Global vaccine equity demands reparative justice-not charity

By late April, more than 80% of the world’s COVID-19 vaccines had gone to people in wealthy countries, with just 0.3% to people in low-income countries.1 This reprehensible imbalance is no accident. High-income countries have used neocolonial negotiating power, global policy leverage and capital to procure enough doses to cover 245% of their citizens while leaving few doses for poorer countries.2 As a result, lower-income countries may not be able to vaccinate their populations until 2023.3 Such inequity is yet another example of how the interests of racial capitalism run roughshod over the golden rule of global solidarity—attend to the highest risk first.4 Currently, older and medically vulnerable individuals are dying from COVID-19 disproportionately in poor countries, while young, healthy individuals are getting vaccinated in wealthy ones.5 Vaccine apartheid is a not novel phenomenon. The notion that only certain corners of the world get to benefit from life-saving treatments is an everyday reality of a global health system driven by a capitalist, philanthropic model.6 7 But in times of crises—and as new variants threaten the vaccination plans of wealthy countries—these inequities and their solutions come to the forefront of global debate.8 Policy-makers in rich nations are aware of these issues. But the solutions they have proposed so far do nothing to address the underlying structural problems. They offer charitable donations and partial, temporary fixes that are designed to deflect the substantive demands for reform that global South countries are fighting for, including challenges to unethical intellectual property (IP) regimes.9 This approach will not work, because it is not designed to ‘work.’ If we want to end vaccine apartheid, we need to target the root causes of global health inequities. We need reparative justice. There are currently three approaches to reduce inequity in

Correlation between compartmental tenofovir concentrations and an ex vivo rectal biopsy model of tissue infectibility in the RMP-02/MTN-006 phase 1 study

Design: Phase 1, randomized, two-site (US), double-blind, placebo-controlled study of sexually-abstinent males and females

A multi-compartment single and multiple dose pharmacokinetic comparison of rectally applied tenofovir 1% gel and oral tenofovir disoproxil fumarate

This Phase 1, randomized, two-site (United States), double-blind, placebo-controlled study enrolled 18 sexually abstinent men and women. All received a single 300-mg dose of oral tenofovir disoproxil fumarate (TDF) and were then randomized 2:1 to receive single and then seven daily rectal exposures of vaginally-formulated tenofovir (TFV) 1% gel or a hydroxyethyl cellulose (HEC) placebo gel. Blood, colonic biopsies and rectal and vaginal mucosal fluids were collected after the single oral TDF, the single topical TFV gel dose, and after 7 days of topical TFV gel dosing for extracellular analysis of TFV and intracellular analysis of the active metabolite tenofovir diphosphate (TFVdp) in peripheral blood mononuclear cells (PBMCs) and isolated mucosal mononuclear cells (MMC), including CD4+ and CD4- cell subsets. With a single rectal dose, TFV plasma concentrations were 24-33 fold lower and half-life was 5 h shorter compared to a single oral dose (p = 0.02). TFVdp concentrations were also undetectable in PBMCs with rectal dosing. Rectal tissue exposure to both TFV and TFVdp was 2 to 4-log10 higher after a single rectal dose compared to a single oral dose, and after 7 daily doses, TFVdp accumulated 4.5 fold in tissue. TFVdp in rectal tissue homogenate was predictive (residual standard error, RSE = 0.47) of tissue MMC intracellular TFVdp concentration, with the CD4+ cells having a 2-fold higher TFVdp concentration than CD4- cells. TFV concentrations from rectal sponges was a modest surrogate indicator for both rectal tissue TFV and TFVdp (RSE = 0.67, 0.66, respectively) and plasma TFV (RSE = 0.38). TFV penetrates into the vaginal cavity after oral and rectal dosing, with rectal dosing leading to higher vaginal TFV concentrations (p<0.01)

Biological and technical variables affecting immunoassay recovery of cytokines from human serum and simulated vaginal fluid: A multicenter study

The increase of proinflammatory cytokines in vaginal secretions may serve as a surrogate marker of unwanted inflammatory reaction to microbicide products topically applied for the prevention of sexually transmitted diseases, including HIV-1. Interleukin (IL)-1β and IL-6 have been proposed as indicators of inflammation and increased risk of HIV-1 transmission; however, the lack of information regarding detection platforms optimal for vaginal fluids and interlaboratory variation limit their use for microbicide evaluation and other clinical applications. This study examines fluid matrix variants relevant to vaginal sampling techniques and proposes a model for interlaboratory comparisons across current cytokine detection technologies. IL-1β and IL-6 standards were measured by 12 laboratories in four countries, using 14 immunoassays and four detection platforms based on absorbance, chemiluminescence, electrochemiluminescence, and fluorescence. International reference preparations of cytokines with defined biological activity were spiked into (1) a defined medium simulating the composition of human vaginal fluid at pH 4.5 and 7.2, (2) physiologic salt solutions (phosphate-buffered saline and saline) commonly used for vaginal lavage sampling in clinical studies of cytokines, and (3) human blood serum. Assays were assessed for reproducibility, linearity, accuracy, and significantly detectable fold difference in cytokine level. Factors with significant impact on cytokine recovery were determined by Kruskal−Wallis analysis of variance with Dunn’s multiple comparison test and multiple regression models. All assays showed acceptable intra-assay reproducibility; however, most were associated with significant interlaboratory variation. The smallest reliably detectable cytokine differences (P < 0.05) derived from pooled interlaboratory data varied from 1.5- to 26-fold depending on assay, cytokine, and matrix type. IL-6 but not IL-1β determinations were lower in both saline and phosphate-buffered saline as compared to vaginal fluid matrix, with no significant effect of pH. The (electro)chemiluminescence-based assays were most discriminative and consistently detected <2-fold differences within each matrix type. The Luminex-based assays were less discriminative with lower reproducibility between laboratories. These results suggest the need for uniform vaginal sampling techniques and a better understanding of immunoassay platform differences and cross-validation before the biological significance of cytokine variations can be validated in clinical trials. This investigation provides the first standardized analytic approach for assessing differences in mucosal cytokine levels and may improve strategies for monitoring immune responses at the vaginal mucosal interface

Filmic geographies: audio-visual, embodied-material

Although conventionally described as a ‘visual’ method, film-making is also increasingly used within research on embodiment. However, much remains to be said about the ability of filmic methods to enhance researchers’ capacity to think and research through the body. Drawing on my experience of making four research films, in this paper, I attempt to advance this agenda in three steps. First, I introduce anthropological work on the filming body to shed light on the technologically-mediated encounters that enfold around a camera and discuss how they might inform geographical thinking. Second, I describe the corporeally-mediated object ecologies that take shape within the filming setting and highlight how a camera might make objects ‘speak’. Finally, I discuss the affective dimension of screening research films to research participants and the contribution of such intense events to the articulation of collective matters of concerns. Through these three themes, I make the case for understanding knowledge production as located not merely in encounters with filmed audio-visual content, but also in the embodied-material encounters of bodies and objects around the filming and screening apparatus. I finally discuss the implications of these reflections for conceptualising the ‘body’ within embodied methods in social and cultural geography

How tolerant can you be? Carnap on rationality

In this paper I examine a neglected question concerning the centerpiece of Carnap's philosophy: the principle of tolerance. The principle of tolerance states that we are free to devise and adopt any well-defined form of language or linguistic framework we please. A linguistic framework defines framework-internal standards of correct reasoning that guide is in our first-order scientific pursuits. The choice of a linguistic framework, on the other hand, is an `external' question to be settled on pragmatic grounds and so not itself constrained by these (framework-internal) standards. However, even if choosing a framework is a practical matter, we would nevertheless expect the process of framework selection to be subject to rational norms. But which norms might those be? And where do they come from? I begin by showing that these questions are crucial to the success of Carnap's entire philosophical project. I then offer a response on behalf of the Carnapian which guarantees the rationality of the process of framework selection, while remaining true to Carnap's firm commitment to tolerance

Relating rheology and tribology of commercial dairy colloids to sensory perception

This study aims to investigate the relationship between rheological and tribological properties of commercial full fat and fat-free/ low fat versions of liquid and soft solid colloidal systems (milk, yoghurt, soft cream cheese) with their sensory properties. Oscillatory measurements (strain, frequency), flow curves and tribological measurements (lubricational behaviour using Stribeck analysis) were conducted. Oral condition was mimicked using artificial saliva at 37 ○C. Discrimination test was conducted by 63 untrained consumers, followed by a qualitative questionnaire. Consumers significantly discriminated the fat-free/low fat from the full fat versions (p0.05). Full fat and fat free yoghurts had similar yielding behaviour and elastic modulus (G'), even in simulated oral conditions. However, in case of soft cream cheese, the full fat version had a moderately higher G’ than the low fat counterpart. Even in presence of artificial saliva, there was slight but significant difference in viscoelasticity between the cream cheese variants depending on fat content (p0.05). Results suggest that sensory distinction between fat-free and full fat versions, particularly in semi-solid systems could be better predicted by lubrication data as compared to bulk rheology

1-Hydroxypyrene–A Biochemical Marker for PAH Pollution Assessment of Aquatic Ecosystem

The aim of the present study was to assess aquatic contamination by polycyclic aromatic hydrocarbons (PAH), using the 1-hydroxypyrene (1-OHP) content in fish bile as a biochemical marker. A total of 71 chub (Leuciscus cephalus L.) were collected from seven locations on the Svitava and Svratka rivers in and around the industrial city of Brno, Czech Republic. The levels of 1-OHP were determined by reverse phase HPLC with fluorescence detection after deconjugation. Normalising the molar concentration of the biliary 1-OHP to the biliary protein content reduced sample variation. The content of 1-OHP was correlated with the PAH level in bottom sediment and semi-permeable membrane devices (SPMD), which was analyzed by a combination of HPLC/FLD and GC/MS methods. The highest mean values of 1-OHP were found in fish caught at the Svratka River at locations Modřice (169.2 ± 99.7 ng·mg−1 protein) and Rajhradice (152.2 ± 79.7 ng·mg−1 protein), which are located downstream from Brno. These values were significantly (P < 0.05) higher than those obtained from localities Kníničky (98.4 ± 66.1 ng·mg−1 protein) and Bílovice nad Svitavou (64.1 ± 31.4 ng·mg−1 protein). The lowest contents of PAH in sediment and SPMD were found at location Kníničky (1.5 mg·kg−1 dry mass and 19.4 ng·L−1, respectively). The highest contents of PAH in sediment and SPMD were found in Rajhradice (26.0 mg·kg−1 dry mass) and Svitava before junction (65.4 ng·L−1), respectively. A Spearman correlation test was applied to determine the relationship between biliary 1-OHP and the sum of PAH in sediment and SPMD. A positive, but no statistically significant correlation was found. The main impact sources of elevated level of PAHs in sites located downstream from Brno are most probably intensive industrial and agricultural activities and domestic waste

Analytical advances in the ex vivo challenge efficacy assay

The ex vivo challenge assay is being increasingly used as an efficacy endpoint during early human clinical trials of HIV prevention treatments. There is no standard methodology for the ex vivo challenge assay, although the use of different data collection methods and analytical parameters may impact results and reduce the comparability of findings between trials. In this analysis, we describe the impact of data imputation methods, kit type, testing schedule and tissue type on variability, statistical power, and ex vivo HIV growth kinetics. Data were p24 antigen (pg/ml) measurements collected from clinical trials of candidate microbicides where rectal (n = 502), cervical (n = 88), and vaginal (n = 110) tissues were challenged with HIV-1BaL ex vivo. Imputation of missing data using a nonlinear mixed effect model was found to provide an improved fit compared to imputation using half the limit of detection. The rectal virus growth period was found to be earlier and of a relatively shorter duration than the growth period for cervical and vaginal tissue types. On average, only four rectal tissue challenge assays in each treatment and control group would be needed to find a one log difference in p24 to be significant (alpha = 0.05), but a larger sample size was predicted to be needed for either cervical (n = 21) or vaginal (n = 10) tissue comparisons. Overall, the results indicated that improvements could be made in the design and analysis of the ex vivo challenge assay to provide a more standardized and powerful assay to compare efficacy of microbicide products