A viable mouse model of factor X deficiency provides evidence for maternal transfer of factor X.

BackgroundActivated factor X (FXa) is a vitamin K-dependent serine protease that plays a pivotal role in blood coagulation by converting prothrombin to thrombin. There are no reports of humans with complete deficiency of FX, and knockout of murine F10 is embryonic or perinatal lethal.ObjectiveWe sought to generate a viable mouse model of FX deficiency.MethodsWe used a socket-targeting construct to generate F10-knockout mice by eliminating F10 exon 8 (knockout allele termed F10(tm1Ccmt), abbreviated as '-'; wild-type '+'), and a plug-targeting construct to generate mice expressing a FX variant with normal antigen levels but low levels of FX activity [4-9% normal in humans carrying the defect, Pro343-->Ser, termed FX Friuli (mutant allele termed F10(tm2Ccmt), abbreviated as F)].ResultsF10 knockout mice exhibited embryonic or perinatal lethality. In contrast, homozygous Friuli mice [F10 (F/F)] had FX activity levels of approximately 5.5% (sufficient to rescue both embryonic and perinatal lethality), but developed age-dependent iron deposition and cardiac fibrosis. Interestingly, F10 (-/F) mice with FX activity levels of 1-3% also showed complete rescue of lethality. Further study of this model provides evidence supporting a role of maternal FX transfer in the embryonic survival.ConclusionsWe demonstrate that, while complete absence of FX is incompatible with murine survival, minimal FX activity as low as 1-3% is sufficient to rescue the lethal phenotype. This viable low-FX mouse model will facilitate the development of FX-directed therapies as well as investigation of the FX role in embryonic development

Robust Structured Low-Rank Approximation on the Grassmannian

Over the past years Robust PCA has been established as a standard tool for reliable low-rank approximation of matrices in the presence of outliers. Recently, the Robust PCA approach via nuclear norm minimization has been extended to matrices with linear structures which appear in applications such as system identification and data series analysis. At the same time it has been shown how to control the rank of a structured approximation via matrix factorization approaches. The drawbacks of these methods either lie in the lack of robustness against outliers or in their static nature of repeated batch-processing. We present a Robust Structured Low-Rank Approximation method on the Grassmannian that on the one hand allows for fast re-initialization in an online setting due to subspace identification with manifolds, and that is robust against outliers due to a smooth approximation of the $\ell_p$-norm cost function on the other hand. The method is evaluated in online time series forecasting tasks on simulated and real-world data

High-birefringence nematic liquid crystal for broadband THz applications

Liquid crystals (LCs) have been studied extensively in the visible range for their dielectric tunability, and the characterisation in the terahertz (THz) range has gained increasing interest due to the need for active THz modulation and switching devices. In this paper, we use THz time-domain spectroscopy to measure the frequency-dependent birefringence and the absorption coefficient of a number of commercial and non-commercial nematic LCs, including E7, BL037, MDA-98-1602, LCMS-107, GT3-23001 and 1825, over a range of bias voltages at room temperature. Furthermore, several basic components of LC mixture are analysed to establish their contributions to birefringence and theoretical model is used to fit the absorption spectra. The large tunability and low loss measured for a range of samples show that the LCs are useful tunable dielectrics for compact, efficient and broadband THz devices.The authors would like to thank the UK Engineering and Physical Sciences Research Council (EPSRC) for the support through the Platform Grant for Liquid Crystal Photonics (EP/F00897X/1).This is the final version of the article. It first appeared from Taylor & Francis via https://doi.org/10.1080/02678292.2016.115373

Treating Disinfectant By-products as Mixtures: Using Total Organic Halogen Content and the Growth Inhibition Assay as Potential Indicators of Toxicity in Drinking Water

Since the 1970s when the first disinfection by-products (DBFs) were discovered in drinking water, over 600 of them have been reported in literature, however, the U. S. Environmental Protection Agency currently regulates only 11 of these species. Many toxicological studies have been performed to assess the health and exposure impacts of a subset of DBFs on various living systems including rodents, bacteria, and mammalian cells. Epidemiologists have found weak linkages between individual DBFs and incidences of bladder cancer, spontaneous abortions, and reproductive problems in humans. While these studies have provided valuable information on possible health endpoints associated with single chemical species, what is more relevant to public health are the exposure effects from DBF mixtures in drinking water which consumers come in contact with on a daily basis. The challenge with the study of mixtures is that they are complex and difficult to study leading many toxicologists to avoid incorporating them into their research and, as a result, little is known about their applicability to toxicity assays. Our present understanding of DBFs is that the bromine- and iodine-containing species are more geno- and cytotoxic than their chlorine-containing counterparts, but for now we only have individual measures of toxicity for these compounds. In an effort to evaluate the exposure effects of mixtures of DBFs in real drinking waters, the study described in this report took two approaches. The first was to chemically analyze drinking waters that underwent different treatment scenarios as part of a pilot plant study, including UV irradiance. Individual concentrations of the most commonly occurring DBFs were measured, along with total organic halogen (TOX), total organic chlorine (TOCl), and total organic bromine (TOBr) content. The proportions of known and unknown TOX, TOCl, and TOBr in the water samples were also determined. The second approach aimed to tie together the chemical analysis of real drinking waters with their inherent toxicities. The first attempt at using a mixture of DBFs with the growth inhibition assay (GIA) involved spiking two very toxic DBFs, bromoacetic acid (BrAA) and iodoacetic acid (IAA), into the same matrix to evaluate whether the combination of the two caused a synergistic or antagonistic effect on the growth inhibition of human colon cells. Several preliminary experiments were also performed to evaluate the toxicity (by GIA) of water concentrated 10-fold by reverse osmosis from different disinfection scenarios. Results from both approaches included but were not limited to the following findings. In the pilot plant study samples, the percentage of TOX in real drinking waters that was not accounted for by the measurement of 9 DBPs was between 40% and 80%. UV irradiation followed by post- disinfection treatments created higher TOBr concentrations than in samples that were not UV irradiated, while ozonation (O3) contributed to formation of a greater proportion of unknown TOBr than TOCl in chloraminated waters. This suggests that in waters containing bromide, the use of UV or O3 can potentially increase the toxicity of the water. The combination of BrAA and IAA in the same matrix produced an apparent toxicity that was greater than the sum of the effects of the two individual species, leading to the postulate that studies of the toxicity (and by inference concentrations) of individual DBFs cannot accurately predict the potential impact of a mixture. This work demonstrates that current techniques for determining exposure effects of individual DBFs do not truly reflect the toxicity of the drinking water matrix. Thus, drinking water should be treated as a mixture of DBFs, not as individual compounds. Measuring TOX, TOCl, and TOBr content in addition to individual THM and HAA species chemically characterized mixtures, while the GIA evaluated their toxic potency. Applying both methods to the same types of waters would provide a better evaluation of the drinking water quality resulting from different source waters and treatment processes.Master of Science in Public Healt

The role of sexual orientation, age, living arrangements and self-rated health in planning for end-of-life care for lesbian, gay and bisexual (LGB) older people in the UK

© The Author(s) 2020. The final, definitive version of this paper has been published in Sexualities by Sage Publications Ltd. All rights reserved. It is available at: https://doi.org/10.1177/1363460720932381.This article reports on findings from the quantitative phase of a two-year research project designed to explore end-of-life care experiences and needs of lesbian, gay, bisexual and transgender people. We draw on a subset of the sample (N = 180/237) to analyse the relationship between advance care planning, sexual orientation, living arrangements and self-rated health. The results contribute to a growing body of evidence on how sexual minorities approach and make decisions on advance care planning. A greater understanding of such patterns could help inform the way healthcare professionals engage in conversations about end-of-life care planning with older LGB people.Peer reviewe

Low Sensitivity of T-Cell Based Detection of Tuberculosis among HIV Co-Infected Tanzanian In-Patients

Objective: To evaluate the performance of QuantiFERON-TB GOLD (QFTG) in a resource-poor setting among patients with and without HIV infection.Design: Cross-sectional study.Setting: Two hospitals in Northern Tanzania.Subjects: Eighty three adult male and female inpatients.Intervention: All patients were screened for HIV infection and underwent tuberculin skin test (TST) and QFTG.Results: Eighty-three subjects were enrolled, and 29 (35%) of 83 were HIV-infected. QFTG yielded indeterminate results in 12 (22%; 95%CI 12%-34%) of 54 HIV-uninfected and 13 (45%; 95%CI 26%-64%) of 29 HIV-infected subjects (p=0.0323). Among those with smear-positive pulmonary tuberculosis, TST was positive in 40 (100%; 95%CI 91%-100%) of 40 HIV-uninfected subjects compared with seven (54%; 95%CI 25%- 81%) of 13 HIV-infected subjects (p<0.0001), and QFTG was positive in 28(70%; 95%CI 53%-83%) of 40 HIV-uninfected subjects compared with three (23%; 95%CI 5%-54%) of 13 HIV-infected subjects (p=0.0029). Among medical inpatients at risk for latent tuberculosis infection, TST was positive in seven (50%) of 14 HIV-uninfected patients and three (19%) of 16 HIV-infected patients (p=0.0701) and QFTG was positive among two (14%) of 14 HIV-uninfected patients and three (19%) of 16 HIV-infected patients (p=0.7437).Conclusions: The presence of HIV co-infection was associated with a significant reduction in sensitivity of both the TST (p<0.0001) and QFTG (p=0.0029) for the diagnosis of active M.tuberculosis infection. The high proportion of indeterminate QFTG and lack of sensitivity, particularly among HIV-infected patients, may limit its applicability in settings like Tanzania. Larger studies in resource-poor settings are required.

Higgsing M2 to D2 with gravity: N=6 chiral supergravity from topologically gauged ABJM theory

We present the higgsing of three-dimensional N=6 superconformal ABJM type theories coupled to conformal supergravity, so called topologically gauged ABJM theory, thus providing a gravitational extension of previous work on the relation between N M2 and N D2-branes. The resulting N=6 supergravity theory appears at a chiral point similar to that of three-dimensional chiral gravity introduced recently by Li, Song and Strominger, but with the opposite sign for the Ricci scalar term in the lagrangian. We identify the supersymmetry in the broken phase as a particular linear combination of the supersymmetry and special conformal supersymmetry in the original topologically gauged ABJM theory. We also discuss the higgsing procedure in detail paying special attention to the role played by the U(1) factors in the original ABJM model and the U(1) introduced in the topological gauging.Comment: 53 pages, Late

Lack of association of -607 C/A and -137 G/C polymorphisms in interleukin 18 gene with susceptibility to gout disease in Chinese Han male population

To identify association of IL18-607 C/A and -137 G/C polymorphism with susceptibility to gout in Chinese Han male population, We evaluate the genetic contribution of the IL18-607 C/A and -137 G/C polymorphism in 202 gout male patients and 493 gout-free control of Chinese Han population by allele-specific polymerase chain reaction assay. Our results reveal no significant association between the polymorphisms -607C/A and -137G/C in IL18 with gout. Our study might suggest that -607 C/A and -137 G/C polymorphisms in the promoter of IL18 are not associated with susceptibility to gout and thus do not play a major role in the development of gout in the Chinese Han male population