Area under Rapeseed Cultivation as a Factor Differentiating the Economic Performance of Biodiesel Producers

The aim of this study was to assess the impact of the area under rapeseed cultivation on the economic performance and organization of farms. The study was conducted in 164 rapeseed farms in different Polish voivodeships. A targeted sampling procedure was used to select farms for the study. The studied population was divided into four groups depending on area under rapeseed cultivation rates. The selected farms were located in voivodeships with the highest rapeseed acreage rates of the total cropped area. The economic performance of the examined farms improved with increases in rapeseed area. Farms with larger rapeseed areas were characterized by higher production values and better economic performance. On average, the total production value per farm was highest in the group of farms with rapeseed areas of 20.1–30 ha. Similar results were noted when total production values were expressed per ha of arable land, per full-time employee and per man-hour. Total production value was lowest in farms with the smallest rapeseed areas. Farms with the largest areas under rapeseed cultivation achieved the highest farm household income. The farm household income values per full-time employee and per man-hour were highest in farms with the largest areas under rapeseed cultivation. The values of fixed assets and current assets increased with increases in rapeseed area. Most farms were run by owners with secondary school education. The highest percentages of farmers with university education were noted in farms with rapeseed areas of 10–20.1 ha (37.5%) and above 30 ha (30.4%). The vast majority of farms from all groups were run by male farmers. The research results could be useful for policy makers, because they indicate that rapeseed production can not only be profitable but can also be used for biofuel production.

Identification and Development of PHE885: A Novel and Highly Potent Fully Human Anti-BCMA CAR-T Manufactured with a Novel T-Charge TM Platform for the Treatment of Multiple Myeloma

Background : Chimeric antigen receptor T cell (CAR-T) therapies for multiple myeloma (MM) targeting B cell maturation antigen (BCMA) have demonstrated promising efficacy; however, many patients with relapsed/refractory (r/r) MM will ultimately relapse. To improve on existing BCMA CAR-Ts, two critical attributes of the CAR-T product were investigated: 1) the potency of the BCMA CAR construct, and 2) a rapid manufacturing process that would both preserve the stemness of T cells to ensure longer duration of response and provide timely access for patients with rapidly progressing, aggressive disease. Through extensive panning and discriminating CAR-T functional assays to assess performance, we have identified a superior anti-BCMA CAR construct that when combined with an innovative T-Charge™ manufacturing platform, produces a highly potent product. Methods and Results : We have developed a novel anti-BCMA CAR-T product for the treatment of MM. Our anti-BCMA CAR consists of an extracellular single chain variable fragment (scFv) targeting BCMA, fused to the CD8α hinge and transmembrane domains, followed by CD137 (4-1BB) co-stimulatory and CD3ζ chain signaling domains. Selection of our development candidate was based on a screening of seventeen anti-BCMA CARs, each comprising a distinct scFv derived from phage display libraries and hybridoma with a wide range of affinities and epitopes. One candidate clone from the fully human B cell library was identified after rigorous assessment of transduction efficiency, CAR expression, antigen specificity/selectivity and CAR-T cell function against a MM cell line, both in vitro and in vivo. This scFv also demonstrates high specificity to human BCMA by Retrogenix platform using a commercial human plasma membrane protein array assay. CAR expression and functionality of the CAR constructs were compared in the CAR-T cells generated with two different cell processes: a traditional manufacturing (TM) in which CAR-T cells are expanded in vitro for 9-10 days and a novel T-Charge TM process, which is an expansionless CAR-T manufacturing process that takes <2days to generate functional CAR-Ts. PHE885 generated with the novel T-Charge TM manufacturing platform, retains naïve/ stem cell memory T cell (T scm) (CD45RO -/CCR7 +) while the traditionally manufactured cell product carrying the same scFv (TM_PHE885) mainly contains central-memory T cells (CD45RO +/CCR7 +). In addition to its unique phenotype, PHE885 secretes up to 25 fold more target specific IL-2 and ~7 fold more IFN gamma in vitro, when comparing to the TM products either using the same lentiviral vector (TM_PHE885) or a clinically validated anti-BCMA vector (MCM998). In an immunodeficient NOD-scid IL2R gamma null (NSG) mouse model of MM, PHE885 induced tumor regression at a very low dose in a dose-dependent manner, and was up to 5 fold more efficacious in eradicating tumors compared to the two TM products. This enhanced efficacy was accompanied by higher cellular expansion in vivo (up to 3 fold higher C max and AUC 0-21d). The ability of PHE885 to control the tumor at lower doses with a greater expansion profile confirms the robustness and potency of the PHE885 cells. Furthermore, unlike the TM products, PHE885 induced earlier graft-versus-host disease at medium and high tested doses in this mouse model, suggesting the stemness of the product is most likely the driver of stronger T cell expansion. Conclusions : PHE885 was discovered and designed to enhance potency and drive persistence of CAR-T through the combination of a novel CAR construct carrying a fully human anti-BCMA scFv fused to 4-1BB/CD3ζ signaling domains and a novel T-Charge TM manufacturing platform, which enables rapid and reliable patient access. The novel T-Charge TM platform allows PHE885 to preserve a significantly higher proportion of naïve/ T scm cells, enabling PHE885 to effectively engraft, expand and reject tumors at a dose of 5 fold lower than TM CAR-T cells. Based on these results, a Phase 1, open-label trial assessing PHE885 in patients with r/r MM (NCT04318327) was initiated. Initial data from the dose escalation portion of the Phase 1 study will be presented separately. Figure 1 Figure 1. Disclosures Bu: Novartis: Current Employment, Patents & Royalties: Co-inventor on patent applications. Bennett: BMS: Current Employment; Novartis: Ended employment in the past 24 months, Other: PB was a full-time employee of Novartis at the time of the study. Barton: BMS: Current Employment; Novartis: Other: NB was a full-time employee of Novartis at the time of the study. Bradshaw: Novartis: Other: LB was a full-time employee of Novartis at the time of the study; AstraZeneca: Current Employment. Pinon-Ortiz: NIBR: Current Employment, Current holder of stock options in a privately-held company. Li: Novartis: Current Employment. Vaidya: NIBR: Current Employment. Zhu: Novartis: Current equity holder in publicly-traded company; NIBR: Current Employment. Mansfield: Novartis: Current Employment. Granda: Novartis: Current Employment, Patents & Royalties: No royalties as company-held patents. Guimaraes: Novartis: Current Employment, Patents & Royalties: Co-inventor on patent applications. Treanor: Novartis: Current Employment, Current holder of individual stocks in a privately-held company, Divested equity in a private or publicly-traded company in the past 24 months, Patents & Royalties: no royalties as company-held patents. Brogdon: Novartis Institutes for Biomedical Research: Current Employment.

Cost of Care of Rare Hematologic Disorders in the United States: Call to Action for Policy Supporting Pharmacologic Innovation

BACKGROUND: Rare diseases (RD) present a societal concern because of lack of treatment availability and difficulty developing new treatments. Even when treatment options exist, there are considerable barriers to diagnosis and access to specialty care. OBJECTIVES: To estimate direct (attributable to patient care), indirect (patients' and caregivers' loss of productivity), and mortality-related costs of 5 rare hematologic disorders (atypical hemolytic uremic syndrome [aHUS], acute intermittent porphyria, acquired aplastic anemia, beta thalassemia major, and sickle cell disease) and evaluate burden of care, both when treatment is available and when no treatment exists. We compared these costs with mass market (MM) diseases, including a common hematologic disorder, deep vein thrombosis (DVT), to highlight the need to better serve RD individuals. METHODS: We evaluated peer-reviewed published articles and databases (e.g., Orphanet, the Genetic and Rare Disease Information Center, NORD, NIH), conducted interviews with patient advocacy groups (e.g., Global Gene, the EveryLife Foundation for Rare Diseases, NORD) and key opinion leaders (e.g., Penn Blood Disorders Center), and referred to the US Bureau of Labor Statistics and Medi-Span Price Rx. We performed a statistical analysis to confirm that the sample size of patients covered in our disease selection was significant. In-depth analyses were performed to assess the per patient per year (PPPY) direct, indirect, and mortality costs associated with the 5 disorders, as well as costs for MM diseases, including DVT. While treatments exist for each of these 5 rare disorders, there are no universal curative options. Cost data for MM diseases, including DVT, were derived from literature reviews. RESULTS: The economic burden of rare hematologic disorders in the US is considerable. For most diseases, treatment costs account for the majority of total direct costs (52-90%). Indirect and mortality costs account for 4% and 22% of the total burden cost, respectively, but mortality costs vary widely (4-74% of total costs). Highest overall direct cost observed was for aHUS ($530k) due to challenging diagnosis, persistent treatment, and poor prognosis. Productivity loss is 2 hours/week for patients and 2-4 hours/week for caregivers. The life expectancy of aHUS patients is ~60 years, but if untreated this may be shortened to ~35 years. The lowest overall direct cost was for beta thalassemia major ($69k). The majority of direct costs are split between treatment costs and medical procedures. Patient productivity loss is estimated to be >3.5 weeks of work loss/year in the 60% of patients who require bimonthly transfusions. Caregiver burden constitutes 9.2 hours/week of work loss. New therapies are likely to offset mortality costs in the future. Although the direct, indirect, and mortality costs of these 5 disorders are high (average total cost $228k), the burden of cost is higher in all scenarios if treatments did not exist (60% increase in overall cost). As would be expected under the "no treatment" scenarios, the direct costs attributed to each disease decreased, but indirect and mortality costs increased. Value of treatment is demonstrated by decreases in PPPY indirect costs. When no treatments were available, the range for productivity loss was ~$33k to $61k for patients and ~$25k to $61k for caregivers, compared with ~$3k to $22k for patients and ~$4k to $5k for caregivers when treatments were available. The average PPPY costs of MM diseases for which treatments are available, including DVT, are estimated to be between $6k to $27k for direct costs, $10k to $16k for indirect costs, and $3k to $24k for mortality costs. In comparison with MM diseases, including DVT, the 5 rare disorders had average direct costs of ~$169k (a 6.25- to 26-fold increase), indirect costs of ~$9k (a modest decrease), and mortality costs of ~$50k (a 2.1- to 15-fold increase). CONCLUSIONS: These scenario analyses demonstrate that RD therapies generate positive economic value. Further, analysis shows that RD pose a greater social economic burden than MM diseases. This information can be utilized to further efforts by the RD community for increased governmental investment in RD treatment, diagnosis, and access. Disclosures Andreu Perez: Chiesi Global Rare Diseases: Other: PA is a full-time employee IQVIA. The employer of PA received consulting fees from Chiesi Global Rare Diseases for this analysis. Cioffi: Chiesi Global Rare Diseases: Current Employment. Karam: Chiesi Global Rare Diseases: Other: JK is a full-time employee IQVIA. The employer of JK received consulting fees from Chiesi Global Rare Diseases for this analysis. Child: Chiesi Global Rare Diseases: Other: CC is a full-time employee IQVIA. The employer of CC received consulting fees from Chiesi Global Rare Diseases for this analysis. Tricta: Chiesi Canada Corp: Current Employment. Chiesi: Chiesi Farmaceutici SpA: Current Employment.

Current Employment and Academic Status of Recent Dental Graduates in Dhaka City

This descriptive type of cross-sectional study was conducted with an objective to find out the present employment and academic status of recent dental graduates in Dhaka city. The study was conducted for one year from July 2019 to June 2020 at different work places of recent dental graduates and residence of unemployed dental graduates in Dhaka city. A total of 414 recent dental graduates were the respondents of the study. Study revealed that 212 (51.2%) of the respondents were male and 202 (48.8%) of the respondents were female. With regards to employment, it was revealed that 340 (82.1%) of the respondents were employed as dental surgeon and 57 (13.8%) of the respondents were yet to get formal employment. Among the employed dental graduates, 203 (57%) were full-time employee and 154 (47%) were part-time. Only 55 (15.4%) dental surgeons among them were working in government sector and rest were non-government employee or self-employed. Self-employment as a dental surgeon was the main source of income for 179 (43.2%) of total respondents. Regarding the job satisfaction, 139 (33.6%) were moderately satisfied and 182 (44%) were not satisfied with their pay standard. With regards to further academic engagement, 88 (21.2%) respondents were enrolled in different postgraduation courses whereas 205 (49.5%) of the respondents were also engaged in learning activities to get admitted into postgraduation courses. Study recommended that newly graduated dental surgeons could be utilized by engaging into both urban and rural areas by creating scope in both government and nongovernment sectors. Further academic engagement may be ensured by initiating new courses of dentistry and by increasing number of affiliated institutes for post-graduation. Bangladesh Journal of Medical Education Vol.12(2) July 2021: 10-17

THE INCOME SITUATION IN AGRICULTURE AFTER POLAND ENTERED THE EUROPEAN UNION

The main purpose of the article was to assess Poland’s income situation in agriculture after the country acceded to the European Union. The analysis included, among others, changes in agricultural income per full-time employee and a comparison of household income of farmers and other professional groups. The sources of the materials were data from the Eurostat and CSO databases. The research period covered the years 2005–2018. The real income of the agricultural population in the analyzed period showed an upward trend but was still lower not only than the national average, but also the income of households of employees. Financial resources transferred from direct payments and structural funds under the Common Agricultural Policy had a significant impact on the improvement of the income situation of farmers.

Effective communications and individual donors: a case study

Background: The monies donated by individual donors to Healthy Minds Canada (HMC), a national charitable organization, have been decreasing since 2006. This Major Research Paper provides HMC with communication strategies to increase its funding. The strategies are based on the literature and on best practices. The literature review explores rhetoric as a method to appeal to donors. Other strategies that are examined include appeal letters, websites, and other communications such as providing donors with communication options and thanking donors. In addition, a comparative analysis is conducted between HMC and two other organizations, the Tourette Syndrome Foundation of Canada (TSFC) and Amyotrophic Lateral Scleroses Ontario (ALS Ontario). Conclusions: The analysis of rhetorical appeals determined that communications with donors should apply all three methods of Aristotle’s rhetorical theory of persuasion. These modes include the appeal to emotions (pathos), the appeal to reason (logos), and the appeal of personality or character (ethos). The exploration of appeal letters showed that HMC should thank donors for past or anticipated support, conclude with pleasantries, use negatively framed local mental health statistics, and include positive and moving stories. Moreover, images should be included where possible. Many recommendations are made for HMC’s website but in particular, engaging in social media is emphasized. Furthermore, in all communications to individual donors, HMC should provide these supporters with choices to receive direct mail or electronic mail, and offer opt-out options. Personal accounts can also be set up on HMC’s website that allow donors to select their communication preferences. It is also suggested that there be four mail-outs per year, the newsletter be recommenced, and thank-you letters be sent out within 24 hours of receiving a donation. Lastly, it is recommended that HMC hire another full-time employee to help with its donor communications.

Effective communications and individual donors: a case study

Background: The monies donated by individual donors to Healthy Minds Canada (HMC), a national charitable organization, have been decreasing since 2006. This Major Research Paper provides HMC with communication strategies to increase its funding. The strategies are based on the literature and on best practices. The literature review explores rhetoric as a method to appeal to donors. Other strategies that are examined include appeal letters, websites, and other communications such as providing donors with communication options and thanking donors. In addition, a comparative analysis is conducted between HMC and two other organizations, the Tourette Syndrome Foundation of Canada (TSFC) and Amyotrophic Lateral Scleroses Ontario (ALS Ontario). Conclusions: The analysis of rhetorical appeals determined that communications with donors should apply all three methods of Aristotle’s rhetorical theory of persuasion. These modes include the appeal to emotions (pathos), the appeal to reason (logos), and the appeal of personality or character (ethos). The exploration of appeal letters showed that HMC should thank donors for past or anticipated support, conclude with pleasantries, use negatively framed local mental health statistics, and include positive and moving stories. Moreover, images should be included where possible. Many recommendations are made for HMC’s website but in particular, engaging in social media is emphasized. Furthermore, in all communications to individual donors, HMC should provide these supporters with choices to receive direct mail or electronic mail, and offer opt-out options. Personal accounts can also be set up on HMC’s website that allow donors to select their communication preferences. It is also suggested that there be four mail-outs per year, the newsletter be recommenced, and thank-you letters be sent out within 24 hours of receiving a donation. Lastly, it is recommended that HMC hire another full-time employee to help with its donor communications.

POS0966 IDENTIFICATION OF PATIENTS AFFECTED WITH ANKYLOSING SPONDYLITIS AND INFLAMMATORY BOWEL DISEASE OVERLAP USING COLLAGEN BIOMARKERS

Background:Chronic inflammatory arthritis is a hallmark of Ankylosing Spondylitis (AS), where co-existence of inflammatory bowel disease, such as Crohn’s Disease (CD) is prominent. The clinical overlap of AS and CD has raised the hypothesis that these conditions may have similar pathophysiological mechanisms. Both indications are characterized by an altered extracellular matrix turnover, where particularly collagens are remodeled.Objectives:We investigated the association between biomarkers of collagen degradation in healthy controls and patients with AS, CD and AS/CD overlap, with the aim to investigate the biomarkers’ ability to identify patients with AS/CD overlap.Methods:Patients with AS fulfilling ASAS criteria (n=13), biopsy-proven CD (n=14), subjects with AS and CD overlap (n=10) and healthy controls (n=11) undergoing standard of care colonoscopies were included in the study. The collagen degradation biomarkers measuring type III, IV, VI and X collagen (C3M, C4M, C6M and C10C, respectively) were measured in EDTA plasma samples from all subject groups. Biomarkers were measured by competitive ELISAs. Statistical analysis was performed using an ANCOVA adjusted for age, an AUROC analysis and spearman correlations.Results:The collagen biomarker C4M was significantly higher in patients with AS/CD overlap compared to AS, CD and HCs (all p<0.0001, Figure 1A). The blood levels of C4M in AS patients were significantly lower than HC (p=0.0003), while CD also showed a lower level compared to HC though not significant (p=0.0798). No difference was found between AS and CD alone. In an AUROC analysis, C4M showed a complete separation between the patients with AS/CD overlap compared to HC, AS and CD with an AUC=1.00; p=0.0001. No differences were found between the patient groups for C3M, C6M and C10C (Figure 1, B-D). 91.3 % of patients with AS, 92.8% of patients with CD and 60 % of patients with AS and IBD overlap were actively treated with TNF-α inhibitors, which may explain the suppression of the collagen degradation biomarker levels in AS, CD and AS/IBD overlap compared to healthy controls[1,2]. No correlations were found between the collagen biomarkers and CRP, BASDAI, SCCAI or HBI scores.Conclusion:Degradation of type IV collagen quantified by C4M showed a complete separation of patients with AS/IBD overlap, compared to AS, CD and HC patients, which indicates an excessive collagen degradation and epithelial turnover. This biomarker could potentially be used to identify patients affected by both manifestations, and guide treatment decisions.References:[1]van Haaften WT, Mortensen JH, Dige AK, Grønbæk H, Hvas CL, Bay-Jensen AC, et al. Serological Biomarkers of Tissue Turnover Identify Responders to Anti-TNF Therapy in Crohn’s Disease: A Pilot Study. Clin Transl Gastroenterol. 2020;11:e00217.[2]Siebuhr AS, Bay-Jensen AC, Karsdal MA, Lories RJ, de Vlam K. CRP and a biomarker of type I collagen degradation, C1M, can differentiate anti-inflammatory treatment response in ankylosing spondylitis. Biomark Med. 2016;10:197–208.Figure 1.Levels of C4M (A), C3M (B), C6M (C) and C10C (D) in EDTA plasma from patients diagnosed with AS (n=13), CD (n=14), AS and CD overlap (n=10) and HC (n=11). Graphs are presented as Tukey box plots. Statistical significance: ****p<0.0001.Disclosure of Interests:Signe Holm Nielsen Employee of: Full time PostDoc at Nordic Bioscience and Technical University of Denmark, Andrew Stahly: None declared, Emilie H. Regner: None declared, Anne-Christine Bay-Jensen Shareholder of: Stocks at Nordic Bioscience, Employee of: Full-time employee at Nordic Bioscience, Morten Karsdal Shareholder of: Stocks at Nordic Bioscience, Employee of: Full-time employee at Nordic Bioscience, Kristine A. Kuhn: None declared.