Toward partial redirection of energy policy for responsible development

This paper addresses the surprising lack of quality control on the analysis and selection on energy policies observable in the last decades. As an example, we discuss the delusional idea that it is possible to replace fossil energy with large scale ethanol production from agricultural crops. But if large scale ethanol production is not practical in energetic terms, why huge amount of money has been invested in it and is it still being invested? In order to answer this question we introduce two concepts useful to frame, in general terms, the predicament of quality control in science: (i) the concept of “granfalloons” proposed by K. Vonnegut (1963) flagging the danger of the formation of “crusades to save the world” void of real meaning. These granfalloons are often used by powerful lobbies to distort policy decisions; and (ii) the concept of Post-Normal science by S. Funtowicz and J. Ravetz (1990) indicating a standard predicament faced by science when producing information for governance. When mixing together uncertainty, multiple-scale and legitimate but contrasting views it becomes impossible to deal with complex issue using the conventional scientific approach based on reductionism. We finally discuss the implications of a different approach to the assessment of alternative energy sources by introducing the concept of Promethean technology.

Results and harmonization guidelines from two large-scale international Elispot proficiency panels conducted by the Cancer Vaccine Consortium (CVC/SVI).

The Cancer Vaccine Consortium of the Sabin Vaccine Institute (CVC/SVI) is conducting an ongoing large-scale immune monitoring harmonization program through its members and affiliated associations. This effort was brought to life as an external validation program by conducting an international Elispot proficiency panel with 36 laboratories in 2005, and was followed by a second panel with 29 participating laboratories in 2006 allowing for application of learnings from the first panel. Critical protocol choices, as well as standardization and validation practices among laboratories were assessed through detailed surveys. Although panel participants had to follow general guidelines in order to allow comparison of results, each laboratory was able to use its own protocols, materials and reagents. The second panel recorded an overall significantly improved performance, as measured by the ability to detect all predefined responses correctly. Protocol choices and laboratory practices, which can have a dramatic effect on the overall assay outcome, were identified and lead to the following recommendations: (A) Establish a laboratory SOP for Elispot testing procedures including (A1) a counting method for apoptotic cells for determining adequate cell dilution for plating, and (A2) overnight rest of cells prior to plating and incubation, (B) Use only pre-tested serum optimized for low background: high signal ratio, (C) Establish a laboratory SOP for plate reading including (C1) human auditing during the reading process and (C2) adequate adjustments for technical artifacts, and (D) Only allow trained personnel, which is certified per laboratory SOPs to conduct assays. Recommendations described under (A) were found to make a statistically significant difference in assay performance, while the remaining recommendations are based on practical experiences confirmed by the panel results, which could not be statistically tested. These results provide initial harmonization guidelines to optimize Elispot assay performance to the immunotherapy community. Further optimization is in process with ongoing panels.

Early detection of lung cancer: a statement from an expert panel of the Swiss university hospitals on lung cancer screening.

The discussion about setting up a program for lung cancer screening was launched with the publication of the results of the National Lung Screening Trial, which suggested reduced mortality in high-risk subjects undergoing CT screening. However, important questions about the benefit-harm balance and the details of a screening program and its cost-effectiveness remain unanswered. A panel of specialists in chest radiology, respiratory medicine, epidemiology, and thoracic surgery representing all Swiss university hospitals prepared this joint statement following several meetings. The panel argues that premature and uncontrolled introduction of a lung cancer screening program may cause substantial harm that may remain undetected without rigorous quality control. This position paper focuses on the requirements of running such a program with the objective of harmonizing efforts across the involved specialties and institutions and defining quality standards. The underlying statement includes information on current evidence for a reduction in mortality with lung cancer screening and the potential epidemiologic implications of such a program in Switzerland. Furthermore, requirements for lung cancer screening centers are defined, and recommendations for both the CT technique and the algorithm for lung nodule assessment are provided. In addition, related issues such as patient management, registry, and funding are addressed. Based on the current state of the knowledge, the panel concludes that lung cancer screening in Switzerland should be undertaken exclusively within a national observational study in order to provide answers to several critical questions before considering broad population-based screening for lung cancer.

Laboratory Investigation of Bridge Strip Seal Joint Termination Details, SPR RB08-014, 2016

Bridge expansion joints, if not properly designed, constructed, and maintained, often lead to the deterioration of critical substructure elements. Strip seal expansion joints consisting of a steel extrusion and neoprene gland are one type of expansion joint and are commonly used by the Iowa Department of Transportation (DOT). Strip seal expansion joints are susceptible to tears and pull outs that allow water, chlorides, and debris to infiltrate the joint, and subsequently the bearings below. One area of the strip seal that is particularly problematic is where it terminates at the interface between the deck and the barrier rail. The Iowa DOT has noted that the initial construction quality of the current strip seal termination detail is not satisfactory, nor ideal, and a need exists for re-evaluation and possibly re-design of this detail. Desirable qualities of a strip seal termination detail provide a seal that is simple and fast to construct, facilitate quick gland removal and installation, and provide a reliable, durable barrier to prevent chloride-contaminated water from reaching the substructure. To meet the objectives of this research project, several strip seal termination details were evaluated in the laboratory. Alternate termination details may not only function better than the current Iowa DOT standard, but are also less complicated to construct, facilitating better quality control. However, uncertainties still exist regarding the long-term effects of using straight-through details, with or without the dogleg, that could not be answered in the laboratory in the short time frame of the research project.

The use of the SeDeM diagram expert system for the formulation of Captopril SR matrix tablets by direct compression

The SeDeM Diagram Expert System has been used to study excipients, Captopril and designed formulations for their galenic characterization and to ascertain the critical points of the formula affecting product quality to obtain suitable formulations of Captopril Direct Compression SR Matrix Tablets. The application of the Sedem Diagram Expert System enables selecting excipients with in order to optimize the formula in the preformulation and formulation studies. The methodology is based on the implementation of ICH Q8, establishing the design space of the formula with the use of experiment design, using the parameters of the SeDeM Diagram Expert System as system responses.

Development and Evaluation of a Portable Device for Measuring Curling and Warping in Concrete Pavements, 2016

Portland cement concrete (PCC) pavement undergoes repeated environmental load-related deflection resulting from temperature and moisture variations across pavement depth. This has been recognized as resulting in PCC pavement curling and warping since the mid-1920s. Slab curvature can be further magnified under repeated traffic loads and may ultimately lead to fatigue failures, including top-down and bottom-up transverse, longitudinal, and corner cracking. It is therefore significant to measure the “true” degree of curling and warping in PCC pavements, not only for quality control (QC) and quality assurance (QA) purposes, but also for better understanding of its relationship to long-term pavement performance. Although several approaches and devices—including linear variable differential transducers (LVDTs), digital indicators, and some profilers—have been proposed for measuring curling and warping, their application in the field is subject to cost, inconvenience, and complexity of operation. This research therefore explores developing an economical and simple device for measuring curling and warping in concrete pavements with accuracy comparable to or better than existing methodologies. Technical requirements were identified to establish assessment criteria for development, and field tests were conducted to modify the device to further enhancement. The finalized device is about 12 inches in height and 18 pounds in weight, and its manufacturing cost is just $320. Detailed development procedures and evaluation results for the new curling and warping measuring device are presented and discussed, with a focus on achieving reliable curling and warping measurements in a cost effective manner.

Simultaneous determination of human plasma levels of citalopram, paroxetine, sertraline, and their metabolites by gas chromatography-mass spectrometry.

A gas chromatography-mass spectrometry method is presented which allows the simultaneous determination of the plasma concentrations of the selective serotonin reuptake inhibitors citalopram, paroxetine, sertraline, and their pharmacologically active N-demethylated metabolites (desmethylcitalopram, didesmethylcitalopram, and desmethylsertraline) after derivatization with the reagent N-methyl-bis(trifluoroacetamide). No interferences from endogenous compounds are observed following the extraction of plasma samples from six different human subjects. The standard curves are linear over a working range of 10-500 ng/mL for citalopram, 10-300 ng/mL for desmethylcitalopram, 5-60 ng/mL for didesmethylcitalopram, 20-400 ng/mL for sertraline and desmethylsertraline, and 10-200 ng/mL for paroxetine. Recoveries measured at three concentrations range from 81 to 118% for the tertiary amines (citalopram and the internal standard methylmaprotiline), 73 to 95% for the secondary amines (desmethylcitalopram, paroxetine and sertraline), and 39 to 66% for the primary amines (didesmethylcitalopram and desmethylsertraline). Intra- and interday coefficients of variation determined at three concentrations range from 3 to 11% for citalopram and its metabolites, 4 to 15% for paroxetine, and 5 to 13% for sertraline and desmethylsertraline. The limits of quantitation of the method are 2 ng/mL for citalopram and paroxetine, 1 ng/mL for sertraline, and 0.5 ng/mL for desmethylcitalopram, didesmethylcitalopram, and desmethylsertraline. No interferences are noted from 20 other psychotropic drugs. This sensitive and specific method can be used for single-dose pharmacokinetics. It is also useful for therapeutic drug monitoring of these three drugs and could possibly be adapted for the quantitation of the two other selective serotonin reuptake inhibitors on the market, namely fluoxetine and fluvoxamine.

2 years' review of pediatric emergencies admitted in the resuscitation room of a Swiss university hospital

Introduction: Paediatric resuscitation is an intense, stressful andchallenging process performed in a specific surrounding. In theresuscitation room (RR), a dedicated pediatric team is not alwaysavailable and its composition varies according to local resources. Aregular review of the children admitted in the resuscitation room andthe assessment of various outcome measures are the basis of qualitycontrol (QC). The epidemiology of Potentially Life ThreateningPaediatric (LTP) emergencies admitted in a Swiss university hospitalhas never been reported. The aims of this study were to review theLTP emergency population with regards to origin, patients'demographics, reason for admission and final diagnosis, treatmentmodalities, critical events and outcome.Methods: A retrospective observational cohort study of prospectivelycollected data was conducted, including all LTP emergencies admittedover a period of 2 years in the RR of a Swiss university hospitalfunctioning as a tertiary level referral centre. Multiple variablesincluding indication for transfer, mode of pre-hospital transportation,diagnosis and the time spent in RR were assessed. Data assessmenttook place 2 years after the implementation of a quality control (QC)team assessing the pediatric resuscitations occurring within theinstitution on a monthly basis.Results: Out of 60 939 pediatric emergencies treated in LausanneUniversity Medical center over 2 years, a total of 277 LTP emergencies(0.46%) were admitted to the RR, including 160 boys and 117 girls,aged 6 days to 15.95 years (mean 6.69 years, median 5.06). The tablebelow illustrates in more details the identified problems, average age,time in hospital and outcome of both surgical and medical groups ofpatients.Conclusions: With the need for health care quality improvement andfinancial restrictions, an excellent knowledge of the characteristics ofLTP emergencies is unavoidable. A thorough understanding of theresuscitation process and humans resources involved can be achievedwith a systematic review of the cases. A dedicated quality control teamevaluating LTP emergencies in a hospital will identify areas forimprovement. A LTP registry at the national level would be of greatvalue in Switzerland.

Interplay of oxidative, nitrosative/nitrative stress, inflammation, cell death and autophagy in diabetic cardiomyopathy.

Diabetes is a recognized risk factor for cardiovascular diseases and heart failure. Diabetic cardiovascular dysfunction also underscores the development of diabetic retinopathy, nephropathy and neuropathy. Despite the broad availability of antidiabetic therapy, glycemic control still remains a major challenge in the management of diabetic patients. Hyperglycemia triggers formation of advanced glycosylation end products (AGEs), activates protein kinase C, enhances polyol pathway, glucose autoxidation, which coupled with elevated levels of free fatty acids, and leptin have been implicated in increased generation of superoxide anion by mitochondria, NADPH oxidases and xanthine oxidoreductase in diabetic vasculature and myocardium. Superoxide anion interacts with nitric oxide forming the potent toxin peroxynitrite via diffusion limited reaction, which in concert with other oxidants triggers activation of stress kinases, endoplasmic reticulum stress, mitochondrial and poly(ADP-ribose) polymerase 1-dependent cell death, dysregulates autophagy/mitophagy, inactivates key proteins involved in myocardial calcium handling/contractility and antioxidant defense, activates matrix metalloproteinases and redox-dependent pro-inflammatory transcription factors (e.g. nuclear factor kappaB) promoting inflammation, AGEs formation, eventually culminating in myocardial dysfunction, remodeling and heart failure. Understanding the complex interplay of oxidative/nitrosative stress with pro-inflammatory, metabolic and cell death pathways is critical to devise novel targeted therapies for diabetic cardiomyopathy, which will be overviewed in this brief synopsis. This article is part of a Special Issue entitled: Autophagy and protein quality control in cardiometabolic diseases.

Prévalence des maladies infectieuses au Centre hospitalier universitaire vaudois [Prevalence of infectious diseases at the Vaud University Hospital Center].

The prevalence of infectious diseases at our hospital (Centre hospitalier universitaire vaudois, Lausanne [CHUV], 900 beds) was studied retrospectively over a two years period (1980-1981). The medical diagnosis of 30203 patients recorded in the computerized medical archives, representing 93% of the patients admitted during the period of observation, was reviewed. To assess the reliability of the computerized data, quality control was carried out through detailed analysis of all the histologically proven appendicitis recorded during 1981. 88% of the histologically proven appendicitis were registered in the computer and the diagnosis was specific in 87% of cases. An infectious disease was the primary reason for admission in 12.8% of the patients (3873) during the study period. Altogether, 20.2% of patients presented with an infection during their hospital stay. Because of the retrospective nature of the study it was not possible to determine whether these additional infections were nosocomially acquired. The organ systems most frequently infected were the respiratory tract (28.5% of all infections), the digestive tract (20.5%), the skin and osteoarticular system (16%) and the urogenital tract (11.6%). An infection was the primary reason for admission of 40.2% of the patients hospitalized in the dermatology service, of 19.7% of patients admitted in internal medicine, of 15-17% of the patients admitted in pediatrics, ENT and general surgery, and of 1-2% of the patients admitted in neurosurgery and radiotherapy. These observations highlight the continuing importance of infectious diseases in a modern hospital, in spite of high socio-economic levels, stringent hygiene and epidemiologic measures, and modern antibiotic availability.

Experiencia de 10 años de innovación docente en la Unidad de Laboratorios Docentes (ULD) de la Facultad de Farmacia

[spa]En este trabajo se describe la experiencia de innovación docente desarrollada en la ULD a lo largo de los 10 años de existencia. Se comentan algunos de los indicadores del sistema de gestión de la calidad así como su evolución y los resultados más representativos obtenidos en su alimentación. El objetivo de este proyecto es introducir aspectos de la gestión de la calidad, seguridad, salud y medio ambiente en la formación de los estudiantes para que los apliquen a lo largo del desarrollo de las prácticas. De esta forma, podrán adquirir una formación transversal adicional que difícilmente le será transmitida a través de las diferentes asignaturas de la licenciatura y que mejorará sus competencias y facilitará su acceso al ámbito laboral. También se pretende contribuir en la mejora del funcionamiento y las infraestructuras de los laboratorios de prácticas de la facultad. [eng] In the following work it is summarized the innovative experience carried out by the ULD besides showing the results obtained from the different indicators that allow to evaluate the efficiency of the quality management system. The aim is to improve the management of the practical teaching by introducing aspects of quality management, safety, health and environment in the formation of the students. In such a way, they would be able to acquire a transverse additional formation that difficultly would be transmitted across the different subjects of the degree and that would improve their competitions when acceding to the working world.

eggNOG v4.0: nested orthology inference across 3686 organisms

With the increasing availability of various 'omics data, high-quality orthology assignment is crucial for evolutionary and functional genomics studies. We here present the fourth version of the eggNOG database (available at http://eggnog.embl.de) that derives nonsupervised orthologous groups (NOGs) from complete genomes, and then applies a comprehensive characterization and analysis pipeline to the resulting gene families. Compared with the previous version, we have more than tripled the underlying species set to cover 3686 organisms, keeping track with genome project completions while prioritizing the inclusion of high-quality genomes to minimize error propagation from incomplete proteome sets. Major technological advances include (i) a robust and scalable procedure for the identification and inclusion of high-quality genomes, (ii) provision of orthologous groups for 107 different taxonomic levels compared with 41 in eggNOGv3, (iii) identification and annotation of particularly closely related orthologous groups, facilitating analysis of related gene families, (iv) improvements of the clustering and functional annotation approach, (v) adoption of a revised tree building procedure based on the multiple alignments generated during the process and (vi) implementation of quality control procedures throughout the entire pipeline. As in previous versions, eggNOGv4 provides multiple sequence alignments and maximum-likelihood trees, as well as broad functional annotation. Users can access the complete database of orthologous groups via a web interface, as well as through bulk download.

Erään hienopaperikoneen paksuusprofiilin hallinta

Työn kirjallisuusosassa perehdytään paperikoneen online-mittarien toimintaan, poikkisuuntaisten profiilien säätämiseen ja kalanterointiin. Työn tavoitteena oli löytää syyt erään hienopaperikoneen heikkoon paksuusprofiiliin ja siitä aiheutuvaan suureen rullahylkymäärään. Syitä heikkoon paksuusprofiiliin on haettu kalanterin, päällystysasemien ja laatusäätöjärjestelmän toiminnoista. Työssä on tutkittu myös karheusprofiilin vaikutusta paksuusmittaukseen. Työssä löydettiin selvä yhteys paperin karheusprofiilin ja paperikoneen paksuusmittarin mittaaman paksuusprofiilin välille. Radan reuna-alueiden karheus suurentaa online-paksuusmittarin mittaustulosta. Karheusprofiili ei kuitenkaan vaikuta laboratoriomittareilla mitattuun paksuusprofiiliin. Paperikoneen onlinepaksuusmittarin mittausvirhe on kompensoitava, jotta paperin todellinen paksuusprofiili saadaan suoraksi. Työssä tehtyjen tutkimusten perusteella muodostettiin ajomalli, jolla ajettiin koeajojakso. Ajomallin päällimmäinen tarkoitus oli kompensoida paperikoneen online- paksuusmittarin mittausvirhe. Koeajo onnistui hyvin. Koeajojakson profiilivioista johtuva rullahylyn määräoli merkittävästi pienempi kuin referenssijakson profiilivioista johtuva rullahylyn määrä.

Experiencia de 10 años de innovación docente en la Unidad de Laboratorios Docentes (ULD) de la Facultad de Farmacia

[spa]En este trabajo se describe la experiencia de innovación docente desarrollada en la ULD a lo largo de los 10 años de existencia. Se comentan algunos de los indicadores del sistema de gestión de la calidad así como su evolución y los resultados más representativos obtenidos en su alimentación. El objetivo de este proyecto es introducir aspectos de la gestión de la calidad, seguridad, salud y medio ambiente en la formación de los estudiantes para que los apliquen a lo largo del desarrollo de las prácticas. De esta forma, podrán adquirir una formación transversal adicional que difícilmente le será transmitida a través de las diferentes asignaturas de la licenciatura y que mejorará sus competencias y facilitará su acceso al ámbito laboral. También se pretende contribuir en la mejora del funcionamiento y las infraestructuras de los laboratorios de prácticas de la facultad. [eng] In the following work it is summarized the innovative experience carried out by the ULD besides showing the results obtained from the different indicators that allow to evaluate the efficiency of the quality management system. The aim is to improve the management of the practical teaching by introducing aspects of quality management, safety, health and environment in the formation of the students. In such a way, they would be able to acquire a transverse additional formation that difficultly would be transmitted across the different subjects of the degree and that would improve their competitions when acceding to the working world.