Making Markets for Merit Goods: The Political Economy of Antiretrovirals

This paper examines the role of policy entrepreneurs and global activists in shaping the international market for antiretroviral drugs to combat HIV/AIDS. When ARVs first came on the market in the 1990s they were exceedingly expensive; the cost of treatment was upwards of $10,000 per year. These drugs were thus accessible only to those patients who had high incomes. But in 2006, the “international community,” meeting at a United Nations General Assembly Special Session (UNGASS), made an astonishing pledge to those who were infected with HIV. It proclaimed that there should be universal access to ARV treatment. This UNGASS, following up on an earlier historic UN special session devoted entirely to AIDS in 2001, marked the first time in history that the international community pledged itself to chronic care for the ill, which in this case includes the approximately 30 million people around the world estimated to be HIV positive. How do we explain the transformation of ARVs from private goods, which only a few could afford, into merit goods that were (at least declaratively) to be made available to everyone? In other words, how does a norm of “universal access to treatment”—that no person should be denied these life-extending drugs—become the ethical basis for global public policy with respect to pharmaceutical allocation? What are the lessons of the ARV story for other global issues? These are the primary questions we explore in this paper. Briefly, we argue that the policy entrepreneurs and activists who promoted the creation of a universal access to treatment regime—of the transformation of ARVs into global merit goods—relied on a combination of moral arguments and ideas with favorable material circumstances. From the ethical perspective, the task of these entrepreneurs was to convince the “international community” that access to ARVs was a “human right,” or conversely to convince decision-makers that it was morally wrong to allocate these life-enhancing drugs solely on the basis of ability to pay. But from a material standpoint, these arguments were greatly facilitated by the lowering prices of ARVs caused by a combination of differential pricing (that is, lower prices for drugs in the developing world than in the advanced welfare states) and competition from generics producers, coupled with increases in foreign aid spending devoted to HIV/AIDS and other diseases.HIV/AIDS; ARVs; antiretrovirals; activists; policy entrepreneurs; merit goods; international community; global public health; global public policy; foreign aid

Interrupting the social amplification of risk process: a case study in collective emissions reduction

One of the main approaches we have for studying the progressive divergence of understandings around a risk issue is that of social risk amplification. This article describes a case study of a particular environmental contaminant, a chemical flame retardant that could be interpreted as having produced a risk amplifying process. It describes in particular how a group of industrial organizations acted collectively to reduce emissions of this contaminant, in an apparent attempt to avert regulation and boycotts—that is, to intercept the social amplification process and avoid its secondary effects. The aim of the study was to investigate the constitutive qualities of this collective action: the qualities that defined it and made it effective in the eyes of those involved. These include institutionalisation and independence, the ability to confer individual as well as collective benefit, the capacity to attract (rather than avoid) criticism, and the ‘branding’ that helps communicate what otherwise appear to be a set of unconnected, local actions. Although the risk amplification framework has been criticised for implying that there is some externally given risk level that is subsequently amplified, it does appear to capture the mentality of actors involved in issues of this kind. They talk and act as though they believe they are participants in a risk amplification process

Computation of steady and unsteady quasi-one-dimensional viscous/inviscid interacting internal flows at subsonic, transonic, and supersonic Mach numbers

Computations of viscous-inviscid interacting internal flowfields are presented for steady and unsteady quasi-one-dimensional (Q1D) test cases. The unsteady Q1D Euler equations are coupled with integral boundary-layer equations for unsteady, two-dimensional (planar or axisymmetric), turbulent flow over impermeable, adiabatic walls. The coupling methodology differs from that used in most techniques reported previously in that the above mentioned equation sets are written as a complete system and solved simultaneously; that is, the coupling is carried out directly through the equations as opposed to coupling the solutions of the different equation sets. Solutions to the coupled system of equations are obtained using both explicit and implicit numerical schemes for steady subsonic, steady transonic, and both steady and unsteady supersonic internal flowfields. Computed solutions are compared with measurements as well as Navier-Stokes and inverse boundary-layer methods. An analysis of the eigenvalues of the coefficient matrix associated with the quasi-linear form of the coupled system of equations indicates the presence of complex eigenvalues for certain flow conditions. It is concluded that although reasonable solutions can be obtained numerically, these complex eigenvalues contribute to the overall difficulty in obtaining numerical solutions to the coupled system of equations

Paleogeographic and tectonic setting of axial and western metamorphic framework rocks of the southern Sierra Nevada, California

This paper represents an update of our 1978 S.E.P.M. Mesozoic Paleogeography synthesis for the southern Sierra Nevada. We originally postulated that much of the southern Sierra Nevada pre-batholithic metamorphic framework consisted of lower Mesozoic siliciclastic, carbonate and pelitic strata with variable arc volcanic admixtures (Kings sequence). Recent syntheses, however, have attempted to minimize the importance of early Mesozoic strata in the region and to extend coherent Paleozoic terranes into the framework as the predominant protoliths. Neither lithologic correlations nor structural analysis can substantiate such a view, however, and the proposed configuration of the Paleozoic terranes is in conflict with the petrochemical zonation pattern of the Cretaceous batholith. We present stratigraphic relations for the relatively well-preserved lower Mesozoic stratified rocks of the southern Sierra which in general supports our 1978 synthesis. As pointed out by more recent syntheses, however, we now recognize the likelihood of Paleozoic basement rocks occurring in some or many of the Kings sequence pendants. Such rocks are disparate fragments of a highly dismembered polygenetic basement composed of Paleozoic ophiolitic, Shoo Fly, miogeoclinal and possibly Antler belt rocks rather than coherent terranes or crustal blocks. The lower stratal levels of the lower Mesozoic Kings sequence appears to have formed part of a regional post-Sonoman (Triassic) marine overlap sequence above this basement complex. Dismemberment and accretion of the basement complex involved transform truncation of the southwest Cordillera and Foothills ophiolite belt emplacement prior to and coincident with Sonoman thrust tectonics. Following the establishment of a Carnian-Norian carbonate platform as part of the overlap sequence, the region subsided and became part of a regional Early Jurassic forearc to intra-arc extensional basin system with the deposition of Kings sequence turbidites and olistostromes. The basin system was destroyed by Middle and Late Jurassic thrusting. The assertion that much of the Kings sequence is Paleozoic in age is based on the discovery of probable Eocambrian-Cambrian miogeoclinal strata in the Snow Lake pendant of the east-central Sierra Nevada (Lahren and others, 1991). These authors offer a reconstruction of the displacement of these strata as part of a large crustal block from the western Mojave region through the axial Sierra Nevada along a now cryptic fault. The bounds of the hypothetical crustal block, however, are at odds with batholithic petrochemical patterns. We propose a more conservative offset history for the Snow Lake pendant rocks which considers a broader uncertainty in the bounds of the possible source area for the rocks, and satisfies offsets of both batholithic petrochemical patterns and igneous-metamorphic assemblages of the Sierran batholithic complex

Genome-wide SNP analysis of Southern African populations provides new insights into the dispersal of Bantu-speaking groups

The expansion of Bantu-speaking agropastoralist populations had a great impact on the genetic, linguistic, and cultural variation of sub-Saharan Africa. It is generally accepted that Bantu languages originated in an area around the present border between Cameroon and Nigeria approximately 5,000 years ago, from where they spread South and East becoming the largest African linguistic branch. The demic consequences of this event are reflected in the relatively high genetic homogeneity observed across most of sub-Saharan Africa populations. In this work, we explored genome-wide single nucleotide polymorphism data from 28 populations to characterize the genetic components present in sub-Saharan African populations. Combining novel data from four Southern African populations with previously published results, we reject the hypothesis that the "non-Bantu" genetic component reported in South-Eastern Africa (Mozambique) reflects extensive gene flow between incoming agriculturalist and resident hunter-gatherer communities. We alternatively suggest that this novel component is the result of demographic dynamics associated with the Bantu dispersal

Systematic comparison of monoclonal versus polyclonal antibodies for mapping histone modifications by ChIP-seq.

BackgroundThe robustness of ChIP-seq datasets is highly dependent upon the antibodies used. Currently, polyclonal antibodies are the standard despite several limitations: They are non-renewable, vary in performance between lots and need to be validated with each new lot. In contrast, monoclonal antibody lots are renewable and provide consistent performance. To increase ChIP-seq standardization, we investigated whether monoclonal antibodies could replace polyclonal antibodies. We compared monoclonal antibodies that target five key histone modifications (H3K4me1, H3K4me3, H3K9me3, H3K27ac and H3K27me3) to their polyclonal counterparts in both human and mouse cells.ResultsOverall performance was highly similar for four monoclonal/polyclonal pairs, including when we used two distinct lots of the same monoclonal antibody. In contrast, the binding patterns for H3K27ac differed substantially between polyclonal and monoclonal antibodies. However, this was most likely due to the distinct immunogen used rather than the clonality of the antibody.ConclusionsAltogether, we found that monoclonal antibodies as a class perform equivalently to polyclonal antibodies for the detection of histone post-translational modifications in both human and mouse. Accordingly, we recommend the use of monoclonal antibodies in ChIP-seq experiments

Full regularity for a C*-algebra of the Canonical Commutation Relations. (Erratum added)

The Weyl algebra,- the usual C*-algebra employed to model the canonical commutation relations (CCRs), has a well-known defect in that it has a large number of representations which are not regular and these cannot model physical fields. Here, we construct explicitly a C*-algebra which can reproduce the CCRs of a countably dimensional symplectic space (S,B) and such that its representation set is exactly the full set of regular representations of the CCRs. This construction uses Blackadar's version of infinite tensor products of nonunital C*-algebras, and it produces a "host algebra" (i.e. a generalised group algebra, explained below) for the \sigma-representation theory of the abelian group S where \sigma(.,.):=e^{iB(.,.)/2}. As an easy application, it then follows that for every regular representation of the Weyl algebra of (S,B) on a separable Hilbert space, there is a direct integral decomposition of it into irreducible regular representations (a known result). An Erratum for this paper is added at the end.Comment: An erratum was added to the original pape

Hemoglobin genotype has minimal influence on the physiological response of juvenile atlantic cod (Gadus morhua) to environmental challenges

Hemoglobin (Hb) polymorphism in cod is associated with temperature‐related differences in biogeographical distribution, and several authors have suggested that functional characteristics of the various hemoglobin isoforms (HbIs) directly influence phenotypic traits such as growth rate. However, no study has directly examined whether Hb genotype translates into physiological differences at the whole animal level. Thus, we generated a family of juvenile Atlantic cod consisting of all three main Hb genotypes (HbI‐1/1, HbI‐2/2, and HbI‐1/2) by crossing a single pair of heterozygous parents, and we compared their metabolic and cortisol responses to an acute thermal challenge (10&deg;C to their critical thermal maximum [CTM] or 22&deg;C, respectively) and tolerance of graded hypoxia. There were no differences in routine metabolism (at 10&deg;C), maximum metabolic rate, metabolic scope, CTM (overall mean 22.9&deg; &plusmn; 0.2&deg;C), or resting and poststress plasma cortisol levels among Hb genotypes. Further, although the HbI‐1/1 fish grew more (by 15%&ndash;30% during the first 9 mo) when reared at 10&deg; &plusmn; 1&deg;C and had a slightly enhanced hypoxia tolerance at 10&deg;C (e.g., the critical O2 levels for HbI‐1/1, HbI‐2/2, and HbI‐1/2 cod were 35.56% &plusmn; 1.24%, and 40.20% &plusmn; 1.99% air saturation, respectively), these results are contradictory to expectations based on HbI functional properties. Thus, our findings (1) do not support previous assumptions that growth rate differences among cod Hb genotypes result from a more efficient use of the oxygen supply&mdash;that is, reduced standard metabolic rates and/or increased metabolic capacity&mdash;and (2) suggest that in juvenile cod, there is no selective advantage to having a particular Hb genotype with regards to the capacity to withstand ecologically relevant environmental challenges.<br /

Relaxation Dynamics of Pseudomonas aeruginosa Re^I(C)O_3(α-diimine)(HisX)^+ (X=83, 107, 109, 124, 126)Cu-^(II) Azurins

Photoinduced relaxation processes of five structurally characterized Pseudomonas aeruginosa Re^I(CO)_3(α-diimine)(HisX) (X = 83, 107, 109, 124, 126)Cu^(II) azurins have been investigated by time-resolved (ps−ns) IR spectroscopy and emission spectroscopy. Crystal structures reveal the presence of Re-azurin dimers and trimers that in two cases (X = 107, 124) involve van der Waals interactions between interdigitated diimine aromatic rings. Time-dependent emission anisotropy measurements confirm that the proteins aggregate in mM solutions (D2O, KPi buffer, pD = 7.1). Excited-state DFT calculations show that extensive charge redistribution in the ReI(CO)_3 → diimine ^3MLCT state occurs: excitation of this ^3MLCT state triggers several relaxation processes in Re-azurins whose kinetics strongly depend on the location of the metallolabel on the protein surface. Relaxation is manifested by dynamic blue shifts of excited-state ν(CO) IR bands that occur with triexponential kinetics: intramolecular vibrational redistribution together with vibrational and solvent relaxation give rise to subps, 2, and 8−20 ps components, while the ~10^2 ps kinetics are attributed to displacement (reorientation) of the Re^I(CO)_3(phen)(im) unit relative to the peptide chain, which optimizes Coulombic interactions of the Re^I excited-state electron density with solvated peptide groups. Evidence also suggests that additional segmental movements of Re-bearing β-strands occur without perturbing the reaction field or interactions with the peptide. Our work demonstrates that time-resolved IR spectroscopy and emission anisotropy of Re^I carbonyl−diimine complexes are powerful probes of molecular dynamics at or around the surfaces of proteins and protein−protein interfacial regions

Social parasitism and the molecular basis of phenotypic evolution

Contrasting phenotypes arise from similar genomes through a combination of losses, gains, co-option and modifications of inherited genomic material. Understanding the molecular basis of this phenotypic diversity is a fundamental challenge in modern evolutionary biology. Comparisons of the genes and their expression patterns underlying traits in pairs of closely related species offer an unrivalled opportunity to evaluate the extent to which genomic material is reorganised to produce novel traits. Advances in molecular methods now allow us to dissect the molecular machinery underlying phenotypic diversity in almost any organism, from single-celled organisms to the most complex vertebrates. Here we discuss how comparisons of social parasites and their free-living hosts may provide unique insights into the molecular basis of phenotypic evolution. Social parasites evolve from a social ancestor and are specialised to exploit the socially acquired resources of their closely-related, free-living social host. Molecular comparisons of such species pairs can reveal how genomic material is re-organised in the loss of ancestral traits (i.e. of free-living traits in the parasites) and the gain of new ones (i.e. specialist traits required for a parasitic lifestyle). We define hypotheses on the molecular basis of phenotypes in the evolution of social parasitism and discuss their wider application in understanding the molecular basis of phenotypic diversity within the theoretical framework of phenotypic plasticity and shifting reaction norms. Currently there are no data available to test these hypotheses, and so we also provide some proof of concept data for our conceptual model using the paper wasp social parasite-host system (Polistes sulcifer - Polistes dominula). This conceptual framework and first empirical data provide a spring-board for directing future genomic analyses on exploiting social parasites as a route to understanding the evolution of phenotypic specialisation