Trials using a crossover design and ambulatory blood pressure recordings to determine the efficacy of antihypertensive agents in individual patients.

The antihypertensive effects of the beta-blocking agent betaxolol and the calcium entry blocker verapamil were compared in a crossover single-blind trial. Seventeen patients with uncomplicated essential hypertension took either betaxolol or a slow-release formulation of verapamil for two consecutive 6-week periods. The sequence of treatment phases was randomly allocated and a 2-week washout period preceded each treatment. The antihypertensive effect of the test drugs was assessed both at the physician's office and during everyday activities using a portable blood pressure recorder. The crossover design of the trial made it possible to evaluate the antihypertensive efficacy of betaxolol and verapamil both in the group as a whole and in the individual patient. The individual patient response to one of these agents was not a reliable indicator of the same patient's response to the alternative agent. Betaxolol brought both office and ambulatory recorded blood pressures under control in a larger fraction of patients than verapamil, although the magnitude of the blood pressure fall in the responders was equal for each drug. These observations stress the need for an individualized approach to the evaluation of antihypertensive therapy. The present results also demonstrate that optimal antihypertensive therapy is still a matter of trial and error. The precise methodology that ought to characterize crossover trials may make it possible to improve the therapeutic approach to hypertensive patients.

Regulation of Electricity Transmission and Distribution in Russia

The regulation of electricity transmission and distribution business is an essential issue for any electricity market; it is widely introduced in developed electricity markets of Great Britain, Scandinavian countries and United States of America and other. Those markets which were liberalized recently also need well planned regulation model to be chosen and implemented. In open electricity markets the sectors of electricity distribution and transmission remain monopolies, so called "natural monopolies", as introducing the competition into these sectors in most cases appears to be inefficient. Thatis why regulation becomes very important as its main tasks are: to set reasonable tariffs for customers, to ensure non-discriminating process of electricity transmission and distribution, at the same time to provide distribution companies with incentives to operate efficiently and the owners of the companies with reasonable profits as well; the problem of power quality should be solved at the same time. It should be mentioned also, that there is no incentive scheme which will be suitable for any conditions, that is why it is essential to study differentregulation models in order to form the best one for concrete situation. The aim of this Master's Thesis is to give an overview over theregulation of electricity transmission and distribution in Russia. First, the general information about theory of regulation of natural monopolies will be described; the situation in Russian network business and the importance of regulation process for it will be discussed next. Then there is a detailed description ofexisting regulatory system and the process of tariff calculation with an example. And finally, in the work there is a brief analysis of problems of present scheme of regulation, an attempt to predict the following development of regulationin Russia and the perspectives and risks connected to regulation which could face the companies that try to enter Russian electricity market (such as FORTUM OY).

Federal Dynamics in Times of Economic and Financial Crisis

The global economic and financial crisis is a challenge for all governments, but particularly for federal states because divided and/or shared territorial powers make federations susceptible to coordination problems in fiscal policy making. This article explores the effects of the ongoing crisis on federal relations. Three kinds of problems that may become the cause of federal tensions and conflicts are evoked: opportunism of subgovernments, centralisation and erosion of solidarity among members of the federation. Our analysis of fiscal policies and federal conflicts of 11 federations between 2007 and the present reveals three kinds of coordination problems: shirking in the use of federal government grants, rent-seeking in equalisation payments, and over-borrowing and over-spending. Our results show that shirking remained limited to few cases and occurred only in the first part of the crisis. However, rent-seeking and over-borrowing and over-spending led to a reduction of solidarity among subgovernments and to increased regulation of the fiscal discretion of the members of the federation. Subsequently, tensions in federal relations increased - although only in one case did this challenged the federal order.

Forensic intelligence framework-Part I: induction of a transversal model by comparing illicit drugs and false identity documents monitoring

Forensic intelligence is a distinct dimension of forensic science. Forensic intelligence processes have mostly been developed to address either a specific type of trace or a specific problem. Even though these empirical developments have led to successes, they are trace-specific in nature and contribute to the generation of silos which hamper the establishment of a more general and transversal model. Forensic intelligence has shown some important perspectives but more general developments are required to address persistent challenges. This will ensure the progress of the discipline as well as its widespread implementation in the future. This paper demonstrates that the description of forensic intelligence processes, their architectures, and the methods for building them can, at a certain level, be abstracted from the type of traces considered. A comparative analysis is made between two forensic intelligence approaches developed independently in Australia and in Europe regarding the monitoring of apparently very different kind of problems: illicit drugs and false identity documents. An inductive effort is pursued to identify similarities and to outline a general model. Besides breaking barriers between apparently separate fields of study in forensic science and intelligence, this transversal model would assist in defining forensic intelligence, its role and place in policing, and in identifying its contributions and limitations. The model will facilitate the paradigm shift from the current case-by-case reactive attitude towards a proactive approach by serving as a guideline for the use of forensic case data in an intelligence-led perspective. A follow-up article will specifically address issues related to comparison processes, decision points and organisational issues regarding forensic intelligence (part II).

A prospective, randomized, and controlled study of fluid management in children with severe head injury: lactated Ringer's solution versus hypertonic saline.

OBJECTIVES: Resuscitation in severe head injury may be detrimental when given with hypotonic fluids. We evaluated the effects of lactated Ringer's solution (sodium 131 mmol/L, 277 mOsm/L) compared with hypertonic saline (sodium 268 mmol/L, 598 mOsm/L) in severely head-injured children over the first 3 days after injury. DESIGN: An open, randomized, and prospective study. SETTING: A 16-bed pediatric intensive care unit (ICU) (level III) at a university children's hospital. PATIENTS: A total of 35 consecutive children with head injury. INTERVENTIONS: Thirty-two children with Glasgow Coma Scores of <8 were randomly assigned to receive either lactated Ringer's solution (group 1) or hypertonic saline (group 2). Routine care was standardized, and included the following: head positioning at 30 degrees; normothermia (96.8 degrees to 98.6 degrees F [36 degrees to 37 degrees C]); analgesia and sedation with morphine (10 to 30 microg/kg/hr), midazolam (0.2 to 0.3 mg/kg/hr), and phenobarbital; volume-controlled ventilation (PaCO2 of 26.3 to 30 torr [3.5 to 4 kPa]); and optimal oxygenation (PaO2 of 90 to 105 torr [12 to 14 kPa], oxygen saturation of >92%, and hematocrit of >0.30). MEASUREMENTS AND MAIN RESULTS: Mean arterial pressure and intracranial pressure (ICP) were monitored continuously and documented hourly and at every intervention. The means of every 4-hr period were calculated and serum sodium concentrations were measured at the same time. An ICP of 15 mm Hg was treated with a predefined sequence of interventions, and complications were documented. There was no difference with respect to age, male/female ratio, or initial Glasgow Coma Score. In both groups, there was an inverse correlation between serum sodium concentration and ICP (group 1: r = -.13, r2 = .02, p < .03; group 2: r = -.29, r2 = .08, p < .001) that disappeared in group 1 and increased in group 2 (group 1: r = -.08, r2 = .01, NS; group 2: r = -.35, r2 =.12, p < .001). Correlation between serum sodium concentration and cerebral perfusion pressure (CPP) became significant in group 2 after 8 hrs of treatment (r = .2, r2 = .04, p = .002). Over time, ICP and CPP did not significantly differ between the groups. However, to keep ICP at <15 mm Hg, group 2 patients required significantly fewer interventions (p < .02). Group 1 patients received less sodium (8.0 +/- 4.5 vs. 11.5 +/- 5.0 mmol/kg/day, p = .05) and more fluid on day 1 (2850 +/- 1480 vs. 2180 +/- 770 mL/m2, p = .05). They also had a higher frequency of acute respiratory distress syndrome (four vs. 0 patients, p = .1) and more than two complications (six vs. 1 patient, p = .09). Group 2 patients had significantly shorter ICU stay times (11.6 +/- 6.1 vs. 8.0 +/- 2.4 days; p = .04) and shorter mechanical ventilation times (9.5 +/- 6.0 vs. 6.9 +/- 2.2 days; p = .1). The survival rate and duration of hospital stay were similar in both groups. CONCLUSIONS: Treatment of severe head injury with hypertonic saline is superior to that treatment with lactated Ringer's solution. An increase in serum sodium concentrations significantly correlates with lower ICP and higher CPP. Children treated with hypertonic saline require fewer interventions, have fewer complications, and stay a shorter time in the ICU.

Courtship and mating behaviour of the Mediterranean corn borer, Sesamia nonagrioides (Lepidoptera: Noctuidae)

Se describe la secuencia de cortejo y apareamiento de machos y hembras de Sesamia nonagrioides (Lefèbvre) en el laboratorio. Esta secuencia no varió en presencia o ausencia de plantas de maíz. Se estudió la capacidad de atracción de un sexo sobre el otro atando el individuo de un sexo y dejando libre al complementario. La secuencia de cortejo y apareo de las hembras atadas fue la misma que la de las no atadas, pero los machos atados permanecieron absolutamente inactivos. La edad de los adultos (1 día versus 2 días) no afectó al porcentaje de apareamiento. Se encontraron diferencias en la hora del inicio de la llamada de las hembras y en la edad de las hembras en la primera llamada entre la población estudiada y lo descrito para una población griega, diferencias que podrían estar relacionadas con el origen geográfico. Se discute el papel de los penachos abdominales de los machos en el vuelo de cortejo, rechazándose que estimulen el comportamiento de llamada de las hembras o que las atraigan. Cuando no se aplicaron feromonas, el porcentaje de apareamiento en el laboratorio o en el campo no varió cuando aumentó la densidad de la población. Sin embargo, en los campos en que se aplicó confusión sexual, el porcentaje de apareamiento aumentó al aumentar la densidad de adultos. En la discusión se aportan algunas consecuencias para la investigación de la composición de las feromonas y su uso para el seguimiento de plagas y el control mediante confusión sexual.

Quadrant/octant sequencing and the role of coherent structures in bed load sediment entrainment

To permit the tracking of turbulent flow structures in an Eulerian frame from single-point measurements, we make use of a generalization of conventional two-dimensional quadrant analysis to three-dimensional octants. We characterize flow structures using the sequences of these octants and show how significance may be attached to particular sequences using statistical mull models. We analyze an example experiment and show how a particular dominant flow structure can be identified from the conditional probability of octant sequences. The frequency of this structure corresponds to the dominant peak in the velocity spectra and exerts a high proportion of the total shear stress. We link this structure explicitly to the propensity for sediment entrainment and show that greater insight into sediment entrainment can be obtained by disaggregating those octants that occur within the identified macroturbulence structure from those that do not. Hence, this work goes beyond critiques of Reynolds stress approaches to bed load entrainment that highlight the importance of outward interactions, to identifying and prioritizing the quadrants/octants that define particular flow structures. Key Points <list list-type=''bulleted'' id=''jgrf20196-list-0001''> <list-item id=''jgrf20196-li-0001''>A new method for analysing single point velocity data is presented <list-item id=''jgrf20196-li-0002''>Flow structures are identified by a sequence of flow states (termed octants) <list-item id=''jgrf20196-li-0003''>The identified structure exerts high stresses and causes bed-load entrainment

An outbreak of Arthroderma vanbreuseghemii dermatophytosis at a veterinary school associated with an infected horse.

We report a case of an outbreak of inflammatory dermatophytoses caused by Arthroderma vanbreuseghemii (formally Trichophyton mentagrophytes pro parte) that involved an infected horse, the owner and at least 20 students, staff and stablemen at a veterinary school in Bern (Switzerland) that presented highly inflammatory dermatitis of the body and the face. Transmission from human to human was also recorded as one patient was the partner of an infected person. Both the phenotypic characteristics and ITS sequence of the dermatophytes isolated from the horse and patients were identical, consistent with the conclusion that the fungus originated from the horse. Three infected persons had not been in direct contact with the horse. Although direct transmission from human to human cannot be ruled out, fomites were most likely the source of infection for these three patients. Inspection of the literature at the end of the nineteenth and beginning of the twentieth century revealed that this dermatophyte was frequently transmitted from horses to humans in contact with horses (stablemen, coachmen, carters and artillery soldiers). The rarity of the present case report at the present time is likely related to the transformation of civilisation from the nineteenth century to nowadays in Europe with the change of horse husbandry. In addition, the inadequate immune response of the horse and the high number of people in contact with it at the equine clinic may explain the exceptional aspect of this case report.

Transferring control demands across incidental learning tasks - Stronger sequence usage in serial reaction task after shortcut option in letter string checking

After incidentally learning about a hidden regularity, participants can either continue to solve the task as instructed or, alternatively, apply a shortcut. Past research suggests that the amount of conflict implied by adopting a shortcut seems to bias the decision for vs. against continuing instruction-coherent task processing. We explored whether this decision might transfer from one incidental learning task to the next. Theories that conceptualize strategy change in incidental learning as a learning-plus-decision phenomenon suggest that high demands to adhere to instruction-coherent task processing in Task 1 will impede shortcut usage in Task 2, whereas low control demands will foster it. We sequentially applied two established incidental learning tasks differing in stimuli, responses and hidden regularity (the alphabet verification task followed by the serial reaction task, SRT). While some participants experienced a complete redundancy in the task material of the alphabet verification task (low demands to adhere to instructions), for others the redundancy was only partial. Thus, shortcut application would have led to errors (high demands to follow instructions). The low control demand condition showed the strongest usage of the fixed and repeating sequence of responses in the SRT. The transfer results are in line with the learning-plus-decision view of strategy change in incidental learning, rather than with resource theories of self-control.

Incidence, prevalence and clinical significance of abnormal hematological indices in compensated cirrhosis.

Background & Aims: Patients with cirrhosis develop abnormal hematologic indices (HI) from multiple factors, including hypersplenism. We aimed to analyze the sequence of events and determine whether abnormal HI has prog-nostic significance. Methods: We analyzed a database of 213 subjects with compensated cirrhosis without esopha-geal varices. Subjects were followed for approximately 9 years until the development of varices or variceal bleeding or completion of the study; 84 subjects developed varices. Abnormal HI was defined as anemia at baseline (hemoglo-bin,<13.5 g/dL for men and 11.5 g/dL for women), leuko-penia (white blood cell counts,<4000/mm 3 ), or thrombo-cytopenia (platelet counts, < 150,000/mm 3 ). The primary end points were death or transplant surgery. Results: Most subjects had thrombocytopenia at baseline. Kaplan-Meier analysis showed that leukopenia occurred by 30 months (95% confidence interval, 18.5-53.6), and anemia occurred by 39.6 months (95% confidence interval, 24.1-49.9). Baseline thrombocytopenia (P .0191) and leukope-nia (P.0383) were predictors of death or transplant, after adjusting for baseline hepatic venous pressure gradient (HVPG), and Child-Pugh scores. After a median of 5 years,a significant difference in death or transplant, mortality,and clinical decompensation was observed in patients who had leukopenia combined with thrombocytopenia at base- line compared with patients with normal HI (P < .0001). HVPG correlated with hemoglobin and white blood cell count (hemoglobin, r 0.35, P < .0001; white blood cell count, r 0.31, P < .0001). Conclusions: Thrombocy-topenia is the most common and first abnormal HI to occurin patients with cirrhosis, followed by leukopenia and anemia. A combination of leukopenia and thrombocytopenia at baselin predicted increased morbidity and mortality.

Intercultural business communication between Arabs of the United Arab Emirates and Finns

Kun kauppaa käydään eri maanosien välillä, törmätään vieraisiin kulttuureihin ja erilaisiin kaupankäyntitapoihin. Tämä tutkimus keskittyy suomalaisten liikemiesten ja - naisten työhön Yhdistyneissä Arabiemiraateissa kulttuurierojen näkökulmasta. Tavoitteena on kuvata kulttuurierojen vaikutuksia kaupankäyntiprosessiin ja löytää niitä ongelmia, joita tämän prosessin aikana kohdataan. Tavoitteena on tuottaa tietoa, jonka avulla kulttuurieroista johtuvia ongelmia voidaan vähentää tulevaisuudessa. Tutkimuksen teoreettinen tausta perustuu Hofsteden kulttuurista vaihtelua kuvaaviin dimensioihin ja Ting Toomeyn kulttuurisen identiteetin neuvotteluprosessin malliin. Näihin malleihin perustuen luotiin tähän tutkimukseen oma kulttuurien välisen kohtaamisen malli. Tutkimusongelmia ovat: 1) Miten suomalaiset liikemiehet kuvailevat arabien kaupantekokulttuuria? Kuinka vastapuoli kuvailee omaa kaupantekokulttuuriaan? 2) Minkälainen on suomalaisten ja arabien välinen kaupankäyntiprosessi? 3) Minkälaisia ongelmia kohdataan tehtäessä kauppaa suomalaisten ja arabien kesken? Tutkimus on etnografinen, laadullinen haastattelututkimus (n=12). Haastattelut tehtiin suurimmaksi osaksi Yhdistyneissä Arabiemiraateissa, osin Suomessa. Erilainen kulttuuritausta näkyy kaupankäynnissä. Kollektivistinen, maskuliininen, islamilaisen uskontoon ja vain vähäisessä määrin suoraan kielelliseen koodistoon perustuva kulttuuri heijastuu kaupankäyntiprosessiin. Ystävyyden ja sukulaisten sekä muiden verkostojen merkitys korostuu. Ruumiin kieleen, ilmeisiin ja eleisiin liittyvä kommunikaatio on erilaista ja voi aiheuttaa väärinkäsityksiä. Myös aikakäsitys ja sopimuskäytäntö poikkeavat suomalaisesta. Kaikki nämä voivat aiheuttaa ongelmia kaupankäyntiprosessissa. Tärkeimmiksi tekijöiksi ongelmien kohtaamisessa nousivat ammattitaidon lisäksi kärsivällisyys ja joustavuus. Ongelmia voidaan vähentää huolellisella valmistautumisella ennen ulkomaille lähtöä. Toinen tapa on jatkuviin työkokemuksiin perustuen oppia paikallista kulttuuria ja sen piirteitä.

The radiosensitizing activity of the SMAC-mimetic, Debio 1143, is TNFα-mediated in head and neck squamous cell carcinoma.

BACKGROUND AND PURPOSE: Second mitochondria-derived activator of caspase (SMAC)-mimetics are a new class of targeted drugs that specifically induce apoptotic cancer cell death and block pro-survival signaling by antagonizing selected members of the inhibitor of apoptosis protein (IAP) family. MATERIAL AND METHODS: The present study was designed to investigate the radiosensitizing effect and optimal sequence of administration of the novel SMAC-mimetic Debio 1143 in vitro and in vivo. Apoptosis, alteration of DNA damage repair (DDR), and tumor necrosis factor-alpha (TNF-α) signaling were examined. RESULTS: In vitro, Debio 1143 displayed anti-proliferative activity and enhanced intrinsic radiation sensitivity in 5/6 head and neck squamous cell carcinoma (HNSCC) cell lines in a synergistic manner. In vivo, Debio 1143 dose-dependently radio-sensitized FaDu and SQ20B xenografts, resulting in complete tumor regression in 8/10 FaDu-xenografted mice at the high dose level. At the molecular level, Debio 1143 combined with radiotherapy (RT) induced enhancement of caspase-3 activity, increase in Annexin V-positive cells and karyopyknosis, and increase in TNF-α mRNA levels. Finally, in a neutralization experiment using a TNF-α-blocking antibody and a caspase inhibitor, it was shown that the radiosensitizing effect of Debio 1143 is mediated by caspases and TNF-α. CONCLUSIONS: These results demonstrate that the novel SMAC-mimetic Debio 1143 is a radiosensitizing agent that is worthy of further investigation in clinical trials in combination with radiotherapy.

Soil quality assessment through a multi-approach analysis in soils of abandoned terraced land in NE Spain

The abandonment of agricultural land in mountainous areas has been an outstanding problem along the last century and has captured the attention of scientists, technicians and administrations, for the dramatic consequences sometimes occurred due to soil instability, steep slopes, rainfall regimes and wildfires. Hidromorfological and pedological alterations causing exceptional floods and accelerated erosion processes has therefore been studied, identifying the cause in the loss of landscape heterogeneity. Through the disappearance of agricultural works and drainage maintenance, slope stability has resulted severely affected. The mechanization of agriculture has caused the displacement of vines, olives and corks trees cultivation in terraced areas along the Mediterranean catchment towards more economically suitable areas. On the one hand, land use and management changes have implicated sociological changes as well, transforming areas inhabited by agricultural communities into deserted areas where the colonization of disorganized spontaneous vegetation has buried a valuable rural patrimony. On the other hand, lacking of planning and management of the abandoned areas has produced badlands and infertile soils due to wildfire and high erosion rates strongly degrading the whole ecosystems. In other cases, after land abandonment a process of soil regeneration has been recorded. Investigations have been conducted in a part of NE Spain where extended areas of terraced soils previously cultivated have been abandoned in the last century. The selected environments were semi-abandoned vineyards, semi-abandoned olive groves, abandoned stands of cork trees, abandoned stands of pine trees, scrubland of Cistaceaea, scrubland of Ericaceaea, and pasture. The research work was focused on the study of most relevant physical, chemical and biological soil properties, as well as runoff and erosion under soils with different plant cover to establish the abandonment effect on soil quality, due to the peculiarity and vulnerability of these soils with a much reduced depth. The period of observation was carried out from autumn 2009 to autumn 2010. The sediment concentration of soil erosion under vines was recorded as 34.52 g/l while under pasture it was 4.66 g/l. In addition, the soil under vines showed the least amount of organic matter, which was 12 times lower than all other soil environments. The carbon dioxide (CO2) and total glomalin (TG) ratio to soil organic carbon (SOC) in this soil was 0.11 and 0.31 respectively. However, the soil under pasture contained a higher amount of organic matter and showed that the CO2 and TG ratio to SOC was 0.02 and 0.11 respectively indicating that the soil under pasture better preserves the soil carbon pool. A similar trend was found in the intermediate soils in the sequence of land use change and abandonment. Soil structural stability increased in the two soil fractions investigated (0.25-2.00 mm, 2.0-5.6 mm) especially in those soils that did not undergo periodical perturbations like wildfires. Soil quality indexes were obtained by using relevant physical and chemical soil parameters. Factor analysis carried out to study the relationship between all soil parameters allowed to related variables and environments and identify those areas that better contribute to soil quality towards others that may need more attention to avoid further degradation processes

The octagon, the hendecagon and the approximation of pi: the geometric design of the clypeus in the enclosure of Imperial cult in Tarraco

The ancient temple dedicated to the Roman Emperor Augustus on the hilltop of Tarraco (today’s Tarragona), was the main element of the sacred precinct of the Imperial cult. It was a two hectare square, bordered by a portico with an attic decorated with a sequence of clypeus (i.e. monumental shields) made with marble plates from the Luni-Carrara’s quarries. This contribution presents the results of the analysis of a three-dimensional photogrammetric survey of one of these clipeus, partially restored and exhibited at the National Archaeological Museum of Tarragona. The perimeter ring was bounded by a sequence of meanders inscribed in a polygon of 11 sides, a hendecagon. Moreover, a closer geometric analysis suggests that the relationship between the outer meander rim and the oval pearl ring that delimited the divinity of Jupiter Ammon can be accurately determined by the diagonals of an octagon inscribed in the perimeter of the clypeus. This double evidence suggests a combined layout, in the same design, of an octagon and a hendecagon. Hypothetically, this could be achieved by combining the octagon with the approximation to Pi used in antiquity: 22/7 of the circle’s diameter. This method allows the drawing of a hendecagon with a clearly higher precision than with other ancient methods. Even the modelling of the motifs that separate the different decorative stripes corroborates the geometric scheme that we propose.

PERC rule to exclude the diagnosis of pulmonary embolism in emergency low-risk patients: study protocol for the PROPER randomized controlled study.

BACKGROUND: The diagnosis of Pulmonary Embolism (PE) in the emergency department (ED) is crucial. As emergency physicians fear missing this potential life-threatening condition, PE tends to be over-investigated, exposing patients to unnecessary risks and uncertain benefit in terms of outcome. The Pulmonary Embolism Rule-out Criteria (PERC) is an eight-item block of clinical criteria that can identify patients who can safely be discharged from the ED without further investigation for PE. The endorsement of this rule could markedly reduce the number of irradiative imaging studies, ED length of stay, and rate of adverse events resulting from both diagnostic and therapeutic interventions. Several retrospective and prospective studies have shown the safety and benefits of the PERC rule for PE diagnosis in low-risk patients, but the validity of this rule is still controversial. We hypothesize that in European patients with a low gestalt clinical probability and who are PERC-negative, PE can be safely ruled out and the patient discharged without further testing. METHODS/DESIGN: This is a controlled, cluster randomized trial, in 15 centers in France. Each center will be randomized for the sequence of intervention periods: a 6-month intervention period (PERC-based strategy) followed by a 6-month control period (usual care), or in reverse order, with 2 months of "wash-out" between the 2 periods. Adult patients presenting to the ED with a suspicion of PE and a low pre test probability estimated by clinical gestalt will be eligible. The primary outcome is the percentage of failure resulting from the diagnostic strategy, defined as diagnosed venous thromboembolic events at 3-month follow-up, among patients for whom PE has been initially ruled out. DISCUSSION: The PERC rule has the potential to decrease the number of irradiative imaging studies in the ED, and is reported to be safe. However, no randomized study has ever validated the safety of PERC. Furthermore, some studies have challenged the safety of a PERC-based strategy to rule-out PE, especially in Europe where the prevalence of PE diagnosed in the ED is high. The PROPER study should provide high-quality evidence to settle this issue. If it confirms the safety of the PERC rule, physicians will be able to reduce the number of investigations, associated subsequent adverse events, costs, and ED length of stay for patients with a low clinical probability of PE. TRIAL REGISTRATION: NCT02375919 .