Social mobility and inflammatory and metabolic markers at older ages: the English Longitudinal Study of Ageing

BACKGROUND: Since our knowledge of the associations between socioeconomic position (SEP) over the life course and inflammatory and metabolic markers, which are excellent predictors of cardiovascular disease, remains limited, we examined the association between social mobility over the life course and these markers at older ages. METHODS: Our study used cross-sectionally collected data from 6142 participants aged 50 years and older from the English Longitudinal Study of Ageing. We estimated linear and logistic models of the associations between social mobility, using information on childhood and adult SEP, C reactive protein (CRP), fibrinogen, glycated haemoglobin (HbA1c) and high-density lipoprotein (HDL) cholesterol. Our models were gradually adjusted for age, sex, chronic diseases, obesity, physical activity, alcohol consumption, smoking status and depressive symptoms. RESULTS: Participants who experienced upward social mobility had higher CRP, fibrinogen and HbA1c levels compared with those who had stable high SEP over the life course, but lower compared with those who experienced downward social mobility or had stable low SEP. They also had lower HDL levels compared with those who had stable high SEP or downwardly mobile. Adjustment for covariates partially explained the associations between social mobility and CRP and HDL, and fully explained those between social mobility and fibrinogen and HbA1c. CONCLUSIONS: Social mobility is associated with inflammatory and metabolic markers at older ages with some of the observed associations persisting after accounting for covariates. Upward social mobility appears to partially reverse the damaging effect of childhood social disadvantage on inflammatory profiles in older ages

Educational level as a cause of type 2 diabetes mellitus: Caution from triangulation of observational and genetic evidence

Background and objective: Education might be causal to type 2 diabetes mellitus (T2DM). We triangulated cohort and genetic evidence to consolidate the causality between education and T2DM. / Methods: We obtained observational evidence from the English Longitudinal Study of Ageing (ELSA). Self-reporting educational attainment was categorised as high (post-secondary and higher), middle (secondary), and low (below secondary or no academic qualifications) in 6,786 community-dwelling individuals aged ≥ 50 years without diabetes at ELSA wave 2, who were followed until wave 8 for the first diabetes diagnosis. Additionally, we performed two-sample Mendelian randomisation (MR) using an inverse-variance weighted (IVW), MR-Egger, weighted median (WM), and weighted mode-based estimate (WMBE) method. Steiger filtering was further applied to exclude single-nucleotide polymorphisms (SNPs) that were correlated with an outcome (T2DM) stronger than exposure (education attainment). / Results: We observed 598 new diabetes cases after 10.4 years of follow-up. The adjusted hazard ratios (95% CI) of T2DM were 1.20 (0.97–1.49) and 1.58 (1.28–1.96) in the middle- and low-education groups, respectively, compared to the high-education group. Low education was also associated with increased glycated haemoglobin levels. Psychosocial resources, occupation, and health behaviours fully explained these inverse associations. In the MR analysis of 210 SNPs (R2 = 0.0161), the odds ratio of having T2DM per standard deviation-decreasing years (4.2 years) of schooling was 1.33 (1.01–1.75; IVW), 1.23 (0.37–4.17; MR-Egger), 1.56 (1.09–2.27; WM), and 2.94 (0.98–9.09; WMBE). However, applying Steiger filtering attenuated most MR results towards the null. / Conclusions: Our inconsistent findings between cohort and genetic evidence did not support the causality between education and T2DM

RRx-001, an epigenetic-based radio- and chemosensitizer, has vascular normalizing effects on SCCVII and U87 tumors

BACKGROUND: The tumor-specific microregional effects of the anticancer agent RRx-001, a novel epigenetic-based radio/chemosensitizer with nitrogen oxide-donating properties in phase II clinical trials, were investigated with whole tissue section quantitative immunohistological staining in mouse SCCVII and human U87 tumors. RESULTS: SCCVII tumors exhibited regions of intermittent perfusion exemplified by co-localization of vessels with the hypoxia marker pimonidazole commonly occurring throughout the tissue. A moderate increase in perfusion (21 to 28 %) was observed after a bolus dose of the perivascular stain DiOC(7)(3), however, with the absence of an increase in tissue oxygenation. U87 tumors showed an absence of blood flow over large areas of treated tumors after dosing with RRx-001. However, these areas did not become necrotic and returned to near normal levels after 12 h. No significant change in tumor hypoxia was seen at 90 min or 12 h. For both tumor types, RRx-001 treatment resulted in the loss of perfusion in the large regions of the tumor; however, at the 12-h time point, both tumor types showed an increase in vessel perfusion but no significant decrease in hypoxia. CONCLUSIONS: These data suggest a redistribution of blood flow within the tumor for both tumor types akin to vascular normalization. Differences between the tumors were related to tumor architecture and distribution of alpha-smooth muscle actin (α-SMA). RRx-001 shows promise for short-term blood flow redistribution in tumors with a pericyte- and α-SMA-rich vasculature. Expression of α-SMA in tumor vasculature could therefore be useful for predicting tumor response to RRx-001

Classical Conformal Blocks and Accessory Parameters from Isomonodromic Deformations

Classical conformal blocks naturally appear in the large central charge limit of 2D Virasoro conformal blocks. In the $AdS_{3}/CFT_{2}$ correspondence, they are related to classical bulk actions and are used to calculate entanglement entropy and geodesic lengths. In this work, we discuss the identification of classical conformal blocks and the Painlev\'e VI action showing how isomonodromic deformations naturally appear in this context. We recover the accessory parameter expansion of Heun's equation from the isomonodromic $\tau$-function. We also discuss how the $c = 1$ expansion of the $\tau$-function leads to a novel approach to calculate the 4-point classical conformal block.Comment: 32+10 pages, 2 figures; v3: upgraded notation, discussion on moduli space and monodromies, numerical and analytic checks; v2: added refs, fixed emai

Nebuliser therapy in the intensive care unit

The relationship between identity, lived experience, sexual practices and the language through which these are conveyed has been widely debated in sexuality literature. For example, ‘coming out’ has famously been conceptualised as a ‘speech act’ (Sedgwick 1990) and as a collective narrative (Plummer 1995), while a growing concern for individuals’ diverse identifications in relations to their sexual and gender practices has produced interesting research focusing on linguistic practices among LGBT-identified individuals (Leap 1995; Kulick 2000; Cameron and Kulick 2006; Farqhar 2000). While an explicit focus on language remains marginal to literature on sexualities (Kulick 2000), issue of language use and translation are seldom explicitly addressed in the growing literature on intersectionality. Yet intersectional perspectives ‘reject the separability of analytical and identity categories’ (McCall 2005:1771), and therefore have an implicit stake in the ‘vernacular’ language of the researched, in the ‘scientific’ language of the researcher and in the relationship of continuity between the two. Drawing on literature within gay and lesbian/queer studies and cross-cultural studies, this chapter revisits debates on sexuality, language and intersectionality. I argue for the importance of giving careful consideration to the language we choose to use as researchers to collectively define the people whose experiences we try to capture. I also propose that language itself can be investigated as a productive way to foreground how individual and collective identifications are discursively constructed, and to unpack the diversity of lived experience. I address intersectional complexity as a methodological issue, where methodology is understood not only as the methods and practicalities of doing research, but more broadly as ‘a coherent set of ideas about the philosophy, methods and data that underlie the research process and the production of knowledge’ (McCall 2005:1774). My points are illustrated with examples drawn from my ethnographic study on ‘lesbian’ identity in urban Russia, interspersed with insights from existing literature. In particular, I aim to show that an explicit focus on language can be a productive way to explore the intersections between the global, the national and the local in cross-cultural research on sexuality, while also addressing issues of positionality and accountability to the communities researched

Effect of Culture at Low Oxygen Tension on the Expression of Heat Shock Proteins in a Panel of Melanoma Cell Lines

Tumours are commonly hypoxic and this can be associated with aggressive tumour type, metastasis and resistance to therapy. Heat shock proteins (hsps) are induced in response to hypoxia, provide cancer cells with protection against tumour-associated stressors and chaperone oncoproteins that drive tumour proliferation. This study examined the effect of different oxygen concentrations on the expression of hsps in melanoma cell lines.Melanoma cell lines were cultured in 2% and 20% O(2). Expression of Hsp90, Hsp70, Hsp60, Hsp40 and Hsp32 proteins were determined by flow cytometry.Growth rates and viability were reduced in the majority of cell lines by culture in 2% O(2). Hsp expression was different in 2% compared to 20% O(2) and changes in Hsp90 expression correlated with cell line generation time (P<0.005) and viability (P<0.01). Greater total hsp expression correlated with improved viability in 2% but not 20% O(2) (P<0.05). Relative expression of the different hsps was consistent across cell lines and each correlated with the others (P = 0.0001) but not with Hsp32. Hsp expression was inversely correlated with cell line adhesion to laminin as well as collagen type IV and Breslow depth of the original primary tumour tissue (P<0.05), but not with Clark level or patient survival. All five hsps were identified on the cell surface.Culture in 2% O(2) variably altered hsp expression in a panel of melanoma cell lines. Hsp expression was associated with certain cell line characteristics and clinical parameters of the originating tumour

Matrix Model Conjecture for Exact BS Periods and Nekrasov Functions

We give a concise summary of the impressive recent development unifying a number of different fundamental subjects. The quiver Nekrasov functions (generalized hypergeometric series) form a full basis for all conformal blocks of the Virasoro algebra and are sufficient to provide the same for some (special) conformal blocks of W-algebras. They can be described in terms of Seiberg-Witten theory, with the SW differential given by the 1-point resolvent in the DV phase of the quiver (discrete or conformal) matrix model (\beta-ensemble), dS = ydz + O(\epsilon^2) = \sum_p \epsilon^{2p} \rho_\beta^{(p|1)}(z), where \epsilon and \beta are related to the LNS parameters \epsilon_1 and \epsilon_2. This provides explicit formulas for conformal blocks in terms of analytically continued contour integrals and resolves the old puzzle of the free-field description of generic conformal blocks through the Dotsenko-Fateev integrals. Most important, this completes the GKMMM description of SW theory in terms of integrability theory with the help of exact BS integrals, and provides an extended manifestation of the basic principle which states that the effective actions are the tau-functions of integrable hierarchies.Comment: 14 page

Different genes interact with particulate matter and tobacco smoke exposure in affecting lung function decline in the general population

BACKGROUND: Oxidative stress related genes modify the effects of ambient air pollution or tobacco smoking on lung function decline. The impact of interactions might be substantial, but previous studies mostly focused on main effects of single genes. OBJECTIVES: We studied the interaction of both exposures with a broad set of oxidative-stress related candidate genes and pathways on lung function decline and contrasted interactions between exposures. METHODS: For 12679 single nucleotide polymorphisms (SNPs), change in forced expiratory volume in one second (FEV(1)), FEV(1) over forced vital capacity (FEV(1)/FVC), and mean forced expiratory flow between 25 and 75% of the FVC (FEF(25-75)) was regressed on interval exposure to particulate matter >10 microm in diameter (PM10) or packyears smoked (a), additive SNP effects (b), and interaction terms between (a) and (b) in 669 adults with GWAS data. Interaction p-values for 152 genes and 14 pathways were calculated by the adaptive rank truncation product (ARTP) method, and compared between exposures. Interaction effect sizes were contrasted for the strongest SNPs of nominally significant genes (p(interaction)>0.05). Replication was attempted for SNPs with MAF<10% in 3320 SAPALDIA participants without GWAS. RESULTS: On the SNP-level, rs2035268 in gene SNCA accelerated FEV(1)/FVC decline by 3.8% (p(interaction) = 2.5x10(-6)), and rs12190800 in PARK2 attenuated FEV1 decline by 95.1 ml p(interaction) = 9.7x10(-8)) over 11 years, while interacting with PM10. Genes and pathways nominally interacting with PM10 and packyears exposure differed substantially. Gene CRISP2 presented a significant interaction with PM10 (p(interaction) = 3.0x10(-4)) on FEV(1)/FVC decline. Pathway interactions were weak. Replications for the strongest SNPs in PARK2 and CRISP2 were not successful. CONCLUSIONS: Consistent with a stratified response to increasing oxidative stress, different genes and pathways potentially mediate PM10 and tobac smoke effects on lung function decline. Ignoring environmental exposures would miss these patterns, but achieving sufficient sample size and comparability across study samples is challengin

Nested Algebraic Bethe Ansatz for Open Spin Chains with Even Twisted Yangian Symmetry

We present a nested algebraic Bethe ansatz for a one dimensional open spin chain whose boundary quantum spaces are irreducible so2n- or sp2n-representations and the monodromy matrix satisfies the defining relations of the Olshanskii twisted Yangian Y±(gl2n). We use a generalization of the Bethe ansatz introduced by De Vega and Karowski which allows us to relate the spectral problem of a so2n- or sp2n-symmetric open spin chain to that of a gln-symmetric periodic spin chain. We explicitly derive the structure of the Bethe vectors and the nested Bethe equations

Cyclophilin A interacts with diverse lentiviral capsids

BACKGROUND: The capsid (CA) protein of HIV-1 binds with high affinity to the host protein cyclophilin A (CypA). This binding positively affects some early stage of the viral life-cycle because prevention of binding either by drugs that occupy that active site of cyclophilin A, by mutation in HIV-1 CA, or RNAi that knocks down intracellular CypA level diminishes viral infectivity. The closely related lentivirus, SIVcpz also binds CypA, but it was thought that this interaction was limited to the HIV-1/SIVcpz lineage because other retroviruses failed to interact with CypA in a yeast two-hybrid assay. RESULTS: We find that diverse lentiviruses, FIV and SIVagmTAN also bind to CypA. Mutagenesis of FIV CA showed that an amino acid that is in a homologous position to the proline at amino acid 90 of HIV-1 CA is essential for FIV interactions with CypA. CONCLUSION: These results demonstrate that CypA binding to lentiviruses is more widespread than previously thought and suggest that this interaction is evolutionarily important for lentiviral infection