Arthroscopic transosseous rotator cuff repair: A prospective study on cost savings, surgical time, and outcomes

Objectives: Health expenditures in the United States are outpacing national income, and affordability has become a major policy issue. Over 500,000 rotator cuff repairs (RCR) are performed annually in the United States making RCR a potential source of cost savings. Arthroscopic trans-osseous equivalent (TOE) repair using a double row of anchors has shown superior biomechanical strength compared to other techniques, but at a higher cost. The arthroscopic transosseous (TO) repair is a novel technique allowing arthroscopic rotator cuff repair to be performed without suture anchors. Arthroscopic TO repair may be a means to provide similarly excellent patient outcomes while lowering the cost of care. The primary purpose is to compare the price differential and time of surgery for an arthroscopic rotator cuff repair using anchorless TO repair verses an anchor trans-osseous equivalent (TOE) repair. A secondary purpose of the study was to evaluate outcomes at 6 months postoperatively. Methods: A prospective, case-controlled study evaluating arthroscopic rotator cuff repair using two techniques was performed. The study group consisting of 21 patients undergoing TO repair was compared to a control group consisting of 22 patients undergoing TOE repair. The groups were controlled for size of tear, biceps treatment, acromioplasty, distal clavicle excision, and labral pathology. The primary outcome measures were surgical time as well as total cost of implants and equipment for each surgery, determined by an independent third party, Atlanticare Hospital. Secondary outcomes were changes in the SST, VAS, and SANE scores. Results: Mean total surgical implant/equipment cost per procedure for TOE repair was $2348.03 (SD 490.30) and for TO repair was$1204.97 (SD 330.69; p\u3c0.0001). Mean cut to close time for TOE repair was 85 minutes (95% CI is 77-90) verses 74 (95% CI = 71-98) for TO repair. A log rank test revealed no difference in time (p =0.95). A linear regression model was developed to evaluate the change in SST, VAS, and SANE scores from pre-op to 6 months follow-up. Our study was underpowered but no difference in outcome was observed. Conclusion: Arthroscopic TO rotator cuff repair is a cost savings and time neutral technique compared to TOE repair. A mean of $1100 can be saved in surgical cost per case. In a country that performs over 500,000 RCRs annually, utilizing a TO repair technique can provide substantial cost savings to the healthcare system. © The Author(s) 2015

Measurement of Thermal Noise in Multilayer Coatings with Optimized Layer Thickness

A standard quarter-wavelength multilayer optical coating will produce the highest reflectivity for a given number of coating layers, but in general it will not yield the lowest thermal noise for a prescribed reflectivity. Coatings with the layer thicknesses optimized to minimize thermal noise could be useful in future generation interferometric gravitational wave detectors where coating thermal noise is expected to limit the sensitivity of the instrument. We present the results of direct measurements of the thermal noise of a standard quarter-wavelength coating and a low noise optimized coating. The measurements indicate a reduction in thermal noise in line with modeling predictions.Comment: 8 pages, 14 figure

Gene expression patterns that predict sensitivity to epidermal growth factor receptor tyrosine kinase inhibitors in lung cancer cell lines and human lung tumors

BACKGROUND: Increased focus surrounds identifying patients with advanced non-small cell lung cancer (NSCLC) who will benefit from treatment with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI). EGFR mutation, gene copy number, coexpression of ErbB proteins and ligands, and epithelial to mesenchymal transition markers all correlate with EGFR TKI sensitivity, and while prediction of sensitivity using any one of the markers does identify responders, individual markers do not encompass all potential responders due to high levels of inter-patient and inter-tumor variability. We hypothesized that a multivariate predictor of EGFR TKI sensitivity based on gene expression data would offer a clinically useful method of accounting for the increased variability inherent in predicting response to EGFR TKI and for elucidation of mechanisms of aberrant EGFR signalling. Furthermore, we anticipated that this methodology would result in improved predictions compared to single parameters alone both in vitro and in vivo. RESULTS: Gene expression data derived from cell lines that demonstrate differential sensitivity to EGFR TKI, such as erlotinib, were used to generate models for a priori prediction of response. The gene expression signature of EGFR TKI sensitivity displays significant biological relevance in lung cancer biology in that pertinent signalling molecules and downstream effector molecules are present in the signature. Diagonal linear discriminant analysis using this gene signature was highly effective in classifying out-of-sample cancer cell lines by sensitivity to EGFR inhibition, and was more accurate than classifying by mutational status alone. Using the same predictor, we classified human lung adenocarcinomas and captured the majority of tumors with high levels of EGFR activation as well as those harbouring activating mutations in the kinase domain. We have demonstrated that predictive models of EGFR TKI sensitivity can classify both out-of-sample cell lines and lung adenocarcinomas. CONCLUSION: These data suggest that multivariate predictors of response to EGFR TKI have potential for clinical use and likely provide a robust and accurate predictor of EGFR TKI sensitivity that is not achieved with single biomarkers or clinical characteristics in non-small cell lung cancers

New challenges in studying nutrition-disease interactions in the developing world.

Latest estimates indicate that nutritional deficiencies account for 3 million child deaths each year in less-developed countries. Targeted nutritional interventions could therefore save millions of lives. However, such interventions require careful optimization to maximize benefit and avoid harm. Progress toward designing effective life-saving interventions is currently hampered by some serious gaps in our understanding of nutrient metabolism in humans. In this Personal Perspective, we highlight some of these gaps and make some proposals as to how improved research methods and technologies can be brought to bear on the problems of undernourished children in the developing world

The effect of an acute bout of resistance exercise on carotid artery strain and strain rate

Arterial wall mechanics likely play an integral role in arterial responses to acute physiological stress. Therefore, this study aimed to determine the impact of low and moderate intensity double-leg press exercise on common carotid artery (CCA) wall mechanics using 2D vascular strain imaging. Short-axis CCA ultrasound images were collected in 15 healthy men (age: 21 ± 3 years; stature: 176.5 ± 6.2 cm; body mass; 80.6 ± 15.3 kg) before, during, and immediately after short-duration isometric double-leg press exercise at 30% and 60% of participants’ one-repetition maximum (1RM: 317 ± 72 kg). Images were analyzed for peak circumferential strain (PCS), peak systolic and diastolic strain rate (S-SR and D-SR) and arterial diameter. Heart rate (HR), systolic and diastolic blood pressure (SBP and DBP) were simultaneously assessed and arterial stiffness indices were calculated post hoc. A two-way repeated measures ANOVA revealed that during isometric contraction, PCS and S-SR decreased significantly (P < 0.01) before increasing significantly above resting levels post-exercise (P < 0.05 and P < 0.01 respectively). Conversely, D-SR was unaltered throughout the protocol (P = 0.25). No significant differences were observed between the 30% and 60% 1RM trials. Multiple regression analysis highlighted that HR, BP and arterial diameter did not fully explain the total variance in PCS, S-SR and D-SR. Acute double-leg press exercise is therefore associated with similar transient changes in CCA wall mechanics at low and moderate intensities. CCA wall mechanics likely provide additional insight into localized intrinsic vascular wall properties beyond current measures of arterial stiffness

High-throughput testing in head and neck squamous cell carcinoma identifies agents with preferential activity in human papillomavirus-positive or negative cell lines.

Head and neck squamous cell carcinoma (HNSCC) is a common cancer diagnosis worldwide. Despite advances in treatment, HNSCC has very poor survival outcomes, emphasizing an ongoing need for development of improved therapeutic options. The distinct tumor characteristics of human papillomavirus (HPV)-positive vs. HPV-negative disease necessitate development of treatment strategies tailored to tumor HPV-status. High-throughput robotic screening of 1,433 biologically and pharmacologically relevant compounds at a single dose (4 μM) was carried out against 6 HPV-positive and 20 HPV-negative HNSCC cell lines for preliminary identification of therapeutically relevant compounds. Statistical analysis was further carried out to differentiate compounds with preferential activity against cell lines stratified by the HPV-status. These analyses yielded 57 compounds with higher activity in HPV-negative cell lines, and 34 with higher-activity in HPV-positive ones. Multi-point dose-response curves were generated for six of these compounds (Ryuvidine, MK-1775, SNS-032, Flavopiridol, AZD-7762 and ARP-101), confirming Ryuvidine to have preferential potency against HPV-negative cell lines, and MK-1775 to have preferential potency against HPV-positive cell lines. These data comprise a valuable resource for further investigation of compounds with therapeutic potential in the HNSCC

Repurposing Albendazole: new potential as a chemotherapeutic agent with preferential activity against HPV-negative head and neck squamous cell cancer.

Albendazole is an anti-helminthic drug that has been shown to exhibit anti-cancer properties, however its activity in head and neck squamous cell cancer (HNSCC) was unknown. Using a series of in vitro assays, we assessed the ability of albendazole to inhibit proliferation in 20 HNSCC cell lines across a range of albendazole doses (1 nM-10 μM). Cell lines that responded to treatment were further examined for cell death, inhibition of migration and cell cycle arrest. Thirteen of fourteen human papillomavirus-negative HNSCC cell lines responded to albendazole, with an average IC50 of 152 nM. In contrast, only 3 of 6 human papillomavirus-positive HNSCC cell lines responded. Albendazole treatment resulted in apoptosis, inhibition of cell migration, cell cycle arrest in the G2/M phase and altered tubulin distribution. Normal control cells were not measurably affected by any dose tested. This study indicates that albendazole acts to inhibit the proliferation of human papillomavirus-negative HNSCC cell lines and thus warrants further study as a potential chemotherapeutic agent for patients suffering from head and neck cancer

Titania-doped tantala/silica coatings for gravitational-wave detection

Reducing thermal noise from optical coatings is crucial to reaching the required sensitivity in next generation interferometric gravitational-wave detectors. Here we show that adding TiO2 to Ta2O5 in Ta2O5/SiO2 coatings reduces the internal friction and in addition present data confirming it reduces thermal noise. We also show that TiO2-doped Ta2O5/SiO2 coatings are close to satisfying the optical absorption requirements of second generation gravitational-wave detectors