Iron nutrition and possible lead toxicity: an appraisal of geophagy undertaken by pregnant women of UK Asian communities

A cultural transfer of geophagy is evident in the UK, with soils imported from Bengal being deliberately consumed mainly by pregnant Asian women. Two samples purchased from ethnic shops were subjected to a 2-part acid–alkaline in vitro physiologically based extraction test (PBET) procedure, representing the stomach and small intestine of the human digestive system respectively, to determine the bioaccessibility of elements. Despite the low bioaccessibility of Fe, with the quantity of soil consumed one sample can provide 41–54% of this mineral nutrient required by a 15–18 year old female, with the other sample providing 90–119%. Significant amounts of Ca, Cu and Mn are also supplied to the consumer, whilst further research investigating the possible effects of Pb toxicity on the geophagist would seem to be justifie

Theory of Supersolidity

After reviewing some experimental facts, and early theories, I sketch the Hartree-Fock description of Boson solids, emphasizing the contrast with the Fermion case in that the natural solution is a product of local wave-functions. I then investigate the Boson Hubbard model to demonstrate that the local functions are not orthogonal and exemplify a novel state of matter which has superflow but not ODLRO, below a cooperative thermal transition. I then discuss whether or not these ideas actually apply to solid He

BCC vs. HCP - The Effect of Crystal Symmetry on the High Temperature Mobility of Solid 4^4He

We report results of torsional oscillator (TO) experiments on solid $^4$He at temperatures above 1K. We have previously found that single crystals, once disordered, show some mobility (decoupled mass) even at these rather high temperatures. The decoupled mass fraction with single crystals is typically 20- 30%. In the present work we performed similar measurements on polycrystalline solid samples. The decoupled mass with polycrystals is much smaller, $\sim$ 1%, similar to what is observed by other groups. In particular, we compared the properties of samples grown with the TO's rotation axis at different orientations with respect to gravity. We found that the decoupled mass fraction of bcc samples is independent of the angle between the rotation axis and gravity. In contrast, hcp samples showed a significant difference in the fraction of decoupled mass as the angle between the rotation axis and gravity was varied between zero and 85 degrees. Dislocation dynamics in the solid offers one possible explanation of this anisotropy.Comment: 10 pages, 5 figures, to appear in Journal of Low Temperature Physics - special issue on Supersolidit

A glassy contribution to the heat capacity of hcp 4^4He solids

We model the low-temperature specific heat of solid $^4$He in the hexagonal closed packed structure by invoking two-level tunneling states in addition to the usual phonon contribution of a Debye crystal for temperatures far below the Debye temperature, $T < \Theta_D/50$. By introducing a cutoff energy in the two-level tunneling density of states, we can describe the excess specific heat observed in solid hcp $^4$He, as well as the low-temperature linear term in the specific heat. Agreement is found with recent measurements of the temperature behavior of both specific heat and pressure. These results suggest the presence of a very small fraction, at the parts-per-million (ppm) level, of two-level tunneling systems in solid $^4$He, irrespective of the existence of supersolidity.Comment: 11 pages, 4 figure

Defects and glassy dynamics in solid He-4: Perspectives and current status

We review the anomalous behavior of solid He-4 at low temperatures with particular attention to the role of structural defects present in solid. The discussion centers around the possible role of two level systems and structural glassy components for inducing the observed anomalies. We propose that the origin of glassy behavior is due to the dynamics of defects like dislocations formed in He-4. Within the developed framework of glassy components in a solid, we give a summary of the results and predictions for the effects that cover the mechanical, thermodynamic, viscoelastic, and electro-elastic contributions of the glassy response of solid He-4. Our proposed glass model for solid He-4 has several implications: (1) The anomalous properties of He-4 can be accounted for by allowing defects to freeze out at lowest temperatures. The dynamics of solid He-4 is governed by glasslike (glassy) relaxation processes and the distribution of relaxation times varies significantly between different torsional oscillator, shear modulus, and dielectric function experiments. (2) Any defect freeze-out will be accompanied by thermodynamic signatures consistent with entropy contributions from defects. It follows that such entropy contribution is much smaller than the required superfluid fraction, yet it is sufficient to account for excess entropy at lowest temperatures. (3) We predict a Cole-Cole type relation between the real and imaginary part of the response functions for rotational and planar shear that is occurring due to the dynamics of defects. Similar results apply for other response functions. (4) Using the framework of glassy dynamics, we predict low-frequency yet to be measured electro-elastic features in defect rich He-4 crystals. These predictions allow one to directly test the ideas and very presence of glassy contributions in He-4.Comment: 33 pages, 13 figure

The glassy response of solid He-4 to torsional oscillations

We calculated the glassy response of solid He-4 to torsional oscillations assuming a phenomenological glass model. Making only a few assumptions about the distribution of glassy relaxation times in a small subsystem of otherwise rigid solid He-4, we can account for the magnitude of the observed period shift and concomitant dissipation peak in several torsion oscillator experiments. The implications of the glass model for solid He-4 are threefold: (1) The dynamics of solid He-4 is governed by glassy relaxation processes. (2) The distribution of relaxation times varies significantly between different torsion oscillator experiments. (3) The mechanical response of a torsion oscillator does not require a supersolid component to account for the observed anomaly at low temperatures, though we cannot rule out its existence.Comment: 9 pages, 4 figures, presented at QFS200

Cyclin E overexpression sensitizes triple negative breast cancer to Wee1 kinase Inhibition

Purpose: Poor prognosis in triple-negative breast cancer (TNBC) is due to an aggressive phenotype and lack of biomarker-driven targeted therapies. Overexpression of cyclin E and phosphorylated-CDK2 are correlated with poor survival in TNBC patients, and the absence of CDK2 desensitizes cells to inhibition of Wee1 kinase, a key cell cycle regulator. We hypothesize that cyclin E expression can predict response to therapies, which include the Wee1 kinase inhibitor, AZD1775. Experimental Design: Mono and combination therapies with AZD1775 were evaluated in TNBC cell lines and multiple patient derived xenograft (PDX) models with different cyclin E expression profiles. The mechanism(s) of cyclin E-mediated replicative stress were investigated following cyclin E induction or CRISPR/Cas9 knockout by a number of assays in multiple cells lines. Results: Cyclin E overexpression (1) is enriched in TNBCs with high recurrence rates, (2) sensitizes TNBC cell lines and PDX models to AZD1775, (3) leads to CDK2-dependent activation of DNA replication stress pathways and (4) increases Wee1 kinase activity. Moreover, treatment of cells with either CDK2 inhibitors or carboplatin leads to transient transcriptional induction of cyclin E (in cyclin E-low tumors) and result in DNA replicative stress. Such drug mediated cyclin E induction in TNBC cells and PDX models sensitizes them to AZD1775 in a sequential treatment combination strategy. Conclusions: Cyclin E is a potential biomarker of response (1) for AZD1775 as monotherapy in cyclin E high TNBC tumors and (2) for sequential combination therapy with CDK2 inhibitor or carboplatin followed by AZD1775 in cyclin E low TNBC tumors

Relationship between CD4 T cell turnover, cellular differentiation and HIV persistence during ART

The precise role of CD4 T cell turnover in maintaining HIV persistence during antiretroviral therapy (ART) has not yet been well characterized. In resting CD4 T cell subpopulations from 24 HIV-infected ART-suppressed and 6 HIV-uninfected individuals, we directly measured cellular turnover by heavy water labeling, HIV reservoir size by integrated HIV-DNA (intDNA) and cell-associated HIV-RNA (caRNA), and HIV reservoir clonality by proviral integration site sequencing. Compared to HIV-negatives, ART-suppressed individuals had similar fractional replacement rates in all subpopulations, but lower absolute proliferation rates of all subpopulations other than effector memory (TEM) cells, and lower plasma IL-7 levels (p = 0.0004). Median CD4 T cell half-lives decreased with cell differentiation from naïve to TEM cells (3 years to 3 months, p<0.001). TEM had the fastest replacement rates, were most highly enriched for intDNA and caRNA, and contained the most clonal proviral expansion. Clonal proviruses detected in less mature subpopulations were more expanded in TEM, suggesting that they were maintained through cell differentiation. Earlier ART initiation was associated with lower levels of intDNA, caRNA and fractional replacement rates. In conclusion, circulating integrated HIV proviruses appear to be maintained both by slow turnover of immature CD4 subpopulations, and by clonal expansion as well as cell differentiation into effector cells with faster replacement rates

Topological doping and the stability of stripe phases

We analyze the properties of a general Ginzburg-Landau free energy with competing order parameters, long-range interactions, and global constraints (e.g., a fixed value of a total ``charge'') to address the physics of stripe phases in underdoped high-Tc and related materials. For a local free energy limited to quadratic terms of the gradient expansion, only uniform or phase-separated configurations are thermodynamically stable. ``Stripe'' or other non-uniform phases can be stabilized by long-range forces, but can only have non-topological (in-phase) domain walls where the components of the antiferromagnetic order parameter never change sign, and the periods of charge and spin density waves coincide. The antiphase domain walls observed experimentally require physics on an intermediate lengthscale, and they are absent from a model that involves only long-distance physics. Dense stripe phases can be stable even in the absence of long-range forces, but domain walls always attract at large distances, i.e., there is a ubiquitous tendency to phase separation at small doping. The implications for the phase diagram of underdoped cuprates are discussed.Comment: 18 two-column pages, 2 figures, revtex+eps

Antiretroviral drug class and anaemia risk in the current treatment era among people living with HIV in the USA: a clinical cohort study

OBJECTIVE: Anaemia is common among people living with HIV (PLWH) and has been associated with certain, often older, antiretroviral medications. Information on current antiretroviral therapy (ART) and anaemia is limited. The objective was to compare the associations between anaemia incidence or haemoglobin change with core ART classes in the current ART era. DESIGN: Retrospective cohort study. SETTING: USA-based prospective clinical cohort of PLWH aged 18 and above receiving care at eight sites between January 2010 and March 2018. PARTICIPANTS: 16 505 PLWH were included in this study. MAIN OUTCOME MEASURES: Anaemia risk and haemoglobin change were estimated among PLWH for person-time on a protease inhibitor (PI) or an integrase strand transfer inhibitor (INSTI)-based regimen, relative to a non-nucleoside reverse transcriptase inhibitor (NNRTI)-based reference. We also examined PLWH on regimens containing multiple core classes. Cox proportional hazards regression analyses were conducted to measure the associations between time-updated ART classes and incident anaemia or severe anaemia. Linear mixed effects models were used to examine the relationships between ART classes and haemoglobin change. RESULTS: During a median of 4.9 years of follow-up, 1040 developed anaemia and 488 developed severe anaemia. Compared with NNRTI use, INSTI-based regimens were associated with an increased risk of anaemia (adjusted HR (aHR) 1.26, 95% CI 1.00 to 1.58) and severe anaemia (aHR 1.51, 95% CI 1.07 to 2.11) and a decrease in haemoglobin level. Time on multiple core classes was also associated with increased anaemia risk (aHR 1.39, 95% CI 1.13 to 1.70), while no associations were found for PI use. CONCLUSION: These findings suggest INSTI use may increase the risk of anaemia. If confirmed, screening for anaemia development in users of INSTIs may be beneficial. Further research into the underlying mechanisms is warranted