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The aim of this paper is to re-examine Andreas Andréadès' contribution to the economic policy literature. Emphasis is given to the connection between his theoretical ideas and postulates, and his analysis of the public finance in Greece during the interwar era. His research activity was bounded by two Greek sovereign defaults and five military campaigns which overwhelmingly affected the country's public finances. Andréadès remained critical towards extensive government intervention in the market process, proposing instead liberal economic policies that could safeguard institutions from compromising their independence by economic interests and political interference in bureaucratic decision-making. [ABSTRACT FROM AUTHOR]

Background: Transfusion-associated graft-versus-host disease (TA-GVHD) is a rare, often fatal complication of blood transfusion that can occur in immunocompromised or immunocompetent recipients and is the result of viable T cells present in the blood components transfused.Study Design and Methods: We examined the TA-GVHD clinical case literature including numerous original clinical case reports and several comprehensive case series. We also evaluated recent in vitro experimental data on the inhibition of T cell proliferation, comparing the effect of a specific pathogen inactivation (PI) technology to that of the Food and Drug Administration-recommended gamma irradiation dose of 2500 cGy.Results: We identified 12 published TA-GVHD cases with atypical/milder or delayed symptom presentations and/or an atypical clinical course; these included cases attributed to leukoreduced or suboptimally irradiated units. We summarize recent in vitro data using a sensitive limiting dilution assay that establish that, compared to irradiation at the recommended 2500 cGy dose, PI using amotosalen/ultraviolet A, or amustaline/glutathione achieves a greater degree of inhibition of T cell proliferation.Conclusion: We propose that TA-GVHD has a spectrum of disease severity indicating that additional mild cases may still occur but be undiagnosed and/or underreported, opening up the possibility, supported by in vitro experimental data, that irradiation at the currently established dose may not be fully protective. Furthermore, since many US institutions use component irradiation selectively only for immunocompromised patients, immunocompetent recipients are not fully protected. PI technologies appear to be at least equal to, if not better than, gamma irradiation in abrogating the ability of T cells to proliferate, and if applied to all blood components, protection against TA-GVHD would be an additional benefit that would allow for the elimination of component irradiation. [ABSTRACT FROM AUTHOR]

This paper reports on in situ measurements of the linear energy transfer spectra of galactic cosmic rays and their progeny and of trapped Van Allen belt protons as recorded by a pulse height analyzer (PHA) radiation spectrometer which flew on the STS-95 DISCOVERY mission on the Hubble Orbital Systems Test cradle. The shuttle was launched on October 29, 1998 and had a mission duration of 8.5 days during the minimum phase of the solar activity cycle. The orbit of the STS-95 was about 550 km altitude and 28.5° inclination. Close agreement was seen between radiation environment model predictions and the measurements of the PHA. Agreement is obtained by considering the directionality of the radiation interacting with the shuttle structure. [ABSTRACT FROM PUBLISHER]

Background: Red blood cell (RBC) transfusion risks could be reduced if a robust technology for pathogen inactivation of RBC (PI-RBCs) were to be approved.Materials and Methods: Estimates of per-unit and per-patient aggregate infectious risks for conventional RBCs were calculated; the latter used patient diagnosis as a determinant of estimated lifetime exposure to RBC units. Existing in vitro data for the two technologies under development for producing PI-RBCs and the status of current clinical trials are reviewed.Results: Minimum and maximum per-unit risk were calculated as 0.0003% (1 in 323,000) and 0.12% (1 in 831), respectively. The minimum estimate is for known lower-risk pathogens while the maximal estimate also includes an emerging infectious agent (EIA) and endemic area Babesia risk. Minimum and maximum per-patient lifetime risks by diagnosis grouping were estimated as 1.5 and 3.3%, respectively, for stem cell transplantation (which includes additional risk for cytomegalovirus transmission); 1.2 and 3.7%, respectively, for myelodysplastic syndrome; and 0.2 and 44%, respectively, for hemoglobinopathy.Discussion: There is potential for PI technologies to reduce infectious RBC risk and to provide additional benefits (e.g., prevention of transfusion-associated graft-versus-host disease and possible reduction of alloimmunization) due to white blood cell inactivation. PI-RBCs should be viewed in the context of having a fully PI-treated blood supply, enabling a blood safety paradigm shift from reactive to proactive. Providing insurance against new EIAs. Further, when approved, the use of PI for all components may catalyze operational changes in blood donor screening, laboratory testing, and component manufacturing. [ABSTRACT FROM AUTHOR]

Abstract: This work presents a framework for video search and retrieval without metadata, based on the sequences of detected events. These sequences encompass time information in the form of interval durations and are the basis of our method. By examining Bernoulli trials we elaborate on the confidence in locating the query clip within the video content. Both the query clip and the video content to be searched are considered as imperfect images of inaccessible reference sources, since some of the events may be miss detected or events may be the outcome of false alarms. Tolerances on the certainty of event presence and placement in time are inherently foreseen. A comparison of event sequences is thus performed between two imperfect images shifted in time by an amount which has to be determined. By counting event mismatches a decision on the presence and location of a query clip within the video content base can be taken. Totally avoiding semantic or content analysis, our approach achieves high speed at the cost of accuracy. It is thus ideally suited for a drastic and very efficient narrowing down of the candidate space. It can be used as a first preselection layer outputting potentially matching candidates for more elaborate but costly content search in the video, audio or even (transcribed) text domain. [Copyright &y& Elsevier]

The influence of humidity on streamer propagation at conditions from the threshold for propagation to those for streamer-induced breakdown was investigated in a uniform field in air at atmospheric pressure. Experiments were carried out in a three electrode arrangement consisting of a 12 cm long parallel-plane gap, with an auxiliary needle in the earthed anode. Positive streamers were initiated by applying at the needle electrode a pulse voltage which varied in amplitude. These propagated towards the upper plane electrode which was stressed by a negative dc voltage. Under natural atmospheric conditions, propagation and breakdown probability curves were obtained for several values of absolute humidity in the range between 5 and 22 g/m3. Thus, distributions of the electric field required for streamer propagation and breakdown were obtained and the associated velocity of propagation and time to breakdown were measured. Besides humidity, the amplitude of the voltage used for streamer initiation and the ambient electric field were considered as influencing parameters on streamer properties. Empirical equations are presented expressing the effects of the above parameters on the intrinsic streamer properties. A comparison with previous work in the literature is made and this leads to the conclusion that the influence of humidity on streamer propagation and breakdown can be placed in a sounder quantitative basis. [ABSTRACT FROM AUTHOR]

This paper considers H.323 v4 VoIP networks consisting of gateways and gatekeepers, addressing the task of terminating calls to multiple ISDN networks. Our goal is the maximal utilization of the gatekeeper's centralized routing mechanism for call termination to ISDN networks based on load balancing and resource availability indication (RAI), thus minimizing the need for usage of unwanted (second attempt) overflow mechanisms. We elaborate on the drawbacks of overflow mechanisms and give an overview on different solutions offered in practice by vendors. The discussion justifies the emphasis on load balancing, thus we present an algorithm and tool assisted approach for the systematic assignment of PRIs from ISDN networks to gateways. We follow strictly defined design criteria that lead to an optimized network dial-plan. We thus offer a stand alone, off-line solution without the need of any extra add-ons or upgrades. This is intended to replace the purely intuitive approach followed by today's planners. Our scope is the design rather than the runtime environment; the latter continues to feature the simplicity of a single global RAI per gateway. We consider desirable and non-desirable link distribution topologies between gateways and ISDN networks based on operational and economic evaluation criteria. These measure the number of ‘wasted’ gateway ports or ‘inappropriately’ allocated network interfaces. Our approach is illustrated through a worked out example showing key features of the proposed algorithm and revealing characteristic cases met in the ISDN interface allocation. Finally, we show how the presented methodology, which presently addresses a H.323 design issue, can provide performance benefits in the VoIP technologies of the immediate future. Copyright © 2005 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Abstract: The photoluminescence properties of zinc oxide (ZnO) ceramic thin films, prepared by spin coating of ZnO nanoparticle aqueous suspensions, were studied with emphasis on the influence of film structure and surface morphology on the observation of random laser action. Surface processing employing laser annealing transforms the particulate grain structure of the as-deposited films into a porous channel-like network. This modification was shown to be critical for achieving random laser action as it favors efficient coupling of the pump light into the film material. [Copyright &y& Elsevier]

The sparkover behaviour of sphere-rod gaps under standard impulse voltages is investigated by assessing the influence of gap spacing, impulse voltage waveshape and polarity, and atmospheric conditions on the distribution of the sparkover voltage. At sparkover the growth of streamers of both polarities can be estimated since a value of 2 MV/m is found to be characteristic for the average negative streamer gradient. The IEC atmospheric conditions correction is discussed and compared with a new optimised correction procedure. The feasibility of using the sphere-rod gap as substandard for measuring impulse voltages, replacing the conventional more expensive sphere gap, is examined. [ABSTRACT FROM AUTHOR]

The LIULIN-3M instrument is a further development of the LIULIN dosimeter-radiometer, used on the MIR space station during the 1988–1994 time period. The LIULIN-3M is designed for continuous monitoring of the radiation environment during the BION-12 satellite flight in 1999. A semiconductor detector with 1 mm thickness and 1 cm2 area is contained in the instrument. Pulse high analysis technique is used to determine the energy losses in the detector. The final data from the instrument are the flux and the dose rate for the exposure time and 256 channels of absorbed dose spectra based on the assumption that the particle flux is normal to the detector. The LIULIN-3M instrument was calibrated by proton fluxes with different energies at the Indiana University Cyclotron Facility in June 1997 and had been used for radiation measurements during commercial aircraft flights. The calibration procedure and some flight results are presented in this paper. [Copyright &y& Elsevier]

Examines the role of postactivated neocarzinostatin chromophore (NCS-chrom) in the formation of DNA bulge structure. Identification on the DNA chain cleavage properties of NCS-chrom; Occurrence of bulge-DNA sequences; Mechanisms involved in the formation of binding and cleaving species.

Presents the results of a study which characterized the base-catalyzed thiol-independent cleavage reaction of neocarzinostatin chromophore with long single-stranded DNA in order to use this reaction as a selective probe for the tertiary structure of naturally occurring ss nucleic acid. Base-catalyzed drug reaction with RNA.

Investigates the specific binding of the biradical analog of the anticancer antibiotic neocarzinostatin chromophore to bulged DNA. Mechanisms for thiol-dependent cleavage; Oligodeoxynucleotides in the bulged structure; Fluorescence quenching.

Reports three-dimensional structure of glutathione post activated neocarzinostatin chromophore-DNA complex by NMR and distance geometry molecular-dynamics simulation techniques. Description of materials and methods; Results and discussion; Conclusions.

New experimental results at the onset of turbulence in a gravity-driven pipe flow are presented, and a simple phenomenological model is introduced to describe the intermittent behavior observed. In this model slugs are stochastically produced at the pipe inlet, and the decrease in velocity due to turbulent friction is taken into account. The present approach shows that stochastic arguments account well for several experimental observations at low intermittency factors. In particular, it is shown that special intermittency routes to chaos are not needed to explain the exponentially decaying inverse cumulative distribution of laminar times. [ABSTRACT FROM AUTHOR]

Studies the solution structure of the complex between an analog of the bulge-specific cleaving species and an oligodeoxynucleotide containing a two-base bulge. Cleavage targets for the enediyne antitumor antibiotic neocarzinostatin chromophore; Design of bulge-specific nucleic acid binding molecules.

Attempts to derive the universal scaling exponents characterizing the onset of spatiotemporal chaos in coupled-map lattices. Transition regime to spatiotemporal chaos via the quasiperiodic route; Utilization of space-time renormalization-group analysis; Identification of universality classes for the different types of coupling at various routes to chaos.

A letter to the editor is presented regarding the applicability of severe combined immunodeficiency (SCID) mouse model to the human acute lung injury (ALI).

In the rapidly emerging field of biomedical applications, multifunctional nanoparticles, especially those containing magnetic and plasmonic components, have gained significant attention due to their combined properties. These hybrid systems, often composed of iron oxide and gold, provide both magnetic and optical functionalities and offer promising avenues for applications in multimodal bioimaging, hyperthermal therapies, and magnetically driven selective delivery. This paper focuses on the implementation of advanced characterization methods, comparing statistical analyses of individual multifunctional particle properties with macroscopic properties as a way of fine-tuning synthetic methodologies for their fabrication methods. Special emphasis is placed on the size-dependent properties, biocompatibility, and challenges that can arise from this versatile nanometric system. In order to ensure the quality and applicability of these particles, various novel methods for characterizing the magnetic gold particles, including the analysis of their morphology, optical response, and magnetic response, are also discussed, with the overall goal of optimizing the fabrication of this complex system and thus enhancing its potential as a preferred diagnostic agent. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "A comparison of methods of pathogen inactivation of FFP," by G. Rock in the 2011 issue.

Optically active zinc oxide-silica, inorganic-inorganic nanohybrid materials have been synthesized via a sol-gel process utilizing a room temperature scheme that does not require high temperature annealing. Random laser action is demonstrated from these ZnO-silica nanocomposites. The ZnO nanoparticles act as both the gain and the strong scattering medium, which leads to random optical feedback due to multiple elastic scattering, while the amorphous silica matrix offers a high degree of material stability. Optical pumping of the nanocomposites by ultraviolet laser pulses, of duration shorter than the ZnO photoluminescence lifetime, leads to a profound optical gain behavior and random laser action above a certain threshold value of the excitation energy density. In this context, the effects of laser and material parameters on the observed random lasing are investigated for a series of nanocomposites. The observed dependence of the emission wavelength on excitation energy and the excitation energy density value of the random laser threshold are interpreted on the basis of the formation and the inversion of an electron-hole plasma, respectively. [ABSTRACT FROM AUTHOR]

Presents an obituary for George J. Brucker, a nuclear and radiation physicist, who died on August 01, 2003.

Geriatric patients with complex medical comorbidities who sustain minor injuries may warrant admission to nonsurgical services. The Nelson score provides an objective scoring system that helps identify patients appropriate for nonsurgical admission (NSA). The purpose of this study is to assess the utility of the Nelson criteria in determining the most appropriate admission service. A retrospective review was performed on patients ≥65 years admitted from 12/2016 to 11/2020. 2410 patients met the inclusion criteria. Patients with Nelson score ≥6 were older with more comorbidities, had a lower injury severity score (7.5 vs 12.5, p<0.0001), and a higher rate of NSA (29.2% vs 12.7%, p<0.0001) compared to patients with Nelson score <6. On the multivariable logistic regression, admission service was not identified as an independent predictor of mortality. Utilizing the Nelson criteria may provide an objective measure to stratify and identify patients who would benefit from NSA. [ABSTRACT FROM AUTHOR]

Background: Trauma patients are at high risk for venous thromboembolism (VTE). Opportunity for chemical VTE prophylaxis improvement was identified and practice was altered to start chemoprophylaxis on admission in most patients. The purpose of this study was to determine if early VTE prophylaxis is safe and reduces VTE.Methods: The trauma registry was queried over a 12-month period for patients admitted greater than 1 day for traumatic injury. The study spanned 6 months on either side of instituting aggressive chemoprophylaxis. Patients were risk adjusted on demographics, Injury Severity Score, transfusions, procedure type, length of stay, and mortality. Pre-intervention patients were then compared to patients in the aggressive cohort with the primary outcome of VTE. Secondary outcomes included transfusions, mortality, and length of stay (LOS).Results: 1597 patients were identified over the study period with 754 (47%) patients in the aggressive period. There were no differences in age, sex, Injury Severity Score, transfusions, procedures, or LOS between cohorts. Pre-algorithm patients were more likely to have penetrating mechanism (9.3% vs 6.6%; P = .009) and longer time to VTE prophylaxis (23.3 vs 13.9 hours; P < .001). No differences were noted in anticoagulant, VTE rate (2.0% vs 1.2%; P = .195), or mortality. Linear regression analysis identified time to chemical prophylaxis as significant predictor of VTE (β = 43.9, P < .001).Conclusions: Early aggressive chemical VTE prophylaxis is safe without increasing transfusions. Venous thromboembolism rates were decreased, but did not reach statistical significance. [ABSTRACT FROM AUTHOR]

We performed a risk-benefit analysis for implementation of pathogen-inactivated ( PI) apheresis platelets ( APs) in the United States, focusing on the amotosalen/ultraviolet- A system. Risks and benefits were quantified per patient assuming a mean of 6 AP units per treatment cycle and using available clinical data, mathematical modeling, and observational studies. Current risks associated with AP transfusion can be divided into known partially addressed risks, known well-addressed risks, and unknown risks associated with acute or chronic emerging infectious agents ( EIAs). Bacterial contamination dominates the first category, at a per-patient rate of 1:250, which correlates with an estimated septic transfusion reaction rate of 1:1000. Quantitation of per-patient EIA risk was modeled to be between 1:370 (acute) and 1:667 (chronic). Due to its broad range of action PI is expected to reduce or eliminate these infectious risks and also to reduce the rate of febrile transfusion reactions and possibly alloimmunization. These benefits are weighed against 1) concerns for excess bleeding, 2) an apparent increase in acute respiratory distress syndrome in the initial report of the SPRINT clinical trial, and 3) the possible toxicity associated with the introduction of a new chemical into platelet ( PLT) units. However, transfusion of an estimated 100,000 patients with PI PLTs worldwide has occurred without reported serious adverse effects. We conclude that evidence indicates a favorable risk-benefit profile for the implementation of PLT PI and argues for a path forward toward US regulatory approval. [ABSTRACT FROM AUTHOR]

The breakdown mechanism of dielectric–covered rod/plane air gaps under positive lightning impulse voltages is investigated. Several gap lengths, varying between 2.5 and 15 cm, were employed and the simple air gaps were regarded as reference. The basic characteristics of coronas, namely inception time and voltage, were measured at applied voltages just sufficient for their inception up to voltages causing breakdown. Multiple level tests were conducted; thus, corona inception and breakdown probability distributions were obtained and time to breakdown was measured at several voltage levels. Interpretation of the results was made based on oscillograms of the electric field strength at the earthed plane, which was monitored through a capacitive probe, geometric field calculations and still photographs of the discharge at breakdown. In the dielectric-covered rod/plane gaps, breakdown occurs at higher applied voltages as a result of increase in both corona inception voltages and discharge path. The development of the discharge depends on the electric field distribution as modified by both space and surface charges associated with coronas preceding breakdown. Surface charge accumulation may affect the discharge path at breakdown. [ABSTRACT FROM AUTHOR]

The objective of this study was to examine the effects of polyethylene glycol (PEG) treated red blood cells (RBCs) on the microcirculation in a hamster back skin window chamber model. Donor hamster RBCs were PEGylated through an incubation with an activated PEG solution, washed, resuspended, and infused through a 10% volume top loading procedure into the carotid artery in an awake Syrian Golden hamster. Eight hamster groups were treated with activated PEG different sizes and concentrations: 0.05 mM-5 kDa PEG, 0.5 mM-5 kDa PEG, 1.1 mM-5 kDa PEG, 2.2 mM-5 kDa PEG, 22 mM-5 kDa PEG, 0.05 mM-20 kDa PEG, 0.5 mM-20 kDa PEG, and 5 mM-20 kDa PEG. Non-treated RBCs were used as control. The microvascular bed under observation was videotaped 30 min before the infusion and followed for 30 min post infusion. The diameter of individual blood vessels and blood flow velocities in selected vessels was measured. Hematocrit and hemoglobin concentration were recorded before infusion and at the end of experiment. Tissue pO2 was also monitored. Results showed the hamsters tolerated the PEGylated RBCs without apparent ill effects. No significant changes were recorded for the hematocrit, the hemoglobin concentration, the blood vessel diameters, blood flow velocities, and the interstitial partial oxygen pressure (pO2) before, during, and after the injections of PEG-RBCs (P > 0.05). Unlike most hemoglobin-based oxygen carrying compounds, which can cause vasoconstriction, the PEGylated RBCs did not produce any measurable vasoactivity. Together with the absence of rouleaux formation and the fact that PEG molecules can mask the surface antigens on RBCs, PEGylation appeared promising as a circulation enhancement treatment. [ABSTRACT FROM AUTHOR]

We examine the automatic configuration of consumer electronics devices delivering remote services to the home network. This environment has two particular aspects; it addresses a mass market, hence any automated approach for streamlined deployment, operation and scalability is of prime importance; it also relies on standardization due to its high dependency on communication protocols and services. Modern standards in this domain, along with the invocation of state of the art technologies around XML, give a totally new look at old management problems. More importantly, these standards directly and primarily address configuration issues in a structured and comprehensive way. This paper promotes the view that these standardizations work, pursued and presented in text form by the relevant standardization bodies. It also suggests standard-based methodologies and tools for remote configuration, management, life-cycle support and testing of devices. This inherently ensures compliance to the standards and enables a streamlined design, thus facilitating the provisioning and management of services offered to subscribers. Our contribution concerns relevant tool suites covering to some variable extend all of these aspects. We emphasize the logical succession of each consecutive step/tool and draw attention to the fact that the resulting interrelationships originate from a common source (i.e. the TR-069 standard) and reflect generic needs of the user/player in question. [ABSTRACT FROM AUTHOR]

The positive impulse breakdown behaviour of conductor-rod gaps 50 cm in length is investigated while negative DC voltages pre-stress the gap. Breakdown voltage and time to breakdown variations are discussed in terms of the parameters influencing the discharge mechanism such as the gap geometry, the amplitude of the pre-stress negative DC voltage applied at the rod, the waveshape of the applied impulse voltage at the conductor and the variation of absolute humidity. It is shown that pre-stressing, by producing sufficient DC coronas at both electrodes, results in a significant increase in the breakdown voltage. There is a threshold value of the pre-stress DC voltage above which the gap factor against breakdown may double its value. Both absolute humidity and pre-stressing affect, in a combined way, the dielectric strength of the gaps. [ABSTRACT FROM AUTHOR]

XML technology is penetrating network management in the IETF, UPnP, and DSL Forum suite of standards and protocols. The advantages of XML are offered at the cost of long byte streams due to XML's inherently verbose nature, The increase in packet size for remote configuration and management can pose problems, if executed in a point-to-multipoint arrangement comprising one automatic configuration server and thousands of home gateways and multimedia devices. We investigate and exploit the repetitive nature of text patterns in typical XML documents as produced by the configuration and management tasks and as coded in SOAP RPCs. The solution mainly comes from application of the Lempel-Ziv compression algorithm, with minimal additions in the proposed DSL Forum standard. Numerical and experimental results support the applicability and advantages of the proposed approach and provide insight on how these are attributable to different layers of the employed protocol stack. [ABSTRACT FROM AUTHOR]

Examines the progress on developing models of the radiation environment since the 1960s with emphasis on models that can be applied to predicting the performance of microelectronics used in spacecraft and instruments. Overview of the radiation environment; Trapped radiation belts; Solar proton event model development.

Summary The mglA gene encodes a 22 kDa GTPase that is critical for single-cell (A) gliding, type IV pili-mediated (S) gliding and development of Myxococcus xanthus . To identify components that interact with MglA to control these processes, second-site mutations that restore movement to non-motile mglA mutants were sought. An allele-specific extragenic suppressor of mglA8 , named mas815 (mglA8 s uppressor 15), was obtained. mas815 does not bypass the requirement for MglA, yet it restores type IV pili-mediated motility and starvation-induced development. Single-cell (A) motility is not restored. The suppressing mutation maps to the 3′ end of a gene, masK , in an operon immediately upstream of the mglBA operon. masK encodes a protein of the STY kinase family. When the masK gene was used as bait against a library carrying M. xanthus DNA in the yeast two-hybrid system, eight positive, independent clones containing fusions of mglA to GAL4 were obtained, thus confirming the interaction between MglA and MasK. MasK, expressed in Escherichia coli , was shown to phosphorylate at a tyrosine residue(s). The gain-of-function in the masK815 mutant was correlated with increased production of extracellular fibrils, which are required for adhesion, cell–cell contact and sensing phosphatidylethanolamine chemoattractants. These data suggest that the interaction between MasK and MglA is an essential part of a signal transduction pathway controlling motility and development. [ABSTRACT FROM AUTHOR]

In this paper a practical routing algorithm is proposed that increases the network throughput irrespective of the network traffic load. Its effectiveness is based on an efficient cost function which achieves a successful trade-off between the use of the minimum-hop routes and the application of the load-balancing concept. Moreover, it employs the known Trunk Reservation notion according to a probability that increases linearly with the traffic load. This results in an effective compromise of the performance of the algorithm between light and heavy traffic loads. Finally, its simplicity and its suitability for a real-time application render it as an efficient routing algorithm for ATM networks. Copyright © 1999 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

During a series of presentations of scientific papers 40.6% of 276 subjects reported dreaming, but only 18.1% actually fell asleep. The frequency of dreaming was significantly increased by the addition of either "very boring" or "very interesting" slides to the usual ones, but not by "neutral" slides. The recall of lecture content and the proportion of audience asleep were (surprisingly) not greatly affected by the addition of extraneous slides of any sort. On the other hand, adding "very interesting" slides greatly increases audience enjoyment. [ABSTRACT FROM PUBLISHER]

Background: The INTERCEPT Blood System pathogen reduction technology (PRT), which uses amotosalen and ultraviolet A light treatment (amotosalen/UV-PRT), inactivates pathogens in plasma and platelet components (PCs). This review summarizes data describing the inactivation efficacy of amotosalen/UVA-PRT for a broad spectrum of viruses and parasites.Methods: Twenty-five enveloped viruses, six nonenveloped viruses (NEVs), and four parasites species were evaluated for sensitivity to amotosalen/UVA-PRT. Pathogens were spiked into plasma and PC at high titers. Samples were collected before and after PRT and assessed for infectivity with cell cultures or animal models. Log reduction factors (LRFs) were defined as the difference in infectious titers before and after amotosalen/UV-PRT.Results: LRFs of ≥4.0 log were reported for 19 pathogens in plasma (range, ≥4.0 to ≥7.6), 28 pathogens in PC in platelet additive solution (PC-PAS; ≥4.1-≥7.8), and 14 pathogens in PC in 100% plasma (PC-100%; (≥4.3->8.4). Twenty-five enveloped viruses and two NEVs were sensitive to amotosalen/UV-PRT; LRF ranged from >2.9 to ≥7.6 in plasma, 2.4 or greater to greater than 6.9 in PC-PAS and >3.5 to >6.5 in PC-100%. Infectious titers for four parasites were reduced by >4.0 log in all PC and plasma (≥4.9 to >8.4).Conclusion: Amotosalen/UVA-PRT demonstrated effective infectious titer reduction for a broad spectrum of viruses and parasites. This confirms the capacity of this system to reduce the risk of viral and parasitic transfusion-transmitted infections by plasma and PCs in various geographies. [ABSTRACT FROM AUTHOR]

Background: Risk of transfusion-transmitted (TT) malaria is mainly associated with whole blood (WB) or red blood cell (RBC) transfusion. Risk mitigation relies mostly on donor deferral while a limited number of countries perform blood testing, both negatively impacting blood availability. This study investigated the efficacy of the pathogen reduction system using amustaline and glutathione (GSH) to inactivate Plasmodium falciparum in WB.Study Design and Methods: WB units were spiked with ring stage P. falciparum infected RBCs. Parasite loads were measured in samples at time of infection, after 24 hours at room temperature (RT), and after a 24-hour incubation at RT post-treatment with 0.2 mM amustaline and 2 mM GSH. Serial 10-fold dilutions of the samples were inoculated to RBC cultures and maintained up to 4 weeks. Parasitemia was quantified by cytometry.Results: The P. falciparum viability assay has a limit of detection of a single live parasite per sample. Input parasite titer was >5.7 log10 TCID50 per mL. A 24-hour incubation at RT paused parasite development in controls, but they retained viability and infectivity when tested in culture. In contrast, no infectious parasites were detected in the amustaline/GSH-treated sample after 4 weeks of culture.Conclusion: A robust level of P. falciparum inactivation was achieved in WB using amustaline/GSH treatment. Parasite log reduction was >5.7 log10 TCID50 per mL. Development of such a pathogen reduction system may provide an opportunity to reduce the risk of TT malaria and improve blood availability. [ABSTRACT FROM AUTHOR]

Background and objectives: Pathogen reduction of donor platelets with amotosalen/UVA has been shown to effectively inactivate pathogens and also contaminating white blood cells (WBCs). We wanted to determine whether WBC inactivation could also decrease alloimmune refractoriness to donor platelets. Materials and methods: Platelets were prepared from a donor dog's whole blood, and the platelets were either transfused without modification [standard (STD) platelets] or treated with amotosalen/UVA under conditions modelling the amotosalen/UVA Blood System for human platelets (APR) using either 4 or 3 J/cm2 of UVA exposure. Platelets were transfused weekly from a single donor dog for 8 weeks or until the recipient dog became refractory to their donor's platelets. Antibody samples were drawn weekly and tested against the donor dog's platelets and WBCs (CD8 and B cells). Results: Only 1/7 (14%) dogs that received STD platelets accepted 8 weeks of donor transfusions. Following APR 4 J/cm2 donor transfusions, 3/9 (33%) recipients accepted their donor's transfusions, but only one recipient remained antibody negative. Following APR 3 J/cm2 donor transfusions, the same dose as used for human platelet transfusions, 7/10 (70%) recipients accepted their donor's transfusions, but only two remained antibody negative. Conclusion: As a very high percentage of recipient dogs (70%) accepted APR 3 J/cm2 donor transfusions, these data suggest that preventing alloimmune platelet refractoriness may be another benefit of pathogen reduction using amotosalen/UVA. [ABSTRACT FROM AUTHOR]

Background Herpes zoster (HZ) develops in up to 50% of unvaccinated individuals, accounting for >1 million cases annually in the United States. A live attenuated HZ vaccine (LAV) is Food and Drug Administration approved for those age 50 years or older, though Advisory Committee on Immunization Practices recommendations are only for those age 60 years or older. LAV efficacy is ~70% for persons 50–59 years of age, with lower efficacy in older adults. A new 2-dose adjuvanted subunit vaccine (SUV) has >95% efficacy in persons 50–69 years of age and remains ~90% efficacious in persons vaccinated at age 70 years. Methods To estimate the relative cost-effectiveness of SUV, LAV, and no vaccination (NoV) strategies, a Markov model was developed based on published data on vaccine efficacy, durability of protection, quality of life, resource utilization, costs, and disease epidemiology. The perspective was US societal, and the cycle length was 1 year with a lifelong time horizon. SUV efficacy was estimated to wane at the same rate as LAV. Outcomes evaluated included lifetime costs, discounted life expectancy, and incremental cost-effectiveness ratios (ICERs). Results For individuals vaccinated at age 50 years, the ICER for LAV vs NoV was $118 535 per quality-adjusted life-year (QALY); at age 60 years, the ICER dropped to $42 712/QALY. SUV was more expensive but had better ICERs than LAV. At age 50, the ICER was $91 156/QALY, and it dropped to $19 300/QALY at age 60. Conclusions Vaccination with SUV was more cost-effective than LAV in all age groups studied. Vaccination with SUV at age 50 years appears cost-effective, with an ICER <$100 000/QALY. [ABSTRACT FROM AUTHOR]

Background: Leukoreduction (LR) of platelet concentrate (PC) has evolved as the standard to mitigate risks of alloimmunization, clinical refractoriness, acute transfusion reactions (ATRs), and cytomegalovirus infection, but does not prevent transfusion-associated graft-versus-host disease (TA-GVHD). Amotosalen-ultraviolet A pathogen reduction (A-PR) of PC reduces risk of transfusion-transmitted infection and TA-GVHD. In vitro data indicate that A-PR effectively inactivates WBCs and infectious pathogens.Study Design and Methods: A sequential cohort study evaluated A-PR without LR, gamma irradiation, and bacterial screening in hematopoietic stem cell transplant (HSCT) recipients. The first cohort received conventional PC (control) processed without LR, but with gamma irradiation and bacterial screening. The second cohort received A-PR PC (test) processed without: LR, bacterial screening, or gamma irradiation. The primary efficacy outcome was the 1-hour corrected count increment. The primary safety outcome was treatment-emergent ATR. Secondary outcomes included clinical refractoriness, and 100-day status for engraftment, TA-GVHD, HSCT-GVHD, infections, and mortality.Results: Mean corrected count increment (× 103 ) of 33 test PC recipients was similar (18.9 ± 8.8 vs. 16.6 ± 8.4; p = 0.296) to that of 31 control PC recipients. Test recipients had a reduced, but nonsignificant, incidence of ATR (test = 9.1%, Control = 19.4%; p = 0.296). The frequencies of clinical refractoriness (0 of 33 vs. 4 of 31 patients) and refractory transfusions (6.6% vs. 19.3%) were lower in the test cohort (p = 0.05 and 0.02), respectively. No patient in either cohort had TA-GVHD. Day 100 engraftment, HSCT-GVHD, mortality, and infectious disease complications were similar between cohorts.Conclusions: This study indicated that A-PR PC without LR, gamma irradiation, or bacterial screening is feasible for support of HSCT. [ABSTRACT FROM AUTHOR]

The ISBT Working Party on Transfusion‐Transmitted Infectious Diseases, Bacterial Subgroup (TTID‐WP‐BS) held a meeting during the 2017 ISBT Congress covering topics on safety of platelet components (PC), which are highlighted in this review. The TTID‐WP‐BS along with the Paul Ehrlich Institute have pioneered the development of bacterial strain repositories for PC and red blood cells (RBC) to be used for the validation of detection and pathogen reduction (PR) technologies. Results of the development of the RBC repository strains indicated that six bacterial strains were selected for further testing in international studies, complementing the previous study developed for PC. The THERAFLEX UV‐Platelets PR technology has used the bacterial strain repository for PC to test the effectiveness of the system with data presented in this report. Other PR studies described herein include a report of inactivation of Serratia marcescens by the INTERCEPT Blood System for PC at the levels of the PR claim. Furthermore, a summary of current and future developments of the Mirasol PR system was presented with emphasis on PR in whole blood. Advances in PC screening for bacterial contamination were covered by a comparative study of the BacT/ALERT 3D and BacT/ALERT VIRTUO systems, demonstrating that the latter has a shorter time to detection. Finally, data on septic transfusion reactions involving PC produced in plasma and platelet additive solutions indicated different clinical outcomes and screening results. The topics covered during the TTID‐WP‐BS meeting generated insightful scientific discussions and advanced knowledge, one of the most relevant activities of the Bacterial Subgroup. [ABSTRACT FROM AUTHOR]

Introduction: Transfusion-associated graft-versus-host disease (TA-GVHD) is a rare complication after transfusion of components containing viable donor T cells. Gamma irradiation with doses that stop T-cell proliferation is the predominant method to prevent TA-GVHD. Treatment with pathogen inactivation methodologies has been found to also be effective against proliferating white blood cells, including T cells. In this study, T-cell inactivation was compared, between amotosalen/ultraviolet A (UVA) treatment and gamma-irradiation (2500 cGy), using a sensitive limiting dilution assay (LDA) with an enhanced dynamic range.Methods and Materials: Matched plasma units (N = 8), contaminated with 1 × 106 peripheral blood mononuclear cells (PBMCs) per mL, were either treated with amotosalen/UVA or gamma irradiation, or retained as untreated control. Posttreatment, cells were cultured under standardized conditions. T-cell proliferation was determined by the incorporation of 3 H-thymidine and correlated with microscopic detection.Results: Range-finding experiments showed that after gamma irradiation (2500 cGy), significant T-cell proliferation could be observed at a 1 × 107 cell culture density, some proliferation at 1 × 106 , and none at 1 × 105 cells/well. Based on these facts, a quantitative comparison was carried out between amotosalen/UVA at the highest challenge of 1 × 107 PBMCs/well, and gamma irradiation at 1 × 106 and 1 × 105 PBMCs/well. Complete inactivation of the T cells after amotosalen/UVA treatment was observed, equivalent to greater than 6.2 log inactivation. Complete inactivation of the T cells was also observed after gamma irradiation when 1 × 105 PBMCs/well were cultured (>4.2 log inactivation). Proliferation was observed when 1 × 106 PBMCs/well were cultured (≤5.2 log inactivation) after gamma irradiation.Conclusion: Amotosalen/UVA treatment more effectively inactivates T cells than the current standard of gamma irradiation (2500 cGy) for the prevention of TA-GVHD. [ABSTRACT FROM AUTHOR]

Background and objectives: Chikungunya virus (CHIKV) infections have been reported in all continents, and the potential risk for CHIKV transfusion‐transmitted infections (TTIs) was demonstrated by the detection of CHIKV RNA‐positive donations in several countries. TTIs can be reduced by pathogen inactivation (PI) of blood products. In this study, we evaluated the efficacy of amustaline and glutathione (S‐303/GSH) to inactivate CHIKV in red‐blood‐cell concentrates (RBCs). Material and Methods: Red‐blood‐cells were spiked with high level of CHIKV. Infectious titres and RNA loads were measured before and after PI treatment. Residual CHIKV infectivity was also assessed after five successive cell culture passages. Results: The mean CHIKV titres in RBCs before inactivation was 5·81 ± 0·18 log10 50% tissue culture infectious dose (TCID50)/mL, and the mean viral RNA load was 10·49 ± 0·15 log10 genome equivalent (GEq)/mL. No CHIKV TCID was detected after S‐303 treatment nor was replicative CHIKV particles and viral RNA present after five cell culture passages of samples obtained immediately after S‐303 treatment. Conclusion: Chikungunya virus was previously shown to be inactivated by the PI technology using amotosalen and ultraviolet A light for the treatment of plasma and platelets. This new study demonstrates that S‐303/GSH can inactivate high titres of CHIKV in RBCs. [ABSTRACT FROM AUTHOR]

Background: Chikungunya virus, a mosquito-borne arbovirus, often co-circulates with the Zika, dengue, and yellow fever viruses in Aedes mosquito-infested areas where cases of arbovirus transfusion-transmitted infections have been reported. Building on past experience to help maintain the availability of safe components during major outbreaks of chikungunya virus in La Reunion, Italy, and Thailand and of Zika virus in the Pacific, the Caribbean, and the Americas, pathogen inactivation is a mitigation strategy to reduce the risk of transfusion-transmitted infection. Inactivation of chikungunya virus was investigated for platelets in 100% plasma using amotosalen/ultraviolet A light, and in red blood cells using amustaline/glutathione.Study Design and Methods: Platelets in 100% plasma and red blood cells (RBCs) were spiked with chikungunya virus. Infectious chikungunya virus titers were measured in contaminated blood products before and after treatment with amotosalen/ultraviolet A light for platelets in 100% plasma and after treatment with amustaline/glutathione for RBCs. Viral infectivity was quantified by plaque assay.Results: The mean chikungunya virus infectivity titers before inactivation were 6.50 log10 plaque-forming units/mL for platelets in 100% plasma and 7.60 log10 plaque-forming units/mL for RBCs. No infectivity was detected after amotosalen/ultraviolet A light or amustaline/glutathione treatment, corresponding to greater than 6.5 log10 plaque-forming units/mL and greater than 7.1 log10 plaque-forming units/mL of inactivation, respectively.Conclusion: Robust levels of chikungunya virus inactivation were achieved for platelets in 100% plasma and for RBC components. The licensed amotosalen/ultraviolet A light technology and the amustaline/glutathione pathogen-reduction system under development may provide an opportunity for comprehensive mitigation of the risk of chikungunya virus transfusion-transmitted infection by plasma, platelets, and RBCs. [ABSTRACT FROM AUTHOR]

Background: Dengue virus (DENV) is an arbovirus primarily transmitted through mosquito bite; however, DENV transfusion-transmitted infections (TTIs) have been reported and asymptomatic DENV RNA-positive blood donors have been identified in endemic countries. DENV is considered a high-risk pathogen for blood safety. One of the mitigation strategies to prevent arbovirus TTIs is pathogen inactivation. In this study we demonstrate that the amustaline and glutathione (S-303/GSH) treatment previously found effective against Zika virus in red blood cells (RBCs) is also effective in inactivating DENV.Study Design and Methods: Red blood cells were spiked with high levels of DENV. Viral RNA loads and infectious titers were measured in the untreated control and before and after pathogen inactivation treatment of RBC samples. DENV infectivity was also assessed over five successive cell culture passages to detect any potential residual replicative virus.Results: The mean ± SD DENV titer in RBCs before inactivation was 6.61 ± 0.19 log 50% tissue culture infectious dose (TCID50 )/mL and the mean viral RNA load was 8.42 log genome equivalents/mL. No replicative DENV was detected either immediately after completion of treatment using S-303/GSH or after cell culture passages.Conclusion: Treatment using S-303/GSH inactivated high levels of DENV in RBCs to the limit of detection. In combination with previous studies showing the effective inactivation of DENV in plasma and platelets using the licensed amotosalen/UVA system, this study demonstrates that high levels of DENV can be inactivated in all blood components. [ABSTRACT FROM AUTHOR]

Background: With an increasing number of recognized transfusion-transmitted (TT) babesiosis cases, Babesia microti is the most frequently TT parasite in the United States. We evaluated the inactivation of B. microti in red blood cells (RBCs) prepared in Optisol (AS-5) using amustaline and glutathione (GSH) and in platelet components (PCs) in 100% plasma using amotosalen and low-energy ultraviolet A (UVA) light.Study Design and Methods: Individual RBCs and apheresis PCs were spiked with B. microti-infected hamster RBCs (iRBCs) to a final concentration of 106 iRBCs/mL and treated with the respective inactivation systems according to the manufacturer's instruction. Samples were collected before (control) and after (test) each treatment. Dilutions of the control samples to 10-6 were inoculated into hamsters, while the test samples were inoculated neat or at 10-1 dilution. At 3 and 5 weeks postinoculation, hamsters were evaluated for B. microti infection by microscopic observation of blood smears and 50% infectivity titers (ID50 ) were determined. Log reduction was calculated as control log ID50 minus test log ID50 .Results: Parasitemia was detected in hamsters injected with as low as 100,000-fold diluted control samples, while no parasites were detectable in the blood smears of any hamsters receiving neat test samples. Mean log reduction was more than 5 log/mL by amustaline/GSH for RBCs and more than 4.5 log/mL by amotosalen/UVA for PCs.Conclusion: B. microti was inactivated to the limit of detection in RBCs and PCs after the respective inactivation treatment. Complete inactivation of B. microti was achieved in this animal infectivity model, and pathogen reduction treatment inhibited transmission of infection. [ABSTRACT FROM AUTHOR]

Background: Concerned over the risk of Zika virus (ZIKV) transfusion transmission, public health agencies recommended the implementation of mitigation strategies for its prevention. Those strategies included the use of pathogen inactivation for the treatment of plasma and platelets. The efficacy of amotosalen/ultraviolet A to inactivate ZIKV in plasma had been previously demonstrated, and the efficacy of inactivation in platelets with the same technology was assumed. These studies quantify ZIKV inactivation in platelet components using amotosalen/ultraviolet A.Study Design and Methods: Platelet components were spiked with ZIKV, and ZIKV infectious titers and RNA loads were measured by cell culture-based assays and real-time polymerase chain reaction in spiked platelet components before and after photochemical treatment using amotosalen/ultraviolet A.Results: The mean ZIKV infectivity titers and RNA loads in platelet components before inactivation were either 4.9 log10 plaque forming units per milliliter, or 4.4 log10 50% tissue culture infective dose per milliliter and 7.5 log10 genome equivalents per milliliter, respectively. No infectivity was detected immediately after amotosalen/ultraviolet A treatment. No replicative virus remained after treatment, as demonstrated by multiple passages on Vero cell cultures; and ZIKV RNA was not detected from the first passage after inactivation. Additional experiments in this study demonstrated efficient inactivation to the limit of detection in platelets manufactured in 65% platelet additive solution, 35% plasma, or 100% plasma.Conclusion: As previously demonstrated for plasma, robust levels of ZIKV inactivation were achieved in platelet components. With inactivation of higher levels of ZIKV than those reported in asymptomatic, RNA-reactive blood donors, the pathogen-inactivation system using amotosalen/ultraviolet A offers the potential to mitigate the risk of ZIKV transmission by plasma and platelet transfusion. [ABSTRACT FROM AUTHOR]