New directions in cellular therapy of cancer: a summary of the summit on cellular therapy for cancer

A summit on cellular therapy for cancer discussed and presented advances related to the use of adoptive cellular therapy for melanoma and other cancers. The summit revealed that this field is advancing rapidly. Conventional cellular therapies, such as tumor infiltrating lymphocytes (TIL), are becoming more effective and more available. Gene therapy is becoming an important tool in adoptive cell therapy. Lymphocytes are being engineered to express high affinity T cell receptors (TCRs), chimeric antibody-T cell receptors (CARs) and cytokines. T cell subsets with more naïve and stem cell-like characteristics have been shown in pre-clinical models to be more effective than unselected populations and it is now possible to reprogram T cells and to produce T cells with stem cell characteristics. In the future, combinations of adoptive transfer of T cells and specific vaccination against the cognate antigen can be envisaged to further enhance the effectiveness of these therapies

Strain threshold for ventilator-induced lung injury

Introduction Unphysiological lung strain (tidal volume/functional residual capacity, TV/FRC) may cause ventilator-induced lung injury (VILI) [1]. Whether VILI develops proportionally to the applied strain or only above a critical threshold remains unknown. Methods In 20 healthy, mechanically ventilated pigs, FRC and lung weight were measured by computed tomography. Animals were then ventilated for up to 54 hours with a TV set to produce a predetermined strain. At the end, lung weight was measured with a balance. VILI was defi ned as fi nal lung weight exceeding the initial one. Results Lung weight either did not increase at all (no-VILI group; lung weight change \u201373 \ub1 42 g, n = 9) or markedly augmented (VILI group; 264 \ub1 80 g, n = 11). In the two groups, strain was 1.38 \ub1 0.68 and 2.16 \ub1 0.50 (P <0.01), respectively. VILI occurred only when lung strain reached or exceeded a critical threshold, between 1.5 and 2.1 (Figure 1). Conclusions In animals with healthy lungs VILI only occurs when lung strain exceeds a critical threshold. Reference 1. Gattinoni L, Carlesso E, Cadringher P, et al.: Physical and biological triggers of ventilator-induced lung injury and its prevention [review]. Eur Respir J 2003, 22(Suppl 47):15s-25s

A new rating system for hydrogeological risk management along railway infrastructures in Prealpine zone (northern Italy)

AbstractRailway infrastructures in mountain areas often develop along hillslopes affected by geomorphological and hydrogeological processes which might lead hazardous events. Therefore, specific tools for risk analysis and management are required. This paper develops a new rating system (Railway Hydrogeological Management System, RHMS), based on a heuristic method which considers the susceptibility to different types of slope instabilities, as well as the peculiar features affecting the railway vulnerability. The proposed method introduces an iterative approach for the risk assessment, based on the definition of acceptability thresholds for the residual risk. The application of this method to a test area pointed out its feasibility, as well as its operational capability to identify the critical sections of the infrastructure, in which protection or mitigation measures are needed in order to reduce the risk

Adsorption of the prototypical organic corrosion inhibitor benzotriazole on the Cu(100) surface

The interaction of benzotriazole (BTAH) with Cu(100) has been studied as a function of BTAH exposure in a joint experimental and theoretical effort. Scanning tunnelling microscopy (STM), X-ray photoelectron spectroscopy (XPS), high resolution electron energy loss spectroscopy (HREELS) and density functional theory (DFT) calculations have been combined to elucidate the structural and chemical characteristics of this system. BTAH is found to deprotonate upon adsorption on the copper surface and to adopt an orientation that depends on the molecular coverage. Benzotriazolate (BTA) species initially lie with their planes parallel to the substrate but, at a higher molecular coverage, a transition occurs to an upright adsorption geometry. Upon increasing the BTAH exposure, different phases of vertically aligned BTAs are observed with increasing molecular densities until a final, self-limiting monolayer is developed. Both theory and experiment agree in identifying CuBTA and Cu(BTA)2 metal-organic complexes as the fundamental building blocks of this monolayer. This work shows several similarities with the results of previous studies on the interaction of benzotriazole with other low Miller index copper surfaces, thereby ideally completing and concluding them. The overall emerging picture constitutes an important starting point for understanding the mechanism for protection of copper from corrosion

Gas exchange calculation may estimate changes in pulmonary blood flow during veno-arterial extracorporeal membrane oxygenation in a porcine model.

BACKGROUND Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is used as rescue for severe cardiopulmonary failure. We tested whether the ratio of CO2 elimination at the lung and the ECMO (VCO2ECMO/VCO2Lung) would reflect the ratio of respective blood flows and could be used to estimate changes in pulmonary blood flow (QLUNG), i. e. native cardiac output. METHODS Four healthy pigs were centrally cannulated for VA-ECMO. We measured blood flows with an ultrasonic flow probes. VCO2ECMO and VCO2Lung were calculated from sidestream capnographs under constant pulmonary ventilation during ECMO weaning with changing sweep gas and/or ECMO blood flow. If ventilation/perfusion (V/Q) ratio of ECMO was not one, the VCO2ECMO was normalized to V/Q=1 (VCO2ECMONORM). Changes in pulmonary blood flow were calculated using the relationship between changes in CO2 elimination and ECMO blood flow. RESULTS QECMO correlated strongly with VCO2ECMONORM (r2 0.95 - 0.99). QLUNG correlated well with VCO2LUNG (r2 0.65 - 0.89, p<=0.002). Absolute QLung could not be calculated in a non-steady state. Calculated pulmonary blood flow changes had a bias of 76 (-266 to 418) ml/min and correlated with measured QLUNG (r2 0.974 - 1.000, p = 0.1 to 0.006) for cumulative ECMO flow reductions. CONCLUSIONS VCO2 of the lung correlated strongly with pulmonary blood flow. Our model could predict pulmonary blood flow changes within clinically acceptable margins of error. The prediction is made possible with a normalization to a V/Q of 1 for ECMO. This approach depends on measurements readily available and may allow immediate assessment of the cardiac output response

Stress in nursing staff: a comparative analysis between intensive care units and general medicine units

It's a current belief that stress is an outstanding feature of intensive care units, in particular within nursing staff. The aim of this study was to compare some variables belonging to stress (i.e. anxiety, depression and `Burnout' syndrome) between nurses working in intensive care units (ICUs) and general medicine units (GMUs). Materials and methods We studied a population of 883 nurses working in ICUs, distributed in 79 Italian hospitals (70.1 % female) and 509 nurses working in GMUs, distributed in 35 Italian hospitals (80.2 % female). We asked them to fill in a form including: 1) general data and his/her work environment; 2) different evaluation standardized scales - the Hospital Anxiety and Depression Scale, divided into anxiety (HAD A) and depression (HAD D) status 0-7 `non cases', 8-10 `doubtful cases', 11-21 `cases'; the S.T.A.I. scale, divided into acute anxiety (Y-1) and chronic anxiety (Y-2) status; the Maslach Burnout Inventory-Human Services Survey (MBI.) divided into Emotional Exhaustion (EE), 64 18 `low', 19-26 `average', 65 27 `high', Depersonalization (DP) and Personal Accomplishment (PA). We also evaluated the different reasons of anxiety through individual questions (higher value, more anxiety): A1, a critically ill patient; A2, a young patient; A3, an old patient; A4, a suicidal patient; A5, a terminal patient; A6, presence of mechanical supports; A7, relationship with patients' relatives. The comparison between the two groups was performed by the Mann-Whitney Rank Sum test and z-test; statistical significance was accepted as P<0.05. Results The results, expressed as median value, with 25th and 75th percentile in brackets, are shown in Tables 1 and 2. Table 1 also shows the proportions of nurses that had a highest value of HAD A and M.B.I. EE. Conclusions Pathologic anxiety and emotional exhaustion are more prevalent in nurses working in GMUs. Thus, contrary to a common belief, `stress' is a more distinctive peculiarity of general medicine units than intensive care units