Faculty Bibliography

Functional analysis of a clinical microbiome facilitates the elucidation of mechanisms by which microbiome perturbation can cause a phenotypic change in the patient. The direct approach for the analysis of the functional capacity of the microbiome is via shotgun metagenomics. An inexpensive method to estimate the functional capacity of a microbial community is through collecting 16S rRNA gene profiles then indirectly inferring the abundance of functional genes. This inference approach has been implemented in the PICRUSt and Tax4Fun software tools. However, those tools have important limitations since they rely on outdated functional databases and uncertain phylogenetic trees and require very specific data pre-processing protocols. Here we introduce Piphillin, a straightforward algorithm independent of any proposed phylogenetic tree, leveraging contemporary functional databases and not obliged to any singular data pre-processing protocol. When all three inference tools were evaluated against actual shotgun metagenomics, Piphillin was superior in predicting gene composition in human clinical samples compared to both PICRUSt and Tax4Fun (p<0.01 and p<0.001, respectively) and Piphillin's ability to predict disease associations with specific gene orthologs exhibited a 15% increase in balanced accuracy compared to PICRUSt. From laboratory animal samples, no performance advantage was observed for any one of the tools over the others and for environmental samples all produced unsatisfactory predictions. Our results demonstrate that functional inference using the direct method implemented in Piphillin is preferable for clinical biospecimens. Piphillin is publicly available for academic use at http://secondgenome.com/Piphillin.

BACKGROUND: The profunda artery perforator flap was first introduced for breast reconstruction in 2010. In this article, the authors analyze the results of all profunda artery perforator flaps performed by their group to date. METHODS: A retrospective review was completed of consecutive profunda artery perforator flaps performed by the senior author (R.J.A.) from 2010 to 2014. Patient demographics, indications, operative techniques, flap specifics, complications, and number of operations were recorded. RESULTS: Ninety-six patients have undergone 164 profunda artery perforator flap operations for breast reconstruction since 2010. Reconstructions were performed following breast cancer management (59.5 percent), following prophylactic mastectomy for cancer risk reduction (35.7 percent), and for congenital breast deformity (4.8 percent). The average age of the patients was 48 years (range, 24 to 64 years) and their average body mass index was 22.5 kg/m. Average flap weight was 367.4 g and average pedicle length was found to be 10.2 cm. The success rate of the profunda artery perforator flap was greater than 99 percent, with a 3 percent take-back rate and only one flap loss recorded. Complications included hematoma (1.9 percent), seroma (6 percent), fat necrosis (7 percent), and donor-site infection (1.9 percent). CONCLUSIONS: The profunda artery perforator flap is an excellent option for breast reconstruction. Advantages include a reliable blood supply, long pedicle, thick donor tissue, and a favorable donor site. Currently, the profunda artery perforator flap is second only to the deep inferior epigastric artery perforator among flaps used by the authors for breast reconstruction. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

BACKGROUND: Implementation science holds promise for better ensuring that research is translated into evidence-based policy and practice, but interventions often fail or even worsen the problems they are intended to solve due to a lack of understanding of real world structures and dynamic complexity. While systems science alone cannot possibly solve the major challenges in public health, systems-based approaches may contribute to changing the language and methods for conceptualising and acting within complex systems. The overarching goal of this paper is to improve the modelling used in dissemination and implementation research by applying best principles of systems science. DISCUSSION: Best principles, as distinct from the more customary term 'best practices', are used to underscore the need to extract the core issues from the context in which they are embedded in order to better ensure that they are transferable across settings. Toward meaningfully grappling with the complex and challenging problems faced in adopting and integrating evidence-based health interventions and changing practice patterns within specific settings, we propose and illustrate four best principles derived from our systems science experience: (1) model the problem, not the system; (2) pay attention to what is important, not just what is quantifiable; (3) leverage the utility of models as boundary objects; and (4) adopt a portfolio approach to model building. To improve our mental models of the real world, system scientists have created methodologies such as system dynamics, agent-based modelling, geographic information science and social network simulation. To understand dynamic complexity, we need the ability to simulate. Otherwise, our understanding will be limited. The practice of dynamic systems modelling, as discussed herein, is the art and science of linking system structure to behaviour for the purpose of changing structure to improve behaviour. A useful computer model creates a knowledge repository and a virtual library for internally consistent exploration of alternative assumptions. CONCLUSION: Among the benefits of systems modelling are iterative practice, participatory potential and possibility thinking. We trust that the best principles proposed here will resonate with implementation scientists; applying them to the modelling process may abet the translation of research into effective policy and practice.

OBJECTIVE: To evaluate the fatigue life of zirconia-veneered and metal-ceramic crowns comprised by an even thickness or a modified framework design when loaded on marginal ridges. METHODS: Eighty marginal ridges were present after fabrication of forty molar crowns cemented onto composite-resin replicas and divided (n=20/each), in the following groups: metal-ceramic with even thickness (MCev) or with a modified framework design (MCm, lingual collar with proximal struts); porcelain-fused to zirconia with even thickness (PFZev) or with the modified framework design (PFZm). Each marginal ridge (mesial and distal) was subjected to cyclic loading separately with a lithium disilicate indenter for 106 cycles or until fracture. Kruskal-Wallis and Wilcoxon matched pair test (p<0.05) evaluated both marginal ridges. Every 125,000 cycles, the test was interrupted for damage inspection. Weibull distribution (90% confidence bounds) determined the probability of survival (reliability). RESULTS: Weibull 2-parameter contour-plot showed significantly higher fatigue life for PFZev compared to MC, and comparable with PFZm. A significant decrease in reliability was observed between groups from 625,000 until 106 cycles. Metal-ceramic groups presented significantly lower probability of survival at 106 cycles (MCev=0.66% and MCm=4.73%) compared to PFZm (23.41%) and PFZev (36.68%). Fractographic marks showed a consistent fracture origin and direction of crack propagation. Reliability was higher for porcelain-fused to zirconia than for metal ceramic crowns, regardless of framework design. SIGNIFICANCE: Zirconia-veneered crowns presented decreased fracture rates compared to metal ceramics, even when loaded at marginal ridges, regardless of framework design.

This study evaluated the probability of survival (reliability) of platform-switched fixed dental prostheses (FDPs) cemented on different implant-abutment connection designs. Eighty-four-three-unit FDPs (molar pontic) were cemented on abutments connected to two implants of external or internal hexagon connection. Four groups (n = 21 each) were established: external hexagon connection and regular platform (ERC); external hexagon connection and switched platform (ESC); internal hexagon and regular platform (IRC); and internal hexagon and switched platform (ISC). Prostheses were subjected to step-stress accelerated life testing in water. Weibull curves and probability of survival for a mission of 100,000 cycles at 400 N (two-sided 90% CI) were calculated. The beta values of 0.22, 0.48, 0.50, and 1.25 for groups ERC, ESC, IRC, and ISC, respectively, indicated a limited role of fatigue in damage accumulation, except for group ISC. Survival decreased for both platform-switched groups (ESC: 74%, and ISC: 59%) compared with the regular matching platform counterparts (ERC: 95%, and IRC: 98%). Characteristic strength was higher only for ERC compared with ESC, but not different between internal connections. Failures chiefly involved the abutment screw. Platform switching decreased the probability of survival of FDPs on both external and internal connections. The absence in loss of characteristic strength observed in internal hexagon connections favor their use compared with platform-switched external hexagon connections.