Academic literature on the topic 'Planning advisory committees'

Co-management of forests has been reported from more than fifty countries and stakeholder advisory committees have become central to forest planning in Canada. Scientists tend to agree that local users are capable of self-organising to manage resources more effectively than state agencies alone, whether jointly with governments or with considerable autonomy. Little, however, is known about how the network of contextual influences helps, hinders, or overrides the deliberation that facilitates the development of cooperation critical for co-management success. The objectives of the paper are to identify the relative influence of contextual factors, participants’ sense of control over contextual factors, and effects on performance. In a comparative case study of two stakeholder advisory committees in Ontario, Canada, the objectives are addressed by identifying and analysing advisory committee thinking about consensus building using network analysis of group cognitive maps. The paper concludes with three lessons regarding how the mix of hierarchical, market, and community institutions that influence community-based deliberation can be coordinated for effective forest management.

Tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of patients with chronic myeloid leukemia (CML) ushering in an era where, in select patient populations, treatment planning goals have shifted towards the achievement of treatment free remission (TFR) after TKI cessation. Both duration and depth of response to TKI therapy are predictors of future success in achieving a lasting TFR and with improved outcomes independent of TKI cessation. Unfortunately, molecular residual disease (MRD) persists in many patients despite optimal therapy and predicts for worse outcomes over time and decreased ability to maintain a TFR after TKI cessation. Achievement of a major molecular response (MMR) and probability of TFR have been associated with increased numbers of NK cells, particularly mature cytolytic NK cells. Kiadis K-NK003 cells are off-the-shelf NK cells from a universal donor expanded using PM21, proprietary membrane particles modified to express membrane bound IL-21 and 4-1bb ligand. The resulting expanded K-NK003 cells have a hyperfunctional phenotype that are simultaneously highly cytotoxic with high release of perforin and Granzyme B, and potent producers of the cytokines IFN-γ, TNF-α and IL-2. This is an open label, non-randomized, prospective phase I pilot study designed to evaluate safety and to examine whether the addition of K-NK003 to ongoing TKI therapy for CML patients with persistent MRD will allow patients to achieve MRD negative status. Patients will be treated with K-NK003 on day 1 of each 14 day cycle, for a total of 6 cycles, in conjunction with their ongoing TKI therapy. The primary endpoint is safety. The efficacy objective is to estimate the rate of optimal molecular responses (negative to at least MR4.5). Secondary and exploratory endpoints include the proportion of patients with a reduction in BCR-ABL transcripts and NK cell number and function. Adult patients with chronic phase CML who have been on TKI therapy for at least 1 year prior to enrollment in the study will be eligible. Patients must have been on their most recent TKI consistently for at least 6 months prior to enrollment on study and must be expected to remain on current TKI for the duration of the study. Patients with current accelerated or blast crisis phase disease will be excluded. Disclosures Rein: Celgene: Consultancy; Blueprint Medicine: Consultancy; Novartis: Consultancy; Clinical Care Options: Consultancy, Other: Speaker. Rizzieri:Bayer: Membership on an entity's Board of Directors or advisory committees; AROG: Membership on an entity's Board of Directors or advisory committees; Celltrion: Membership on an entity's Board of Directors or advisory committees; abbvie: Membership on an entity's Board of Directors or advisory committees; Mustang: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees; Teva: Membership on an entity's Board of Directors or advisory committees; Acrobiotech: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Incyte: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Stemline: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Seattle Genetics: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Jazz: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Kite: Honoraria, Speakers Bureau; Karyopharm: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

Introduction: African-Americans (AA) with breast cancer continue to experience worse morbidity and mortality than white patients. In addition to barriers to care, an active area of investigation has been the etiology of the increased risk adverse events (AEs) related to chemotherapy. An emerging question is if sickle cell trait (i.e., heterozygotes for hemoglobin beta gene), present in an estimated 1 in 12 of the AA population, confers increased susceptibility to chemotherapy-related complications. We posit that conditions of high physiological stress might be manifest during systemic treatment with toxic agents resulting in alterations of red blood cells (RBCs). Using an experimental biomechanical model system, we hypothesized that RBCs from SCT carriers would be prone to increased adhesiveness after exposure to a common systemic anti-cancer agent used in breast cancer. Increased adhesiveness of RBCs can be a precipitating factor of blocked vasculature and subsequent sickling crises, potentially leading to AEs during treatment. Methods: Our study testedex vivoRBCs from two groups of healthy female participants: 20 African-American sickle cell trait carriers (AA-SCT); and 15 white subjects with wild-type hemoglobin (W-WT). Isolated RBCs were treated with scaled Daunorubicin (DNR) doses. The unbinding forces between αvβ3 ligands and intercellular adhesion molecule-4 (ICAM-4) receptors are reported using the frequency distribution, which states the percentage of events whose unbinding forces are within each width of the bin. We then compared the median values of the forces measured in experiments without and with treatment for each drug. The collective frequency (CF%) is related to the population of active ICAM-4 receptors and is defined as the percentage of all unbinding events divided by the total number of measurements, which is 32 × 32 =1024 for each cell multiplied by the number of tested cells for each blood sample. Results: For AA-SCT RBCs, pre-treatment baseline CF of active ICAM-4 receptors was 4.88 ± 0.87%, which was significantly increased after administration of DNR (13.13 ± 2.30%, p<0.0001). In contrast, treatment of W-WT RBCs held the CF of active ICAM-4 receptors at a comparable level as untreated RBCs (9.54 ± 1.48%; 7.47 ± 1.07%, p=0.50, respectively). Conclusion: Our findings could support hypotheses for adhesion-related RBC clumping among AAs with SCT during systemic treatment with anti-neoplastic agents, and, putatively, resultant AEs. Given past studies showing African-American women with breast cancer have higher rates of self-withdrawal from treatment, further exploration with additional systemic agents are warranted. Our novel study is limited by a small sample size as well lack of potential confounding factors in analyses. Future studies are planned with additional agent(s) and AAs without SCT. Should it be confirmed that SCT carrier status predicts RBC alterations during systemic treatment for breast cancer, and are linked to subsequent adverse events, it could lead to precision treatment planning. Disclosures Andemariam: Novartis:Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding;Hemanext:Membership on an entity's Board of Directors or advisory committees;Global Blood Therapeutics:Consultancy, Membership on an entity's Board of Directors or advisory committees;Vertex:Honoraria;Imara:Research Funding;Emmaus:Membership on an entity's Board of Directors or advisory committees;bluebird bio:Consultancy, Membership on an entity's Board of Directors or advisory committees;NovoNordisk:Consultancy, Membership on an entity's Board of Directors or advisory committees;CRISPR/Vertex:Consultancy, Membership on an entity's Board of Directors or advisory committees;CHNCT:Consultancy;Accordant:Membership on an entity's Board of Directors or advisory committees;Guidepoint:Honoraria;Sanofi Genzyme:Consultancy, Membership on an entity's Board of Directors or advisory committees;Terumo BCT:Consultancy, Membership on an entity's Board of Directors or advisory committees;Roche:Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees;Cyclerion:Consultancy, Membership on an entity's Board of Directors or advisory committees;Pfizer:Consultancy, Membership on an entity's Board of Directors or advisory committees.

Abstract Background: Vecabrutinib (formerly SNS-062, the succinate salt of vecabrutinib) is a reversible, noncovalent BTKi that has demonstrated in vitro activity in BTK wild-type and C481S mutated cells (Binnerts AACR-NCI-EORTC 2015; Fabian AACR 2017; Libre EHA 2018). Acquired mutations of BTK at C481 (BTK C481), the covalent binding site for ibrutinib, were reported prior to, and at, clinical progression in ibrutinib-treated patients (pts); therefore, vecabrutinib may have therapeutic potential in this setting. A phase 1a study of vecabrutinib in healthy subjects showed favorable safety pharmacokinetic (PK)/pharmacodynamic (PD) profiles, supporting twice-daily (BID) oral dosing (Neuman ASH 2016). Here we report preliminary results of the ongoing phase 1b/2 study of vecabrutinib in adult pts with relapsed/refractory (R/R) advanced B-cell malignancies. Methods: The phase 1b dose-escalation portion of the study employs a standard 3+3 design in pts with histologically confirmed R/R chronic lymphocytic leukemia (CLL), mantle cell lymphoma (MCL), Waldenström macroglobulinemia (WM), diffuse large B-cell lymphoma, and follicular lymphoma who have received ≥2 prior lines of systemic therapy, including use of a covalent BTKi where approved for their disease. The objectives of this study are to assess safety, establish the maximum tolerated dose, and identify the recommended phase 2 dose of vecabrutinib. Pts aged ≥18 years with an Eastern Cooperative Oncology Group performance status (ECOG PS) of ≤2 are eligible. Dose-limiting toxicity (DLT) is assessed over an initial 4-week period (1 treatment cycle). Molecular profiles, PK, and PD (inhibition of BTK phosphorylation [pBTK] and cytokine levels) are evaluated throughout Cycle 1. Vecabrutinib succinate dose levels from 25 to 500 mg BID were specified for evaluation. Early safety, PK, and PD data from pts treated to date at dose levels of 25 and 50 mg BID are reported. Results: Nine pts (CLL, n=6; MCL, n=2; WM, n=1) have been treated in the phase 1b portion of the study (25 mg BID, n=3; 50 mg BID, n=6). Median pt age was 66 years (range: 47-75), all had an ECOG PS of 0 or 1, 78% were male, and median number of prior regimens was 5 (range: 2-7). Prior therapies included ≥1 chemotherapy regimen (n=9), BTKi (ibrutinib, n=8; acalabrutinib, n=1), venetoclax (n=4), and chimeric antigen receptor T-cell therapy (n=2). At baseline, 67% (6/9) of pts had TP53 mutations or deletions. The CLL pts had 83% (5/6) unmutated IGHV, 83% (5/6) deleted or mutated TP53, 50% (3/6) detectable BTK C481 mutations by next-generation sequencing (C481S: n=2, variant allelic frequency [VAF]: 16%, 58%; C481R: n=1, VAF: 77%), and no mutations in PLCg2 were detected. No mutations in BTK 481 or PLCg2 were found in MCL or WM pts. The most common treatment-emergent adverse events (TEAEs) of any grade were anemia and night sweats (43%, 3/7 each), and leukopenia, neutropenia, thrombocytopenia, abdominal distension, constipation, fatigue, alanine aminotransferase levels (ALT) increased, aspartate aminotransferase levels increased, back pain, and pyrexia (29%, 2/7 each). In the second cohort, 1 pt experienced a DLT of an inadequate number of Cycle 1 doses administered due to a grade 3 ALT elevation. This resulted in expansion of the cohort to 6 pts. Grade ≥3 TEAEs considered related to study drug thus far occurred only in this 1 pt (anemia, neutropenia, and ALT levels increased). Three pts from the 50-mg cohort experienced disease progression prior to the end of Cycle 1 requiring replacement. Pts evaluable for DLT have remained on study up to 5 cycles (range: 1-5), but no responses have been observed to date. The vecabrutinib PK profile was consistent with the results from the phase 1a study (Figure 1). Vecabrutinib was rapidly absorbed (median time to maximum concentration [Tmax]: 2 hr [range: 1-6]), and exposure increased with dose. Decreased pBTK was observed in 2 CLL pts and 1 MCL pt; no consistent effect on chemokines has yet been observed. BTK C481S VAF appeared stable at end of treatment (EOT) in the two CLL pts with baseline mutations who provided EOT samples. Conclusions: These data show sustained vecabrutinib exposure throughout the dosing interval, and preliminary evidence of PD activity in pts with R/R B-lymphoid malignancies. The study (NCT03037645) continues enrollment in the dose-escalation phase. Planning is ongoing for subsequent phase 2 expansion cohorts in selected indications. Disclosures Allan: Acerta: Consultancy; AbbVie: Membership on an entity's Board of Directors or advisory committees; Sunesis: Membership on an entity's Board of Directors or advisory committees; Genentech: Membership on an entity's Board of Directors or advisory committees; Verastem: Membership on an entity's Board of Directors or advisory committees. Wierda:AbbVie, Inc: Research Funding; Genentech: Research Funding. Patel:Genentech: Consultancy, Speakers Bureau; Sunesis Pharmaceuticals: Consultancy; Pharmacyclics/Janssen: Speakers Bureau; Juno Therapeutics: Consultancy; AstraZeneca: Consultancy, Research Funding, Speakers Bureau; Celgene: Consultancy. O'Brien:Acerta: Research Funding; Pharmacyclics: Consultancy, Research Funding; Alexion: Consultancy; Abbvie: Consultancy; Kite Pharma: Research Funding; Sunesis: Consultancy, Research Funding; Gilead: Consultancy, Research Funding; Janssen: Consultancy; Celgene: Consultancy; Vaniam Group LLC: Consultancy; Aptose Biosciences Inc.: Consultancy; Regeneron: Research Funding; TG Therapeutics: Consultancy, Research Funding; Astellas: Consultancy; Amgen: Consultancy; GlaxoSmithKline: Consultancy; Pfizer: Consultancy, Research Funding. Mato:Janssen: Consultancy, Honoraria; AstraZeneca: Consultancy; Acerta: Research Funding; Celgene: Consultancy; Regeneron: Research Funding; TG Therapeutics: Research Funding; Prime Oncology: Speakers Bureau; Sunesis: Honoraria, Research Funding; Abbvie: Consultancy; Pharmacyclics: Consultancy, Honoraria, Research Funding. Davids:Celgene: Consultancy; Surface Oncology: Research Funding; BMS: Research Funding; Astra-Zeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy; Gilead: Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy; Sunesis: Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy; TG Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; MEI Pharma: Consultancy, Research Funding; Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharmacyclics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Consultancy; Sunesis: Membership on an entity's Board of Directors or advisory committees; Astra-Zeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Sunesis: Membership on an entity's Board of Directors or advisory committees; MEI Pharma: Consultancy, Research Funding; Merck: Consultancy; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Verastem: Consultancy, Research Funding; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; TG Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; MEI Pharma: Consultancy, Research Funding; Surface Oncology: Research Funding; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Astra-Zeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharmacyclics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Verastem: Consultancy, Research Funding; BMS: Research Funding; Roche: Consultancy; Merck: Consultancy; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees; BMS: Research Funding; Merck: Consultancy; Gilead: Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Verastem: Consultancy, Research Funding; Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; TG Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Surface Oncology: Research Funding. Furman:Gilead: Consultancy; Janssen: Consultancy; Genentech: Consultancy; AbbVie: Consultancy; Loxo Oncology: Consultancy; Sunesis: Consultancy; TG Therapeutics: Consultancy; Verastem: Consultancy; Pharmacyclics LLC, an AbbVie Company: Consultancy; Acerta: Consultancy, Research Funding; Incyte: Consultancy, Other: DSMB. Pagel:Pharmacyclics, an AbbVie Company: Consultancy; Gilead: Consultancy. Fox:Sunesis Pharmaceuticals: Employment; Amphivena Therapeutics: Employment. Ward:Sunesis Pharmaceuticals: Consultancy. Taverna:Sunesis Pharmaceuticals: Employment. Brown:Boehringer: Consultancy; Sunesis: Consultancy; Invectys: Membership on an entity's Board of Directors or advisory committees; Beigene: Membership on an entity's Board of Directors or advisory committees; Acerta / Astra-Zeneca: Membership on an entity's Board of Directors or advisory committees; Roche/Genentech: Consultancy; Verastem: Consultancy, Research Funding; Morphosys: Membership on an entity's Board of Directors or advisory committees; Sun Pharmaceutical Industries: Research Funding; Abbvie: Consultancy; Pharmacyclics: Consultancy; Loxo: Consultancy; Genentech: Consultancy; Celgene: Consultancy; Gilead: Consultancy, Research Funding; TG Therapeutics: Consultancy; Janssen: Consultancy.

Background: CD19-targeted chimeric antigen receptor T cell (CAR T) therapies have remarkable overall response rates (ORR) for relapsed diffuse large B cell lymphoma (DLBCL). There is strong rationale to use a radiotherapy (RT) bridge during the cell manufacturing process including palliation, local control and cytoreduction with limited count impact. Recent data from our institution suggests RT may augment an immune response and sensitize antigen negative cells to CAR-mediated death. This series details our early experience using RT conditioning. Methods: 13 patients (median age 64 years) with DLBCL (n=9) or transformed follicular lymphoma (n=4) were analyzed. Overall, patients had a median of 2 prior therapies (range 1-8) including 3 with autologous transplant, 3 with distant RT and 1 with CAR T infusion. Several CAR products were used, including axicabtagene ciloleucel (n=8), JCAR017 (n=3, per NCT02631044), tisagenlecleucel (n=1) and EGFRt/19-28z/4-1BBL "armored" CAR (n=1, per NCT03085173). Most patients (n=10) began RT post apheresis with median duration between RT and CAR infusion of 20d (range 13-80, Figure 2). The most common RT regimen (n=8) was 20 Gy in 5 fractions (range 20-47 Gy) but 2 received our pre-transplant regimen of 30 Gy in 20 BID fractions. None received concurrent chemotherapy with RT but one had a cycle post RT and pre CAR. All had cyclophosphamide and fludarabine lymphodepletion. PET response was evaluated by Lugano criteria. Results: Three patients had limited stage PET avid disease at RT and were treated comprehensively pre-CAR. The remaining 10 were advanced stage and were treated palliatively to limited sites. Irradiated sites included the pelvis/groin (n=4), neck (n=3), intraabdominal (n=2) and extremity (n=2). Most (n=10) had intensity modulated radiotherapy. RT fields were large (median planning treatment volume of 887 cc, range 163-1641). Post RT PET interpretation was challenging given a short interval since RT ended (median 11d) but of 11 evaluable patients, many (n=8, 73%) had partial response (PR). Though locally controlled, most (n=10, 91%) had out of field progressive disease (PD) pre-CAR. Post CAR T, no severe adverse events in the RT field were noted, 9/13 had cytokine release syndrome (n=1 grade 3, n=2 grade 2) and 4 had neurotoxicity (n=3 grade 3). At day 30, ORR was 90%; of 10 evaluable patients, 7 had complete response (CR) and 2 had partial response (PR). Of the 7 evaluable patients at day 90, 4 (57%) had continued CR and the other 3 (43%) had PD and subsequently died from DLBCL. One relapsed at 95d post armored CAR both in and out of the RT field, and the other relapsed at 64d post JCAR017 primarily out of field. Conclusions: Use of RT as a CAR T bridging strategy is feasible and associated with excellent pre-CAR local control and initial post CAR ORR in a cohort of heavily pre-treated DLBCL patients. We observed moderate serious CAR toxicity that did not appear to be augmented by RT. Future efforts should clarify the optimal RT timing/dose and assess the potential for incremental immunogenicity with combined therapy. Disclosures Palomba: Hemedicus: Other: Immediate Family Member, Speakers Bureau ; Merck & Co Inc.: Other: Immediate Family Member, Consultancy (includes expert testimony); Seres Therapeutics: Other: Immediate Family Member, Equity Ownership and Membership on an entity's Board of Directors or advisory committees; STRAXIMM: Other: Immediate Family Member, Membership on an entity's Board of Directors or advisory committees; Kite Pharmaceuticals: Other: Immediate Family Member, Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Membership on an entity's Board of Directors or advisory committees; Noble Insights: Consultancy; Evelo: Other: Immediate family member, Equity Ownership; MSK (IP for Juno and Seres): Other: Immediate Family Member, Patents & Royalties - describe: intellectual property rights . Batlevi:Juno Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees. Giralt:Celgene: Consultancy, Research Funding; Takeda: Consultancy; Sanofi: Consultancy, Research Funding; Amgen: Consultancy, Research Funding. Noy:Medscape: Honoraria; Prime Oncology: Honoraria; Pharamcyclics: Research Funding; Raphael Pharma: Research Funding; NIH: Research Funding; Janssen: Consultancy. Park:Amgen: Consultancy; Autolus: Consultancy; AstraZeneca: Consultancy; GSK: Consultancy; Incyte: Consultancy; Kite Pharma: Consultancy; Novartis: Consultancy; Takeda: Consultancy; Allogene: Consultancy. Sauter:Juno Therapeutics: Consultancy, Research Funding; Genmab: Consultancy; GSK: Consultancy; Spectrum Pharmaceuticals: Consultancy; Novartis: Consultancy; Celgene: Consultancy; Kite/Gilead: Consultancy; Precision Biosciences: Consultancy; Sanofi-Genzyme: Consultancy, Research Funding. Scordo:Angiocrine Bioscience, Inc.: Consultancy; McKinsey & Company: Consultancy. Shah:Janssen: Research Funding; Amgen: Research Funding. Sadelain:Memorial Sloan Kettering Cancer Center: Employment; Juno Therapeutics: Consultancy, Patents & Royalties, Research Funding; Fate Therapeutics: Consultancy, Patents & Royalties. Perales:Bellicum: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol-Meyers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Incyte: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Nektar Therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Omeros: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Merck: Consultancy, Honoraria; MolMed: Membership on an entity's Board of Directors or advisory committees; NexImmune: Membership on an entity's Board of Directors or advisory committees; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Medigene: Membership on an entity's Board of Directors or advisory committees; Servier: Membership on an entity's Board of Directors or advisory committees; Kyte/Gilead: Research Funding; Miltenyi: Research Funding.

Abstract Backgroud. The treatment landscape of mantle cell lymphoma (MCL) has significantly changed in last decades. Improvement in diagnosis and understanding of disease biology has been coupled with emergence of new therapeutic options, including targeted agents. While MCL outcome data comes primarily from clinical trials (CT), the impact of therapeutic advances on pattern of care (POC) and outcome in MCL in the general population is not well characterized. This study sought to characterize changes in pattern of care and outcomes of patients with MCL in a prospective observational series in the rituximab era. Methods. The study included consenting adult patients with newly diagnosed MCL that were prospectively enrolled into the University of Iowa/Mayo Clinic Lymphoma Specialized Program of Research Excellence (SPORE) Molecular Epidemiology Resource, from 09/01/2002 to 06/30/2015. Demographic, clinical and prognostic factors were abstracted, and all patients were actively followed for re-treatment, relapse and death. Since bendamustine-rituximab (BR) regimen starting to be used in 2010, we defined patients enrolled from 09/01/2002 to 12/31/2009 as era 1 and those enrolled 01/01/2010 to 06/30/2015 as era 2. Baseline characteristics and outcomes, evaluated in terms of event free survival (EFS), overall survival (OS) and cause of death, were analyzed and compared between the two eras identified. Results. 348 patients with newly diagnosed MCL were enrolled. Five patients had no available data for front-line treatment and were excluded. The analysis was thus conducted on 343 patients: 169 patients were diagnosed in era 1 with a median follow-up of 131.2 months vs. 174 in era 2 with a median follow-up of 58.9 months. Baseline clinical characteristics and MIPI score were similar across the two eras ( Table 1). Frontline induction treatment was significantly different in the two eras. BR use was 0 vs 49 (28.2% ), R-CHOP/CHOP like regimen in 89 (52.7%) vs 45 (25.9%), high-dose cytarabine (HiDAC)-based therapy in 1 (0.6%) vs 28 (16.1%), intensified regimens (HyperCVAD) in 16 (9.5%) vs 8 (4.5%), other regimens (including R-cladribine, R-fludarabine-mitoxantrone, rituximab monotherapy) in 35 (20.7%) vs 13 (7.5%) patients in era 1 vs era 2 respectively. Non-systemic treatment (observation, surgery or radiation only) was performed in 25 (14.8%) vs 31 (17.8%), while 9 (8%) vs 12 (7.7%) patients were enrolled in clinical trials, in era 1 vs era 2 respectively. Autologous stem cell transplantation (ASCT) as consolidation of first line treatment or use of Rituximab maintenance was not different between Era 1 and Era 2. Among the entire cohort of 343 MCL patients, 3y-EFS and 3y-OS were 51.9% (95% IC 46.7-57.6) and 73.5 (95% CI 68.8-78.4), respectively (Figure 1). 3y-EFS was 45.9% (95% CI 39.0-54.1%) vs 58.4 (95% CI, 51.2-66.6%) in Era 1 vs Era 2 (HR 0.69 (0.51-0.92), p=0.006), 3y-OS was 70.9% (95% CI, 63.4-78.1%) vs 76.1% (95% CI, 69.7-83.1%) in Era 1 vs Era 2 (HR 0.87 (0.61-1.24), p=0.26), respectively (Figure 1). In a univariate analysis, high risk simplified MIPI was prognostic of lower EFS and OS in both the era groups. Conclusion. The BR regimen entered front line therapy of MCL resulting in decline of R-CHOP use in the MER. While rates of ASCT remain similar over the two eras, high dose cytarabine usage in induction therapy has increased. While POC in MCL continue to evolve, the introduction of bendamustine and high-dose citarabine based regimens resulted in an improvement in EFS but not OS in this observational cohort-based analysis. Findings in this study are important for design and planning of future clinical trials incorporating novel agents in induction therapy of MCL. Figure 1. Figure 1. Disclosures Cohen: Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Infinity Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; BioInvent: Consultancy; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Research Funding; Bristol-Myers Squibb: Research Funding; Infinity Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Research Funding; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Millennium: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Research Funding; Pharmacyclics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Millennium: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda: Research Funding; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; BioInvent: Consultancy; Seattle Genetics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharmacyclics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda: Research Funding. Witzig:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Cerhan:Celgene: Research Funding; Jannsen: Other: Scientific Advisory Board; Nanostring: Research Funding.

Background Recently, treatment options for RRMM have increased substantially with multiple approvals of novel agents/combination, making the treatment algorithm increasingly complex, with changes driven chiefly by access to novel agents/regimens. Furthermore, patient (pt) and disease characteristics have a profound impact on treatment decisions. To understand the impact of recently approved novel regimens on real-world (RW) treatment patterns, we conducted a multi-national survey to investigate the management of RRMM across Europe. Methods Retrospective, anonymized data from RRMM pts, treated in academic or community hospitals/clinics in 8 countries were extracted from Jan 2016 to Dec 2018. Data were analyzed overall and for Germany, Austria, and Switzerland (DACH) vs other countries (Belgium, France, Greece, Spain and UK) due to differences in treatment access. Results The cumulative number of pts included was 2782 in 2016, 3902 in 2017, and 4658 in 2018. Of the pts enrolled in 2016, 2017 and 2018, 40%, 49% and 51%, respectively, were in 3rd+ line (≥3L), potentially reflecting the increasing availability of treatment options for RRMM and extended survival in MM. Median age at diagnosis in pts enrolling in 2016, 2017, and 2018, was 68, 69, and 70 years, respectively, with 23%, 24%, 26% aged >75 years, underlining the fact that MM remains a disease of the elderly. The data revealed a difficult-to-treat RW population: 31%-36% of pts had an ECOG PS ≥2 at 2nd line (2L) in 2016-2018; increasing to 44%-49% at 4th+ lines (≥4L). At 2L, 42%-45% of pts presented ≥1 treatment-dependent comorbidity in 2016-2018, including hypertension (23-27%) and renal impairment (9-10%). Cytogenetic risk, evaluated in 38%-42% of pts at initial diagnosis, was reported as high in 8%-10% of the total population. Treatment initiation due to biochemical relapse was reported in 33%/36% of pts at 2L/3L in 2016, and in 30%/28% in 2018, indicating that ~1/3 of pts manifested an asymptomatic rather than clinical relapse. The proportion of pts treated with triplet regimens increased from 26%, 26%, and 30% at 2L, 3L and ≥4L in 2016 to 43%, 40%, and 38% in 2018, reflecting the adoption of newly approved triplets in RRMM, particularly in DACH countries. Use of proteasome inhibitor (PI)-based regimens increased from 35%, 30% and 34% at 2L, 3L and ≥4L in 2016, to 43%, 37% and 37% in 2018, driven by increased/earlier use of novel PIs (carfilzomib and ixazomib). These trends were more obvious in DACH, highlighting the impact of earlier access to modern treatment in these countries. Similarly, the proportion of pts on daratumumab-based regimens increased from 0, 5%, and 20% at 2L, 3L and ≥4L in 2016, to 10%, 24% and 31% in 2018. From 2016 to 2018, prior IMiD exposure at 2L increased from 11% to 20% in DACH, but remained stable at 42% in other countries; at 3L, there was an increase from 77% to 82% in all countries reflecting the uptake of novel triplet combinations. Most pts were IMiD-exposed or IMiD-refractory at ≥4L. Regarding the treatment algorithm, the rate of PI-based treatment at 1L was 74%-75%. PI- to IMiD-based therapy was the commonest treatment sequence from 1L to 2L, at 64%-66%, while PI- to PI-based therapy at 1L to 2L increased from 22% in 2016 to 30% in 2018. Key disease/pt characteristics associated with the selection of regimens at 2L and 3L are summarized in the Table. Prior IMiD treatment limited the use of IMiD-based therapy in subsequent lines. The use of KRd, IRd and DRd was mostly associated with ISS stage III, while the use of KRd was less frequently reported in pts with cardiac comorbidities. In pts with prior PI treatment, KRd and IRd (but not Kd) were more common at 2L, while DRd was preferred at 3L. A higher proportion of fit, young, or prior-SCT pts were treated with KRd or DRd, while IRd was the preferred treatment in pts with biochemical relapse. Conclusions Multiple drug approvals for RRMM in Europe have resulted in marked changes in the treatment algorithm, with a more immediate impact in countries with earlier access to new treatment options. Multiple decision drivers such as age, fitness, comorbidities and prior treatment are associated with uptake of different novel regimens at 2L and 3L. The increasing range of treatment options has resulted in pts receiving more lines of therapy for RRMM, highlighting the need for cautious planning of treatment sequencing to optimize the use of available combinations according to pt characteristics and disease factors. Disclosures Merz: Janssen: Other: Travel grants; Amgen: Membership on an entity's Board of Directors or advisory committees, Other: Travel grants; Abbvie: Other: Travel grants; Celgene: Other: Travel grants; Takeda Vertrieb GmbH: Other: Travel grants, Research Funding. Pérez:Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees. Kolb:Amgen: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Janssen: Other: travel and registration for my participation to international medical congres (ASH). Symeonidis:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Research Funding; Roche: Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Research Funding; Tekeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead: Membership on an entity's Board of Directors or advisory committees, Research Funding; MSD: Membership on an entity's Board of Directors or advisory committees, Research Funding. Zomas:Takeda: Employment. Gonzalez:Takeda: Employment. Kellermann:Amgen: Research Funding; BMS: Research Funding; Celgene: Research Funding; Janssen: Research Funding; Sanofi: Research Funding; Takeda: Research Funding. Goldschmidt:Chugai: Honoraria, Other: Grants and/or provision of Investigational Medicinal Product, Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; John Hopkins University: Other: Grants and/or provision of Investigational Medicinal Product; Adaptive Biotechnology: Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Research Funding; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Grants and/or provision of Investigational Medicinal Product, Research Funding; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Grants and/or provision of Investigational Medicinal Product, Research Funding; ArtTempi: Honoraria; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Grants and/or provision of Investigational Medicinal Product, Research Funding; MSD: Research Funding; Molecular Partners: Research Funding; Mundipharma: Research Funding; Amgen: Membership on an entity's Board of Directors or advisory committees, Other: Grants and/or provision of Investigational Medicinal Product, Research Funding; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other, Research Funding; Dietmar-Hopp-Foundation: Other: Grants and/or provision of Investigational Medicinal Product.

Abstract This study traces the claims of a ‘scientization’ and a ‘participatory turn’ in modern governance within the system of temporary policy advisory committees in Norway. It analyzes whether there is evidence of the two claims in these key governance institutions and to what extent these shifts are compatible with each other. As expressions of a participatory turn, a growing emphasis on citizen involvement and transparency in the committee system is searched for. A growing relevance of researchers and of science-based claims in the committees’ reports are taken as indicators of scientization. The longitudinal study shows an overall shift both towards science- and expertise-based governance and towards an increasing openness and public engagement, as well as some variation between policy fields.

Effective public participation is a key part of sustainable forest management on publicly owned lands. However, long-term monitoring data that seek to measure effectiveness of public participation in forest management planning is lacking. Here, measures based on attitudes and satisfaction ratings associated with suspected criteria of public participation effectiveness were developed and applied to forest resource advisory group members from Ontario, Canada. Using data from four social surveys (2001, 2004, 2010, and 2014), advisory group members were, on average, satisfied and held positive attitudes towards the advisory group, their participation in the group, and forest management planning. In many instances, these positive evaluations increased from 2001 to 2014, especially for statements related to fairness. One concern about Local Citizens Committees (LCCs) related to their composition. Advisory group members were male dominated (about 88%) and were increasingly overrepresented by individuals between 50 and 69 years old in 2014 (67%). Given that male and female LCC members held different perceptions of the effectiveness of some public participation criteria, these concerns suggest that composition of LCCs might impair the ability of the groups to consider all viewpoints related to forest management planning. Finally, the research illustrates the importance of designing and collecting long-term monitoring data to understand how evaluations of public participation and composition of participants changes over time.

Despite progress with immunotherapy and targeted agents, treatment of refractory disease remains challenging, in particular for patients with T-ALL. Identification of genomic lesions defining actionable targets had limited impact on patient care so far. The complexity of biological systems highlights the need to develop complementary functional approaches. We and others have established platforms with a library of 120 drugs based on current treatment and (pre-)clinical development, to detect ex-vivo drug response phenotypes on leukemia samples at single cell resolution by high content image analysis. We demonstrated that drug response profiling (DRP) identifies dependencies not predicted by genetic alterations adding a functional information layer for clinicians. Here we report first correlations with clinical outcome using DRP in a non-interventional setting. From 2016 to 2019 we performed DRP in the framework of European ALL first- and second- line protocols upon request by treating centers. Here we analyze retrospectively treatment decisions and outcome for 23 T- and 50 BCP-ALL patients. To evaluate drug responses, we compared dose response curves of individual patients to data recorded for all patients. Sensitivity and resistance were defined based on the IC50 outlier analysis using cut-offs depending on distribution (normal gaussian vs. skewed). From 73 patients tested, clinical outcome data has been available for 36 BCP- and 15 T-ALL patients. NGS data provided by the INFORM registry has been available in 8 BCP- and 2 T-ALL patients. In first line BCP-ALL patients, ex-vivo Dexamethasone response predicted clinical response to prephase prednisone (d8) and minimal residual disease (MRD) reduction measured by flow cytometry at d15 of first line AIEOP BFM 2009 induction (Fig. 1). For refractory and relapsed ALL we observed an association of DRP and response to targeted agents in 14 out of 16 patients (87.5 %; Table 1). Data for the r/r BCP-ALL cohort is limited because most patients underwent CD19 and / or CD22-directed immunotherapy. Sensitivity and resistance to Calicheamicin correlated with clinical response to Inotuzumab, suggesting functional testing to be evaluated in future studies. In contrast, lack of correlation of ex-vivo sensitivity to MEK-inhibitors with presence of RAS-pathway alterations caution the exclusive use of molecular information to predict response to these agents. Most therapeutic decisions based on DRP information were made for patients with r/r T-ALL. Bortezomib ex-vivo sensitivity correlated with clinical responses in 5 T-ALL patients (Fig. 2). Both patients predicted to respond to Bortezomib and treated on Bortezomib + Venetoclax experienced good MRD response providing a bridge to stem cell transplantation (SCT). However, these patients relapsed after SCT emphasizing the need for additional consolidative therapeutic elements for heavily pretreated patients. In line with previous reports, we confirmed a T-ALL with high sensitivity to Dasatinib (IC50 1.9 nM; Fig. 3). Dasatinib monotherapy induced a molecular remission. A 2nd T-ALL showing an ex- vivo Dasatinib IC50 at 80 nM was refractory to treatment with Dasatinib + Daunoxome-FLAG. A 3rd ABL1-fusion positive T-ALL, ex-vivo resistant to Imatinib and Dasatinib, had only short- term response to Imatinib + chemotherapy. Finally, treating a T-ALL patient based on high sensitivity to the XPO1 inhibitor Selinexor as 4th line monotherapy led to significant decrease of PB blasts from d1 25 G/L to 0.7 G/L at d13 of treatment (Fig. 4). The patient experienced improved quality of life, minimizing need of hospitalization with stable disease for 3 months on maintenance with Selinexor. Given the promising preclinical data with this class of agents and current lack of established biomarkers, we propose that DRP should be evaluated for this class of agents. In conclusion, we established first associations between DRP and clinical response for various agents providing a rationale for the evaluation of DRP in prospective clinical trials. Integration of molecular and functional information may improve the selection of more specific treatment options for patients with resistant disease. The international BFM Study Group and ITCC Consortium are planning an international multiarm early clinical trial for treatment of r/r ALL patients that will include DRP for evaluation in order to improve selection of targeted therapy. Disclosures Cario: Jazz Pharmaceuticals: Consultancy, Other: travel support; Novartis: Consultancy, Other: travel support. Hrusak:Amgen: Other: MRD investigations funded by Amgen, Research Funding. Kulozik:Novartis: Consultancy, Honoraria; bluebird bio, Inc.: Consultancy, Honoraria. von Stackelberg:Morphosys: Membership on an entity's Board of Directors or advisory committees, Other: Personal fees, advisory committees and speakers bureau, Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees, Other: Personal fees, advisory committees and speakers bureau, Speakers Bureau; Jazz: Membership on an entity's Board of Directors or advisory committees, Other: Personal fees, advisory committees and speakers bureau, Speakers Bureau; Amgen: Membership on an entity's Board of Directors or advisory committees, Other: Personal fees, advisory committees and speakers bureau, Speakers Bureau; Shire: Membership on an entity's Board of Directors or advisory committees, Other: Personal fees, advisory committees and speakers bureau, Speakers Bureau. Jacoby:Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Lonza: Membership on an entity's Board of Directors or advisory committees. Bourquin:Servier: Other: Travel Support.

Traditional models of public participation in planning have been criticized as 'top-down' segregating planners from ordinary citizens; thus, there has been a quest for greater public involvement in planning decisions and policy-making. The public demands a greater voice in planning and development affairs. To provide public input into the planning process, planning agencies often establish Citizen Advisory Committees (CAC) to involve the public in planning decisions. The increasing redevelopment pressure in inner city suburbs in most Australian cities has led to the creation of many advisory groups for advising planning agencies and Ministers for Planning on planning and development matters. These advisory committees usually consist of people of diverse backgrounds elected, selected and/or appointed by the planning agency to provide community input into planning policy making. However, little is known about the context and operational process in the consultation processes of advisory committees. Much of the existing literature on public participation lacks widely applicable evaluation approaches for determining whether the existing context and process is fair and effective in the participation process. As complex social phenomena, public participation processes are influenced by contextual factors. This thesis examines the Terms of Reference and the operational process of planning advisory committees, and evaluates them through two proposed meta-criteria: fairness and effectiveness. LAPACs in Canberra have been selected for the evaluation of the participation process, providing a basis to develop a conceptual model for its improvement. The analysis is based on a theoretical framework, which focuses on the criteria of fairness and effectiveness in the public participation process. This study uses a qualitative approach to data analysis using multi-method techniques such as focus interviews, document analysis and participant observation. The interviews were conducted with LAPAC members and other planning community who were directly or indirectly involved in the ACT's consultation process, and aware of its planning decisions. They are development proponents, the enthusiastic wider public, planning staff, the Minister for Planning, and planning spokespersons of political parties. The data provide insight into the details of the proposed criteria to evaluate the fairness and effectiveness of a participation process. The results suggest that improving the participation process in a planning advisory committee requires changes in committee protocols, operational processes and planner roles in conducting the participation processes. Specifically, there needs to be a move away from static processes toward more strategic, active and accountable processes. This thesis suggests some practical steps, in order to ensure greater fairness and effectiveness in the participation process of a planning advisory committee, and recommends the proposed evaluative criteria as a new framework for evaluating planning advisory committees.

This study has contributed to two areas of growing interest and involvement: the knowledge base of public participation in community workshops for design practitioners and Muncie's White River project.Two community workshops were conducted and compared to study their processes and end results. All variables were constant between both workshops with the exception of a video, When the Wind Stops by Dianne Haak and Bernard Wilets, shown at the beginning of only one workshop. The group dynamics of the workshops were reviewed to understand their influence. It was determined that group size, persons conducting the workshops, the video, and the composition of the participants all affected the workshops' process and results.Focusing on the proposed White River Corridor Greenway, participants generated 183 ideas for increasing use and extending ownership of the river to the community. Participants produced 51 benefits, 85 potential physical development, and 47 programs and activities for improving connections to the creation and use of the river greenway.
Department of Landscape Architecture

Wildlife management requires understanding resources and involving stakeholders. The process Virginia Department of Game and Inland Fisheries (VDGIF) and Virginia Tech used to develop a black bear (Ursus americanus) management plan during 1999-2001 provided me with opportunities to understand diverse stakeholders and examine influences of participation on stakeholder knowledge, attitudes, and opinions concerning bear management. I used focus groups (with 5 key stakeholder groups), pre- and post-planning surveys, and interviews. I surveyed VDGIF biologists and managers (N = 21), members of a stakeholders advisory committee (N = 15), and members of 3 constituent groups representing bear hunters (N = 459), beekeepers (N = 442), and environmental interests (N = 500). I interviewed advisory committee members to validate survey results and evaluate the bear management plan. Participation apparently improved constituents' knowledge about bear management and their image of VDGIF bear management, and increased their support for controversial management options (e.g., lethal methods), but did not affect their opinions about bear hunting. Participation apparently had little effect on VDGIF staff opinions about bear management. Knowledge varied widely among constituent organizations. Bear hunting continues to be one of the most central, yet divisive, bear management issues in Virginia. Advisory committee members and VDGIF staff expressed satisfaction with the bear management plan and the planning process. Recommendations for wildlife decision-making processes include: balance science and public values in management, use multiple public involvement techniques, establish collaborative forums among stakeholders, reach out to all stakeholders, and nurture relationships with constituents during implementation.
Master of Science

This project examines the role of immunization registries and their effect on a health care delivery system. Recent efforts to attain coverage of child populations by recommended vaccines have included initiatives by federal and state agencies, as well as private foundations, to develop and implement statewide community-based childhood immunization registries.

It is now widely accepted that public involvement is a critical component of sustainable forest management (SFM). However, achieving meaningful participation continues to be a challenge. Problems with public involvement in SFM tend to be directed at the continued use of passive involvement techniques such as open houses by forest products companies (FPCs) and governments at the expense of more participatory methods. In an effort to provide more active involvement, many FPCs have started to use an advisory committee approach. There are few empirical studies, however, that evaluate advisory committee processes, and that clarify the roles of such committees in forest management and planning. The purpose of the study was to help fill these gaps. The specific objectives were to: 1) establish the degree of overall success of stakeholder advisory committees (SACs) in forest management and planning in Manitoba; 2) determine the involvement techniques used in the advisory committee processes and identify the preferred techniques; 3) consider whether informal learning occurred among the participants on the committees; 4) determine what barriers exist to involvement on the committees; and 5) provide recommendations on how to improve the public involvement capabilities of SAC's in SFM. The study focused on the advisory committees of the three FPCs that hold forest management licences in Manitoba, Canada: Tembec, located in Pine Falls; Louisiana-Pacific, in Swan River; and Tolko, based in The Pas. A qualitative research approach was used to address the goals of the research, including: l) standardized open-ended interviews with selected members of each committee (N=25); 2) a meeting with key...

Advisory committees are part and parcel of policy-making in every government agency. Their input is used at many levels, ranging from high level strategic initiatives and planning to very specific input into narrowly defined decisions. This chapter describes an operational overview of the different approaches used by science agencies in the United States and documents the heterogeneous way in which they are used. It suggests that some of the principles that motivated the establishment of advisory committees are not always fully served in practice. It also finds that that the financial structure and incentives of some entities, might usefully be reviewed. The chapter concludes by observing that the structure of committees might be improved by developing a more scientific approach to their constitution.

The study examines the peculiarities of the implementation of gender policy in the field of security and defense by the example of the UN and NATO. To achieve this goal, we considered the legal regulation of gender equality in the field of security and defense of the UN and NATO; analyzed the work of institutional mechanisms for the implementation of gender policy in the field of security and defense by the example of the UN and NATO; characterized the peculiarities of cooperation between Ukraine, the UN and NATO in ensuring gender equality in the field of security and defense. The legal regulation of gender equality at the UN and NATO levels was considered, in particular a number of resolutions (UN Security Council Resolutions on Women, Peace and Security No. 1325, No. 1820, No. 1888, No. 1889, No. 1960, No. 2106, No. 2122, No. 2422, No. 2467, No. 2493), which recognizes the importance of involving women and gender mainstreaming in peace negotiations, humanitarian planning, peacekeeping, post-conflict peacebuilding, governance, and equal participation of women at all levels of conflict prevention or protection from sexual violence. Also the authors analyzed the work of institutional mechanisms responsible for the implementation of gender policy of the UN and NATO, in particular, their expertise and scope of activities. It was clarified that the following persons responsible for the implementation of UN Security Council Resolutions in NATO: Special Representative of the Secretary-General for Women, Peace and Security; NATO Gender Office; Gender Adviser at the International Military Staff; a number of advisory committees and working groups led by NATO Strategic Command; Civil Society Advisory Council on Women, Peace and Security. At the same time, the UN has seven expert institutions and regional independent human rights experts to combat discrimination and gender-based violence against women and girls: UN Special Rapporteur on Violence against Women; UN Committee on the Elimination of Discrimination against Women; UN Working Group on Discrimination against Women and Girls; Committee of Experts on the Follow-up Mechanism to the Belem-Par Convention; Expert Group on Combating Violence against Women and Domestic Violence; Special Rapporteur on Human Rights in Africa of the African Commission on Human Rights; Human Rights Rapporteur. In addition, a number of sub-organizations and programs have been established at the UN level to achieve gender equality in all spheres of life, such as the United Nations Development Program (UNDP), the HeForShe IMPACT 10x10x10 movement and the UN-Women. Aspects of Ukraine's cooperation with the UN and NATO in ensuring gender equality in the field of security and defense are highlighted separately. The importance and effectiveness of cooperation between Ukraine and the Alliance during the war in Eastern Ukraine have been established. The support by the UN of Ukraine in fulfilling the obligations within the international regulatory framework on the introduction of gender equality and women’s rights was also analyzed.

This chapter discusses the role of industrialists as advisers to the Committee of Imperial Defence and, crucially, the information such civilian businessmen were able to glean from the government as to future defence requirements. The role of Lithgow, Weir, and Balfour is explained in the context of these developments. How this information was used is the focus of the end of this chapter and subsequent chapters.

The Vietnam War followed a biased decisional pattern. The Johnson administration, with Robert McNamara as secretary of defense, committed early to a military solution. It extended the US mission to include a full-blown air war (Rolling Thunder) that was true to neither a political nor a military strategy, and the administration fought a full-blown ground war without concern for the war’s critical political dimension. Then, when reaching its limit, the administration sought mainly to manage the US mission’s costs, despite the apparent success of a pacification strategy. Finally, when victory proved elusive, Richard Nixon and his national security adviser, Henry Kissinger, escalated the war by invading Cambodia, supporting the invasion of Laos, and initiating the Linebacker bombing campaigns over North Vietnam. They nonetheless prioritized an exit from the conflict, as registered in the terms of the 1973 Paris Peace Accord.

This chapter describes the importance of the census for public health. The US Constitution mandates that each resident of the country be counted at least every 10 years. As the 2020 census approached, the Trump administration launched an effort to meddle with how to perform this head count, by adding a question about citizenship to the census. This move was roundly criticized by the Census Bureau’s Scientific Advisory committee and became the target of lawsuits. It looked very much like an attempt to depress the 2020 population count in immigrant-rich and predominantly Democratic areas, in advance of redistricting in 2021. Accurate census data are critical for the public's health. These data drive federal grants to states for the Special Supplemental Nutrition Program for Women, Infants, and Children. They guide disaster response and disease outbreak planning. Moreover, the Centers for Disease Control and Prevention (CDC) uses census information to locate geographic areas with low education levels and high poverty rates, so as to expand screening and outreach programs. Thus, these data inform the building of roads, schools, and health centers. As such, political moves to influence the census is a matter of great concern for public health.

Judith Weisz's story of the politics of drug risk management shifts its focus to Depo-Provera's lengthy FDA marketing approval process. Here her story explores the scientific and political controversy over the FDA's assessment of the drug's risk and its policy judgments about the risk acceptability of its marketing approval. The controversy was dominated by the fear that the drug could cause breast, endometrial, and cervical cancer, and by Depo-Provera's uniqueness as a long-acting contraceptive and its use in international population control programs. The controversy began when the FDA relied on its Obstetrics and Gynecology Advisory Committee to grant the drug limited marketing approval in 1974, which it withdrew after congressional criticism, and then, following an intra-agency review, disapproved the drug for general contraceptive marketing which, once again, brought congressional scrutiny because of its impact on international family planning programs. An FDA Public Board of Inquiry, convened at Upjohn's request and chaired by Judith Weisz, conducted an intensive scientific assessment of the drug's animal and human studies at its 1983 hearings and then made a recommendation, accepted by the FDA in 1986, to disapprove the drug for general contraceptive marketing.

The Regional Municipality of York is located immediately north of the City of Toronto. It is the fastest growing municipality in Ontario. The rapid expansion of residential, industrial and commercial development in the municipality has led to a weakness in the electrical and gas infrastructure. The Ontario Power Authority (the agency responsible for managing the power requirements in the Province of Ontario) has recognized this weakness and has developed plans calling for a new gas-fired generating station and improvements to the electrical grid. The shortages of gas supply and electricity have not developed overnight. Hydro One, which runs the electrical grid, initiated a supply study in 2002. The study recommended upgrading a 115 kV transmission line to a double circuit 230 kV transmission line on the existing corridor. The ensuing public outcry resulted in the municipality passing a resolution against the upgrade. Similarly, a large gas-fired generating station proposal was abandoned as the result of citizen opposition. In 2003, the Ontario Energy Board approved new Environmental Guidelines for the Location, Construction and Operation of Hydrocarbon Pipelines and Facilities in Ontario. The guidelines include specific new requirements for planning pipelines in urban areas. Among other things, these requirements involve the identification of indirectly affected landowners and a more detailed analysis of public issues and how they were resolved. It became clear that in order to achieve regulatory success, not only would the public have to become actively engaged in the decision-making early in the process, the technical reviewers (federal, provincial and municipal agencies) would likewise have to be actively involved. Through the use of two case studies of proposed large-diameter natural gas pipelines initiated in York Region in 2005, this paper describes the techniques used to engage the public and the regulators. It also describes how the public involvement requirements contained in the Ontario Energy Board’s new guidelines were incorporated into the planning process. The case studies begin with a rationale for the study area selected. A description of issues follows. The techniques used to address these issues and the success of the program are documented. Techniques include face-to-face project initiation meetings, use of technical and citizens’ advisory committees, sub-committee meetings to resolve specific issues and site-specific field work. The study results illustrate that it is possible to plan a right-of-way in such a manner as to satisfy the general public and regulators, be compatible with existing development, conform to the new Ontario Energy Board guidelines and minimize the amount of remedial work required to mitigate the impacts occurring on and adjacent to the right-of-way.

Orkney Islands Council is the Statutory Harbour Authority for Scapa Flow – a 324.5km2 area of deep water and sheltered anchorage in the Orkney Islands, north of mainland Scotland, with a long history and present use by all types of shipping. This paper will provide a short introduction to the development of the IMO and EU Directive compliant Ballast Water Management Policy for Scapa Flow which was approved by the competent planning authority in December 2013. Scapa Flow is in an environmentally sensitive area, this along with best practice was taken into account when developing the Policy – which includes strict and enforceable requirements on vessels and the Harbour Authority with regards to operations, monitoring and reporting. Since its approval there have been thirty-three occasions where ballast water discharge into Scapa Flow (by various types of vessels) has been requested. The Policy requires that vessels requesting to discharge ballast water into Scapa Flow must exchange and treat (where a treatment system is fitted) on every visit to Scapa Flow (no exceptions or exemptions allowed). To date thirty-one vessels have carried out exchange and two have carried out exchange and treat – all as per the Policy. This paper will deal with the setting of an IMO compliant Ballast Water Policy through to practical application by a Statutory Harbour Authority for a period of three years from 2013 to present day – with examples of ship types, amounts, any restrictions imposed, checks and reports made. It will include – with input from the Harbour Authority’s Marine Environment Unit lead by Jenni Kakkonen –a review of the positive actions, problems, solutions and overall results obtained so far regarding taking ballast water samples from these vessels, analysing the same and recording of details. There is a continual review and reporting process with regards to the effectiveness of the Policy to the Orkney Marine Environment Protection Committee (comprising of all the relevant statutory advisors and interested groups). The paper will contain the Harbour Authority’s way ahead in order to remain compliant, maintain its knowledge base of new technologies and environmental reports – all with the continued aim of maintaining the environment and commercial sustainability of Scapa Flow as a leading port and harbour.

This research program was sponsored by the Federal Railroad Administration (FRA) Office of Research and Development in support of the advancement of improved safety standards for passenger rail vehicles. FRA and the Volpe National Transportation Systems Center (Volpe Center) have conducted a research program to develop alternative methods for demonstrating occupied volume integrity (OVI) of passenger rail cars using a combination of testing and analysis. Previous publications have addressed the planning and progress of a series of tests intended to examine the collision load path through the occupant volume of passenger cars equipped with crash energy management (CEM) systems. This program has included an elastic 800-kip buff strength test, two quasi-static tests that loaded a passenger car to its ultimate (crippling) capacity, and corresponding finite element (FE) analyses of each test. This paper discusses the two crippling tests and the companion FE analyses. One alternative method for evaluating OVI moves the applied loads from the line of draft to the collision load path. This alternative methodology also permits a combination of testing and analysis to be used to demonstrate the car’s OVI, in contrast to the conventional methodology (as prescribed in existing FRA regulations) which only permits testing. The alternative methodology was adopted as the recommendations developed by the Railroad Safety Advisory Committee’s (RSAC) Engineering Task Force (ETF) in its “Technical Criteria and Procedures for Evaluating the Crashworthiness and Occupant Protection Performance of Alternatively-Designed Passenger Rail Equipment for Use in Tier I Service.” The research program was undertaken to verify the efficacy of using a combination of elastic testing and plastic analysis to evaluate the OVI of a passenger car loaded along its collision load path as prescribed in the ETF report. Earlier in this research program an elastic test of a Budd Pioneer car was used to validate an FE model of the car, per the ETF’s procedures. This model was then modified to reflect the condition of the car in its crippling test configuration. The model was used to simulate the crippling behavior of the car, following the ETF’s procedures. Two Pioneer cars were then tested to crippling to provide additional data to validate the FE model and the proposed alternative OVI evaluation. Because the test cars used in this research program were equipped with CEM systems, the alternative evaluation loads were placed at the locations where the energy-absorbing components attached to the occupant volume. During both crippling tests, loads were measured at each energy-absorber support location on the live and restrained ends of the car. Additional instrumentation used in the second crippling test included strain gages on the major longitudinal structural members, displacement transducers at each load location, and vertical, lateral, and longitudinal displacement transducers on the underframe of the car. The results of the FE analysis compare favorably with the results of the crippling tests. In particular, the crippling loads are consistent between the tests and analysis: crippling loads for the first and second cars tested were 1.15 and 1.19 million pounds respectively, and the pre-test FEA estimated a crippling load of 1.19 million pounds. The research program has established a technical basis for the alternative OVI requirements and methodology.