On the behaviour of a rumour process with random stifling

We propose a realistic generalization of the Maki-Thompson rumour model by assuming that each spreader ceases to propagate the rumour right after being involved in a random number of stifling experiences. We consider the process with a general initial configuration and establish the asymptotic behaviour (and its fluctuation) of the ultimate proportion of ignorants as the population size grows to $\infty$. Our approach leads to explicit formulas so that the limiting proportion of ignorants and its variance can be computed.Comment: 12 pages, to appear in Environmental Modelling & Softwar

Novel Phases in the Field Induced Spin Density Wave State in (TMTSF)_2PF_6

Magnetoresistance measurements on the quasi one-dimensional organic conductor (TMTSF)_2PF_6 performed in magnetic fields B up to 16T, temperatures T down to 0.12K and under pressures P up to 14kbar have revealed new phases on its P-B-T phase diagram. We found a new boundary which subdivides the field induced spin density wave (FISDW) phase diagram into two regions. We showed that a low-temperature region of the FISDW diagram is characterized by a hysteresis behavior typical for the first order transitions, as observed in a number of studies. In contrast to the common believe, in high temperature region of the FISDW phase diagram, the hysteresis and, hence, the first order transitions were found to disappear. Nevertheless, sharp changes in the resistivity slope are observed both in the low and high temperature domains indicating that the cascade of transitions between different subphases exists over all range of the FISDW state. We also found that the temperature dependence of the resistance (at a constant B) changes sign at about the same boundary. We compare these results with recent theoretical models.Comment: LaTex, 4 pages, 4 figure

Racial Differences in the Effects of Hormone Therapy on Incident Open-Angle Glaucoma in a Randomized Trial

Purpose: We conducted a secondary analysis of a randomized, placebo-controlled trial to test if hormone therapy (HT) altered the risk of open-angle glaucoma (OAG), and if the risk reduction varied by race. Design: Secondary analysis of randomized controlled trial data. Methods: We linked Medicare claims data to 25 535 women in the Women's Health Initiative. Women without a uterus were randomized to receive either oral conjugated equine estrogens (CEE 0.625 mg/day) or placebo, and women with a uterus received oral CEE and medroxyprogesterone acetate (CEE 0.625 mg/day + MPA 2.5 mg/day) or placebo. We used Cox proportional hazards models to calculate hazard ratios (HR) and 95% confidence interval. Results: After exclusion of women with prevalent glaucoma or without claims for eye care provider visits, the final analysis included 8102 women (mean age = 68.5 ± 4.8 years). The OAG incidence was 7.6% (mean follow-up = 11.5 ± 5.2 years; mean HT duration = 4.4 ± 2.3 years). Increased age (P trend =.01) and African-American race (HR = 2.69, 95% CI = 2.13–3.42; white as a reference) were significant risk factors for incident OAG. We found no overall benefit of HT in reducing incident OAG (HR = 1.01, 95% CI = 0.79–1.29 in the CEE trial, and HR = 1.05, 95% CI = 0.85–1.29 in the CEE + MPA trial). However, race modified the relationship between CEE use and OAG risk (P interaction =.01), and risk was reduced in African-American women treated with CEE (HR = 0.49, 95% CI = 0.27–0.88), compared to placebo. Race did not modify the relation between CEE + MPA use and OAG risk (P interaction =.68). Conclusions: Analysis suggests that HT containing estrogen, but not a combination of estrogen and progesterone, reduces the risk of incident OAG among African-American women. Further investigation is needed

Nonadiabatic approach to dimerization gap and optical absorption coefficient of the Su-Schrieffer-Heeger model

An analytical nonadiabatic approach has been developed to study the dimerization gap and the optical absorption coefficient of the Su-Schrieffer-Heeger model where the electrons interact with dispersive quantum phonons. By investigating quantitatively the effects of quantum phonon fluctuations on the gap order and the optical responses in this system, we show that the dimerization gap is much more reduced by the quantum lattice fluctuations than the optical absorption coefficient is. The calculated optical absorption coefficient and the density of states do not have the inverse-square-root singularity, but have a peak above the gap edge and there exist a significant tail below the peak. The peak of optical absorption spectrum is not directly corresponding to the dimerized gap. Our results of the optical absorption coefficient agree well with those of the experiments in both the shape and the peak position of the optical absorption spectrum.Comment: 14 pages, 7 figures. to be published in PR

Cognitive changes during the menopausal transition: a longitudinal study in women with and without HIV

OBJECTIVE: To assess longitudinal changes in cognitive performance across menopause stages in a sample comprised primarily of low-income women of color, including women with HIV (WWH). METHODS: A total of 443 women (291 WWH; 69% African American; 18% Hispanic; median age = 42 y) from the Women's Interagency HIV Study completed tests of verbal learning and memory, attention/working memory, processing speed, verbal fluency, motor skills, and executive function first at an index premenopausal visit and thereafter once every 2 years for up to six visits (mean follow-up = 5.7 y). General linear-mixed effects regression models were run to estimate associations between menopause stages and cognition, in the overall sample and in WWH. We examined both continuous scores and categorical scores of cognitive impairment (yes/no >1 standard deviation below the mean). RESULTS: Adjusting for age and relevant covariates, the overall sample and WWH showed longitudinal declines in continuous measures of learning, memory, and attention/working memory domains from the premenopause to the early perimenopause and from the premenopause to the postmenopause, Ps < 0.05 to < 0.001. Effects on those same domains were also evident in categorical scores of cognitive impairment, with the increased odds of impairment ranging from 41% to 215%, Ps < 0.05 to < 0.001. The increase in predicted probability of impairment by menopausal stage (% affected) ranged from 4% to 13%. CONCLUSIONS: Menopause stage was a key determinant of cognition in a sample of low-income women of color, including WWH. Many of these changes reached a clinically significant level of cognitive impairment

An IRAK1-PIN1 signalling axis drives intrinsic tumour resistance to radiation therapy

Drug-based strategies to overcome tumour resistance to radiotherapy (R-RT) remain limited by the single-agent toxicity of traditional radiosensitizers (for example, platinums) and a lack of targeted alternatives. In a screen for compounds that restore radiosensitivity in p53 mutant zebrafish while tolerated in non-irradiated wild-type animals, we identified the benzimidazole anthelmintic oxfendazole. Surprisingly, oxfendazole acts via the inhibition of IRAK1, a kinase thus far implicated in interleukin-1 receptor (IL-1R) and Toll-like receptor (TLR) immune responses. IRAK1 drives R-RT in a pathway involving IRAK4 and TRAF6 but not the IL-1R/TLR-IRAK adaptor MyD88. Rather than stimulating nuclear factor-κB, radiation-activated IRAK1 prevented apoptosis mediated by the PIDDosome complex (comprising PIDD, RAIDD and caspase-2). Countering this pathway with IRAK1 inhibitors suppressed R-RT in tumour models derived from cancers in which TP53 mutations predict R-RT. Moreover, IRAK1 inhibitors synergized with inhibitors of PIN1, a prolyl isomerase essential for IRAK1 activation in response to pathogens and, as shown here, in response to ionizing radiation. These data identify an IRAK1 radiation-response pathway as a rational chemoradiation therapy target

Degree of Polypharmacy and Cognitive Function in Older Women with HIV

The number of people with HIV (PWH) experiencing age-associated comorbidities including those treated with medications and cognitive impairment is increasing. We examined associations between polypharmacy and cognition in older women with HIV (WWH) given their vulnerability to this comorbidity. Cross-sectional analysis capitalizing on Women's Interagency HIV Study data collected between 2014 and 2017. WWH meeting the following criteria were analyzed: age ≥50 years; availability of self-reported non-antiretroviral therapy (ART) medications data; and neuropsychological data. The number of non-ART medications used regularly in the prior 6 months was summed. Polypharmacy was categorized as none/low (0-4), moderate (5-9), or severe (≥10). Multivariable linear regression analyses examined polypharmacy-cognition (T-score) associations in the total sample and among virally suppressed (VS; < 20 copies/mL)-WWH after covariate adjustment for enrollment site, income, depressive symptoms, substance use (smoking, heavy alcohol, marijuana, crack, cocaine, and/or heroin), the Veterans Aging Cohort Study index (indicators of HIV disease and organ system function, hepatitis C virus serostatus), ART use, nadir CD4 count, and specific ART drugs (efavirenz, integrase inhibitors). We included 637 women (median age = 55 years; 72% Black). Ninety-four percent reported ART use in the past 6 months and 75% had HIV RNA <20 copies/mL. Comorbidity prevalence was high (61% hypertension; 26% diabetes). Moderate and severe polypharmacy in WWH were 34% and 24%. In WWH, severe polypharmacy was associated with poorer executive function (p = .007) and processing speed (p = .01). The same pattern of findings remained among VS-WWH. Moderate polypharmacy was not associated with cognition. Moderate and severe polypharmacy were common and associated with poorer executive function and processing speed in WWH. Severe polypharmacy may be a major contributor to the persistence of domain-specific cognitive complications in older WWH above and beyond the conditions that these medications are used to treat

Factors Predicting Detrimental Change in Declarative Memory Among Women With HIV: A Study of Heterogeneity in Cognition

Objective: Statistical techniques used to study cognitive function in HIV typically yield normative estimates and can mask the heterogeneity in cognitive trajectories over time. We applied a novel statistical approach to identify clusters of individuals with distinct patterns of change in declarative memory in HIV-seropositive (HIV+) and HIV-seronegative (HIV−) women. Methods: 1731 women from the Women’s Interagency HIV Study, a multi-center, prospective cohort study, completed the Hopkins Verbal Learning Test-Revised (HLVT-R) at >2 visits. To derive subgroups with similar patterns of decline by HIV-serostatus, we used a mixed-effects framework that modeled the trajectory of multiple declarative memory outcomes over time, while simultaneously clustering individuals. Results: Of the 1731 participants, 1149 were HIV+ (70% Black/African American [AA]; 30% White/Other [W/O]) and 582 were HIV− (68% AA; 32% W/O). Race stratification was necessary to optimize clustering. Among HIV+AA’s, four subgroups emerged: a subgroup with minimal decline, two with accelerated decline, and one with stable but low performance. In HIV− AA, three subgroups emerged: one with minimal decline and two with accelerated decline. In multivariable-adjusted models among HIV+, individuals with accelerated decline were less educated (P < 0.001) and more likely to have a history of depression (P < 0.001) versus those with minimal decline. Similar subgroups were identified in W/O HIV+ and W/O HIV− participants. Conclusion: We identified clinically meaningful subgroups of women with distinct phenotypes of declarative memory decline, which depend on race and HIV-serostatus using a data driven approach. Identification of underlying mechanisms and risk factors contributing to the observed differences are warranted. More broadly our modeling approach could be other populations to identify risk factors for accelerated cognitive decline and to personalize interventions

Associations between Antiretrovirals and Cognitive Function in Women with HIV

Cognitive complications persist in antiretroviral therapy(ART)-treated people with HIV. However, the pattern and severity of domain-specific cognitive performance is variable and may be exacerbated by ART-mediated neurotoxicity. 929 women with HIV(WWH) from the Women’s Interagency HIV Study who were classified into subgroups based on sociodemographic and longitudinal behavioral and clinical data using semi-parametric latent class trajectory modelling. Five subgroups were comprised of: 1) well-controlled HIV with vascular comorbidities(n = 116); 2) profound HIV legacy effects(CD4 nadir <250 cells/μL; n = 275); 3) primarily <45 year olds with hepatitis C(n = 165); 4) primarily 35–55 year olds(n = 244), and 5) poorly-controlled HIV/substance use(n = 129). Within each subgroup, we fitted a constrained continuation ratio model via penalized maximum likelihood to examine adjusted associations between recent ART agents and cognition. Most drugs were not associated with cognition. However, among the few drugs, non-nucleoside reverse transcriptase inhibitor (NNRTIs) and protease inhibitors(PIs) were most commonly associated with cognition, followed by nucleoside reverse transcriptase inhibitors(NRTIs) and integrase inhibitors(IIs). Directionality of ART-cognition associations varied by subgroup. Better psychomotor speed and fluency were associated with ART for women with well-controlled HIV with vascular comorbidities. This pattern contrasts women with profound HIV legacy effects for whom poorer executive function and fluency were associated with ART. Motor function was associated with ART for younger WWH and primarily 35–55 year olds. Memory was associated with ART only for women with poorly-controlled HIV/substance abuse. Findings demonstrate interindividual variability in ART-cognition associations among WWH and highlight the importance of considering sociodemographic, clinical, and behavioral factors as an underlying contributors to cognition