Framing Expectations in Early HIV Cure Research

Language used to describe clinical research represents a powerful opportunity to educate volunteers. In the case of HIV cure research there is an emerging need to manage expectations by using the term ‘experiment’. Cure experiments are proof-of-concept studies designed to evaluate novel paradigms to reduce persistent HIV-1 reservoirs, without any expectation of medical benefit

Secondary HIV Infection and Mitigation in Cure-Related HIV Trials During Analytical Treatment Interruptions

To the Editor—We are writing to express concerns regarding facts reported in 2 recent Journal of Infectious Diseases articles pertaining to the ANRSLIGHT study, conducted in 18 clinical sites in France between September 2013 and May 2015. Initially, we were delighted to see the authors implemented several inclusion criteria that we believe were likely to ensure safety of participants during the analytical treatment interruption (ATI) that occurred during the trial, for example a nadir of CD4+ T-cell count of ≥300 cells/mm3 and an initial CD4+ T-cell count of ≥600/mm3. However, other aspects are dismaying, including the detailed identifying information about the index participant and partner. We fear it is possible to identify both persons from the elaborate medical and nonmedical history provided. After contacting the study Principal Investigator, Dr Lelièvre, through a European colleague, it appears there were no consents to disclose this information. Thus, we feel strongly that it was inappropriate to include such comprehensive, potentially identifying details

The effect of cellulose nanocrystals on latex and adhesive properties in emulsion- based polymer nanocomposites

Pressure sensitive adhesives (PSAs) adhere quickly and firmly to surfaces with the application of light pressure, and can be removed without leaving a residue. Their mechanical performance is measured by tack, peel strength and shear strength. A balanced combination between the three mechanical performance measurements depends on the specific end-use application and is challenging to achieve. This is particularly so when replacing solvent-based technologies with more sustainable, water-based (i.e., emulsion polymerization) technologies. PSAs synthesized using emulsion polymerization tend to have a lower shear strength due to poor gel network formation. As a result, conventional emulsion-based PSAs suffer from the inability to increase certain adhesive properties (e.g., tack and peel strength) while simultaneously increasing shear strength. Nanomaterials are often used in polymer composites to improve polymer properties (e.g., tensile strength). They are particularly effective in low quantities (e.g., \u3c2 \u3ewt.%) because of their high surface area. Cellulose nanocrystals (CNCs) are a “green alternative” to common nanomaterials and are isolated from natural cellulose. CNCs have been used more commonly, in the past, as rheological modifiers and interface stabilizers.[1] Because CNCs form colloidally stable dispersions in water, they can be incorporated/processed in water-based systems, eliminating the need for organic solvents.[2] The most common method to produce CNCs is through acid hydrolysis with sulfuric acid; this process preferentially degrades the disordered cellulose regions and leaves behind the crystalline CNCs with grafted anionic sulfate half ester groups.[1] The resulting nanoparticles are whisker-shaped and have a high aspect ratio.[3] CNCs provide composite material reinforcement in the range of other nanomaterials. In the past, CNCs have been blended with polymers and significant strength improvements were noted.[4] Our studies demonstrate how to incorporate CNCs in a nanocomposite using an in situ semi-batch emulsion polymerization protocol.[5] PSA nanocomposite films were generated for a broad variety of copolymer systems including monomers such as iso-butyl acrylate, n-butyl acrylate, 2-ethyl hexyl acrylate, methyl methacrylate, styrene and vinyl acetate. In all cases, the monomer composition of the reaction formulations was manipulated to achieve a suitable range of polymer glass transition temperatures. CNC loadings were varied from 0 to 0.5 to 1 wt.% (based on monomer weight). The addition of CNC was shown to significantly and simultaneously increase tack, peel strength, and shear strength.[6] References [1] Dufresne, A., Nanocellulose, De Gruyter, Saint Martin D’Heres Cedex, France 2012. [2] Flauzino Neto, W. P., Mariano, M., da Silva, I. S. V., Silvério, H. A., Putaux, J.-L., Otaguro, H., Pasquini, D., Dufresne, A., Carbohydr. Polym. 2016, 153, 143. [3] Moon, R. J., Martini, A., Nairn, J., Simonsen, J., Youngblood, J., Chem. Soc. Rev., 2011, 40, 3941. [4] Rajisha, K. R., Maria, H. J., Pothan, L. A., Ahmad, Z., Thomas, S., Int. J. Biol. Macromol., 2014, 67, 147. [5] Dastjerdi, Z., Cranston, E. D., Dubé, M. A., Macromol. React. Eng., 2018, in press. [6] Dastjerdi, Z., Cranston, E. D., Dubé, M. A., Int. J. Adh. Adh. 2018, 81, 36-42

Applying the Functional Behavioral and Social Sciences Research (BSSR) Framework to HIV Cure Research

Introduction The search for an HIV cure involves important behavioural and social processes that complement the domains of biomedicine. However, the field has yet to tap into the full potential of behavioural and social sciences research (BSSR). In this article, we apply Gaist and Stirratt’s BSSR Functional Framework to the field of HIV cure research. Discussion The BSSR Functional Framework describes four key research domains: (1) basic BSSR (understanding basic behavioural and social factors), (2) elemental BSSR (advancing behavioural and social interventions), (3) supportive BSSR (strengthening biomedically focused clinical trials), and (4) integrative BSSR (building multi-disciplinary combination approaches for real-world implementation). In revisiting and applying the BSSR Functional Framework, we clarify the importance of BSSR in HIV cure research by drawing attention to such things as: how language and communication affect the meaning of “cure” to people living with HIV (PLHIV) and broader communities; how cure affects the identity and social position of PLHIV; counselling and support interventions to address the psychosocial needs and concerns of study participants related to analytical treatment interruptions (ATIs); risk reduction in the course of ATI study participation; motivation, acceptability, and decision-making processes of potential study participants related to different cure strategies; HIV care providers’ perceptions and attitudes about their patients’ participation in cure research; potential social harms or adverse social events associated with cure research participation; and the scalability of a proven cure strategy in the context of further advances in HIV prevention and treatment. We also discuss the BSSR Functional Framework in the context of ATIs, which involve processes at the confluence of the BSSR domains. Conclusions To move HIV cure regimens through the translational research pathway, attention will need to be paid to both biomedical and socio-behavioural elements. BSSR can contribute an improved understanding of the human and social dimensions related to HIV cure research and the eventual application of HIV cure regimens. The BSSR Functional Framework provides a way to identify advances, gaps and opportunities to craft an integrated, multi-disciplinary approach at all stages of cure research to ensure the real-world applicability of any strategy that shows promise

Interface Equations for Capillary Rise in Random Environment

We consider the influence of quenched noise upon interface dynamics in 2D and 3D capillary rise with rough walls by using phase-field approach, where the local conservation of mass in the bulk is explicitly included. In the 2D case the disorder is assumed to be in the effective mobility coefficient, while in the 3D case we explicitly consider the influence of locally fluctuating geometry along a solid wall using a generalized curvilinear coordinate transformation. To obtain the equations of motion for meniscus and contact lines, we develop a systematic projection formalism which allows inclusion of disorder. Using this formalism, we derive linearized equations of motion for the meniscus and contact line variables, which become local in the Fourier space representation. These dispersion relations contain effective noise that is linearly proportional to the velocity. The deterministic parts of our dispersion relations agree with results obtained from other similar studies in the proper limits. However, the forms of the noise terms derived here are quantitatively different from the other studies

Human Chromosomes: Evaluation of Processing Techniques for Scanning Electron Microscopy

Methods for scanning electron microscopy (SEM) of chromosomes have been developed in the last two decades. Technical limitations in the study of human chromosomes, however, have hindered the routine use of SEM in clinical and experimental human cytogenetics. We compared different methodologies, including metal impregnation, air drying and specimen coating. SEM preparation of human chromosomes in which osmium impregnation is mediated by tannic acid, yielded more reproducible results when compared with osmium impregnation protocols previously described. The level of osmium impregnation was systematically evaluated by imaging chromosomes in the backscattering mode. Critical point drying and a light gold-palladium coating were essential for appropriate secondary electron imaging of chromosomes. With this method, and in a preliminary quantitative analysis, we show that our SEM technique is mere sensitive than light microscopy for the detection of aphidicolin-induced fragile sites. This technical approach is useful for chromosomal studies requiring resolution higher than that obtained by light microscopy. Also, it allows the use of clinical and archival chromosomal samples prepared by routine cytogenetic techniques

Perceptions of HIV Virologic Control Strategies among Younger and Older Age Groups of People Living with HIV in the United States: A Cross-Sectional Survey

Two HIV virologic control advances are in various stages of development, including long-acting antiretroviral therapy (ART) formulations and strategies aimed at sustained ART-free HIV control. Perceptions of risks and benefits toward HIV virologic control strategies may be different based on an individual's age due to differing experiences of the impacts of the domestic HIV epidemic, altruistic attitudes toward research participation, and general levels of engagement in health care. We examined preferences of HIV virologic control strategies by age groups. In 2018, we conducted a nationwide, online cross-sectional survey to examine differences in HIV virologic control strategies among a sample of people living with HIV who were = 50 years of age. From a total of 281 participants, 3 findings were noteworthy: (1) Participants = 50 years; (2) participants >= 50 years of age were more motivated by altruistic notions compared with those = 50 years. Our analysis provides a deeper understanding of differences in perceptions among various age groups regarding desirable future ART characteristics, and motivations and barriers to participating in HIV cure-related strategies. Our findings can help inform community engagement and education, and assist researchers in tailoring study design and recruitment efforts to major age groups

Manipulation and Detection of a Trapped Yb+ Ion Hyperfine Qubit

We demonstrate the use of trapped ytterbium ions as quantum bits for quantum information processing. We implement fast, efficient state preparation and state detection of the first-order magnetic field-insensitive hyperfine levels of 171Yb+, with a measured coherence time of 2.5 seconds. The high efficiency and high fidelity of these operations is accomplished through the stabilization and frequency modulation of relevant laser sources.Comment: 10 pages, 9 figures, 1 tabl

Noncyclic covers of knot complements

Hempel has shown that the fundamental groups of knot complements are residually finite. This implies that every nontrivial knot must have a finite-sheeted, noncyclic cover. We give an explicit bound, $\Phi (c)$, such that if $K$ is a nontrivial knot in the three-sphere with a diagram with $c$ crossings and a particularly simple JSJ decomposition then the complement of $K$ has a finite-sheeted, noncyclic cover with at most $\Phi (c)$ sheets.Comment: 29 pages, 8 figures, from Ph.D. thesis at Columbia University; Acknowledgments added; Content correcte