Self-assembled monolayers of phosphonates promote primary chondrocyte adhesion to silicon dioxide and polyvinyl alcohol materials

The optimal solution for articular cartilage repair has not yet been identified, in part because of the challenges in achieving integration with the host. Coatings have the potential to transform the adhesive features of surfaces, but their application to cartilage repair has been limited. Self-assembled monolayer of phosphonates (SAMPs) have been demonstrated to increase the adhesion of various immortalized cell types to metal and polymer surfaces, but their effect on primary chondrocyte adhesion has not been studied. The objective of this study was to investigate the response of primary chondrocytes to SAMP coatings. We hypothesized a SAMP terminated with an α,ω-bisphosphonic acid, in particular butane-1,4-diphosphonic acid, would increase the number of adherent primary chondrocytes to polyvinyl alcohol (PVA). To test our hypothesis, we first established our ability to successfully modify silicon dioxide (SiO₂) surfaces to enable chondrocytes to attach to the surface, without substantial changes in gene expression. Secondly, we applied identical chemistry to PVA, and quantified chondrocyte adhesion. SAMP modification to SiO₂ increased chondrocyte adhesion by ×3 after 4?hr and ×4.5 after 24?hr. PVA modification with SAMPs increased chondrocyte adhesion by at least ×31 after 4 and 24?hours. Changes in cell morphology indicated that SAMP modification led to improved chondrocyte adhesion and spreading, without changes in gene expression. In summary, we modified SiO₂ and PVA with SAMPs and observed an increase in the number of adherent primary bovine chondrocytes at 4 and 24?hr post-seeding. Mechanisms of chondrocyte interaction with SAMP-modified surfaces require further investigation.     

Adverse birth outcomes in relation to maternal marital and cohabitation status in Canada

Purpose

An increasing percentage of children are born to couples who cohabit but are not legally married. Using data from a nationally representative Canadian sample, we estimated associations of maternal marital and cohabitation status with stillbirth, infant mortality, preterm birth (PTB), and small- and large-for-gestational-age (SGA and LGA) birth.

The influence of MCAT and GPA preadmission academic metrics on interview scores

Medical school admissions interviews are used to assess applicants’ nonacademic characteristics as advocated by the Association of American Medical Colleges’ Advancing Holistic Review Initiative. The objective of this study is to determine whether academic metrics continue to significantly influence interviewers’ scores in holistic processes by blinding interviewers to applicants’ undergraduate grade point averages (uGPA) and Medical College Admission Test (MCAT). This study examines academic and demographic predictors of interview scores for two applicant cohorts at the University of Michigan Medical School. In 2012, interviewers were provided applicants’ uGPA and MCAT scores; in 2013, these academic metrics were withheld from interviewers’ files. Hierarchical regression analysis was conducted to examine the influence of academic and demographic variables on overall cohort interview scores. When interviewers were provided uGPA and MCAT scores, academic metrics explained more variation in interview scores (7.9%) than when interviewers were blinded to these metrics (4.1%). Further analysis showed a statistically significant interaction between cohort and uGPA, indicating that the association between uGPA and interview scores was significantly stronger for the 2012 unblinded cohort compared to the 2013 blinded cohort (β = .573, P < .05). By contrast, MCAT scores had no interactive effects on interviewer scores. While MCAT scores accounted for some variation in interview scores for both cohorts, only access to uGPA significantly influenced interviewers’ scores when looking at interaction effects. Withholding academic metrics from interviewers’ files may promote assessment of nonacademic characteristics independently from academic metrics.     

Validity of environmental audits using GigaPan<Superscript>®</Superscript> and Google Earth Technology

Background

Health behaviors are shaped by the context in which people live. However, documenting environmental context has remained a challenge. More specifically, direct observation techniques require large investments in time and resources and auditing the environment through web-based platforms has limited stability in spatio-temporal imagery. This study examined the validity of a new methodology, using GigaPan^® imagery, where we took photos locally and, stitched them together using GigaPan^® technology, and quantified environmental attributes from the resulting panoramic photo. For comparison, we examined validity using Google Earth imagery.

Methods

A total of 464 street segments were assessed using three methods: GigaPan^® audits, Google Earth audits, and direct observation audits. Thirty-seven different attributes were captured representing three broad constructs: land use, traffic and safety, and amenities. Sensitivity (i.e. the proportion of true positives) and specificity (i.e. the proportion of true negatives) were used to estimate the validity of GigaPan^® and Google Earth audits using direct observation audits as the gold standard.

Results

Using GigaPan^®, sensitivity was 80% or higher for 6 of 37 items and specificity was 80% or higher for 31 of 37 items. Using Google Earth, sensitivity was 80% or higher for 8 of 37 items and specificity was 80% or higher for 30 of 37 items. The validity of GigaPan^® and Google Earth was similar, with significant differences in sensitivity and specificity for 7 items and 2 items, respectively.

Conclusion

GigaPan^® performed well, especially when identifying features absent from the environment. A major strength of the GigaPan^® technology is its ability to be implemented quickly in the field relative to direct observation. GigaPan^® is a method to consider as an alternative to direct observation when temporality is prioritized or Google Earth imagery is unavailable.

     

Cost-effectiveness of vedolizumab compared with infliximab,adalimumab, and golimumab in patients with ulcerative colitis in the United Kingdom

Objective

To examine the clinical and economic impact of vedolizumab compared with infliximab, adalimumab, and golimumab in the treatment of moderately to severely active ulcerative colitis (UC) in the United Kingdom (UK).

Methods

A decision analytic model in Microsoft Excel was used to compare vedolizumab with other biologic treatments (infliximab, adalimumab, and golimumab) for the treatment of biologic-naïve patients with UC in the UK. Efficacy data were obtained from a network meta-analysis using placebo as the common comparator. Other inputs (e.g., unit costs, adverse-event disutilities, probability of surgery, mortality) were obtained from published literature. Costs were presented in 2012/2013 British pounds. Outcomes included quality-adjusted life-years (QALYs). Costs and outcomes were discounted by 3.5% per year. Incremental cost-effectiveness ratios were presented for vedolizumab compared with other biologics. Univariate and multivariate probabilistic sensitivity analyses were conducted to assess model robustness to parameter uncertainty.

Results

The model predicted that anti-tumour necrosis factor-naïve patients on vedolizumab would accrue more QALY than patients on other biologics. The incremental results suggest that vedolizumab is a cost-effective treatment compared with adalimumab (incremental cost-effectiveness ratio of £22,735/QALY) and dominant compared with infliximab and golimumab. Sensitivity analyses suggest that results are most sensitive to treatment response and transition probabilities. However, vedolizumab is cost-effective irrespective of variation in any of the input parameters.

Conclusions

Our model predicted that treatment with vedolizumab improves QALY, increases time in remission and response, and is a cost-effective treatment option compared with all other biologics for biologic-naïve patients with moderately to severely active UC.

     

Associations Between Neighborhood Characteristics,Social Cohesion,and Perceived Sex Partner Risk and Non-Monogamy Among HIV-Seropositive and HIV-Seronegative Women in the Southern U.S.

Neighborhood social and physical factors shape sexual network characteristics in HIV-seronegative adults in the U.S. This multilevel analysis evaluated whether these relationships also exist in a predominantly HIV-seropositive cohort of women. This cross-sectional multilevel analysis included data from 734 women enrolled in the Women’s Interagency HIV Study’s sites in the U.S. South. Census tract-level contextual data captured socioeconomic disadvantage (e.g., tract poverty), number of alcohol outlets, and number of non-profits in the census tracts where women lived; participant-level data, including perceived neighborhood cohesion, were gathered via survey. We used hierarchical generalized linear models to evaluate relationships between tract characteristics and two outcomes: perceived main sex partner risk level (e.g., partner substance use) and perceived main sex partner non-monogamy. We tested whether these relationships varied by women’s HIV status. Greater tract-level socioeconomic disadvantage was associated with greater sex partner risk (OR 1.29, 95% CI 1.06–1.58) among HIV-seropositive women and less partner non-monogamy among HIV-seronegative women (OR 0.69, 95% CI 0.51–0.92). Perceived neighborhood trust and cohesion was associated with lower partner risk (OR 0.83, 95% CI 0.69–1.00) for HIV-seropositive and HIV-seronegative women. The tract-level number of alcohol outlets and non-profits were not associated with partner risk characteristics. Neighborhood characteristics are associated with perceived sex partner risk and non-monogamy among women in the South; these relationships vary by HIV status. Future studies should examine causal relationships and explore the pathways through which neighborhoods influence partner selection and risk characteristics.