Increasing the Effectiveness of Vaginal Microbicides: A Biophysical Framework to Rethink Behavioral Acceptability

Microbicide candidates delivered via gel vehicles are intended to coat the vaginal epithelium after application. The coating process depends on intrinsic biophysical properties of the gel texture, which restricts the potential choices for an effective product: the gel first must be physically synthesizable, then acceptable to the user, and finally applied in a manner promoting timely adequate coating, so that the user adherence is optimized. We present a conceptual framework anchoring microbicide behavioral acceptability within the fulfillment of the product biophysical requirements.We conducted a semi-qualitative/quantitative study targeting women aged 18-55 in Northern California to assess user preferences for microbicide gel attributes. Attributes included: (i) the wait time between application and intercourse, (ii) the gel texture and (iii) the trade-off between wait time and gel texture. Wait times were assessed using a mathematical model determining coating rates depending upon the gel's physical attributes.71 women participated. Results suggest that women would independently prefer a gel spreading rapidly, in 2 to 15 minutes (P<0.0001), as well as one that is thick or slippery (P<0.02). Clearly, thick gels do not spread rapidly; hence the motivation to study the trade-off. When asked the same question 'constrained' by the biophysical reality, women indicated no significant preference for a particular gel thickness (and therefore waiting time) (P>0.10) for use with a steady partner, a preference for a watery gel spreading rapidly rather than one having intermediate properties for use with a casual partner (P = 0.024).Biophysical constraints alter women's preferences regarding acceptable microbicide attributes. Product developers should offer a range of formulations in order to address all preferences. We designed a conceptual framework to rethink behavioral acceptability in terms of biophysical requirements that can help improve adherence in microbicide use ultimately enhancing microbicide effectiveness

Enhancement of the high-field critical current density of superconducting MgB2 by proton irradiation

A relatively high critical temperature, Tc, approaching 40 K, places the recently-discovered superconductor magnesium diboride (MgB2) intermediate between the families of low- and copper-oxide-based high-temperature superconductors (HTS). Supercurrent flow in MgB2 is unhindered by grain boundaries, unlike the HTS materials. Thus, long polycrystalline MgB2 conductors may be easier to fabricate, and so could fill a potentially important niche of applications in the 20 to 30 K temperature range. However, one disadvantage of MgB2 is that in bulk material the critical current density, Jc, appears to drop more rapidly with increasing magnetic field than it does in the HTS phases. The magnitude and field dependence of Jc are related to the presence of structural defects that can "pin" the quantised magnetic vortices that permeate the material, and prevent them from moving under the action of the Lorentz force. Vortex studies suggest that it is the paucity of suitable defects in MgB2 that causes the rapid decay of Jc with field. Here we show that modest levels of atomic disorder, induced by proton irradiation, enhance the pinning, and so increase Jc significantly at high fields. We anticipate that chemical doping or mechanical processing should be capable of generating similar levels of disorder, and so achieve technologically-attractive performance in MgB2 by economically-viable routes.Comment: 5 pages, 4 figures, to be published in Nature (in press

Young women's use of a microbicide surrogate: The complex influence of relationship characteristics and perceived male partners' evaluations

This is the post-print version of the article. The official published version can be found at the link below.Currently in clinical trials, vaginal microbicides are proposed as a female-initiated method of sexually transmitted infection prevention. Much of microbicide acceptability research has been conducted outside of the United States and frequently without consideration of the social interaction between sex partners, ignoring the complex gender and power structures often inherent in young women’s (heterosexual) relationships. Accordingly, the purpose of this study was to build on existing microbicide research by exploring the role of male partners and relationship characteristics on young women’s use of a microbicide surrogate, an inert vaginal moisturizer (VM), in a large city in the United States. Individual semi-structured interviews were conducted with 40 young women (18–23 years old; 85% African American; 47.5% mothers) following use of the VM during coital events for a 4 week period. Overall, the results indicated that relationship dynamics and perceptions of male partners influenced VM evaluation. These two factors suggest that relationship context will need to be considered in the promotion of vaginal microbicides. The findings offer insights into how future acceptability and use of microbicides will be influenced by gendered power dynamics. The results also underscore the importance of incorporating men into microbicide promotion efforts while encouraging a dialogue that focuses attention on power inequities that can exist in heterosexual relationships. Detailed understanding of these issues is essential for successful microbicide acceptability, social marketing, education, and use.This study was funded by a grant from National Institutes of Health (NIHU19AI 31494) as well as research awards to the first author: Friends of the Kinsey Institute Research Grant Award, Indiana University’s School of HPER Graduate Student Grant-in-Aid of Research Award, William L. Yarber Sexual Health Fellowship, and the Indiana University Graduate and Professional Student Organization Research Grant

Genetic Variations in IL28B and Allergic Disease in Children

Environmental changes affecting the relationship between the developing immune system and microbial exposure have been implicated in the epidemic rise of allergic disease in developed countries. While early developmental differences in T cell function are well-recognised, there is now emerging evidence that this is related to developmental differences in innate immune function. In this study we sought to examine if differences associated with innate immunity contribute to the altered immune programming recognised in allergic children. Here, we describe for the first time, the association of carriage of the T allele of the tagging single nucleotide polymorphism rs12979860 3 kb upstream of IL28B, encoding the potent innate immune modulator type III interferon lambda (IFN-λ3), and allergy in children (p = 0.004; OR 4.56). Strikingly, the association between rs12979860 genotype and allergic disease is enhanced in girls. Furthermore, carriage of the T allele at rs12979860 correlates with differences in the pro-inflammatory profile during the first five years of life suggesting this contributes to the key differences in subsequent innate immune development in children who develop allergic disease. In the context of rising rates of disease, these immunologic differences already present at birth imply very early interaction between genetic predisposition and prenatal environmental influences

Dose to level I and II axillary lymph nodes and lung by tangential field radiation in patients undergoing postmastectomy radiation with tissue expander reconstruction

<p>Abstract</p> <p>Background</p> <p>To define the dosimetric coverage of level I/II axillary volumes and the lung volume irradiated in postmastectomy radiotherapy (PMRT) following tissue expander placement.</p> <p>Methods and Materials</p> <p>Twenty-three patients were identified who had undergone postmastectomy radiotherapy with tangent only fields. All patients had pre-radiation tissue expander placement and expansion. Thirteen patients had bilateral expander reconstruction. The level I/II axillary volumes were contoured using the RTOG contouring atlas. The patient-specific variables of expander volume, superior-to-inferior location of expander, distance between expanders, expander angle and axillary volume were analyzed to determine their relationship to the axillary volume and lung volume dose.</p> <p>Results</p> <p>The mean coverage of the level I/II axillary volume by the 95% isodose line (V_D95%) was 23.9% (range 0.3 - 65.4%). The mean Ipsilateral Lung V_D50%was 8.8% (2.2-20.9). Ipsilateral and contralateral expander volume correlated to Axillary V_D95%in patients with bilateral reconstruction (p = 0.01 and 0.006, respectively) but not those with ipsilateral only reconstruction (p = 0.60). Ipsilateral Lung V_D50%correlated with angle of the expander from midline (p = 0.05).</p> <p>Conclusions</p> <p>In patients undergoing PMRT with tissue expanders, incidental doses delivered by tangents to the axilla, as defined by the RTOG contouring atlas, do not provide adequate coverage. The posterior-superior region of level I and II is the region most commonly underdosed. Axillary volume coverage increased with increasing expander volumes in patients with bilateral reconstruction. Lung dose increased with increasing expander angle from midline. This information should be considered both when placing expanders and when designing PMRT tangent only treatment plans by contouring and targeting the axilla volume when axillary treatment is indicated.</p

A quantitative model for estimating risk from multiple interacting natural hazards: an application to northeast Zhejiang, China

Multi-hazard risk assessment is a major concern in risk analysis, but most approaches do not consider all hazard interactions when calculating possible losses. We address this problem by developing an improved quantitative model - Model for multi-hazard Risk assessment with a consideration of Hazard Interaction (MmhRisk-HI). This model calculates the possible loss caused by multiple hazards, with an explicit consideration of interaction between those hazards. There are two main components to the model. In the first, based on the hazard-forming environment, relationships among hazards are classified into four types for calculation of the exceedance probability of multiple hazards occurrence. In the second, a Bayesian network is used to calculate possible loss caused by multiple hazards with different exceedance probabilities. A multi-hazard risk map can then be drawn addressing the probability of multi-hazard occurrence and corresponding loss. This model was applied in northeast Zhejiang, China and validated by comparison against an observed multi-hazard sequence. The validation results show that the model can more effectively represent the real world, and that the modelled outputs, possible loss caused by multiple hazards, are reliable. The outputs can additionally help to identify areas at greatest risk, and allows a determination of the factors that contribute to that risk, and hence the model can provide useful further information for planners and decision-makers concerned with risk mitigation

Topical microbicides to prevent the transmission of HIV: formulation gaps and challenges

The efforts of the topical microbicide field to identify a safe and effective topical microbicide were realized in July of 2010 with the reporting of the results of the Centre for the AIDS Programme of Research in South Africa 004 trial. In this trial, a 1% tenofovir gel was found to reduce women’s risk for HIV acquisition by 39% compared to placebo. To understand the impact of this trial on future microbicide development, we must view it from the historical perspective of previous phases 2 and 3 clinical trials with detergents and sulfated polyanions. This knowledge and emerging information must then be parlayed into the next steps needed to create a safe, effective, and acceptable topical microbicide. This review will look at the lessons learned from preclinical and clinical development of topical microbicides, focusing on two significant future challenges: (1) topical microbicide formulation safety and (2) the critical role that adherence to product use has in determining safety and efficacy in clinical trials and ultimately commercial viability of the licensed product. In addition to framing these issues within our current understanding of formulation and prevention of HIV acquisition, recent advances in our understanding of the mechanism of HIV transmission and how it informs on future formulation strategies will be briefly discussed

Organizational Support and Contract Fulfillment as Moderators of the Relationship Between Preferred Work Status and Performance

Purpose The purpose of this study was to examine organizational context variables as moderators of the relationship between preferred work status and job performance. The moderators were perceived organizational support (POS) and psychological contract fulfillment. Design/Methodology/Approach Survey data was collected from 164 participants working in a health and fitness organization. These participants ranged in age from 18 to 79 years old (M = 40, SD = 12.5) and held various positions including middle managers, clerical workers, maintenance workers, and sports trainers. Findings The relationship between preferred work status and extra-role performance was negative when POS was higher but not when POS was lower. Also, the relationship between preferred work status and extra-role performance was positive when contract fulfillment was lower but not when it was higher. No moderating effects were found when examining in-role performance. Implications Given the large and growing use of part-time workers it is important to understand differences across various subgroups of them in order to better inform human resource policies and practices. Specifically, the results highlight a key role for the management of reciprocity perceptions. Originality/Value The literature on part-time workers suggests there are important differences between employees who work part-time because they prefer it and those who work part-time but prefer to work full-time. Research regarding the relationship between preferred work status and performance has produced mixed results. This study helps reconcile conflicting results regarding the relationship between preferred work status and performance by examining the moderating effects of theoretically relevant variables

Tumor markers in breast cancer - European Group on Tumor Markers recommendations

Recommendations are presented for the routine clinical use of serum and tissue-based markers in the diagnosis and management of patients with breast cancer. Their low sensitivity and specificity preclude the use of serum markers such as the MUC-1 mucin glycoproteins ( CA 15.3, BR 27.29) and carcinoembryonic antigen in the diagnosis of early breast cancer. However, serial measurement of these markers can result in the early detection of recurrent disease as well as indicate the efficacy of therapy. Of the tissue-based markers, measurement of estrogen and progesterone receptors is mandatory in the selection of patients for treatment with hormone therapy, while HER-2 is essential in selecting patients with advanced breast cancer for treatment with Herceptin ( trastuzumab). Urokinase plasminogen activator and plasminogen activator inhibitor 1 are recently validated prognostic markers for lymph node-negative breast cancer patients and thus may be of value in selecting node-negative patients that do not require adjuvant chemotherapy. Copyright (C) 2005 S. Karger AG, Basel