Економіко-математичне моделювання оптимізації фінансування заходів щодо збереження біорізноманіття (Economic modeling optimization funding for biodiversity)

Удосконалено організаційно-економічний механізм збереження біорізноманіття України відповідно до умов збалансованого розвитку. Обґрунтовано концептуальні положення збереження біорізноманіття, які базуються на соціо-еколого-економічній оцінці функціонування екосистем. Розроблено методологічні підходи до врахування збереження біорізноманіття у національних рахунках держави, що ґрунтуються на визначенні економічної оцінки функціонування природних екосистем. Поглиблено методологію збереження біорізноманіття на основі поєднання і розвитку теорії систем та інституціональної економіки. Розширено механізми застосування інноваційних інструментів збереження біорізноманіття. Розроблено концептуальні підходи маркетингової стратегії розвитку природно-заповідних територій на основі формування їх позитивного іміджу й адаптації до ринкових умов. (The investigation is devoted to the organization-economic mechanism improvement of the biodiversity conservation in Ukraine in relation to the sustainable development conditions. The conceptual principles of the biodiversity that are based on ecological and social and economic assessment of ecosystem functioning were scientifically proved for the first time in this research. The methodological approaches to the biodiversity conservation in the national state accounts were developed and they are based on the new calculations of the economic evaluation of the natural ecosystem functioning. The methodology and tools of the economic mechanism for resolving environmental conflicts at international level are improved. The methodology of the biodiversity conservation which is based on the institutional economics theory and the systems theory was improved. The innovative mechanisms for biodiversity conservation tools were expanded.

Additional file 2: of Splenic vein resection together with the pancreatic parenchyma versus separated resection after isolation of the parenchyma during distal pancreatectomy (COSMOS-DP trial): study protocol for a randomised controlled trial

SPIRIT 2013 Checklist: Recommended items to address in a clinical trial protocol and related documents. (DOC 121 kb

Image_1_Immunological analysis of hybrid neoantigen peptide encompassing class I/II neoepitope-pulsed dendritic cell vaccine.jpeg

Neoantigens/ are tumor-specific antigens that evade central immune tolerance mechanisms in the thymus. Long-term tumor-specific cytotoxic T lymphocyte activity maintenance requires class II antigen-reactive CD4+ T cells. We had previously shown that intranodal vaccination with class I neoantigen peptide-pulsed dendritic cells (DCs) induced a robust immune response in a subset of patients with metastatic cancer. The present study aimed to perform a detailed ex vivo analysis of immune responses in four patients receiving an intranodal hybrid human leukocyte antigen class II neoantigen peptide encompassing a class I neoantigen epitope (hybrid neoantigen)-pulsed DC vaccine. After vaccination, strong T-cell reactions against the hybrid class II peptide and the class I-binding neoantigen peptide were observed in all four patients. We found that hybrid class II neoantigen peptide-pulsed DCs stimulated CD4+ T cells via direct antigen presentation and CD8+ T cells via cross-presentation. Further, we demonstrated that hybrid class II peptides encompassing multiple class I neoantigen epitope-pulsed DCs could present multiple class I peptides to CD8+ T cells via cross-presentation. Our findings provide insight into the mechanisms underlying hybrid neoantigen-pulsed DC vaccine therapy and suggest future neoantigen vaccine design.</p

BRCAness as a Biomarker for Predicting Prognosis and Response to Anthracycline-Based Adjuvant Chemotherapy for Patients with Triple-Negative Breast Cancer

<div><p>Background</p><p>Triple-negative breast cancer (TNBC) is a heterogeneous tumor that encompasses many different subclasses of the disease. In this study, we assessed BRCAness, defined as the shared characteristics between sporadic and <i>BRCA1</i>-mutated tumors, in a large cohort of TNBC cases.</p><p>Methods</p><p>The BRCAness of 262 patients with primary TNBCs resected between January 2004 and December 2014 was determined through the isolation of DNA from tumor tissue. Classification of BRCAness was performed using multiple ligation-dependent probe amplification (MLPA). The tumor subtypes were determined immunohistochemically using resected specimens.</p><p>Results</p><p>Of the 262 TNBCs, the results of the MLPA assays showed that 174 (66.4%) tumors had BRCAness. Patients with BRCAness tumors were younger than patients with non-BRCAness tumors (<i>P</i> = 0.003). There was no significant difference between the two groups regarding their pathological stages. The BRCAness group had a significantly shorter recurrence-free survival (RFS) compared with the non-BRCAness group (<i>P</i> = 0.04) and had a shorter overall survival (OS) although this did not reach statistical significance. Adjuvant treatments with anthracycline-based regimens provided significantly greater benefits to the BRCAness group (<i>P</i> = 0.003 for RFS, and <i>P</i> = 0.03 for OS). Multivariate Cox proportional hazard model analysis showed that BRCAness was an independent negative prognostic factor, and the anthracycline-based adjuvant chemotherapy was an independent positive prognostic factor for both RFS and OS in TNBC.</p><p>Conclusions</p><p>The 66.4% patients of TNBCs showed BRCAness. BRCAness is essential as a biomarker in the subclassification of TNBCs and might be of use for predicting their prognosis. Furthermore, this biomarker might be a predictive factor for the effectiveness of anthracycline-based adjuvant chemotherapy for patients with TNBCs.</p></div

Patients and tumor characteristics (<i>n</i> = 262).

<p>Patients and tumor characteristics (<i>n</i> = 262).</p

Kaplan–Meier analysis of patients who received anthracycline-based adjuvant chemotherapy versus non-anthracycline-based adjuvant chemotherapy.

<p>(A) Recurrence-free survival (RFS) of BRCAness tumors (<i>n</i> = 126). (B) Overall survival (OS) of BRCAness tumors (<i>n</i> = 126). (C) RFS of non-BRCAness tumors (<i>n</i> = 53). (D) OS of non-BRCAness tumors (<i>n</i> = 53). Anthracycline or Anthra, anthracycline-based adjuvant chemotherapy; Non-Anthracycline or Non-Anthra, non-anthracycline-based adjuvant chemotherapy.</p

Cox proportional hazards model for recurrence-free survival and overall survival (<i>n</i> = 262).

<p>Cox proportional hazards model for recurrence-free survival and overall survival (<i>n</i> = 262).</p

Kaplan–Meier analysis of patients with TNBC (<i>n</i> = 262).

<p>(A) Recurrence-free survival of BRCAness tumors versus non-BRCAness tumors. (B) Overall survival of BRCAness tumors versus non-BRCAness tumors.</p