Feasibility of MRI based extracellular volume fraction and partition coefficient measurements in thigh muscle

OBJECTIVE: This study aimed to assess the feasibility of extracellular volume-fraction (ECV) measurement, and time to achieve contrast equilibrium (CE), in healthy muscles, and to determine whether in-flow and partial-volume errors in the femoral artery affect measurements, and if there are differences in the partition coefficient (λ) between muscles. METHODS: T1 was measured in the biceps femoris, vastus intermedius, femoral artery and aorta of 10 healthy participants. This was repeated alternately between the thigh and aorta for ≥25 min following a bolus of gadoterate meglumine. λ was calculated for each muscle/blood measurement. Time to CE was assessed semi-quantitatively. RESULTS: 8/10 participants achieved CE. Time to CE = 19±2 min (mean ± 95% confidence interval). Measured λ: biceps femoris/aorta = 0.210±0.034, vastus intermedius/aorta = 0.165±0.015, biceps femoris/femoral artery = 0.265±0.054, vastus intermedius/femoral artery = 0.211±0.026. There were significant differences in λ between the muscles when using the same vessel (p < 0.05), and between λ calculated in the same muscle when using different vessels (p < 0.05). CONCLUSION: ECV measurements in the thigh are clinically feasible. The use of the femoral artery for the blood measurement is associated with small but significant differences in λ. ECV measurements are sensitive to differences between muscles within the healthy thigh. ADVANCES IN KNOWLEDGE: This paper determines the time to contrast equilibrium in the healthy thigh and describes a method for measuring accurately ECV in skeletal muscle. This can aid in the diagnosis and understanding of inflammatory auto-immune diseases

In-situ fluorescence spectroscopy is a more rapid and resilient indicator of faecal contamination risk in drinking water than faecal indicator organisms

Faecal indicator organisms (FIOs) are limited in their ability to protect public health from the microbial contamination of drinking water because of their transience and time required to deliver a result. We evaluated alternative rapid, and potentially more resilient, approaches against a benchmark FIO of thermotolerant coliforms (TTCs) to characterise faecal contamination over 14 months at 40 groundwater sources in a Ugandan town. Rapid approaches included: in-situ tryptophan-like fluorescence (TLF), humic-like fluorescence (HLF), turbidity; sanitary inspections; and total bacterial cells by flow cytometry. TTCs varied widely in six sampling visits: a third of sources tested both positive and negative, 50% of sources had a range of at least 720 cfu/100 mL, and a two-day heavy rainfall event increased median TTCs five-fold. Using source medians, TLF was the best predictor in logistic regression models of TTCs ≥10 cfu/100 mL (AUC 0.88) and best correlated to TTC enumeration (ρs 0.81), with HLF performing similarly. Relationships between TLF or HLF and TTCs were stronger in the wet season than the dry season, when TLF and HLF were instead more associated with total bacterial cells. Source rank-order between sampling rounds was considerably more consistent, according to cross-correlations, using TLF or HLF (min ρs 0.81) than TTCs (min ρs 0.34). Furthermore, dry season TLF and HLF cross-correlated more strongly (ρs 0.68) than dry season TTCs (ρs 0.50) with wet season TTCs, when TTCs were elevated. In-situ TLF or HLF are more rapid and resilient indicators of faecal contamination risk than TTCs

Spatial Models of Abundance and Habitat Preferences of Commerson’s and Peale’s Dolphin in Southern Patagonian Waters

Funding: This research was possible with the support of the Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET). Funding for travel to and accommodation for NAD in Aberdeen, Scotland was provided by CONICET and Cetacean Society International. The work of NAD was part of a postdoctoral fellowship funded by CONICET. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

Predicting Impacts of Climate Change on Fasciola hepatica Risk

Fasciola hepatica (liver fluke) is a physically and economically devastating parasitic trematode whose rise in recent years has been attributed to climate change. Climate has an impact on the free-living stages of the parasite and its intermediate host Lymnaea truncatula, with the interactions between rainfall and temperature having the greatest influence on transmission efficacy. There have been a number of short term climate driven forecasts developed to predict the following season's infection risk, with the Ollerenshaw index being the most widely used. Through the synthesis of a modified Ollerenshaw index with the UKCP09 fine scale climate projection data we have developed long term seasonal risk forecasts up to 2070 at a 25 km square resolution. Additionally UKCIP gridded datasets at 5 km square resolution from 1970-2006 were used to highlight the climate-driven increase to date. The maps show unprecedented levels of future fasciolosis risk in parts of the UK, with risk of serious epidemics in Wales by 2050. The seasonal risk maps demonstrate the possible change in the timing of disease outbreaks due to increased risk from overwintering larvae. Despite an overall long term increase in all regions of the UK, spatio-temporal variation in risk levels is expected. Infection risk will reduce in some areas and fluctuate greatly in others with a predicted decrease in summer infection for parts of the UK due to restricted water availability. This forecast is the first approximation of the potential impacts of climate change on fasciolosis risk in the UK. It can be used as a basis for indicating where active disease surveillance should be targeted and where the development of improved mitigation or adaptation measures is likely to bring the greatest benefits

A comprehensive 1000 Genomes-based genome-wide association meta-analysis of coronary artery disease

Existing knowledge of genetic variants affecting risk of coronary artery disease (CAD) is largely based on genome-wide association studies (GWAS) analysis of common SNPs. Leveraging phased haplotypes from the 1000 Genomes Project, we report a GWAS meta-analysis of 185 thousand CAD cases and controls, interrogating 6.7 million common (MAF>0.05) as well as 2.7 million low frequency (0.005<MAF<0.05) variants. In addition to confirmation of most known CAD loci, we identified 10 novel loci, eight additive and two recessive, that contain candidate genes that newly implicate biological processes in vessel walls. We observed intra-locus allelic heterogeneity but little evidence of low frequency variants with larger effects and no evidence of synthetic association. Our analysis provides a comprehensive survey of the fine genetic architecture of CAD showing that genetic susceptibility to this common disease is largely determined by common SNPs of small effect siz

IgG1 Is Required for Optimal Protection after Immunization with the Purified Porin OmpD from Salmonella Typhimurium

In mice, the IgG subclass induced after Ag encounter can reflect the nature of the Ag. Th2 Ags such as alum-precipitated proteins and helminths induce IgG1, whereas Th1 Ags, such as Salmonella Typhimurium, predominantly induce IgG2a. The contribution of different IgG isotypes to protection against bacteria such as S. Typhimurium is unclear, although as IgG2a is induced by natural infection, it is assumed this isotype is important. Previously, we have shown that purified S. Typhimurium porins including outer membrane protein OmpD, which induce both IgG1 and IgG2a in mice, provide protection to S. Typhimurium infection via Ab. In this study we report the unexpected finding that mice lacking IgG1, but not IgG2a, are substantially less protected after porin immunization than wild-type controls. IgG1-deficient mice produce more porin-specific IgG2a, resulting in total IgG levels that are similar to wild-type mice. The decreased protection in IgG1-deficient mice correlates with less efficient bacterial opsonization and uptake by macrophages, and this reflects the low binding of outer membrane protein OmpD-specific IgG2a to the bacterial surface. Thus, the Th2-associated isotype IgG1 can play a role in protection against Th1-associated organisms such as S. Typhimurium. Therefore, individual IgG subclasses to a single Ag can provide different levels of protection and the IgG isotype induced may need to be a consideration when designing vaccines and immunization strategies

Tunable symmetry breaking and helical edge transport in a graphene quantum spin Hall state

Low-dimensional electronic systems have traditionally been obtained by electrostatically confining electrons, either in heterostructures or in intrinsically nanoscale materials such as single molecules, nanowires and graphene. Recently, a new method has emerged with the recognition that symmetry-protected topological (SPT) phases1, 2, which occur in systems with an energy gap to quasiparticle excitations (such as insulators or superconductors), can host robust surface states that remain gapless as long as the relevant global symmetry remains unbroken. The nature of the charge carriers in SPT surface states is intimately tied to the symmetry of the bulk, resulting in one- and two-dimensional electronic systems with novel properties. For example, time reversal symmetry endows the massless charge carriers on the surface of a three-dimensional topological insulator with helicity, fixing the orientation of their spin relative to their momentum3, 4. Weakly breaking this symmetry generates a gap on the surface5, resulting in charge carriers with finite effective mass and exotic spin textures6. Analogous manipulations have yet to be demonstrated in two-dimensional topological insulators, where the primary example of a SPT phase is the quantum spin Hall state7, 8. Here we demonstrate experimentally that charge-neutral monolayer graphene has a quantum spin Hall state9, 10 when it is subjected to a very large magnetic field angled with respect to the graphene plane. In contrast to time-reversal-symmetric systems7, this state is protected by a symmetry of planar spin rotations that emerges as electron spins in a half-filled Landau level are polarized by the large magnetic field. The properties of the resulting helical edge states can be modulated by balancing the applied field against an intrinsic antiferromagnetic instability11, 12, 13, which tends to spontaneously break the spin-rotation symmetry. In the resulting canted antiferromagnetic state, we observe transport signatures of gapped edge states, which constitute a new kind of one-dimensional electronic system with a tunable bandgap and an associated spin texture.United States. Dept. of Energy (Office of Science, BES Program, contract no. FG02-08ER46514)Gordon and Betty Moore FoundationGordon and Betty Moore Foundation (grant GBMF2931)United States. Dept. of Energy (Office of Science, BES Office, BES Office, Division of Materials Sciences and Engineering, under award DE-SC0001819)Massachusetts Institute of Technology (Pappalardo Fellowship in Physics

Trading or coercion? Variation in male mating strategies between two communities of East African chimpanzees

Across taxa, males employ a variety of mating strategies, including sexual coercion and the provision, or trading, of resources. Biological Market theory (BMT) predicts that trading of commodities for mating opportunities should exist only when males cannot monopolise access to females and/or obtain mating by force, in situations where power differentials between males are low; both coercion and trading have been reported for chimpanzees (Pan troglodytes). Here, we investigate whether the choice of strategy depends on the variation in male power differentials, using data from two wild communities of East African chimpanzees (P.t. schweinfurthii): the structurally despotic Sonso community (Budongo, Uganda) and the structurally egalitarian M-group (Mahale, Tanzania). We found evidence of sexual coercion by male Sonso chimpanzees, and of trading—of grooming for mating—by M-group males; females traded sex for neither meat nor protection from male aggression. Our results suggest that the despotism–egalitarian axis influences strategy choice: male chimpanzees appear to pursue sexual coercion when power differentials are large and trading when power differentials are small and coercion consequently ineffective. Our findings demonstrate that trading and coercive strategies are not restricted to particular chimpanzee subspecies; instead, their occurrence is consistent with BMT predictions. Our study raises interesting, and as yet unanswered, questions regarding female chimpanzees’ willingness to trade sex for grooming, if doing so represents a compromise to their fundamentally promiscuous mating strategy. It highlights the importance of within-species cross-group comparisons and the need for further study of the relationship between mating strategy and dominance steepness

Impact of Simian Immunodeficiency Virus Infection on Chimpanzee Population Dynamics

Like human immunodeficiency virus type 1 (HIV-1), simian immunodeficiency virus of chimpanzees (SIVcpz) can cause CD4+ T cell loss and premature death. Here, we used molecular surveillance tools and mathematical modeling to estimate the impact of SIVcpz infection on chimpanzee population dynamics. Habituated (Mitumba and Kasekela) and non-habituated (Kalande) chimpanzees were studied in Gombe National Park, Tanzania. Ape population sizes were determined from demographic records (Mitumba and Kasekela) or individual sightings and genotyping (Kalande), while SIVcpz prevalence rates were monitored using non-invasive methods. Between 2002–2009, the Mitumba and Kasekela communities experienced mean annual growth rates of 1.9% and 2.4%, respectively, while Kalande chimpanzees suffered a significant decline, with a mean growth rate of −6.5% to −7.4%, depending on population estimates. A rapid decline in Kalande was first noted in the 1990s and originally attributed to poaching and reduced food sources. However, between 2002–2009, we found a mean SIVcpz prevalence in Kalande of 46.1%, which was almost four times higher than the prevalence in Mitumba (12.7%) and Kasekela (12.1%). To explore whether SIVcpz contributed to the Kalande decline, we used empirically determined SIVcpz transmission probabilities as well as chimpanzee mortality, mating and migration data to model the effect of viral pathogenicity on chimpanzee population growth. Deterministic calculations indicated that a prevalence of greater than 3.4% would result in negative growth and eventual population extinction, even using conservative mortality estimates. However, stochastic models revealed that in representative populations, SIVcpz, and not its host species, frequently went extinct. High SIVcpz transmission probability and excess mortality reduced population persistence, while intercommunity migration often rescued infected communities, even when immigrating females had a chance of being SIVcpz infected. Together, these results suggest that the decline of the Kalande community was caused, at least in part, by high levels of SIVcpz infection. However, population extinction is not an inevitable consequence of SIVcpz infection, but depends on additional variables, such as migration, that promote survival. These findings are consistent with the uneven distribution of SIVcpz throughout central Africa and explain how chimpanzees in Gombe and elsewhere can be at equipoise with this pathogen