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Objective: To verify the effect of PRP and its combination with rhBMP-2 as a controlled delivery system during sagittal suture distraction osteogenesis. Methods: Thirty six-week white rabbits were randomly assigned to sagittal suture distraction osteogenesis groups treated with group one PRP gel alone; and group two PRP gel mixed with 10 μg rhBMP-2 (PRP/rhBMP-2), and a control group untreated. The suture morphology was evaluated by Micro-CT and histology. Results: The amount of suture separation in the control group and the PRP gel group were statistically greater (P＜0.05) than in the PRP/rhBMP-2 gel group. The average degree of suture fusion in the PRP/rhBMP-2 gel group was 15.3 ± 9.5 % of bone thickness. And the average thickness of cranium bone in the PRP/rhBMP-2 gel group was statistically greater (P＜0.05) than in the control group and the PRP gel group. Conclusion: This study showed that both PRP gel and PRP/rhBMP-2 gel are effective in improving new bone formation in suture distraction osteogenesis. PRP gel induces suture bone formation without suture fusion and accelerates the suture wound healing, while the PRP/rhBMP-2 gel group, in which the sutures fused prematurely, showed powerful bone formation ability aided by rhBMP-2. [ABSTRACT FROM AUTHOR]

The problem of pin-constrained electrowetting-ondielectric (EWOD) biochips becomes a serious issue to realize complex bio-chemical operations. Due to limited number of control pins and routing resources, additional Printed Circuit Board (PCB) routing layers may be required which potentially raises the fabrication cost. Previous state-of-the-art work has tried to develop a framework that uses a network-flow-based method for broadcast electrodeaddressing EWOD biochips. Nevertheless, greedily merging of electrical pins in previous works is at high risk of producing unroutable design. Routability should have higher priority than pin reduction. While previous works dedicated their effort on pin reduction, we have addressed our attention on routability of broadcast addressing. Experimental results demonstrate that taking routability into consideration can even have higher pin reduction. Viewed in this light, we present ACER, a routability driven clustering algorithm followed by escape routing using integer linear programming that effectively solves both pin merging and routing in broadcast addressing framework. Our proposed algorithm does not greedily focus on pin-reduction. Instead, routability is taken into consideration through agglomerative clustering. Compared to previous state-of-the-art, our proposed algorithm can further reduce required control pins by an average of 13% and route the design using 68% less wirelength. [ABSTRACT FROM PUBLISHER]

Background The occurrence of mandibular defects caused by tumors has been continuously increasing in China in recent years. Conversely, results of the repair of mandibular defects affect the recovery of oral function and patient appearance, and the requirements for accuracy and high surgical quality must be more stringent. Digital techniques - including model reconstruction based on medical images, computer-aided design, and additive manufacturing - have been widely used in modern medicine to improve the accuracy and quality of diagnosis and surgery. However, some special software platforms and services from international companies are not always available for most of researchers and surgeons because they are expensive and time-consuming. Methods Here, a new technical solution for guided surgery for the repair of mandibular defects is proposed, based on general popular tools in medical image processing, 3D (3 dimension) model reconstruction, digital design, and fabrication via 3D printing. First, CT (computerized tomography) images are processed to reconstruct the 3D model of the mandible and fibular bone. The defect area is then replaced by healthy contralateral bone to create the repair model. With the repair model as reference, the graft shape and cutline are designed on fibular bone, as is the guide for cutting and shaping. The physical model, fabricated via 3D printing, including surgical guide, the original model, and the repair model, can be used to preform a titanium locking plate, as well as to design and verify the surgical plan and guide. In clinics, surgeons can operate with the help of the surgical guide and preformed plate to realize the predesigned surgical plan. Results With sufficient communication between engineers and surgeons, an optimal surgical plan can be designed via some common software platforms but needs to be translated to the clinic. Based on customized models and tools, including three surgical guides, preformed titanium plate for fixation, and physical models of the mandible, grafts for defect repair can be cut from fibular bone, shaped with high accuracy during surgery, and fixed with a well-fitting preformed locking plate, so that the predesigned plan can be performed in the clinic and the oral function and appearance of the patient are recovered. This method requires 20% less operating time compared with conventional surgery, and the advantages in cost and convenience are significant compared with those of existing commercial services in China. Conclusions This comparison between two groups of cases illustrates that, with the proposed method, the accuracy of mandibular defect repair surgery is increased significantly and is less timeconsuming, and patients are satisfied with both the recovery of oral function and their appearance. Until now, more than 15 cases have been treated with the proposed methods, so their feasibility and validity have been verified. [ABSTRACT FROM AUTHOR]

Background: Epidermal growth factor receptor (EGFR) gene mutations identify patients with non-small cell lung cancer (NSCLC) who have a high likelihood of benefiting from treatment with anti-EGFR tyrosine kinase inhibitors. Sanger sequencing is widely used for mutation detection but can be technically challenging, resulting in longer turn-around-time, with limited sensitivity for low levels of mutations. This manuscript details the technical performance verification studies and external clinical reproducibility studies of the cobas EGFR Mutation Test, a rapid multiplex real-time PCR assay designed to detect 41 mutations in exons 18, 19, 20 and 21. Methods: The assay's limit of detection was determined using 25 formalin-fixed paraffin-embedded tissue (FFPET)-derived and plasmid DNA blends. Assay performance for a panel of 201 specimens was compared against Sanger sequencing with resolution of discordant specimens by quantitative massively parallel pyrosequencing (MPP). Internal and external reproducibility was assessed using specimens tested in duplicate by different operators, using different reagent lots, instruments and at different sites. The effects on the performance of the cobas EGFR test of endogenous substances and nine therapeutic drugs were evaluated in ten FFPET specimens. Other tests included an evaluation of the effects of necrosis, micro-organisms and homologous DNA sequences on assay performance, and the inclusivity of the assay for less frequent mutations. Results: A >95% hit rate was obtained in blends with >5% mutant alleles, as determined by MPP analysis, at a total DNA input of 150 ng. The overall percent agreement between Sanger sequencing and the cobas test was 96.7% (negative percent agreement 97.5%; positive percent agreement 95.8%). Assay repeatability was 98% when tested with two operators, instruments, and reagent lots. In the external reproducibility study, the agreement was > 99% across all sites, all operators and all reagent lots for 11/12 tumors tested. Test performance was not compromised by endogenous substances, therapeutic drugs, necrosis up to 85%, and common micro-organisms. All of the assessed less common mutations except one (exon 19 deletion mutation 2236_2248 > AGAC) were detected at a similar DNA input level as that for the corresponding predominant mutation. Conclusion: The cobas EGFR Mutation Test is a sensitive, accurate, rapid, and reproducible assay. [ABSTRACT FROM AUTHOR]

Abstract: Suture compression is a widely used approach to inhibit maxillary growth; however, biological responses in sutures to compressive force are still unclear. The objective of this pilot study was to investigate the matrix metalloproteinase (MMP) expression and osteoclast activities during the midpalatal suture compression. Methods: 56 six-week old male C57BL/6 mice were randomly assigned to the control and compression groups. The mice in the compression and control groups received helix springs bonded to the maxillary molars delivering initial compressive forces of 0.20 and 0N (no activation), respectively. On Days 1, 4, 7 and 14, animals were sacrificed and scanned using micro-computed tomography to quantify suture width and bone mineral density. Serial histological sections were stained with HE, TRAP, and immunohistochemistry to observe changes in bone resorption, osteoclast activities, and MMP-1, 8, and 13 expressions. Bone volume/total volume (Bv/Tv) ratio, osteoclast count, osteoclast covering area, and MMP expression intensity were measured. The Mann–Whitney and the Kruskal–Wallis tests with Bonferroni post-hoc corrections were performed to compare differences between groups and between time points in the same group at significant level of P<0.05. Results: Compared to the control, suture width in the compression group was significantly reduced on Day 1, but continuously widened with reduced bone mineral density afterwards. With MMP-1 and ‐13 evidently intensified expressions, osteoclast number and activities significantly increased, leading to reduced Bv/Tv ratio and progressive bone resorption from Days 4 to 14. Conclusions: Suture compression elevated the MMP-1 and 13 expressions, activated osteoclasts, reduced bone density, and induced bone resorption adjacent to the suture. It suggests that suture compression can be used for bone volume reduction. [Copyright &y& Elsevier]

Background: The occurrence of mandibular defects caused by tumors has been continuously increasing in China in recent years. Conversely, results of the repair of mandibular defects affect the recovery of oral function and patient appearance, and the requirements for accuracy and high surgical quality must be more stringent. Digital techniques--including model reconstruction based on medical images, computer-aided design, and additive manufacturing--have been widely used in modern medicine to improve the accuracy and quality of diagnosis and surgery. However, some special software platforms and services from international companies are not always available for most of researchers and surgeons because they are expensive and time-consuming.Methods: Here, a new technical solution for guided surgery for the repair of mandibular defects is proposed, based on general popular tools in medical image processing, 3D (3 dimension) model reconstruction, digital design, and fabrication via 3D printing. First, CT (computerized tomography) images are processed to reconstruct the 3D model of the mandible and fibular bone. The defect area is then replaced by healthy contralateral bone to create the repair model. With the repair model as reference, the graft shape and cutline are designed on fibular bone, as is the guide for cutting and shaping. The physical model, fabricated via 3D printing, including surgical guide, the original model, and the repair model, can be used to preform a titanium locking plate, as well as to design and verify the surgical plan and guide. In clinics, surgeons can operate with the help of the surgical guide and preformed plate to realize the predesigned surgical plan.Results: With sufficient communication between engineers and surgeons, an optimal surgical plan can be designed via some common software platforms but needs to be translated to the clinic. Based on customized models and tools, including three surgical guides, preformed titanium plate for fixation, and physical models of the mandible, grafts for defect repair can be cut from fibular bone, shaped with high accuracy during surgery, and fixed with a well-fitting preformed locking plate, so that the predesigned plan can be performed in the clinic and the oral function and appearance of the patient are recovered. This method requires 20% less operating time compared with conventional surgery, and the advantages in cost and convenience are significant compared with those of existing commercial services in China.Conclusions: This comparison between two groups of cases illustrates that, with the proposed method, the accuracy of mandibular defect repair surgery is increased significantly and is less time-consuming, and patients are satisfied with both the recovery of oral function and their appearance. Until now, more than 15 cases have been treated with the proposed methods, so their feasibility and validity have been verified. [ABSTRACT FROM AUTHOR]

Background: Epidermal growth factor receptor (EGFR) gene mutations identify patients with non-small cell lung cancer (NSCLC) who have a high likelihood of benefiting from treatment with anti-EGFR tyrosine kinase inhibitors. Sanger sequencing is widely used for mutation detection but can be technically challenging, resulting in longer turn-around-time, with limited sensitivity for low levels of mutations. This manuscript details the technical performance verification studies and external clinical reproducibility studies of the cobas EGFR Mutation Test, a rapid multiplex real-time PCR assay designed to detect 41 mutations in exons 18, 19, 20 and 21.Methods: The assay's limit of detection was determined using 25 formalin-fixed paraffin-embedded tissue (FFPET)-derived and plasmid DNA blends. Assay performance for a panel of 201 specimens was compared against Sanger sequencing with resolution of discordant specimens by quantitative massively parallel pyrosequencing (MPP). Internal and external reproducibility was assessed using specimens tested in duplicate by different operators, using different reagent lots, instruments and at different sites. The effects on the performance of the cobas EGFR test of endogenous substances and nine therapeutic drugs were evaluated in ten FFPET specimens. Other tests included an evaluation of the effects of necrosis, micro-organisms and homologous DNA sequences on assay performance, and the inclusivity of the assay for less frequent mutations.Results: A >95% hit rate was obtained in blends with >5% mutant alleles, as determined by MPP analysis, at a total DNA input of 150 ng. The overall percent agreement between Sanger sequencing and the cobas test was 96.7% (negative percent agreement 97.5%; positive percent agreement 95.8%). Assay repeatability was 98% when tested with two operators, instruments, and reagent lots. In the external reproducibility study, the agreement was > 99% across all sites, all operators and all reagent lots for 11/12 tumors tested. Test performance was not compromised by endogenous substances, therapeutic drugs, necrosis up to 85%, and common micro-organisms. All of the assessed less common mutations except one (exon 19 deletion mutation 2236_2248 > AGAC) were detected at a similar DNA input level as that for the corresponding predominant mutation.Conclusion: The cobas EGFR Mutation Test is a sensitive, accurate, rapid, and reproducible assay. [ABSTRACT FROM AUTHOR]