, randomized, phase 1 study, 24 adults (18−45 years) received NEPA in a fed or fasted state during the first treatment period and in the alternative state in the next treatment period. Twelve elderly subjects (≥65 years) received NEPA in a fasted state. Blood samples were taken for netupitant and palonosetron PK analysis. In the fed condition, netupitant plasma exposure increased, whereas palonosetron PK parameters were not affected. Furthermore, elderly subjects showed increased netupitant and palonosetron exposure compared with adults. All adverse events were mild/moderate, with constipation and headache the most common. Although food intake and age altered NEPA PK, dose adjustments were not needed, as netupitant and palonosetron exposure increases did not lead to safety concerns in healthy subjects. [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]

Current guidelines recommend the combination of a neurokinin-1 (NK1) receptor antagonist (RA) and a 5-hydroxytryptamine-3 (5-HT3) RA, together with corticosteroids, in order to prevent chemotherapy-induced nausea and vomiting with anthracycline-cyclophosphamide and highly emetogenic chemotherapy, and it is to be considered with moderately emetogenic chemotherapy. Netupitant and palonosetron (NEPA) is a fixed-dose combination of netupitant, a novel, highly selective NK1 RA, and palonosetron, a new-generation 5-HT3 RA, targeting two major emetic pathways in a single oral capsule. In clinical trials, NEPA administered on day 1 together with dexamethasone was highly effective and well tolerated in the prevention of chemotherapy-induced nausea and vomiting in patients with solid tumors undergoing moderately emetogenic chemotherapy or highly emetogenic chemotherapy. NEPA offers maximal convenience, and as a simple guideline-based regimen, has the potential to improve adherence to guidelines. [ABSTRACT FROM AUTHOR]