Leis de potência em economia e finanças

Nesta dissertação aborda-se a aplicação de Leis de Potência (LPs), também designadas de Leis de Pareto ou Leis de Zipf, a dados económicos. As LPs são distribuições estatísticas amplamente usadas na compreensão de sistemas naturais e artificiais. O aparecimento das LPs deve-se a Vilfredo Pareto que, no século XIX, publicou o manual de economia política,“Cours d’Economie Politique”. Nesse manual refere que grande parte da economia mundial segue uma LP, em que 20% da população reúne 80% da riqueza do país. Esta propriedade carateriza uma variável que segue uma distribuição de Pareto (ou LP). Desde então, as LPs foram aplicadas a outros fenómenos, nomeadamente a ocorrência de palavras em textos, os sobrenomes das pessoas, a variação dos rendimentos pessoais ou de empresas, o número de vítimas de inundações ou tremores de terra, os acessos a sítios da internet, etc. Neste trabalho, é estudado um conjunto de dados relativos às fortunas particulares ou coletivas de pessoas ou organizações. Mais concretamente são analisados dados recolhidos sobre as fortunas das mulheres mais ricas do mundo, dos homens mais ricos no ramo da tecnologia, das famílias mais ricas, das 20 mulheres mais ricas da América, dos 400 homens mais ricos da América, dos homens mais ricos do mundo, dos estabelecimentos mais ricos do mundo, das empresas mais ricas do mundo e dos países mais ricos do mundo, bem como o valor de algumas empresas no mercado de ações. Os resultados obtidos revelam uma boa aproximação de parte desses dados a uma LP simples e uma boa aproximação pelos restantes dados a uma LP dupla. Observa-se, assim, diferenciação na forma de crescimento das fortunas nos diferentes casos estudados. Como trabalho futuro, procurar-se-á analisar estes e outros dados, utilizando outras distribuições estatísticas, como a exponencial ou a lognormal, que possuem comportamentos semelhantes à LP, com o intuito de serem comparados os resultados. Um outro aspeto interessante será o de encontrar a explicação analítica para as vantagens da aproximação de dados económicos por uma LP simples vs por uma LP dupla.

Entropy Analysis of Industrial Accident Data Series

Complex industrial plants exhibit multiple interactions among smaller parts and with human operators. Failure in one part can propagate across subsystem boundaries causing a serious disaster. This paper analyzes the industrial accident data series in the perspective of dynamical systems. First, we process real world data and show that the statistics of the number of fatalities reveal features that are well described by power law (PL) distributions. For early years, the data reveal double PL behavior, while, for more recent time periods, a single PL fits better into the experimental data. Second, we analyze the entropy of the data series statistics over time. Third, we use the Kullback–Leibler divergence to compare the empirical data and multidimensional scaling (MDS) techniques for data analysis and visualization. Entropy-based analysis is adopted to assess complexity, having the advantage of yielding a single parameter to express relationships between the data. The classical and the generalized (fractional) entropy and Kullback–Leibler divergence are used. The generalized measures allow a clear identification of patterns embedded in the data.

Structure of a putative ancestral protein encoded by a single sequence repeat from a multidomain proteinase inhibitor gene from Nicotiana alata

Background: The ornamental tobacco Nicotiana alata produces a series of proteinase inhibitors (Pls) that are derived from a 43 kDa precursor protein, NaProPl. NaProPl contains six highly homologous repeats that fold to generate six separate structural domains, each corresponding to one of the native Pls. An unusual feature of NaProPl is that the structural domains lie across adjacent repeats and that the sixth Pl domain is generated from fragments of the first and sixth repeats. Although the homology of the repeats suggests that they may have arisen from gene duplication, the observed folding does not appear to support this. This study of the solution structure of a single NaProPl repeat (aPl1) forms a basis for unravelling the mechanism by which this protein may have evolved, Results: The three-dimensional structure of aPl1 closely resembles the triple-stranded antiparallel beta sheet observed in each of the native Pls. The five-residue sequence Glu-Glu-Lys-Lys-Asn, which forms the linker between the six structural domains in NaProPl, exists as a disordered loop in aPl1. The presence of this loop in aPl1 results in a loss of the characteristically flat and disc-like topography of the native inhibitors. Conclusions: A single repeat from NaProPl is capable of folding into a compact globular domain that displays native-like Pl activity. Consequently, it is possible that a similar single-domain inhibitor represents the ancestral protein from which NaProPl evolved.

Consequences of the multipatient use of a single-patient capillary blood sampling device (CBSD)

Introduction/objectives: Multipatient use of a single-patient CBSD occurred inan outpatient clinic during 4 to 16 months before itsnotification. We looked for transmission of blood-bornepathogens among exposed patients.Methods: Exposed patients underwent serology testing for HBV,HCV and HIV. Patients with isolated anti-HBc receivedone dose of hepatitis B vaccine to look for a memoryimmune response. Possible transmissions were investigatedby mapping visits and sequencing of the viral genomeif needed.Results: Of 280 exposed patients, 9 had died without suspicionof blood-borne infection, 3 could not be tested, and 5declined investigations. Among the 263 (93%) testedpatients, 218 (83%) had negative results. We confirmeda known history of HCV infection in 6 patients (1 coinfectedby HIV), and also identified resolved HBVinfection in 37 patients, of whom 18 were alreadyknown. 2 patients were found to have a previouslyunknown HCV infection. According to the time elapsedfrom the closest previous visit of a HCV-infected potentialsource patient, we could rule out nosocomial transmissionin one case (14 weeks) but not in the other (1day). In the latter, however, transmission was deemedvery unlikely by 2 reference centers based on thesequences of the E1 and HVR1 regions of the virus.Conclusion: We did not identify any transmission of blood-bornepathogens in 263 patients exposed to a single-patientCBSD, despite the presence of potential source cases.Change of needle and disinfection of the device betweenpatients may have contributed to this outcome.Although we cannot exclude transmission of HBV, previousacquisition in endemic countries is a more likelyexplanation in this multi-national population.

Stable transmission of targeted gene modification using single-stranded oligonucleotides with flanking LNAs.

Targeted mutagenesis directed by oligonucleotides (ONs) is a promising method for manipulating the genome in higher eukaryotes. In this study, we have compared gene editing by different ONs on two new target sequences, the eBFP and the rd1 mutant photoreceptor betaPDE cDNAs, which were integrated as single copy transgenes at the same genomic site in 293T cells. Interestingly, antisense ONs were superior to sense ONs for one target only, showing that target sequence can by itself impart strand-bias in gene editing. The most efficient ONs were short 25 nt ONs with flanking locked nucleic acids (LNAs), a chemistry that had only been tested for targeted nucleotide mutagenesis in yeast, and 25 nt ONs with phosphorothioate linkages. We showed that LNA-modified ONs mediate dose-dependent target modification and analyzed the importance of LNA position and content. Importantly, when using ONs with flanking LNAs, targeted gene modification was stably transmitted during cell division, which allowed reliable cloning of modified cells, a feature essential for further applications in functional genomics and gene therapy. Finally, we showed that ONs with flanking LNAs aimed at correcting the rd1 stop mutation could promote survival of photoreceptors in retinas of rd1 mutant mice, suggesting that they are also active in vivo.

MMP-9 as predictive factor for response and progression free survival in breast cancer patients treated with bevacizumab and pegylated liposomal doxorubicin. A multicenter, single-arm phase II trial (SAKK24/06). On behalf of the Swiss Group for Clinical Cancer Research (SAKK).

The benefit of bevacizumab (Bv) has been shown in different tumors including colorectal cancer, renal cancer, pulmonary non-small cell cancer and also breast cancer. However to date, there is no established test evaluating the angiogenic status of a patient and monitoring the effects of anti-angiogenic treatments. Tumor angiogenesis is the result of a balance between multiple pro- and anti¬angiogenic molecules. There is very little published clinical data exploring the impact of the anti-angiogenic therapy on the different angiogenesis-related molecules and the potential role of these molecules as prognostic or predictive factors.

Risky single occasion drinking frequency and alcohol-related consequences: can abstinence during early adulthood lead to alcohol problems?

QUESTIONS UNDER STUDY: the main purpose of this longitudinal study was to determine the impact of risky single occasion drinking (RSOD) frequency on alcohol dependence and drinking consequences reported 15 months later. METHODS: As a baseline sample, 5,990 young men were assessed on their drinking habits including the frequency of RSOD. Of them, 5,196 were reassessed at follow-up 15 months later on RSOD frequency, alcohol dependence and alcohol related consequences in thze interceding year. Drop out biases were investigated. RESULTS: Around 45% of the baseline participants reported regular RSOD (every month or more frequently). Despite the fact that RSOD distribution was generally stable during the initial sample, 47.4% reported a variation of their RSOD frequency 15 months later. Around 25% of the sample reported reduced RSOD frequency. Nonetheless, occasional RS drinkers were more likely to become regular (monthly) RSO drinkers at follow up. Daily and weekly RSOD were associated with high proportions of alcohol dependence and detrimental consequences of drinking. Surprisingly, abstainers at baseline were more likely to be at risk of alcohol dependence and consequences at follow up than non-RSO drinkers. CONCLUSIONS: Despite the fact that alcohol abstinence is logically the best way to avoid the detrimental consequences of alcohol drinking, abstainers at baseline reported as many problems due to alcohol use at follow up as occasional or monthly RSO drinkers. The few participants who had become RSO drinkers during the follow up period were indeed likely to engage in detrimental behaviour. Non-RSO drinkers had the fewest problems due to alcohol use. This substantiates the early occurrence of drinking consequences among inexperienced RSO drinkers.

A single high dose of oral vitamin D3 is insufficient to correct a deficiency in a rheumatologic population

Introduction Vitamin D plays a major role in bone metabolismand neuromuscular function. Supplementation with vitamin D iseffective to reduce the risk of fall and of fracture. However adherenceto oral daily vitamin D is low. Screening and correcting vitamin Dinsufficiency in a rheumatologic population could improve bothmorbidity and quality of life. After determining the prevalence ofvitamin D deficiency in this population, we evaluated if supplementationwith a single high dose of oral 25-OH vitamin D3 wassufficient to correct this abnormality.Methods During one month (November 2009), levels of 25-OHvitamin D were systematically determined in our rheumatology outpatientclinic and classified in: vitamin D deficiency (< 10 μg/l),vitamin D insufficiency (10 to 30 μg/l) or normal vitamin D (> 30 μg/l).Patients with insufficiency or deficiency received respectively a singlehigh dose of 300'000 IU or 600'000 IU oral vitamin D3. In addition,all patients with osteoporosis were prescribed daily supplement ofcalcium (1 g) and vitamin D (800 IU). 25-OH vitamin D levels werereevaluated after 3 months.Results Vitamin D levels were initially determined in 292 patients(mean age 53, 211 women, 87 % Caucasian). 77 % had inflammatoryrheumatologic disease (IRD), 20 % osteoporosis (OP) and 12 %degenerative disease (DD). Vitamin D deficiency was present in 20(6.8 %), while 225 (77.1 %) had insufficiency. Of the 245 patientswith levels < 30μg/l, a new determination of vitamin D level wasavailable in 173 (71 %) at 3 months.Conclusion Vitamin D insufficiency is highly prevalent in ourrheumatologic population (84 %), and is not adequately correctedby a single high dose of oral vitamin D3 in > 50 % of the patientswith IRD and DD. In patients with OP, despite association of asingle high dose with daily oral vitamin D supplementation, 40 %of patients are still deficient when reevaluated at 3 months.

Single cell analysis reveals similar functional competence of dominant and nondominant CD8 T-cell clonotypes.

Immune protection from infectious diseases and cancer is mediated by individual T cells of different clonal origin. Their functions are tightly regulated but not yet fully characterized. Understanding the contribution of each T cell will improve the prediction of immune protection based on laboratory assessment of T-cell responses. Here we developed techniques for simultaneous molecular and functional assessment of single CD8 T cells directly ex vivo. We studied two groups of patients with melanoma after vaccination with two closely related tumor antigenic peptides. Vaccination induced T cells with strong memory and effector functions, as found in virtually all T cells of the first patient group, and fractions of T cells in the second group. Interestingly, high functionality was not restricted to dominant clonotypes. Rather, dominant and nondominant clonotypes acquired equal functional competence. In parallel, this was also found for EBV- and CMV-specific T cells. Thus, the nondominant clonotypes may contribute similarly to immunity as their dominant counterparts.

Evaluation of a Single Dose of Ferric Carboxymaltose in Fatigued, Iron-Deficient Women - PREFER a Randomized, Placebo-Controlled Study

BACKGROUND: Unexplained fatigue is often left untreated or treated with antidepressants. This randomized, placebo-controlled, single-blinded study evaluated the efficacy and tolerability of single-dose intravenous ferric carboxymaltose (FCM) in iron-deficient, premenopausal women with symptomatic, unexplained fatigue. METHODS: Fatigued women (Piper Fatigue Scale [PFS] score ≥5) with iron deficiency (ferritin <50 µg/L and transferrin saturation <20%, or ferritin <15 µg/L) and normal or borderline hemoglobin (≥115 g/L) were enrolled in 21 sites in Austria, Germany, Sweden and Switzerland, blinded to the study drug and randomized (computer-generated randomization sequence) to a single FCM (1000 mg iron) or saline (placebo) infusion. Primary endpoint was the proportion of patients with reduced fatigue (≥1 point decrease in PFS score from baseline to Day 56). RESULTS: The full analysis included 290 women (FCM 144, placebo 146). Fatigue was reduced in 65.3% (FCM) and 52.7% (placebo) of patients (OR 1.68, 95%CI 1.05-2.70; p = 0.03). A 50% reduction of PFS score was achieved in 33.3% FCM- vs. 16.4% placebo-treated patients (p<0.001). At Day 56, all FCM-treated patients had hemoglobin levels ≥120 g/L (vs. 87% at baseline); with placebo, the proportion decreased from 86% to 81%. Mental quality-of-life (SF-12) and the cognitive function scores improved better with FCM. 'Power of attention' improved better in FCM-treated patients with ferritin <15 µg/L. Treatment-emergent adverse events (placebo 114, FCM 209; most frequently headache, nasopharyngitis, pyrexia and nausea) were mainly mild or moderate. CONCLUSION: A single infusion of FCM improved fatigue, mental quality-of-life, cognitive function and erythropoiesis in iron-deficient women with normal or borderline hemoglobin. Although more side effects were reported compared to placebo, FCM can be an effective alternative in patients who cannot tolerate or use oral iron, the common treatment of iron deficiency. Overall, the results support the hypothesis that iron deficiency can affect women's health, and a normal iron status should be maintained independent of hemoglobin levels. TRIAL REGISTRATION: ClinicalTrials.gov NCT01110356.

Antitumour effects of single or combined monoclonal antibodies directed against membrane antigens expressed by human B cells leukaemia.

Background: The increasing availability of different monoclonal antibodies (mAbs) opens the way to more specific biologic therapy of cancer patients. However, despite the significant success of therapy in breast and ovarian carcinomas with anti-HER2 mAbs as well as in non-Hodkin B cell lymphomas with anti-CD20 mAbs, certain B cell malignancies such as B chronic lymphocytic leukaemia (B-CLL) respond poorly to anti-CD20 mAb, due to the low surface expression of this molecule. Thus, new mAbs adapted to each types of tumour will help to develop personalised mAb treatment. To this aim, we analyse the biological and therapeutic properties of three mAbs directed against the CD5, CD71 or HLA-DR molecules highly expressed on B-CLL cells. Results: The three mAbs, after purification and radiolabelling demonstrated high and specific binding capacity to various human leukaemia target cells. Further in vitro analysis showed that mAb anti-CD5 induced neither growth inhibition nor apoptosis, mAb anti-CD71 induced proliferation inhibition with no early sign of cell death and mAb anti-HLA-DR induced specific cell aggregation, but without evidence of apoptosis. All three mAbs induced various degrees of ADCC by NK cells, as well as phagocytosis by macrophages. Only the anti-HLA-DR mAb induced complement mediated lysis. Coincubation of different pairs of mAbs did not significantly modify the in vitro results. In contrast with these discrete and heterogeneous in vitro effects, in vivo the three mAbs demonstrated marked anti-tumour efficacy and prolongation of mice survival in two models of SCID mice, grafted either intraperitoneally or intravenously with the CD5 transfected JOK1-5.3 cells. This cell line was derived from a human hairy cell leukaemia, a type of malignancy known to have very similar biological properties as the B-CLL, whose cells constitutively express CD5. Interestingly, the combined injection of anti-CD5 with anti-HLA-DR or with anti-CD71 led to longer mouse survival, as compared to single mAb injection, up to complete inhibition of tumour growth in 100% mice treated with both anti-HLA-DR and anti-CD5. Conclusions: Altogether these data suggest that the combined use of two mAbs, such as anti-HLA-DR and anti-CD5, may significantly enhance their therapeutic potential.

Contribution of genome-wide significant single-nucleotide polymorphisms and antiretroviral therapy to dyslipidemia in HIV-infected individuals : a longitudinal study

Rapport de synthèse :Les individus HIV-positifs constituent une population à risque pour les maladies cardiovasculaires telles que |'infarctus cardiaque ou cérébrale. Celles-ci découlent d'une formation accélérée d'athéroscIérose. Ces pathologies s'expliquent en grande partie par une dyslipidémie observée au sein de cette population et qui sont dues à des facteurs externes tels que : l'immunosuppression avancée, la virémie non-contrôlée, et les effets de la thérapie antirétrovirale. Récemment, des polymorphismes nucléotidiques simples (SNP) associés à la dyslipidémie ont été mis en évidence d'une manière globale par des Genome-Wide Association Studies (GWAS). Le but principal de cette étude est d'éva|uer et de valider |'effet cumulatif des SNP identifiés dans ces GWAS pour la dyslipidémie chez des patients HIV-positifs. De plus, |'identification des facteurs non-génétiques qui contribuent à la dyslipidémie démontrent |'importance des facteurs externes, tels que mentionnés ci- dessus, et en particulier à ceux de la thérapie antirétrovirale.Les participants de l'étude proviennent de trois groupes: 426 personnes sélectionnées pour une étude précédente, 222 personnes sélectionnées de façon arbitraire dans la "Cohorte HIV Suisse" et 103 personnes sélectionnées avec un "New-Onset Diabetes mellitus" identifiées lors d'études précédentes. Ces individus ont contribué à plus de 34'000 mesures de lipides sur une durée moyenne supérieure à 7 ans. Pour l'étude, 33 SNP identifiés dans des GWAS et 9 SNP identifiés dans d'autres études publiées dans la littérature non-couverte par des GWAS ont été repris. Le génotypage a été complété pour 745 (99.2%) des 751 participants. Pour les analyses statistiques, les thérapies antirétrovirales ont été divisées en trois groupes (favorisant peu, moyennement et fortement la dyslipidémie), et trois scores génétiques ont été créés (profil favorable, moyennement favorable, non favorable/favorisant la dyslipidémie). Dans un premier temps, l'effet sur la valeur des lipides d'un ou deux allèles variants a été analysé au moyen d'un modèle de régression pour chaque SNP en ajustant le modèle pour les variables non- génétiques. Dans un deuxième temps, les SNP ayant une valeur p >= à 0.2 ont été repris dans un model Multi-SNP, ce modèle est également ajusté pour les variables non-génétiques. Puisque cette étude se base sur des SNP précédemment identifiés, celle-ci évalue uniquement l'association établie entre chaque SNP et les critères qui ont été établis au préalable, tels que : Cholestérol totale, HDL Cholestérol, non-HDL Cholestérol ou Triglycérides. Les résultats trouvés lors de |'étude confirment les résultats de la littérature. Cette étude montre que les SNP associés à la dyslipidémie doivent être analysés dans le contexte d'une thérapie antirétrovirale en tenant compte de la démographie et en considérant les valeurs du HIV (CD4+, virémie). Ces SNP montrent une tendance à prédire une dyslipidémie prolongée chez l'individu. En effet, un patient avec une thérapie antirétrovirale favorisant la dyslipidémie et un patrimoine génétique non-favorable a un risque qui est 3-f0is plus important d'avoir un Non-HDL- Cholestérol élevé, 5-fois plus important d'avoir un HDL-Cholestérol abaissé, et 4 à 5-fois plus important d'avoir une hypertriglycéridémie qu'un patient qui suit une thérapie antirétrovirale favorisant peu la dyslipidémie qui a un patrimoine génétique favorable. Vu la corrélation entre les SNP et la thérapie antirétrovirale, les cliniciens devraient intégrer les informations génétiques afin de choisir une thérapie antirétrovirale en fonction du patrimoine génétique.

Decoding sequence learning from single-trial intracranial EEG in humans.

We propose and validate a multivariate classification algorithm for characterizing changes in human intracranial electroencephalographic data (iEEG) after learning motor sequences. The algorithm is based on a Hidden Markov Model (HMM) that captures spatio-temporal properties of the iEEG at the level of single trials. Continuous intracranial iEEG was acquired during two sessions (one before and one after a night of sleep) in two patients with depth electrodes implanted in several brain areas. They performed a visuomotor sequence (serial reaction time task, SRTT) using the fingers of their non-dominant hand. Our results show that the decoding algorithm correctly classified single iEEG trials from the trained sequence as belonging to either the initial training phase (day 1, before sleep) or a later consolidated phase (day 2, after sleep), whereas it failed to do so for trials belonging to a control condition (pseudo-random sequence). Accurate single-trial classification was achieved by taking advantage of the distributed pattern of neural activity. However, across all the contacts the hippocampus contributed most significantly to the classification accuracy for both patients, and one fronto-striatal contact for one patient. Together, these human intracranial findings demonstrate that a multivariate decoding approach can detect learning-related changes at the level of single-trial iEEG. Because it allows an unbiased identification of brain sites contributing to a behavioral effect (or experimental condition) at the level of single subject, this approach could be usefully applied to assess the neural correlates of other complex cognitive functions in patients implanted with multiple electrodes.

Response Prediction in Chronic Hepatitis C by Assessment of IP-10 and IL28B-Related Single Nucleotide Polymorphisms.

BACKGROUND: High baseline levels of IP-10 predict a slower first phase decline in HCV RNA and a poor outcome following interferon/ribavirin therapy in patients with chronic hepatitis C. Several recent studies report that single nucleotide polymorphisms (SNPs) adjacent to IL28B predict spontaneous resolution of HCV infection and outcome of treatment among HCV genotype 1 infected patients. METHODS AND FINDINGS: In the present study, we correlated the occurrence of variants at three such SNPs (rs12979860, rs12980275, and rs8099917) with pretreatment plasma IP-10 and HCV RNA throughout therapy within a phase III treatment trial (HCV-DITTO) involving 253 Caucasian patients. The favorable SNP variants (CC, AA, and TT, respectively) were associated with lower baseline IP-10 (P = 0.02, P = 0.01, P = 0.04) and were less common among HCV genotype 1 infected patients than genotype 2/3 (P<0.0001, P<0.0001, and P = 0.01). Patients carrying favorable SNP genotypes had higher baseline viral load than those carrying unfavorable variants (P = 0.0013, P = 0.029, P = 0.0004 respectively). Among HCV genotype 1 infected carriers of the favorable C, A, or T alleles, IP-10 below 150 pg/mL significantly predicted a more pronounced reduction of HCV RNA from day 0 to 4 (first phase decline), which translated into increased rates of RVR (62%, 53%, and 39%) and SVR (85%, 76%, and 75% respectively) among homozygous carriers with baseline IP-10 below 150 pg/mL. In multivariate analyses of genotype 1-infected patients, baseline IP-10 and C genotype at rs12979860 independently predicted the first phase viral decline and RVR, which in turn independently predicted SVR. CONCLUSIONS: Concomitant assessment of pretreatment IP-10 and IL28B-related SNPs augments the prediction of the first phase decline in HCV RNA, RVR, and final therapeutic outcome.