Contribution of geometric design parameters to knee implant performance: Conflicting impact of conformity on kinematics and contact mechanics

Background: Articular geometry of knee implant has a competing impact on kinematics and contact mechanics of total knee arthroplasty (TKA) such that geometry with lower contact pressure will impose more constraints on knee kinematics. The geometric parameters that may cause this competing effect have not been well understood. This study aimed to quantify the underlying relationships between implant geometry as input and its performance metrics as output. Methods: Parametric dimensions of a fixed-bearing cruciate retaining implant were randomized to generate a number of perturbed implant geometries. Performance metrics (i.e., maximum contact pressure, anterior–posterior range of motion [A-P ROM] and internal–external range of motion [I-E ROM]) of each randomized design were calculated using finite element analysis. The relative contributions of individual geometric variables to the performance metrics were then determined in terms of sensitivity indices (SI). Results: The femoral and tibial distal or posterior radii and femoral frontal radius are the key parameters. In the sagittal plane, distal curvature of the femoral and tibial influenced both contact pressure, i.e., SI = 0.57; SI = 0.65, and A-P ROM, i.e., SI = 0.58; SI = 0.6, respectively. However, posterior curvature of the femoral and tibial implants had a smaller impact on the contact pressure, i.e., SI = 0.31; SI = 0.23 and a higher impact on the I-E ROM, i.e., SI = 0.72; SI = 0.58. It is noteworthy that in the frontal plane, frontal radius of the femoral implant impacted both contact pressure (SI = 0.38) and I-E ROM (SI = 0.35). Conclusion: Findings of this study highlighted how changes in the conformity of the femoral and tibial can impact the performance metrics

Perceptional components of brand equity: Configuring the Symmetrical and Asymmetrical Paths to brand loyalty and brand purchase intention

\ua9 2018 This research investigates the impact of brand perception on brand loyalty and brand purchase intention using the lenses of complexity theory. First, the study conceptualizes and operationalizes perceptional and behavioral components of brand equity. It then examines the dimensions of brand perception, and by assessing the consequences of favorable brand perception, the study enables a better understanding regarding whether a brand marketing approach helps to improve marketing performance. The research was conducted using a mixed methodology, beginning with interviews in order to gain a better understanding of the relationship between the dimensions of brand perception. These were followed by a questionnaire survey, and the resulting data were analyzed through content analysis and fuzzy-set qualitative comparative analysis (fsQCA). The results indicate that brand awareness, perceived quality, brand association, brand fondness, brand image, and product country image have a strong impact on the management of brand perception. The finding illustrates that it is the combinations of various perceptional elements of brand equity rather than any single factor that have strong impacts on brand loyalty and brand purchasing intention. The results support the importance of brand perception for the fashion industry, which needs to be more interactive in order to increase their customers\u27 brand loyalty and brand purchasing intention

A current perspective on cancer immune therapy: Step‑by‑step approach to constructing the magic bullet

Immunotherapy is the new trend in cancer treatment due to the selectivity, long lasting effects, and demonstrated improved overall survival and tolerance, when compared to patients treated with conventional chemotherapy. Despite these positive results, immunotherapy is still far from becoming the perfect magic bullet to fight cancer, largely due to the facts that immunotherapy is not effective in all patients nor in all cancer types. How and when will immunotherapy overcome these hurdles? In this review we take a step back to walk side by side with the pioneers of immunotherapy in order to understand what steps need to be taken today to make immunotherapy effective across all cancers. While early scientists, such as Coley, elicited an unselective but effective response against cancer, the search for selectivity pushed immunotherapy to the side in favor of drugs focused on targeting cancer cells. Fortunately, the modern era would revive the importance of the immune system in battling cancer by releasing the brakes or checkpoints (anti-CTLA-4 and anti-PD-1/PD-L1) that have been holding the immune system at bay. However, there are still many hurdles to overcome before immunotherapy becomes a universal cancer therapy. For example, we discuss how the redundant and complex nature of the immune system can impede tumor elimination by teeter tottering between different polarization states: one eliciting anti-cancer effects while the other promoting cancer growth and invasion. In addition, we highlight the incapacity of the immune system to choose between a fight or repair action with respect to tumor growth. Finally we combine these concepts to present a new way to think about the immune system and immune tolerance, by introducing two new metaphors, the “push the accelerator” and “repair the car” metaphors, to explain the current limitations associated with cancer immunotherapyThis work was supported by NIH R00 CA154605 and Louisiana Board of Regents LEQSF(2016-17)-RD-C-14 (H.L.M.), a Rámon y Cajal Merit Award from the Ministerio de Economía y Competitividad, Spain (B.S.Jr) and a Clinic and Laboratory Integration Program (CLIP) grant from the Cancer Research Institute, NY (B.S.Jr)

Coordination of opposing sex-specific and core muscle groups regulates male tail posture during Caenorhabditis elegans male mating behavior

Background To survive and reproduce, animals must be able to modify their motor behavior in response to changes in the environment. We studied a complex behavior of Caenorhabditis elegans, male mating behavior, which provided a model for understanding motor behaviors at the genetic, molecular as well as circuit level. C. elegans male mating behavior consists of a series of six sub-steps: response to contact, backing, turning, vulva location, spicule insertion, and sperm transfer. The male tail contains most of the sensory structures required for mating, in addition to the copulatory structures, and thus to carry out the steps of mating behavior, the male must keep his tail in contact with the hermaphrodite. However, because the hermaphrodite does not play an active role in mating and continues moving, the male must modify his tail posture to maintain contact. We provide a better understanding of the molecular and neuro-muscular pathways that regulate male tail posture during mating. Results Genetic and laser ablation analysis, in conjunction with behavioral assays were used to determine neurotransmitters, receptors, neurons and muscles required for the regulation of male tail posture. We showed that proper male tail posture is maintained by the coordinated activity of opposing muscle groups that curl the tail ventrally and dorsally. Specifically, acetylcholine regulates both ventral and dorsal curling of the male tail, partially through anthelmintic levamisole-sensitive, nicotinic receptor subunits. Male-specific muscles are required for acetylcholine-driven ventral curling of the male tail but dorsal curling requires the dorsal body wall muscles shared by males and hermaphrodites. Gamma-aminobutyric acid activity is required for both dorsal and ventral acetylcholine-induced curling of the male tail and an inhibitory gamma-aminobutyric acid receptor, UNC-49, prevents over-curling of the male tail during mating, suggesting that cross-inhibition of muscle groups helps maintain proper tail posture. Conclusion Our results demonstrated that coordination of opposing sex-specific and core muscle groups, through the activity of multiple neurotransmitters, is required for regulation of male tail posture during mating. We have provided a simple model for regulation of male tail posture that provides a foundation for studies of how genes, molecular pathways, and neural circuits contribute to sensory regulation of this motor behavior

Acupuncture reduces crying in infants with infantile colic: a randomised, controlled, blind clinical study

OBJECTIVE: To investigate whether acupuncture reduces the duration and intensity of crying in infants with colic. Patients and methods 90 otherwise healthy infants, 2-8 weeks old, with infantile colic were randomised in this controlled blind study. 81 completed a structured programme consisting of six visits during 3 weeks to an acupuncture clinic in Sweden. Parents blinded to the allocation of their children met a blinded nurse. The infant was subsequently given to another nurse in a separate room, who handled all infants similarly except that infants allocated to receive acupuncture were given minimal, standardised acupuncture for 2 s in LI4. RESULTS: There was a difference (p=0.034) favouring the acupuncture group in the time which passed from inclusion until the infant no longer met the criteria for colic. The duration of fussing was lower in the acupuncture group the first (74 vs 129 min; p=0.029) and second week (71 vs 102 min; p=0.047) as well as the duration of colicky crying in the second intervention week (9 vs 13 min; p=0.046) was lower in the acupuncture group. The total duration of fussing, crying and colicky crying (TC) was lower in the acupuncture group during the first (193 vs 225 min; p=0.025) and the second intervention week (164 vs 188 min; p=0.016). The relative difference from baseline throughout the intervention weeks showed differences between groups for fussing in the first week (22 vs 6 min; p=0.028), for colicky crying in the second week (92 vs 73 min; p=0.041) and for TC in the second week (44 vs 29 min; p=0.024), demonstrating favour towards the acupuncture group. CONCLUSIONS: Minimal acupuncture shortened the duration and reduced the intensity of crying in infants with colic. Further research using different acupuncture points, needle techniques and intervals between treatments is required

Topological mechanochemistry of graphene

In view of a formal topology, two common terms, namely, connectivity and adjacency, determine the quality of C-C bonds of sp2 nanocarbons. The feature is the most sensitive point of the inherent topology of the species so that such external action as mechanical deformation should obviously change it and result in particular topological effects. The current paper describes the effects caused by uniaxial tension of a graphene molecule in due course of a mechanochemical reaction. Basing on the molecular theory of graphene, the effects are attributed to both mechanical loading and chemical modification of edge atoms of the molecule. The mechanical behavior is shown to be not only highly anisotropic with respect to the direction of the load application, but greatly dependent on the chemical modification of the molecule edge atoms thus revealing topological character of the graphene deformation.Comment: 9 pages, 10 figures, 1 table. arXiv admin note: text overlap with arXiv:1301.094

Influenza nucleoprotein delivered with aluminium salts protects mice from an influenza virus that expresses an altered nucleoprotein sequence

Influenza virus poses a difficult challenge for protective immunity. This virus is adept at altering its surface proteins, the proteins that are the targets of neutralizing antibody. Consequently, each year a new vaccine must be developed to combat the current recirculating strains. A universal influenza vaccine that primes specific memory cells that recognise conserved parts of the virus could prove to be effective against both annual influenza variants and newly emergent potentially pandemic strains. Such a vaccine will have to contain a safe and effective adjuvant that can be used in individuals of all ages. We examine protection from viral challenge in mice vaccinated with the nucleoprotein from the PR8 strain of influenza A, a protein that is highly conserved across viral subtypes. Vaccination with nucleoprotein delivered with a universally used and safe adjuvant, composed of insoluble aluminium salts, provides protection against viruses that either express the same or an altered version of nucleoprotein. This protection correlated with the presence of nucleoprotein specific CD8 T cells in the lungs of infected animals at early time points after infection. In contrast, immunization with NP delivered with alum and the detoxified LPS adjuvant, monophosphoryl lipid A, provided some protection to the homologous viral strain but no protection against infection by influenza expressing a variant nucleoprotein. Together, these data point towards a vaccine solution for all influenza A subtypes

Coherent coupling between radio frequency, optical, and acoustic waves in piezo-optomechanical circuits

The interaction of optical and mechanical modes in nanoscale optomechanical systems has been widely studied for applications ranging from sensing to quantum information science. Here, we develop a platform for cavity optomechanical circuits in which localized and interacting 1550 nm photons and 2.4 GHz phonons are combined with photonic and phononic waveguides. Working in GaAs facilitates manipulation of the localized mechanical mode either with a radio frequency field through the piezo-electric effect, or optically through the strong photoelastic effect. We use this to demonstrate a novel acoustic wave interference effect, analogous to coherent population trapping in atomic systems, in which the coherent mechanical motion induced by the electrical drive can be completely cancelled out by the optically-driven motion. The ability to manipulate cavity optomechanical systems with equal facility through either photonic or phononic channels enables new device and system architectures for signal transduction between the optical, electrical, and mechanical domains

Proliferation and estrogen signaling can distinguish patients at risk for early versus late relapse among estrogen receptor positive breast cancers

Introduction: We examined if a combination of proliferation markers and estrogen receptor (ER) activity could predict early versus late relapses in ER-positive breast cancer and inform the choice and length of adjuvant endocrine therapy. Methods: Baseline affymetrix gene-expression profiles from ER-positive patients who received no systemic therapy (n = 559), adjuvant tamoxifen for 5 years (cohort-1: n = 683, cohort-2: n = 282) and from 58 patients treated with neoadjuvant letrozole for 3 months (gene-expression available at baseline, 14 and 90 days) were analyzed. A proliferation score based on the expression of mitotic kinases (MKS) and an ER-related score (ERS) adopted from Oncotype DX® were calculated. The same analysis was performed using the Genomic Grade Index as proliferation marker and the luminal gene score from the PAM50 classifier as measure of estrogen-related genes. Median values were used to define low and high marker groups and four combinations were created. Relapses were grouped into time cohorts of 0-2.5, 0-5, 5-10 years. Results: In the overall 10 years period, the proportional hazards assumption was violated for several biomarker groups indicating time-dependent effects. In tamoxifen-treated patients Low-MKS/Low-ERS cancers had continuously increasing risk of relapse that was higher after 5 years than Low-MKS/High-ERS cancers [0 to 10 year, HR 3.36; p = 0.013]. High-MKS/High-ERS cancers had low risk of early relapse [0-2.5 years HR 0.13; p = 0.0006], but high risk of late relapse which was higher than in the High-MKS/Low-ERS group [after 5 years HR 3.86; p = 0.007]. The High-MKS/Low-ERS subset had most of the early relapses [0 to 2.5 years, HR 6.53; p < 0.0001] especially in node negative tumors and showed minimal response to neoadjuvant letrozole. These findings were qualitatively confirmed in a smaller independent cohort of tamoxifen-treated patients. Using different biomarkers provided similar results. Conclusions: Early relapses are highest in highly proliferative/low-ERS cancers, in particular in node negative tumors. Relapses occurring after 5 years of adjuvant tamoxifen are highest among the highly-proliferative/high-ERS tumors although their risk of recurrence is modest in the first 5 years on tamoxifen. These tumors could be the best candidates for extended endocrine therapy

Model construction of medical endoscope service evaluation system-based on the analysis of Delphi method

Background: Medical endoscope is widely used in clinical practice for the purpose of diagnosis and treatment, occupying around 5% of the medical device market. Evaluating the true service level of medical endoscope is essential and necessary to improve overall performance of medical diagnosis and treatment, and to maintain competitiveness of endoscope manufacturers, however, such a tool is not available in the market. This study develops an Evaluation Index System (EIS) to assess service level of medical endoscope, and to provide suggestions for improving the service level through the Delphi method. Methods: Firstly, the possible factors influencing the service level were identified from literature review. In parallel, the Delphi expert method questionnaire was designed and 25 experts were invited to conduct three rounds of questionnaire, to evaluate and rate the possible factors. Finally, we determined the weights associated with the factors, using the analytic hierarchy process (AHP) and percentage method, and developed the service level EIS. Results: The EIS consists of 3 first-level indicators, 24 s-level indicators and 68 third-level indicators. According to the weights computed using AHP, first-level indicators are ranked as post-sale (0.62), in-sale (0.25) and pre-sale (0.13). Through case verification, the medical endoscope brand Olympus had a total score of 4.17, Shanghai Aohua had a total score of 3.71, and Shanghai Chengyun had a total score of 3.28, which matches its market popularity and ranking in terms of market share. The results obtained from the EIS are consistent with the reality. Conclusions: The EIS established in this study is comprehensive, reliable and reasonable with strong practicality. The EIS can act as a tool for the endoscope users to evaluate potential products and make informed choices. It also provides a measurable basis for endoscope manufacturers and service providers to improve service quality