Can static optimization detect changes in peak medial knee contact forces induced by gait modifications?

Medial knee contact force (MCF) is related to the pathomechanics of medial knee osteoarthritis. However, MCF cannot be directly measured in the native knee, making it difficult for therapeutic gait modifications to target this metric. Static optimization, a musculoskeletal simulation technique, can estimate MCF, but there has been little work validating its ability to detect changes in MCF induced by gait modifications. In this study, we quantified the error in MCF estimates from static optimization compared to measurements from instrumented knee replacements during normal walking and seven different gait modifications. We then identified minimum magnitudes of simulated MCF changes for which static optimization correctly identified the direction of change (i.e., whether MCF increased or decreased) at least 70% of the time. A full-body musculoskeletal model with a multi-compartment knee and static optimization was used to estimate MCF. Simulations were evaluated using experimental data from three subjects with instrumented knee replacements who walked with various gait modifications for a total of 115 steps. Static optimization underpredicted the first peak (mean absolute error = 0.16 bodyweights) and overpredicted the second peak (mean absolute error = 0.31 bodyweights) of MCF. Average root mean square error in MCF over stance phase was 0.32 bodyweights. Static optimization detected the direction of change with at least 70% accuracy for early-stance reductions, late-stance reductions, and early-stance increases in peak MCF of at least 0.10 bodyweights. These results suggest that a static optimization approach accurately detects the direction of change in early-stance medial knee loading, potentially making it a valuable tool for evaluating the biomechanical efficacy of gait modifications for knee osteoarthritis.

Understanding the Patient Experience: Analysis of 2-Word Assessment and Its Relationship to Likelihood to Recommend in Outpatient Hand Surgery.

BACKGROUND: Actionable feedback from patients after a clinic visit can help inform ways to better deliver patient-centered care. A 2-word assessment may serve as a proxy for lengthy post-visit questionnaires. We tested the use of a 2-word assessment in an outpatient hand clinic. METHODS: New patients were asked to provide a 2-word assessment of the following: (1) their physician; (2) their overall experience; and (3) recommendations for improvement and their likelihood to recommend (LTR) after their clinic visit. Sentiment analysis was used to categorize results into positive, neutral, or negative sentiment. Recommendations for improvement were classified into physician issue, system issue, or neither. We evaluated the relationship between LTR status, sentiment, actionable improvement opportunities, and classification (physician issue, system issue, or neither). Recommendations for improvement were classified into themes based on prior literature. RESULTS: Sixty-seven (97.1%) patients noted positive sentiment toward their physician; 67 (97.1%) noted positive sentiment toward their overall experience. About 31% of improvement recommendations were system-based, 5.9% were physician-based, and 62.7% were neither. Patients not LTR were more likely to leave actionable opportunities for improvement than those LTR (P = .01). Recommendations for improvement were classified into predetermined themes relating to: (1) physician interaction; (2) check-in process; (3) facilities; (4) unnecessary visit; and (5) appointment delays. CONCLUSION: Patients not likely to recommend provided actionable opportunities for improvement using a simple 2-word assessment. Implementation of a 2-word assessment in a hand clinic can be used to obtain actionable, real-time patient feedback that can inform operational change and improve the patient experience.

Tendency of Driving to the Basket Is Associated With Increased Risk of Anterior Cruciate Ligament Tears in National Basketball Association Players: A Cohort Study.

BACKGROUND: Driving to the basket in basketball involves acceleration, deceleration, and lateral movements, which may expose players to increased anterior cruciate ligament (ACL) injury risk. It is unknown whether players who heavily rely on driving have decreased performance on returning to play after ACL reconstruction (ACLR). HYPOTHESIS: Players with a greater tendency to drive to the basket would be more likely to tear their ACL versus noninjured controls and would experience decreased performance when returning to play after ACLR. STUDY DESIGN: Case-control study; Level of evidence, 3. METHODS: Season-level performance statistics and ACL injuries were aggregated for National Basketball Association (NBA) seasons between 1980 and 2017 from publicly available sources. Players' tendency to drive was calculated using 49 common season-level performance metrics. Each ACL-injured player was matched with 2 noninjured control players by age, league experience, and style of play metrics. Points, playing minutes, driving, and 3-point shooting tendencies were compared between players with ACL injuries and matched controls. Independent-samples t test was utilized for comparisons. RESULTS: Of 86 players with a total of 96 ACL tears identified in the NBA, 50 players were included in the final analysis. Players who experienced an ACL tear had a higher career-average drive tendency than controls (P = .047). Players with career-average drive tendency ≥1 standard deviation above the mean were more likely to tear their ACL than players with drive tendency <1 standard deviation (5.2% vs 2.7%; P = .026). There was no significant difference in total postinjury career points (P = .164) or career minutes (P = .237) between cases and controls. There was also no significant change in drive tendency (P = .152) or 3-point shooting tendency (P = .508) after return to sport compared with controls. CONCLUSION: NBA players with increased drive tendency were more likely to tear their ACL. However, players who were able to return after ACLR did not underperform compared with controls and did not alter their style of play compared with the normal changes seen with age. This information can be used to target players with certain playing styles for ACL injury prevention programs.

Open Source Software for Automatic Subregional Assessment of Knee Cartilage Degradation Using Quantitative T2 Relaxometry and Deep Learning.

OBJECTIVE: We evaluated a fully automated femoral cartilage segmentation model for measuring T2 relaxation values and longitudinal changes using multi-echo spin-echo (MESE) magnetic resonance imaging (MRI). We open sourced this model and developed a web app available at https://kl.stanford.edu into which users can drag and drop images to segment them automatically. DESIGN: We trained a neural network to segment femoral cartilage from MESE MRIs. Cartilage was divided into 12 subregions along medial-lateral, superficial-deep, and anterior-central-posterior boundaries. Subregional T2 values and four-year changes were calculated using a radiologist's segmentations (Reader 1) and the model's segmentations. These were compared using 28 held-out images. A subset of 14 images were also evaluated by a second expert (Reader 2) for comparison. RESULTS: Model segmentations agreed with Reader 1 segmentations with a Dice score of 0.85 ± 0.03. The model's estimated T2 values for individual subregions agreed with those of Reader 1 with an average Spearman correlation of 0.89 and average mean absolute error (MAE) of 1.34 ms. The model's estimated four-year change in T2 for individual subregions agreed with Reader 1 with an average correlation of 0.80 and average MAE of 1.72 ms. The model agreed with Reader 1 at least as closely as Reader 2 agreed with Reader 1 in terms of Dice score (0.85 vs. 0.75) and subregional T2 values. CONCLUSIONS: Assessments of cartilage health using our fully automated segmentation model agreed with those of an expert as closely as experts agreed with one another. This has the potential to accelerate osteoarthritis research.

Relationship between industry royalty and licensing payments and patent authorship among orthopedic spine surgeons.

BACKGROUND CONTEXT: The Physician Payments Sunshine Act requires manufacturers of drugs, medical devices, medical supplies, and biologics to record all financial relationships with physicians in the Open Payments database with the goal of increasing transparency for patients and the general public. The majority of total money going to orthopedic surgeons has been found to go to a small number of surgeons in the form of royalties and licensing payments. This category of payment is intended to compensate physicians for use of their intellectual property. However, little research has been done to investigate the degree to which these physicians own intellectual property. PURPOSE: To the authors' knowledge, the association between patents and industry payments to orthopedic surgeons has not been explored. We quantify the association between the patents and academic productivity of orthopedic spine surgeons and the amount of royalty and licensing fees they receive. We then compared this with the associations observed for other categories of payments. STUDY DESIGN: Cross-sectional study METHODS: Top royalty and licensing earners, defined as those who collectively earned 50% of all royalty and licensing payments over the period August 2013-December 2018, were identified. The h-index, publication count, and patent count of this group were compared with top earners of other payment categories using the Mann-Whitney U test. The association between (1) earnings and patent counts, (2) earnings and manuscript counts, and (3) earnings and h-index among the top royalty and licensing earners was assessed using Spearman correlation. RESULTS: Top royalty and licensing earners had significantly more patents than every comparison group except the top earners of money derived from ownership in a biomedical company. For this one exception, there was a trend toward the top eight royalty and licensing earners having more patents (p=.054). The top royalty and licensing earners had significantly more manuscripts than three of the five comparison groups and significantly higher h-indices than four of the five comparison groups. Among the top royalty and licensing earners, receiving more royalty and licensing payments was associated with holding more patents, but not with publishing more papers or having higher h-indices. CONCLUSIONS: There is a strong association between the number of patents authored by individual orthopedic spine surgeons and the amount of royalty and licensing fees they receive from industry. This supports the hypothesis that these payments serve as compensation to inventor-surgeons for their intellectual property. CLINICAL SIGNIFICANCE: Our findings provide new, important context for the largest category of industry payments to orthopedic spine surgeons and suggests that physicians' patents should be considered when evaluating financial transactions between industry and physicians.

Automated Classification of Radiographic Knee Osteoarthritis Severity Using Deep Neural Networks.

PURPOSE: To develop an automated model for staging knee osteoarthritis severity from radiographs and to compare its performance to that of musculoskeletal radiologists. MATERIALS AND METHODS: Radiographs from the Osteoarthritis Initiative staged by a radiologist committee using the Kellgren-Lawrence (KL) system were used. Before using the images as input to a convolutional neural network model, they were standardized and augmented automatically. The model was trained with 32 116 images, tuned with 4074 images, evaluated with a 4090-image test set, and compared to two individual radiologists using a 50-image test subset. Saliency maps were generated to reveal features used by the model to determine KL grades. RESULTS: With committee scores used as ground truth, the model had an average F1 score of 0.70 and an accuracy of 0.71 for the full test set. For the 50-image subset, the best individual radiologist had an average F1 score of 0.60 and an accuracy of 0.60; the model had an average F1 score of 0.64 and an accuracy of 0.66. Cohen weighted κ between the committee and model was 0.86, comparable to intraexpert repeatability. Saliency maps identified sites of osteophyte formation as influential to predictions. CONCLUSION: An end-to-end interpretable model that takes full radiographs as input and predicts KL scores with state-of-the-art accuracy, performs as well as musculoskeletal radiologists, and does not require manual image preprocessing was developed. Saliency maps suggest the model's predictions were based on clinically relevant information. Supplemental material is available for this article. © RSNA, 2020.

Evaluation of the Rhizosphere Contribution to the Environmental Fate of the Herbicide Prometryn.

Plant protection products (PPPs) undergo rigorous regulatory assessment to ensure that they do not pose unacceptable risks to the environment. Elucidation of their fate and behavior in soil is an integral part of this environmental risk assessment. The active substance degradation in soil of PPPs is first assessed in laboratory studies (typically following Organisation for Economic Co-operation and Development [OECD] test guideline 307). Conditions in guideline laboratory studies are far removed from those occurring under agricultural use, and the contribution of crop roots has currently not been assessed. We integrated viable plant root systems, representative of 3 different crop types, into the OECD test guideline 307 design to assess their impact on the dissipation of the herbicide prometryn. Significantly faster decline of parent residue and higher formation of nonextractable residues were observed in all 3 planted systems. This led to a reduction in the time required for 50% of the compound to dissipate (DT50) of approximately one-half in the presence of rye grass and hot pepper and of approximately one-third in the presence of red clover. These findings imply that plants and their associated root networks can have a significant influence on PPP dissipation. Based on these data, greater environmental realism could be added to the standardized laboratory study design by the inclusion of plant root systems into higher tier studies, which, in turn, could serve to improve the environmental risk assessment process. Environ Toxicol Chem 2020;39:450-457. © 2019 SETAC.

Preparation and preliminary evaluation of 63Zn-zinc citrate as a novel PET imaging biomarker for zinc.

UNLABELLED: Abnormalities of zinc homeostasis are indicated in many human diseases. A noninvasive imaging method for monitoring zinc in the body would be useful to understand zinc dynamics in health and disease. To provide a PET imaging agent for zinc, we have investigated production of (63)Zn (half-life, 38.5 min) via the (63)Cu(p,n)(63)Zn reaction using isotopically enriched solutions of (63)Cu-copper nitrate. A solution target was used for rapid isolation of the (63)Zn radioisotope from the parent (63)Cu ions. Initial biologic evaluation was performed by biodistribution and PET imaging in normal mice. METHODS: To produce (63)Zn, solutions of (63)Cu-copper nitrate in dilute nitric acid were irradiated by 14-MeV protons in a low-energy cyclotron. An automated module was used to purify (63)Zn from (63)Cu in the target solution. The (63)Cu-(63)Zn mixture was trapped on a cation-exchange resin and rinsed with water, and the (63)Zn was eluted using 0.05 N HCl in 90% acetone. The resulting solution was neutralized with NaHCO3, and the (63)Zn was then trapped on a carboxymethyl cartridge, washed with water, and eluted with isotonic 4% sodium citrate. Standard quality control tests were performed on the product according to current good manufacturing practice, including radionuclidic identity and purity, and measurement of nonradioactive Zn(+2), Cu(+2), Fe(+3), and Ni(+2) by ion-chromatography high-performance liquid chromatography. Biodistribution and PET imaging studies were performed in B6.SJL mice after intravenous administration of (63)Zn-zinc citrate. (63)Cu target material was recycled by eluting the initial resin with 4N HNO3. RESULTS: Yields of 1.07 ± 0.22 GBq (uncorrected at 30-36 min after end of bombardment) of (63)Zn-zinc citrate were obtained with a 1.23 M (63)Cu-copper nitrate solution. Radionuclidic purity was greater than 99.9%, with copper content lower than 3 µg/batch. Specific activities were 41.2 ± 18.1 MBq/µg (uncorrected) for the (63)Zn product. PET and biodistribution studies in mice at 60 min showed expected high uptake in the pancreas (standard uptake value, 8.8 ± 3.2), liver (6.0 ± 1.9), upper intestine (4.7 ± 2.1), and kidney (4.2 ± 1.3). CONCLUSION: A practical and current good manufacturing practice-compliant preparation of radionuclidically pure (63)Zn-zinc citrate has been developed that will enable PET imaging studies in animal and human studies. (63)Zn-zinc citrate showed the expected biodistribution in mice.

Assessing the metabolic potential of phototrophic communities in surface water environments: fludioxonil as a model compound.

Differences are often apparent in the observed rates of degradation between laboratory water-sediment studies and outdoor studies in surface water environments. Indeed, previous work has shown that including phototrophic communities in laboratory systems can result in the enhancement of degradation, when compared against systems that exclude phototrophs, incubated in darkness. In phototroph-inclusive systems, a range of metabolic processes and community effects are absent in the standard laboratory systems: metabolism by macrophytes, algae, and periphyton, as well as enhancement of bacterial and fungal communities by macrophyte root structures, algal biofilms, and planktonic algae. Here, the authors demonstrate the metabolic capability of algae and macrophytes in isolation from bacterial and fungal communities. The authors have isolated subcommunities and individual species from complex, phototroph-inclusive test systems, and demonstrated significant degradation of the fungicide fludioxonil in their presence. They have also shown the intrinsic metabolic competence of Elodea canadensis as well as algae from three phyla (Chlorophyta, Cyanophyta, and Bacillariophyta [diatoms]), demonstrating that phototrophic communities have the potential to play a direct role in metabolism in surface water environments. Thus, it seems that current laboratory test systems are failing to consider the role of active, competent organisms that are likely to be involved in the degradation of crop protection products in surface water environments.

Assessing the potential for algae and macrophytes to degrade crop protection products in aquatic ecosystems.

Rates of pesticide degradation in aquatic ecosystems often differ between those observed within laboratory studies and field trials. Under field conditions, a number of additional processes may well have a significant role, yet are excluded from standard laboratory studies, for example, metabolism by aquatic plants, phytoplankton, and periphyton. These constituents of natural aquatic ecosystems have been shown to be capable of metabolizing a range of crop protection products. Here we report the rate of degradation of six crop protection products assessed in parallel in three systems, under reproducible, defined laboratory conditions, designed to compare aquatic sediment systems which exclude macrophytes and algae against those in which macrophytes and/or algae are included. All three systems remained as close as possible to the Organisation for Economic Co-operation and Development (OECD) 308 guidelines, assessing degradation of parent compound in the total system in mass balanced studies using ((14) C) labeled compounds. We observed, in all cases where estimated, significant increases in the rate of degradation in both the algae and macrophyte systems when compared to the standard systems. By assessing total system degradation within closed, mass balanced studies, we have shown that rates of degradation are enhanced in water/sediment systems that include macrophytes and algae. The contribution of these communities should therefore be considered if the aquatic fate of pesticides is to be fully understood.

Bioresorbable film for the prevention of adhesion to the anterior spine after anterolateral discectomy.

BACKGROUND CONTEXT: The development of scar tissue and adhesions postoperatively is a natural consequence of healing but can be associated with medical complications and render reoperation difficult. Many biocompatible products have been evaluated as barriers or deterrents to adhesions. PURPOSE: To evaluate the efficacy of a bioresorbable polylactide film as a barrier to adhesion formation after anterolateral discectomy. STUDY DESIGN: Experimental study. METHODS: Seven, skeletally mature female sheep underwent a retroperitoneal approach to the anterolateral lumbar spine. A discectomy was performed at two levels with an intervening unoperated disc site. One site was treated with a polylactide film barrier (Hydrosorb Shield; MacroPore Biosurgery, San Diego, CA) affixed with tacks manufactured from the same material. The second site was left untreated. Treatment and control sites were randomly assigned. Postmortem analysis included scar tenacity scoring on five spines and histological evaluation on two spines. RESULTS: The application of the Hydrosorb film barrier allowed a definite dissection plane during scar tenacity scoring and there was a significant difference in the development of adhesions to the disc between the control and treated sites. Histological evaluation revealed evidence of barrier formation to scar tissue and no significant adverse inflammatory reactions. CONCLUSIONS: Hydrosorb Shield appears to be an effective postoperative barrier to scar tissue adhesion after anterolateral discectomy. The use of polylactide tacks was beneficial to affix the barrier film in place. Safety issues associated with delayed healing or adverse response to the film or tacks were not observed. Hydrosorb film may be useful as an antiadhesion barrier facilitating dissection during surgical revision in anterior approaches to the spine. Further studies are indicated to evaluate the performance of the bioresorbable material as an antiadhesion barrier in techniques of spinal fusion and disc replacement.

Bioresorbable polylactide interbody implants in an ovine anterior cervical discectomy and fusion model: three-year results.

STUDY DESIGN: In vivo study of anterior discectomy and fusion using a bioresorbable 70:30 poly(l-lactide-co-d,l-lactide) interbody implant in an ovine model. OBJECTIVE: To evaluate the efficacy of the polylactide implant to function as an interbody fusion device, and to assess the tissue reaction to the material during the resorption process. SUMMARY OF BACKGROUND DATA: The use of polylactide as a cervical interbody implant has several potential advantages when compared with traditional materials. Having an elastic modulus very similar to bone minimizes the potential for stress shielding, and as the material resorbs additional loading is transferred to the developing fusion mass. Although preclinical and clinical studies have demonstrated the suitability of polylactide implants for lumbar interbody fusion, detailed information on cervical anterior cervical discectomy and fusion (ACDF) with polylactide devices is desirable. METHODS: Single level ACDF was performed in 8 skeletally mature ewes. Bioresorbable 70:30 poly (l-lactide-co-d,l-lactide) interbody implants packed with autograft were used with single-level metallic plates. Radiographs were made every 3 months up to 1 year, and yearly thereafter. The animals were killed at 6 months (3 animals), 12 months (3 animals), and 36 months (2 animals). In addition to the serial plain radiographs, the specimens were evaluated by nondestructive biomechanical testing and undecalcified histologic analysis. RESULTS: The bioresorbable polylactide implants were effective in achieving interbody fusion. The 6-month animals appeared fused radiographically and biomechanically, whereas histologic sections demonstrated partial fusion (in 3 of 3 animals). Radiographic fusion was confirmed histologically and biomechanically at 12 months (3 of 3 animals) and 36 months (2 of 2 animals). A mild chronic inflammatory response to the resorbing polylactide implant was observed at both 6 months and 12 months. At 36 months, the operative levels were solidly fused and the implants were completely resorbed. No adverse tissue response was observed in any animal at any time period. CONCLUSION: Interbody fusion was achieved using bioresorbable polylactide implants, with no evidence of implant collapse, extrusion, or adverse tissue response to the material. The use of polylactide as a cervical interbody device appears both safe and effective based on these ACDF animal model results.

Sterilization and strength of 70/30 polylactide cages: e-beam versus ethylene oxide.

STUDY DESIGN: In vitro and in vivo studies on the degradation of 70/30 poly(L,DL-lactide) (PLDLLA) cages. OBJECTIVE: To evaluate the effect of e-beam and ethylene oxide sterilization on degradation and strength. SUMMARY OF BACKGROUND DATA: e-beam-sterilized PLDLLA cages were shown to maintain mechanical strength for at least 6 months during degradation studies in vitro. Yet failure of the cages was observed after only 3 months in vivo. We hypothesized that degradation characteristics and mechanical strength could be improved by sterilizing the cages through ethylene oxide (EtO) instead of e-beam. METHODS: PLDLLA cages were sterilized either by e-beam or EtO, and degraded in phosphate-buffered saline. Each month, cages were compressed until failure. Inherent viscosity was determined as a measure of degradation. For the in vivo evaluation, e-beam- or EtO-sterilized cages were implanted at L3-L4 in a standardized goat model. After 3 or 6 months, retrieved segments were scanned by high-resolution magnetic resonance imaging. Also, inherent viscosity of the polymer was measured. RESULTS: e-beam sterilization strongly decreased inherent viscosity of PLDLLA compared with EtO sterilization, but initial strength was only affected marginally. After 6 months, the strength of the e-beam-sterilized cages dropped, while that of EtO-sterilized cages was maintained. Degradation in vivo was slightly faster than in vitro. In both groups, however, mechanical failure occurred at 3 months after implantation. CONCLUSIONS: Inherent viscosity decreases with degradation time, but strength only decreases when inherent viscosity is below a certain threshold. Above this threshold, mechanical strength is a property of the polymer and independent of inherent viscosity. e-beam sterilization strongly decreases inherent viscosity and thus advances mechanical degradation. EtO sterilization delays degradation but does not increase initial strength. Early failure of PLDLLA cages in the goat model thus is unrelated to sterilization method and requires further study.

Enhanced retention of polymer physical characteristics and mechanical strength of 70:30 poly(L-lactide-co-D,L-lactide) after ethylene oxide sterilization.

This study examined the effect of ethylene oxide (EtO) and electron beam (e-beam) irradiation on the properties of 70:30 poly(L-lactide-co-D,L-lactide). The effects of sterilization upon the polymer physical characteristics and strength retention of the material were examined, both initially and after being subjected to real time ageing. Commercially available 70:30 poly(L-lactide-co-D,L-lactide) material was fabricated into rectangular, cylindrical, screw, and sheet designs, and tested in compression, shear, or tension. Sterilization of 70:30 poly(L-lactide-co-D,L-lactide) by ethylene oxide had a nearly negligible effect on the physical properties of the polymer, regardless of specimen size or manufacturing technique. The molecular weight and inherent viscosity of the specimens decreased by approximately 3% after sterilization by EtO. However, sterilization of 70:30 poly(L-lactide-co-D,L-lactide) by e-beam irradiation resulted in immediate changes to some of the physical properties of the polymer. Specimens sterilized by e-beam irradiation displayed an immediate decrease in inherent viscosity of approximately 67% as compared to the respective nonsterile samples. The immediate decrease in inherent viscosity and molecular weight with e-beam irradiation required approximately 39 weeks of real time ageing of the EtO sterilized parts. At all time points investigated in the present study, the strength retention of the EtO sterilized devices equaled or exceeded that of the e-beam irradiated samples.

Evaluation of a bioresorbable polylactide sheet for the reduction of pelvic soft tissue attachments in a porcine animal model.

In an adult porcine model, the effectiveness of a bioresorbable film to minimize soft tissue attachment to the pelvic viscera was evaluated at 4-week and 12-week endpoints. Following a transperitoneal laparotomy through a midline incision, the bladder and uterus were abraded in all animals to promote soft tissue attachment to the viscera. Control animals received no further treatment. The experimental group animals were treated with bioresorbable polylactide (PLa) sheets, 0.02 mm thick, one between the bladder and the abdominal wall, and a second sheet between the bladder and the uterus. Quantitative assessment of the severity and location of soft tissue attachments, and qualitative histologic assessment were performed at 4 and 12 weeks post-operatively. Statistically significant differences in the quantitative soft tissue attachment scores were observed in comparing the PLa film treated animals versus the control animals, at both the 4-week and 12-week time points. In the control animals, the formation of numerous thick fibrous bands was observed at both time points. Histology revealed no adverse reaction to the bioresorbable PLa barrier film. The bioresorbable PLa sheet provided an effective barrier between adjacent anatomical structures and minimized soft tissue attachments to the device when in contact with the viscera as compared to the control groups. Surgical dissection planes between the abdominal wall and adjacent soft tissues were maintained with the use of the PLa sheet at both time points.

Essential and overlapping roles for laminin alpha chains in notochord and blood vessel formation.

Laminins are major constituents of basement membranes and have wide ranging functions during development and in the adult. They are a family of heterotrimeric molecules created through association of an alpha, beta and gamma chain. We previously reported that two zebrafish loci, grumpy (gup) and sleepy (sly), encode laminin beta1 and gamma1, which are important both for notochord differentiation and for proper intersegmental blood vessel (ISV) formation. In this study we show that bashful (bal) encodes laminin alpha1 (lama1). Although the strongest allele, bal(m190), is fully penetrant, when compared to gup or sly mutant embryos, bal mutants are not as severely affected, as only anterior notochord fails to differentiate and ISVs are unaffected. This suggests that other alpha chains, and hence other isoforms, act redundantly to laminin 1 in posterior notochord and ISV development. We identified cDNA sequences for lama2, lama4 and lama5 and disrupted the expression of each alone or in mutant embryos also lacking laminin alpha1. When expression of laminin alpha4 and laminin alpha1 are simultaneously disrupted, notochord differentiation and ISVs are as severely affected as sly or gup mutants. Moreover, live imaging of transgenic embryos expressing enhanced green fluorescent protein in forming ISVs reveals that the vascular defects in these embryos are due to an inability of ISV sprouts to migrate correctly along the intersegmental, normally laminin-rich regions.

Characterization of a faster resorbing polymer after real time aging.

This study evaluated the in vitro strength retention and polymer characteristics of specimens made from commercially available 85:15 poly(D,L-lactide-co-glycolide). Test samples included dogbone tensile specimens with a nominal thickness of either 0.75 and 1.0 mm, which were machined from compression-molded sheets, and screws with a major diameter of 2.71 mm and minor diameter of 2.14 mm, which were manufactured by injection molding. All samples were sterilized by e-beam irradiation prior to in vitro aging following a standard methodology. Mechanical testing and polymer analysis were performed at time zero and weekly up to 15 weeks of real time aging. The time zero maximum tensile strength of the 0.75 mm dogbone specimens averaged 55.86 +/- 0.72 MPa. The 1.0-mm dogbone specimens tested at time zero had an average maximum tensile strength of 34.55 +/- 0.36 MPa. The 0.75-mm and 1.0-mm thick dogbone specimens exhibited a controlled decrease in their tensile strength. The initial shear strength of the injection-molded screws was 32.86 +/- 4.15 MPa. After 3 weeks of real time in vitro aging, the screws maintained approximately 70% of their initial (time zero) strength. The inherent viscosity and molecular weight (Mw) at time zero averaged approximately 0.9 dL/g and 98,000 g/mol respectively, and decreased at similar rates for both dogbones and screws. These results demonstrate a controlled, rapid degradation in the mechanical properties of 85:15 poly(D,L-lactide-co-glycolide) material, with sufficient strength for pediatric craniofacial applications.

Strength retention of 70:30 poly(L-lactide-co-D,L-lactide) following real-time aging.

This study evaluated the in vitro strength retention and polymer characteristics of plates and screws made from commercially available 70:30 poly(L-lactide-co-D,L-lactide) over a 2-year time period. Test samples included three routine manufacturing lots each of plates (1.2 mm thick, 41.70 mm long, with 2.5-mm holes), which were machined from compression-molded sheets, and screws (2.4-mm major diameter and 1.86-mm minor diameter), which were manufactured by injection molding. All samples were sterilized by e-beam irradiation prior to in vitro aging following a standard methodology. Mechanical testing and polymer analysis was performed after 0, 6, 13, 26, 39, 52, 65, 78, and 104 weeks. The initial (time zero) tensile strength of the plates averaged 33.2+/-1.9 MPa; the plates retained 100% of this strength at 6 weeks, 84% at 13 weeks, and 34% at 39 weeks. The screws had an initial (time zero) shear strength of 29.8+/-4.2 MPa, and maintained 97% of this strength at 26 weeks and 73% of this strength at 39 weeks. The inherent viscosity and molecular weight (M(w)) at time zero averaged approximately 1.4 dL/g and 165,000 g/mol, respectively, and decreased at similar rates for both the plates and screws. These results demonstrate excellent strength retention of devices fabricated from 70:30 poly(L-lactide-co-D,L-lactide) over time periods exceeding those associated with normal bone healing.