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Objectives: To implement a system for unsupervised extraction of tumor stage and prognostic data in patients with genitourinary cancers using clinicopathological and radiology text., Methods: A corpus of 1054 electronic notes (clinician notes, radiology reports and pathology reports) was annotated for tumor stage, prostate specific antigen (PSA) and Gleason grade. Annotations from five clinicians were reconciled to form a gold standard dataset. A training dataset of 386 documents was sequestered. The Medtex algorithm was adapted using the training dataset., Results: Adapted Medtex equaled or exceeded human performance in most annotations, except for implicit M stage (F-measure of 0.69 vs 0.84) and PSA (0.92 vs 0.96). Overall Medtex performed with an F-measure of 0.86 compared to human annotations of 0.92. There was significant inter-observer variability when comparing human annotators to the gold standard., Conclusions: The Medtex algorithm performed similarly to human annotators for extracting stage and prognostic data from varied clinical texts., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Purpose: To investigate the role of quantitative pre-treatment dual-energy computed tomography (DECT) for prediction of loco-regional recurrence (LRR) in patients with larynx/hypopharynx squamous cell cancer (L/H SCC)., Methods: Patients with L/H SCC treated with curative intent loco-regional radiotherapy and that underwent treatment planning with contrast-enhanced DECT of the neck were included. Primary and nodal gross tumor volumes (GTVp and GTVn) were contoured and transferred into a Matlab® workspace. Using a two-material decomposition, GTV iodine concentration (IC) maps were obtained. Quantitative histogram statistics (maximum, mean, standard deviation, kurtosis and skewness) were retrieved from the IC maps. Cox regression analysis was conducted to determine potential predictive factors of LRR., Results: Twenty-five patients, including 20 supraglottic and 5 pyriform sinus tumors were analysed. Stage I, II, III, IVa and IVb constituted 4% (1 patient), 24%, 36%, 28% and 8% of patients, respectively; 44% had concurrent chemo-radiotherapy and 28% had neodjuvant chemotherapy. Median follow-up was 21 months. Locoregional control at 1 and 2 years were 75% and 69%, respectively. For the entire cohort, GTVn volume (HR 1.177 [1.001-1.392], p = 0.05), voxel-based maximum IC of GTVp (HR 1.099 [95% CI: 1.001-1.209], p = 0.05) and IC standard deviation of GTVn (HR 9.300 [95% CI: 1.113-77.725] p = 0.04) were predictive of LRR. On subgroup analysis of patients treated with upfront radiotherapy +/- chemotherapy, both voxel-based maximum IC of GTVp (HR 1.127 [95% CI: 1.010-1.258], p = 0.05) and IC kurtosis of GTVp (HR 1.088 [95% CI: 1.014-1.166], p = 0.02) were predictive of LRR., Conclusion: This exploratory study suggests that pre-radiotherapy DECT-derived IC quantitative analysis of tumoral volume may help predict LRR in L/H SCC., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Purpose/objective(s): To evaluate the impact of positron emission tomography (PET) staging on overall survival (OS) and progression-free survival (PFS) in patients with early-stage (stages I and II) follicular lymphoma (ESFL) treated with radiation therapy alone., Materials/methods: Eighty-five patients with ESFL treated with curative-intent radiation therapy (RT) between December 2000 and May 2011 were identified. Of those, 13 who had no PET staging and 25 who received additional systemic therapy were excluded from the analysis. Thus, we analyzed 47 patients with PET-staged ESFL treated with definitive radiation therapy alone (dose > 23Gy). Tumour features, pre-treatment computed tomography (CT) and PET stage, dose fractionation, and radiation therapy field extent were recorded. The Kaplan-Meier method was used to estimate the OS and PFS. Patterns of failure were assessed as cumulative incidences assuming competing risks., Results: Median age was 57 years (range 24-83); 43% were females. Most were PET stage 1 (76.6%). Median maximum nodal diameter was 3 cm. Median pre-treatment lactate dehydrogenase (LDH) was 327.5 (range 123-607, upper normal limit = 220). Twenty-six patients (55.3%) had infra-diaphragmatic disease. All received 30-36Gy in 15-24 fractions, with 59.6% treated with involved-field radiation therapy (IFRT) techniques. There was no significant difference in PFS between CT stage I and stage II (HR 1.30 95% CI [0.25-6.72], p = 0.75) with a 5-year PFS of 77% and 78% respectively. However, stage I on PET staging had a significantly better PFS than stage II (HR 4.66 95% CI [1.15-18.8], p = 0.038), with 5-year PFS of 84% and 60% respectively. Ten patients had recurrent disease, with distant disease being the first site of failure in seven patients. Seven-year OS was 91% (95% CI 79-100) for the whole cohort., Conclusion: FDG-PET should be considered an essential element in the evaluation of patients with ESFL being considered for RT.

Purpose: Patients with p16/human papilloma virus (HPV)-associated oropharyngeal squamous cell carcinoma have a favorable outcome after treatment. In this group of patients who could have a long life expectancy, the optimal surveillance strategy and modality is not well established. We aim to determine the ability of a negative postradiation positron emission tomography (PET)/computed tomography scan to predict the risk of subsequent relapse in these patients., Materials and Methods: A retrospective analysis of patients with p16/HPV-associated oropharyngeal squamous cell carcinoma who completed definitive (chemo)radiation therapy and had a posttreatment PET/computed tomography scan from 2006 to 2013 was performed. Patient, tumor, and treatment characteristics and clinical outcomes were recorded. Tumors were considered HPV/p16 positive if either HPV (by in situ hybridization) or p16 (by immunohistochemistry) was positive. Disease-free survival and overall survival rates were estimated using the Kaplan-Meier method., Results: In our study, 327 patients were evaluated. The median age was 57 years. The most common primary sites were base of tongue (50%) and tonsil (48%). Of the patients evaluated, 291 (89%) had a negative posttreatment PET scan. For these 291 patients who had a complete metabolic response after treatment, the 5-year disease-free survival and overall survival rates were 91% and 89%, respectively. The median time to development of recurrence was 16 months. Of the 291 patients, 24 patients (8%) had disease recurrence; 13 recurrences were locoregional, and 13 were distant. Eleven (4%) patients with recurrence had further surgery or radiation, and 8 patients (3%) were without disease as of the last follow-up., Conclusions: Patients who achieve a complete metabolic response on posttreatment PET imaging have an excellent prognosis, and the risk of developing a recurrence in the future is very low. Therefore, a more cost effective surveillance program should be considered for this subgroup of patients., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background:: The midsole is an essential assembly of footwear for retaining the shape of the shoe, delivering support to the foot, and serving as a cushioning and stability device for walking. To improve leg muscle balance and muscle co-contraction, we propose a new midsole design for high heels with different hardness levels at the forefoot region., Methods:: Five healthy women participated in the study, with a mean ± SD age of 21.80 ± 4.09 years, and duration of high-heeled shoe wear of 5.20 ± 4.09 years. Two midsole conditions, control and multiple-hardness midsole (MHM), with heel heights of 2 (flat), 5, and 8 cm were used. The main outcome measures were to examine the acute effects of MHM by electromyography on muscle activity balance and co-contraction at varying heel heights during shuttle walk., Results:: Use of the MHM significantly reduced the muscle activity ratio between the medial and lateral gastrocnemius muscles ( P = .043) during push-off to heel strike with a heel height of 5 cm (-22.74%) and heel strike to midstance with a heel height of 8 cm (-22.26%). The increased co-contraction indices of the tibialis anterior-peroneus longus muscles (14.35% with an 8-cm heel height) and tibialis anterior-soleus muscles (15.18% with a 5-cm heel height) are significant ( P = .043), with a large effect size ( d = 0.8)., Conclusions:: These results deliver important implications in advancing the engineering of MHM design without changing the in-shoe volume to enhance leg muscle balance and co-contraction during walking.

New approaches are needed to assess the effects of inhaled substances on human health. These approaches will be based on mechanisms of toxicity, an understanding of dosimetry, and the use of in silico modeling and in vitro test methods. In order to accelerate wider implementation of such approaches, development of adverse outcome pathways (AOPs) can help identify and address gaps in our understanding of relevant parameters for model input and mechanisms, and optimize non-animal approaches that can be used to investigate key events of toxicity. This paper describes the AOPs and the toolbox of in vitro and in silico models that can be used to assess the key events leading to toxicity following inhalation exposure. Because the optimal testing strategy will vary depending on the substance of interest, here we present a decision tree approach to identify an appropriate non-animal integrated testing strategy that incorporates consideration of a substance's physicochemical properties, relevant mechanisms of toxicity, and available in silico models and in vitro test methods. This decision tree can facilitate standardization of the testing approaches. Case study examples are presented to provide a basis for proof-of-concept testing to illustrate the utility of non-animal approaches to inform hazard identification and risk assessment of humans exposed to inhaled substances., (Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Magnetic resonance imaging (MRI) has improved capacity to visualize tumor and soft tissue involvement in head and neck cancers. Using advanced MRI, we can interrogate cell density using diffusion weighted imaging, a quantitative imaging that can be used during radiotherapy, when diffuse inflammatory reaction precludes PET imaging, and can assist with target delineation as well. Correlation of circulating tumor cells (CTCs) measurements with 3D quantitative tumor characterization could potentially allow selective, patient-specific response-adapted escalation or de-escalation of local therapy, and improve the therapeutic ratio, curing the greatest number of patients with the least toxicity., Methods: The proposed study is designed as a prospective observational study and will collect pretreatment CT, MRI and PET/CT images, weekly serial MR imaging during RT and post treatment CT, MRI and PET/CT images. In addition, blood sample will be collected for biomarker analysis at those time intervals. CTC assessments will be performed on the CellSave tube using the FDA-approved CellSearch® Circulating Tumor Cell Kit (Janssen Diagnostics), and plasma from the EDTA blood samples will be collected, labeled with a de-identifying number, and stored at - 80 °C for future analyses., Discussion: The primary objective of the study is to evaluate the prognostic value and correlation of weekly tumor response kinetics (gross tumor volume and MR signal changes) and circulating tumor cells of mucosal head and neck cancers during radiation therapy using MRI in predicting treatment response and clinical outcomes. This study will provide landmark information as to the utility of CTCs ('liquid biopsy) and tumor-specific functional quantitative imaging changes during treatment to guide personalization of treatment for future patients. Combining the biological information from CTCs and the structural information from MRI may provide more information than either modality alone. In addition, this study could potentially allow us to determine the optimal time to obtain MR imaging and/ or CTCs during radiotherapy to assess tumor response and provide guidance for patient selection and stratification for future dose escalation or de-escalation strategies., Trial Registration: Clinicaltrials.gov ( NCT03491176 ). Date of registration: 9 th April 2018. (retrospectively registered). Date of enrolment of the first participant: 30 th May 2017.

Background: Current standard radiotherapy for oropharynx cancer (OPC) is associated with high rates of severe toxicities, shown to adversely impact patients' quality of life. Given excellent outcomes of human papilloma virus (HPV)-associated OPC and long-term survival of these typically young patients, treatment de-intensification aimed at improving survivorship while maintaining excellent disease control is now a central concern. The recent implementation of magnetic resonance image - guided radiotherapy (MRgRT) systems allows for individual tumor response assessment during treatment and offers possibility of personalized dose-reduction. In this 2-stage Bayesian phase II study, we propose to examine weekly radiotherapy dose-adaptation based on magnetic resonance imaging (MRI) evaluated tumor response. Individual patient's plan will be designed to optimize dose reduction to organs at risk and minimize locoregional failure probability based on serial MRI during RT. Our primary aim is to assess the non-inferiority of MRgRT dose adaptation for patients with low risk HPV-associated OPC compared to historical control, as measured by Bayesian posterior probability of locoregional control (LRC)., Methods: Patients with T1-2 N0-2b (as per AJCC 7th Edition) HPV-positive OPC, with lymph node <3 cm and <10 pack-year smoking history planned for curative radiotherapy alone to a dose of 70 Gy in 33 fractions will be eligible. All patients will undergo pre-treatment MRI and at least weekly intra-treatment MRI. Patients undergoing MRgRT will have weekly adaptation of high dose planning target volume based on gross tumor volume response. The stage 1 of this study will enroll 15 patients to MRgRT dose adaptation. If LRC at 6 months with MRgRT dose adaptation is found sufficiently safe as per the Bayesian model, stage 2 of the protocol will expand enrollment to an additional 60 patients, randomized to either MRgRT or standard IMRT., Discussion: Multiple methods for safe treatment de-escalation in patients with HPV-positive OPC are currently being studied. By leveraging the ability of advanced MRI techniques to visualize tumor and soft tissues through the course of treatment, this protocol proposes a workflow for safe personalized radiation dose-reduction in good responders with radiosensitive tumors, while ensuring tumoricidal dose to more radioresistant tumors. MRgRT dose adaptation could translate in reduced long term radiation toxicities and improved survivorship while maintaining excellent LRC outcomes in favorable OPC., Trial Registration: ClinicalTrials.gov ID: NCT03224000; Registration date: 07/21/2017.

Background: The aim of this study was to determine the interdisciplinary agreement in identifying the post-operative tumor bed., Methods: Three radiation oncologists (ROs), four surgeons, and three radiologists segmented post-operative tumor and nodal beds for three patients with oral cavity cancer. Specialty cohort composite contours were created by STAPLE algorithm implementation results for interspecialty comparison. Dice similarity coefficient and Hausdorff distance were utilized to compare spatial differentials between specialties., Results: There were significant differences between disciplines in target delineation. There was unacceptable variation in Dice similarity coefficient for each observer and discipline when compared to the STAPLE contours. Within surgery and radiology disciplines, there was good consistency in volumes. ROs and radiologists have similar Dice similarity coefficient scores compared to surgeons., Conclusion: There were significant interdisciplinary differences in perceptions of tissue-at-risk. Better communication and explicit description of at-risk areas between disciplines is required to ensure high-risk areas are adequately targeted.

The role of radiotherapy for locally advanced pancreatic cancer (LAPC) is unclear based on studies that used conventional doses and fractionation schedules. Modern radiotherapy techniques have not been studied in depth, however. We reviewed the literature on emerging methods of delivering higher doses of conformal radiotherapy using stereotactic body radiation, intensity modulated radiation, and particle beam radiation, highlighting clinical outcomes and toxicities. The literature review suggests low rates of acute and late toxicities when higher doses of radiation are given with careful attention to normal tissue dose constraints, including for stereotactic body radiotherapy (SBRT), escalated doses with intensity modulated radiation therapy (IMRT), and particle-based therapy. Retrospective evidence suggests prolonged survival for patients who receive biological equivalent doses above 70 Gy. Prospective trials that evaluate modern radiotherapy techniques are warranted for LAPC., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Smart materials have attracted considerable attention in the medical field. In particular, shape memory alloys (SMAs) are most commonly utilized for their superelasticity (SE) in orthopaedic treatment. In this study, the resin struts of a flexible brace for adolescent idiopathic scoliosis (AIS) are replaced with different conventional materials and an SMA. The corrective mechanism mainly depends on the compressive force applied by the brace at the desired location. Therefore, the mechanical properties of the materials used and the interface pressure are both critical factors that influence the treatment effectiveness. The results indicate that titanium is the most rigid among the five types of materials, whereas the brace with SMA struts presents the best recovery properties and the most stable interface pressure. A radiographic examination of two patients with AIS is then conducted to validate the results, which shows that the SMA struts can provide better correction of thoracic curvature. These findings suggest that SMAs can be applied in orthoses because their SE allows for continuous and controllable corrective forces.

Background: In efficacy trials of a tetravalent dengue vaccine (CYD-TDV), excess hospitalizations for dengue were observed among vaccine recipients 2 to 5 years of age. Precise risk estimates according to observed dengue serostatus could not be ascertained because of the limited numbers of samples collected at baseline. We developed a dengue anti-nonstructural protein 1 (NS1) IgG enzyme-linked immunosorbent assay and used samples from month 13 to infer serostatus for a post hoc analysis of safety and efficacy., Methods: In a case-cohort study, we reanalyzed data from three efficacy trials. For the principal analyses, we used baseline serostatus determined on the basis of measured (when baseline values were available) or imputed (when baseline values were missing) titers from a 50% plaque-reduction neutralization test (PRNT 50 ), with imputation conducted with the use of covariates that included the month 13 anti-NS1 assay results. The risk of hospitalization for virologically confirmed dengue (VCD), of severe VCD, and of symptomatic VCD according to dengue serostatus was estimated by weighted Cox regression and targeted minimum loss-based estimation., Results: Among dengue-seronegative participants 2 to 16 years of age, the cumulative 5-year incidence of hospitalization for VCD was 3.06% among vaccine recipients and 1.87% among controls, with a hazard ratio (vaccine vs. control) through data cutoff of 1.75 (95% confidence interval [CI], 1.14 to 2.70). Among dengue-seronegative participants 9 to 16 years of age, the cumulative incidence of hospitalization for VCD was 1.57% among vaccine recipients and 1.09% among controls, with a hazard ratio of 1.41 (95% CI, 0.74 to 2.68). Similar trends toward a higher risk among seronegative vaccine recipients than among seronegative controls were also found for severe VCD. Among dengue-seropositive participants 2 to 16 years of age and those 9 to 16 years of age, the cumulative incidence of hospitalization for VCD was 0.75% and 0.38%, respectively, among vaccine recipients and 2.47% and 1.88% among controls, with hazard ratios of 0.32 (95% CI, 0.23 to 0.45) and 0.21 (95% CI, 0.14 to 0.31). The risk of severe VCD was also lower among seropositive vaccine recipients than among seropositive controls., Conclusions: CYD-TDV protected against severe VCD and hospitalization for VCD for 5 years in persons who had exposure to dengue before vaccination, and there was evidence of a higher risk of these outcomes in vaccinated persons who had not been exposed to dengue. (Funded by Sanofi Pasteur; ClinicalTrials.gov numbers, NCT00842530 , NCT01983553 , NCT01373281 , and NCT01374516 .).

The objective of this study is to collate and analyse adverse event reports associated with the use of complementary health products (CHP) submitted to the Health Sciences Authority (HSA) of Singapore for the period 2010-2016 to identify various trends and signals for pharmacovigilance purposes. A total of 147,215 adverse event reports suspected to be associated with pharmaceutical products and CHP were received by HSA between 2010 and 2016. Of these, 143,191 (97.3%) were associated with chemical drugs, 1,807 (1.2%) with vaccines, 1,324 (0.9%) with biological drugs (biologics), and 893 (0.6%) with CHP. The number of adverse event reports associated with Chinese Proprietary Medicine, other complementary medicine and health supplements are presented. Eight hundred and ninety three adverse event reports associated with CHP in the 7-year period have been successfully collated and analyzed. In agreement with other studies, adverse events related to the "skin and appendages disorders" were the most commonly reported. Most of the cases involved dermal allergies (e.g., rashes) associated with the use of glucosamine products and most of the adulterated products were associated with the illegal addition of undeclared drugs for pain relief. Dexamethasone, chlorpheniramine, and piroxicam were the most common adulterants detected. Reporting suspected adverse events is strongly encouraged even if the causality is not confirmed because any signs of clustering will allow rapid regulatory actions to be taken. The findings from this study help to create greater awareness on the health risks, albeit low, when consuming CHP and dispelling the common misconception that "natural" means "safe." In particular, healthcare professionals and the general public should be aware of potential adulteration of CHP. The analysis of spontaneously reported adverse events is an important surveillance system in monitoring the safety of CHP and helps in the understanding of the risk associated with the use of such products. Greater collaboration and communication between healthcare professionals, regulators, patients, manufacturers, researchers, and the general public are important to ensure the quality and safety of CHP.

In this report, titanium nitride thin film synthesized with reactive magneto-sputtering technique is proposed as an alternative surface plasmon resonance sensing material. The physical and chemical natures were initially studied by atomic force microscopy, X-ray diffraction and X-ray photoelectron spectroscopy. In virtue of white-light common-path sensing system, the wavelength modulated TiN films achieved tunable evanescent plasmonic field from 573 nm to 627 nm. The optimized TiN film with 29.8 nm thickness exhibited good differential phase sensitivity (i.e. 1.932 × 10 -7 RIU) to refractive index alteration, which is comparable to the performance of gold film. We have also attained direct measurement of biotin adsorption on the TiN and monitored sub-sequential biotin-streptavidin conjugation. It was found that TiN films have significantly higher binding affinity toward biotin than that of gold in experiments, so we are able to detect biotin directly to 0.22 µg/ml (0.90 µM) in label-free manner. The adsorption mechanism of biotin on TiN(200) are also explored with periodic density functional theory (DFT) via computer simulation and it was found that the exceptional biotin-TiN affinity may be due to the stacking formation of both N-Ti and O-Ti bonds. Also, the adsorption energy of biotin-TiN was found to be - 1.85 eV, which was two times higher than that of biotin-gold. Both experimental and computational results indicate, for the first time, that the TiN film can be directly functionalized with biotin molecules, thus it serves as an alternative plasmonic material to existing gold-based SPR biosensors., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Enterococci are important human commensals and significant opportunistic pathogens. Biofilm-related enterococcal infections, such as endocarditis, urinary tract infections, wound and surgical site infections, and medical device-associated infections, often become chronic upon the formation of biofilm. The biofilm matrix establishes properties that distinguish this state from free-living bacterial cells and increase tolerance to antimicrobial interventions. The metabolic versatility of the enterococci is reflected in the diversity and complexity of environments and communities in which they thrive. Understanding metabolic factors governing colonization and persistence in different host niches can reveal factors influencing the transition to biofilm pathogenicity. Here, we report a form of iron-dependent metabolism for Enterococcus faecalis where, in the absence of heme, extracellular electron transfer (EET) and increased ATP production augment biofilm growth. We observe alterations in biofilm matrix depth and composition during iron-augmented biofilm growth. We show that the ldh gene encoding l-lactate dehydrogenase is required for iron-augmented energy production and biofilm formation and promotes EET. IMPORTANCE Bacterial metabolic versatility can often influence the outcome of host-pathogen interactions, yet causes of metabolic shifts are difficult to resolve. The bacterial biofilm matrix provides the structural and functional support that distinguishes this state from free-living bacterial cells. Here, we show that the biofilm matrix can immobilize iron, providing access to this growth-promoting resource which is otherwise inaccessible in the planktonic state. Our data show that in the absence of heme, Enterococcus faecalis l-lactate dehydrogenase promotes EET and uses matrix-associated iron to carry out EET. Therefore, the presence of iron within the biofilm matrix leads to enhanced biofilm growth., (Copyright © 2018 Keogh et al.)

Background: Orthotic insoles that are made of foam material often have less breathability and thus cause discomfort to the wearer. Given that a sandwich structure offers better porosity and breathability that would improve comfort, the impact of custom-made insoles made with three-dimensional spacer fabric is studied., Objectives: To examine the biomechanical effects and subjective comfort of spacer-fabric insoles during walking., Study Design: Repeated measures., Methods: Plantar pressure and lower limb muscle activity data are collected from 12 subjects. Subjective perceived comfort is measured after five successful walking trials for each of the three different insoles worn: traditional insoles made with ethylene vinyl acetate and two types of spacer-fabric insoles., Results: Compared to the use of traditional insoles, there is a statistically significant reduction in the peak pressure (>8%) and pressure-time integral (>16%) in the toes and metatarsal head 1 with the use of the spacer-fabric insoles as the top layer. Insoles with two layers of spacer fabrics have the highest perceived comfort ( p < 0.01). However, there is no significant difference in the selected muscle activity for all three insoles., Conclusion: Insoles with different arrangements of spacer fabrics allow changes in pressure patterns across the plantar foot and perception of comfort while walking. The findings enhance current understanding on the use of textile-fabricated materials, which provide alternative solutions for modifying insoles. Clinical relevance The key features of spacer fabric offer a viable option for different orthotic insole applications. The results will greatly contribute toward insole prescription, potentially enhancing the efficacy of orthotic performance and increasing the range of insole materials.

Objectives: To investigate the impact of 3-Diminsional (3D) tumor volume (TV) and extent of involvement of primary tumor on treatment outcomes in a large uniform cohort of T3 laryngeal carcinoma patients treated with nonsurgical laryngeal preservation strategies., Materials and Methods: The pretreatment contrast-enhanced computed tomography images of 90 patients with T3 laryngeal carcinoma were reviewed. Primary gross tumor volume (GTVp) was delineated to calculate the 3D TV and define the extent of invasion. Cartilage and soft tissue involvement was coded. The extent of invasion was dichotomized into non/limited invasion versus multiple invasion extension (MIE), and was subsequently correlated with survival outcomes., Results: The median TV was 6.6 cm 3 . Sixty-five patients had non/limited invasion, and 25 had MIE. Median follow-up for surviving patients was 52 months. The 5-year local control and overall survival rates for the whole cohort were 88% and 68%, respectively. There was no correlation between TV and survival outcomes. However, patients with non/limited invasion had better 5-year local control (LC) than those with MIE (95% vs 72%, p = .009) but did not have a significantly higher rate of overall survival (OS) (74% vs 67%, p = .327). In multivariate correlates of LC, MIE maintained statistical significance whereas baseline airway status showed a statistically significance trend with poor LC (p = .0087 and 0.06, respectively). Baseline good performance status was an independent predictor of improved OS (p = .03) in multivariate analysis., Conclusion: The extent of primary tumor invasion is an independent prognostic factor of LC of the disease after definitive radiotherapy in T3 larynx cancer., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: There are few published studies to guide the treatment of carcinoma metastatic to the neck from an unknown primary (CUP). In this regard, the objective of the current study was to share the authors' current experience treating patients with CUP using intensity-modulated radiation therapy (IMRT), which principally targeted both sides of the neck, the nasopharynx, and the oropharynx., Methods: This was a retrospective study in which an institutional database search was conducted to identify patients with CUP who received IMRT. Data analysis included frequency tabulation, survival analysis, and multivariable analysis., Results: Two-hundred sixty patients met inclusion criteria. The most common lymph node category was N2b (54%). IMRT volumes included the entire pharyngolaryngeal mucosa in 78 patients, the nasopharynx and oropharynx in 167 patients, and treatment limited to the involved neck in 11 patients. Eighty-four patients underwent neck dissections. The 5-year overall survival, regional control, and distant metastases-free survival rates were 84%, 91%, and 94%, respectively. Over 40% of patients had gastrostomy tubes during therapy, and 7% patients were diagnosed with chronic radiation-associated dysphagia. Higher lymph node burden was associated with worse disease-related outcomes, and in subgroup analysis, patients with human papillomavirus-associated disease had better outcomes. No therapeutic modality was statistically associated with either disease-related outcomes or toxicity., Conclusions: Comprehensive IMRT with treatment to both sides of the neck and to the oropharyngeal and nasopharyngeal mucosa results in high rates of disease control and survival. The investigators were unable to demonstrate that treatment intensification with chemotherapy or surgery added benefit or excessive toxicity. Cancer 2018;124:1415-27. © 2018 American Cancer Society., (© 2018 American Cancer Society.)

Pancreatic cancer is a devastating disease with poor survival outcomes. Recent studies have shown that the addition of radiotherapy to chemotherapy in the setting of locally advanced pancreatic cancer did not improve overall survival outcome. These studies commonly utilize conventional radiotherapy treatment fractionation and technique (typically 3-D conformal radiotherapy or intensity modulated radiotherapy). Although no clear benefit in overall survival was demonstrated in those studies, those who received radiotherapy did have a clear benefit in terms of local control. Therefore, there is increasing interest in exploring different techniques and/or modality of radiotherapy and dose/fractionation. Stereotactic radiotherapy, which employs a hypofractionated regimen, has the potential advantage of delivering a high dose of radiation to the tumor in a short period of time (typically over 5 days) with minimal dose to the surrounding normal structures. Particle therapy such as proton and carbon ion therapy are being explored as potential radiation modality that could cause greater biological damage to the tumor compared to photon treatment, with rapid dose falloff resulting in minimal to no dose to adjacent structures. This review will discuss the current literature and emerging roles of stereotactic radiotherapy and particle therapy in pancreatic cancer., Competing Interests: The authors declare no conflict of interest.

A highly efficient and pH-universal hydrogen evolution reaction (HER) electrocatalyst with a sandwich-architecture constructed using zero-dimensional N- and P-dual-doped core-shell Co 2 P@C nanoparticles embedded into a 3 D porous carbon sandwich (Co 2 P@N,P-C/CG) was synthesized through a facile two-step hydrothermal carbonization and pyrolysis method. The interfacial electron transfer rate and the number of active sites increased owing to the synergistic effect between the N,P-dual-doped Co 2 P@C core-shell and sandwich-nanostructured substrates. The presence of a high surface area and large pore sizes improved the mass-transfer dynamics. This nanohybrid showed remarkable electrocatalytic activity toward the HER in a wide pH range with good stability. The computational study and experiments revealed that the carbon atoms close to the N and P dopants on the shell of Co 2 P@N,P-C were effective active sites for HER catalysis and that both Co 2 P and the N,P dopants gave rise to an optimized binding free energy of H on the active sites., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Syngeneic murine tumor models have been widely used by researchers to assess changes in tumor susceptibility associated with exposure to toxicants. Two common tumor models used to define host resistance against transplanted tumors in vivo are EL4 mouse lymphoma cells (established from a lymphoma induced in a C57BL/6 mouse by 9,10-dimethyl-1,2-benzanthracene) and B16F10 mouse melanoma cells (derived through variant selection from a B16 melanoma arising spontaneously in C57BL/6 mice). While C57BL/6 mice are commonly used as the syngeneic host for these tumor models, other mouse strains such as B 6 C 3 F 1 (C57BL/6 × C3H) can also be used. Tumor challenge of the host can be done by subcutaneous (sc) or intravenous (iv) injection, depending upon whether the effects are to be examined on local tumor development or experimental/artificial metastasis. Materials and methodologies for injection of both tumor cell models are described in detail in the subsequent sections.

Adolescent idiopathic scoliosis (AIS) is a multifactorial, three-dimensional deformity of the spine and trunk. School scoliosis screening (SSS) is recommended by researchers as a means of early detection of AIS to prevent its progression in school-aged children. The traditional screening technique for AIS is the forward bending test because it is simple, non-invasive and inexpensive. Other tests, such as the use of Moiré topography, have reduced the high false referral rates. The use of infrared (IR) thermography for screening purposes based on the findings of previous studies on the asymmetrical paraspinal muscle activity of scoliotic patients compared with non-scoliotic subjects was explored in this study. IR thermography is performed with an IR camera to determine the temperature differences in paraspinal muscle activity. A statistical analysis showed that scoliotic subjects demonstrate a statistically significant difference between the left and right sides of the regions of interest. This difference could be due to the higher IR emission of the convex side of the observed area, thereby creating a higher temperature distribution. The findings of this study suggest the feasibility of incorporating IR thermography as part of SSS. However, future studies could also consider a larger sample of both non-scoliotic and scoliotic subjects to further validate the findings.

Background: The purpose of this study was to present our experience with retropharyngeal node reirradiation using highly conformal radiotherapy (RT)., Methods: A retrospective screen of 2504 consecutively irradiated patients with head and neck malignancies between 2005 and 2015 identified 19 patients who underwent reirradiation for retropharyngeal node metastasis. Clinical and toxicity outcomes were assessed in these patients., Results: Thirteen patients (68%) had squamous cell carcinoma. Eleven patients (58%) received conventionally fractionated intensity-modulated radiotherapy (IMRT) or proton therapy, and 8 patients (42%) received single-fractionated or hypofractionated stereotactic RT. Fourteen patients (74%) received chemotherapy. Median follow-up was 14.7 months. The 1-year local control, locoregional control, overall survival, and progression-free survival rates were 100%, 94%, 92%, and 92%, respectively. Three patients (16%) experienced acute grade 3 toxicity and occurred in those treated with IMRT. There was no late grade ≥3 toxicity., Conclusion: Retropharyngeal node reirradiation with conformal therapy is well tolerated and associated with excellent short-term disease control., (© 2017 Wiley Periodicals, Inc.)

Angiopoietin-like 4 (ANGPTL4) is a secretory protein that can be cleaved to form an N-terminal and a C-terminal protein. Studies performed thus far have linked ANGPTL4 to several cancer-related and metabolic processes. Notably, several point mutations in the C-terminal ANGPTL4 (cANGPTL4) have been reported, although no studies have been performed that ascribed these mutations to cancer-related and metabolic processes. In this study, we compared the characteristics of tumors with and without wild-type (wt) cANGPTL4 and tumors with cANGPTL4 bearing the T266M mutation (T266M cANGPTL4). We found that T266M cANGPTL4 bound to integrin α5β1 with a reduced affinity compared to wt, leading to weaker activation of downstream signaling molecules. The mutant tumors exhibited impaired proliferation, anoikis resistance, and migratory capability and had reduced adenylate energy charge. Further investigations also revealed that cANGPTL4 regulated the expression of Glut2. These findings may explain the differences in the tumor characteristics and energy metabolism observed with the cANGPTL4 T266M mutation compared to tumors without the mutation., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Indoor slippers with a strap across the dorsal forefoot are popular with older women. However, their influence on the foot motion has not been reported. This study evaluated the range of movement in the knee and ankle joints during walking and changes in trunk displacement during sit-to-stand when 10 healthy older women wore two types of slippers and were barefoot. Compared to barefeet, walking in slippers results in significant increases in the knee flexion angle in the swing phase. However, there is nonsignificant differences in the ankle angle in any phase across all conditions. During the sit-stand transition when slippers are worn, there is a significant reduction in the peak trunk tilt angle and range, as well as the duration of the weight shift when motion is initiated. The findings therefore provide a better understanding of slipper features and designs associated with changes in foot kinematics in older women.

Threatened miscarriage is the most common gynecological emergency, occurring in about 20% of pregnant women. Approximately one in four of these patients go on to have spontaneous miscarriage and the etiology of miscarriage still remains elusive. In a bid to identify possible biomarkers and novel treatment targets, many studies have been undertaken to elucidate the pathways that lead to a miscarriage. Luteal phase deficiency has been shown to contribute to miscarriages, and the measurement of serum progesterone as a prognostic marker and the prescription of progesterone supplementation has been proposed as possible diagnostic and treatment methods. However, luteal phase deficiency only accounts for 35% of miscarriages. In order to understand the other causes of spontaneous miscarriage and possible novel urine biomarkers for miscarriage, we looked at the changes in urinary metabolites in women with threatened miscarriage. To this end, we performed a case-control study of eighty patients who presented with threatened miscarriage between 6 and 10 weeks gestation. Urine metabolomics analyses of forty patients with spontaneous miscarriages and forty patients with ongoing pregnancies at 16 weeks gestation point to an impaired placental mitochondrial β-oxidation of fatty acids as the possible cause of spontaneous miscarriage. This study also highlighted the potential of urine metabolites as a non-invasive screening tool for the risk stratification of women presenting with threatened miscarriage.

Extracellular vesicles (EVs) are abundant in various biological fluids including blood, saliva, urine, as well as extracellular milieu. Accumulating evidence has indicated that EVs, which contain functional proteins and small RNAs, facilitate intercellular communication between neighbouring cells, and are critical to maintain various physiological processes. In contrast, EV-derived toxic signals can spread out over the tissues adjacent to the injured area in certain diseases, including brain tumors and neurodegenerative disorders. This demands better characterization of EVs which can be employed for liquid biopsy clinically as well as for the study of intercellular signalling. Exosomes and microvesicles share a number of similar characteristics, but it is important to distinguish between these two types of EVs. Here, we report for the first time that our in-house developed Localized Surface Plasmon Resonance biosensor with self-assembly gold nanoislands (SAM-AuNIs) can be used to detect and distinguish exosomes from MVs isolated from A-549 cells, SH-SY5Y cells, blood serum, and urine from a lung cancer mouse model. Exosomes, compared with MVs, produced a distinguishable response to the bare LSPR biosensor without functionalization, suggesting a different biophysical interaction between exosomes and MVs with SAM AuNIs. This sensor attains the limit of detection to 0.194µg/ml, and the linear dynamic range covers 0.194-100µg/ml. This discovery not only reveals great insight into the distinctive membrane property of tumor-derived exosomes and MVs, but also facilitate the development of novel LSPR biosensors for direct detection and isolation of heterogeneous EVs., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Surface modification by metal doping is an effective treatment technique for improving surface properties for CO 2 reduction. Herein, the effects of doped Pd, Ru, and Cu on the adsorption, activation, and reduction selectivity of CO 2 on CeO 2 (111) were investigated by periodic density functional theory. The doped metals distorted the configuration of a perfect CeO 2 (111) by weakening the adjacent Ce-O bond strength, and Pd doping was beneficial for generating a highly active O vacancy. The analyses of adsorption energy, charge density difference, and density of states confirmed that the doped metals were conducive for enhancing CO 2 adsorption, especially for Cu/CeO 2 (111). The initial reductive dissociation CO 2 → CO* + O* on metal-doped CeO 2 (111) followed the sequence of Cu- > perfect > Pd- > Ru-doped CeO 2 (111); the reductive hydrogenation CO 2 + H → COOH* followed the sequence of Cu- > perfect > Ru- > Pd-doped CeO 2 (111), in which the most competitive route on Cu/CeO 2 (111) was exothermic by 0.52 eV with an energy barrier of 0.16 eV; the reductive hydrogenation CO 2 + H → HCOO* followed the sequence of Ru- > perfect > Pd-doped CeO 2 (111). Energy barrier decomposition analyses were performed to identify the governing factors of bond activation and scission along the initial CO 2 reduction routes. Results of this study provided deep insights into the effect of surface modification on the initial reduction mechanisms of CO 2 on metal-doped CeO 2 (111) surfaces.

Plasmonic enhanced dye-sensitized solar cells (DSSCs) with metallic nanostructures suffer from corrosion problems, especially with the presence of the iodine/triiodide redox couple in the electrolyte. Herein, we introduce an alternative approach by compensating the corrosion with a modified liquid electrolyte. In contrast to the existing method of surface preservation for plasmonic nanostructures, the redox-controlled electrolyte (RCE) contains iodoaurate intermediates, i.e. gold(i) diiodide (AuI 2 - ) and gold(iii) tetraiodide (AuI 4 - ) with optimal concentrations, such that these intermediates are readily reduced to gold nanoparticles during the operation of DSSCs. As corrosion and redeposition of gold occur simultaneously, it effectively provides corrosion compensation to the plasmonic gold nanostructures embedded in the photoanode. Cycling tests of the specific amount of gold contents in the RCE of DSSCs support the fact that the dissolution and deposition of gold are reversible and repeatable. This gold deposition on the TiO 2 photoanode results in forming a Schottky barrier (SB) at the metal-semiconductor interface and effectively inhibits the recombination of electron-hole pairs. Therefore, the RCE increases the short-circuit current, amplifies the open-circuit voltage, and reduces the impedance of the TiO 2 /dye interface. The power conversion efficiency of DSSCs was improved by 57% after incorporating the RCE.

Regulation of blood glucose requires precise coordination between different endocrine systems and multiple organs. Type 2 diabetes mellitus (T2D) arises from a dysregulated response to elevated glucose levels in the circulation. Globally, the prevalence of T2D has increased dramatically in all age groups. T2D in older adults is associated with higher mortality and reduced functional status, leading to higher rate of institutionalization. Despite the potential healthcare challenges associated with the presence of T2D in the elderly, the pathogenesis and phenotype of late-onset T2D is not well studied. Here we applied untargeted metabolite profiling of urine samples from people with and without late-onset T2D using ultra-performance liquid-chromatography mass-spectrometry (UPLC-MS) to identify urinary biomarkers for late-onset T2D in the elderly. Statistical modeling of measurements and thorough validation of structural assignment using liquid chromatography tandem mass-spectrometry (LC-MS/MS) have led to the identification of metabolite biomarkers associated with late-onset T2D. Lower levels of phenylalanine, acetylhistidine, and cyclic adenosine monophosphate (cAMP) were found in urine samples of T2D subjects validated with commercial standards. Elevated levels of 5'-methylthioadenosine (MTA), which previously has only been implicated in animal model of diabetes, was found in urine of older people with T2D.

An immunological Correlate of Protection (CoP) is an immune response that is statistically interrelated with protection. Identification of CoPs for enteric vaccines would help design studies to improve vaccine performance of licensed vaccines in low income settings, and would facilitate the testing of future vaccines in development that might be more affordable. CoPs are lacking today for most existing and investigational enteric vaccines. In order to share the latest information on CoPs for enteric vaccines and to discuss novel approaches to correlate mucosal immune responses in humans with protection, the Foundation Mérieux organized an international conference of experts where potential CoPs for vaccines were examined using case-studies for both bacterial and viral enteric pathogens. Experts on the panel concluded that to date, all established enteric vaccine CoPs, such as those for hepatitis A, Vi typhoid and poliovirus vaccines, are based on serological immune responses even though these may poorly reflect the relevant gut immune responses or predict protective efficacy. Known CoPs for cholera, norovirus and rotavirus could be considered as acceptable for comparisons of similarly composed vaccines while more work is still needed to establish CoPs for the remaining enteric pathogens and their candidate vaccines. Novel approaches to correlate human mucosal immune responses with protection include the investigation of gut-originating antibody-secreting cells (ASCs), B memory cells and follicular helper T cells from samples of peripheral blood during their recirculation., (Copyright © 2017.)

3-nitro-l-tyrosine (3-NT) is believed to be a biomarker of neurodegenerative diseases and metal doped graphene possess exceptionally high binding energy of 3-NT with metal-nitro chemisorption. Here we report a novel label-free detection scheme of 3-NT via nickel-doped graphene (NDG) as the functionalized receptor on our phase detecting localized surface plasmon resonance (LSPR) biosensor. When compared with reported 3-NT immunoassay with enzyme-linked immunosorbent assay (ELISA), our NDG-LSPR platform offers two advantages i.e. 1) label-free and 2) capture of 3-NT by direct chemisorption. Our limit of detection for 3-NT in PBS was found to be 0.13pg/ml and the linear dynamic range of response was from 0.5pg/ml to 1ng/ml, i.e. four orders of magnitude. The specificity of our NDG receptor to 3-NT was also verified with l-tyrosine of equivalent concentrations in PBS and diluted human serum, for which the NDG receptor shows negligible responses. In addition, the adsorption of 3-NT and l-tyrosine to the NDG receptor were also investigated by atomic force microscopy and further verified by surface enhanced Raman spectroscopy. Therefore, our NDG-LSPR biosensor competes favorably against ELISA and we believe it should be an attractive and economical solution to early diagnostic of 3-NT related disorders for clinical applications., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: This prospective study aims to determine the impact of PET/CT on radiotherapy planning and outcomes in patients with oesophageal cancer., Methods: All patients underwent PET/CT scanning in the radiotherapy treatment position, and received treatment planned using the PET/CT dataset. GTV was defined separately on PET/CT (GTV-PET) and CT (GTV-CT) datasets. A corresponding PTV was generated for each patient. Volumetric and spatial analysis quantified the proportion of FDG-avid disease not included in CT-based volumes. Clinical data was collected to determine locoregional control and overall survival rates., Results: 13 (24.1%) of 57 accrued patients had metastatic disease detected on PET. Median follow up was 4 years. FDG-avid disease would have been excluded from GTV-CT in 29 of 38 patients (76%). In 5 patients, FDG-avid disease would have been completely excluded from the PTV-CT. GTV-CT underestimated the cranial and caudal extent of FDG-avid tumour in 14 (36%) and 10 (26%) patients. 4-Year overall survival and locoregional failure free survival were 37% and 65%., Conclusions: PET/CT altered the delineation of tumour volumes when compared to CT alone, and should be considered standard for treatment planning. Although clinical outcomes were not improved with PET/CT planning, it did allow the use of smaller radiotherapy volumes.

Background/purpose: Individuals with low income bear a number of health challenges to healthcare services. Vancouver's Downtown Eastside (DTES) is known to be a low-income community in a metropolitan city. Because it is difficult to reach, the oral health (OH) status of these residents is unknown. The objectives of this study are (1) to design a tool and strategy to collect OH information in a low-income community, (2) to characterize the OH status and related factors among low-income adults, and (3) to identify the explanatory factors for their OH status., Materials and Methods: Mobile screening clinics were established in the gathering centers of the DTES, and those of 19 years of age or older were recruited. Data were collected through survey interviews and clinical examinations. Potential explanatory factors were investigated by regression analysis., Results: The 356 screened participants were mostly males, middle-aged, less educated, and living with low income (≤CAD$20,000/y). About 80% had dental coverage, mostly from public programs (94%). Many (86%) perceived a dental need. Among dentate participants ( n  = 306), on average, 3.8 decayed, 8.6 missing, 4.9 filled teeth, and a care index of 41.5% were observed. Social factors (barriers to care and length of DTES residence), dental hygiene (brushing/flossing), and personal (hepatitis C virus infection/methadone usage) factors contributed to their care index level., Conclusion: This is the first time that comprehensive information regarding OH status has been collected from a low-income, inner-city community in Canada. Further investigations in the challenges and needs in accessing dental care may develop solutions for better OH in similar communities.

Background: Prostate cancer management involves a balance between the risks of cancer death against those from other causes. To evaluate the performance of several comorbidity indices in predicting comorbid death in a prostate cancer radiotherapy cohort., Methods: 2,131 men with localised prostate cancer treated with radical radiotherapy between 1999 and 2007 were studied. Tumour features, androgen deprivation usage, age, number of prescription medications (PMN) and Adult Comorbidity Evaluation-27 Index (ACE-27) were recorded. Death from prostate cancer (DPC) and death from other causes (DOC) were analysed as competing causes of death using a competing risks model, with discrimination assessed using the concordance index., Results: ACE-27 scores correlated with patient's PMN (median PMN = 2). Tumour features were independent of ACE-27 scores. Estimated cumulative incidences of DOC and DPC at 10 years were 16.4% and 7.7% respectively. In the low/intermediate risk group ( n  = 1026) there was a 3.4-fold predominance of DOC inside 10 years (cumulative incidence: 15.8% DOC vs 3.4% DPC). High-risk men had approximately equal rates of DPC and DOC at 10 years. Multivariable analysis showed age, ACE-27 score ≥ 1 and PMN to have significant associations with DOC ( P  < 0.002 for all). A multivariable model incorporating all 3 variables resulted in C-Index = 0.646., Conclusion: Age, ACE-27 score and PMN act as independent prognostic factors for DOC in prostate cancer patients and can improve patient's life expectancy prediction.

Using self-assembly gold nanoislands (SAM-AuNIs) functionalized by poly(m-phenylenediamine-co-aniline-2-sulfonic acid) (poly(mPD-co-ASA)) copolymer nanoparticles as specific receptors, a highly sensitive localized surface plasmon resonance (LSPR) optochemical sensor is demonstrated for detection of trace lead cation (Pb(II)) in drinking water. The copolymer receptor is optimized in three aspects: (1) mole ratio of mPD:ASA monomers, (2) size of copolymer nanoparticles, and (3) surface density of the copolymer. It is shown that the 95:5 (mPD:ASA mole ratio) copolymer with size less than 100 nm exhibits the best Pb(II)-sensing performance, and the 200 times diluted standard copolymer solution contributes to the most effective functionalization protocol. The resulting poly(mPD-co-ASA)-functionalized LSPR sensor attains the detection limit to 0.011 ppb toward Pb(II) in drinking water, and the linear dynamic range covers 0.011 to 5000 ppb (i.e., 6 orders of magnitude). In addition, the sensing system exhibits robust selectivity to Pb(II) in the presence of other metallic cations as well as common anions. The proposed functional copolymer functionalized on AuNIs is found to provide excellent Pb(II)-sensing performance using simple LSPR instrumentation for rapid drinking-water inspection.

Open-toe mule slippers are popular footwear worn at home especially by older women. However, their biomechanical effects are still poorly understood. The objective of this study is to therefore evaluate the physical properties of two typical types of open-toe mule slippers and the changes in plantar pressure and lower limb muscle activity of older women when wearing these slippers. Five walking trials have been carried out by ten healthy women. The results indicate that compared to barefoot, wearing slippers results in significant increases in the contact area of the mid-foot regions which lead to plantar pressure redistribution from metatarsal heads 2-3 and the lateral heel to the midfoot regions. However, there is no significant difference in the selected muscle activity across all conditions. The findings enhance our understanding of slipper features associated with changes in biomechanical measures thereby providing the basis of slipper designs for better foot protection and comfort., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Turning during locomotion involves considerable changes of the body's center of mass and reduced stability, as well as lower limb kinematics and kinetics. However, many previous studies have been carried out to evaluate the effectiveness and applications of orthotic insoles as well as different types of orthotic materials in various clinical symptoms, which are focused primarily on straight line walking. Hence, the influence of custom-made insoles with the use of advanced three-dimensional spacer fabrics on biomechanics parameters in terms of plantar pressure distribution and lower limb electromyography during turning movement was studied., Methods: Twelve subjects performed 180-degree turning at a speed 3.07-3.74 km/h for five successful trials under 3 insoles conditions: wearing traditional ethylene vinyl acetate insoles and two different spacer-fabricated insoles, with the plantar pressure and lower limb muscle activity collected simultaneously. Turning movement was broken down into 3 phases for analysis: Turning initiation, turn around and turn termination., Results: There was a statistically significance difference in plantar pressure between the traditional insoles and the insoles made of a spacer fabric as the top layer (p < 0.05). Compared to the traditional insoles, insoles made of a spacer fabric reduced the peak pressure (>12 %) and pressure-time integral (>13 %) in toes, metatarsal head 1 and metatarsal heads 2-3 at turning initiation; (>15 %) and (>17 %) in medial midfoot and medial heel at turn around. Insoles with spacer fabrics on the top and middle layer reduced both pressure parameters (>18 %) in toes and MTH 1 at turn termination. In terms of muscle activities, insoles with two-layer spacer fabrics could lower maximum muscle activities of vastus lateralis (>16 %; p < 0.05) at turn around., Conclusions: Insoles with different fabrications could offer various pressure offloading patterns across the plantar and muscle activity changes while turning. Insoles with a spacer fabric on the top tend to reduce plantar pressure loading at different regions during turn initiation and turn around phases, while two-layer spacer-fabricated insoles may contribute to reduced vastus lateralis muscle activation during turn around. More importantly, this study provides a new dimension in the potential use of the textile-fabricated insoles which may widen the range of insole materials selection in the design and development of insoles so as to enhance the effectiveness of orthotic treatment.

PtSn alloy, which is a potential material for use in direct methanol fuel cells, can efficiently promote methanol oxidation and alleviate the CO poisoning problem. Herein, methanol decomposition on Pt3Sn(111) was systematically investigated using periodic density functional theory and microkinetic modeling. The geometries and energies of all of the involved species were analyzed, and the decomposition network was mapped out to elaborate the reaction mechanisms. Our results indicated that methanol and formaldehyde were weakly adsorbed, and the other derivatives (CHxOHy, x = 1-3, y = 0-1) were strongly adsorbed and preferred decomposition rather than desorption on Pt3Sn(111). The competitive methanol decomposition started with the initial O-H bond scission followed by successive C-H bond scissions, (i.e., CH3OH → CH3O → CH2O → CHO → CO). The Brønsted-Evans-Polanyi relations and energy barrier decomposition analyses identified the C-H and O-H bond scissions as being more competitive than the C-O bond scission. Microkinetic modeling confirmed that the vast majority of the intermediates and products from methanol decomposition would escape from the Pt3Sn(111) surface at a relatively low temperature, and the coverage of the CO residue decreased with an increase in the temperature and decrease in partial methanol pressure.

Pressure therapy garments apply pressure to suppress the growth and flatten hypertrophic scars caused by serious burns. The amount of pressure given by the pressure garments is critical to the treatment adherence and outcomes. In the present study, a biomechanical model for simulating the pressure magnitudes and distribution over hand dorsum given by a pressure glove was developed by using finite element method. In this model, the shape geometry of the hand, the mechanical properties of the glove and human body tissues were incorporated in the numerical stress analyses. The geometry of the hand was obtained by a 3D laser scanner. The material properties of two warp knitted fabrics were considered in the glove fabric model that developed from the glove production pattern with 10% size reduction in circumferential dimensions. The glove was regarded an isotropic elastic shell and the hand was assumed to be a homogeneous, isotropic and linearly elastic body. A glove wearing process was carried in the finite element analysis and the surface-to-surface contact pressure between hand and glove fabric was hence obtained. Through validation, the simulated contact pressure showed a good agreement with the experimental interface pressure measurement. The simulation model can be used to predict and visualise the pressure distribution exerted by a pressure therapy glove onto hand dorsum. It can provide information for optimising the material mechanical properties in pressure garment design and development, give a clue to understand the mechanisms of pressure action on hypertrophic scars and ultimately improve the medical functions of pressure garment., (Copyright © 2015 Elsevier Ltd and ISBI. All rights reserved.)

Cigarette smoke exposure has been considered a risk factor for infection with Chlamydia pneumoniae. C. pneumoniae infection is associated with respiratory tract infection and chronic respiratory disease, which is a serious public health concern. To determine whether prior exposure to cigarette smoke worsens C. pneumoniae infection (specifically, increases infectious burden and systemic dissemination) as well as alters cytokine responses in mice, adult female C57BL/6 mice were exposed to either filtered air (FA) or mainstream cigarette smoke (MCS) (15 mg/m(3), total suspended particulates) for 5 days/week for 2 weeks and then infected with C. pneumoniae (10(5) IFU) via intratracheal instillation. Mice were euthanized on Days 7, 14 or 26 post-infection (p.i.). Chlamydial burdens in the lungs and spleen were quantified by quantitative PCR (qPCR) and histologic analyses were performed; cytokine levels (TNFα, IL-4, IFNγ) in bronchoalveolar lavage fluid and serum were assayed by enzyme-linked immunosorbent assay (ELISA). The results indicated that: (1) mice exposed to either FA or MCS had similar chlamydial burdens in the lungs and spleen on Days 14 and 26 p.i.; (2) proximal and distal airway inflammation was observed on Day 14 p.i. in both FA and MCS mice, but persisted in MCS mice until Day 26 p.i.; FA exposed mice demonstrated resolution of distal airway inflammation; and (3) MCS mice displayed higher serum levels of IFNγ and IL-4 on Day 26 p.i. These findings indicate that exposure of mice to MCS (at a concentration equivalent to smoking < 1 pack cigarettes/day) led to greater C. pneumoniae-induced inflammation, as indicated by prolonged inflammatory changes.

Cases of synchronous prostate and colorectal adenocarcinomas have been sporadically reported. There are case reports on patients with synchronous prostate and rectal cancers treated with external beam radiotherapy alone or combined with high-dose rate brachytherapy boost to the prostate. Here, we illustrate a patient with synchronous prostate and rectal cancers treated using the volumetric arc therapy (VMAT) technique. The patient was treated with radical radiotherapy to 50.4 Gy in 28 fractions to the pelvis, incorporating the involved internal iliac node and the prostate. A boost of 24 Gy in 12 fractions was delivered to the prostate only, using VMAT. Treatment-related toxicities and follow-up prostate-specific antigen and carcinoembryonic antigen were collected for data analysis. At 12 months, the patient achieved complete response for both rectal and prostate cancers without significant treatment-related toxicities.

Purpose: To assess the diagnostic performance of pretreatment (18)F-fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) and its impact on radiation therapy treatment decisions in patients with locally advanced breast cancer (LABC)., Methods and Materials: Patients with LABC with Eastern Cooperative Oncology Group performance status <2 and no contraindication to neoadjuvant chemotherapy, surgery, and adjuvant radiation therapy were enrolled on a prospective trial. All patients had pretreatment conventional imaging (CI) performed, including bilateral breast mammography and ultrasound, bone scan, and CT chest, abdomen, and pelvis scans performed. Informed consent was obtained before enrolment. Pretreatment whole-body (18)F-FDG PET/CT scans were performed on all patients, and results were compared with CI findings., Results: A total of 154 patients with LABC with no clinical or radiologic evidence of distant metastases on CI were enrolled. Median age was 49 years (range, 26-70 years). Imaging with PET/CT detected distant metastatic disease and/or locoregional disease not visualized on CI in 32 patients (20.8%). Distant metastatic disease was detected in 17 patients (11.0%): 6 had bony metastases, 5 had intrathoracic metastases (pulmonary/mediastinal), 2 had distant nodal metastases, 2 had liver metastases, 1 had pulmonary and bony metastases, and 1 had mediastinal and distant nodal metastases. Of the remaining 139 patients, nodal disease outside conventional radiation therapy fields was detected on PET/CT in 15 patients (10.8%), with involvement of ipsilateral internal mammary nodes in 13 and ipsilateral level 5 cervical nodes in 2., Conclusions: Imaging with PET/CT provides superior diagnostic and staging information in patients with LABC compared with CI, which has significant therapeutic implications with respect to radiation therapy management. Imaging with PET/CT should be considered in all patients undergoing primary staging for LABC., (Crown Copyright © 2015. Published by Elsevier Inc. All rights reserved.)

Objective: The impact of pressure glove tightness on maximum grip force, muscle activity, and psychophysical responses is investigated to facilitate the prescription of a suitable reduction factor (RF) for pressure treatment., Background: The wearing of pressure therapy gloves is often considered to hinder hand performance and cause discomfort, resulting in unsatisfactory treatment adherence during burn rehabilitation., Method: A wear trial was carried out with 10 participants for three custom-made pressure gloves that consist of different RFs-10%, 15% and 20%-as well as for the bare hand. The surface electromyography of three forearm muscles was measured during tasks that involve moving marbles, buttoning a shirt, and typing. The psychophysical responses were also recorded., Results: The use of pressure gloves results in a reduction in the maximum gripping force. Gloves with tighter pressure contribute to lower perceived comfort and ease of hand motion. Increased glove tightness (with RFs of 15% and 20%) decreases muscle activity as compared to the bare-hand condition when buttoning a shirt. In terms of typing, the forearm muscle activity increases with high glove pressure (RF of 20%)., Conclusion: The forearm muscles are significantly affected by glove tightness in performing different daily tasks that required gripping, pinching, and typing. The increase of RF of pressure gloves causes negative impact on psychophysical response and handgrip strength. Glove tightness in relation to hand performance and comfort is important in prescribing an optimal pressure therapy glove for hypertrophic scar treatment., Application: The findings give insight into the impacts of pressure glove tightness on muscle activity, thus providing a reference for glove development., (© 2015, Human Factors and Ergonomics Society.)

The exponential growth in the employment of nanomaterials (NMs) has given rise to the field of nanotoxicology; which evaluates the safety of engineered NMs. Initial nanotoxicological studies were limited by a lack of both available materials and accurate biodispersion characterization tools. However, the years that followed were marked by the development of enhanced synthesis techniques and characterization technologies; which are now standard practice for nanotoxicological evaluation. Paralleling advances in characterization, significant progress was made in correlating specific physical parameters, such as size, morphology, or coating, to resultant physiological responses. Although great strides have been made to advance the field, nanotoxicology is currently at a crossroads and faces a number of obstacles and technical limitations not associated with traditional toxicology. Some of the most pressing and influential challenges include establishing full characterization requirements, standardization of dosimetry, evaluating kinetic rates of ionic dissolution, improving in vitro to in vivo predictive efficiencies, and establishing safety exposure limits. This Review will discuss both the progress and future directions of nanotoxicology: highlighting key previous research successes and exploring challenges plaguing the field today., (Published by Oxford University Press on behalf of the Society of Toxicology 2015. This work is written by US Government employees and is in the public domain in the US.)