Measuring the impact of health policies using Internet search patterns: the case of abortion

<p>Abstract</p> <p>Background</p> <p>Internet search patterns have emerged as a novel data source for monitoring infectious disease trends. We propose that these data can also be used more broadly to study the impact of health policies across different regions in a more efficient and timely manner.</p> <p>Methods</p> <p>As a test use case, we studied the relationships between abortion-related search volume, local abortion rates, and local abortion policies available for study.</p> <p>Results</p> <p>Our initial integrative analysis found that, both in the US and internationally, the volume of Internet searches for abortion is inversely proportional to local abortion rates and directly proportional to local restrictions on abortion.</p> <p>Conclusion</p> <p>These findings are consistent with published evidence that local restrictions on abortion lead individuals to seek abortion services outside of their area. Further validation of these methods has the potential to produce a timely, complementary data source for studying the effects of health policies.</p

Complete mitochondrial DNA sequences provide new insights into the Polynesian motif and the peopling of Madagascar

More than a decade of mitochondrial DNA (mtDNA) studies have given the 'Polynesian motif' renowned status as a marker for tracing the late-Holocene expansion of Austronesian speaking populations. Despite considerable research on the Polynesian motif in Oceania, there has been little equivalent work on the western edge of its expansion - leaving major issues unresolved regarding the motif's evolutionary history. This has also led to considerable uncertainty regarding the settlement of Madagascar. In this study, we assess mtDNA variation in 266 individuals from three Malagasy ethnic groups: the Mikea, Vezo, and Merina. Complete mtDNA genome sequencing reveals a new variant of the Polynesian motif in Madagascar; two coding region mutations define a Malagasy-specific sub-branch. This newly defined 'Malagasy motif' occurs at high frequency in all three ethnic groups (13-50%), and its phylogenetic position, geographic distribution, and estimated age all support a recent origin, but without conclusively identifying a specific source region. Nevertheless, the haplotype's limited diversity, similar to those of other mtDNA haplogroups found in our Malagasy groups, best supports a small number of initial settlers arriving to Madagascar through the same migratory process. Finally, the discovery of this lineage provides a set of new polymorphic positions to help localize the Austronesian ancestors of the Malagasy, as well as uncover the origin and evolution of the Polynesian motif itself

A Dynamic Landscape for Antibody Binding Modulates Antibody-Mediated Neutralization of West Nile Virus

Neutralizing antibodies are a significant component of the host's protective response against flavivirus infection. Neutralization of flaviviruses occurs when individual virions are engaged by antibodies with a stoichiometry that exceeds a required threshold. From this “multiple-hit” perspective, the neutralizing activity of antibodies is governed by the affinity with which it binds its epitope and the number of times this determinant is displayed on the surface of the virion. In this study, we investigated time-dependent changes in the fate of West Nile virus (WNV) decorated with antibody in solution. Experiments with the well-characterized neutralizing monoclonal antibody (MAb) E16 revealed a significant increase in neutralization activity over time that could not be explained by the kinetics of antibody binding, virion aggregation, or the action of complement. Additional kinetic experiments using the fusion-loop specific MAb E53, which has limited neutralizing activity because it recognizes a relatively inaccessible epitope on mature virions, identified a role of virus “breathing” in regulating neutralization activity. Remarkably, MAb E53 neutralized mature WNV in a time- and temperature-dependent manner. This phenomenon was confirmed in studies with a large panel of MAbs specific for epitopes in each domain of the WNV envelope protein, with sera from recipients of a live attenuated WNV vaccine, and in experiments with dengue virus. Given enough time, significant inhibition of infection was observed even for antibodies with very limited, or no neutralizing activity in standard neutralization assays. Together, our data suggests that the structural dynamics of flaviviruses impacts antibody-mediated neutralization via exposure of otherwise inaccessible epitopes, allowing for antibodies to dock on the virion with a stoichiometry sufficient for neutralization

HACCP-based quality risk management approach to udder health problems on dairy farms

Against the background of prevailing udder health problems on dairy farms, this paper discusses a new approach to mastitis control. Current udder health control programmes, such as the 'five-point plan', are highlighted and their drawbacks indicated. The concept and principles of hazard analysis critical control points (HACCP) are introduced. The eight core elements of this concept are dealt with by using the example of a dairy herd with a mastitis problem due to Staphylococcus aureus. The various steps to be taken in the development of a HACCP-based quality risk management programme are illustrated through the application of core elements. Finally, it is shown that the HACCP key words, structure, organisation, planning, communication and formalisation; which do not frequently appear in conventional herd health and production management programmes can contribute to better udder health. The role of the veterinarian can be paramount and of added value, if he/she is willing to invest in new knowledge and skills, such as the HACCP concept, farm economics, animal nutrition, and particularly the role of coach to the dairy farmer in the implementation of preventative measures in relation to udder health

Effects of climate and snow depth on Bromus tectorum population dynamics at high elevation

Invasive plants are thought to be especially capable of range shifts or expansion in response to climate change due to high dispersal and colonization abilities. Although highly invasive throughout the Intermountain West, the presence and impact of the grass Bromus tectorum has been limited at higher elevations in the eastern Sierra Nevada, potentially due to extreme wintertime conditions. However, climate models project an upward elevational shift of climate regimes in the Sierra Nevada that could favor B. tectorum expansion. This research specifically examined the effects of experimental snow depth manipulations and interannual climate variability over 5 years on B. tectorum populations at high elevation (2,175 m). Experimentally-increased snow depth had an effect on phenology and biomass, but no effect on individual fecundity. Instead an experimentally-increased snowpack inhibited population growth in 1 year by reducing seedling emergence and early survival. A similar negative effect of increased snow was observed 2 years later. However, a strong negative effect on B. tectorum was also associated with a naturally low-snow winter, when seedling emergence was reduced by 86%. Across 5 years, winters with greater snow cover and a slower accumulation of degree-days coincided with higher B. tectorum seedling density and population growth. Thus, we observed negative effects associated with both experimentally-increased and naturally-decreased snowpacks. It is likely that the effect of snow at high elevation is nonlinear and differs from lower elevations where wintertime germination can be favorable. Additionally, we observed a doubling of population size in 1 year, which is alarming at this elevation

Melanesian mtDNA Complexity

Melanesian populations are known for their diversity, but it has been hard to grasp the pattern of the variation or its underlying dynamic. Using 1,223 mitochondrial DNA (mtDNA) sequences from hypervariable regions 1 and 2 (HVR1 and HVR2) from 32 populations, we found the among-group variation is structured by island, island size, and also by language affiliation. The more isolated inland Papuan-speaking groups on the largest islands have the greatest distinctions, while shore dwelling populations are considerably less diverse (at the same time, within-group haplotype diversity is less in the most isolated groups). Persistent differences between shore and inland groups in effective population sizes and marital migration rates probably cause these differences. We also add 16 whole sequences to the Melanesian mtDNA phylogenies. We identify the likely origins of a number of the haplogroups and ancient branches in specific islands, point to some ancient mtDNA connections between Near Oceania and Australia, and show additional Holocene connections between Island Southeast Asia/Taiwan and Island Melanesia with branches of haplogroup E. Coalescence estimates based on synonymous transitions in the coding region suggest an initial settlement and expansion in the region at ∼30–50,000 years before present (YBP), and a second important expansion from Island Southeast Asia/Taiwan during the interval ∼3,500–8,000 YBP. However, there are some important variance components in molecular dating that have been overlooked, and the specific nature of ancestral (maternal) Austronesian influence in this region remains unresolved

A Cell-Based Model for Quorum Sensing in Heterogeneous Bacterial Colonies

Although bacteria are unicellular organisms, they have the ability to act in concert by synthesizing and detecting small diffusing autoinducer molecules. The phenomenon, known as quorum sensing, has mainly been proposed to serve as a means for cell-density measurement. Here, we use a cell-based model of growing bacterial microcolonies to investigate a quorum-sensing mechanism at a single cell level. We show that the model indeed predicts a density-dependent behavior, highly dependent on local cell-clustering and the geometry of the space where the colony is evolving. We analyze the molecular network with two positive feedback loops to find the multistability regions and show how the quorum-sensing mechanism depends on different model parameters. Specifically, we show that the switching capability of the network leads to more constraints on parameters in a natural environment where the bacteria themselves produce autoinducer than compared to situations where autoinducer is introduced externally. The cell-based model also allows us to investigate mixed populations, where non-producing cheater cells are shown to have a fitness advantage, but still cannot completely outcompete producer cells. Simulations, therefore, are able to predict the relative fitness of cheater cells from experiments and can also display and account for the paradoxical phenomenon seen in experiments; even though the cheater cells have a fitness advantage in each of the investigated groups, the overall effect is an increase in the fraction of producer cells. The cell-based type of model presented here together with high-resolution experiments will play an integral role in a more explicit and precise comparison of models and experiments, addressing quorum sensing at a cellular resolution

In-Depth Analysis of the Antibody Response of Individuals Exposed to Primary Dengue Virus Infection

Humans who experience a primary dengue virus (DENV) infection develop antibodies that preferentially neutralize the homologous serotype responsible for infection. Affected individuals also generate cross-reactive antibodies against heterologous DENV serotypes, which are non-neutralizing. Dengue cross-reactive, non-neutralizing antibodies can enhance infection of Fc receptor bearing cells and, potentially, exacerbate disease. The actual binding sites of human antibody on the DENV particle are not well defined. We characterized the specificity and neutralization potency of polyclonal serum antibodies and memory B-cell derived monoclonal antibodies (hMAbs) from 2 individuals exposed to primary DENV infections. Most DENV-specific hMAbs were serotype cross-reactive and weakly neutralizing. Moreover, many hMAbs bound to the viral pre-membrane protein and other sites on the virus that were not preserved when the viral envelope protein was produced as a soluble, recombinant antigen (rE protein). Nonetheless, by modifying the screening procedure to detect rare antibodies that bound to rE, we were able to isolate and map human antibodies that strongly neutralized the homologous serotype of DENV. Our MAbs results indicate that, in these two individuals exposed to primary DENV infections, a small fraction of the total antibody response was responsible for virus neutralization

Aboriginal Australian mitochondrial genome variation - An increased understanding of population antiquity and diversity

Aboriginal Australians represent one of the oldest continuous cultures outside Africa, with evidence indicating that their ancestors arrived in the ancient landmass of Sahul (present-day New Guinea and Australia) ∼55 thousand years ago. Genetic studies, though limited, have demonstrated both the uniqueness and antiquity of Aboriginal Australian genomes. We have further resolved known Aboriginal Australian mitochondrial haplogroups and discovered novel indigenous lineages by sequencing the mitogenomes of 127 contemporary Aboriginal Australians. In particular, the more common haplogroups observed in our dataset included M42a, M42c, S, P5 and P12, followed by rarer haplogroups M15, M16, N13, O, P3, P6 and P8. We propose some major phylogenetic rearrangements, such as in haplogroup P where we delinked P4a and P4b and redefined them as P4 (New Guinean) and P11 (Australian), respectively. Haplogroup P2b was identified as a novel clade potentially restricted to Torres Strait Islanders. Nearly all Aboriginal Australian mitochondrial haplogroups detected appear to be ancient, with no evidence of later introgression during the Holocene. Our findings greatly increase knowledge about the geographic distribution and phylogenetic structure of mitochondrial lineages that have survived in contemporary descendants of Australia's first settlers. © The Author(s) 2017