Survey of patient-specific quality assurance practice for IMRT and VMAT.

A first-time survey across 15 cancer centers in Ontario, Canada, on the current practice of patient-specific quality assurance (PSQA) for intensity modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT) delivery was conducted. The objectives were to assess the current state of PSQA practice, identify areas for potential improvement, and facilitate the continued improvement in standardization, consistency, efficacy, and efficiency of PSQA regionally. The survey asked 40 questions related to PSQA practice for IMRT/VMAT delivery. The questions addressed PSQA policy and procedure, delivery log evaluation, instrumentation, measurement setup and methodology, data analysis and interpretation, documentation, process, failure modes, and feedback. The focus of this survey was on PSQA activities related to routine IMRT/VMAT treatments on conventional linacs, including stereotactic body radiation therapy but excluding stereotactic radiosurgery. The participating centers were instructed to submit answers that reflected the collective view or opinion of their department and represented the most typical process practiced. The results of the survey provided a snapshot of the current state of PSQA practice in Ontario and demonstrated considerable variations in the practice. A large majority (80%) of centers performed PSQA measurements on all VMAT plans. Most employed pseudo-3D array detectors with a true composite (TC) geometry. No standard approach was found for stopping or reducing frequency of measurements. The sole use of delivery log evaluation was not widely implemented, though most centers expressed interest in adopting this technology. All used the Gamma evaluation method for analyzing PSQA measurements; however, no universal approach was reported on how Gamma evaluation and pass determination criteria were determined. All or some PSQA results were reviewed regularly in two-thirds of the centers. Planning related issues were considered the most frequent source for PSQA failures (40%), whereas the most frequent course of action for a failed PSQA was to review the result and decide whether to proceed to treatment.

Method of computing direction-dependent margins for the development of consensus contouring guidelines.

BACKGROUND: Clinical target volume (CTV) contouring guidelines are frequently developed through studies in which experts contour the CTV for a representative set of cases for a given treatment site and the consensus CTVs are analyzed to generate margin recommendations. Measures of interobserver variability are used to quantify agreement between experts. In cases where an isotropic margin is not appropriate, however, there is no standard method to compute margins in specified directions that represent possible routes of tumor spread. Moreover, interobserver variability metrics are often measures of volume overlap that do not account for the dependence of disagreement on direction. To aid in the development of consensus contouring guidelines, this study demonstrates a novel method of quantifying CTV margins and interobserver variability in clinician-specified directions. METHODS: The proposed algorithm was applied to 11 cases of non-spine bone metastases to compute the consensus CTV margin in each direction of intraosseous and extraosseous disease. The median over all cases for each route of spread yielded the recommended margins. The disagreement between experts on the CTV margin was quantified by computing the median of the coefficients of variation for intraosseous and extraosseous margins. RESULTS: The recommended intraosseous and extraosseous margins were 7.0 mm and 8.0 mm, respectively. The median coefficient of variation quantifying the margin disagreement between experts was 0.59 and 0.48 for intraosseous and extraosseous disease. CONCLUSIONS: The proposed algorithm permits the generation of margin recommendations in relation to adjacent anatomy and quantifies interobserver variability in specified directions. This method can be applied to future consensus CTV contouring studies.

Using lactic acid bacteria and packaging with grapefruit seed extract for controlling Listeria monocytogenes growth in fresh soft cheese.

Various cheese products are involved in outbreaks of listeriosis worldwide due to high consumption and prolonged refrigerated storage. The objective of this study was to determine the efficacy of using lactic acid bacteria and packaging with grapefruit seed extract (GSE) for controlling Listeria monocytogenes growth in soft cheese. Leuconostoc mesenteroides and Lactobacillus curvatus isolated from kimchi were used as a starter culture to make a soft cheese, which was inoculated with a cocktail strain of L. monocytogenes. The soft cheese was packed with low-density polyethylene, biodegradable polybutylene adipate-co-terephthalate (PBAT), low-density polyethylene with GSE, or PBAT with GSE and stored at 10°C and 15°C. Leuconostoc mesenteroides (LcM) better inhibited the growth of L. monocytogenes than Lb. curvatus. The PBAT with GSE film showed the best control for the growth of L. monocytogenes. When both LcM and PBAT with GSE were applied to the soft cheese, the growth of L. monocytogenes was inhibited significantly more than the use of LcM or PBAT with GSE alone. In all test groups, water activity, pH, and moisture on a fat-free basis decreased, and titratable acidity increased compared with the control group. These results suggest that LcM isolated from kimchi and PBAT with GSE packaging film can be used as a hurdle technology to lower the risk of L. monocytogenes in soft cheese at the retail market.

Physical properties and bonding quality of laminated veneer lumber produced with veneers peeled from small-diameter rubberwood logs.

The peeling of small-diameter rubberwood logs from the current short-rotation practices undoubtedly will produce lower grade veneers compared to the veneers from conventional planting rotation. Hence, this raises the question of the properties of the produced laminated veneer lumber (LVL) from veneers peeled from small-diameter rubberwood logs using the spindleless lathe technology. Different thicknesses of rubberwood veneers was peeled from rubberwood logs with diameter less than 20 cm using a spindleless lathe. Three-layer LVLs were prepared using phenol formaldehyde (PF) adhesive and hot pressed at different temperatures. During the peeling of veneer, lathe checks as deep as 30-60% of the veneer thickness are formed. Owing to deeper lathe check on 3 mm rubberwood veneer, higher pressing temperature significantly increased the gluebond shear strength of the PF-bonded LVL. In addition, lathe check frequency was also shown to influence the bond strength. The presence of higher lathe check frequency on 2 mm veneer increased the wettability, thus facilitating optimum penetration of adhesive for stronger bonding. These findings stress the importance of measuring and considering the lathe check depth and frequency during the lamination process to get a better understanding of bonding quality in veneer-based products.

Knowledge, attitudes and practices of schoolchildren toward whole grains and nutritional outcomes in Malaysia.

Whole grains play an important role in regulating body weight. However, interventions aimed to increase whole grains consumption have had limited impact on body mass index for age z-score (BAZ) due to insufficient understanding of knowledge, attitudes and practices (KAP) toward whole grains. This survey aimed to evaluate whole grains KAP among schoolchildren, as well as to investigate the associations of whole grains KAP with BAZ among the schoolchildren in Negeri Sembilan, Malaysia. This cross-sectional survey was conducted among 380 schoolchildren aged 9-11 years, cluster sampled from six randomly selected schools. Data were collected through a validated self-administered guided questionnaire. Body weight and height were measured. A majority of the schoolchildren had normal body weight (56.6%), moderate whole grains knowledge (42.6%), as well as neutral attitudes (66.1%) and poor practices (58.9%) toward whole grains consumption. Significant positive associations were found between knowledge and attitudes (r = 0.337; p < .01), attitudes and practices (r = 0.150; p < .01) and knowledge and practices (r = 0.190; p < .01). Further, whole grains consumption's practices was associated with BAZ after adjusting for sex, gender, race and area where children lived in (p < .001). Outcome of this present study implies that positive change in whole grain knowledge would help to inculcate positive attitudes and cultivate better practices toward whole grain consumption, which may be useful in lower BAZ among schoolchildren in Negeri Sembilan, Malaysia. This study reveals the importance of KAP toward whole grains among children to assist in identification of specific preventive childhood obesity actions.

First demonstration of surface enhanced-stimulated Raman spectroscopy (SE-SRS) using low-power CW sources.

Using commercially available nanoparticles, continuous wave Surface-Enhanced Stimulated Raman spectroscopy (CW SE-SRS) is demonstrated for the first time using two Ti:Sapphire lasers producing a pump beam (785 nm, 100 mW) and appropriately varying probe/Stokes beams (860-870 nm, 120 mW). The Ti-Sapphire lasers are co-pumped by a 10 W low noise 532 nm Spectra Physics Millennia laser. Pulsed SE-SRS is also demonstrated using a Coherent Chameleon Ultra laser for the Stokes/probe (863-871 nm) beam and a Coherent Ultra II as the pump laser (785 nm). In both cases lock-in techniques are used to extract the small signal (1 in 109) successfully. These experiments convincingly demonstrate that SRS with CW sources is possible using appropriate nanoparticles, and this realization creates opportunities for a wider range of stimulated Raman spectroscopy applications.

Early biomarker for radiation-induced wounds: day one post-irradiation assessment using hemoglobin concentration measured from diffuse optical reflectance spectroscopy.

Normal tissue radiation toxicities are evaluated subjectively and cannot predict the development of severe side-effects. Using a hand-held diffuse reflectance optical spectroscopy probe, we measured optical parameters in mouse skin 1-4 days after irradiation. Using a radiation toxicity model and a therapeutic mitigator described previously [BMC Cancer14, 614 (2014)], we found that hemoglobin (Hb) levels increased sharply 24 h after irradiation only in the irradiated group without the mitigator. This group also had the largest peak wound areas after 14 days. We conclude that increased Hb one day after skin irradiation predicts the severity of the subsequent irradiation-induced wound.

Entropy production and irreversibility of dissipative trajectories in electric circuits.

We experimentally examine the equivalence between the entropy production evaluated from irreversibility of trajectories and the physical dissipation in dissipative processes via electric resistor-capacitor (RC) circuits. The examinations are performed for two nonequilibrium steady states that are driven by an injected current and temperature difference, respectively. Such an equivalence demonstrates a parameter-free method to evaluate the entropy production of a system. The effects of configurational and temporal resolutions are also studied.

Electrical autonomous Brownian gyrator.

We study experimentally and theoretically the steady-state dynamics of a simple stochastic electronic system featuring two resistor-capacitor circuits coupled by a third capacitor. The resistors are subject to thermal noises at real temperatures. The voltage fluctuation across each resistor can be compared to a one-dimensional Brownian motion. However, the collective dynamical behavior, when the resistors are subject to distinct thermal baths, is identical to that of a Brownian gyrator, as first proposed by Filliger and Reimann [Phys. Rev. Lett. 99, 230602 (2007)PRLTAO0031-900710.1103/PhysRevLett.99.230602]. The average gyrating dynamics is originated from the absence of detailed balance due to unequal thermal baths. We look into the details of this stochastic gyrating dynamics, its dependences on the temperature difference and coupling strength, and the mechanism of heat transfer through this simple electronic circuit. Our work affirms the general principle and the possibility of a Brownian ratchet working near room temperature scale.

Accuracy of MRI in the diagnosis of meniscal tears in patients with chronic ACL tears.

PURPOSE: This study was conducted to evaluate the accuracy of magnetic resonance imaging (MRI) in diagnosing meniscal tears in patients with anterior cruciate ligament (ACL) tears and to determine the frequency of missed meniscal tears on MRI. METHODS: This prospective comparative study was conducted from 2009 to 2012. Patients with ACL injuries who underwent knee arthroscopy and MRI were included in the study. Two radiologists who were blinded to the clinical history and arthroscopic findings reviewed the pre-arthroscopic MR images. The presence and type of meniscal tears on MRI and arthroscopy were recorded. Arthroscopic findings were used as the reference standard. The accuracy, sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) of MRI in the evaluation of meniscal tears were calculated. RESULTS: A total of 65 patients (66 knees) were included. The sensitivity, specificity, accuracy, PPV, and NPV for the MRI diagnosis of lateral meniscal tears in our patients were 83, 97, 92, 96, and 90 %, respectively, whereas those for medial meniscus tears were 82, 92, 88, 82, and 88 %, respectively. There were five false-negative diagnoses of medial meniscus tears and four false-negative diagnoses of lateral meniscus tears. The majority of missed meniscus tears on MRI affected the peripheral posterior horns. CONCLUSION: The sensitivity for diagnosing a meniscal tear was significantly higher when the tear involved more than one-third of the meniscus or the anterior horn. The sensitivity was significantly lower for tears located in the posterior horn and for vertically oriented tears. Therefore, special attention should be given to the peripheral posterior horns of the meniscus, which are common sites of injury that could be easily missed on MRI. The high NPVs obtained in this study suggest that MRI is a valuable tool prior to arthroscopy.

Inflammatory markers in cord blood or maternal serum for early detection of neonatal sepsis-a systemic review and meta-analysis.

OBJECTIVE: To perform a quantitative review of the evidence on the diagnostic value of inflammatory markers in maternal serum or umbilical cord blood for the diagnosis of early-onset neonatal sepsis (EONS). STUDY DESIGN: We searched multiple databases for studies published through March 2013 that evaluated the diagnostic performance of procalcitonin (PCT), C-reactive protein (CRP) and interleukin-6 (IL-6), and leukocyte count (white blood cell, WBC) in either umbilical cord blood or maternal serum for diagnosis of EONS. We summarized test performance characteristics with the use of forest plots, hierarchical summary receiver operating characteristic curves and bivariate random effects models. RESULT: Our search identified 3874 citations, of which 15 studies evaluating 2178 episodes of suspected neonatal infection were included for analysis. IL-6 in cord blood with a pooled-positive likelihood ratio (LR+) of 9.47 (95% confidence interval: 3.86 to 23.3), PCT in cord blood with a LR+ of 5.72 (1.56 to 21.0) and IL-6 in maternal serum with a LR+ of 5.47 (2.10 to 14.2) can be qualified as a valid rule-in test. IL-6 in cord blood with a LR- of 0.10 (0.05 to 0.21) and PCT in cord blood with a LR- of 0.20 (0.12-0.37) can be qualified as a useful rule-out test. Either CRP or WBC was inadequate for diagnosis of EONS. CONCLUSION: For cord blood sample, IL-6 or PCT can be used as reliable rule-in and rule-out tool. For maternal serum, only IL-6 appeared to be sufficient for rule-in diagnosis. An interventional study may be needed to answer whether the addition of these tests will improve the outcome of patients with EONS.

Non-homologous end joining pathway is the major route of protection against 4ß-hydroxywithanolide E-induced DNA damage in MCF-7 cells.

4ß-Hydroxywithanolide E is a bioactive withanolide extracted from Physalis peruviana. 4ß-Hydroxywithanolide E caused reactive oxygen species production and cell apoptosis in human breast cancer MCF-7 cells. We further found that 4ß-hydroxywithanolide E induced DNA damage and regulated the DNA damage signaling in MCF-7 cells. The DNA damage sensors and repair proteins act promptly to remove DNA lesions by 4ß-hydroxywithanolide E. The ataxia-telangiectasia mutated protein (ATM)-dependent DNA damage signaling pathway is involved in 4ß-hydroxywithanolide E-induced apoptosis of MCF-7 cells. Non-homologous end joining pathway, but not homologous recombination, is the major route of protection of MCF-7 cells against 4ß-hydroxywithanolide E-induced DNA damage. 4ß-Hydroxywithanolide E had no significant impact on the base excision repair pathway. In this study, we examined the 4ß-hydroxywithanolide E-induced DNA damage as a research tool in project investigating the DNA repair signaling in breast cancer cells. We also suggest that 4ß-hydroxywithanolide E assert its anti-tumor activity in carcinogenic progression and develop into a dietary chemopreventive agent.

Successful treatment of isolated fibular bone metastasis in a uterine endometrial cancer of clear cell carcinoma.

Clear cell carcinoma of the endometrium is an uncommon histological subtype and isolated metastasis to bone is rare. The authors present a case of a 61-year-old woman who underwent laparoscopic staging surgery for clear cell carcinoma of uterine endometrium (FIGO Stage IB) and early recurrence with isolated fibular bone metastasis three months later. With salvage radiotherapy (RT), she remains disease-free after 46 months. Curative-intended treatment with RT is possible as in this case.

A common environmental pollutant, 4-nonylphenol, promotes allergic lung inflammation in a murine model of asthma.

BACKGROUND: Exposure to environmental hormones, such as alkylphenols, has been suggested to be associated with the development of asthma, but the mechanism of action remains unclear. OBJECTIVE: This study examined the effect of 4-nonylphenol (NP), one of the most important alkylphenols, on conventional dendritic cells (cDCs) and adaptive T-cell responses. It also explored the role of aryl hydrocarbon receptor (AhR) in NP's effect. METHODS: NP-conditioned bone marrow-derived DCs (BM-DCs) and splenic CD11c(+) cDCs were assessed regarding function in a murine model under conditions relevant to route and level of exposure in humans. RESULTS: Our results showed that splenic cDCs from NP-exposed mice have potent Th2-skewing ability and secrete increased levels of IL-6 and TNF-α, but not IL-10 and IL-12, at baseline and after stimulation with LPS. Further, bone marrow-derived DCs were cultured in the presence of NP and showed similar cytokine pattern and influenced the antigen-specific T cells secreting significantly less IFN-γ. Importantly, NP-exposed mice developed more severe OVA-induced allergic lung inflammation compared with control group. Interestingly, in a congenic strain of mice carrying low-affinity, ligand-binding mutant AhR (AhR(d) ), NP's effect on DC functions and lung inflammation was not observed in vitro and in vivo. CONCLUSION: These results suggested that NP may disturb physiologic function of DCs through, in part, AhR-dependent mechanisms, supporting the importance of NP exposure on the regulation of DC functions and allergic inflammation.

Imaging of Osteo-odontokeratoprosthesis(OOKP) Using Multidetector Computed Tomography: A UKMMC Experience.

Osteo-odontokeratoprosthesis (OOKP) surgery is a technique used to replace damaged cornea in blind patients for whom cadaveric transplantation is not feasible. OOKP surgery is a complex procedure requiring lifetime follow-up. The preservation of the osteo-odontolamina is the vital feature in maintaining the stability of the OOKP. Early detection of lamina resorption enables early prophylactic measures to be taken and prevent resorption-related complications. This case illustrates the radiological findings of the first OOKP surgery in Malaysia and the role of multidetector computed tomography (MDCT) in postoperative management of OOKP surgery.

Elevated plasma high-mobility group box 1 protein is a potential marker for neuromyelitis optica.

High-mobility group box 1 protein (HMGB1) has cytokine activities and mediates systemic inflammation as well as immune responses. The aim of this study was to determine if plasma HMGB1 level can be used as a marker for neuromyelitis optica (NMO) and to differentiate NMO from multiple sclerosis (MS). We measured plasma levels of HMGB1, tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), and interleukin 17 (IL-17) in 29 patients with NMO and 20 patients with MS at enrollment and at 2years follow-up (at the time of definitive diagnosis) by enzyme-linked immunosorbent assay. Plasma HMGB1 level was significantly greater in the NMO group compared to the MS group (P<0.001). Plasma levels of TNF-α, IFN-γ, and IL-17 were significantly greater in the NMO group compared to the MS group, and HMGB1 level was positively correlated with TNF-α, IFN-γ, and IL-17 levels. Univariate logistic regression analysis showed a significant association of HMGB1 level, and IFN-γ level with NMO diagnosis. Although this study included a limited sample size, we attempted to determine an optimized cutoff point for HMGB1 (≥2 ng/ml), which provided 89.7% sensitivity and 95.0% specificity for the diagnosis of NMO. These results indicate that plasma HMGB1 level might serve as a surrogate marker for NMO disease activity and aid in the differentiation of NMO from MS at the early disease stage.

Glycodelin-A modulates syncytialization of human BeWo choriocarcinoma cell line.

Cytotrophoblasts are the key trophoblast cells which differentiate into different trophoblast lineages. In this report, glycodelin-A action on fusion of a cytotrophoblast-like cell line (BeWo) was investigated. It significantly reduced the spontaneous fusion of BeWo cells. The treatment enhanced the invasion and extracellular-signal regulated kinases activation of BeWo cells. The mRNA expression of syncytialization markers, human chorionic gonadotrophin and glial cells missing homolog 1 were suppressed upon glycodelin-A treatment. The data suggest a possible function of glycodelin-A in mediating cytotrophoblast differentiation.