An investigation of cognitive processes in chronic pain

This thesis examines information-processing in chronic pain. "Schematic" processing is investigated selective memory for pain-related information is explored in depressed and non-depressed chronic pain patients, depressed non pain-patients and controls. A memory bias for sensory adjectives is found in the non depressed chronic pain group, while a tendency to over-recall both sensory and affective compared to neutral information is found in the depressed chronic pain group. No memory bias is observed in an acute pain group, and the implications of this are discussed. A possible cognitive avoidance mechanism is identified in depression. A questionnaire assessing beliefs about pain ("conceptual" processing) is developed and validated, and shown to differentiate between chronic pain patients and controls. The impact of two interventions for chronic pain (surgery and cognitive-behavioural management) on schematic and conceptual processing is investigated prospectively. In general the endorsement of organic beliefs decreases while the emphasis on psychological beliefs increases post-intervention. Evidence is found to suggest that surgery, but not cognitive-behavioural treatment, reverses pain-related memory biases. This is discussed in relation to changes in pain intensity. Evidence is provided to suggest that beliefs are causally related to several pain-related measures including anxiety, depression, health locus of control, cognitive coping strategies and activity levels. A word completion paradigm is employed to explore further the role of schematic processing in chronic pain, and finally, a lexical decision task is used to assess the role of word frequency effects in information-processing in chronic pain. These results suggest that memory biases in chronic pain cannot be explained by frequency effects, hence addressing the validity of the memory biases described earlier in the thesis

Diploptene δ13C values from contemporary thermokarst lake sediments show complex spatial variation

Cryospheric changes in northern high latitudes are linked to significant greenhouse gas flux to the atmosphere, for example, methane that originates from organic matter decomposition in thermokarst lakes. The set of pathways that link methane production in sediments, via oxidation in the lake system, to the flux of residual methane to the atmosphere is complex and exhibits temporal and spatial variation. The isotopic signal of bacterial biomarkers (hopanoids, e.g. diploptene) in sediments has been used to identify contemporary ocean-floor methane seeps and, in the geological record, periods of enhanced methane production (e.g. the PETM). The biomarker approach could potentially be used to assess temporal changes in lake emissions through the Holocene via the sedimentary biomarker record. However, there are no data on the consistency of the signal of isotopic depletion in relation to source or on the amount of noise (unexplained variation) in biomarker values from modern lake sediments. We assessed methane oxidation as represented by the isotopic signal of biomarkers from methane oxidising bacteria (MOB) in multiple surface sediment samples in three distinct areas known to emit varying levels of methane in two shallow Alaskan thermokarst lakes. Diploptene was present and had δ13C values lower than -38g‰ in all sediments analysed, suggesting methane oxidation was widespread. However, there was considerable variation in δ13C values within each area. The most 13C-depleted diploptene was found in an area of high methane ebullition in Ace Lake (diploptene δ13C values between -68.2 and -50.1‰). In contrast, significantly higher diploptene δ13C values (between -42.9 and -38.8g‰) were found in an area of methane ebullition in Smith Lake. δ13C values of diploptene between -56.8 and -46.9g‰ were found in the centre of Smith Lake, where ebullition rates are low but diffusive methane efflux occurs. The small-scale heterogeneity of the samples may reflect patchy distribution of substrate and/or MOB within the sediments. The two ebullition areas differ in age and type of organic carbon substrate, which may affect methane production, transport, and subsequent oxidation. Given the high amount of variation in surface samples, a more extensive calibration of modern sediment properties, within and among lakes, is required before down-core records of hopanoid isotopic signatures are developed. © Author(s) 2016

Racial/Ethnic and Age Differences in the Direct and Indirect Effects of the COVID-19 Pandemic on US Mortality

Objectives. To estimate the direct and indirect effects of the COVID-19 pandemic on overall, race/ ethnicity-specific, and age-specific mortality in 2020 in the United States. Methods. Using surveillance data, we modeled expected mortality, compared it to observed mortality, and estimated the share of "excess" mortality that was indirectly attributable to the pandemic versus directly attributed to COVID-19. We present absolute risks and proportions of total pandemic-related mortality, stratified by race/ethnicity and age. Results. We observed 16.6 excess deaths per 10 000 US population in 2020; 84% were directly attributed to COVID-19. The indirect effects of the pandemic accounted for 16% of excess mortality, with proportions as low as 0% among adults aged 85 years and older and more than 60% among those aged 15 to 44 years. Indirect causes accounted for a higher proportion of excess mortality among racially minoritized groups (e.g., 32% among Black Americans and 23% among Native Americans) compared with White Americans (11%). Conclusions. The effects of the COVID-19 pandemic on mortality and health disparities are underestimated when only deaths directly attributed to COVID-19 are considered. An equitable public health response to the pandemic should also consider its indirect effects on mortality

Leveraging auxiliary data to improve precision in inverse probability-weighted analyses

Purpose: To demonstrate improvements in the precision of inverse probability-weighted estimators by use of auxiliary variables, i.e., determinants of the outcome that are independent of treatment, missingness or selection. Methods: First with simulated data, and then with public data from the National Health and Nutrition Examination Survey (NHANES), we estimated the mean of a continuous outcome using inverse probability weights to account for informative missingness. We assessed gains in precision resulting from the inclusion of auxiliary variables in the model for the weights. We compared the performance of robust and nonparametric bootstrap variance estimators in this setting. Results: We found that the inclusion of auxiliary variables reduced the empirical variance of inverse probability-weighted estimators. However, that reduction was not captured in standard errors computed using the robust variance estimator, which is widely used in weighted analyses due to the non-independence of weighted observations. In contrast, a nonparametric bootstrap estimator properly captured the precision gain. Conclusions: Epidemiologists can leverage auxiliary data to improve the precision of weighted estimators by using bootstrap variance estimation, or a closed-form variance estimator that properly accounts for the estimation of the weights, in place of the standard robust variance estimator

A Geography of Risk: Structural Racism and Coronavirus Disease 2019 Mortality in the United States

Coronavirus disease 2019 (COVID-19) is disproportionately burdening racial and ethnic minority groups in the United States. Higher risks of infection and mortality among racialized minorities are a consequence of structural racism, reflected in specific policies that date back centuries and persist today. Yet our surveillance activities do not reflect what we know about how racism structures risk. When measuring racial and ethnic disparities in deaths due to COVID-19, the Centers for Disease Control and Prevention statistically accounts for the geographic distribution of deaths throughout the United States to reflect the fact that deaths are concentrated in areas with different racial and ethnic distributions from those of the larger United States. In this commentary, we argue that such an approach misses an important driver of disparities in COVID-19 mortality, namely the historical forces that determine where individuals live, work, and play, and that consequently determine their risk of dying from COVID-19. We explain why controlling for geography downplays the disproportionate burden of COVID-19 on racialized minority groups in the United States. Finally, we offer recommendations for the analysis of surveillance data to estimate racial disparities, including shifting from distribution-based to risk-based measures, to help inform a more effective and equitable public health response to the pandemic

The burden of HIV among female sex workers, men who have sex with men and transgender women in Haiti: results from the 2016 Priorities for Local AIDS Control Efforts (PLACE) study

Introduction: Despite the higher risk of HIV among female sex workers (FSWs), men who have sex with men (MSM) and transgender women (TGW), these populations are under-represented in the literature on HIV in Haiti. Here, we present the first nationally representative estimates of HIV prevalence and the first care and treatment cascade for FSWs, MSM and TGW in Haiti. We also examine the social determinants of HIV prevalence in these groups and estimate FSW and MSM population size in Haiti. Methods: Data were collected between April 2016 and February 2017 throughout the 10 geographical departments of Haiti. The Priorities for Local AIDS Control Efforts (PLACE) method was used to: (1) recruit participants for a behavioural survey; (2) provide rapid testing, counselling and linkage to care for syphilis and HIV; and (3) measure viral load using dried blood spots for participants testing HIV positive. Results: Study participants included 990 FSWs, 520 MSM and 109 TGW. HIV prevalence was estimated at 7.7% (95% CI 6.2%, 9.6%) among FSWs, 2.2% (0.9%, 5.3%) among MSM and 27.6% (5.0%, 73.5%) among TGW. Of participants who tested positive for syphilis, 17% of FSWs, 19% of MSM and 74% of TGW were co-infected with HIV. Economic instability and intimate partner violence (IPV) were significantly associated with HIV among MSM; food insecurity, economic instability and history of rape were significantly associated with HIV among TGW. Fewer than one-third of participants living with HIV knew their status, and more than a quarter of those who knew their status were not on treatment. While approximately four in five FSW and MSM participants on treatment for HIV were virally suppressed, viral suppression was less common among TGW participants at only 46%. Conclusions: This study demonstrates a need for targeted interventions to prevent and treat HIV among key populations in Haiti. Potential high-impact interventions may include venue-based, peer navigator-led outreach and testing for HIV and syphilis and improving screening and case management for structural violence and IPV. TGW are in urgent need of such interventions due to our observations of alarmingly high HIV prevalence and low frequency of HIV viral suppression among TGW

Locally continuously perfect groups of homeomorphisms

The notion of a locally continuously perfect group is introduced and studied. This notion generalizes locally smoothly perfect groups introduced by Haller and Teichmann. Next, we prove that the path connected identity component of the group of all homeomorphisms of a manifold is locally continuously perfect. The case of equivariant homeomorphism group and other examples are also considered.Comment: 14 page

Human rhinovirus-induced inflammatory responses are inhibited by phosphatidylserine containing liposomes

Human rhinovirus (HRV) infections are major contributors to the healthcare burden associated with acute exacerbations of chronic airway disease, such as chronic obstructive pulmonary disease and asthma. Cellular responses to HRV are mediated through pattern recognition receptors that may in part signal from membrane microdomains. We previously found Toll-like receptor signaling is reduced, by targeting membrane microdomains with a specific liposomal phosphatidylserine species, 1-stearoyl-2-arachidonoyl-sn-glycero-3-phospho-L-serine (SAPS). Here we explored the ability of this approach to target a clinically important pathogen. We determined the biochemical and biophysical properties and stability of SAPS liposomes and studied their ability to modulate rhinovirus-induced inflammation, measured by cytokine production, and rhinovirus replication in both immortalized and normal primary bronchial epithelial cells. SAPS liposomes rapidly partitioned throughout the plasma membrane and internal cellular membranes of epithelial cells. Uptake of liposomes did not cause cell death, but was associated with markedly reduced inflammatory responses to rhinovirus, at the expense of only modest non-significant increases in viral replication, and without impairment of interferon receptor signaling. Thus using liposomes of phosphatidylserine to target membrane microdomains is a feasible mechanism for modulating rhinovirus-induced signaling, and potentially a prototypic new therapy for viral-mediated inflammation

Proof of a conjecture of Polya on the zeros of successive derivatives of real entire functions

We prove Polya's conjecture of 1943: For a real entire function of order greater than 2, with finitely many non-real zeros, the number of non-real zeros of the n-th derivative tends to infinity with n. We use the saddle point method and potential theory, combined with the theory of analytic functions with positive imaginary part in the upper half-plane.Comment: 26 page

Demographic Trends in US HIV Diagnoses, 2008–2017: Data Movies

In this editorial, we introduce the data movie as a tool for investigating and communicating changing patterns of disease using the example of HIV in the United States. The Centers for Disease Control and Prevention currently tracks all new HIV diagnoses through the National HIV Surveillance System. Understanding what these data tell us is critical to the goal of ending the HIV epidemic in the United States.1 However, summarizing trends across multiple population characteristics simultaneously—for example, exploring how the age distribution of new diagnoses varies by geographic region and how that relationship has changed over time—can be difficult. Because data movies allow us to visualize complex relationships more easily than large tables or paneled figures, they can help us take full advantage of our increasingly rich national surveillance data