The humoral response to HIV-1: new insights, renewed focus.

During the past 2 decades, significant advances in our understanding of the humoral immune response to human immunodeficiency virus type 1 (HIV-1) infection have been made, yet a tremendous amount of work lies ahead. Despite these advances, strategies to reliably induce antibodies that can control HIV-1 infection are still critically needed. However, recent advances in our understanding of the kinetics, specificity, and function of early humoral responses offer alternative new approaches to attain this goal. These results, along with the new broadly neutralizing antibody specificities, the role for other antibody functions, the increased understanding of HIV-1-induced changes to B cell biology, and results from the RV144 "Thai" trial showing potential modest sterilizing protection by nonneutralizing antibody responses, have renewed focus on the humoral system. In this review, recent advances in our understanding of the earliest humoral responses are discussed, highlighting presentations from the meeting on the Biology of Acute HIV Infection.

Cost-effectiveness analysis of the diagnosis of meniscus tears.

BACKGROUND: Diagnostic imaging represents the fastest growing segment of costs in the US health system. This study investigated the cost-effectiveness of alternative diagnostic approaches to meniscus tears of the knee, a highly prevalent disease that traditionally relies on MRI as part of the diagnostic strategy. PURPOSE: To identify the most efficient strategy for the diagnosis of meniscus tears. STUDY DESIGN: Economic and decision analysis; Level of evidence, 1. METHODS: A simple-decision model run as a cost-utility analysis was constructed to assess the value added by MRI in various combinations with patient history and physical examination (H&P). The model examined traumatic and degenerative tears in 2 distinct settings: primary care and orthopaedic sports medicine clinic. Strategies were compared using the incremental cost-effectiveness ratio (ICER). RESULTS: In both practice settings, H&P alone was widely preferred for degenerative meniscus tears. Performing MRI to confirm a positive H&P was preferred for traumatic tears in both practice settings, with a willingness to pay of less than US$50,000 per quality-adjusted life-year. Performing an MRI for all patients was not preferred in any reasonable clinical scenario. The prevalence of a meniscus tear in a clinician's patient population was influential. For traumatic tears, MRI to confirm a positive H&P was preferred when prevalence was less than 46.7%, with H&P preferred above that. For degenerative tears, H&P was preferred until the prevalence reaches 74.2%, and then MRI to confirm a negative was the preferred strategy. In both settings, MRI to confirm positive physical examination led to more than a 10-fold lower rate of unnecessary surgeries than did any other strategy, while MRI to confirm negative physical examination led to a 2.08 and 2.26 higher rate than H&P alone in primary care and orthopaedic clinics, respectively. CONCLUSION: For all practitioners, H&P is the preferred strategy for the suspected degenerative meniscus tear. An MRI to confirm a positive H&P is preferred for traumatic tears for all practitioners. Consideration should be given to implementing alternative diagnostic strategies as well as enhancing provider education in physical examination skills to improve the reliability of H&P as a diagnostic test. CLINICAL RELEVANCE: Alternative diagnostic strategies that do not include the use of MRI may result in decreased health care costs without harm to the patient and could possibly reduce unnecessary procedures.

Heavy metal accumulation reflecting natural sedimentary processes and anthropogenic activities in two contrasting coastal wetland ecosystems, eastern China

Due to the impacts of natural processes and anthropogenic activities, different coastal wetlands are faced with variable patterns of heavy metal contamination. It is important to quantify the contributions of pollutant sources, in order to adopt appropriate protection measures for local ecosystems. The aim of this research was to compare the heavy metal contamination patterns of two contrasting coastal wetlands in eastern China. In addition, the contributions from various metal sources were identified and quantified, and influencing factors, such as the role of the plant Spartina alterniflora, were evaluated. Materials and methods Sediment samples were taken from two coastal wetlands (plain-type tidal flat at the Rudong (RD) wetland vs embayment-type tidal flat at Luoyuan Bay (LY)) to measure the content of Al, Fe, Co, Cr, Cu, Mn, Mo, Ni, Sr, Zn, Pb, Cd, and As. Inductively coupled plasma atomic emission spectrometry, flame atomic absorption spectrometry, and atomic fluorescence spectrometry methods were used for metal detection. Meanwhile, the enrichment factor and geoaccumulation index were applied to assess the pollution level. Principle component analysis and receptor modeling were used to quantify the sources of heavy metals. Results and discussion Marked differences in metal distribution patterns between the two systems were present. Metal contents in LY were higher than those in RD, except for Sr and Mo. The growth status of S. alterniflora influenced metal accumulations in RD, i.e., heavy metals were more easily adsorbed in the sediment in the following sequence: Cu > Cd > Zn > Cr > Al > Pb ≥ Ni ≥ Co > Fe > Sr ≥ Mn > As > Mo as a result of the presence and size of the vegetation. However, this phenomenon was not observed in LY. A higher potential ecological risk was associated with LY, compared with RD, except for Mo. Based on a receptor model output, sedimentary heavy metal contents at RD were jointly influenced by natural sedimentary processes and anthropogenic activities, whereas they were dominated by anthropogenic activities at LY. Conclusions A combination of geochemical analysis and modeling approaches was used to quantify the different types of natural and anthropogenic contributions to heavy metal contamination, which is useful for pollution assessments. The application of this approach reveals that natural and anthropogenic processes have different influences on the delivery and retention of metals at the two contrasting coastal wetlands. In addition, the presence and size of S. alterniflora can influence the level of metal contamination in sedimentary environments.

Transdisciplinary Science: A Path to Understanding the Interactions Among Ocean Acidification, Ecosystems, and Society

The global nature of ocean acidification (OA) transcends habitats, ecosystems, regions, and science disciplines. The scientific community recognizes that the biggest challenge in improving understanding of how changing OA conditions affect ecosystems, and associated consequences for human society, requires integration of experimental, observational, and modeling approaches from many disciplines over a wide range of temporal and spatial scales. Such transdisciplinary science is the next step in providing relevant, meaningful results and optimal guidance to policymakers and coastal managers. We discuss the challenges associated with integrating ocean acidification science across funding agencies, institutions, disciplines, topical areas, and regions, and the value of unifying science objectives and activities to deliver insights into local, regional, and global scale impacts. We identify guiding principles and strategies for developing transdisciplinary research in the ocean acidification science community.

A species invasion mediated through habitat structure, intraguild predation and parasitism.

With field, laboratory, and modeling approaches, we examined the interplay among habitat structure, intraguild predation (IGP), and parasitism in an ongoing species invasion. Native Gammarus duebeni celticus (Crustacea: Amphipoda) are often, but not always, replaced by the invader Gammarus pulex through differential IGP. The muscle-wasting microsporidian parasite Pleistophora mulleri infects the native but not the invader. We found a highly variable prevalence of P. mulleri in uninvaded rivers, with 0–91% of hosts parasitized per sample. In addition, unparasitized natives dominated fast-flowing riffle patches of river, whereas parasitized individuals dominated slower- flowing, pooled patches. We examined the survivorship of invader and native in single and mixed-species microcosms with high, intermediate, and zero parasite prevalence. G. pulex survivorship was high in all treatments, whereas G. duebeni subsp. celticus survivorship was significantly lower in the presence of the invader. Further, parasitized G. duebeni subsp. celticus experienced near-total elimination. Models of the species replacement process implied that parasite-enhanced IGP would make invasion by G. pulex more likely, regardless of habitat and parasite spatial structure. However, where heterogeneity in parasite prevalence creates a landscape of patches with different susceptibilities to invasion, G. pulex may succeed in cases where invasion would not be possible if patches were equivalent. The different responses of parasitized and unparasitized G. duebeni subsp. celticus to environmental heterogeneity potentially link landscape patterns to the success or failure of the invasion process.

Intellectual Property management in publicly funded R&D centres—A comparison of university-based and company-based research centres

Recent thinking on open innovation and the knowledge-based economy have stressed the importance of external knowledge sources in stimulating innovation. Policy-makers have recognised this, establishing publicly funded Centres of R&D Excellence with the objective of stimulating industry–science links and localised innovation spillovers. Here, we examine the contrasting IP management practices of a group of 18 university- and company-based R&D centres supported by the same regional programme. Our analysis covers all but one of the Centres supported by the programme and suggests marked contrasts between the IP strategies of the university-based and company-based centres. This suggests the potential for very different types of knowledge spillovers from publicly funded R&D centres based in different types of organisations, and a range of alternative policy approaches to the future funding of R&D centres depending on policy-makers’ objectives.

Numerical and Experimental Investigation of Aircraft Panel Deformations During Riveting Process

In collaboration with Airbus-UK, the dimensional growth of aircraft panels while being riveted with stiffeners is investigated. Small panels are used in this investigation. The stiffeners have been fastened to the panels with rivets and it has been observed that during this operation the panels expand in the longitudinal and transverse directions. It has been observed that the growth is variable and the challenge is to control the riveting process to minimize this variability. In this investigation, the assembly of the small panels and longitudinal stiffeners has been simulated using static stress and nonlinear explicit finite element models. The models have been validated against a limited set of experimental measurements; it was found that more accurate predictions of the riveting process are achieved using explicit finite element models. Yet, the static stress finite element model is more time efficient, and more practical to simulate hundreds of rivets and the stochastic nature of the process. Furthermore, through a series of numerical simulations and probabilistic analyses, the manufacturing process control parameters that influence panel growth have been identified. Alternative fastening approaches were examined and it was found that dimensional growth can be controlled by changing the design of the dies used for forming the rivets.

Conceptualizing a transformative research agenda

Transformative consumer researchers seek to enhance consumer well-being by tackling some of the more difficult and intractable social problems and getting the results into the hands of stakeholders who can apply the research findings. Although traditional research approaches offer a viable path for doing research seeking positive social change, alternative research approaches exist that are uniquely suited to the challenges of Transformative Consumer Research. This article examines the standard research process from the perspective of a transformative research agenda to highlight steps in the process that can be better adapted and suggests innovations inspired from other translational research programs.

The p-hub Model with Hub-catchment Areas, Existing Hubs, and Simulation: A Case Study of Serbian Intermodal Terminals

This paper addresses the problem of optimally locating intermodal freight terminals in Serbia. To solve this problem and determine the effects of the resulting scenarios, two modeling approaches were combined. The first approach is based on multiple-assignment hub-network design, and the second is based on simulation. The multiple-assignment p-hub network location model was used to determine the optimal location of intermodal terminals. Simulation was used as a tool to estimate intermodal transport flow volumes, due to the unreliability and unavailability of specific statistical data, and as a method for quantitatively analyzing the economic, time, and environmental effects of different scenarios of intermodal terminal development. The results presented here represent a summary, with some extension, of the research realized in the IMOD-X project (Intermodal Solutions for Competitive Transport in Serbia).

Comparison of lagrangian and eulerian simulations of slurry flows in a sudden expansion

From a review of technical literature, it was not apparent if the Lagrangian or the Eulerian dispersed phase modeling approach was more valid to simulate dilute erosive slurry flow. In this study, both modeling approaches were employed and a comparative analysis of performances and accuracy between the two models was carried out. Due to an impossibility to define, for the Eulerian model already implemented in FLUENT, a set of boundary conditions consistent with the Lagrangian impulsive equations, an Eulerian dispersed phase model was integrated in the FLUENT code using subroutines and user-defined scalar equations. Numerical predictions obtained from the two different approaches for two-phase flow in a sudden expansion were compared with the measured data. Excellent agreement was attained between the predicted and observed fluid and particle velocity in the axial direction and for the kinetic energy. Erosion profiles in a sudden expansion computed using the Lagrangian scheme yielded good qualitative agreement with measured data and predicted a maximum impact angle of 29 deg at the fluid reattachment point. The Eulerian model was adversely affected by the reattachment of the fluid phase to the wall and the simulated erosion profiles were not in agreement with the Lagrangian or measured data. Furthermore, the Eulerian model under-predicted the Lagrangian impact angle at all locations except the reattachment point. © 2010 American Society of Mechanical Engineers.

Structural Breaks in Mortality Models and their Consequences

In recent years, the issue of life expectancy has become of upmost importance to pension providers, insurance companies and the government bodies in the developed world. Significant and consistent improvements in mortality rates and, hence, life expectancy have led to unprecedented increases in the cost of providing for older ages. This has resulted in an explosion of stochastic mortality models forecasting trends in mortality data in order to anticipate future life expectancy and, hence, quantify the costs of providing for future aging populations. Many stochastic models of mortality rates identify linear trends in mortality rates by time, age and cohort, and forecast these trends into the future using standard statistical methods. The modeling approaches used failed to capture the effects of any structural change in the trend and, thus, potentially produced incorrect forecasts of future mortality rates. In this paper, we look at a range of leading stochastic models of mortality and test for structural breaks in the trend time series.

Investigation of Aircraft Panel Deformations during Riveting Process

In collaboration with Airbus-UK, the dimensional growth of small panels while being riveted with stiffeners is investigated. The stiffeners have been fastened to the panels with rivets and it has been observed that during this operation the panels expand in the longitudinal and transverse directions. It has been observed that the growth is variable and the challenge is to control the riveting process to minimize this variability. In this investigation, the assembly of the small panels and longitudinal stiffeners has been simulated using low and high fidelity nonlinear finite element models. The models have been validated against a limited set of experimental measurements; it was found that more accurate predictions of the riveting process are achieved using high fidelity explicit finite element models. Furthermore, through a series of numerical simulations and probabilistic analyses, the manufacturing process control parameters that influence panel growth have been identified. Alternative fastening approaches were examined and it was found that dimensional growth can be controlled by changing the design of the dies used for forming the rivets.

Effective grain size distribution analysis for interpretation of tidal-deltaic facies: West Bengal Sundarbans

Research over the past two decades on the Holocene sediments from the tide dominated west side of the lower Ganges delta has focussed on constraining the sedimentary environment through grain size distributions (GSD). GSD has traditionally been assessed through the use of probability density function (PDF) methods (e.g. log-normal, log skew-Laplace functions), but these approaches do not acknowledge the compositional nature of the data, which may compromise outcomes in lithofacies interpretations. The use of PDF approaches in GSD analysis poses a series of challenges for the development of lithofacies models, such as equifinal distribution coefficients and obscuring the empirical data variability. In this study a methodological framework for characterising GSD is presented through compositional data analysis (CODA) plus a multivariate statistical framework. This provides a statistically robust analysis of the fine tidal estuary sediments from the West Bengal Sundarbans, relative to alternative PDF approaches.

The application of metabolomic biomarker screening tools for improved Bovine Respiratory Disease diagnosis and management

Bovine Respiratory Disease (BRD) is considered to be one of the most significant causes of economic loss in cattle worldwide. The disease has multifactorial aetiology, where viral induced respiratory damage can predispose animals to developing secondary bacterial infections. Accurate identification of viral infected animals prior to the onset of bacterial infection is necessary to reduce the overuse of antimicrobial treatments and minimize further economic losses from reduced production capacity and death. This research focuses on Bovine Parainfluenza Virus Type 3 (BPIV-3), one of the viruses involved in generating BRD. Vaccination measures for BPIV-3 can induce a level of immunity preventing disease progression, however, not all animals respond equally and immunization can complicate disease diagnosis. Alternative diagnostic approaches are required to identify animals which fail to respond to vaccination during infection outbreaks and are therefore likely to be more susceptible to secondary bacterial infections. Mass spectrometry based metabolomics was employed to identify plasma markers capable of differentiating between vaccinated and non-vaccinated calves after challenge with BPIV-3. Differentiation of vaccinated and non-vaccinated study groups (n=6) was possible as early as day 2 post-BPIV-3 challenge up until day 20 using a panel of potential metabolite markers. This study illustrates the potential for metabolomics to provide more detailed information on animal vaccination status that could be used to develop tools for improved herd health management, reduce economic loss through rapid identification and isolation of animals without immune protection (improving herd level immunity) and help reduce the usage of antimicrobial therapeutic treatments in animals.

Interchange of entire communities: microbial community coalescence

Microbial communities are enigmatically diverse. We propose a novel view of processes likely affecting microbial assemblages, which could be viewed as the Great American Interchange en miniature: the wholesale exchange among microbial communities resulting from moving pieces of the environment containing entire assemblages. Incidental evidence for such ‘community coalescence’ is accumulating, but such processes are rarely studied, likely because of the absence of suitable terminology or a conceptual framework. We provide the nucleus for such a conceptual foundation for the study of community coalescence, examining factors shaping these events, links to bodies of ecological theory, and we suggest modeling approaches for understanding coalescent communities. We argue for the systematic study of community coalescence because of important functional and applied consequences.