Assessing risks of multiple sclerosis therapies.

Over the last two decades, thanks to the discovery of several pharmaceutical agents, multiple sclerosis (MS) has been transformed into a treatable disorder although the degree of therapeutic response may vary considerably. As more medications find their entry into the MS market, a clinician faces a mounting challenge of comparing risk and benefit profiles of various agents in an attempt to find the best treatment approach for each individual patient. In this review, we aim to summarize the available data on safety profiles of available MS therapies while focusing mostly on serious medication specific potential adverse events without discussing the teratogenic potential of each agent (unless there is a black box warning) or hypersensitivity reactions. Our goal is to provide a clinician with guidance on assuring the appropriate safety monitoring for patients treated with one of the agents discussed. We also comment on the future of risk management in MS and discuss possible enhancements to the current model of drug approval process and general strategies to improve the patient safety.

Aging effects on selective attention-related electroencephalographic patterns during face encoding.

Previous electrophysiological studies revealed that human faces elicit an early visual event-related potential (ERP) within the occipito-temporal cortex, the N170 component. Although face perception has been proposed to rely on automatic processing, the impact of selective attention on N170 remains controversial both in young and elderly individuals. Using early visual ERP and alpha power analysis, we assessed the influence of aging on selective attention to faces during delayed-recognition tasks for face and letter stimuli, examining 36 elderly and 20 young adults with preserved cognition. Face recognition performance worsened with age. Aging induced a latency delay of the N1 component for faces and letters, as well as of the face N170 component. Contrasting with letters, ignored faces elicited larger N1 and N170 components than attended faces in both age groups. This counterintuitive attention effect on face processing persisted when scenes replaced letters. In contrast with young, elderly subjects failed to suppress irrelevant letters when attending faces. Whereas attended stimuli induced a parietal alpha band desynchronization within 300-1000 ms post-stimulus with bilateral-to-right distribution for faces and left lateralization for letters, ignored and passively viewed stimuli elicited a central alpha synchronization larger on the right hemisphere. Aging delayed the latency of this alpha synchronization for both face and letter stimuli, and reduced its amplitude for ignored letters. These results suggest that due to their social relevance, human faces may cause paradoxical attention effects on early visual ERP components, but they still undergo classical top-down control as a function of endogenous selective attention. Aging does not affect the face bottom-up alerting mechanism but reduces the top-down suppression of distracting letters, possibly impinging upon face recognition, and more generally delays the top-down suppression of task-irrelevant information.

Does Prison Substance Abuse Treatment Reduce Recidivism?Performance Audit Report Iowa Department of Corrections Licensed Substance Abuse Programs, May 25, 2007

The Iowa Department of Corrections faces a growing prison population expected to quickly exceed current capacities. Additionally, nine out of every ten offenders have a history of alcohol or drug problems often both. Research suggests that alcohol and drugs lead to criminal behavior, which lead offenders right back to prison creating a vicious circle and placing a financial and societal burden on the state. However, research also shows that substance abuse treatment can minimize criminal behavior, and offers a way to shut the revolving prison door. Substance abuse programming attempts to change offender thinking patterns and behavior in order to facilitate re-entry back into the community, lessen substance abuse relapse and reduce recidivism. Yet nearly 60% of offenders with identified needs are not treated, and many lacking treatment are high risk. Additionally, the percentage of offenders returning to prison varies significantly from program to program and some programs can not show they have reduced recidivism when compared to offender groups with substance abuse problems and receiving no treatment at all. All of which minimize the effect substance Abuse programming has in curbing prison population growth and reducing crime.

Bundling and competition for slots: Sequential pricing

In this paper we study, as in Jeon-Menicucci (2009), competition between sellerswhen each of them sells a portfolio of distinct products to a buyer having limitedslots. This paper considers sequential pricing and complements our main paper (Jeon-Menicucci, 2009) that considers simultaneous pricing.First, Jeon-Menicucci (2009) find that under simultaneous individual pricing, equilibriumoften does not exist and hence the outcome is often inefficient. By contrast,equilibrium always exists under sequential individual pricing and we characterize it inthis paper. We find that each seller faces a trade-off between the number of slots heoccupies and surplus extraction per product, and there is no particular reason thatthis leads to an efficient allocation of slots.Second, Jeon-Menicucci (2009) find that when bundling is allowed, there alwaysexists an efficient equilibrium but inefficient equilibria can also exist due to purebundling (for physical products) or slotting contracts. Under sequential pricing,we find that all equilibria are efficient regardless of whether firms can use slottingcontracts, and both for digital goods and for physical goods. Therefore, sequentialpricing presents an even stronger case for laissez-faire in the matter of bundling thansimultaneous pricing.

Strong minimax lower bounds for learning

Minimax lower bounds for concept learning state, for example, thatfor each sample size $n$ and learning rule $g_n$, there exists a distributionof the observation $X$ and a concept $C$ to be learnt such that the expectederror of $g_n$ is at least a constant times $V/n$, where $V$ is the VC dimensionof the concept class. However, these bounds do not tell anything about therate of decrease of the error for a {\sl fixed} distribution--concept pair.\\In this paper we investigate minimax lower bounds in such a--stronger--sense.We show that for several natural $k$--parameter concept classes, includingthe class of linear halfspaces, the class of balls, the class of polyhedrawith a certain number of faces, and a class of neural networks, for any{\sl sequence} of learning rules $\{g_n\}$, there exists a fixed distributionof $X$ and a fixed concept $C$ such that the expected error is larger thana constant times $k/n$ for {\sl infinitely many n}. We also obtain suchstrong minimax lower bounds for the tail distribution of the probabilityof error, which extend the corresponding minimax lower bounds.

A simple permutation test for clusteredness

Hierarchical clustering is a popular method for finding structure in multivariate data,resulting in a binary tree constructed on the particular objects of the study, usually samplingunits. The user faces the decision where to cut the binary tree in order to determine the numberof clusters to interpret and there are various ad hoc rules for arriving at a decision. A simplepermutation test is presented that diagnoses whether non-random levels of clustering are presentin the set of objects and, if so, indicates the specific level at which the tree can be cut. The test isvalidated against random matrices to verify the type I error probability and a power study isperformed on data sets with known clusteredness to study the type II error.

Consultoria em Gestão de Recursos Naturais – Áreas Protegidas São Nicolau

São Nicolau apresenta uma configuração da qual ressaltam duas situações distintas: - um corpo principal, cujo contorno se assemelha ao do continente africano e um prolongamento oriental de 22.5 km, localmente designado por Ponta Norte. O corpo principal estende-se no sentido N-S e em 22.5 km, desde a Ponta Espechim à Ponta da Vermelharia e no sentido W-E desde a Ponta Bronco até à base N (alt. 138 m) no Campo da Preguiça, ao longo de 15.3 km. A extensão oriental vai desde o Campo da Preguiça até à Ponta à Ponta Pélam, no extremo leste. Na morfologia geral de S. Nicolau, com realce para as formações salientes de relevo, destacam-se: as plataformas costeiras de cotas baixas que contornam quase toda a ilha e que se relacionam com os derrames basálticos da última fase lávica, em parte recobertos por materiais piroclásticos ou depósitos de materiais de escorrimento; as formas de relevo acidentado que se erguem continuamente da superfície costeira e a crista montanhosa central, de relevos majestosos e miudamente talhados pela erosão e que são mais influenciados pelos ventos húmidos que sopram de Nordeste. O clima da ilha tem, em grande parte, características de extrema aridez, aridez acentuada e semi-aridez. Toda plataforma circundante, de baixo relevo, exceptuando a correspondente à fachada exposta a nordeste, apresenta características de extrema aridez. As faces viradas a E, S e W, plataformas de colinas salientes, formas residuais de relevo e vertentes escarpadas, demarcam-se pela sua acentuada aridez, enquanto que a fachada montanhosa exposta a NE apresenta características de região semi-árida. A fachada montanhosa exposta a NE, apresenta, características, de zonas sub-húmidas, a partir de 200/300 m até 600/700 m e de zonas húmidas, nas zonas do ponto culminante da ilha ou seja, Monte Gordo. Monte Gordo, Monte do Alto das Cabaças, considerados os centros de maior concentração de espécies da flora autóctone e da vegetação natural da ilha, e Fajã de Cima e Lombo Pelado, zonas de maior concentração do dragoeiro (Dracaena draco), são as áreas propostas para protecção.

Insider Trading and Real Investment

In this paper I analyze the effects of insider trading on real investmentand the insurance role of financial markets. There is a single entrepreneurwho, at a first stage, chooses the level of investment in a risky business.At the second stage, an asset with random payoff is issued and then the entrepreneurreceives some privileged information on the likely realization of productionreturn. At the third stage, trading occurs on the asset market, where theentrepreneur faces the aggregate demand coming from a continuum of rationaluniformed traders and some noise traders. I compare the equilibrium withinsider trading (when the entrepreneur trades on her inside information in theasset market) with the equilibrium in the same market without insider trading. Ifind that permitting insider trading tends to decrease the level of realinvestment. Moreover, the asset market is thinner and the entrepreneur's netsupply of the asset and the hedge ratio are lower, although the asset priceis more informative and volatile.

Regulating financial conglomerates

We investigate the optimal regulation of financial conglomerates which combinea bank and a non-bank financial institution. The conglomerate s risk-taking incentivesdepend upon the level of market discipline it faces, which in turn isdetermined by the conglomerate s liability strucure. We examine optimal capitalrequirements for standalone institutions, for integrated financial conglomerates,and for financial conglomerates that are structured as holding companies.For a given risk profile, integrated conglomerates have a lower probability offailure than either their standalone or decentralised equivalent. However, whenrisk profiles are endogenously selected conglomeration may extend the reachof the deposit insurance safety net and hence provide incentives for increasedrisk-taking. As a result, integrated conglomerates may optimally attract highercapital requirements. In contrast, decentralised conglomerates are able to holdassets in the socially most efficient place. Their optimal capital requirementsencourage this. Hence, the practice of regulatory arbitrage , or of transferingassets from one balance sheet to another, is welfare-increasing. We discuss thepolicy implications of our finding in the context not only of the present debateon the regulation of financial conglomerates but also in the light of existingUS bank holding company regulation.

Dinâmica populacional de ácaros fitófagos (Acari, Eriophyidae, Tenuipalpidae) em seis clones de seringueira no sul do Estado de Mato Grosso

Foi estudada a dinâmica populacional de Calacarus heveae Feres, 1992, Phyllocoptruta seringueirae Feres, 1998 (Eriophyidae) e Tenuipalpus heveae Baker, 1945 (Tenuipalpidae) em seis clones de seringueira (Hevea brasiliensis Muell. Arg.), com o intuito de conhecer a sazonalidade e as possíveis diferenças nos níveis de infestação dessas espécies sobre os diferentes clones, em seringal localizado no sul do Estado de Mato Grosso. Para isso, no período de março de 2004 a março de 2005, foram realizadas coletas num intervalo médio de catorze dias em seis parcelas clonais. Em cada amostragem, foram analisados 100 folíolos de cada parcela, registrando-se o número total de ácaros encontrados em ambas as faces. Os níveis de infestação das espécies variaram entre os diferentes clones. O clone RRIM 600 apresentou maior abundância de T. heveae, enquanto que PB 235 e PB 260 de P. seringueira e C. heveae, respectivamente. Por outro lado, esse último clone apresentou menor número de indivíduos de T. heveae e P. seringueirae, e PB 235 de C. heveae. O primeiro semestre foi o período crítico de infestação, porém a duração da ocorrência e o pico de abundância dos fitófagos variaram nos diferentes clones.

Avaliação Ecológica das Terras Salgadas - Ilha do Maio, Cabo Verde para Possível Estabelecimento de uma Nova População da Laverca do Raso (Alauda Razae)

A laverca do Raso (Alauda razae) é uma espécie em risco crítico de extinção pois só existe num pequeno ilhéu de 7km2, o ilhéu do Raso em Cabo Verde. As medidas de protecção já adoptadas, não são, aparentemente, suficientes para prevenir os riscos a que esta espécie está ou poderá estar sujeita e que podem incluir grandes períodos de seca, ocorrência de uma catástrofe natural ou a introdução acidental de mamíferos predadores, como gatos e ratos. Assim, torna-se urgente a adopção de outras medidas de protecção da espécie, como por exemplo o estabelecimento de novas populações noutras ilhas. A ilha do Maio, localizada no grupo sul do arquipélago de Cabo Verde, a 200km do Raso, poderá ser um bom local para estabelecer uma nova população da laverca do Raso. A zona litoral das Terras Salgadas é um local potencial para este efeito, uma vez que é um Parque Nacional, protegido por lei e apresenta um habitat potencialmente semelhante ao encontrado no Ilhéu do Raso. No presente estudo procedeu-se à avaliação ecológica das Terras Salgadas de modo a avaliar a possibilidade de aí se estabelecer uma nova população da laverca do Raso. Foram selecionadas 4 áreas litorais (cada uma com 25ha) que foram caracterizadas quanto ao tipo de ocupação do solo, à flora e à fauna, através de pontos de amostragem, transectos lineares, captura de ratos e contagem de insectos nocturnos. Foi dada particular atenção aos factores favoráveis à sobrevivência da cotovia-do-Raso (presença de plantas e insectos de que se alimenta e de locais favoráveis à nidificação) bem como àqueles que constituem riscos (influência humana e presença de predadores). Todos estes dados foram georreferenciados e mapeados. Os resultados obtidos permitiram concluir que, apesar da existência de factores de risco para a introdução da laverca do Raso, existem pelo menos duas áreas estudadas que reúnem as condições potencialmente adequadas ao estabelecimento bem-sucedido de uma nova população desta espécie.

Balance Between Investment Protection and Sustainable Development in BITs: the Example of Switzerland

The objective of this article is to examine how substantive and procedural rights granted to foreign investors by Swiss bits are gradually being balanced with social and environmental provisions. Switzerland has enjoyed a long bit practice, as it signed its first treaty with Tunisia fifty years ago. Swiss bits rely on the post-establishment model and include usual standards of treatment. From 1981, they also systematically provide for a dispute settlement mechanism for disputes arising between an investor and a host State. Since the Switzerland - El Salvador bit in 1994, sustainable development concerns have been expressly inserted in some Swiss bits, as well as in several recent free trade agreements. Provisions on this theme are however far from being systematic in Switzerland's bit practice and essentially remain declaratory in nature. The trend towards wider inclusion of sustainable development provisions in bits still faces several practical and political challenges.

Specialization and rent-seeking in moral enforcement: The case of confession

Moral codes are produced and enforced by more or less specialized means and are subject to standard economic forces. This paper argues that the intermediary role played by the Catholic Church between God and Christians, a key difference from Protestantism, faces the standard trade-off of specialization benefits and agency costs. It applies this trade-off hypothesis to confession of sins to priests, an institution that epitomizes such intermediation, showing that this hypothesis fits cognitive, historical and econometric evidence better than a simpler rent-seeking story. In particular, Catholics who confess more often are observed to comply more with the moral code; however, no relationship is observed between mass attendance and moral compliance. The data also links the current decline in confession to the rise in education, which makes moral self-enforcement less costly, and to the productivity gap suffered by confession services, given its necessarily interpersonal nature.

Cape Verde - Diagnostic Trade Inttegration study Update - 2013

This Report is an update of the Cape Verde Diagnostic Trade Integration Study, titled Cape Verde’s Insertion into the Global Economy, produced and validated by the Government of Cape Verde in December 2008. Like the previous 2008 study, this Cape Verde Diagnostic Trade Integration Study Update provides a critical examination of the major institutional and production constraints that hinder Cape Verde’s ability to capitalize fully on the growth and welfare gains from its integration into the world economy. As a policy report, this study offers a set of priority policies and measures that can be implemented by both the public and private sectors to mitigate and surmount these supply side and institutional constraints. These recommendations are summarized in an Action Matrix. The Report is fruit of the generous support of the multi-donor program the Enhanced Integrated Framework (EIF). In every crisis there is an opportunity. Four years after the validation of the country’s first Diagnostic Trade Integration Study in 2008, Cape Verde finds itself in a drastically altered external environment. Cape Verde faces a worsened external environment than four years ago, when it was also traversing years of crisis as global food and energy prices escalated. Just as the country was validating its first trade study in late 2008, and celebrating its graduation from the list of Least Developed Countries, the onset of the deepest global recession in recent memory triggered an even worse external situation as the country’s principal source of markets, investments, remittances and aid, the Eurozone, unraveled economically and politically. As the Eurozone crisis spread, it was Cape Verde’s misfortune that the crisis contaminated precisely its biggest Eurozone partners and donors, such as Portugal, Spain and Italy. For such a highly dependent and exposed economy like that of Cape Verde, the deteriorating external sector has had a substantial negative impact on its macroeconomic performance. At the time of the validation workshop and graduation in 2008, no one could have foreseen or predicted the severity of the global crisis that followed. Despite traversing these years of adversity and external shocks, and suffering palpable setbacks, Cape Verde’s economy had proven surprisingly resilient, especially its principal sector, tourism. To its great credit, the country’s economic fundamentals are solid, and have been carefully and prudently managed over the years. For this reason alone, the country has thus far weathered the global and Eurozone crisis. Yet the near and medium term future remains uncertain. The country’s margin for maneuver has narrowed, its options far more limited, and hard choices lie ahead. Thus, there is no better time than now to analyze Cape Verde’s position in the global economy, and to examine the many challenges and opportunities it faces. The first diagnostic trade study outlined an ambitious agenda and set of policy strategies to enhance Cape Verde’s participation in the global economy. Written prior to the global crisis, the study did not, and could not, anticipate the scope and depth of the subsequent global and Eurozone crises. A few short months before the validation of the first DTIS Cape Verde joined the World Trade Organization (WTO). It has spent these four years adjusting to this status and implementing its commitments. At the same time, the country seeks greater economic integration with the European Union. Since 2008 the government has been investing heavily in the country’s economic infrastructure, focusing especially on fostering transformation in key sectors like agriculture, fisheries, tourism and creative industries. For these and many other reasons, it is both timely and urgent to review the road traveled since 2008. It is an opportune moment to reassess the country’s options, to rethink strategies, and to chart a new way forward that it is practical, implementable, and that builds on the country’s competitive advantages and current successes.

Long run relationships and price rigidity

I study a repeated buyer-seller relationship for the exchange of a givengood. Asymmetric information over the buyer's reservation price, which issubject to random shocks, may lead the seller to use a rigid pricing policydespite the possibility of making higher profits through price discriminationacross the different satates of the buyer's reservation price. The existence of a flexible price subgame perfect equilibrium is shown for the buyerssufficiently locked-in. When the seller faces a population of buyers whose degree of involvmentin the relatioship is unknown, the flexible price equilibrium is notnecessarily optimal. Thus tipically the seller will prefer to use therigid price strategy. A learning process allowing the seller to screenthe population of buyers is derived abd the existence of a switching pointbetween the two regimes (i.e. price rigidity and price felxibility) isshown.