Fine structural variations of alphabeta TCRs selected by vaccination with natural versus altered self-antigen in melanoma patients

Immunotherapy of cancer is often performed with altered "analog" peptide Ags optimized for HLA class I binding, resulting in enhanced immunogenicity, but the induced T cell responses require further evaluation. Recently, we demonstrated fine specificity differences and enhanced recognition of naturally presented Ag by T cells after vaccination with natural Melan-A/MART-1 peptide, as compared with analog peptide. In this study, we compared the TCR primary structures of 1489 HLA-A*0201/Melan-A26-35-specific CD8 T cells derived from both cohorts of patients. Although a strong preference for TRAV12-2 segment usage was present in nearly all patients, usage of particular TRAJ gene segments and CDR3 composition differed slightly after vaccination with natural vs analog peptide. Moreover, TCR β-chain repertoires were broader after natural than analog peptide vaccination. In all patients, we observed a marked conservation of the CDR3β amino acid composition with recurrent sequences centered on a glycyl-leucyl/valyl/alanyl-glycyl motif. In contrast to viral-specific TCR repertoires, such "public" motifs were primarily expressed by nondominant T cell clonotypes, which contrasted with "private" CDR3β signatures frequently found in T cell clonotypes that dominated repertoires of individual patients. Interestingly, no differences in functional avidity were observed between public and private T cell clonotypes. Collectively, our data indicate that T cell repertoires generated against natural or analog Melan-A peptide exhibited slightly distinct but otherwise overlapping and structurally conserved TCR features, suggesting that the differences in binding affinity/avidity of TCRs toward pMHC observed in the two cohorts of patients are caused by subtle structural TCR variations.

Prevalence of measured and self-reported multimorbidity in the Swiss-CoLaus population-based study

Introduction: The prevalence of multimorbidity (MM) in hospitalized patients is increasing and recognized as an important factor that may modify the strategies of treatment and increase the length of stay. Little is currently known about the prevalence of MM in the general population and if measured or self-reported diseases are different in the outpatient setting compared to hospitalized patients. The objective of the study was, therefore, to assess the prevalence of self-reported and measured MM in representative sample of the general population aged 35-75 years in Switzerland. Method: Data were obtained from the population based CoLaus Study: 3712 participants (1965 women, 50±9 years). MM was defined as presenting >=2 morbidities according to a list of 27 items (either measured or self-reported data, according to Barret et al.) or a Functional Comorbidity Index (FCI) (18 items, measured only). Results: The prevalence of MM according to these three definitions is summarized in the table 1. For all definitions prevalence of MM was higher in women, elderly participants, those with lower education levels, Swiss nationals, former smokers and obese participants. The prevalence of MM when measured data were used was significantly higher than according to self-reported (p<0.001). Multivariate analysis confirmed most of these associations, except that no difference was found for educational level and for overweight participants. Conclusion: The prevalence of MM is high in the general population, ranging from 13.8 and 50.3% even in the younger age group. The prevalence is higher in women, and increases with age and weight. The prevalence varies considerably according to the definition and is lower when using self-reported compared to measured data.

Self-perception of aging and vulnerability to adverse outcomes at the age of 65-70 years.

OBJECTIVES. This study examines the relationship between self-perception of aging and vulnerability to adverse outcomes in adults aged 65-70 years using data from a cohort of 1,422 participants in Lausanne, Switzerland. METHODS: A positive or negative score of perception of aging was established using the Attitudes Toward Own Aging subscale including 5 items of the Philadelphia Geriatric Center Morale Scale. Falls, hospitalizations, and difficulties in basic and instrumental activities of daily living (ADL) collected in the first 3 years of follow-up were considered adverse outcomes. The relationship between perception and outcomes were evaluated using multiple logistic regression models adjusting for chronic medical conditions, depressive feelings, living arrangement, and socioeconomic characteristics. RESULTS: The strongest associations of self-perception of aging with outcomes were observed for basic and instrumental ADL. Associations with falls and hospitalizations were not constant but could be explained by health characteristics. CONCLUSIONS: A negative self-perception of aging is an indicator of risk for future disability in ADL. Factors such as a low-economic status, living alone, multiple chronic medical conditions, and depressive feelings contribute to a negative self-perception of aging but do not explain the relationship with incident activities of daily living disability.

Do Objective Measures of Blood Alcohol Concentrations Make More Sense than Self-reports in Emergency Department Studies?

Purpose: Concerns about self-reports have led to calls for objective measures of blood alcohol concentration (BAC). The present study compared objective measures with self-reports. Methods: BAC from breath or blood samples were obtained from 272 randomly sampled injured patients who were admitted to a Swiss emergency department (ED). Self-reports were compared a) between those providing and refusing a BAC test, and b) to estimated peak BAC (EPBAC) values based on BACs using the Widmark formula. Results: Those providing BACs were significantly (P < 0.05) younger, more often male, and less often reported alcohol consumption before injury, but consumed higher quantities when drinking. Eighty-eight percent of those with BAC measures gave consistent reports (positive or negative). Significantly more patients reported consumption with negative BAC measures (N = 29) than vice versa (N = 3). Duration of consumption and times between injury and BAC measurement predicted EPBAC better than did the objective BAC measure. Conclusions: There is little evidence that patients who provide objective BAC measures deliberately conceal consumption. ED studies must rely on self-reports, eg, take the time period between injury and ED admission into account. Clearly, objective measures are of clinical relevance, eg, to provide optimal treatment in the ED. However, they may be less relevant to establishing effects in an epidemiologic sense, such as estimating risk relationships. In this respect, efforts to increase the validity and reliability of self-reports should be preferred over the collection of additional objective measures.

Efficient self-synchronised blind audio watermarking system based on time domain and FFT amplitude modification

Many audio watermarking schemes divide the audio signal into several blocks such that part of the watermark is embedded into each of them. One of the key issues in these block-oriented watermarking schemes is to preserve the synchronisation, i.e. to recover the exact position of each block in the mark recovery process. In this paper, a novel time domain synchronisation technique is presented together with a new blind watermarking scheme which works in the Discrete Fourier Transform (DFT or FFT) domain. The combined scheme provides excellent imperceptibility results whilst achieving robustness against typical attacks. Furthermore, the execution of the scheme is fast enough to be used in real-time applications. The excellent transparency of the embedding algorithm makes it particularly useful for professional applications, such as the embedding of monitoring information in broadcast signals. The scheme is also compared with some recent results of the literature.

Prevention and management of potential adverse events during transapical aortic valve replacement.

BACKGROUND AND AIM OF THE STUDY: Transapical transcatheter aortic valve replacement (TAVR) is a new minimally invasive technique with a known risk of unexpected intra-procedural complications. Nevertheless, the clinical results are good and the limited amount of procedural adverse events confirms the usefulness of a synergistic surgical/anesthesiological management in case of unexpected emergencies. METHODS: A review was made of the authors' four-year database and other available literature to identify major and minor intra-procedural complications occurring during transapical TAVR procedures. All implants were performed under general anesthesia with a balloon-expandable Edwards Sapien stent-valve, and followed international guidelines on indications and techniques. RESULTS: Procedural success rates ranged between 94% and 100%. Life-threatening apical bleeding occurred very rarely (0-5%), and its incidence decreased after the first series of implants. Stent-valve embolization was also rare, with a global incidence ranging from 0-2%, with evidence of improvement after the learning curve. Rates of valve malpositioning ranged from 0% to < 3%, whereas the risk of coronary obstruction ranged from 0% to 3.5%. Aortic root rupture and dissection were dramatic events reported in 0-2% of transapical cases. Stent-valve malfunction was rarely reported (1-2%), whereas the valve-in-valve bailout procedure for malpositioning, malfunctioning or severe paravalvular leak was reported in about 1.0-3.5% of cases. Sudden hemodynamic management and bailout procedures such as valve-in-valve rescue or cannulation for cardiopulmonary bypass were more effective when planned during the preoperative phase. CONCLUSION: Despite attempts to avoid pitfalls, complications during transapical aortic valve procedures still occur. Preoperative strategic planning, including hemodynamic status management, alternative cannulation sites and bailout procedures, are highly recommended, particularly during the learning curve of this technique.

Superior flow for bridge to life with self-expanding venous cannulas.

BACKGROUND: Recently, a compact cardiopulmonary support (CPS) system designed for quick set-up for example, during emergency cannulation, has been introduced. Traditional rectilinear percutaneous cannulas are standard for remote vascular access with the original design. The present study was designed to assess the potential of performance increase by the introduction of next-generation, self-expanding venous cannulas, which can take advantage of the luminal width of the venous vasculature despite a relatively small access orifice. METHODS: Veno-arterial bypass was established in three bovine experiments (69+/-10 kg). The Lifebridge (Lifebridge GmbH, Munich, Germany) system was connected to the right atrium in a trans-jugular fashion with various venous cannulas; and the oxygenated blood was returned through the carotid artery with a 17 F percutaneous cannula. Two different venous cannulas were studied, and the correlation between the centrifugal pump speed (1500-3900 RPM), flow and the required negative pressure on the venous side was established: (A) Biomedicus 19 F (Medtronic, Tolochenaz, Switzerland); (B) Smart canula 18 F/36 F (Smartcanula LLC, Lausanne, Switzerland). RESULTS: At 1500 RPM, the blood flow was 0.44+/-0.26 l min(-1) for the 19 F rectilinear cannula versus 0.73+/-0.34 l min(-1) for the 18/36 F self-expanding cannula. At 2500 RPM the blood flow was 1.63+/-0.62 l min(-1) for the 19F rectilinear cannula versus 2.13+/-0.34 l min(-1) for the 18/36 F self-expanding cannula. At 3500 RPM, the blood flow was 2.78+/-0.47 l min(-1) for the 19 F rectilinear cannula versus 3.64+/-0.39 l min(-1) for the 18/36 F self-expanding cannula (p<0.01 for 18/36 F vs 19 F). At 1500 RPM, the venous line pressure was 18+/-8 mmHg for the 19F rectilinear cannula versus 19+/-5 mmHg for the 18/36 F self-expanding cannula. At 2500 RPM the venous line pressure accounted for -22+/-32 mmHg for the 19 F rectilinear cannula versus 2+/-5 mmHg for the 18/36 F self-expanding cannula. At 3500 RPM, the venous line pressure was -112+/-42 mmHg for the rectilinear cannula versus 28+/-7 mmHg for the 18/36 F self-expanding cannula (p<0.01 for 18 F/36 F vs 19 F). Conclusions: The negative pressure required to achieve adequate venous drainage with the self-expanding venous cannula accounts for approximately 31% of the pressure necessary with the 19 F rectilinear cannula. In addition, a pump flow of more than 4 l min(-1) can be achieved with the self-expanding design and a well-accepted negative inlet pressure for minimal blood trauma of less than 50 mmHg.

Quette place pour l'automesure glycémique dans la prise en charge du diabète de type 2 [Which role for self-monitoring of blood glucose in type 2 diabetes?]

There is a sustained controversy in the literature about the role and utility of self-monitoring of blood glucose (SMBG) in type 2 diabetes. The study results in this field do not provide really useful clues for the integration of SMBG in the follow-up of the individual patient, because they are based on a misconception of SMBG. It is studied as if it was a medical treatment whose effect on glycemic control is to be isolated. However, SMBG has no such intrinsic effect. It gains its purpose only as an inseparable component of a comprehensive and structured educational strategy. To be appropriate this strategy cannot be based on the health care professionals' view on diabetes only. It rather has to be tailored to the individual patient's needs through an ongoing process of shared reflection with him.

Removal of unusual, large high-velocity metallic maxillary sinus foreign bodies by a modified free bone flap technique.

Metallic foreign bodies are rarely found in the maxillary sinus, and usually they have a dental origin.Potential complications related to foreign bodies include recurrent sinusitis, rhinolith formation, cutaneous fistula,chemical poisoning, facial neuralgic pain and even malignancies.Two main surgical approaches are currently used for the removal of foreign bodies in the maxillary sinus: the bone flap and the endoscopic sinus techniques. We are reporting two unusual cases of large high-velocity foreign bodies removed by a modified maxillary lateral antrotomy,with free bone flap repositioning and fixation with a titanium miniplate.

The Child Occupational Self Assessment (COSA, version 2.1) : lasten toimintamahdollisuuksien itsearviointi COSA:n esittely ja suomentamisprosessi

Tämän opinnäytetyön tarkoituksena on aloittaa lapsille ja nuorille suunnatun The Child Occupational Self Assessment (COSA, version 2.1) itsearviointimenetelmän suomenkielisen version käännöstyö. COSA on asiakaslähtöinen itsearviointi, jolla kartoitetaan lasten ja nuorten kokemusta toiminnallisesta pätevyydestään ja jokapäiväisten toimintojen tärkeydestä heille. COSA pohjaa Inhimillisen toiminnan malliin ja sen toteutus seuraa asiakaslähtöistä teoriaa. COSA:n avulla voidaan asettaa toimintaterapialle tavoitteet ja tarkastella niiden toteutumista. Työssämme suomennamme arviointimenetelmän nimen muotoon; Lasten toimintamahdollisuuksien itsearviointi COSA. Arviointimenetelmän käännöstyö tehdään Helsingin ammattikorkeakoulu Stadian toimintaterapian koulutusohjelmalle. Opinnäytetyössä esittelemme ensin arviointia ja tavoitteiden asettamista lasten toimintaterapiassa sekä itsearvioinnin käyttämistä arviointimenetelmänä. Esittelemme COSA itsearviointimenetelmän sekä sen taustalla vaikuttavat Inhimillisen toiminnan mallin sisällön ja asiakaslähtöisyyden. Kartoitamme myös The Child Occupational Self Assessment (COSA, version 2.1 )itsearviointimenetelmän kehittymistä, sitä edeltäneitä arviointimenetelmiä ja COSA:sta aiemmin tehtyjä tutkimuksia. Opinnäytetyössä suomennamme COSA:n arviointilomakkeen. Arviointilomakkeessa on 25 lasten ja nuorten toiminnallista pätevyyttä ja jokapäiväisten toimintojen tärkeyttä kartoittava väittämää. Suomentamisprosessissa selvitämme COSA:n arviointilomakkeen väittämien suomennosten ymmärrettävyyden onnistumista kahdeksan käyttökokeiluun ja haastatteluun osallistuvan lapsen avulla. Saimme arviointilomakkeen suomentamisprosessiin apua neljältä lasten kanssa työskentelevältä toimintaterapeutilta sekä koulutusohjelmamme koulutuspäälliköltä. Käyttökokeiluiden sekä toimintaterapeuttien palautteiden avulla viimeistelimme suomennetun arviointilomakkeen väittämät. Opinnäytetyön lopuksi pohdimme arviointilomakkeen suomentamisprosessin vaiheita sekä mahdollisia jatkotutkimusehdotuksia. Luovutimme Lasten toimintamahdollisuuksien itsearviointi COSA:n arviointilomakkeen koulutusohjelmamme käyttöön ja mahdollisten jatkotutkimusten kohteeksi.

Optical evidence for the proximity to a spin-density-wave metallic state in Na0.7CoO2

We present the optical properties of Na0.7CoO2 single crystals, measured over a broad spectral range as a function of temperature (T). The capability to cover the energy range from the far-infrared up to the ultraviolet allows us to perform reliable Kramers-Kronig transformation, in order to obtain the absorption spectrum (i.e., the complex optical conductivity). To the complex optical conductivity we apply the generalized Drude model, extracting the frequency dependence of the scattering rate (Gamma) and effective mass (m*) of the itinerant charge carriers. We find that Gamma(omega) at low temperatures and for similar to omega. This suggests that Na0.7CoO2 is at the verge of a spin-density-wave metallic phase.