Simple estimation of incident HIV infection rates in notification cohorts based on window periods of algorithms for evaluation of line-immunoassay result patterns.

BACKGROUND: Tests for recent infections (TRIs) are important for HIV surveillance. We have shown that a patient's antibody pattern in a confirmatory line immunoassay (Inno-Lia) also yields information on time since infection. We have published algorithms which, with a certain sensitivity and specificity, distinguish between incident (< = 12 months) and older infection. In order to use these algorithms like other TRIs, i.e., based on their windows, we now determined their window periods. METHODS: We classified Inno-Lia results of 527 treatment-naïve patients with HIV-1 infection < = 12 months according to incidence by 25 algorithms. The time after which all infections were ruled older, i.e. the algorithm's window, was determined by linear regression of the proportion ruled incident in dependence of time since infection. Window-based incident infection rates (IIR) were determined utilizing the relationship 'Prevalence = Incidence x Duration' in four annual cohorts of HIV-1 notifications. Results were compared to performance-based IIR also derived from Inno-Lia results, but utilizing the relationship 'incident = true incident + false incident' and also to the IIR derived from the BED incidence assay. RESULTS: Window periods varied between 45.8 and 130.1 days and correlated well with the algorithms' diagnostic sensitivity (R(2) = 0.962; P<0.0001). Among the 25 algorithms, the mean window-based IIR among the 748 notifications of 2005/06 was 0.457 compared to 0.453 obtained for performance-based IIR with a model not correcting for selection bias. Evaluation of BED results using a window of 153 days yielded an IIR of 0.669. Window-based IIR and performance-based IIR increased by 22.4% and respectively 30.6% in 2008, while 2009 and 2010 showed a return to baseline for both methods. CONCLUSIONS: IIR estimations by window- and performance-based evaluations of Inno-Lia algorithm results were similar and can be used together to assess IIR changes between annual HIV notification cohorts.

Expression and one-step purification of Plasmodium proteins in dictyostelium.

Nearly full-length Circumsporozoite protein (CSP) from Plasmodium falciparum, the C-terminal fragments from both P. falciparm and P. yoelii CSP and a fragment comprising 351 amino acids of P.vivax MSPI were expressed in the slime mold Dictyostelium discoideum. Discoidin-tag expression vectors allowed both high yields of these proteins and their purification by a nearly single-step procedure. We exploited the galactose binding activity of Discoidin Ia to separate the fusion proteins by affinity chromatography on Sepharose-4B columns. Inclusion of a thrombin recognition site allowed cleavage of the Discoidin-tag from the fusion protein. Partial secretion of the protein was obtained via an ER independent pathway, whereas routing the recombinant proteins to the ER resulted in glycosylation and retention. Yields of proteins ranged from 0.08 to 3 mg l(-1) depending on the protein sequence and the purification conditions. The recognition of purified MSPI by sera from P. vivax malaria patients was used to confirm the native conformation of the protein expressed in Dictyostelium. The simple purification procedure described here, based on Sepharose-4B, should facilitate the expression and the large-scale purification of various Plasmodium polypeptides.

La crisis en el sector del automóvil

La industria del automóvil es un sector vital para la economía mundial y dentro de la actividad industrial en general, ya que, a su vez, influye en otros sectores industriales: sectores de bienes de equipo, tecnologías de la información, plásticos, caucho, entre muchos otros. Por este y otros motivos que expondremos más adelante hemos decidido encaminar este trabajo hacia un análisis exhaustivo de ese sector, a partir de su evolución histórica y su situación actual. Cabe decir que nuestro trabajo se centra exclusivamente en el ámbito español ya que, en otro caso, nuestro análisis hubiese sido muy generalizado y no hubiésemos podido profundizar más en el tema estudiado

La Crisis y el sector textil

El objetivo de nuestro trabajo es ver como la situación económica actual ha afectado al sector textil, cuáles han sido las consecuencias que ha sufrido y como los consumidores se han adaptado. Para introducirnos en el tema hemos investigado cuáles han sido las consecuencias de este sector. Todo nuestro trabajo se va a basar en el estudio diferenciado en lastiendas convencionales y las empresas low cost, ya que nuestra hipótesis principal es cómo las empresas outlet han ganado terreno a las tiendas convencionales. Nos centraremos en el centro comercial outlet ‘La Roca Village’. Para poder hacerlo nos desplazaremos hasta allí para conocer su historia y su funcionamiento. Se trata de un estudio pedagógico que realizaremos mediante una pequeña muestra y noticias recopiladas de diferentes periódicos económicos.En primer lugar, con un cuestionario podremos comprobar si los consumidores tienen conocimiento de la existencia de outlets y si a partir de la crisis acuden a ellos, haciendo distinción en un ranking de cinco tipos de tienda para conocer el perfil del consumidor.A continuación, a través de un cuestionario y una serie de experimentos vamos a analizar nuestras hipótesis.Por otro lado, realizaremos tres tipos de experimentos para confirmar o refutar nuestras hipótesis principales:El primero consiste en comparar la afluencia de gente entre tienda outlet y tienda convencional en veinte minutos, distinguiendo también un día entre semana y fin de semana.El segundo experimento se trata de comparar el número de compras realizadas entre semana y en fin de semana para tienda outlet y para tienda convencional.El tercer experimento se trata de escoger seis conjuntos de ropa aleatoriamente de la misma marca en tienda outlet, realizar lo mismo en la tienda convencional, calcular su precio medio y plantear la hipótesis de que resulta más costoso vestirse en la tienda convencional que en la tienda outlet. La marca escogida es ZARA y Lefties, ambas pertenecientes a la misma cadena, Inditex.En segundo lugar realizaremos distintas entrevistas a los responsables de tiendas convencionales y tiendas outlet de distintas marcas, de las cuáles realizaremos un resumen sintetizado.Una vez realizado esto, vamos a poder afirmar o refutar las hipótesis y proceder a nuestras conclusiones.

Les Crisis asiàtiques i el procés de globalització : el cas de Corea del Sud

Corea del Sud ha vist en els últims 50 anys com la seva economia creixia a unsritmes espectaculars fins arribar a situar-se entre les primeres del món. El seu ascenssemblava imparable fins que l’any 1997, de forma inesperada per la majoria, esclatà lacrisis. En aquells moments, Corea del Sud s’havia convertit en la undècima economiadel planeta i la sisena potència comercial, sent el primer productor de vaixells imemòries DRAM, el quart de béns electrònics de consum, el cinquè d’automòbils i deproductes petroquímics, els sisè d’acer i el setè de productes tèxtils,A mitjans dels anys 50 el país tenia una economia agrària afectada per unapobresa massiva, la seva renta per càpita era inferior a les d’Angola o Moçambic, peròentre 1962 i 1996 el seu PNB per càpita passà de 87 dòlars a més de 12.000 i el seuPIB es multiplicà per 12, amb una taxa anual mitja de creixement del 8%, convertint-seen un país industrial avançat. A més, durant els anys 70 i 80 havia resistitsorprenentment bé les perturbacions (energètiques, monetàries i comercials) externes,malgrat el seu model de creixement depenia molt de les importacions de petroli, deldeute extern (fins mitjans dels 80) i de les exportacions de manufactures als mercatsoccidentals, i havia superat bé els problemes de deute extern que afectaren a altrespaïsos en vies de desenvolupament.Durant els anys 90 el procés de globalització financera contribuí, aparentment,a sostenir aquest creixement, amb l’entrada d’una quantitat ingent de fluxos de capitalestranger i la integració cada cop més plena dins dels mercats mundials de la mà d’unprocés de liberalització financera i comercial, arribant a aconseguir a finals de 1996 laseva admissió a la Organització de Cooperació i Desenvolupament Econòmic (OCDE).Però aquests factors que contribuïren al creixement li passarien factura, al propiciaruna sèrie de vulnerabilitats macroeconòmiques que acabarien sortint a la llum en elcontext de la crisis asiàtica del 97 i mostrarien la necessitat d’un canvi en el model dedesenvolupament, tan exitós durant anys, però incapaç d’adaptar-se per si sol alsnous paràmetres de l’economia globalitzada.2Com a continuació es veurà, la crisis coreana té unes característiques concretes,que la diferencien de la patida per la resta de països afectats per la crisis asiàtica del97, però comparteix també elements en comú. La crisis coreana s’entén millor dins elmarc en què es produí, el de les crisis asiàtiques. Però encara podem anar més lluny, jaque per molts experts les crisis del 97 han estat les primeres grans crisis de laglobalització i per tant és des d’aquí que s’ha d’analitzar, fins arribar al cas concret deCorea del Sud, incomprensible sense tot el context general.Les debilitats estructurals de les diferents economies asiàtiques afectadespoden explicar parcialment la gènesis de la crisis, però es tracta per molts d’una crisissistèmica global, que s’insereix en un context molt més ampli. Per això s’ha dividit elsegüent anàlisi en tres parts: els efectes de la globalització en general, les crisisasiàtiques i finalment el cas concret de Corea del Sud.

ILS-ESP An efficient, simple, and parameter-free algorithm for solving the permutation flow-shop problem

From a managerial point of view, the more effcient, simple, and parameter-free (ESP) an algorithm is, the more likely it will be used in practice for solving real-life problems. Following this principle, an ESP algorithm for solving the Permutation Flowshop Sequencing Problem (PFSP) is proposed in this article. Using an Iterated Local Search (ILS) framework, the so-called ILS-ESP algorithm is able to compete in performance with other well-known ILS-based approaches, which are considered among the most effcient algorithms for the PFSP. However, while other similar approaches still employ several parameters that can affect their performance if not properly chosen, our algorithm does not require any particular fine-tuning process since it uses basic "common sense" rules for the local search, perturbation, and acceptance criterion stages of the ILS metaheuristic. Our approach defines a new operator for the ILS perturbation process, a new acceptance criterion based on extremely simple and transparent rules, and a biased randomization process of the initial solution to randomly generate different alternative initial solutions of similar quality -which is attained by applying a biased randomization to a classical PFSP heuristic. This diversification of the initial solution aims at avoiding poorly designed starting points and, thus, allows the methodology to take advantage of current trends in parallel and distributed computing. A set of extensive tests, based on literature benchmarks, has been carried out in order to validate our algorithm and compare it against other approaches. These tests show that our parameter-free algorithm is able to compete with state-of-the-art metaheuristics for the PFSP. Also, the experiments show that, when using parallel computing, it is possible to improve the top ILS-based metaheuristic by just incorporating to it our biased randomization process with a high-quality pseudo-random number generator.

On Certain Greedoid Polyhedra, Partially Indexable Scheduling Problems, and Extended Restless Bandit Allocation Indices

We present a polyhedral framework for establishing general structural properties on optimal solutions of stochastic scheduling problems, where multiple job classes vie for service resources: the existence of an optimal priority policy in a given family, characterized by a greedoid (whose feasible class subsets may receive higher priority), where optimal priorities are determined by class-ranking indices, under restricted linear performance objectives (partial indexability). This framework extends that of Bertsimas and Niño-Mora (1996), which explained the optimality of priority-index policies under all linear objectives (general indexability). We show that, if performance measures satisfy partial conservation laws (with respect to the greedoid), which extend previous generalized conservation laws, then the problem admits a strong LP relaxation over a so-called extended greedoid polytope, which has strong structural and algorithmic properties. We present an adaptive-greedy algorithm (which extends Klimov's) taking as input the linear objective coefficients, which (1) determines whether the optimal LP solution is achievable by a policy in the given family; and (2) if so, computes a set of class-ranking indices that characterize optimal priority policies in the family. In the special case of project scheduling, we show that, under additional conditions, the optimal indices can be computed separately for each project (index decomposition). We further apply the framework to the important restless bandit model (two-action Markov decision chains), obtaining new index policies, that extend Whittle's (1988), and simple sufficient conditions for their validity. These results highlight the power of polyhedral methods (the so-called achievable region approach) in dynamic and stochastic optimization.

A Simple Access Pricing Rule to Achieve the Ramsey Outcome in Two-Way Access

In this paper, I consider a general and informationally effcient approach to determine the optimal access rule and show that there exists a simple rule that achieves the Ramsey outcome as the unique equilibrium when networks compete in linear prices without network-based price discrimination. My approach is informationally effcient in the sense that the regulator is required to know only the marginal cost structure, i.e. the marginal cost of making and terminating a call. The approach is general in that access prices can depend not only on the marginal costs but also on the retail prices, which can be observed by consumers and therefore by the regulator as well. In particular, I consider the set of linear access pricing rules which includes any fixed access price, the Efficient Component Pricing Rule (ECPR) and the Modified ECPR as special cases. I show that in this set, there is a unique access rule that achieves the Ramsey outcome as the unique equilibrium as long as there exists at least a mild degree of substitutability among networks' services.

The Simple Economics of Conglomeration with Bankruptcy Costs: Separate or Joint Financing?

Which projects should be financed through separate non-recourse loans (or limited- liability companies) and which should be bundled into a single loan? In the pres- ence of bankruptcy costs, this conglomeration decision trades off the benefit of co- insurance with the cost of risk contamination. This paper characterize this tradeoff for projects with binary returns, depending on the mean, variability, and skewness of returns, the bankruptcy recovery rate, the correlation across projects, the number of projects, and their heterogeneous characteristics. In some cases, separate financing dominates joint financing, even though it increases the interest rate or the probability of bankruptcy.

Partial gene deletion of endothelial nitric oxide synthase predisposes to exaggerated high-fat diet-induced insulin resistance and arterial hypertension.

Nitric oxide (NO) plays a major role in the regulation of cardiovascular and metabolic homeostasis, as evidenced by insulin resistance and arterial hypertension in endothelial NO synthase (eNOS) null mice. Extrapolation of these findings to humans is difficult, however, because eNOS gene deficiency has not been reported. eNOS gene polymorphism and impaired NO synthesis, however, have been reported in several cardiovascular disease states and could predispose to insulin resistance. High-fat diet induces insulin resistance and arterial hypertension in normal mice. To test whether partial eNOS deficiency facilitates the development of insulin resistance and arterial hypertension during metabolic stress, we examined effects of an 8-week high-fat diet on insulin sensitivity (euglycemic clamp) and arterial pressure in eNOS(+/-) mice. When fed a normal diet, these mice had normal insulin sensitivity and were normotensive. When fed a high-fat diet, however, eNOS(+/-) mice developed exaggerated arterial hypertension and had fasting hyperinsulinemia and a 35% lower insulin-stimulated glucose utilization than control mice. The partial deletion of the eNOS gene does not alter insulin sensitivity or blood pressure in mice. When challenged with nutritional stress, however, partial eNOS deficiency facilitates the development of insulin resistance and arterial hypertension, providing further evidence for the importance of this gene in linking metabolic and cardiovascular disease.