Influence of age on the haemoglobin concentration of malaria-infected patients in a reference centre in the Brazilian Amazon

Anaemia is amongst the major complications of malaria, a major public health problem in the Amazon Region in Latin America. We examined the haemoglobin (Hb) concentrations of malaria-infected patients and compared it to that of malaria-negative febrile patients and afebrile controls. The haematological parameters of febrile patients who had a thick-blood-smear performed at an infectious diseases reference centre of the Brazilian Amazon between December 2009-January 2012 were retrieved together with clinical data. An afebrile community control group was composed from a survey performed in a malaria-endemic area. Hb concentrations and anaemia prevalence were analysed according to clinical-epidemiological status and demographic characteristics. In total, 7,831 observations were included. Patients with Plasmodium falciparum infection had lower mean Hb concentrations (10.5 g/dL) followed by P. vivax-infected individuals (12.4 g/dL), community controls (12.8 g/dL) and malaria-negative febrile patients (13.1 g/dL) (p < 0.001). Age, gender and clinical-epidemiological status were strong independent predictors for both outcomes. Amongst malaria-infected individuals, women in the reproductive age had considerably lower Hb concentrations. In this moderate transmission intensity setting, both vivax and falciparum malaria are associated with reduced Hb concentrations and risk of anaemia throughout a wide age range.

Nonparametric estimation of Value-at-Risk

A method to estimate an extreme quantile that requires no distributional assumptions is presented. The approach is based on transformed kernel estimation of the cumulative distribution function (cdf). The proposed method consists of a double transformation kernel estimation. We derive optimal bandwidth selection methods that have a direct expression for the smoothing parameter. The bandwidth can accommodate to the given quantile level. The procedure is useful for large data sets and improves quantile estimation compared to other methods in heavy tailed distributions. Implementation is straightforward and R programs are available.

Prevalence of human papillomavirus infection, distribution of viral types and risk factors in cervical samples from human immunodeficiency virus-positive women attending three human immunodeficiency virus-acquired immune deficiency syndrome reference centres in northeastern Brazil

Human immunodeficiency virus (HIV)-positive patients have a greater prevalence of coinfection with human papillomavirus (HPV) is of high oncogenic risk. Indeed, the presence of the virus favours intraepithelial squamous cell lesion progression and may induce cancer. The aim of this study was to evaluate the prevalence of HPV infection, distribution of HPV types and risk factors among HIV-positive patients. Cervical samples from 450 HIV-positive patients were analysed with regard to oncotic cytology, colposcopy and HPV presence and type by means of polymerase chain reaction and sequencing. The results were analysed by comparing demographic data and data relating to HPV and HIV infection. The prevalence of HPV was 47.5%. Among the HPV-positive samples, 59% included viral types of high oncogenic risk. Multivariate analysis showed an association between HPV infection and the presence of cytological alterations (p = 0.003), age greater than or equal to 35 years (p = 0.002), number of partners greater than three (p = 0.002), CD4+ lymphocyte count < 200/mm3 (p = 0.041) and alcohol abuse (p = 0.004). Although high-risk HPV was present in the majority of the lesions studied, the low frequency of HPV 16 (3.3%), low occurrence of cervical lesions and preserved immunological state in most of the HIV-positive patients were factors that may explain the low occurrence of precancerous cervical lesions in this population.

Selection of Reference Genes for Quantitative Real Time PCR (qPCR) Assays in Tissue from Human Ascending Aorta.

Dilatation of the ascending aorta (AAD) is a prevalent aortopathy that occurs frequently associated with bicuspid aortic valve (BAV), the most common human congenital cardiac malformation. The molecular mechanisms leading to AAD associated with BAV are still poorly understood. The search for differentially expressed genes in diseased tissue by quantitative real-time PCR (qPCR) is an invaluable tool to fill this gap. However, studies dedicated to identify reference genes necessary for normalization of mRNA expression in aortic tissue are scarce. In this report, we evaluate the qPCR expression of six candidate reference genes in tissue from the ascending aorta of 52 patients with a variety of clinical and demographic characteristics, normal and dilated aortas, and different morphologies of the aortic valve (normal aorta and normal valve n = 30; dilated aorta and normal valve n = 10; normal aorta and BAV n = 4; dilated aorta and BAV n = 8). The expression stability of the candidate reference genes was determined with three statistical algorithms, GeNorm, NormFinder and Bestkeeper. The expression analyses showed that the most stable genes for the three algorithms employed were CDKN1β, POLR2A and CASC3, independently of the structure of the aorta and the valve morphology. In conclusion, we propose the use of these three genes as reference genes for mRNA expression analysis in human ascending aorta. However, we suggest searching for specific reference genes when conducting qPCR experiments with new cohort of samples.

Discrimination in Bankruptcy Situations

In a bankruptcy situation, not all claimants are affected in the same way. In particular, some depositors may enter into a situation of personal bankruptcy if they lose part of their investments. Events of this kind may lead to a social catastrophe. We propose discrimination among the claimants as a possible solution. A fact considered in the American bankruptcy law (among others) that establishes some discrimination on the claimants, or the Santander Bank that in the Madoff’s case reimbursed only the deposits to its particular customers. Moreover, the necessity of discriminating has already been mentioned in different contexts by Young (1988), Bossert (1995), Thomson (2003) and Pulido et al. (2002, 2007), for instance. In this paper, we take a bankruptcy solution as the reference point. Given this initial allocation, we make transfers from richer to poorer with the purpose of distributing not only the personal incurred losses as evenly as possible but also the transfers in a progressive way. The agents are divided into two groups depending on their personal monetary value (wealth, net-income, GDP or any other characteristic). Then, we impose a set of Axioms that bound the maximal transfer that each net-contributor can make and each net-receiver can obtain. Finally, we define a value discriminant solution, and we characterize it by means of the Lorenz criterion. Endogenous convex combinations between solutions are also considered. Keywords: Bankruptcy, Discrimination, Compensation, Rules JEL classification: C71, D63, D71.

Value of F-18-FDG PET/CT for determining malignant pleural effusion in patients with cancer

Objectif : Les épanchements pleuraux sont fréquents chez les patients porteurs de cancer et déterminer s'ils sont de nature tumorale ou non relève d'une grande importance clinique, particulièrement pour le groupe des carcinomes pulmonaires NON à petites cellules (NSCLC). Le PET/CT s'est montré d'une grande utilité et est actuellement indiscutablement reconnu comme outils nécessaire dans la prise en charge et notamment la stadification et le suivi des cancers, et particulièrement des cancers pulmonaires. Sa capacité à pouvoir distinguer les épanchements pleuraux malins des épanchements pleuraux non tumoraux, « bénins » n'est pas précisément connue et n'a pas jusqu'à présent été investiguée de manière approfondie. Matériel et méthodes : Nous avons examiné la captation du FDG (indice SUVmax) des épanchements pleuraux de 50 PET/CT réalisés chez 47 patients (29 hommes, 18 femmes, 60±16 ans) avec épanchements pleuraux et cancer connu (24 NSCLC, 7 lymphomes, 5 cancer du sein, 4 GIST, 3 mésothéliomes, 2 cancer ORL, 2 tératomes malins, 1 carcinome colorectal, 1 carcinome oesophagien, 1 mélanome). Ces résultats ont été corrélés aux résultats des examens cytopathologiques réalisés après ponction de ces mêmes épanchements dans un intervalle médian de 21 jours (interquartile range -3 to 23). L'examen du liquide d'épanchement comportait la mesure du pH, la distribution relative des différents éléments cellulaires (macrophages, neutrophils, éosinophiles, basophiles, lymphocytes, plasmocytes), la numération cellulaire et bien entendu présence de cellules tumorales. Résultats : Parmis les épanchements, 17 étaient malins (34%) (6 NSCLC, 5 lymphomes, 2 cancers mammaires, 2 mésothéliomes, 2 tératomes malins). Les SUV étaient plus élevés dans les épanchements malins que dans les épanchements bénins [3.7 (95%IC 1.8-5.6) vs. 1.7 g/ml (1.5-1.9), p = 0.001], avec une corrélation entre les épanchements malins et le SUV (coefficient de Spearman ρ = 0.50, p = 0.001). Il n'a pas été observé de corrélation entre aucun des autres paramètres cyptopathologiques ou radiologiques analysé (aire sous la courbe ROC 0.83 ± 0.06). En utilisant un seuil du SUV de 2.2-mg/l, 12 examens PET/CT étaient interprétés comme positifs and 38 comme négatifs avec une sensibilité et une spécificité, valeur prédictive positive et négative de 53%, 91%, 75% and 79% respectivement. Concernant le groupe des NSCLC seulement (n = 24), aire sous la courbe ROC était de 0.95 ± 0.04. Sept examens étaient considérés comme positifs et 17 comme négatifs avec une sensibilité, une spécificité, valeur prédictive positive et négative de 83%, 89%, 71 et 94% respectivement. Conclusion : Le PET/CT peut aider à différencier la nature bénigne ou maligne des épanchements avec une haute spécificité chez les patients avec tumeur connue, en particulier dans un contexte de carcinome NON à petites cellules.

Predictive value of anti-neutrophil cygtoplasmic antibodies (ANCA) in small vessel vasculitis

Résumé Valeur prédictive des anticorps dirigés contre le cytoplasme des neutrophiles (ANCA) dans les vasculites des vaisseaux de petit calibre But du travail : Les vasculites sont des pathologies le plus souvent sévères et parfois létales ; elles nécessitent une reconnaissance et un traitement précoces. Il est donc utile de pouvoir disposer de marqueurs diagnostiques, et éventuellement de marqueurs qui puissent prédire l'activité de la maladie. Les « antineutrophil cytoplasm antibodies » (ANCA) constituent une famille d'autoanticorps dirigés contre des antigènes du cytoplasme des neutrophiles, cellules clés du processus inflammatoire au cours des vasculites. De nombreuses études ont tenté de préciser l'utilité des ANCA dans le diagnostic et le suivi des vasculites avec des résultats contradictoires. Le but de ce travail a été de passer en revue l'évolution clinique des patients suivis dans notre service pour une vasculite à ANCA et évaluer la valeur prédictive des ANCA comme marqueur de récidive. Méthode: Les dossiers médicaux de 36 patients, suivis à notre consultation ambulatoire d'immunologie et allergie du CHUV pour une vasculite à ANCA entre janvier 1990 et décembre 2001, ont été analysés de manière rétrospective afin d'établir une base de données. Les données démographiques, le type de vasculite (granulomatose de Wegener ou polyangéite microscopique) et ses caractéristiques (organes touchés), les traitements reçus, les dosages des ANCA (par immunofluorescence et par ELISA avec détermination des anti-PR3 et/ou anti-MPO), et l'évolution clinique (récidive/rémission) ont été considérés. La valeur pronostique des ANCA dans notre population a été calculée utilisant les valeurs prédictives positive et négative, la likelihood et les odds ratios. La valeur statistique a été examinée par les tests Chi-square test ou Fisher's exact test (valeur significative définie comme p <0.05) à l'aide du programme GraphPad Instat software version 3, San Diego, CA. Résultats : Vingt-trois patients atteints d'une maladie de Wegener et treize d'une polyangéite microscopique ont été suivis pour une durée médiane de cinq ans (entre 1 mois et 16 ans). La plupart des patients ont été traités avec des corticostéroïdes associés à du cyclophosphamide. Une rémission a été obtenue chez 21 patients (91 %) atteints d'une maladie de Wegener, mais 74% ont présenté par la suite une récidive. Tous les patients atteints d'une polyangéite microscopique sont entrés en rémission et 33% ont par la suite récidivé. Une élévation persistante (définie comme supérieure à 6 mois) des ANCA ne s'est pas révélée associée à un risque statistiquement significatif de récidive (p=0.14). En revanche, une élévation soudaine du taux des ANCA s'est démontrée prédictive d'une récidive (table 3). Conclusion : Durant le suivi de certaines vasculites, comme la granulomatose de Wegener et la polyangéite microscopique une élévation des ANCA doit faire redouter une exacerbation de la maladie et, par conséquent, justifie une surveillance accrue.

Drug assessment by a Pharmacy and Therapeutics committee: from drug selection criteria to use in clinical practice.

BACKGROUND In Spain, hospital medicines are assessed and selected by local Pharmacy and Therapeutics committees (PTCs). Of all the drugs assessed, cancer drugs are particularly important because of their budgetary impact and the sometimes arguable added value with respect to existing alternatives. This study analyzed the PTC drug selection process and the main objective was to evaluate the degree of compliance of prescriptions for oncology drugs with their criteria for use. METHODS This was a retrospective observational study (May 2007 to April 2010) of PTC-assessed drugs. The variables measured to describe the committee's activity were number of drugs assessed per year and number of drugs included in any of these settings: without restrictions, with criteria for use, and not included in formulary. These drugs were also analyzed by therapeutic group. To assess the degree of compliance of prescriptions, a score was calculated to determine whether prescriptions for bevacizumab, cetuximab, trastuzumab, and bortezomib were issued in accordance with PTC drug use criteria. RESULTS The PTC received requests for inclusion of 40 drugs, of which 32 were included in the hospital formulary (80.0%). Criteria for use were established for 28 (87.5%) of the drugs included. In total, 293 patients were treated with the four cancer drugs in eight different therapeutic indications. The average prescription compliance scores were as follows: bevacizumab, 83% for metastatic colorectal cancer, 100% for metastatic breast cancer, and 82.3% for non-small-cell lung cancer; cetuximab, 62.0% for colorectal cancer and 50% for head and neck cancer; trastuzumab, 95.1% for early breast cancer and 82.4% for metastatic breast cancer; and bortezomib, 63.7% for multiple myeloma. CONCLUSION The degree of compliance with criteria for use of cancer drugs was reasonably high. PTC functions need to be changed so that they can carry out more innovative tasks, such as monitoring conditions for drug use.

Evaluation of a recombinant rhoptry protein 2 enzyme-linked immunoassay for the diagnosis of toxoplasmosis acquired during pregnancy

The aim of this study was to evaluate an enzyme-linked immunoassay with recombinant rhoptry protein 2 (ELISA-rROP2) for its ability to detectToxoplasma gondii ROP2-specific IgG in samples from pregnant women. The study included 236 samples that were divided into groups according to serological screening profiles for toxoplasmosis: unexposed (n = 65), probable acute infection (n = 48), possible acute infection (n = 58) and exposed to the parasite (n = 65). When an indirect immunofluorescence assay forT. gondii-specific IgG was considered as a reference test, the ELISA-rROP2 had a sensitivity of 61.8%, specificity of 62.8%, predictive positive value of 76.6% and predictive negative value of 45.4% (p = 0.0002). The ELISA-rROP2 reacted with 62.5% of the samples from pregnant women with probable acute infection and 40% of the samples from pregnant women with previous exposure (p = 0.0180). Seropositivity was observed in 50/57 (87.7%) pregnant women with possible infection. The results underscored that T. gondii rROP2 is recognised by specific IgG antibodies in both the acute and chronic phases of toxoplasmosis acquired during pregnancy. However, the sensitivity of the ELISA-rROP2 was higher in the pregnant women with probable and possible acute infections and IgM reactivity.

The Strategic value of European renewable energy promotion policy

Encara falta per fer possible una transformació estratègica d'Europa del sistema d'energia, però el que és de la mateixa importància com a objectius a llarg termini de la FER i Reduccions de GEH són vinculants i forts objectius d'eficiència energètica, no només per 2020, però també per al 2030, 2040 i 2050, com aquesta força ajudaria a fixar l'augment de les energies renovables en el total d'energia consum i per reduir el total Emissions de GEH d'Europa en general, i les del sector de l'energia en particular, encara sent un dels majors emissors de gasos d'efecte hivernacle de tots els sectors. La refosa Directiva, prevista per 2011/12 ha de ser un bones finestres d'oportunitat per finalment establir objectius vinculants d'eficiència energètica, l'únic pilar que encara falta en la força energia interdependents i estratègia sobre el clima de la UE, basat en la reducció de gasos d'efecte hivernacle i i l'eficiència energètica.

Prognostic value of arginase-II expression and regulatory T-cell infiltration in head and neck squamous cell carcinoma.

Tumor-infiltrating lymphocytes are present in a variety of tumors and play a central role in antitumor immune responses. Nevertheless, most cancers progress probably because tumors are only weakly immunogenic and develop multiple immunosuppressive mechanisms. In the present study, on head and neck squamous cell carcinoma, we found high intraepithelial infiltration of regulatory FOXP3(+) T cells, and relatively high levels of BDCA2(+) and FOXP3(+) cells in stromal (peripheral) regions of the tumors. Tumor-infiltrating (intraepithelial) FOXP3(+) T cells were significantly more frequent in patients with oropharynx and oral cavity squamous cell carcinoma and in patients without lymph node metastasis. Furthermore, arginase-II (ARG2) was expressed by 60%, inducible nitric oxide synthetase by 9%, cyclooxygenase-2 by 43%, and B-cell lymphoma 2 (BCL2) by 26% of tumors. Interestingly, the absence of ARG2 expression, enhanced stromal infiltration of CD11c(+) myeloid dendritic cells, and high numbers of FOXP3(+) T cells were each significantly associated with prolonged overall survival, and the latter two parameters were also confirmed by multivariate analysis. For disease-free survival, multivariate analysis revealed significant negative correlations with BCL2 and ARG2 expression by tumor cells. These findings shed new light on mechanisms of cancer progression, and provide rationales for therapeutic inhibition of immunosuppressive mechanisms in head and neck squamous cell carcinoma.

Bonafide, type-specific human papillomavirus persistence among HIV-positive pregnant women: predictive value for cytological abnormalities, a longitudinal cohort study

This study investigated the rate of human papillomavirus (HPV) persistence, associated risk factors, and predictors of cytological alteration outcomes in a cohort of human immunodeficiency virus-infected pregnant women over an 18-month period. HPV was typed through L1 gene sequencing in cervical smears collected during gestation and at 12 months after delivery. Outcomes were defined as nonpersistence (clearance of the HPV in the 2nd sample), re-infection (detection of different types of HPV in the 2 samples), and type-specific HPV persistence (the same HPV type found in both samples). An unfavourable cytological outcome was considered when the second exam showed progression to squamous intraepithelial lesion or high squamous intraepithelial lesion. Ninety patients were studied. HPV DNA persistence occurred in 50% of the cases composed of type-specific persistence (30%) or re-infection (20%). A low CD4+T-cell count at entry was a risk factor for type-specific, re-infection, or HPV DNA persistence. The odds ratio (OR) was almost three times higher in the type-specific group when compared with the re-infection group (OR = 2.8; 95% confidence interval: 0.43-22.79). Our findings show that bonafide (type-specific) HPV persistence is a stronger predictor for the development of cytological abnormalities, highlighting the need for HPV typing as opposed to HPV DNA testing in the clinical setting.

Two-sided learning in new keynesian models: dynamics, (lack of) convergence and the value of information

This paper investigates the role of learning by private agents and the central bank (two-sided learning) in a New Keynesian framework in which both sides of the economy have asymmetric and imperfect knowledge about the true data generating process. We assume that all agents employ the data that they observe (which may be distinct for different sets of agents) to form beliefs about unknown aspects of the true model of the economy, use their beliefs to decide on actions, and revise these beliefs through a statistical learning algorithm as new information becomes available. We study the short-run dynamics of our model and derive its policy recommendations, particularly with respect to central bank communications. We demonstrate that two-sided learning can generate substantial increases in volatility and persistence, and alter the behavior of the variables in the model in a signifficant way. Our simulations do not converge to a symmetric rational expectations equilibrium and we highlight one source that invalidates the convergence results of Marcet and Sargent (1989). Finally, we identify a novel aspect of central bank communication in models of learning: communication can be harmful if the central bank's model is substantially mis-specified

Assessment of occlusive arterial disease of abdominal aorta and lower extremities arteries : value of multidetector CT angiography using and adaptative acquisition method

Rapport de synthèse : Objectif : Le but de ce travail est d`étudier l'angiographie par scanner multi-barrette (AS) dans l'évaluation de l'artériopathie oblitérante (AOMI) de l'aorte abdominale et des membres inférieurs utilisant une méthode adaptative d'acquisition pour optimiser le rehaussement artériel en particulier pour le lit artériel distal et les artères des pieds. Matériels et méthodes : Trente-quatre patients pressentant une AOMI ont bénéficié d'une angiographie trans-cathéter (ATC) et d'une AS dans un délai inférieur ou égal à 15 jours. L'AS a été effectuée du tronc coeliaque jusqu'aux artères des pieds en une seule acquisition utilisant une haute résolution spatiale (16x0.625 mm). La vitesse de table et le temps de rotation pour chaque examen ont été choisis selon le temps de transit du produit de contraste, obtenu après un bolus test. Une quantité totale de 130 ml de contraste à 4 ml/s a été utilisée. L'analyse des images de l'AS a été effectuée par deux observateurs et les données ATC ont été interprétées de manière indépendante par deux autres observateurs. L'analyse a inclus la qualité de l'image et la détection de sténose supérieure ou égale à 50 % par patient et par segment artériel. La sensibilité et la spécificité de l'AS ont été calculées en considérant l'ATC comme examen de référence. La variabilité Interobservateur a été mesurée au moyen d'une statistique de kappa. Résultas : L'ATC a été non-conclusive dans 0.7 % des segments, tandis que l'AS était conclusive dans tous les segments. Sur l'analyse par patient, la sensibilité et la spécificité totales pour détecter une sténose significative égale ou supérieure à 50 % étaient de 100 %. L'analyse par segment a montré des sensibilités et de spécificités variant respectivement de 91 à 100 % et de 81 à 100 %. L'analyse des artères distales des pieds a révélé une sensibilité de 100 % et une spécificité de 90 %. Conclusion : L'angiographie par CT multi-barrettes utilisant cette méthode adaptative d'acquisition améliore la qualité de l'image et fournit une technique non-invasive et fiable pour évaluer L'AOMI, y compris les artères distales des pieds.

Light-induced retinal degeneration correlates with changes in iron metabolism gene expression, ferritin level, and aging.

PURPOSE: Retinal degeneration is associated with iron accumulation in several rodent models in which iron-regulating proteins are impaired. Oxidative stress is catalyzed by unbound iron. METHODS: The role of the heavy chain of ferritin, which sequesters iron, in regulating the thickness of the photoreceptor nuclear layer in the 4- and 16-month-old wild-type H ferritin (HFt(+/+)) and heterozygous H ferritin (HFt(+/-)) mice was investigated, before and 12 days after exposure to 13,000-lux light for 24 hours. The regulation of gene expression of the various proteins involved in iron homeostasis, such as transferrin, transferrin receptor, hephaestin, ferroportin, iron regulatory proteins 1 and 2, hepcidin, ceruloplasmin, and heme-oxygenase 1, was analyzed by quantitative (q)RT-PCR during exposure (2, 12, and 24 hours) and 24 hours after 1 day of exposure in the 4-month-old HFt(+/+) and HFt(+/-) mouse retinas. RESULTS: Retinal degeneration in the 4-month-old HFt(+/-) mice was more extensive than in the HFt(+/+) mice. Yet, it was more extensive in both of the 16-month-old mouse groups, revealing the combined effect of age and excessive light. Injury caused by excessive light modified the temporal gene expression of iron-regulating proteins similarly in the HFt(+/-) and HFt(+/+) mice. CONCLUSIONS: Loss of one allele of H ferritin appears to increase light-induced degeneration. This study highlighted that oxidative stress related to light-induced injury is associated with major changes in gene expression of iron metabolism proteins.