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The repair of large bone defects remains a significant challenge in clinical practice and requires bone grafts or substitute materials. In this study, we developed a unique hybrid bone scaffold comprising a three dimensional (3D)-printed metal plate for weight bearing and a biodegradable polymer tube serving as bone conduit. We assessed the long-term effect of the hybrid bone scaffold in repairing radial bone defects in a beagle model.Bone defects were created surgically on the radial bone of three beagle dogs and individually-tailored scaffolds were used for reconstruction with or without injection of autologous bone and decellularized extracellular matrix (dECM). The repaired tissue was evaluated by X-ray, micro-computed tomography, and histological observation 6 months after surgery. The functional integrity of hybrid bone scaffold-mediated reconstructions was assessed by gait analysis.In vivo analysis showed that the hybrid bone scaffolds maintained the physical space and bone conductivity around the defect. New bone was formed adjacent to the scaffolds. Addition of autologous bone and dECM in the polymer tube improved healing by enhancing bone induction and osteoconduction. Furthermore, the beagles' gait appeared normal by 4 months.The future of bone healing and regeneration is closely related to advances in tissue engineering. Bone production using autologous bone and dECM loaded on 3D-printed hybrid bone scaffolds can successfully induce osteogenesis and provide mechanical force for functional bone regeneration, even in large bone defects.

PurposeThis paper aims to determine if single-item (SI) needs' and values' measures have similar reliability and validity values to multi-item (MI) measures of the same constructs and thus could be substituted by sport marketers to predict internal motivating aspects of sport consumer attitudes and behavior. In addition, the authors wish to determine whether a small subset of needs and values listed in current measures are sufficient to predict sport consumer attitudes and behavior.Design/methodology/approachIn this two-study design, the first study was a national sample (N = 439) comparing reliability and validity of single-item scales to multi-item scales. In the second study the authors collected data from fans and spectators of four different teams (N1 = 583; N2 = 1164; N3 = 213; N4 = 404) to determine the impact of needs and values on sport consumer attitudes and behavior.FindingsThe authors determined that in 89% of the scales, single-item measures of needs and values were just as reliable and valid as their associated multi-item measures. The authors also found that a small subset of the needs and values explain a meaningful amount of variance in sport consumer attitudes and behaviors.Research limitations/implicationsThe authors determined that in 89% of the scales, single-item measures of needs and values were just as reliable and valid as their associated multi-item measures. The authors also found that a small subset of the needs and values explain a meaningful amount of variance in sport consumer attitudes and behaviors.Originality/valueThe authors show that as motives for sport consumption, single-item measures of personal needs and values are equivalent to multi-item measures and not all needs and values used in previous sport research are necessary because they do not predict a meaningful amount of variance in sport consumer attitudes and behaviors. The authors identified a small number of single-item measures that practitioners can easily use in short surveys that will predict a statistically meaningful amount of variance in sport consumer attitudes and behaviors.

The limited localization and penetration of monoclonal antibodies (mAb) into solid tumors restricts their antitumor efficacy. Here, we describe a solid tumor–targeting antibody with enhanced tumor penetration activity. We designed a 22-residue peptide (A22p), which was extracted from the C-terminal basic region of semaphorin 3A (Sema3A) but modified to have higher affinity with neuropilin receptors (NRP), and genetically fused it to the C-terminus of Fc of human immunoglobulin G1 via a 15-residue (G4S)3 linker, generating Fc-A22p, for the bivalent binding to NRPs. In contrast to Fc or the monovalent A22p peptide alone, Fc-A22p homed to tumor vessels and induced vascular permeability through VE-cadherin downregulation and penetrated tumor tissues by interacting with NRPs in mice bearing human tumor xenografts. We extended the Fc-A22p platform by generating mAb-A22p antibodies of two clinically approved solid tumor–targeting mAbs, the anti-EGF receptor mAb cetuximab (erbitux), and the anti-Her2 mAb trastuzumab (herceptin). The mAb-A22p antibodies retained the intrinsic antigen binding, natural Fc-like biophysical properties, and productivity in mammalian cell cultures, comparable with those of the parent mAbs. In mouse xenograft tumor models, the mAb-A22p antibodies more efficiently homed to tumor vessels and spread into the extravascular tumor parenchyma, which significantly enhanced antitumor efficacy compared with the parent mAbs. Our results suggest that mAb-A22p is a superior format for solid tumor–targeting antibodies due to its enhanced tumor tissue penetration and greater antitumor efficacy compared with conventional mAbs. Mol Cancer Ther; 13(3); 651–61. ©2014 AACR.

PDF - 2613K, Figure S1: Structural analysis of NRP1, NRP2, and Sema3A, and their interactions to facilitate the understanding of the interactions between Sema3A and NRP1/2. Figure S2: SDS-PAGE analyses of the purified proteins showing that NRP1/2-b1b2 domains, Fc-A22, and Fc-A22p are well prepared. Figure S3: FACS and confocal fluorescence data showing that Fc-A22p, but not Fc, specifically interacts with cell-surface expressed NRP1/2 undergoing cellular internalization. Figure S4: Cell viability data showing that Fc-A22p does not cause significant cytotoxicity on HUVECs and tumor cells. Figure S5: Tumor tissue analyzing data showing that Fc-A22p homes to tumor, induces vascular permeability, and downregulates VE-cadherin in endothelial cells and E-cadherin in tumor cells. Figure S6: Confocal fluorescence data showing that Fc-A22p causes downregulation of VE-/E-cadherin and their dissociation from F-actin cytoskeleton resulting in disruption of cell-cell contacts. Figure S7: Data showing the expression and biochemical characterization of mAb-A22p antibodies, cetuximab-A22p and trastuzumab-A22p, compared with the parent mAbs. Figure S8: Cell proliferation and Western blotting data showing that cetuximab-A22p exerts in vitro biological activities comparable to those of cetuximab in A431 and FaDu tumor cells. Figure S9: Human tumor xenografted mouse data showing that mAb-A22p antibodies show increased tumor homing and penetration and thus superior in vivo anti-tumor efficacy, compared with the parent mAbs. Table S1: SPR data showing the kinetic binding parameters for the interactions of Fc-A22, Fc-A22p, VEGF165, and Sema3A with soluble NRP1-b1b2 and NRP2-b1b2 fragments. Table S2: Purification yields of Fc proteins and antibodies obtained from transient expression in HEK293F cells. Table S3: SPR data showing the kinetic binding parameters for the interactions of mAbs and mAb-A22p antibodies with the indicated proteins. Supplementary Materials and Methods: Detailed description of Reagents; Recombinant protein expression and purification; Construction, expression, and purification of antibodies; Binding analysis by ELISA; Surface plasmon resonance (SPR); Flow cytometric analysis; Cell proliferation assay; Western blotting and immunoprecipitation; Co-localization studies by confocal immunofluorescence microscopy; RNA Interference; Ex vivo tumor penetration assays.

Do agency heads’ public profiles enhance the performance of bureaucratic agencies? Existing studies of public administration emphasize the role of public information in managing government performance. However, whether public attention to agency heads affects the performance of their agencies is largely understudied. Using a unique dataset of agency heads’ public profiles in South Korea, we predict that such profiles have a positive impact on their agencies’ performance. Although agency heads are not held accountable directly to citizens, close public attention to agency heads’ activities may function as an indirect mechanism of accountability and of improving their organizations’ performance. Our analysis supports our prediction and further suggests that an agency head’s high public profile is a benefit, particularly in more salient policy areas where “going public” is more effective for their policy reforms. Our findings have clear implications: the importance of agency heads’ unconventional roles for effective agency management, responding to rapidly changing external environments.

A composite comprising Ti and NaCl powders was sintered similar to a three-dimensional (3D)-printed patient-customized artificial bone scaffold. Additionally, a proper microstructure of the mimetic scaffold and the optimum processing parameters for its development were analyzed. The mechanical properties of the metal-based porous-structured framework used as an artificial bone scaffold were an optimum replacement for the human bone. Thus, it was confirmed that patient-customized scaffolds could be manufactured via 3D printing. The 3D-printed mimetic specimens were fabricated by a powder-sintering method using Ti for the metal parts, NaCl as the pore former, and polylactic acid as the biodegradable binder. Scanning electron microscopy (SEM) images showed that pores were formed homogeneously, while X-ray computed tomography confirmed that open pores were generated. The porosity and pore size distribution were measured using a mercury porosimeter, while the flexural strength and flexural elastic modulus were calculated using the three-point bending test. Based on these measurements, a pore-former content of 15 vol % optimized the density and flexural strength to 2.52 g cm

This study evaluated the efficacy of detergent-based surface cleaning methods against Murine Hepatitis Virus A59 (MHV) as a surrogate coronavirus for SARS-CoV-2. MHV (5% soil load in culture medium or simulated saliva) was inoculated onto four different high-touch materials [stainless steel (SS), Acrylonitrile Butadiene Styrene plastic (ABS), Formica, seat fabric (SF)]. Immediately and 2-hr post-inoculation, coupons were cleaned (damp wipe wiping) with and without pretreatment with detergent solution or 375 ppm hard water. Results identified that physical removal (no pretreatment) removed2.3 log

AimsTo assess low concentration hydrogen peroxide (LCHP) (H2O2) vapor dispersed with a home humidifier for its ability to decontaminate vehicle interiors contaminated with Bacillus anthracis surrogate Bacillus atrophaeus spores.Methods and resultsEfficacy of a vaporized 3% H2O2 solution was evaluated for liquid volumes, on/off vehicle heating, ventilation, and air conditioning (HVAC) system operations, and temperatures that ranged from 5 to 27°C. Survival of the spores was assessed by quantification of remaining viable spores with efficacy quantified in terms of mean log10 reduction. Decontamination efficacy after the 6-day dwell time increased when the 3% H2O2 liquid volume was doubled, increasing from 4-of-10 to 10-of-10 nondetects (zero colonies counted using standard dilution and filter plating) inside the vehicle cabin. Recirculating cabin air through the HVAC system during decontamination decreased efficacy to 6-of-10 non-detects. While no 6-log10 reduction in viable spores was observed on the cabin filter with the cabin filter kept in place, a 6-log10 reduction was achieved after its removal and placement in the cabin during treatment.ConclusionsResults from this study allow for informed decisions on the use of LCHP vapor as an effective decontamination approach for vehicle interiors.

PurposeThis phenomenological study aims to explore how media promote and should promote wheelchair rugby.Design/methodology/approachSemi-structured interviews were conducted with 31 athletes at National Wheelchair Rugby Championship. In using a reflective thematical analysis approach, three themes were identified – media coverage: the promise of an unknown quantity; the battle of inspiration and athleticism; and leverage marketing and promote the “wow”.FindingsLacking fair representation from media resulting in the perception and reception gap between the general public and spectators was identified and explained by most of the athletes. Besides urging increased coverage with a shifting focus on athleticism, the important role of marketing was highlighted.Originality/valueIn short, the “wow” factor of the sport is its aggressiveness which can be its bestselling feature and used by stakeholders for maximum impact when marketing wheelchair rugby.

Reproductive cycle of the blue-striped angelfish, Chaetodontoplus septentrionalis were histologically investigated. Fish were monthly collected in the coastal waters of Munseom, Seogwipo, Jeju-Island from February to December 2018. The gonadosomatic index (GSI) increased from May and maintained high values in August. The reproductive cycle of female fish can be classified by the characteristics observed during gonadal development as followed: growing stage (November to June), early mature stage (May to June), mature and spawning stage (June to September), and degenerative and recovery stage (September to December). In the male, testicular development period was similar to that of ovarian development period, but mature and spawning period was one month longer from June to October. Fecundity of mature female ranged from 4,601 to 22,840 and was correlated positively with total length and body weight. The histological analysis of gonadal development indicated that the C. septentrionalis was summer-spawning type and is considered a multiple spawner during spawning season.

This study explores the Korean final suffix -(u)lkel in the context of stance-taking within the framework of stance triangle and the notion of emergent stance. Using data from one hundred 30-minute telephone calls and 15 video recorded conversations totaling 270 min, this study examines the non-committal epistemic function of -(u)lkel from a conversation analytic approach and demonstrates how speakers mobilize this suffix as a divergent alignment stance marker when confronted with a conflicting, yet unclear understanding of information associated with a stance object. Moreover, the high intonational boundary tone associated with -(u)lkel cedes the floor to the recipient where a negotiation of the conflicting information offers an opportunity for a readjustment of positions towards either a converging-diverging alignment or disalignment (i.e., speakers’ abandonment of a shared stance object). As such, this study shows that a grammatical suffix such as -(u)lkel is not simply deployed to mark propositional information but is also utilized as an interactional resource that enables dialogic speech activities such as co-construction of stance.

An exosuit is a wearable robot that assists the muscular strength of a human that wears it by using multiple wires with similar functions to human muscles. This study focuses on the development of a series elastic tendon actuator (SETA) for the actuation of an exosuit. A gait analysis was performed for walking on stairs to deduce the design requirements of SETA, and the necessary performances were then determined based on these requirements. The SETA is designed to assign compliance to rigid wires using linear springs. The deformation in linear springs generated during tension was measured through an encoder to calculate the human robot interaction (HRI) force. By utilizing the HRI force as feedback of an admittance controller, the SETA was capable of providing wire tensions required by an exosuit. The performance of the SETA was verified through series elastic component (SEC) deformation and force control experiments. The SEC deformation increased from 0 to 3.86 mm when the wire tension increased from 0 to 100 N. This force controller demonstrated a slight vibration owing to the mechanical properties of the springs constituting the SEC during the step input; however, the value gradually converged to 100 N. The developed SETA was applied to an exosuit system for supporting knee strength of the elderly when walking on stairs.

The aim of this study is to provide an effective method to construct a three-dimensionally (3D) printed scaffold to reconstruct a damaged bone. The tibia of a rabbit with a comminuted fracture was scanned by computed tomography. A bio-scaffold was designed using a 3D modeling program for its reconstruction and fabricated by a 3D printer. As the tibia could tolerate a large stress, pure biodegradable materials used alone as scaffold were not effective as they could not sufficiently support the weight of rabbit. Therefore, an external metal scaffold was required as a support. To fabricate the metal scaffold, its mechanical properties were calculated using simulations by the ANSYS static structural program. The simulation showed that the metal scaffold could endure five times the rabbit’s weight with a volume of 2362.93 mm3, area of 3671.23 mm2, and weight of 10.73 g. The proposed design of metal scaffold for a fractured bone exhibited a high supporting ability for the weight of the rabbit. The necessity of an external metal scaffold to support the biodegradable scaffold in bone reconstruction is demonstrated.

The objective of this work is to utilize integrated geomechanics, field vertical seismic profile (VSP) and microseismic data to characterize the complex subsurface stress conditions at the Farnsworth Unit (FWU). The model is based on a five-spot sector model extracted from a primary geomechanical model. The five-spot well injection pattern is characterized by extensive reservoir characterization data, such well logs, extracted cores and borehole geophone data, to facilitate the detailed examination of stress changes and microseismic event occurrences. The study utilizes field vertical seismic volumes acquired from the injection well 13-10A. The seismic volumes successfully provided snapshots of the behavior of the reservoir at distinct times. The use of VSP and microseismic data provided direct and indirect estimates of the dynamic stress changes occurring in the overburden, reservoir and underburden rock formations. In order to illuminate the stress regions and identify rocks that have undergone inelastic failure, microseismic event occurrences were utilized. Microseismic activity has been detected at the FWU; further study of its locations, timing, and magnitude was needed to deduce the nature of the changing stress state. The results of the study revealed that microseismic events were successfully modeled within the Morrow B formation. Moment magnitudes of seismic events were within the same magnitudes for events in the reservoir, suggesting the suitability of the model. The results of the study showed that the computed moment magnitudes for seismic events were insignificant to warrant safety concerns. The study findings showed the usefulness of coupled hydromechanical models in predicting the subsurface stress changes associated with CO2 injection. The knowledge gained from this study will serve as a guideline for industries planning to undertake underground CO2 storage, and characterize the subsurface stress changes.

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The present study aims to evaluate the effectiveness of the Transperineal Pelvic Floor Electrical Stimulation (TPFES) system as a treatment option for females with stress urinary incontinence (SUI). A total of 8 females who were diagnosed with SUI were included in the study. All the patients received TPFES and were educated to use it daily for 12 weeks. The patients completed ‘International Consultation on Incontinence Questionnaire-Urinary Incontinence (ICIQ-UI)’ and ‘Overactive Bladder Symptom Score Questionnaire’ before and after applying NPFES at every visit. Age, body mass index (BMI), maximum flow rate, and postvoid residual of each patient were obtained before the study. Repeated-measures ANOVA was performed using the estimates of variables at each visit to evaluate the effectiveness of TPFES in SUI. Also, a linear mixed model was derived to verify the variables that affect the effectiveness of TPFES treatment. The mean age and BMI of the patients were 61.88 ± 16.49 years and 24.62 ± 2.87 kg/m2, respectively. Among the investigated variables, the mean ICIQ-UI total score showed significant change depending on the duration of TPFES treatment (p

Advancing spring phenology is a well documented consequence of anthropogenic climate change, but it is not well understood how climate change will affect the variability of phenology year to year. Species' phenological timings reflect the adaptation to a broad suite of abiotic needs (e.g., thermal energy) and biotic interactions (e.g., predation and pollination), and changes in patterns of variability may disrupt those adaptations and interactions. Here, we present a geographically and taxonomically broad analysis of phenological shifts, temperature sensitivity, and changes in interannual variability encompassing nearly 10,000 long-term phenology time series representing more than 1000 species across much of the Northern Hemisphere. We show that the timings of leaf-out, flowering, insect first-occurrence, and bird arrival were the most sensitive to temperature variation and have advanced at the fastest pace for early-season species in colder and less seasonal regions. We did not find evidence for changing variability in warmer years in any phenophase groups, although leaf-out and flower phenology have become moderately but significantly less variable over time. Our findings suggest that climate change has not to this point fundamentally altered the patterns of interannual phenological variability.

Trp8Arg polymorphism of the LH beta gene has decreased bioactivity in vivo and previous studies showed conflicting data on the effect of LH beta gene polymorphism on the IVF outcome. In this study,...

Objective We aim to present a clinical guideline for the diagnosis and treatment of insomnia in adults by reviewing and integrating existing clinical guidelines. The purpose of this guideline is to assist clinicians who perform evidence-based insomnia treatment.Methods We selected literature that may be appropriate for use in guideline development from evidence-based practice guidelines that have been issued by an academic or governmental institution within the last five years. The core question of this guideline was made in sentence form including Patient/Problem, Intervention, Comparison, Outcome (PICO) elements. After searching PubMed, EMBASE, and medical guideline issuing agencies, three guidelines were judged to be the most appropriately reviewed, up-to-date, and from trusted sources.Results The Appraisal of Guidelines for Research and Evaluation (AGREE) II tool was used to evaluate the quality of the three clinical guidelines. The final outcome of the guideline development process is a total of 15 recommendations that report the strength of the recommendation, the quality of evidence, a summary of content, and considerations in applying the recommendation.Conclusion It is vital for clinical guidelines for insomnia to be developed and continually updated in order to provide more accurate evidence-based treatments to patients.

Purpose This study aimed to identify whether functional bladder capacity (FBC) differs among subgroups of nocturnal enuresis (NE) patients and can be used to predict treatment response. Methods A total of 69 children with NE were included in this study between July 2017 and February 2019 according to medical chart review, retrospectively. All patients completed a questionnaire about voiding symptoms and 48-hour frequency/volume (48-h F/V) charts. FBC was obtained from the 48-h F/V charts and uroflowmetry (UFM) with post-void residual volume (PVR). All patients were primarily treated with standard urotherapy and pharmacological therapy. The response rate was analyzed at 3 months after treatment. Results The mean age of the 69 patients (42 male, 27 female) was 83.3 ± 22.4 months (range, 5-13 years) at the first visit. The percentages of children with monosymptomatic NE (MNE) and non-monosymptomatic NE (NMNE) on the questionnaire were 40.6% (28/69) and 59.4% (41/69), respectively. FBC of all patients was lower than the normal range of expected bladder capacity, and there were no significant differences between measurement methods, NE types (MNE vs NMNE), or response rates (p > 0.05). Conclusion Children with NE had diminished FBC in both 48-h F/V charts and UFM with PVR. We found no difference in FBC by NE type or treatment outcome. Therefore, FBC cannot be used to distinguish between NE types or predict treatment responses.