Basis for vaccine recommendations

Once a new vaccine has been granted its licensing, a public health expertise is needed in order to support the decision regarding its possible inclusion within the national immunisation schedule. This analysis, based on an assessment of the benefits/risks balance and costs/effectiveness ratio, is a multidisciplinary exercise. Largely based on epidemiological and immunological expertises, it also requires bio-mathematical and economical inputs, if the long term consequences of the vaccination are to be taken into account. Indeed, the main drivers of the decision are the burden of the disease, the characteristics of the vaccine in term of effectiveness and safety, the cost of the vaccination, the feasibility of the adjunction of the vaccine in the schedule, the social demand for this vaccination and the positive or negative indirect effects of a large vaccination on the epidemiology of the disease, in addition to the direct protective effect for vaccinated individuals. New vaccines are generally characterised by a more limited epidemiological impact than older vaccines, in a context of growing requirements from our society regarding drugs, and especially vaccines, safety. Both the real and perceived benefits/risks balances for the more recent vaccines appear questionable. The possibility of detrimental epidemiological consequences of either insufficient vaccination coverage or serotype (or serogroup) replacement is another factor that makes the decision regarding vaccination strategies increasingly complex.     

Basis functions for object-centered representations

In an object-centered representation, the position of the subparts of an object are encoded with respect to a set of axes and an origin centered on the object. Several physiological and neuropsychological results support the existence of such representations in humans and monkeys. An explicit representation would involve neurons with invariant response properties in object-centered coordinates. We consider an alternative scheme using basis functions in which the cells have retinotopic receptive fields modulated by the orientation of the object and task-related signals. We show that this alternative is consistent with single-cell data, is computationally efficient, and accounts for object-centered hemineglect, a syndrome observed in humans after fronto-parietal lesions.     

Statistical Basis for Predicting Technological Progress

Forecasting technological progress is of great interest to engineers, policy makers, and private investors. Several models have been proposed for predicting technological improvement, but how well do these models perform? An early hypothesis made by Theodore Wright in 1936 is that cost decreases as a power law of cumulative production. An alternative hypothesis is Moore''s law, which can be generalized to say that technologies improve exponentially with time. Other alternatives were proposed by Goddard, Sinclair et al., and Nordhaus. These hypotheses have not previously been rigorously tested. Using a new database on the cost and production of 62 different technologies, which is the most expansive of its kind, we test the ability of six different postulated laws to predict future costs. Our approach involves hindcasting and developing a statistical model to rank the performance of the postulated laws. Wright''s law produces the best forecasts, but Moore''s law is not far behind. We discover a previously unobserved regularity that production tends to increase exponentially. A combination of an exponential decrease in cost and an exponential increase in production would make Moore''s law and Wright''s law indistinguishable, as originally pointed out by Sahal. We show for the first time that these regularities are observed in data to such a degree that the performance of these two laws is nearly the same. Our results show that technological progress is forecastable, with the square root of the logarithmic error growing linearly with the forecasting horizon at a typical rate of 2.5% per year. These results have implications for theories of technological change, and assessments of candidate technologies and policies for climate change mitigation.     

A Demographic Basis for Patrilineal Hordes

The evidence for patrilocal group organization among precontact hunter-gatherers is ambiguous. Observations among modern hunter-gatherers suggest that few, if any, are organized into patrilineal hordes or bands, but these observations stem from declining populations in transformed environments. These inadequacies in the data imbue the theoretical arguments concerning hunter-gatherer local organization with special importance. It is shown that ecological arguments against the viability of patrilineal bands fail because they conflate the membership of the camp with the band. The argument that variations in family size preclude patrilineal bands is found to be true in nonpolygynous populations. However, it is argued that patrilineal bands should develop in stable, strongly polygynous populations with small local groups, [hunter-gatherers, local organization, ecology, demography, polygyny]     

A Metabolic Basis for Endothelial-to-Mesenchymal Transition

1. Download high-res image (267KB)
2. Download full-size image

     

On the Molecular Basis for Mechanotransduction

Much is currently known about the signaling pathways that are excited when cells are subjected to a mechanical stimulus, yet we understand little of the process by which the mechanical perturbation is transformed into a biochemical signal. Numerous theories have been proposed, and each has merit. While cells may possess many different ways of responding to stress, the existence of a single unifying principle has much appeal. Here we propose the hypothesis that cells sense mechanical force through changes in protein conformation, leading to altered binding affinities of proteins, ultimately initiating an intracellular signaling cascade or producing changes in the proteins localized to regions of high stress. More generally, this represents an alternative to transmembrane signaling through receptor-ligand interactions providing the cell with a means of reacting to changes in its mechanical, as opposed to biochemical, environment. One example is presented showing how the binding affinity between the focal adhesion targeting domain of focal adhesion kinase and the LD motif of paxillin is influenced by externally applied force.     

A Theoretical Basis for Gompertz'S Curve

GOMPERTZ'S model (1825) has remained a purely empirical one, despite its frequent usage. A theoretical justification is given which permits its employment in cases of accretionary growth.     

A Metabolic Basis for Alzheimer Disease

Most studies of Alzheimer's disease (AD) have focused on a single precipitating alteration as the etiological event rather than global changes closely linked to aging. Recent evidence suggests that the most significant of these global changes are metabolic. Here we present data indicating that metabolic rate, nutrition, and neuronal size are all early indicators of AD. Understanding the cellular and molecular basis for these changes may open a new dimension to understanding AD.     

An Ecological Basis for Integrated Environmental Management

Historically, approaches to environmental management activities have been reactive rather than proactive. Environmental laws and regulations have been generated primarily in response to particular issues (e.g., chemical contamination), creating a piecemeal approach for managing the environment. Responsibilities for managing different resources (e.g., water, air, forests, wildlife) have been assigned to different agencies or groups within government, further fragmenting environmental management. Proactive approaches that recognize the interconnectedness of environmental components are necessary to address complex and long-term environmental management issues. This Perspective proposes an environmental management approach that is comprehensive and systematic, while still being comprehensible to decision-makers and other stakeholders. The proposed approach is based on ecology and environmental values related to decision-making. It considers interrelationships among and between living organisms (including humans) and their physical environment. The proposed approach builds on the ecological risk assessment (ERA) paradigm, including goal (or problem) identification, values identification (ecological and human) for the environment being managed, and data collection and analysis focused on management decision-making. Stakeholder involvement and active participation are essential elements. As demonstrated herein, application of the proposed framework has enabled environmental managers to achieve workable solutions and to avoid or resolve environmental conflicts at both local and regional scales. The proposed framework is demonstrably transportable across political boundaries, applicable to all environments involving natural resources, independent of any particular ideology, and applicable to environmental management activities at all scales.     

Basis set validation for polyatomic cation-water interactions

A study of the effects of counterpoise (CP) corrections in polyatomic cation-water interactions is added to the systematic analysis performed in the past of the basis set superposition error (BSSE) in neutral and anionic adducts. The interaction with water of the ammonium cation and its methyl and -CHO derivatives is considered due to the need to model accurately this functional group, which is common in biological molecules. The basis sets employed are the STO-3G and MINI-1 minimal basis sets and the 3-21G, 4-31G and 6-31G** extended ones. In addition, the 6-311++G (2d,p) and 6-311++G (3d, 2p) basis sets have been used for the smallest system, at the SCF and MP2 levels, both without and with CP correction. These basis sets give an equilibrium distance slightly larger and an interaction energy less favourable than the 6-31G** basis set at the corresponding level, while the inclusion of correlation corrections produces a stronger H-bond at a shorter distance. The results confirm the previous hint of a lower incidence of BSSEs in medium size cationic systems, at a different extent for the various basis sets. While the STO-3G basis set is sharply affected by BSSEs in both the equilibrium distance and the interaction energy, the MINI-1 basis set shows a small BSSE, though its trend is not completely satisfactory because the charge transfer component has an anomalous behaviour with respect to our reference basis set. The 4-31G basis set is the only one able to hold comparison with the 6-31G**, even though the interaction energy produced is slightly overestimated. The 3-21G basis set, when corrected, almost parallels the 4-31G one in this set of compounds. The reliability of the CPED correction is checked and discussed.