Trends in qualifying biomarkers in drug safety. Consensus of the 2011 meeting of the spanish society of clinical pharmacology.

In this paper we discuss the consensus view on the use of qualifying biomarkers in drug safety, raised within the frame of the XXIV meeting of the Spanish Society of Clinical Pharmacology held in Málaga (Spain) in October, 2011. The widespread use of biomarkers as surrogate endpoints is a goal that scientists have long been pursuing. Thirty years ago, when molecular pharmacogenomics evolved, we anticipated that these genetic biomarkers would soon obviate the routine use of drug therapies in a way that patients should adapt to the therapy rather than the opposite. This expected revolution in routine clinical practice never took place as quickly nor with the intensity as initially expected. The concerted action of operating multicenter networks holds great promise for future studies to identify biomarkers related to drug toxicity and to provide better insight into the underlying pathogenesis. Today some pharmacogenomic advances are already widely accepted, but pharmacogenomics still needs further development to elaborate more precise algorithms and many barriers to implementing individualized medicine exist. We briefly discuss our view about these barriers and we provide suggestions and areas of focus to advance in the field.

Atlas of Mexican Triatominae (Reduviidae: Hemiptera) and vector transmission of Chagas disease

Chagas disease is one of the most important yet neglected parasitic diseases in Mexico and is transmitted by Triatominae. Nineteen of the 31 Mexican triatomine species have been consistently found to invade human houses and all have been found to be naturally infected with Trypanosoma cruzi. The present paper aims to produce a state-of-knowledge atlas of Mexican triatomines and analyse their geographic associations with T. cruzi, human demographics and landscape modification. Ecological niche models (ENMs) were constructed for the 19 species with more than 10 records in North America, as well as for T. cruzi. The 2010 Mexican national census and the 2007 National Forestry Inventory were used to analyse overlap patterns with ENMs. Niche breadth was greatest in species from the semiarid Nearctic Region, whereas species richness was associated with topographic heterogeneity in the Neotropical Region, particularly along the Pacific Coast. Three species,Triatoma longipennis, Triatoma mexicana and Triatoma barberi, overlapped with the greatest numbers of human communities, but these communities had the lowest rural/urban population ratios. Triatomine vectors have urbanised in most regions, demonstrating a high tolerance to human-modified habitats and broadened historical ranges, exposing more than 88% of the Mexican population and leaving few areas in Mexico without the potential for T. cruzitransmission.

Assessment of Epstein-Barr virus nucleic acids in gastric but not in breast cancer by next-generation sequencing of pooled Mexican samples

Gastric (GC) and breast (BrC) cancer are two of the most common and deadly tumours. Different lines of evidence suggest a possible causative role of viral infections for both GC and BrC. Wide genome sequencing (WGS) technologies allow searching for viral agents in tissues of patients with cancer. These technologies have already contributed to establish virus-cancer associations as well as to discovery new tumour viruses. The objective of this study was to document possible associations of viral infection with GC and BrC in Mexican patients. In order to gain idea about cost effective conditions of experimental sequencing, we first carried out an in silico simulation of WGS. The next-generation-platform IlluminaGallx was then used to sequence GC and BrC tumour samples. While we did not find viral sequences in tissues from BrC patients, multiple reads matching Epstein-Barr virus (EBV) sequences were found in GC tissues. An end-point polymerase chain reaction confirmed an enrichment of EBV sequences in one of the GC samples sequenced, validating the next-generation sequencing-bioinformatics pipeline.

Social media and political change: The case of the 2011 revolutions in Tunisia and Egypt

Throughout the past decade, social media have come on the scene of various popular revolts. Their role as tools of information and coordination of social movements, from the Iranian Green Movement in 2009 to the Arab uprisings in 2011, has been widely debated. In most cases, online activism through blogs, Facebook, Twitter or other forms of social media has allowed citizens to be part of a social networking exercise and to engage in a public sphere that would have otherwise been unreachable to them due to severe repression. In Tunisia and Egypt, social media helped protests start and expand thanks to their ability to coordinate and disseminate information quickly. The new information and communication tools were an influential factor in accelerating the revolutionary processes across the Arab world, albeit they cannot be seen as neither the spur nor the drivers of any revolution.

Productivity Growth during the English Industrial Revolution: A Dual Approach

This paper presents new estimates of total factor productivity growth in Britain for the period 1770-1860. We use a dual technique recently popularized by Hsieh (1999), and argue that the estimates we derive from factor prices are of similar quality to quantity-based calculations. Our results provide further evidence, derived from this independent set of sources, that productivity growth during the British Industrial Revolution was relatively slow. During the years 1770-1800, TFP growth was close to zero, according to our estimates. The period 1800-1830 experienced an acceleration of productivity growth. The Crafts-Harley view of the Industrial Revolution is thus reinforced. We also consider alternative explanations of slow productivity growth, and reject the interpretation that focuses on the introduction of steam as a general purpose technology.

Credit rationing and crowding out during the Industrial Revolution: Evidence from Hoare's Bank, 1702-1862

Crowding-out during the British Industrial Revolution has long been one of the leadingexplanations for slow growth during the Industrial Revolution, but little empirical evidence exists to support it. We argue that examinations of interest rates are fundamentally misguided, and that the eighteenth- and early nineteenth-century private loan market balanced through quantity rationing. Using a unique set of observations on lending volume at a London goldsmith bank, Hoare s, we document the impact of wartime financing on private credit markets. We conclude that there is considerable evidence that government borrowing, especially during wartime, crowded out private credit.

Why England? Demand, growth and inequality during the Industrial Revolution

Why was England first? And why Europe? We present a probabilistic model that builds on big-push models by Murphy, Shleifer and Vishny (1989), combined with hierarchical preferences. The interaction of exogenous demographic factors (in particular the English low-pressure variant of the European marriage pattern)and redistributive institutions such as the old Poor Law combined to make an Industrial Revolution more likely. Essentially, industrialization is the result of having a critical mass of consumers that is rich enough to afford (potentially) mass-produced goods. Our model is then calibrated to match the main characteristics of the English economy in 1750 and the observed transition until 1850.This allows us to address explicitly one of the key features of the British IndustrialRevolution unearthed by economic historians over the last three decades the slowness of productivity and output change. In our calibration, we find that the probability of Britain industrializing is 5 times larger than France s. Contrary to the recent argument by Pomeranz, China in the 18th century had essentially no chance to industrialize at all. This difference is decomposed into a demographic and a policy component, with the former being far more important than the latter.

Private borrowing during the financial revolution: Hoare’s Bank and its customers, 1702-1724

The financial revolution improved the British government s ability to borrow, andthus its ability to wage war. North andWeingast argued that it also permitted privateparties to borrow more cheaply and widely.We test these inferences with evidencefrom a London bank.We confirm that private bank credit was cheap in the earlyeighteenth century, but we argue that it was not available widely. Importantly, thegovernment reduced the usury rate in 1714, sharply reducing the circle of privateclients that could be served profitably.

The role of Mexico in the first oil shortage: 1918-1922, an international perspective

In 1921 Mexico produced a quarter of world s petroleum, making the country the secondlargest producer in the world, but by 1930 it only accounted for 3 per cent of world sproduction. To date the discussion has mostly relied on events taking place in Mexico forexplaining the decline of the industry. Very little attention has been placed todevelopments in petroleum industry elsewhere, except Venezuela. Practically noattention has been paid to the reasons for the rise of oil output in Mexico. This neglectsthe massive changes taking place in the petroleum industry worldwide during the GreatWar years and its aftermath, and overall ignores the shortage of oil that occurred in theworld s markets between 1918-1921. These are crucial events in order to understand theearly rise of the Mexican oil industry and set the basis for a better understanding of thesubsequent sudden decline.

Description of the third instar larvae of five species of Cyclocephala (Coleoptera, Melolonthidae, Dynastinae) from Mexico

Description of the third instar larvae of five species of Cyclocephala (Coleoptera, Melolonthidae, Dynastinae) from Mexico. Larvae of four species of Cyclocephala are described for the first time based on specimens collected in Mexican localities: C. barrerai Martínez, 1969 from Puebla, C. sinaloae Howden & Endrödi, 1966 from Sinaloa, C. fasciolata Bates, 1888 from Veracruz, and C. jalapensis Casey, 1915 from Hidalgo. Larva of C. lunulata Burmeister, 1847, is redescribed based on specimens from the Mexican states of Morelos, Puebla, and Veracruz. Diagnostic structures are illustrated and the differences and similarities of each species with other previously described larvae of the genus are commented.

Predicting potential distribution of the jaguar (Panthera onca) in Mexico: identification of priority areas for conservation

Aim The jaguar, Panthera onca, is a species of global conservation concern. In Mexico, the northernmost part of its distribution range, its conservation status, is particularly critical, while its potential and actual distribution is poorly known. We propose an ensemble model (EM) of the potential distribution for the jaguar in Mexico and identify the priority areas for conservation.Location Mexico.Methods We generated our EM based on three presence-only methods (Ecological Niche Factor Analysis, Mahalanobis distance, Maxent) and considering environmental, biological and anthropogenic factors. We used this model to evaluate the efficacy of the existing Mexican protected areas (PAs), to evaluate the adequacy of the jaguar conservation units (JCUs) and to propose new areas that should be considered for conservation and management of the species in Mexico.Results Our results outline that 16% of Mexico (c. 312,000 km2) can be considered as suitable for the presence of the jaguar. Furthermore, 13% of the suitable areas are included in existing PAs and 14% are included in JCUs (Sanderson et al., 2002).Main conclusions Clearly much more should be carried out to establish a proactive conservation strategy. Based on our results, we propose here new jaguar conservation and management areas that are important for a nationwide conservation blueprint.

Tectonomagmatic evolution of Western Amazonia: Geochemical characterization and zircon U-Pb geochronologic constraints from the Peruvian Eastern Cordilleran granitoids

The results of a coupled, in situ laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) U-Pb study on zircon and geochemical characterization of the Eastern Cordilleran intrusives of Peru reveal 1.15 Ga of intermittent magmatism along central Western Amazonia, the Earth's oldest active open continental margin. The eastern Peruvian batholiths are volumetrically dominated by plutonism related to the assembly and breakup of Pangea during the Paleozoic-Mesozoic transition. A Carboniferous-Permian (340-285 Ma) continental arc is identified along the regional orogenic strike from the Ecuadorian border (6 degrees S) to the inferred inboard extension of the Arequipa-Antofalla terrane in southern Peru (14 degrees S). Widespread crustal extension and thinning, which affected western Gondwana throughout the Permian and Triassic resulted in the intrusion of the late- to post-tectonic La Merced-San Ramon-type anatectites dated between 275 and 220 Ma, while the emplacement of the southern Cordillera de Carabaya peraluminous granitoids in the Late Triassic to Early Jurassic (220-190 Ma) represents, temporally and regionally, a separate tectonomagmatic event likely related to resuturing of the Arequipa-Antofalla block. Volcano-plutonic complexes and stocks associated with the onset of the present Andean cycle define a compositionally bimodal alkaline suite and cluster between 180 and 170 Ma. A volumetrically minor intrusive pulse of Oligocene age (ca. 30 Ma) is detected near the southwestern Cordilleran border with the Altiplano. Both post-Gondwanide (30-170 Ma), and Precambrian plutonism (691-1123 Ma) are restricted to isolated occurrences spatially comprising less than 15% of the Eastern Cordillera intrusives. Only one remnant of a Late Ordovician intrusive belt is recognized in the Cuzco batholith (446.5 +/- 9.7 Ma) indicating that the Famatinian arc system previously identified in Peru along the north-central Eastern Cordillera and the coastal Arequipa-Antofalla terrane also existed inboard of this parautochthonous crustal fragment. Hitherto unknown occurrences of late Mesoproterozoic and middle Neoproterozoic granitoids from the south-central cordilleran segment define magmatic events at 691 +/- 13 Ma, 751 +/- 8 Ma, 985 +/- 14 Ma, and 1071-1123 +/- 23 Ma that are broadly coeval with the Braziliano and Grenville-Sunsas orogenies, respectively. Our data suggest the existence of a continuous orogenic belt in excess of 3500 km along Western Amazonia during the formation of Rodinia, its ``early'' fragmentation prior to 690 Ma, and support a model of reaccretion of the Paracas-Arequipa-Antofalla terrane to western Gondwana in the Early Ordovician with subsequent detachment of the Paracas segment in form of the Mexican Oaxaquia microcontinent in Middle Ordovician. A tectonomagmatic model involving slab detachment, followed by underplating of cratonic margin by asthenospheric mantle is proposed for the genesis of the volumetrically dominant Late Paleozoic to early Mesozoic Peruvian Cordilleran batholiths.

Surrogate science: The idol of a universal method for scientific inference

The application of statistics to science is not a neutral act. Statistical tools have shaped and were also shaped by its objects. In the social sciences, statistical methods fundamentally changed research practice, making statistical inference its centerpiece. At the same time, textbook writers in the social sciences have transformed rivaling statistical systems into an apparently monolithic method that could be used mechanically. The idol of a universal method for scientific inference has been worshipped since the "inference revolution" of the 1950s. Because no such method has ever been found, surrogates have been created, most notably the quest for significant p values. This form of surrogate science fosters delusions and borderline cheating and has done much harm, creating, for one, a flood of irreproducible results. Proponents of the "Bayesian revolution" should be wary of chasing yet another chimera: an apparently universal inference procedure. A better path would be to promote both an understanding of the various devices in the "statistical toolbox" and informed judgment to select among these.

"Voyage through death/to life upon these shores": the living dead of the Middle Passage

While historical studies of the Atlantic slave trade have amply demonstrated the magnitude of slave mortality during the Middle Passage, only recently have they started to examine how the captives might have endured and coped with this traumatic experience. Although it constitutes a major topos in African diasporic culture, the Middle Passage has only occasionally been represented directly and in details in novels and in films. This article examines three recent narratives of the Middle Passage, Fred D'Aguiar's novel Feeding the Ghosts (1998), Guy Deslauriers's film Passage du milieu (2000), and Stephanie Smallwood's historical study Saltwater Slavery: A Middle Passage from Africa to American Diaspora (2007). Beyond their individual poetic, aesthetic, and scholarly qualities, what is most striking about these three texts is that they all use the figure of the living dead in order to explore the captives' experience of the transatlantic journey. If the ghastly quality of the living dead powerfully captures the life-threatening material and physical conditions the captives endured on the voyage, its dual, liminal character also allows D'Aguiar, Deslauriers, and Smallwood to represent the metaphysical, psychological, social, and cultural journey they were forced to undertake. Through their use of the trope of the living dead, these three texts show that if death is indeed a central aspect of the experience of the Middle Passage, it impacts the captives in ways that go well beyond the issue of mortality.