Assessing the practicalities of joint snakebite and dog rabies control programs:Commonalities and potential pitfalls

Both rabies and snakebite primarily affect underserved and impoverished communities globally, with an estimated 200,000 people dying from these diseases annually, and the greatest burden being in Africa and Asia. Both diseases have been neglected and have thus been denied appropriate prioritization, support, and interventions, and face many of the challenges common to all neglected tropical diseases (NTDs). In line with the call for integrated approaches between NTDs in the recent NTD Roadmap, we sought to build upon previous conceptualizations for an integrated approach by identifying the commonalities between snakebite and rabies to explore the feasibility of an integrated approach. While multiple areas for potential integration are identified, we highlight the potential pitfalls to integrating rabies and snakebite programs, considering the nuances that make each disease and its intervention program unique. We conclude that health system strengthening, and capacity building should be the focus of any integrated approach among NTDs, and that by strengthening overall health systems, both rabies and snakebite can advocate for further support from governments and stakeholders

Group finding in the stellar halo using M-giants in 2MASS: An extended view of the Pisces Overdensity?

A density based hierarchical group-finding algorithm is used to identify stellar halo structures in a catalog of M-giants from the Two Micron All Sky Survey (2MASS). The intrinsic brightness of M-giant stars means that this catalog probes deep into the halo where substructures are expected to be abundant and easy to detect. Our analysis reveals 16 structures at high Galactic latitude (greater than 15 degree), of which 10 have been previously identified. Among the six new structures two could plausibly be due to masks applied to the data, one is associated with a strong extinction region and one is probably a part of the Monoceros ring. Another one originates at low latitudes, suggesting some contamination from disk stars, but also shows protrusions extending to high latitudes, implying that it could be a real feature in the stellar halo. The last remaining structure is free from the defects discussed above and hence is very likely a satellite remnant. Although the extinction in the direction of the structure is very low, the structure does match a low temperature feature in the dust maps. While this casts some doubt on its origin, the low temperature feature could plausibly be due to real dust in the structure itself. The angular position and distance of this structure encompass the Pisces overdensity traced by RR Lyraes in Stripe 82 of the Sloan Digital Sky Survey (SDSS). However, the 2MASS M-giants indicate that the structure is much more extended than what is visible with the SDSS, with the point of peak density lying just outside Stripe 82. The morphology of the structure is more like a cloud than a stream and reminiscent of that seen in simulations of satellites disrupting along highly eccentric orbits.Comment: Accepted for publication in Ap

Galactic googly : the rotation-metallicity bias in the inner stellar halo of the Milky Way

The first and second moments of stellar velocities encode important information about the formation history of the Galactic halo. However, due to the lack of tangential motion and inaccurate distances of the halo stars, the velocity moments in the Galactic halo have largely remained ‘known unknowns’. Fortunately, our off-centric position within the Galaxy allows us to estimate these moments in the galactocentric frame using the observed radial velocities of the stars alone. We use these velocities coupled with the hierarchical Bayesian scheme, which allows easy marginalization over the missing data (the proper motion, and uncertainty-free distance and line-of-sight velocity), to measure the velocity dispersions, orbital anisotropy (β) and streaming motion (vrot) of the halo main-sequence turn-off (MSTO) and K-giant (KG) stars in the inner stellar halo (r ≲ 15 kpc). We study the metallicity bias in kinematics of the halo stars and observe that the comparatively metal-rich ([Fe/H] > −1.4) and the metal-poor ([Fe/H] ≤ −1.4) MSTO samples show a clear systematic difference in vrot ∼ 20-40 km s−1, depending on how restrictive the spatial cuts to cull the disc contamination are. The bias is also detected in KG samples but with less certainty. Both MSTO and KG populations suggest that the inner stellar halo of the Galaxy is radially biased i.e. σr > σθ or σϕ and β ≃ 0.5. The apparent metallicity contrariety in the rotation velocity among the halo sub-populations supports the co-existence of multiple populations in the galactic halo that may have formed through distinct formation scenarios, i.e. in situ versus accretion.Publisher PDFPeer reviewe

Polymorphisms of TNF-enhancer and gene for FcγRIIa correlate with the severity of falciparum malaria in the ethnically diverse Indian population

<p>Abstract</p> <p>Background</p> <p>Susceptibility/resistance to <it>Plasmodium falciparum </it>malaria has been correlated with polymorphisms in more than 30 human genes with most association analyses having been carried out on patients from Africa and south-east Asia. The aim of this study was to examine the possible contribution of genetic variants in the <it>TNF </it>and <it>FCGR2A </it>genes in determining severity/resistance to <it>P. falciparum </it>malaria in Indian subjects.</p> <p>Methods</p> <p>Allelic frequency distribution in populations across India was first determined by typing genetic variants of the <it>TNF </it>enhancer and the <it>FCGR2A </it>G/A SNP in 1871 individuals from 55 populations. Genotyping was carried out by DNA sequencing, single base extension (SNaPshot), and DNA mass array (Sequenom). Plasma TNF was determined by ELISA. Comparison of datasets was carried out by Kruskal-Wallis and Mann-Whitney tests. Haplotypes and LD plots were generated by PHASE and Haploview, respectively. Odds ratio (OR) for risk assessment was calculated using EpiInfo™ version 3.4.</p> <p>Results</p> <p>A novel single nucleotide polymorphism (SNP) at position -76 was identified in the <it>TNF </it>enhancer along with other reported variants. Five <it>TNF </it>enhancer SNPs and the <it>FCGR2A </it>R131H (G/A) SNP were analyzed for association with severity of <it>P. falciparum </it>malaria in a malaria-endemic and a non-endemic region of India in a case-control study with ethnically-matched controls enrolled from both regions. <it>TNF </it>-1031C and -863A alleles as well as homozygotes for the TNF enhancer haplotype CACGG (-1031T>C, -863C>A, -857C>T, -308G>A, -238G>A) correlated with enhanced plasma TNF levels in both patients and controls. Significantly higher TNF levels were observed in patients with severe malaria. Minor alleles of -1031 and -863 SNPs were associated with increased susceptibility to severe malaria. The high-affinity IgG2 binding FcγRIIa AA (131H) genotype was significantly associated with protection from disease manifestation, with stronger association observed in the malaria non-endemic region. These results represent the first genetic analysis of the two immune regulatory molecules in the context of <it>P. falciparum </it>severity/resistance in the Indian population.</p> <p>Conclusion</p> <p>Association of specific <it>TNF </it>and <it>FCGR2A </it>SNPs with cytokine levels and disease severity/resistance was indicated in patients from areas with differential disease endemicity. The data emphasizes the need for addressing the contribution of human genetic factors in malaria in the context of disease epidemiology and population genetic substructure within India.</p

New distances to RAVE stars

Probability density functions are determined from new stellar parameters for the distance moduli of stars for which the RAdial Velocity Experiment (RAVE) has obtained spectra with S/N>=10. Single-Gaussian fits to the pdf in distance modulus suffice for roughly half the stars, with most of the other half having satisfactory two-Gaussian representations. As expected, early-type stars rarely require more than one Gaussian. The expectation value of distance is larger than the distance implied by the expectation of distance modulus; the latter is itself larger than the distance implied by the expectation value of the parallax. Our parallaxes of Hipparcos stars agree well with the values measured by Hipparcos, so the expectation of parallax is the most reliable distance indicator. The latter are improved by taking extinction into account. The effective temperature absolute-magnitude diagram of our stars is significantly improved when these pdfs are used to make the diagram. We use the method of kinematic corrections devised by Schoenrich, Binney & Asplund to check for systematic errors for general stars and confirm that the most reliable distance indicator is the expectation of parallax. For cool dwarfs and low-gravity giants tends to be larger than the true distance by up to 30 percent. The most satisfactory distances are for dwarfs hotter than 5500 K. We compare our distances to stars in 13 open clusters with cluster distances from the literature and find excellent agreement for the dwarfs and indications that we are over-estimating distances to giants, especially in young clusters.Comment: 20 pages accepted by MNRAS. Minor changes to the submitted versio

Variations in host genes encoding adhesion molecules and susceptibility to falciparum malaria in India

<p>Abstract</p> <p>Background</p> <p>Host adhesion molecules play a significant role in the pathogenesis of <it>Plasmodium falciparum </it>malaria and changes in their structure or levels in individuals can influence the outcome of infection. The aim of this study was to investigate the association of SNPs of three adhesion molecule genes, <it>ICAM1</it>, <it>PECAM1 </it>and <it>CD36</it>, with severity of falciparum malaria in a malaria-endemic and a non-endemic region of India.</p> <p>Methods</p> <p>The frequency distribution of seven selected SNPs of <it>ICAM1</it>, <it>PECAM1 </it>and <it>CD36 </it>was determined in 552 individuals drawn from 24 populations across India. SNP-disease association was analysed in a case-control study format. Genotyping of the population panel was performed by Sequenom mass spectroscopy and patient/control samples were genotyped by SNaPshot method. Haplotypes and linkage disequilibrium (LD) plots were generated using PHASE and Haploview, respectively. Odds-ratio (OR) for risk assessment was estimated using EpiInfo™ version 3.4.</p> <p>Results</p> <p>Association of the ICAM1 rs5498 (exon 6) G allele and the CD36 exon 1a A allele with increased risk of severe malaria was observed (severe versus control, OR = 1.91 and 2.66, P = 0.02 and 0.0012, respectively). The CD36 rs1334512 (-53) T allele as well as the TT genotype associated with protection from severe disease (severe versus control, TT versus GG, OR = 0.37, P = 0.004). Interestingly, a SNP of the <it>PECAM1 </it>gene (rs668, exon 3, C/G) with low minor allele frequency in populations of the endemic region compared to the non-endemic region exhibited differential association with disease in these regions; the G allele was a risk factor for malaria in the endemic region, but exhibited significant association with protection from disease in the non-endemic region.</p> <p>Conclusion</p> <p>The data highlights the significance of variations in the <it>ICAM1</it>, <it>PECAM1 </it>and <it>CD36 </it>genes in the manifestation of falciparum malaria in India. The <it>PECAM1 </it>exon 3 SNP exhibits altered association with disease in the endemic and non-endemic region.</p

Assessing the practicalities of joint snakebite and dog rabies control programs : commonalities and potential pitfalls

Both rabies and snakebite primarily affect underserved and impoverished communities globally, with an estimated 200,000 people dying from these diseases annually, and the greatest burden being in Africa and Asia. Both diseases have been neglected and have thus been denied appropriate prioritization, support, and interventions, and face many of the challenges common to all neglected tropical diseases (NTDs). In line with the call for integrated approaches between NTDs in the recent NTD Roadmap, we sought to build upon previous conceptualizations for an integrated approach by identifying the commonalities between snakebite and rabies to explore the feasibility of an integrated approach. While multiple areas for potential integration are identified, we highlight the potential pitfalls to integrating rabies and snakebite programs, considering the nuances that make each disease and its intervention program unique. We conclude that health system strengthening, and capacity building should be the focus of any integrated approach among NTDs, and that by strengthening overall health systems, both rabies and snakebite can advocate for further support from governments and stakeholders.http://www.journals.elsevier.com/toxicon-xhj2022BiochemistryGeneticsMicrobiology and Plant Patholog

The accretion origin of the Milky Way's stellar halo

We have used data from the Sloan Digital Sky Survey (SDSS) Data Release 5 to explore the overall structure and substructure of the stellar halo of the Milky Way using about 4 million color-selected main sequence turn-off stars. We fit oblate and triaxial broken power-law models to the data, and found a `best-fit' oblateness of the stellar halo 0.5<c/a<0.8, and halo stellar masses between Galactocentric radii of 1 and 40kpc of (3.7+/-1.2)x10^8 M_sun. The density profile of the stellar halo is approximately r^{-3}; it is possible that the power law slope is shallower inside 20kpc and steeper outside that radius. Yet, we found that all smooth and symmetric models were very poor fits to the distribution of stellar halo stars because the data exhibit a great deal of spatial substructure. We quantified deviations from a smooth oblate/triaxial model using the RMS of the data around the model profile on scales >~100pc, after accounting for the (known) contribution of Poisson uncertainties. The fractional RMS deviation of the actual stellar distribution from any smooth, parameterized halo model is >~40%: hence, the stellar halo is highly structured. We compared the observations with simulations of galactic stellar halos formed entirely from the accretion of satellites in a cosmological context by analysing the simulations in the same way as the data. While the masses, overall profiles, and degree of substructure in the simulated stellar halos show considerable scatter, the properties and degree of substructure in the Milky Way's halo match well the properties of a `typical' stellar halo built exclusively out of the debris from disrupted satellite galaxies. Our results therefore point towards a picture in which an important fraction of the Milky Way's stellar halo has been accreted from satellite galaxies.Comment: Submitted to the Astrophysical Journal. 14 pages; 11 figure

The GALAH survey: Stellar streams and how stellar velocity distributions vary with Galactic longitude, hemisphere, and metallicity

Using GALAH (GALactic Archaeology with HERMES) survey data of nearby stars, we look at how structure in the planar (u, v) velocity distribution depends on metallicity and on viewing direction within the Galaxy. In nearby stars with distance d≲1 kpc, the Hercules stream is most strongly seen in higher metallicity stars [Fe/H] > 0.2. The Hercules stream peak v value depends on viewed galactic longitude, which we interpret as due to the gap between the stellar stream and more circular orbits being associated with a specific angular momentum value of about 1640 km s−1 kpc. The association of the gap with a particular angular momentum value supports a bar resonant model for the Hercules stream. Moving groups previously identified in Hipparcos(HIgh Precision Parallax COllecting Satellite) observations are easiest to see in stars nearer than 250 pc, and their visibility and peak velocities in the velocity distributions depends on both viewing direction (galactic longitude and hemisphere) and metallicity. We infer that there is fine structure in local velocity distributions that varies over distances of a few hundred pc in the Galaxy.Parts of this research were conducted by the Australian Research Council (ARC) Centre of Excellence for All Sky Astrophysics in 3 Dimensions (ASTRO 3D), through project number CE170100013. JB-H acknowledges a Miller Professorship from the Miller Institute, UC Berkeley, and an ARC Laureate Fellowship which also supports GDS and SS. SM acknowledges support from the ARC through DECRA Fellowship DE140100598. JK is supported by an ARC DP grant awarded to JB-H and TB. MH is supported by ASTRO 3D Centre of Excellence funding to the University of Sydney and an ARC DP grant awarded to KF. LD gratefully acknowledges a scholarship from Zonta International District 24. LD and KF acknowledge support from ARC grant DP160103747. LC is the recipient of an ARC Future Fellowship (project number FT160100402)

The 20-minute whole blood clotting test (20WBCT) for snakebite coagulopathy—A systematic review and meta-analysis of diagnostic test accuracy

Background The 20-minute whole blood clotting test (20WBCT) has been used to detect coagulopathy following snakebite for almost 50 years. A systematic review and meta-analysis of the 20WBCT was conducted to evaluate the accuracy of the 20WBCT to detect coagulopathy, indicative of systemic envenoming. Methods and findings Databases were searched from inception up to 09/12/2020 to identify studies that compared the 20WBCT and INR/fibrinogen on five or more subjects. Data was extracted from full-text articles by two reviewers using a predetermined form. Authors of 29 studies that lacked sufficient details in the manuscript were contacted and included if data meeting the inclusion criteria were provided. Included studies were evaluated for bias using a tailored QUADAS-2 checklist. The study protocol was prospectively registered on PROSPERO database (CRD42020168953). The searches identified 3,599 studies, 15 met the inclusion criteria and 12 were included in the meta-analysis. Data was reported from 6 countries and included a total of 2,270 patients. The aggregate weighted sensitivity of the 20WBCT at detecting INR >1.4 was 0.84 (CI 0.61 to 0.94), the specificity was 0.91 (0.76 to 0.97) and the SROC AUC was 0.94 (CI 0.91 to 0.96). The aggregate weighted sensitivity of the 20WBCT at detecting fibrinogen <100 mg/dL was 0.72 (CI 0.58 to 0.83), the specificity was 0.94 (CI 0.88 to 0.98) and the SROC AUC was 0.93 (0.91 to 0.95). Both analyses that used INR and fibrinogen as the reference test displayed considerable heterogeneity. Conclusions In the absence of laboratory clotting assays, the 20WBCT remains a highly specific and fairly sensitive bedside test at detecting coagulopathy following snakebite. However, clinicians should be aware of the importance of operator training, standardized equipment and the lower sensitivity of the 20WBCT at detecting mild coagulopathy and resolution of coagulopathy following antivenom