Civil Society Monitoring Report on the Implementation of the National Roma Integration Strategy and Decade Action Plan in 2012 in: Hungary

In autumn 2012, the Decade of Roma Inclusion Secretariat Foundation commissioned the Hungarian Civil Consortium to review the first year of the implementation of the National Social Inclusion Strategy of Hungary (hereinafter referred to as NRIS1or the Strategy), with a special focus on the actions and policies targeting Roma inclusion. All the findings are based on interviews, document reviews and citizen consultations that served as a forum for Roma and pro-Roma NGOs, municipalities and representatives of Roma self-governments.The Hungarian Strategy targets several vulnerable groups, for example children, people living in less developed regions and also Roma. Thus, it follows the "explicit but not exclusive targeting" principle, congruent with the 10 Common Basic Principles of Roma Inclusion. Nevertheless, the lack of a very clear Roma focus may pose challenges to a successful and robust policy-making, while various interventions in sectoral policies (for example, change of legislation, launching of programmes, etc.) and partial interventions launched in parallel may further weaken the efforts made in favour of Roma inclusion and the Strategy's implementation

Tumor-Associated Disialylated Glycosphingolipid Antigen-Revealing Antibodies Found in Melanoma Patients' Immunoglobulin Repertoire Suggest a Two-Direction Regulation Mechanism Between Immune B Cells and the Tumor

There is far less information available about the tumor infiltrating B (TIL-B) cells, than about the tumor infiltrating T cells. We focused on discovering the features and potential role of B lymphocytes in solid tumors. Our project aimed to develop innovative strategies to define cancer membrane structures. We chose two solid tumor types, with variable to considerable B cell infiltration. The strategy we set up with invasive breast carcinoma, showing medullary features, has been introduced and standardized in metastatic melanoma. After detecting B lymphocytes by immunohistochemistry, VH-JH, Vκ-Jκ immunoglobulin rearranged V region genes were amplified by RT-PCR, from TIL-B cDNA. Immunoglobulin variable-region genes of interest were cloned, sequenced, and subjected to a comparative DNA analysis. Single-chain variable (scFv) antibody construction was performed in selected cases to generate a scFv library and to test tumor binding capacity. DNA sequence analysis revealed an overrepresented VH3-1 cluster, represented both in the breast cancer and the melanoma TIL-B immunoglobulin repertoire. We observed that our previously defined anti GD3 ganglioside-binder antibody-variable region genes were present in melanoma as well. Our antibody fragments showed binding potential to disialylated glycosphingolipids (GD3 ganglioside) and their O acetylated forms on melanoma cancer cells. We conclude that our results have a considerable tumor immunological impact, as they reveal the power of TIL-B cells to recognize strong tumor-associated glycosphingolipid structures on melanomas and other solid tumors. As tumor-derived gangliosides affect immune cell functions and reduce the B lymphocytes' antibody production, we suspect an important B lymphocyte and cancer cell crosstalk mechanism. We not only described the isolation and specificity testing of the tumor infiltrating B cells, but also showed the TIL-B cells' highly tumor-associated GD3 ganglioside-revealing potential in melanomas. The present data help to identify new cancer-associated biomarkers that may serve for novel cancer diagnostics. The two-direction regulation mechanism between immune B cells and the tumor could eventually be developed into an innovative cancer treatment strategy

Ion acceleration with few cycle relativistic laser pulses from foil targets

Ion acceleration resulting from the interaction of 11 fs laser pulses of ~35 mJ energy with ultrahigh contrast (<10^-10), and 10^19 W/cm^2 peak intensity with foil targets made of various materials and thicknesses at normal (0-degree) and 45-degree laser incidence is investigated. The maximum energy of the protons accelerated from both the rear and front sides of the target was above 1 MeV. A conversion efficiency from laser pulse energy to proton beam is estimated to be as high as ~1.4 % at 45-degree laser incidence using a 51 nm-thick Al target. The excellent laser contrast indicates the predominance of vacuum heating via the Brunels effect as an absorption mechanism involving a tiny pre-plasma of natural origin due to the Gaussian temporal laser pulse shape. Experimental results are in reasonable agreement with theoretical estimates where proton acceleration from the target rear into the forward direction is well explained by a TNSA-like mechanism, while proton acceleration from the target front into the backward direction can be explained by the formation of a charged cavity in a tiny pre-plasma. The exploding Coulomb field from the charged cavity also serves as a source for forward-accelerated ions at thick targets.Comment: 12 pages, 7 figures

Emergence of Collective Territorial Defense in Bacterial Communities: Horizontal Gene Transfer Can Stabilize Microbiomes

Multispecies bacterial communities such as the microbiota of the gastrointestinal tract can be remarkably stable and resilient even though they consist of cells and species that compete for resources and also produce a large number of antimicrobial agents. Computational modeling suggests that horizontal transfer of resistance genes may greatly contribute to the formation of stable and diverse communities capable of protecting themselves with a battery of antimicrobial agents while preserving a varied metabolic repertoire of the constituent species. In other words horizontal transfer of resistance genes makes a community compatible in terms of exoproducts and capable to maintain a varied and mature metagenome. The same property may allow microbiota to protect a host organism, or if used as a microbial therapy, to purge pathogens and restore a protective environment

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Female urethral dilatation (bougierung): a case report

Abstract Background Primary bladder neck obstruction is a rare clinical entity, reported to be responsible for 2.7–8% of lower urinary tract symptoms. It can lead to various urinary storage and voiding symptoms. The mainstay of treatment of female urethral strictures is urethral dilatation. Despite the long history of this method, it is unclear how far the female urethra should be dilated in correlation with residual urine volume. Case presentation A 79-year-old Caucasian woman presented to our institute with urgency (12–15 times/day), nocturia (3 times/night), and reoccurring urinary tract infections. A physical examination revealed no anatomical malformation in her genital organs, 150 mL post-void urine retention, and a significant narrowing in the mid-segment of the urethra (4 mm). After informed consent, our patient underwent urethral dilatation ranging from Ch9 (3 mm) to Ch39 (13 mm), and reported no symptoms at the 4-week follow-up, with no post-void residual urine. Conclusions The relatively low (around 50%) success rate of urethral dilatation might be improved by the utilization of wider dilatators, and the relaxation of the pubourethral ligament, achieved by a gentle downward saggital push during the intervention, although long-term studies with a large number of participants are necessary to prove our hypothesis