Reading of Gafchromic EBT-3 Film using an Overhead Scanner.

Gafchromic film, a commercially available radiochromic film, has been developed and widely used as an effective tool for radiation dose verification and quality assurance in radiotherapy. However, the orientation effect in scanning a film remains a concern for practical application in beam profile monitoring. To resolve this issue, the authors introduced a novel method using an overhead scanner (OHS) coupled with a tracing light board instead of a conventional flatbed scanner (FBS) to read Gafchromic EBT3 films. We investigated the orientation effect of the EBT3 film with a regular hexagonal shape after irradiation with 5 Gy X-rays (160 kV, 6.3 mA) and compared the digitized images acquired using a commercially available OHS (Aura, CZUR) and a conventional FBS (GT-X980, EPSON). As a result, RGB color intensities acquired from the OHS showed significantly lower orientation effect of the color intensities of RGB components than those from FBS. This finding indicates the high potential of the proposed method for achieving more precise two-dimensional dosimetry. Further studies are required to confirm the effectiveness of this method under different irradiation conditions over a wider dose range.

Effect of renin-angiotensin system inhibitors on pemetrexed plus platinum-induced hematological toxicities: a multicenter retrospective study using three propensity score analyses.

Hematological toxicities induced by pemetrexed plus platinum therapy remain a critical issue in clinical practice. We hypothesized that inhibition of the renin-angiotensin system (RAS) can ameliorate pemetrexed-induced hematological toxicities through drug-drug interactions involving organic anion transporters. Thus, this study aimed to clarify whether RAS inhibitors (RASIs) could prevent pemetrexed plus platinum-induced hematological toxicities. We retrospectively analyzed data from 305 consecutive patients with non-small cell lung cancer or malignant pleural mesothelioma who received their first cycle of a pemetrexed plus platinum regimen and were treated with or without RASIs. The primary endpoint was the incidence of severe myelosuppression after the first cycle. Propensity score (PS)-matched, PS-adjusted, and inverse probability of treatment weighting (IPTW) analyses were used. The number of patients with grade ≥3 hematological toxicities was 27 (8.9%). PS-matched analyses revealed that the concomitant use of RASIs was slightly associated with a lower risk of grade ≥3 hematological toxicities (odds ratio [OR], 0.68; 95% confidence interval [CI], 0.20-2.32; p = 0.536). Additionally, sensitivity analyses using PS-adjusted and IPTW methods demonstrated similar results (OR, 0.63; 95% CI, 0.19-2.15; p = 0.463 and OR, 0.37; 95% CI, 0.11-1.29; p = 0.117, respectively). These findings suggest that RASIs might prevent pemetrexed plus platinum-induced hematological toxicities.

Effect of skin antiseptic solutions on the incidence of catheter-related bloodstream infection: a systematic review and network meta-analysis.

BACKGROUND: The most effective skin antiseptic solution to reduce the incidence of catheter-related bloodstream infections (CRBSI) remains unknown. AIM: To compare solutions with different chlorhexidine (CHG)-based concentrations and povidone-iodine (PVI) in adults with a central venous catheter (CVC) or arterial catheter, and identify an association with the incidence of CRBSI. METHODS: This study evaluated randomized controlled trials comparing CHG and PVI antiseptic agents in patients aged ≥18 years with an underlying illness and a CVC or arterial catheter. The primary outcome was CRBSI rate. Network meta-analysis was performed by a frequentist-based approach with multi-variate random effects meta-analysis, and the effect size was expressed as relative risk (RR) with 95% confidence interval (CI). FINDINGS: The search yielded 1511 records, of which five studies (2815 catheters) were included in the network meta-analysis. The risk of CRBSI was significantly lower with 1% CHG-alcohol than with 0.5% CHG-alcohol (RR 0.40, 95% CI 0.16-0.98; high certainty) or 10% PVI-aqueous (RR 0.31, 95% CI 0.15-0.63; high certainty). There was no significant difference in the risk of CRBSI between 1% CHG-alcohol and 2% CHG-aqueous (RR 0.35, 95% CI 0.12-1.04; moderate certainty) or other antiseptic solutions. The hierarchy of efficacy in reducing CRBSI was 1% CHG-alcohol, 0.5% CHG-alcohol, 2% CHG-aqueous and 10% PVI-aqueous. CONCLUSION: Antiseptic agents containing 1% CHG-alcohol were more strongly associated with reduced risk for CRBSI compared with agents containing 0.5% CHG-alcohol or 10% PVI-aqueous.

The natural course of the paravertebral muscles after the onset of osteoporotic vertebral fracture.

This study revealed the change in the paravertebral muscles in patients with osteoporotic vertebral fracture. Increased pain is likely to be the driver for reduced activity, reduced activities of daily living, and consequent increase in fat infiltration of the paravertebral muscles, assumed to be secondary to reduced activity level or, conversely, partial immobilization. INTRODUCTION: To reveal the time courses and impact of the paravertebral muscles (PVMs) on the healing process of osteoporotic vertebral fractures and risk factors for PVM decrease. METHODS: Consecutive patients with symptomatic osteoporotic vertebral fractures were enrolled in 11 hospitals. At enrollment and 3- and 6-month follow-up, PVMs, including the multifidus and erector spinae, were examined using magnetic resonance imaging (MRI). The PVM cross-sectional area (CSA) and fat signal fraction (FSF) were measured at L3. Low back pain (LBP), activities of daily living (ADLs), and risk factors for PVM decrease at the 6-month follow-up were investigated. PVM decrease was defined as > 1 standard deviation decrease of the CSA or > 1 standard deviation increase of the FSF. RESULTS: Among 153 patients who completed the 6-month follow-up, 117 (92 women, 79%) had MRI of L3 at enrollment and 3- and 6-month follow-up (mean age at enrollment, 78.5 years). The CSA did not change 6 months from onset (p for trend = 0.634), whereas the FSF significantly increased (p for trend = 0.033). PVM decrease was observed in 30 patients (26%). LBP was more severe, and delayed union was more frequent in patients with PVM decrease (p = 0.021 mixed-effect model and p = 0.029 chi-square test, respectively). The risk factors for PVM decrease were ADL decline at the 3-month follow-up (adjusted odds ratio = 5.35, p = 0.026). CONCLUSION: PVM decrease was significantly related to LBP and delayed union after osteoporotic vertebral fracture onset. ADL decline at the 3-month follow-up was a risk factor for PVM decrease. Therefore, restoring ADLs within 3 months after onset is important.

Promotion in solid phase reaction of Pt/SiO x bilayer film by electron-orbital-selective-excitation.

A thermally impossible positive free energy reaction can proceed by electron-orbital-selective excitation. When the Si 2p core level is photo-excited in Pt/SiO x bilayer films, Coulomb repulsion at the final two-hole state localized in the valence band by an interatomic Auger transition induces dissociation of the O atom and formation of a Si-Pt bond. Consequently, Pt2Si silicide is formed by a positive free energy reaction. Under a single particle excitation of the valence band, low probability of the coexistence of the two-hole state for picosecond order suppresses to allow the reaction to proceed.

Safety and efficacy of PD-1/PD-L1 blockade in patients with preexisting antinuclear antibodies.

PURPOSE: Immune checkpoint inhibitors (ICIs) show promising clinical activity in advanced cancers. However, the safety and efficacy of PD-1/PD-L1 blockade in patients with preexisting antinuclear antibodies (ANA) are unclear. METHODS: 191 patients treated with nivolumab, pembrolizumab, atezolizumab, or durvalumab for unresectable advanced cancers between September 2014 and December 2018 were identified retrospectively. Patients were divided into positive (ANA titers ≥ 1:160) and negative ANA groups (ANA titers < 1:160). Development of immune-related adverse events (irAEs), the overall response rate (ORR), and disease control rate (DCR) were monitored. RESULTS: Positive ANA titers were seen in 9 out of 191 patients. Four patients in the positive ANA group and 69 patients in the negative group developed irAEs of any grade without a significant difference between the groups. The development of endocrine, pulmonary, and cutaneous irAEs was not significant, whereas positive ANA was significantly higher in patients who developed colitis (2/9) than in patients who did not (3/182, P = 0.0002). DCR in the positive and negative ANA group was 37.5% and 67.5%, respectively, and was not statistically significant, but had better efficacy in patients without ANA (P = 0.08). ANA-related autoimmune diseases such as SLE, Sjögren's syndrome, MCTD, scleroderma, dermatomyositis, and polymyositis was not induced in either group. However, one patient with preexisting dermatomyositis had a flare up after initiation of atezolizumab. CONCLUSION: Further studies to identify predictive factors for the development of irAEs are required to provide relevant patient care and maximize the therapeutic benefits of ICIs.

Kirigami-based Elastic Metamaterials with Anisotropic Mass Density for Subwavelength Flexural Wave Control.

A novel design of an elastic metamaterial with anisotropic mass density is proposed to manipulate flexural waves at a subwavelength scale. The three-dimensional metamaterial is inspired by kirigami, which can be easily manufactured by cutting and folding a thin metallic plate. By attaching the resonant kirigami structures periodically on the top of a host plate, a metamaterial plate can be constructed without any perforation that degrades the strength of the pristine plate. An analytical model is developed to understand the working mechanism of the proposed elastic metamaterial and the dispersion curves are calculated by using an extended plane wave expansion method. As a result, we verify an anisotropic effective mass density stemming from the coupling between the local resonance of the kirigami cells and the global flexural wave propagations in the host plate. Finally, numerical simulations on the directional flexural wave propagation in a two-dimensional array of kirigami metamaterial as well as super-resolution imaging through an elastic hyperlens are conducted to demonstrate the subwavelength-scale flexural wave control abilities. The proposed kirigami-based metamaterial has the advantages of no-perforation design and subwavelength flexural wave manipulation capability, which can be highly useful for engineering applications including non-destructive evaluations and structural health monitoring.

Emergence of dispersive shocks and rarefaction waves in power-law contact models.

In the present work, motivated by generalized forms of the Hertzian dynamics associated with granular crystals, we consider the possibility of such models to give rise to both dispersive shock and rarefaction waves. Depending on the value p of the nonlinearity exponent, we find that both of these possibilities are realizable. We use a quasicontinuum approximation of a generalized inviscid Burgers model in order to predict the solution profile up to times near the formation of the dispersive shock, as well as to estimate when it will occur. Beyond that time threshold, oscillations associated with the highly dispersive nature of the underlying model emerge, which cannot be captured by the quasicontinuum approximation. Our analytical characterization of the above features is complemented by systematic numerical computations.

Down-regulation of the two-component system and cell-wall biosynthesis-related genes was associated with the reversion to daptomycin susceptibility in daptomycin non-susceptible methicillin-resistant Staphylococcus aureus.

Daptomycin (DAP) is widely used in the treatment of methicillin-resistant Staphylococcus aureus (MRSA) infection. The emergence of DAP non-susceptible MRSA strains during therapy is a major concern in clinical settings. Recent studies revealed that MRSA spontaneously reverts to a subsequent methicillin-susceptible S. aureus (MSSA) strain. However, it is not clear whether DAP non-susceptible MRSA has the ability to revert to a susceptible strain. We obtained an MRSA strain pair, DAP non-susceptible strain and subsequent DAP susceptible strain, from a patient. To understand the underlying mechanism by which DAP non-susceptible MRSA reverts to a susceptible strain, we performed genetic and phenotypic analysis in the strain pair. Although whole-genome analysis revealed four missense mutations, including L826F in mprF, in both strains, the net cell-surface charge was similar between the DAP non-susceptible and susceptible strains. However, the thickness of the cell wall was higher in the DAP non-susceptible strain, which was decreased to the same level as the control after reversion to the DAP susceptible strain. Moreover, the non-susceptible strain showed higher mRNA expression of the two-component system (TCS), such as VraSR, yycG and GraS, with the up-regulated transcription levels of cell-wall biosynthesis-related genes. The expression levels of those genes were decreased after reversion to the susceptible strain. These results indicated that DAP non-susceptibility due to up-regulation of the TCS and cell-wall biosynthesis-related genes may be reversible by the discontinuation of DAP, leading to reversion to the DAP susceptible phenotype.

In situ imaging of microstructure formation in electronic interconnections.

The development of microstructure during melting, reactive wetting and solidification of solder pastes on Cu-plated printed circuit boards has been studied by synchrotron radiography. Using Sn-3.0Ag-0.5Cu/Cu and Sn-0.7Cu/Cu as examples, we show that the interfacial Cu6Sn5 layer is present within 0.05 s of wetting, and explore the kinetics of flux void formation at the interface between the liquid and the Cu6Sn5 layer. Quantification of the nucleation locations and anisotropic growth kinetics of primary Cu6Sn5 crystals reveals a competition between the nucleation of Cu6Sn5 in the liquid versus growth of Cu6Sn5 from the existing Cu6Sn5 layer. Direct imaging confirms that the ß-Sn nucleates at/near the Cu6Sn5 layer in Sn-3.0Ag-0.5Cu/Cu joints.

Time course of osteoporotic vertebral fractures by magnetic resonance imaging using a simple classification: a multicenter prospective cohort study.

This study revealed the time course of osteoporotic vertebral fracture by magnetic resonance imaging using a simple classification. Signal changes were associated with the compression degree and mobility of the fractured vertebral body. This classification showed sufficient reliability in categorizing magnetic resonance imaging findings of osteoporotic vertebral fractures. INTRODUCTION: Magnetic resonance imaging (MRI) is useful in diagnosing osteoporotic vertebral fractures (OVFs). This study investigated the time course of OVFs by MRI using a simple classification. METHODS: This multicenter cohort study was performed from 2012 to 2015. Consecutive patients with ≤2-week-old OVFs were enrolled in 11 institutions. MRI was performed at enrollment and at 1-, 3-, 6-, and 12-month follow-up. Signal changes on T1-weighted imaging (T1WI), T2WI, and short τ inversion recovery (STIR) were classified according to signal intensity. Height and angular motion of vertebral bodies were also measured. RESULTS: The 6-month follow-up was completed by 153 patients. At enrollment, fractured vertebrae signal changes were 43 % diffuse and 57 % confined low on T1WI; on T2WI, 56, 24, and 5 % were confined low, high, and diffuse low, respectively; on STIR, 100 % were high. On T1WI, diffuse low remained most common (90 % at 1 month and 60 % at 3 months) until 6 and 12 months, when most were confined low (54 and 52 %, respectively). On T2WI, confined low remained most common (decreasing to 41 % at 12 months). On STIR, high signal change was shown in 98, 87, and 64 % at 3, 6, and 12 months, respectively. At 3, 6, and 12 months, diffuse low signal change was associated with significantly lower vertebral height, and high signal change was associated with significantly greater angular motion. CONCLUSIONS: MRI signal changes were associated with the compression degree and angular motion of fractured vertebrae. This classification showed sufficient reliability in categorizing MRI findings of OVFs.

Lower thigh muscle mass is associated with all-cause and cardiovascular mortality in elderly hemodialysis patients.

BACKGROUND/OBJECTIVES: Higher body mass index appears protective in hemodialysis patients, although it remains to be determined which component of muscle or fat mass is primarily associated with this survival advantage. SUBJECTS/METHODS: Eighty-one hemodialysis patients in our institution were prospectively followed from July 2011 to August 2015. Muscle and fat mass were evaluated by measuring the cross-sectional areas of the thigh and abdomen using computed tomography. The relationship between muscle and fat mass, and all-cause and cardiovascular mortality was studied using the Kaplan-Meier analyses and multivariate Cox proportional hazard models. RESULTS: During more than 4 years of follow-up, 26 patients (32%) died. In the Kaplan-Meier curve analyses, lower thigh muscle mass was significantly associated with all-cause and cardiovascular mortality (log-rank test, P<0.01 and P<0.001, respectively), but there was no such association with thigh fat, abdominal muscle and fat mass levels. In multivariate Cox proportional hazard models, each 0.1 cm2/kg increase in the thigh muscle area adjusted by dry weight was associated with an estimated 22% lower risk of all-cause mortality (95% confidence interval (95% CI), 0.64-0.95, P<0.05) and a 30% lower risk of cardiovascular mortality (95% CI, 0.54-0.90, P<0.01). CONCLUSIONS: Lower thigh muscle mass is significantly associated with all-cause and cardiovascular mortality in hemodialysis patients. Our findings indicate the importance of focusing on the muscle mass of lower extremities to predict the clinical outcomes of hemodialysis patients.

Factors predicting successful discontinuation of continuous renal replacement therapy.

This multicentre, retrospective observational study was conducted from January 2010 to December 2010 to determine the optimal time for discontinuing continuous renal replacement therapy (CRRT) by evaluating factors predictive of successful discontinuation in patients with acute kidney injury. Analysis was performed for patients after CRRT was discontinued because of renal function recovery. Patients were divided into two groups according to the success or failure of CRRT discontinuation. In multivariate logistic regression analysis, urine output at discontinuation, creatinine level and CRRT duration were found to be significant variables (area under the receiver operating characteristic curve for urine output, 0.814). In conclusion, we found that higher urine output, lower creatinine and shorter CRRT duration were significant factors to predict successful discontinuation of CRRT.

ICRP Publication 132: Radiological Protection from Cosmic Radiation in Aviation.

Abstract ­: In this publication, the International Commission on Radiological Protection (ICRP) provides updated guidance on radiological protection from cosmic radiation in aviation, taking into account the current ICRP system of radiological protection, the latest available data on exposures in aviation, and experience gained worldwide in the management of exposures in aviation. The publication describes the origins of cosmic radiation, how it exposes passengers and aircraft crew, the basic radiological protection principles that apply to this existing exposure situation, and the available protective actions. For implementation of the optimisation principle, the Commission recommends a graded approach proportionate to the level of exposure that may be received by individuals. The objective is to keep the exposure of the most exposed individuals to a reasonable level. The Commission also recommends that information be disseminated to raise awareness about cosmic radiation, and to support informed decisions among concerned stakeholders.

Predicting delayed union in osteoporotic vertebral fractures with consecutive magnetic resonance imaging in the acute phase: a multicenter cohort study.

This study demonstrated the predictive values of radiological findings for delayed union after osteoporotic vertebral fractures (OVFs). High-signal changes on T2WI were useful findings. INTRODUCTION: The purpose of the present study is to determine predictive radiological findings for delayed union by magnetic resonance imaging (MRI) and plain X-rays at two time points in the acute phase of OVFs. METHODS: This multicenter cohort study was performed from 2012 to 2015. A total of 218 consecutive patients with OVFs ≤2 weeks old were enrolled. MRIs and plain X-rays were performed at the time of enrollment and at 1- and 6-month follow-ups. Signal changes on T1-weighted imaging (T1WI) were classified as diffuse low-, confined low-, or no-signal change; those on T2WI were classified as high (similar to the intensity of cerebrospinal fluid), confined low-, diffuse low-, or no-signal change. The angular motion of the fractured vertebral body was measured with X-rays. RESULTS: A total of 153 patients completed the 6-month follow-up. A high-signal change on T2WI was most useful in predicting delayed union. Sensitivity, specificity, and positive predictive values were 53.3, 87.8, and 51.6 % at enrollment and 65.5, 84.8, and 51.4 % at the 1-month follow-up, respectively. The positive predictive value increased to 62.5 % with observation of high- or diffuse low-signal changes at both enrollment and the 1-month follow-up. The cutoff value of vertebral motion was 5 degrees. Sensitivity and specificity at enrollment were 52.4 and 74.1 %, respectively. CONCLUSIONS: This study demonstrated the radiological factors predicting delayed union after an OVF. T2 high-signal changes showed the strongest association with delayed union. Consecutive MRIs were particularly useful as a differential tool to predict delayed union following OVFs.

Formation of rarefaction waves in origami-based metamaterials.

We investigate the nonlinear wave dynamics of origami-based metamaterials composed of Tachi-Miura polyhedron (TMP) unit cells. These cells exhibit strain softening behavior under compression, which can be tuned by modifying their geometrical configurations or initial folded conditions. We assemble these TMP cells into a cluster of origami-based metamaterials, and we theoretically model and numerically analyze their wave transmission mechanism under external impact. Numerical simulations show that origami-based metamaterials can provide a prototypical platform for the formation of nonlinear coherent structures in the form of rarefaction waves, which feature a tensile wavefront upon the application of compression to the system. We also demonstrate the existence of numerically exact traveling rarefaction waves in an effective lumped-mass model. Origami-based metamaterials can be highly useful for mitigating shock waves, potentially enabling a wide variety of engineering applications.

Drebrin A regulates hippocampal LTP and hippocampus-dependent fear learning in adult mice.

Structural plasticity of dendritic spines, which underlies higher brain functions including learning and memory, is dynamically regulated by the actin cytoskeleton and its associated proteins. Drebrin A is an F-actin-binding protein preferentially expressed in the brain and localized in the dendritic spines of mature neurons. Isoform conversion from drebrin E to drebrin A and accumulation of the latter in dendritic spines occurs during synapse maturation. We have previously demonstrated that drebrin A plays a pivotal role in spine morphogenesis and plasticity. However, it is unclear whether drebrin A plays a specific role in processes required for structural plasticity, and whether drebrin E can substitute in this role. To answer these questions, we analyzed mutant mice (named DAKO mice), in which isoform conversion from drebrin E to drebrin A is disrupted. In DAKO mouse brain, drebrin E continues to be expressed throughout life instead of drebrin A. Electrophysiological studies using hippocampal slices revealed that long-term potentiation of CA1 synapses was impaired in adult DAKO mice, but not in adolescents. In parallel with this age-dependent impairment, DAKO mice exhibited impaired hippocampus-dependent fear learning in an age-dependent manner; the impairment was evident in adult mice, but not in adolescents. In addition, histological investigation revealed that the spine length of the apical dendrite of CA1 pyramidal cells was significantly longer in adult DAKO mice than in wild-type mice. Our data indicate that the roles of drebrin E and drebrin A in brain function are different from each other, that the isoform conversion of drebrin is critical, and that drebrin A is indispensable for normal synaptic plasticity and hippocampus-dependent fear memory in the adult brain.

Reentrant Origami-Based Metamaterials with Negative Poisson's Ratio and Bistability.

We investigate the unique mechanical properties of reentrant 3D origami structures based on the Tachi-Miura polyhedron (TMP). We explore the potential usage as mechanical metamaterials that exhibit tunable negative Poisson's ratio and structural bistability simultaneously. We show analytically and experimentally that the Poisson's ratio changes from positive to negative and vice versa during its folding motion. In addition, we verify the bistable mechanism of the reentrant 3D TMP under rigid origami configurations without relying on the buckling motions of planar origami surfaces. This study forms a foundation in designing and constructing TMP-based metamaterials in the form of bellowslike structures for engineering applications.

Nonrandom point defect configurations and driving force transitions for grain boundary segregation in trivalent cation doped ZrO2.

The energetically favorable spatial configuration of M(3+) ions and oxide-ion vacancies near a symmetrical grain boundary (GB) in cubic zirconia is determined for various trivalent species M(3+) (M = Al, Sc, Y, Gd, La), and the driving force for grain boundary segregation (GBS) quantitatively examined using atomistic Monte Carlo simulations in conjunction with static lattice calculations. For a high concentration of ∼10 mol %, it is found that point defects near a GB plane preferentially occupy specific sites to minimize total lattice energy, rather than being randomly distributed. Systematic analysis shows that energetically stable configurations of segregants vary depending on their ionic radii. Analysis of the driving force for GBS as a function of dopant concentration reveals that three important factors govern GBS. First, occupation of specific sites by point defects is necessary to minimize the total lattice energy; enrichment of point defects near the GB plane with random configuration does not decrease the total lattice energy significantly because of strong Coulombic interactions. Second, the factors governing GBS change with increasing dopant concentration. At dilute concentrations, relief of bond strain is the dominant factor, while at high concentrations Coulombic interactions, which depend strongly on the specific arrangement of defects, become another dominant factor. Third, the stabilization of matrix cations, Zr(4+) ions, is the dominant factor to lower the driving force for GBS at all concentrations. In contrast, the stabilization of M(3+) ions does not necessarily contribute to GBS of point defects at high concentrations. These findings suggest practical ways to control GBS to enhance materials' properties or minimize detrimental effects.