Antigenicity and immunogenicity of Melan-A/MART-1 derived peptides as targets for tumor reactive CTL in human melanoma.

Some cancer patients mount spontaneous T- and B-cell responses against their tumor cells. Autologous tumor reactive CD8 cytolytic T lymphocyte (CTL) and CD4 T-cell clones as well as antibodies from these patients have been used for the identification of genes encoding the target antigens. This knowledge opened the way for new approaches to the immunotherapy of cancer. In this review, we describe the characterization of the structure-function properties of the melanocyte/melanoma tumor antigen Melan-A/MART-1, the assessment of the T-cell repertoire available against this antigen in healthy individuals, and the analysis of naturally acquired and/or vaccine-induced CTL responses to this antigen in patients with metastatic melanoma.

Cutting edge: stimulation with the cognate self-antigen induces expression of the Ly49A receptor on self-reactive T cells which modulates their responsiveness.

NK cell self-tolerance is maintained by inhibitory receptors specific for MHC class I molecules. Inhibitory NK receptors are also expressed on memory CD8 T cells but their biological relevance on T cells is unclear. In this study, we describe the expression of the Ly49A receptor on a subset of autoreactive T cells which persist in mice double-transgenic for the lymphocytic choriomeningitis virus-derived peptide gp33 and a TCRalphabeta specific for the gp33. No Ly49A-expressing cells are found in TCRalphabeta single-transgenic mice, indicating that the presence of the autoantigen is required for Ly49A induction. Direct evidence for an Ag-specific initiation of Ly49A expression has been obtained in vitro after stimulation of autoreactive TCRalphabeta T cells with the cognate self-Ag. This expression of Ly49A substantially reduces Ag-specific activation of autoreactive T cells. These findings thus suggest that autoantigen-specific induction of inhibitory NK cell receptors on T cells may contribute to peripheral self-tolerance.

Performance of noninvasive ventilation algorithms on ICU ventilators during pressure support: a clinical study.

To evaluate the impact of noninvasive ventilation (NIV) algorithms available on intensive care unit ventilators on the incidence of patient-ventilator asynchrony in patients receiving NIV for acute respiratory failure. Prospective multicenter randomized cross-over study. Intensive care units in three university hospitals. Patients consecutively admitted to the ICU and treated by NIV with an ICU ventilator were included. Airway pressure, flow and surface diaphragmatic electromyography were recorded continuously during two 30-min periods, with the NIV (NIV+) or without the NIV algorithm (NIV0). Asynchrony events, the asynchrony index (AI) and a specific asynchrony index influenced by leaks (AIleaks) were determined from tracing analysis. Sixty-five patients were included. With and without the NIV algorithm, respectively, auto-triggering was present in 14 (22%) and 10 (15%) patients, ineffective breaths in 15 (23%) and 5 (8%) (p = 0.004), late cycling in 11 (17%) and 5 (8%) (p = 0.003), premature cycling in 22 (34%) and 21 (32%), and double triggering in 3 (5%) and 6 (9%). The mean number of asynchronies influenced by leaks was significantly reduced by the NIV algorithm (p < 0.05). A significant correlation was found between the magnitude of leaks and AIleaks when the NIV algorithm was not activated (p = 0.03). The global AI remained unchanged, mainly because on some ventilators with the NIV algorithm premature cycling occurs. In acute respiratory failure, NIV algorithms provided by ICU ventilators can reduce the incidence of asynchronies because of leaks, thus confirming bench test results, but some of these algorithms can generate premature cycling.

Soins intégrés: comment accompagner un changement de culture [Integrated care: how to support a culture change?].

The primary care center at Lausanne University Hospital trains residents to new models of integrated care. The future GPs discover new forms of collaboration with nurses, pharmacists or social workers. The collaboration model includes seeing patients together or delegating care to other providers, with the aim of improving the efficiency of a patient-centered care approach. The article includes examples of integrated care in consultation for travelers, victims of violence, pharmacist medication adherence counseling, medicosocial team work for alcohol use disorders and nurse practitioners' primary care for asylum seekers.

Offering planning with support of roadmapping in project business

Tämän tutkielman tavoitteena on tutkia kuinka roadmapping-tekniikkaa voidaan käyttää tarjonnan suunnittelun tukena uusien tuotteiden valmistamisen yhteydessä. Työ koostuu teoreettisesta ja käytännönläheisestä osasta. Teoreettinen runko on luotu selventämään kuinka tämän hetkisen tutkimus- ja kehitys projektit lopulta muodostavat tulevaisuuden tarjoaman. Menestyksekkään tuotetarjoaman luominen vaatii, sekä uusien teknologioiden kehittämistä, että markkinoilla olevien asiakkaiden tarpeiden ymmärtämistä. Asiakassuuntaisten tuotteiden kehittäminen vaatii toimintaympäristöstä ja asiakasrajapinnasta tulevien signaalien tunnistamista ja niiden ohjaamista tuote- ja teknologia platformeille. Strategia luodaan tukemaan päätöksentekoa prosessin eri vaiheissa. Yrityskohtainen osio koostuu analyysistä, joka on tehty teetetyn kyselyn ja haas-tattelujen pohjalta. Osana analyysia ovat Major project-yksikön tämänhetkinen tarjonnansuunnitteluprosessi, strategian soveltaminen, informaation kerääminen ja priorisointi, portfolionhallinta ja roadmap-tekniikan käyttö. Ratkaisussa on esitet-ty tarjonnan suunnitteluprosessi ja siihen liittyvät kriittiset komponentit. Roadmapping-tekniikkaaon luotu yhdistämään toimintaympäristö, tuotteet ja teknologia toisiinsa. Toimintaympäristö ja tuotteet on yhdistetty myös linked-grids-tekniikan avulla.

Project SKY-EYE: applying UAVs to forest fire fighter support and monitoring

Peer reviewed

Assessing technology-based spin-offs from university support units

This paper takes a regional studies approach to assess spin-offs from a university-based technology transfer network. We first detect the regional objectives, inputs and outputs needed to assess spin-offs from support programmes. We then provide evidence on regional mechanisms for firm creation. We analyse spin-offs created at Catalan universities and find that many efficient spin-offs have formal technology transfer agreements, and emerge from technology-oriented universities. We also find that higher innovation levels and experience from the parent university are associated with higher efficiency, which is positively related to future fundamental profitability. Finally, we propose regional policy making and research directions.

Personalized drug administrations using Support Vector Machine

The decision-making process regarding drug dose, regularly used in everyday medical practice, is critical to patients' health and recovery. It is a challenging process, especially for a drug with narrow therapeutic ranges, in which a medical doctor decides the quantity (dose amount) and frequency (dose interval) on the basis of a set of available patient features and doctor's clinical experience (a priori adaptation). Computer support in drug dose administration makes the prescription procedure faster, more accurate, objective, and less expensive, with a tendency to reduce the number of invasive procedures. This paper presents an advanced integrated Drug Administration Decision Support System (DADSS) to help clinicians/patients with the dose computing. Based on a support vector machine (SVM) algorithm, enhanced with the random sample consensus technique, this system is able to predict the drug concentration values and computes the ideal dose amount and dose interval for a new patient. With an extension to combine the SVM method and the explicit analytical model, the advanced integrated DADSS system is able to compute drug concentration-to-time curves for a patient under different conditions. A feedback loop is enabled to update the curve with a new measured concentration value to make it more personalized (a posteriori adaptation).

Patient-ventilator asynchrony during noninvasive pressure support ventilation and neurally adjusted ventilatory assist in infants and children.

OBJECTIVES: To document the prevalence of asynchrony events during noninvasive ventilation in pressure support in infants and in children and to compare the results with neurally adjusted ventilatory assist. DESIGN: Prospective randomized cross-over study in children undergoing noninvasive ventilation. SETTING: The study was performed in a PICU. PATIENTS: From 4 weeks to 5 years. INTERVENTIONS: Two consecutive ventilation periods (pressure support and neurally adjusted ventilatory assist) were applied in random order. During pressure support (PS), three levels of expiratory trigger (ETS) setting were compared: initial ETS (PSinit), and ETS value decreased and increased by 15%. Of the three sessions, the period allowing for the lowest number of asynchrony events was defined as PSbest. Neurally adjusted ventilator assist level was adjusted to match the maximum airway pressure during PSinit. Positive end-expiratory pressure was the same during pressure support and neurally adjusted ventilator assist. Asynchrony events, trigger delay, and cycling-off delay were quantified for each period. RESULTS: Six infants and children were studied. Trigger delay was lower with neurally adjusted ventilator assist versus PSinit and PSbest (61 ms [56-79] vs 149 ms [134-180] and 146 ms [101-162]; p = 0.001 and 0.02, respectively). Inspiratory time in excess showed a trend to be shorter during pressure support versus neurally adjusted ventilator assist. Main asynchrony events during PSinit were autotriggering (4.8/min [1.7-12]), ineffective efforts (9.9/min [1.7-18]), and premature cycling (6.3/min [3.2-18.7]). Premature cycling (3.4/min [1.1-7.7]) was less frequent during PSbest versus PSinit (p = 0.059). The asynchrony index was significantly lower during PSbest versus PSinit (40% [28-65] vs 65.5% [42-76], p < 0.001). With neurally adjusted ventilator assist, all types of asynchronies except double triggering were reduced. The asynchrony index was lower with neurally adjusted ventilator assist (2.3% [0.7-5] vs PSinit and PSbest, p < 0.05 for both comparisons). CONCLUSION: Asynchrony events are frequent during noninvasive ventilation with pressure support in infants and in children despite adjusting the cycling-off criterion. Compared with pressure support, neurally adjusted ventilator assist allows improving patient-ventilator synchrony by reducing trigger delay and the number of asynchrony events. Further studies should determine the clinical impact of these findings.

Cross-Border Innovation Support Platform for the SMEs: The Case of St. Petersburg Corridor Region

Työssä tutkitaan eri mekanismeja rajojen ylittävään innovaatioiden edistämiseen pienten ja keskisuurten yritysten näkökulmasta. Case ympäristönä on Kaakkois-Suomen ja Luoteis-Venäjän alueeli Pietarin Corridor. Tavoitteena on löytää tarkemmat määritykset ja rajauksetnäille mekanismeille. Teoriassa muodostettiin viitekehys rajojen ylittävälle innovaatioiden edistämismallille. Mallin pohjalta toteutettiinhaastattelututkimus, joka suoritettiin case-ympäristössä. Haastattelujoukko koostui yritysten edustajista, tutkimus-henkilöstöstä sekä julkisista toimijoista. Innovaatiojärjestelmä oli avoin uusille toimintamenetelmille.Menetelmien toteuttamistapa kuitenkin jakoi mielipiteitä. Toimijoiden välille tarvitaan parempaa yhteistyötä ja tämän kautta selkeämpää kommunikointia yritysten suuntaan. Innovaatioiden edistämiseen ehdotetaan Innovation Relay Centre tyyppisen toiminnan laajentamista Corridorin alueelle sekä sen käyttämän teknologioiden välittämismallin sekä kansainvälisen verkoston hyödyntämistä. Edistämisen tukena tulisi käyttää innovaatiotietokanta-työkalua.

Role of peroxynitrite in the cardiovascular dysfunction of septic shock.

The intense systemic inflammatory response characterizing septic shock is associated with an increased generation of free radicals by multiple cell types in cardiovascular and non cardiovascular tissues. The oxygen-centered radical superoxide anion (O2 .-) rapidly reacts with the nitrogen-centered radical nitric oxide (NO.) to form the potent oxidant species peroxynitrite. Peroxynitrite oxidizes multiple targets molecules, either directly or via the secondary generation of highly reactive radicals, resulting in significant alterations in lipids, proteins and nucleic acids, with significant cytotoxic consequences. The formation of peroxynitrite is a key pathophysiological mechanism contributing to the cardiovascular collapse of septic shock, promoting vascular contractile failure, endothelial and myocardial dysfunction, and is also implicated in the occurrence of multiple organ dysfunction in this setting. The recent development of various porphyrin-based pharmacological compounds accelerating the degradation of peroxynitrite has allowed to specifically address these pathophysiological roles of peroxynitrite in experimental septic shock. Such agents, including 5,10,15,20-tetrakis(4- sulfonatophenyl)porphyrinato iron III chloride (FeTTPs), manganese tetrakis(4-N-methylpyridyl)porphyrin (MnTMPyP), Fe(III) tetrakis-2-(N-triethylene glycol monomethyl ether)pyridyl porphyrin) (FP-15) and WW-85, have been shown to improve the cardiovascular and multiple organ failure in small and large animal models of septic shock. Therefore, these findings support the development of peroxynitrite decomposition catalysts as potentially useful novel therapeutic agents to restore cardiovascular function in sepsis.

A support system for evaluating a suitable joining method in the production of sheet metal goods

This report illustrates a comparative study of various joining methods involved in sheet metal production. In this report it shows the selection of joining methods, which includes comparing the advantages and disadvantages of a method over the other ones and choosing the best method for joining. On the basis of various joining process from references, a table is generated containing set of criterion that helps in evaluation of various sheet metal joining processes and in selecting the most suitable process for a particular product. Three products are selected and a comprehensive study of the joining methods is analyzed with the help of various parameters. The table thus is the main part of the analysis process of this study and can be advanced with the beneficial results. It helps in a better and easy understanding and comparing the various methods, which provides the foundation of this study and analysis. The suitability of the joining method for various types of cases of different sheet metal products can be tested with the help of this table. The sections of the created table display the requirements of manufacturing. The important factor has been considered and given focus in the table, as how the usage of these parameters is important in percentages according to particular or individual case. The analysis of the methods can be extended or altered by changing the parameters according to the constraint. The use of this table is demonstrated by pertaining the cases from sheet metal production.

Prosessimaisen toimintatavan soveltuvuus konepajan liiketoimintaprosessien johtamiseen

Kiristyvä kilpailu ja nopeat ympäristömuutokset aiheuttavat haasteita organisaatioiden johtamiseen. Yritykseltä edellytetään samaan aikaan reagointikykyä, joustavuutta, asiakasläheisyyttä sekä kustannustehokkuutta. Näihin haasteisiin voidaanvastata prosessimaisella toimintatavalla. Tämän työn tavoitteena on arvioida prosessimaisen toimintatavan soveltuvuutta konepajan toimintojenjohtamiseen ja arvioida millaisia hyötyjä prosessimaisella toimintatavalla voidaan saavuttaa. Työn teoriaosuudessa on perehdytty prosessiajattelun terminologiaan, prosessimaisen toiminnan kehittämiseen, avainprosessien tunnistamiseen ja prosessien kuvaamiseen sekä prosessien suorituskyvyn mittaamiseen. Työn käytännön osuudessa on perehdytty yrityksen toimintojen johtamiseen ja niissä ilmenneisiin ongelmiin, joihin prosessimaisella toiminnalla voitaisiin vaikuttaa. Lisäksi on huomioitu mitä ongelmia prosessimaisen toiminnan implementoinnissa saattaa esiintyä. Työssä on esitelty malli, jonka mukaisesti prosessimaista toimintaa voidaan yrityksessä kehittää. Työn tuloksena yrityksen avainprosessit on tunnistettu ja niistä on muodostettu prosessikartta sekä yrityksen tarjous- ja myyntiprosessi on kuvattu prosessinkuvausmenetelmällä.

Special commentary : a call for intensive metabolic support.

PURPOSE OF REVIEW: This special commentary addresses recent clinical reviews regarding appropriate nutrition and metabolic support in the critical care setting. RECENT FINDINGS: There are divergent approaches between North America and Europe for the use of early nutrition support and combined enteral nutrition and parenteral nutrition support possibly due to the commercial availability of specific parenteral nutrients. The advent of intensive insulin therapy has changed the landscape of metabolic support in the intensive care unit, and previous notions about infective risk of parenteral nutrition will need to be re-addressed. Patients with brain failure may benefit from an intensive insulin therapy with a blood glucose target that is higher than that used in patients without brain failure. Patients with heart failure may benefit from the addition of nutritional pharmacology that targets proximate oxidative pathophysiological pathways. Intradialytic parenteral nutrition may be viewed as another form of supplemental parenteral nutrition when enteral nutrition is insufficient in patients on hemodialysis in the intensive care unit. SUMMARY: It is proposed that intensive metabolic support be routinely implemented in the intensive care unit based on the following steps: intensive insulin therapy with an appropriate blood glucose target, nutrition risk assessment, early and if needed combined enteral nutrition and parenteral nutrition to target 20-25 kcal/kg/day and 1.2-1.5 g protein/kg/day, and nutritional and metabolic monitoring.