BTLA mediates inhibition of human tumor-specific CD8+ T cells that can be partially reversed by vaccination.

The function of antigen-specific CD8+ T cells, which may protect against both infectious and malignant diseases, can be impaired by ligation of their inhibitory receptors, which include CTL-associated protein 4 (CTLA-4) and programmed cell death 1 (PD-1). Recently, B and T lymphocyte attenuator (BTLA) was identified as a novel inhibitory receptor with structural and functional similarities to CTLA-4 and PD-1. BTLA triggering leads to decreased antimicrobial and autoimmune T cell responses in mice, but its functions in humans are largely unknown. Here we have demonstrated that as human viral antigen-specific CD8+ T cells differentiated from naive to effector cells, their surface expression of BTLA was gradually downregulated. In marked contrast, human melanoma tumor antigen-specific effector CD8+ T cells persistently expressed high levels of BTLA in vivo and remained susceptible to functional inhibition by its ligand herpes virus entry mediator (HVEM). Such persistence of BTLA expression was also found in tumor antigen-specific CD8+ T cells from melanoma patients with spontaneous antitumor immune responses and after conventional peptide vaccination. Remarkably, addition of CpG oligodeoxynucleotides to the vaccine formulation led to progressive downregulation of BTLA in vivo and consequent resistance to BTLA-HVEM-mediated inhibition. Thus, BTLA activation inhibits the function of human CD8+ cancer-specific T cells, and appropriate immunotherapy may partially overcome this inhibition.

Basic life support teaching in the second year predraduate medical curriculum: quality of acquisition after 6 months

Purpose of the study: Basic life support (BLS) and automated externaldefibrillation (AED) represent important skills to be acquired duringpregraduate medical training. Since 3 years, our medical school hasintroduced a BLS-AED course (with certification) for all second yearmedical students. Few reports about quality and persistence over timeof BLS-AED learning are available to date in the medical literature.Comprehensive evaluation of students' acquired skills was performedat the end of the 2008 academic year, 6 month after certification.Materials and methods: The students (N = 142) were evaluated duringa 9 minutes «objective structured clinical examination» (OSCE) station.Out of a standardized scenario, they had to recognize a cardiac arrestsituation and start a resuscitation process. Their performance wererecorded on a PC using an Ambuman(TM) mannequin and the AmbuCPR software kit(TM) during a minimum of 8 cycles (30 compressions:2 ventilations each). BLS parameters were systematically checked. Nostudent-rater interactions were allowed during the whole evaluation.Results: Response of the victim was checked by 99% of the students(N = 140), 96% (N = 136) called for an ambulance and/or an AED. Openthe airway and check breathing were done by 96% (N = 137), 92% (N =132) gave 2 rescue breaths. Pulse was checked by 95% (N=135), 100%(N = 142) begun chest compression, 96% (N = 136) within 1 minute.Chest compression rate was 101 ± 18 per minute (mean ± SD), depthcompression 43 ± 8 mm, 97% (N = 138) respected a compressionventilationratio of 30:2.Conclusions: Quality of BLS skills acquisition is maintained during a6-month period after a BLS-AED certification. Main targets of 2005 AHAguidelines were well respected. This analysis represents one of thelargest evaluations of specific BLS teaching efficiency reported. Furtherfollow-up is needed to control the persistence of these skills during alonger time period and noteworthy at the end of the pregraduatemedical curriculum.

High constant incidence of second primary colorectal cancer.

Patients who had a colorectal cancer have a 1.5- to 2-fold excess risk of a second colorectal cancer as compared to the general population, the excess being higher at younger age at diagnosis. To further investigate the risk and the age-relation of the incidence of second primary colorectal cancer, we considered 9,389 first colon and rectal cancers registered in the Vaud Cancer Registry, Switzerland, between 1974 and 2008, and followed-up to the end of 2008 for a total of 44,113 person-years. There were 136 second colorectal cancers versus 90.5 expected, corresponding to a standardized incidence ratio (SIR) of 1.5 (95% confidence interval, CI, 1.3-1.8). The SIRs were not heterogeneous between men and women, and in strata of calendar year at diagnosis, duration of follow-up, and subsite. However, the SIR was 7.5 (95% CI 4.2-12.4) for subjects diagnosed below age 50 and declined thereafter to reach 1.0 (95% CI 0.6-1.6) at age 80 or over. Consequently, the incidence of second primary colorectal cancer was stable, and exceedingly high, around 300-400/100,000 between age 30-39 and 70 or over. This age pattern is consistent with the existence of a single mutational event in a population of highly susceptible individuals.

Impact of bulk cardiac motion on right coronary MR angiography and vessel wall imaging.

The purpose of this study was to investigate the impact of in-plane coronary artery motion on coronary magnetic resonance angiography (MRA) and coronary MR vessel wall imaging. Free-breathing, navigator-gated, 3D-segmented k-space turbo field echo ((TFE)/echo-planar imaging (EPI)) coronary MRA and 2D fast spin-echo coronary vessel wall imaging of the right coronary artery (RCA) were performed in 15 healthy adult subjects. Images were acquired at two different diastolic time periods in each subject: 1) during a subject-specific diastasis period (in-plane velocity <4 cm/second) identified from analysis of in-plane coronary artery motion, and 2) using a diastolic trigger delay based on a previously implemented heart-rate-dependent empirical formula. RCA vessel wall imaging was only feasible with subject-specific middiastolic acquisition, while the coronary wall could not be identified with the heart-rate-dependent formula. For coronary MRA, RCA border definition was improved by 13% (P < 0.001) with the use of subject-specific trigger delay (vs. heart-rate-dependent delay). Subject-specific middiastolic image acquisition improves 3D TFE/EPI coronary MRA, and is critical for RCA vessel wall imaging.

Automated identification of minimal myocardial motion for improved image quality on MR angiography at 3 T

OBJECTIVE: Imaging during a period of minimal myocardial motion is of paramount importance for coronary MR angiography (MRA). The objective of our study was to evaluate the utility of FREEZE, a custom-built automated tool for the identification of the period of minimal myocardial motion, in both a moving phantom at 1.5 T and 10 healthy adults (nine men, one woman; mean age, 24.9 years; age range, 21-32 years) at 3 T. CONCLUSION: Quantitative analysis of the moving phantom showed that dimension measurements approached those obtained in the static phantom when using FREEZE. In vitro, vessel sharpness, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) were significantly improved when coronary MRA was performed during the software-prescribed period of minimal myocardial motion (p < 0.05). Consistent with these objective findings, image quality assessments by consensus review also improved significantly when using the automated prescription of the period of minimal myocardial motion. The use of FREEZE improves image quality of coronary MRA. Simultaneously, operator dependence can be minimized while the ease of use is improved.

3D coronary vessel wall imaging utilizing a local inversion technique with spiral image acquisition.

Current 2D black blood coronary vessel wall imaging suffers from a relatively limited coverage of the coronary artery tree. Hence, a 3D approach facilitating more extensive coverage would be desirable. The straightforward combination of a 3D-acquisition technique together with a dual inversion prepulse can decrease the effectiveness of the black blood preparation. To minimize artifacts from insufficiently suppressed blood signal of the nearby blood pools, and to reduce residual respiratory motion artifacts from the chest wall, a novel local inversion technique was implemented. The combination of a nonselective inversion prepulse with a 2D selective local inversion prepulse allowed for suppression of unwanted signal outside a user-defined region of interest. Among 10 subjects evaluated using a 3D-spiral readout, the local inversion pulse effectively suppressed signal from ventricular blood, myocardium, and chest wall tissue in all cases. The coronary vessel wall could be visualized within the entire imaging volume.

Assessment of the carotid artery by MRI at 3T: a study on reproducibility

PURPOSE: To examine the reproducibility of carotid artery dimension measurements using 3T MRI. MATERIALS AND METHODS: Ten healthy volunteers underwent three scans on two occasions for assessment of total vessel wall area (TVWA), total luminal area (TLA), and minimum (MinT) and maximum (MaxT) vessel wall thickness. A double inversion-recovery (IR) fast gradient-echo (FGRE) sequence was used on a commercial 3T system. During the first visit the subjects were scanned twice. The third scan was performed at least four days later. One observer traced all scans, and a second observer retraced the first scan series. RESULTS: For TVWA an interclass correlation (ICC) of 0.994 was calculated with all three scans taken into account. The interobserver ICC was 0.984. The agreement between the scans for TLA showed an ICC of 0.982 with an interobserver ICC of 0.998. For MinT and MaxT an ICC of 0.843 and 0.935 were calculated, with interobserver ICCs of 0.860 and 0.726, respectively. CONCLUSION: With the use of a commercial 3T MR system, TVWA, TLA, and wall thickness measurements of the carotid artery can be assessed with good reproducibility.

Pluralité des corps. 2. Le corps vécu [Multifaceted body. 2. The lived body].

Le corps humain est l'objet privilégié d'action de la médecine, mais aussi réalité vécue, image, symbole, représentation et l'objet d'interprétation et de théorisation. Tous ces éléments constitutifs du corps influencent la façon dont la médecine le traite. Dans cette série de trois articles, nous abordons le corps sous différentes perspectives : médicale (1), phénoménologique (2), psychosomatique et socio-anthropologique (3). Nous proposons dans ce deuxième article de faire une différence entre le corps comme objet de connaissance ou de représentation et le corps tel qu'il est vécu (corps propre). Cette distinction, qui trouve son origine dans la psychiatrie phénoménologique, permet une approche du vécu des patients qui ne se limite pas aux catégories somatiques ou psychiques classiques en la matière. The human body is the object upon which medicine is acting, but also lived reality, image, symbol, representation and the object of elaboration and theory. All these elements which constitute the body influence the way medicine is treating it. In this series of three articles, we address the human body from various perspectives: medical (1), phenomenological (2), psychosomatic and socio-anthropological (3). This second article distinguishes between the body as an object of knowledge or representation and the way the body is lived. This distinction which originates in phenomenological psychiatry aims to understand how the patient experiences his body and to surpass the classical somatic and psychiatric classifications.

Immunobiology of human papillomavirus infection and vaccination - implications for second generation vaccines.

Prophylactic human papillomavirus (HPV) L1 virus like particle (VLP) vaccines have been shown, in large clinical trials, to be very immunogenic, well-tolerated and highly efficacious against genital disease caused by the vaccine HPV types. However these vaccines, at the present, protect against only two of the 15 oncogenic genital HPV types, they are expensive, delivered by intramuscular injection and require a cold chain. The challenges are to develop cheap, thermo-stable vaccines that can be delivered by non-injectable methods that provide long term (decades) protection at mucosal surfaces to most, if not all, oncogenic HPV types that is as good as the current VLP vaccines. Current approaches include L1 capsomers, L2 protein and peptides, delivery via recombinant L1 bacterial and viral vectors and large-scale VLP production in plants. Rational design and successful development of such vaccines will be based on an understanding of the immune response, and particularly the 'cross talk' between the innate and adaptive responses. This will be central in the development of adjuvants and vaccine formulations that induce the response to provide effective protection.

Validation of tissue modelization and classification techniques in T1-weighted MR brain images

We propose a deep study on tissue modelization andclassification Techniques on T1-weighted MR images. Threeapproaches have been taken into account to perform thisvalidation study. Two of them are based on FiniteGaussian Mixture (FGM) model. The first one consists onlyin pure gaussian distributions (FGM-EM). The second oneuses a different model for partial volume (PV) (FGM-GA).The third one is based on a Hidden Markov Random Field(HMRF) model. All methods have been tested on a DigitalBrain Phantom image considered as the ground truth. Noiseand intensity non-uniformities have been added tosimulate real image conditions. Also the effect of ananisotropic filter is considered. Results demonstratethat methods relying in both intensity and spatialinformation are in general more robust to noise andinhomogeneities. However, in some cases there is nosignificant differences between all presented methods.