Macrophage-Derived Biomarkers of Idiopathic Pulmonary Fibrosis

Idiopathic pulmonary fibrosis (IPF) is a severe, rapidly progressive diffuse lung disease. Several pathogenetic mechanisms have been hypothesized on the basis of the fibrotic lung damage occurring in this disease, and a potential profibrotic role of activated alveolar macrophages and their mediators in the pathogenesis of IPF was recently documented. This paper focuses on recent literature on potential biomarkers of IPF derived from activated alveolar macrophages. Biomarker discovery and clinical application are a recent topic of interest in the field of interstitial lung diseases (ILDs). Cytokines, CC-chemokines, and other macrophage-produced mediators are the most promising prognostic biomarkers. Many molecules have been proposed in the literature as potential biomarker of IPF; however, a rigorous validation is needed to confirm their clinical utility

Importance sampling for high speed statistical Monte-Carlo simulations

As transistor dimensions of Static Random AccessMemory (SRAM) become smaller with each new technology generation, they become increasingly susceptible to statistical variations in their parameters. These statistical variations can result in failing memory. SRAM is used as a building block for the construction of large Integrated Circuits (IC). To ensure SRAM does not degrade the yield (fraction of functional devices) of ICs, very low failure probabilities of Pfail = 10-10 are strived for. For instance in SRAMmemory design one aims to get a 0.1% yield loss for 10Mbit memory, which means that 1 in 10 billion cells fails (Pfail = 10-10; this corresponds with an occurrence of -6.4s when dealing with a normal distribution). To simulate such probabilities, traditional Monte-Carlo simulations are not sufficient and more advanced techniques are required. Importance Sampling is a technique that is relatively easy to implement and provides sufficiently accurate results. Importance sampling is a well known technique in statistics to estimate the occurrences of rare events. Rare or extreme events can be associated with dramatic costs, like in finance or because of reasons of safety in environment (dikes, power plants). Recently this technique also received new attention in circuit design. Importance sampling tunes Monte Carlo to the area in parameter space from where the rare events are generated. By this a speed up of several orders can be achieved when compared to standard Monte Carlo methods. We describe the underlying mathematics. Experiments reveal the intrinsic power of the method. The efficiency of the method increases when the dimension of the parameter space increases. The method could be a valuable extension to the statistical capacities of any circuit simulator A Matlab implementation is included in the Appendix

Gate Leakage Reduction by Clocked Power Supply of Adiabatic Logic Circuits

Losses due to gate-leakage-currents become more dominant in new technologies as gate leakage currents increase exponentially with decreasing gate oxide thickness. The most promising Adiabatic Logic (AL) families use a clocked power supply with four states. Hence, the full <i>V</i>_<i>DD</i> voltage drops over an AL gate only for a quarter of the clock cycle, causing a full gate leakage only for a quarter of the clock period. The rising and falling ramps of the clocked power supply lead to an additional energy consumption by gate leakage. This energy is smaller than the fraction caused by the constant <i>V</i>_<i>DD</i> drop, because the gate leakage exponentially depends on the voltage across the oxide. To obtain smaller energy consumption, Improved Adiabatic Logic (IAL) has been introduced. IAL swaps all n- and p-channel transistors. The logic blocks are built of p-channel devices which show gate tunneling currents significantly smaller than in n-channel devices. Using IAL instead of conventional AL allows an additional reduction of the energy consumption caused by gate leakage. Simulations based on a 90nm CMOS process show a lowering in gate leakage energy consumption for AL by a factor of 1.5 compared to static CMOS. For IAL the factor is up to 4. The achievable reduction varies depending on the considered AL family and the complexity of the gate

Omalizumab treatment in Samter's triad: case series and review of the literature

OBJECTIVE: Samter’s triad is the combination of asthma, aspirin sensitization, and nasal polyposis. Few data are available on the use of omalizumab in this disease. The study aimed to describe the impact of omalizumab on clinical and functional parameters and the quality of life of a series of patients with Samter’s triad. Moreover, we aimed to provide a review of the literature on this topic. PATIENTS AND METHODS: We retrospectively described four patients with Samter’s triad undergoing omalizumab therapy. Clinical, functional, and immunological data of these patients were collected at baseline and follow-up. RESULTS: Reduction of asthma exacerbations and salbutamol rescue therapy were observed in all patients after anti-IgE treatment together with an improvement in the quality of life. A significant improvement in FEV1, FVC, and FEF25-75 was observed. No major side-effects were observed. A total of 14 studies regarding omalizumab in aspirin-exacerbated respiratory diseases were included in the review, comprising 78 patients. All studies reported a good efficacy in improving asthma control; restoration of aspirin tolerance was repeatedly reported. CONCLUSIONS: The results of our case series and review of the literature suggest that omalizumab effectively improves asthma control, lung function tests, and quality of life in patients with Samter’s triad

Opioid overdose risk during and after drug treatment for heroin dependence: An incidence density case–control study nested in the VEdeTTE cohort

Introduction and Aims: To corroborate protective effects of a range of drug treatment modalities against overdose mortality risk. Design and Methods: Nested case–control study, with incidence density sampling, selecting controls retrospectively at each case event. Cases and controls came from a sub-cohort of opioid-dependent patients (n = 4444) from two Italian regions (Lazio and Piedmont). From 1998 to 2005, there were 91 overdose deaths (cases) matched to 352 controls. The primary outcome was overdose mortality and the primary exposure was drug treatment: opioid agonist treatment (OAT), opioid detoxification, residential community, psychosocial and other pharmacological treatment. Conditional logistic regression models generated intervention effects comparing mortality risk in and out of treatment, adjusting for confounding variables. Results: Overall, drug treatment reduced overdose mortality risk by 80% [adjusted odds ratio (AOR) 0.18, 95% confidence interval (CI) 0.10–0.33, P < 0.001] compared to being out of treatment. There was a particularly strong protective effect of OAT on overdose mortality (AOR 0.08, 95% CI 0.03–0.23, P < 0.001) compared to being out of treatment. There was evidence of a substantially elevated risk of overdose in the first month of leaving treatment (AOR 23.50, 95% CI 7.84–70.19, P < 0.001) compared to being in treatment. Discussion and Conclusions: The nested case–control design strengthened earlier findings that OAT in Italy has strong protective effects on overdose mortality risk, much stronger than has been previously seen in other Western European settings

Over 1200 drugs-related deaths and 190,000 opiate-user-years of follow-up : relative risks by sex and age-group

Heroin users/injectors' risk of drugs-related death by sex and current age is weakly estimated both in individual cohorts of under 1000 clients, 5000 person-years or 50 drugs-related deaths and when using cross-sectional data. A workshop in Cambridge analysed six cohorts who were recruited according to a common European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) protocol from drug treatment agencies in Barcelona, Denmark, Dublin, Lisbon, Rome and Vienna in the 1990s; and, as external reference, opiate-user arrestees in France and hepatitis C diagnosed ever-injectors in Scotland in 1993-2001, both followed by database linkage to December 2001. EMCDDA cohorts recorded approximately equal numbers of drugs-related deaths (864) and deaths from other non-HIV causes (865) during 106,152 person-years of follow-up. External cohorts contributed 376 drugs-related deaths (Scotland 195, France 181) and 418 deaths from non-HIV causes (Scotland 221, France 197) during 86,417 person-years of follow-up (Scotland 22,670, France 63,747). EMCDDA cohorts reported 707 drugs-related deaths in 81,367 man-years {8.7 per 1000 person-years, 95% CI: 8.1 to 9.4} but only 157 in 24,785 person-years for females {6.3 per 1000 person-years, 95% CI: 5.4 to 7.4}. Except in external cohorts, relative risks by current age-group were not particularly strong, and more modest in Poisson regression than in cross-sectional analyses: relative risk was 1.2 (95% CI: 1.0-1.4) for 35-44 year olds compared to 15-24 year 3 olds, but 1.4 for males (95%CI: 1.2-1.6), and dramatically lower at 0.44 after the first year of follow-up (95% CI: 0.37-0.52)

POSEIDON: An integrated system for analysis and forecast of hydrological, meteorological and surface marine fields in the Mediterranean area

The Mediterranean area is characterized by relevant hydrological, meteorological and marine processes developing at horizontal space-scales of the order of 1–100 km. In the recent past, several international programs have been addressed (ALPEX, POEM, MAP, etc.)to “resolving” the dynamics of such motions. Other projects (INTERREG-Flooding, MEDEX, etc.)are at present being developed with special emphasis on catastrophic events with major impact on human society that are, quite often, characterized in their manifestation by processes with the above-mentioned scales of motion. In the dynamical evolution of such events, however, equally important is the dynamics of interaction of the local (and sometimes very damaging)pro cesses with others developing at larger scales of motion. In fact, some of the most catastrophic events in the history of Mediterranean countries are associated with dynamical processes covering all the range of space-time scales from planetary to local. The Prevision Operational System for the mEditerranean basIn and the Defence of the lagOon of veNice (POSEIDON)is an integrated system for the analysis and forecast of hydrological, meteorological, oceanic fields specifically designed and set up in order to bridge the gap between global and local scales of motion, by modeling explicitly the above referred to dynamical processes in the range of scales from Mediterranean to local. The core of POSEIDON consists of a “cascade” of numerical models that, starting from global scale numerical analysisforecast, goes all the way to very local phenomena, like tidal propagation in Venice Lagoon. The large computational load imposed by such operational design requires necessarily parallel computing technology: the first model in the cascade is a parallelised version of BOlogna Limited Area Model (BOLAM)running on a Quadrics 128 processors computer (also known as QBOLAM). POSEIDON, developed in the context of a co-operation between the Italian Agency for New technologies, Energy and Environment (Ente per le Nuove tecnologie, l’Energia e l’Ambiente, ENEA)and the Italian Agency for Environmental Protection and Technical Services (Agenzia per la Protezione dell’Ambiente e per i Servizi Tecnici, APAT), has become operational in 2000 and we are presently in the condition of drawing some preliminary conclusions about its performance. In the paper we describe the scientific concepts that were at the basis of the original planning, the structure of the system, its operational cycle and some preliminary scientific and technical evaluations after two years of experimentation

Macrophage-derived biomarkers of idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is a severe, rapidly progressive diffuse lung disease. Several pathogenetic mechanisms have been hypothesized on the basis of the fibrotic lung damage occurring in this disease, and a potential profibrotic role of activated alveolar macrophages and their mediators in the pathogenesis of IPF was recently documented. This paper focuses on recent literature on potential biomarkers of IPF derived from activated alveolar macrophages. Biomarker discovery and clinical application are a recent topic of interest in the field of interstitial lung diseases (ILDs). Cytokines, CC-chemokines, and other macrophage-produced mediators are the most promising prognostic biomarkers. Many molecules have been proposed in the literature as potential biomarker of IPF; however, a rigorous validation is needed to confirm their clinical utility