Safety of the Combination of PERC and YEARS Rules in Patients With Low Clinical Probability of Pulmonary Embolism: A Retrospective Analysis of Two Large European Cohorts

BACKGROUND: This study aimed to determine the failure rate of a combination of the PERC and the YEARS rules for the diagnosis of pulmonary embolism (PE) in the emergency department (ED). METHODS: We performed a retrospective analysis of two European cohorts of emergency patients with low gestalt clinical probability of PE (PROPER and PERCEPIC). All patients we included were managed using a conventional strategy (D-dimer test, followed, if positive, by computed tomographic pulmonary angiogram (CTPA). We tested a diagnostic strategy that combined PERC and YEARS to rule out PE. The primary endpoint was a thromboembolic event diagnosed in the ED or at 3-months follow-up. Secondary endpoints included a thromboembolic event at baseline in the ED and a CTPA in the ED. Ninety-five percent confidence intervals (CIs) of proportions were calculated with the use of Wilson\u27s continuity correction. RESULTS: We analyzed 1,951 patients (mean ± SD age = 47 ± 18 years, 56% women) with an overall proportion of patients with PE of 3.5%. Both PERC and YEARS strategies were associated with 11 missed PE in the ED: failure rate 0.57 (95% CI = 0.32-1.02). At 3-month follow-up, the overall failure rate was 0.83% (95% CI = 0.51-1.35). Among the 503 patients who underwent a CTPA (26%), the use of the PERC-YEARS combination would have ruled out PE without CTPA in 249 patients (50% [95%CI = 45%-54%], absolute reduction 13% (95% CI = 11%-14%]). CONCLUSION: The combination of PERC then YEARS was associated with a low risk of PE diagnostic failure and would have resulted in a relative reduction of almost half of CTPA

Microarray evidence of glutaminyl cyclase gene expression in melanoma: implications for tumor antigen specific immunotherapy

BACKGROUND: In recent years encouraging progress has been made in developing vaccine treatments for cancer, particularly with melanoma. However, the overall rate of clinically significant results has remained low. The present research used microarray datasets from previous investigations to examine gene expression patterns in cancer cell lines with the goal of better understanding the tumor microenvironment. METHODS: Principal Components Analyses with Promax rotational transformations were carried out with 90 cancer cell lines from 3 microarray datasets, which had been made available on the internet as supplementary information from prior publications. RESULTS: In each of the analyses a well defined melanoma component was identified that contained a gene coding for the enzyme, glutaminyl cyclase, which was as highly expressed as genes from a variety of well established biomarkers for melanoma, such as MAGE-3 and MART-1, which have frequently been used in clinical trials of melanoma vaccines. CONCLUSION: Since glutaminyl cyclase converts glutamine and glutamic acid into a pyroglutamic form, it may interfere with the tumor destructive process of vaccines using peptides having glutamine or glutamic acid at their N-terminals. Finding ways of inhibiting the activity of glutaminyl cyclase in the tumor microenvironment may help to increase the effectiveness of some melanoma vaccines

MAGE-C2/CT10 Protein Expression Is an Independent Predictor of Recurrence in Prostate Cancer

The cancer-testis (CT) family of antigens is expressed in a variety of malignant neoplasms. In most cases, no CT antigen is found in normal tissues, except in testis, making them ideal targets for cancer immunotherapy. A comprehensive analysis of CT antigen expression has not yet been reported in prostate cancer. MAGE-C2/CT-10 is a novel CT antigen. The objective of this study was to analyze extent and prognostic significance of MAGE-C2/CT10 protein expression in prostate cancer. 348 prostate carcinomas from consecutive radical prostatectomies, 29 castration-refractory prostate cancer, 46 metastases, and 45 benign hyperplasias were immunohistochemically analyzed for MAGE-C2/CT10 expression using tissue microarrays. Nuclear MAGE-C2/CT10 expression was identified in only 3.3% primary prostate carcinomas. MAGE-C2/CT10 protein expression was significantly more frequent in metastatic (16.3% positivity) and castration-resistant prostate cancer (17% positivity; p<0.001). Nuclear MAGE-C2/CT10 expression was identified as predictor of biochemical recurrence after radical prostatectomy (p = 0.015), which was independent of preoperative PSA, Gleason score, tumor stage, and surgical margin status in multivariate analysis (p<0.05). MAGE-C2/CT10 expression in prostate cancer correlates with the degree of malignancy and indicates a higher risk for biochemical recurrence after radical prostatectomy. Further, the results suggest MAGE-C2/CT10 as a potential target for adjuvant and palliative immunotherapy in patients with prostate cancer

Preferential Amplification of CD8 Effector-T Cells after Transcutaneous Application of an Inactivated Influenza Vaccine: A Randomized Phase I Trial

Background: Current conventional vaccination approaches do not induce potent CD8 T-cell responses for fighting mostly variable viral diseases such as influenza, avian influenza viruses or HIV. Following our recent study on vaccine penetration by targeting of vaccine to human hair follicular ducts surrounded by Langerhans cells, we tested in the first randomized Phase-Ia trial based on hair follicle penetration (namely transcutaneous route) the induction of virus-specific CD8 T cell responses. Methods and Findings: We chose the inactivated influenza vaccine – a conventional licensed tetanus/influenza (TETAGRIP®) vaccine – to compare the safety and immunogenicity of transcutaneous (TC) versus IM immunization in two randomized controlled, multi-center Phase I trials including 24 healthy-volunteers and 12 HIV-infected patients. Vaccination was performed by application of inactivated influenza vaccine according to a standard protocol allowing the opening of the hair duct for the TC route or needle-injection for the IM route. We demonstrated that the safety of the two routes was similar. We showed the superiority of TC application, but not the IM route, to induce a significant increase in influenza-specific CD8 cytokine-producing cells in healthy-volunteers and in HIV-infected patients. However, these routes did not differ significantly for the induction of influenza-specific CD4 responses, and neutralizing antibodies were induced only by the IM route. The CD8 cell response is thus the major immune response observed after TC vaccination. Conclusions: This Phase Ia clinical trial (Manon05) testing an anti-influenza vaccine demonstrated that vaccines designed for antibody induction by the IM route, generate vaccine-specific CD8 T cells when administered transcutaneously. These results underline the necessity of adapting vaccination strategies to control complex infectious diseases when CD8 cellular responses are crucial. Our work opens up a key area for the development of preventive and therapeutic vaccines for diseases in which CD8 cells play a crucial role

Identification of constraints to banana production in three ecoregions of Rwanda

A survey was carried out in 108 fields in Rwanda to identify constraints to banana productivity in three regions: Ruhengeri (young volcanic soils), Gitarama–Butare (soils derived from granitic rocks), and Kibungo (weathered soils from schistose materials). Data were recorded for the single cultivar Intuntu (AAA)EA). We recorded management practices, and measured nutrient contents in plant and soil, root health parameters and nematode populations. Bunch weights were estimated (r2 = 0.6?) using plant girth and number of fingers. Yield differences were caused by two major factors: soil fertility and management standards. The cation exchange capacity of soils (range: 5-40 cmolc kg-1) was directly governed by organic matter content. Leaf K concentration was strongly related to soil exchangeable K level. Potassium and nitrogen deficiencies were widespread especially in Butare) Gitarama where most soils exhibited exchangeable K levels below 1.5 cmolc kg-1. Two key parameters emerged from management practices: mulching and plant density. The thickness of mulch was significantly higher in Kibungo (leading to more yield???). Plant density was the major factor affecting banana yield: the highest densities (3501 plants/ha) and yields (53.6 t/ha, cycle) were recorded in Ruhengeri, followed by Butare (2631 plants/ha, 27.4 t/ha, cycle) and Kibungo (1600 plants/ha, 25.6 t/ha, cycle). Intercropping had no effect on banana yield. The population density Pratylenchus goodeyi mostly ranged between 0 and 80,000 nematodes/100 g root. We did not detect any evidence of direct impact of nematode population on banana yield

Two new tumor-specific antigenic peptides encoded by gene MAGE-C2 and presented to cytolytic T lymphocytes by HLA-A2

We have identified 2 antigens recognized by several melanoma-specific cytolytic T lymphocyte clones isolated from a melanoma patient with a clinical history of tumor regression after immunotherapy. Both antigens are presented by HLA-A2 and encoded by gene MAGE-C2, a cancer-germline gene shown previously to be silent in normal somatic tissues and expressed in 40% of melanomas and in other tumor types. One antigen corresponds to peptide ALKDVEERV(336-344), whereas the other corresponds to peptide LLFGLALIEV(191-200). The CTL clones recognizing these 2 peptides also recognized allogeneic tumor cell lines expressing MAGE-C2 and HLA-A2. These 2 new peptides are the first known MAGE-C antigens and represent promising targets for cancer immunotherapy

A Computer Aided Design of a Secure Registration Protocol

peer reviewedWe use the formal language LOTOS to specify a registration protocol between a user and a Trusted Third Party, that requires mutual authentication. We explain how a model-based verification method can be used to verify its robustness to attacks by an intruder. This method is also used to find a simpler protocol that remains secure