A 96-well microplate bioreactor platform supporting individual dual perfusion and high-throughput assessment of simple or biofabricated 3D tissue models.

Traditional 2D monolayer cell cultures and submillimeter 3D tissue construct cultures used widely in tissue engineering are limited in their ability to extrapolate experimental data to predict in vivo responses due to their simplistic organization and lack of stimuli. The rise of biofabrication and bioreactor technologies has sought to address this through the development of techniques to spatially organize components of a tissue construct, and devices to supply these tissue constructs with an increasingly in vivo-like environment. Current bioreactors supporting both parenchymal and barrier tissue constructs in interconnected systems for body-on-a-chip platforms have chosen to emphasize study throughput or system/tissue complexity. Here, we report a platform to address this disparity in throughput and both system complexity (by supporting multiple in situ assessment methods) and tissue complexity (by adopting a construct-agnostic format). We introduce an ANSI/SLAS-compliant microplate and docking station fabricated via stereolithography (SLA), or precision machining, to provide up to 96 samples (Ø6 × 10 mm) with two individually-addressable fluid circuits (192 total), loading access, and inspection window for imaging during perfusion. Biofabricated ovarian cancer models were developed to demonstrate the in situ assessment capabilities via microscopy and a perfused resazurin-based metabolic activity assay. In situ microscopy highlighted flexibility of the sample housing to accommodate a range of sample geometries. Utility for drug screening was demonstrated by exposing the ovarian cancer models to an anticancer drug (doxorubicin) and generating the dose-response curve in situ, while achieving an assay quality similar to static wellplate culture. The potential for quantitative analysis of temporal tissue development and screening studies was confirmed by imaging soft- (gelatin) and hard-tissue (calcium chloride) analogs inside the bioreactor via spectral computed tomography (CT) scanning. As a proof-of-concept for particle tracing studies, flowing microparticles were visualized to inform the design of hydrogel constructs. Finally, the ability for mechanistic yet high-throughput screening was demonstrated in a vascular coculture model adopting endothelial and mesenchymal stem cells (HUVEC-MSC), encapsulated in gelatin-norbornene (gel-NOR) hydrogel cast into SLA-printed well inserts. This study illustrates the potential of a scalable dual perfusion bioreactor platform for parenchymal and barrier tissue constructs to support a broad range of multi-organ-on-a-chip applications.

An analysis of the Oxford hip and knee scores and their relationship to early joint revision in the New Zealand Joint Registry.

We analysed data from the Oxford hip and knee questionnaires collected by the New Zealand Joint Registry at six months and five years after joint replacement, to determine if there was any relationship between the scores and the risk of early revision. Logistic regression of the six-month scores indicated that for every one-unit decrease in the Oxford score, the risk of revision within two years increased by 9.7% for total hip replacement (THR), 9.9% for total knee replacement (TKR) and 12.0% for unicompartmental knee replacement (UKR). Our findings showed that 70% of the revisions within two years for TKR and 67% for THR and UKR would have been captured by monitoring the lowest 22%, 28% and 28%, respectively, of the Oxford scores. When analysed using the Kalairajah classification a score of < 27 (poor) was associated with a risk of revision within two years of 7.6% for THR, 7.0% for TKR and 24.3% for UKR, compared with risks of 0.7%, 0.7% and 1.8%, respectively, for scores > 34 (good or excellent). Our study confirms that the Oxford hip and knee scores at six months are useful predictors of early revision after THR and TKR and we recommend their use for the monitoring of the outcome and potential failure in these patients.

Screening for breast cancer: time, travel, and out-of-pocket expenses.

BACKGROUND: We estimated the personal costs to women found to have a breast problem (either breast cancer or benign breast disease) in terms of time spent, miles traveled, and cash payments made for detection, diagnosis, initial treatment, and follow-up. METHODS: We analyzed data from personal interviews with 465 women from four communities in Florida. These women were randomly selected from those with a recent breast biopsy (within 6-8 months) that indicated either breast cancer (208 women) or benign breast disease (257 women). One community was the site of a multifaceted intervention to promote breast screening, and the other three communities were comparison sites for evaluation of that intervention. All P values are two-sided. RESULTS: In comparison with time spent and travel distance for women with benign breast disease (13 hours away from home and 56 miles traveled), time spent and travel distance were statistically significantly higher (P<.001) for treatment and follow-up of women with breast cancer (89 hours and 369 miles). Personal financial costs for treatment of women with breast cancer were also statistically significantly higher (breast cancer = $604; benign breast disease = $76; P < .001) but were statistically significantly lower for detection and diagnosis (breast cancer = $170; benign breast disease = $310; P < .001). Among women with breast cancer, time spent for treatment was statistically significantly lower (P = .013) when their breast cancer was detected by screening (68.9 hours) than when it was detected because of symptoms (84.2 hours). Personal cash payments for detection, diagnosis, and treatment were statistically significantly lower among women whose breast problems were detected by screening than among women whose breast problems were detected because of symptoms (screening detected = $453; symptom detected = $749; P = .045). CONCLUSION: There are substantial personal costs for women who are found to have a breast problem, whether the costs are associated with problems identified through screening or because of symptoms.

Radiological assessment of anterior cruciate ligament deficiency. A new technique.

A new method of demonstrating sagittal laxity in the anterior cruciate-deficient knee is described. Seventy such knees were compared to 70 normal knees. Sagittal laxity was recorded as the average displacement of the medial and lateral femoral condyles. This displacement index was significantly different between the two groups of knees (P less than 0.0001). A range for normal and abnormal knees is discussed. Quantitative assessment of the degree of sagittal laxity by clinical evaluation is shown to be unreliable. Only the pivot-shift test demonstrated any significant correlation with the amount of sagittal displacement (P less than 0.05).