International exercise on 124Sb activity measurements.

An international exercise, registered as EUROMET project no. 907, was launched to measure both the activity of a solution of (124)Sb and the photon emission intensities of its decay. The same solution was sent by LNE-LNHB to eight participating laboratories. In order to identify possible biases, the participants were asked to use all possible activity measurement methods available in their laboratory and then to determine their reference value for comparison. Thus, measurement results from 4pibeta-gamma coincidence/anti-coincidence counting, CIEMAT/NIST liquid-scintillation counting, 4pigamma counting with well-type ionization chambers and well-type crystal detectors were given. The results are compared and show a maximum discrepancy of about 1.6%: possible explanations are proposed.

International recommendations on the diagnosis and treatment of patients with acquired hemophilia A.

Acquired hemophilia A (AHA) is a rare bleeding disorder characterized by autoantibodies directed against circulating coagulation factor (F) VIII. Typically, patients with no prior history of a bleeding disorder present with spontaneous bleeding and an isolated prolonged aPTT. AHA may, however, present without any bleeding symptoms, therefore an isolated prolonged aPTT should always be investigated further irrespective of the clinical findings. Control of acute bleeding is the first priority, and we recommend first-line therapy with bypassing agents such as recombinant activated FVII or activated prothrombin complex concentrate. Once the diagnosis has been achieved, immediate autoantibody eradication to reduce subsequent bleeding risk should be performed. We recommend initial treatment with corticosteroids or combination therapy with corticosteroids and cyclophosphamide and suggest second-line therapy with rituximab if first-line therapy fails or is contraindicated. In contrast to congenital hemophilia, no comparative studies exist to support treatment recommendations for patients with AHA, therefore treatment guidance must rely on the expertise and clinical experience of specialists in the field. The aim of this document is to provide a set of international practice guidelines based on our collective clinical experience in treating patients with AHA and contribute to improved care for this patient group.

International regimes as knowledge syndicates? Energy and trends of global governance

El poder de l'Estat i la sobirania tradicional s'està deteriorant de manera constant, sobretot en termes de la provisió de certs béns públics fonamentals. Els Estats, en particular, són incapaços de manejar el coneixement i la informació que és essencial per mantenir la competitivitat i la sostenibilitat en una economia interdependent. Estructures fiables de la governança mundial i la cooperació internacional estan lluny de ser establertes. Energia com a problema a les agendes p dels governs, les empreses privades i la societat civil és un exemple manifest d'aquesta dinàmica.. L'actual sistema de governança mundial d'energia implica accions polítiques disperses per actors divers. L'Agència Internacional de l'Energia té un paper destacat, però està debilitat per la seva composició limitada i basada en el coneixement- epistèmic en lloc del material o executiu. Aquest treball sosté que ni la mida ni nombre de membres disponibles estan dificultant la governabilitat mundial d'energia. Més aviat, l'energia és una sèrie de béns públics que es troben als llimbs, on els estats no poden pagar la seva disposició, així com els diversos interessos impedir l'establiment d'una autoritat internacional. Després de la introducció de la teoria del règim internacional i el concepte de coneixement basats en les comunitats epistèmiques, l'article revisa l'estat actual de la governabilitat de l'energia mundia. A continuació es presenta una comparació d'aquesta estructura amb els règims de govern nacional i regional, d'una banda, i amb règims globals ambientals i de salut, de l'altra

The Rise of The Swiss Tax Haven in the Interwar Period: An International Comparison

The history of tax havens is still little known for the decades before World War II. Up to now the studies that have focused on the 1920s and 30s have presented either a very general perspective on the development of tax havens or a narrow national point of view. Based on unpublished historical archives of four countries, this paper offers therefore a new comparative look on international tax competition during this period in order to answer the following question: was the Swiss case - already considered as a quintessential tax haven at the time - specific in comparison to other banking centres? This research has two results. On the one hand, the 1920s and 30s appear as something of a golden age of opportunity for avoiding taxation through the relocation of assets. Actually, most of the financial centres granted consistent tax benefits for imported capital, while the extremely limited degree of international cooperation and the usual guarantee of banking secrecy in European countries prevented the taxation of exported assets. On the other hand, within this general balance sheet, the fiscal strategies of a tax haven like Switzerland differed from those of a great financial power like Great Britain. Whereas the Swiss administration readily placed itself at the service of the bankers, the British policy was more balanced between the contradictory interests of the Board of Inland Revenue, the Treasury and the English business circles.

A variant in the gene FUT9 is associated with susceptibility to placental malaria infection

Malaria in pregnancy forms a substantial part of the worldwide burden of malaria, with an estimated annual death toll of up to 200,000 infants, as well as increased maternal morbidity and mortality. Studies of genetic susceptibility to malaria have so far focused on infant malaria, with only a few studies investigating the genetic basis of placental malaria, focusing only on a limited number of candidate genes. The aim of this study therefore was to identify novel host genetic factors involved in placental malaria infection. To this end we carried out a nested case-control study on 180 Mozambican pregnant women with placental malaria infection, and 180 controls within an intervention trial of malaria prevention. We genotyped 880 SNPs in a set of 64 functionally related genes involved in glycosylation and innate immunity. A SNP located in the gene FUT9, rs3811070, was significantly associated with placental malaria infection (OR = 2.31, permutation p-value = 0.028). Haplotypic analysis revealed a similarly strong association of a common haplotype of four SNPs including rs3811070. FUT9 codes for a fucosyl-transferase that is catalyzing the last step in the biosynthesis of the Lewis-x antigen, which forms part of the Lewis blood group-related antigens. These results therefore suggest an involvement of this antigen in the pathogenesis of placental malaria infection.

A targeted association study of immunity genes and networks suggests novel associations with placental malaria infection

A large proportion of the death toll associated with malaria is a consequence of malaria infection during pregnancy, causing up to 200,000 infant deaths annually. We previously published the first extensive genetic association study of placental malaria infection, and here we extend this analysis considerably, investigating genetic variation in over 9,000 SNPs in more than 1,000 genes involved in immunity and inflammation for their involvement in susceptibility to placental malaria infection. We applied a new approach incorporating results from both single gene analysis as well as gene-gene interactionson a protein-protein interaction network. We found suggestive associations of variants in the gene KLRK1 in the single geneanalysis, as well as evidence for associations of multiple members of the IL-7/IL-7R signalling cascade in the combined analysis. To our knowledge, this is the first large-scale genetic study on placental malaria infection to date, opening the door for follow-up studies trying to elucidate the genetic basis of this neglected form of malaria.

Defining the critical hurdles in cancer immunotherapy.

Scientific discoveries that provide strong evidence of antitumor effects in preclinical models often encounter significant delays before being tested in patients with cancer. While some of these delays have a scientific basis, others do not. We need to do better. Innovative strategies need to move into early stage clinical trials as quickly as it is safe, and if successful, these therapies should efficiently obtain regulatory approval and widespread clinical application. In late 2009 and 2010 the Society for Immunotherapy of Cancer (SITC), convened an "Immunotherapy Summit" with representatives from immunotherapy organizations representing Europe, Japan, China and North America to discuss collaborations to improve development and delivery of cancer immunotherapy. One of the concepts raised by SITC and defined as critical by all parties was the need to identify hurdles that impede effective translation of cancer immunotherapy. With consensus on these hurdles, international working groups could be developed to make recommendations vetted by the participating organizations. These recommendations could then be considered by regulatory bodies, governmental and private funding agencies, pharmaceutical companies and academic institutions to facilitate changes necessary to accelerate clinical translation of novel immune-based cancer therapies. The critical hurdles identified by representatives of the collaborating organizations, now organized as the World Immunotherapy Council, are presented and discussed in this report. Some of the identified hurdles impede all investigators; others hinder investigators only in certain regions or institutions or are more relevant to specific types of immunotherapy or first-in-humans studies. Each of these hurdles can significantly delay clinical translation of promising advances in immunotherapy yet if overcome, have the potential to improve outcomes of patients with cancer.

Avaruusinstrumentin mekaniikkasuunnittelu

Tämän insinöörityön tarkoituksena on kehittää avaruusinstrumentti, joka on osa Euroopan avaruusjärjestön ESA:n ja Japanin avaruusjärjestön JAXA:n BepiColombo-yhteistyöhanketta. Satelliitti lähetetään Merkurius-planeetan kiertoradalle vuonna 2013. Avaruusaluksen matka Merkuriukseen kestää yhteensä kuusi vuotta ja on perillä vuonna 2019. Yksi BepiColombo-satelliitin tieteellisistä instrumenteista on Oxford Instruments Analytical Oy:n kehittämä SIXS-instrumentti (Solar Intensity X-ray and particle Spectrometer). Instrumentin tarkoituksena on mitata auringosta tulevaa röntgen- ja partikkelisäteilyä. Se toimii yhteistyössä Merkuriuksen pintaa mittaavan MIXS-instrumentin (Mercury Imaging X-ray Spectrometer) kanssa. Tuloksista pystytään analysoimaan ne alkuaineet, joista Merkuriuksen pinta koostuu. Työn alussa esitellään teoriataustaa alkuaineiden mittauksesta niiltä osin, kuin se tämän työn kannalta on tarpeellista. Työssä syvennytään tarkemmin auringosta tulevan säteilyn mittauksesta vastaavan instrumentin tekniikkaan ja mekaniikkasuunnitteluun. Instrumentin lämpöteknisestä suunnittelusta, värähtelymittauksista ja lujuusanalyysista on työhön sisällytetty pääasiat. Työn tuloksena on kehitetty instrumenttiin tulevan partikkelidetektorin prototyyppi sekä instrumenttikotelon malli. Lopullisen koon instrumenttikotelolle määrittää vaadittavan elektroniikan viemä tila. Mittalaitteen kehitystyö jatkuu Oxford Instruments Analytical Oy:ssä vuoteen 2011 saakka.

The international development of the RGHQoL: a quality of life measure for recurrent genital herpes.

This paper describes the international development and psychometric testing of the Recurrent Genital Herpes Quality of Life Questionnaire (RGHQoL), a condition-specific quality of life (QoL) instrument. The theoretical foundation for the measure is the needs-based model of QoL and the content of the instrument was derived from in-depth qualitative interviews with relevant patients in the UK. Versions of the RGHQoL were required for the UK, USA, Italy, Germany, France and Denmark for use in international clinical trials. The results indicate that the final 20 item measure has good reliability, internal consistency and validity for all language versions. A small responsiveness study in Denmark suggested that the measure is sensitive to changes in QoL associated with the initiation of suppression treatment for recurrent genital herpes (RGH). It is concluded that the RGHQoL is a valuable instrument for inclusion in clinical trials. The psychometric properties of the instrument are such that it may also be used to monitor the progress of individual patients.

Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008.

OBJECTIVE: To provide an update to the original Surviving Sepsis Campaign clinical management guidelines, "Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock," published in 2004. DESIGN: Modified Delphi method with a consensus conference of 55 international experts, several subsequent meetings of subgroups and key individuals, teleconferences, and electronic-based discussion among subgroups and among the entire committee. This process was conducted independently of any industry funding. METHODS: We used the GRADE system to guide assessment of quality of evidence from high (A) to very low (D) and to determine the strength of recommendations. A strong recommendation indicates that an intervention's desirable effects clearly outweigh its undesirable effects (risk, burden, cost), or clearly do not. Weak recommendations indicate that the tradeoff between desirable and undesirable effects is less clear. The grade of strong or weak is considered of greater clinical importance than a difference in letter level of quality of evidence. In areas without complete agreement, a formal process of resolution was developed and applied. Recommendations are grouped into those directly targeting severe sepsis, recommendations targeting general care of the critically ill patient that are considered high priority in severe sepsis, and pediatric considerations. RESULTS: Key recommendations, listed by category, include: early goal-directed resuscitation of the septic patient during the first 6 hrs after recognition (1C); blood cultures prior to antibiotic therapy (1C); imaging studies performed promptly to confirm potential source of infection (1C); administration of broad-spectrum antibiotic therapy within 1 hr of diagnosis of septic shock (1B) and severe sepsis without septic shock (1D); reassessment of antibiotic therapy with microbiology and clinical data to narrow coverage, when appropriate (1C); a usual 7-10 days of antibiotic therapy guided by clinical response (1D); source control with attention to the balance of risks and benefits of the chosen method (1C); administration of either crystalloid or colloid fluid resuscitation (1B); fluid challenge to restore mean circulating filling pressure (1C); reduction in rate of fluid administration with rising filing pressures and no improvement in tissue perfusion (1D); vasopressor preference for norepinephrine or dopamine to maintain an initial target of mean arterial pressure > or = 65 mm Hg (1C); dobutamine inotropic therapy when cardiac output remains low despite fluid resuscitation and combined inotropic/vasopressor therapy (1C); stress-dose steroid therapy given only in septic shock after blood pressure is identified to be poorly responsive to fluid and vasopressor therapy (2C); recombinant activated protein C in patients with severe sepsis and clinical assessment of high risk for death (2B except 2C for post-operative patients). In the absence of tissue hypoperfusion, coronary artery disease, or acute hemorrhage, target a hemoglobin of 7-9 g/dL (1B); a low tidal volume (1B) and limitation of inspiratory plateau pressure strategy (1C) for acute lung injury (ALI)/acute respiratory distress syndrome (ARDS); application of at least a minimal amount of positive end-expiratory pressure in acute lung injury (1C); head of bed elevation in mechanically ventilated patients unless contraindicated (1B); avoiding routine use of pulmonary artery catheters in ALI/ARDS (1A); to decrease days of mechanical ventilation and ICU length of stay, a conservative fluid strategy for patients with established ALI/ARDS who are not in shock (1C); protocols for weaning and sedation/analgesia (1B); using either intermittent bolus sedation or continuous infusion sedation with daily interruptions or lightening (1B); avoidance of neuromuscular blockers, if at all possible (1B); institution of glycemic control (1B) targeting a blood glucose < 150 mg/dL after initial stabilization ( 2C ); equivalency of continuous veno-veno hemofiltration or intermittent hemodialysis (2B); prophylaxis for deep vein thrombosis (1A); use of stress ulcer prophylaxis to prevent upper GI bleeding using H2 blockers (1A) or proton pump inhibitors (1B); and consideration of limitation of support where appropriate (1D). Recommendations specific to pediatric severe sepsis include: greater use of physical examination therapeutic end points (2C); dopamine as the first drug of choice for hypotension (2C); steroids only in children with suspected or proven adrenal insufficiency (2C); a recommendation against the use of recombinant activated protein C in children (1B). CONCLUSION: There was strong agreement among a large cohort of international experts regarding many level 1 recommendations for the best current care of patients with severe sepsis. Evidenced-based recommendations regarding the acute management of sepsis and septic shock are the first step toward improved outcomes for this important group of critically ill patients.

GUINEA-BISSAU: The Role of Local and International NGOs in Environmental Preservation and Sustainability of the Bijagos Archipelago

Bijagos Archipelago in Guinea-Bissau is at present subject to numerous external impacts that affect its centuries old balance. Since 1975 Guinean society has been using its natural resources in an uncontrolled way over the territory and especially in the coastal area. The archipelago has been increasingly raising interest, most of which is incompatible with the guarantee for a long-term sustainable development. It has also displayed a general impoverishment as far as resource preservation is concerned, due to internal demographic pressure of a population that has doubled since 1981 and to external pressure related to neighboring migrations and consequent depletion of non-renewable resources. This article aims to analyze the actions of local and international NGOs in the preservation and sustainability of the Bijagos Archipelago. We seek through an interdisciplinary approach to analyze the phenomena that are configured within the strategies of NGOs, on the assumption that these issues are articulated in the field of geography and sociology, as well as in politics and international cooperation. It is proposed new challenges to environmental issues, especially in a current situation shaken by constant instability internal and external policies.

Registries in rheumatological and musculoskeletal conditions. Paediatric Behçet's disease: an international cohort study of 110 patients. One-year follow-up data.

OBJECTIVE: To set-up an international cohort of patients suspected with Behçet's disease (BD). The cohort is aimed at defining an algorithm for definition of the disease in children. METHODS: International experts have defined the inclusion criteria as follows: recurrent oral aphthosis (ROA) plus one of following-genital ulceration, erythema nodosum, folliculitis, pustulous/acneiform lesions, positive pathergy test, uveitis, venous/arterial thrombosis and family history of BD. Onset of disease is <16 years, disease duration is ≤3 years, future follow-up duration is ≥4 years and informed consent is obtained. The expert committee has classified the included patients into: definite paediatric BD (PED-BD), probable PED-BD and no PED-BD. Statistical analysis is performed to compare the three groups of patients. Centres document their patients into a single database. RESULTS: At January 2010, 110 patients (56 males/54 females) have been included. Mean age at first symptom: 8.1 years (median 8.2 years). At inclusion, 38% had only one symptom associated with ROA, 31% had two and 31% had three or more symptoms. A total of 106 first evaluations have been done. Seventeen patients underwent the first-year evaluation, and 36 had no new symptoms, 12 had one and 9 had two. Experts have examined 48 files and classified 30 as definite and 18 as probable. Twenty-six patients classified as definite fulfilled the International Study Group criteria. Seventeen patients classified as probable did not meet the international criteria. CONCLUSION: The expert committee has classified the majority of patients in the BD group although they presented with few symptoms independently of BD classification criteria.

Variability in urinary oxalate measurements between six international laboratories.

BACKGROUND: Hyperoxaluria is a major risk factor for kidney stone formation. Although urinary oxalate measurement is part of all basic stone risk assessment, there is no standardized method for this measurement. METHODS: Urine samples from 24-h urine collection covering a broad range of oxalate concentrations were aliquoted and sent, in duplicates, to six blinded international laboratories for oxalate, sodium and creatinine measurement. In a second set of experiments, ten pairs of native urine and urine spiked with 10 mg/L of oxalate were sent for oxalate measurement. Three laboratories used a commercially available oxalate oxidase kit, two laboratories used a high-performance liquid chromatography (HPLC)-based method and one laboratory used both methods. RESULTS: Intra-laboratory reliability for oxalate measurement expressed as intraclass correlation coefficient (ICC) varied between 0.808 [95% confidence interval (CI): 0.427-0.948] and 0.998 (95% CI: 0.994-1.000), with lower values for HPLC-based methods. Acidification of urine samples prior to analysis led to significantly higher oxalate concentrations. ICC for inter-laboratory reliability varied between 0.745 (95% CI: 0.468-0.890) and 0.986 (95% CI: 0.967-0.995). Recovery of the 10 mg/L oxalate-spiked samples varied between 8.7 ± 2.3 and 10.7 ± 0.5 mg/L. Overall, HPLC-based methods showed more variability compared to the oxalate oxidase kit-based methods. CONCLUSIONS: Significant variability was noted in the quantification of urinary oxalate concentration by different laboratories, which may partially explain the differences of hyperoxaluria prevalence reported in the literature. Our data stress the need for a standardization of the method of oxalate measurement.

International consensus guidelines on the management of cytomegalovirus in solid organ transplantation.

Cytomegalovirus (CMV) remains one of the most common infections after solid organ transplantation, resulting in significant morbidity, graft loss, and occasional mortality. Management of CMV varies considerably among transplant centers. A panel of experts on CMV and solid organ transplant was convened by The Infectious Diseases Section of The Transplantation Society to develop evidence and expert opinion-based consensus guidelines on CMV management including diagnostics, immunology, prevention, treatment, drug resistance, and pediatric issues.