Addressing the knowledge gap in the genomic landscape and tailored therapeutic approaches to adolescent and young adult cancers.

BACKGROUND: Adolescents and young adults (AYAs) represent a small proportion of patients with cancer. The genomic profiles of AYA patients with cancer are not well-studied, and outcomes of genome-matched therapies remain largely unknown. PATIENTS AND METHODS: We investigated differences between Japanese AYA and older adult (OA) patients in genomic alterations, therapeutic evidence levels, and genome-matched therapy usage by cancer type. We also assessed treatment outcomes. RESULTS: AYA patients accounted for 8.3% of 876 cases. Microsatellite instability-high and/or tumor mutation burden was less common in AYA patients (1.4% versus 7.7% in OA; P = 0.05). However, BRCA1 alterations were more common in AYA patients with breast cancer (27.3% versus 1.7% in OA; P = 0.01), as were MYC alterations in AYA patients with colorectal cancer (23.5% versus 5.8% in OA; P = 0.02) and sarcoma (31.3% versus 3.4% in OA; P = 0.01). Genome-matched therapy use was similar between groups, with overall survival tending to improve in both. However, in AYA patients, the small number of patients prevented statistical significance. Comprehensive genomic profiling-guided genome-matched therapy yielded encouraging results, with progression-free survival of 9.0 months in AYA versus 3.7 months in OA patients (P = 0.59). CONCLUSION: Our study suggests that tailored therapeutic approaches can benefit cancer patients regardless of age.

First Application of Mass Measurements with the Rare-RI Ring Reveals the Solar r-Process Abundance Trend at A=122 and A=123.

The Rare-RI Ring (R3) is a recently commissioned cyclotronlike storage ring mass spectrometer dedicated to mass measurements of exotic nuclei far from stability at Radioactive Isotope Beam Factory (RIBF) in RIKEN. The first application of mass measurement using the R3 mass spectrometer at RIBF is reported. Rare isotopes produced at RIBF-^{127}Sn, ^{126}In, ^{125}Cd, ^{124}Ag, ^{123}Pd-were injected in R3. Masses of ^{126}In, ^{125}Cd, and ^{123}Pd were measured whereby the mass uncertainty of ^{123}Pd was improved. This is the first reported measurement with a new storage ring mass spectrometry technique realized at a heavy-ion cyclotron and employing individual injection of the preidentified rare nuclei. The latter is essential for the future mass measurements of the rarest isotopes produced at RIBF. The impact of the new ^{123}Pd result on the solar r-process abundances in a neutron star merger event is investigated by performing reaction network calculations of 20 trajectories with varying electron fraction Y_{e}. It is found that the neutron capture cross section on ^{123}Pd increases by a factor of 2.2 and ß-delayed neutron emission probability, P_{1 n}, of ^{123}Rh increases by 14%. The neutron capture cross section on ^{122}Pd decreases by a factor of 2.6 leading to pileup of material at A=122, thus reproducing the trend of the solar r-process abundances. The trend of the two-neutron separation energies (S_{2n}) was investigated for the Pd isotopic chain. The new mass measurement with improved uncertainty excludes large changes of the S_{2n} value at N=77. Such large increase of the S_{2n} values before N=82 was proposed as an alternative to the quenching of the N=82 shell gap to reproduce r-process abundances in the mass region of A=112-124.

Bayesian inference of ion velocity distribution function from laser-induced fluorescence spectra.

The velocity distribution function is a statistical description that connects particle kinetics and macroscopic parameters in many-body systems. Laser-induced fluorescence (LIF) spectroscopy is utilized to measure the local velocity distribution function in spatially inhomogeneous plasmas. However, the analytic form of such a function for the system of interest is not always clear under the intricate factors in non-equilibrium states. Here, we propose a novel approach to select the valid form of the velocity distribution function based on Bayesian statistics. We formulate the Bayesian inference of ion velocity distribution function and apply it to LIF spectra locally observed at several positions in a linear magnetized plasma. We demonstrate evaluating the spatial inhomogeneity by verifying each analytic form of the local velocity distribution function. Our approach is widely applicable to experimentally establish the velocity distribution function in plasmas and fluids, including gases and liquids.

Swelling of Doubly Magic

Interaction cross sections for ^{42-51}Ca on a carbon target at 280 MeV/nucleon have been measured for the first time. The neutron number dependence of derived root-mean-square matter radii shows a significant increase beyond the neutron magic number N=28. Furthermore, this enhancement of matter radii is much larger than that of the previously measured charge radii, indicating a novel growth in neutron skin thickness. A simple examination based on the Fermi-type distribution, and mean field calculations point out that this anomalous enhancement of the nuclear size beyond N=28 results from an enlargement of the core by a sudden increase in the surface diffuseness of the neutron density distribution, which implies the swelling of the bare ^{48}Ca core in Ca isotopes beyond N=28.

INVESTIGATION OF A PRACTICAL PATIENT DOSE INDEX FOR ASSESSMENT OF PATIENT ORGAN DOSE FROM CONE-BEAM COMPUTED TOMOGRAPHY IN RADIATION THERAPY USING A MONTE CARLO SIMULATION.

The purpose of this study was to investigate a practical patient dose index for assessing the patient organ dose from a cone-beam computed tomography (CBCT) scan by comparing eight dose indices, i.e. CTDI100, CTDIIEC, CTDI∞, midpoint doses f(0)PMMA for a cylindrical polymethyl methacrylate (PMMA) phantom, f(0)Ap for an anthropomorphic phantom and f(0)Pat for a prostate cancer patient, as well as the conventional size specific dose estimations (SSDEconv) and modified SSDE (SSDEmod), with organ dose for the prostate (ODprost) obtained via Monte Carlo (MC) simulation. The ODprost was the reference dose used to find the practical dose index at the center of the pelvic region of a prostate cancer patient. The smallest error rate with respect to the ODprost of 19.3 mGy (reference) among eight dose indices was 5% for f(0)Pat. The practical patient dose index was the f(0)Pat, which showed the smallest error with respect to the reference dose.

Note: Optimization of magnifying a polarization angle with Littrow layout blazed gratings.

Magnification of a polarization angle with Littrow layout gratings has been developed. High magnification with a factor of 7.7 using two gratings in Littrow layout was experimentally proved. The magnification range was investigated by calculation at a wavelength of 10.6 µm. The method can be applied for a high magnification factor >30. Larger groove numbers and smaller blaze angles are suitable for the large magnification. Statistical fluctuation of the diffracted polarization angle is compared with that of the incident polarization angle.

Eddy, drift wave and zonal flow dynamics in a linear magnetized plasma.

Turbulence and its structure formation are universal in neutral fluids and in plasmas. Turbulence annihilates global structures but can organize flows and eddies. The mutual-interactions between flow and the eddy give basic insights into the understanding of non-equilibrium and nonlinear interaction by turbulence. In fusion plasma, clarifying structure formation by Drift-wave turbulence, driven by density gradients in magnetized plasma, is an important issue. Here, a new mutual-interaction among eddy, drift wave and flow in magnetized plasma is discovered. A two-dimensional solitary eddy, which is a perturbation with circumnavigating motion localized radially and azimuthally, is transiently organized in a drift wave - zonal flow (azimuthally symmetric band-like shear flows) system. The excitation of the eddy is synchronized with zonal perturbation. The organization of the eddy has substantial impact on the acceleration of zonal flow.

A Concept of Cross-Ferroic Plasma Turbulence.

The variety of scalar and vector fields in laboratory and nature plasmas is formed by plasma turbulence. Drift-wave fluctuations, driven by density gradients in magnetized plasmas, are known to relax the density gradient while they can generate flows. On the other hand, the sheared flow in the direction of magnetic fields causes Kelvin-Helmholtz type instabilities, which mix particle and momentum. These different types of fluctuations coexist in laboratory and nature, so that the multiple mechanisms for structural formation exist in extremely non-equilibrium plasmas. Here we report the discovery of a new order in plasma turbulence, in which chained structure formation is realized by cross-interaction between inhomogeneities of scalar and vector fields. The concept of cross-ferroic turbulence is developed, and the causal relation in the multiple mechanisms behind structural formation is identified, by measuring the relaxation rate and dissipation power caused by the complex turbulence-driven flux.

Mieap-regulated mitochondrial quality control is frequently inactivated in human colorectal cancer.

Mieap, a p53-inducible protein, controls mitochondrial quality by repairing or eliminating unhealthy mitochondria. BNIP3 and NIX are critical mediators for the Mieap-regulated mitochondrial quality control. Mieap suppresses murine intestinal tumor via its mitochondrial quality control function. To explore the role of the Mieap-regulated mitochondria quality control function in colorectal cancer patients, we examined the statuses of p53, Mieap, BNIP3 and NIX in 57 primary colorectal cancer tissues. Promoter methylation of the Mieap and BNIP3 genes was found in 9% and 47% of colorectal cancer cases, respectively, whereas p53 mutation was found in more than 50% of colorectal cancer tissues lacking methylation of the Mieap and BNIP3 promoters, implying that the p53/Mieap/BNIP3-regulated mitochondria quality control pathway is inactivated in more than 70% of colorectal cancer patients. In LS174T colorectal cancer cells, hypoxia activated the Mieap-regulated mitochondria quality control function. Knockdown of p53, Mieap or BNIP3 in LS174T cells severely impaired the hypoxia-activated function, leading to the accumulation of unhealthy mitochondria and increase of mitochondrial reactive oxygen species generation. The mitochondrial reactive oxygen species generated by unhealthy mitochondria in the p53/Mieap/BNIP3-deficient cells remarkably enhanced cancer cell migration and invasion under hypoxic condition. These results suggest that the Mieap-regulated mitochondria quality control has a critical role in colorectal cancer suppression in the in vivo hypoxic tumor microenvironment.

Note: Magnification of a polarization angle with a Littrow layout brazed grating.

A new method to magnify a small polarization angle with brazed gratings has been developed. In the method, difference in diffraction efficiency for S and P polarization components is used. The magnification dependence on the incident angle can be small by arranging the grating in Littrow layout. A magnification with a factor ~2.7 has been demonstrated for a 10.6 µm CO2 laser beam as expected from a calculation. The method is applicable in many polarimetry fields.

Natural course of dissecting vertebrobasilar artery aneurysms without stroke.

BACKGROUND AND PURPOSE: The natural history and therapeutic management of dissecting vertebrobasilar aneurysms without ischemic or hemorrhagic stroke (nonstroke dissecting vertebrobasilar aneurysms) are not well-established. We conservatively followed patients with nonstroke dissecting vertebrobasilar aneurysms and evaluated the factors related to clinical and morphologic deterioration. MATERIALS AND METHODS: One hundred thirteen patients were enrolled and divided by clinical presentation at diagnosis: asymptomatic (group 1, n = 52), pain only (group 2, n = 56), and mass effect (group 3, n = 5). Patients were conservatively managed without intervention and antithrombotic therapy. Clinical outcomes and morphologic changes were analyzed. RESULTS: A total of 113 patients who were diagnosed with nonstroke dissecting vertebrobasilar aneurysm had a mean follow-up of 2.9 years (range, 27 days to 8 years). Throughout that period, 1 patient in group 1 (1.9%) and 1 patient in group 2 (1.8%) showed clinical deterioration due to mass effect, and 1 patient in group 3 (20%) developed ischemic stroke followed by subarachnoid hemorrhage. Most patients (97.3%) were clinically unchanged. Three patients who had clinical deterioration showed aneurysm enlargement (P < .001). Aneurysms remained morphologically unchanged in 91 patients (80.5%). Aneurysm enlargement was seen in 5 patients (4.4%); risk of enlargement was significantly associated with either maximum diameter (hazard ratio = 1.30; 95% CI, 1.11-11.52; P = .001) or aneurysm ≥10 mm (hazard ratio = 18.0; 95% CI, 1.95-167; P = .011). CONCLUSIONS: The natural course of these lesions suggests that acute intervention is not always required and close follow-up without antithrombotic therapy is reasonable. Patients with symptoms due to mass effect or aneurysms of >10 mm may require treatment.

Development of a novel telomerase assay using the PPDK-luciferin-luciferase detection system.

Telomerase participates in malignant transformation or immortalization of cells, and has attracted attention as an anticancer drug screening and diagnostic tumor marker. We developed a novel telomerase assay called the PPDK-luciferin-luciferase system bioluminescence assay (PLLBA) using pyruvate phosphate dikinase (PPDK). In this assay, pyrophosphate produced by the telomerase reaction and polymerase chain reaction (PCR) is converted to ATP by PPDK, and ATP is detected by the firefly luciferin-luciferase reaction. In this work, telomerase substrate was obtained in accordance with the telomeric repeat amplification protocol (TRAP). Telomerase-positive (500 cells/assay), -inactive (heated for 10 min at 85 °C) and -negative (only Chaps lysis buffer) samples were used. As a result, the findings clearly showed that the signal-to-noise (S/N) ratio of the positive cells was 39.5. After the telomerase reaction and PCR, PLLBA was completed ~ 120 s later. A high level of reproducibility was obtained with - coefficient of variation (CV) of 4.1% (positive cells). The detection limit for cells using telomerase was one cell per assay. This assay for telomerase activity was also shown to be adaptable to human cancer-derived cell lines.

Validation and initial application of a semiautomatic aneurysm measurement software: a tool for assessing volumetric packing attenuation.

BACKGROUND AND PURPOSE: Precise aneurysm measurements and volume embolization ratios are essential for long-term durability of endovascular coil embolization. We evaluated the accuracy of newly developed semiautomatic cerebral aneurysm measurement software, NeuroVision, and explored the value of volume embolization ratio in the prediction of re-treatment. MATERIALS AND METHODS: We compared software-derived volume measurements of 4 silicone aneurysm models with those calculated with an approximation formula and ground truth values (validation study). We used NeuroVision to retrospectively evaluate outcomes of 100 unruptured aneurysms (97 patients) treated with embolization (clinical study). Aneurysm size (height, width, and neck), volume, and volume embolization ratios were calculated for 3 groups (stable, recanalization, and re-treatment) and were compared. RESULTS: This validation study illustrated higher accuracy of NeuroVision in computing aneurysm volume compared with an approximation formula: percentage absolute errors were 4.50% ± 3.18% and 23.07% ± 17.60%, with maximal percentage absolute errors of 8.99% and 45.63%, respectively. Of 100 unruptured aneurysms, 20 recanalized and 12 were re-treated. Average volume embolization ratios of stable and re-treated aneurysms were 24.88% ± 5.91% and 20.50% ± 4.06%, respectively (P ≤ .01). The optimal volume embolization ratio cutoff point for re-treatment was < 19.15%, at which the Youden index was 0.50 (sensitivity, 58.33%; specificity, 87.50%; area under the receiver operating characteristic curve, 0.74). CONCLUSIONS: The NeuroVision software provided accurate aneurysm volume measurements and may be a useful standardized tool to measure aneurysm size and volume, especially for multicenter clinical studies. Volume embolization ratio may be a valuable predictor of aneurysm occlusion changes.

Justification of unruptured intracranial aneurysm repair: a single-center experience.

BACKGROUND AND PURPOSE: Whether to treat UIAs is controversial. The aim of the study was to compare the clinical outcome of patients with UIAs who were either treated conservatively or preventively. MATERIALS AND METHODS: Patients with UIAs referred to our institution were prospectively enrolled in the study. Data collected included baseline characteristics, aneurysmal features, and procedural and follow-up information. Preventive treatment was recommended if the aneurysm was larger than 5 mm and was considered safely treatable. Endovascular surgery was the first-line therapy if the aneurysmal shape was appropriate for coiling. RESULTS: From January 2003 through April 2008, a total of 879 patients with 1110 UIAs were enrolled; 325 patients with 369 UIAs (mean size, 7.8 mm) were treated (treatment group), and 603 patients with 741 UIAs (mean size, 4.4 mm) were managed conservatively (observation group). Mean follow-up was 692.5 days (1405.5 person-years). In the observation group, 26 aneurysms (3.5%) had ruptured (1.8% per year; 1405.5 person-years), 10 patients died, and 7 were disabled (mRS, 3-6: 2.8%). Aneurysmal size was a significant risk factor for rupture (P = .001). The treatment group included aneurysms treated either with coiling (n=315), clipping (n=32), or a combined approach (n=9); 1 patient died, and 3 were disabled (mRS, 3-6: 1.2%). Therapeutic intervention was equal (UIAs of all sizes) or superior (UIAs > 5 mm; P = .025) to conservative management. CONCLUSIONS: Treatment of UIAs was justified in aneurysms larger than 5 mm, and EVS can be safely applied to nearly 90% of UIAs.

Identification of risk factors for fracture of veneering materials and screw loosening of implant-supported fixed partial dentures in partially edentulous cases.

This retrospective study identified the risk factors for fracture of veneering materials and screw loosening of implant-supported fixed partial dentures in partially edentulous cases. The study group included a total of 182 patients who were installed 219 suprastructures at the Fixed Prosthodontic Clinic of Okayama University Dental Hospital between February 1990 and March 2005 and were subdivided in two subgroups: 120 patients (149 facing suprastructures) were included in the subgroup to investigate the risk factors of fracture of veneering materials, and 81 patients (92 suprastructures) were included in the subgroup to identify the risk factors of abutment screw loosening. Each patient was followed up from the day of suprastructure installation until March, 2005. A Cox proportional hazards regression model was used to identify the risk factors related to technical complications, and eight factors were regarded as candidate risk factors. Screw retention was the significant risk factor for fracture of veneering materials, whereas connection of suprastructures with natural tooth was the significant risk factor for screw loosening. It was suggested that screw retention was a significant risk factor for the fracture of veneering materials, and connection of suprastructures with natural tooth was a significant risk factor for screw loosening. Future studies, involving dynamic factors (e.g. bruxism) as predictors as well, are more helpful to discuss the risk factor of fracture of veneering materials and screw loosening.

'I-shaped' sign in the upper mediastinum: a novel potential marker for antenatal diagnosis of d-transposition of the great arteries.

OBJECTIVES: To investigate the 'I-shaped' sign as a novel echocardiographic marker for antenatal diagnosis of d-transposition of the great arteries (dTGA) in routine cardiac examination, and to compare its prevalence in fetuses with dTGA, those with other congenital heart diseases (CHDs) and those with normal structural hearts. METHODS: This retrospective evaluation involved 1134 fetuses undergoing echocardiography to screen for CHD over a 4-year period. I-shaped sign was defined as the characteristic appearance of the aortic arch, resembling the letter 'I', from the most anterior to the most posterior point of the descending aorta visible in the three vessels and trachea view. The frequency of this sign was evaluated in cases with dTGA, those with other cardiac defects and those with normal cardiac structures. RESULTS: CHD was diagnosed in 671 (59.1%) cases, of which 31 (4.6%) had dTGA. I-shaped sign was observed in 30/31 (96.8%) cases of dTGA, compared with 31/640 (4.8%) cases with other cardiac anomalies, which included single ventricle with pulmonary atresia or severe pulmonary stenosis, hypoplastic left heart syndrome with aortic atresia, corrected transposition of the great arteries, and double outlet right ventricle with malposition of the great arteries. I-shaped sign was detected significantly more frequently in the dTGA group compared with the normal group and with the other CHDs group (both P < 0.001) and had 96.8% sensitivity and 97.1% specificity for diagnosis of dTGA. Importantly, I-shaped sign was never observed in fetuses with structurally normal hearts. CONCLUSIONS: Detection on echocardiography of an extremely long vessel with a marked I-shape should raise suspicion of cardiac anomaly, especially dTGA. This marker may therefore aid in the prenatal diagnosis of dTGA during routine ultrasound examination.

Identification of errors in the electron density measurements of a tangential interferometer∕polarimeter system during a tokamak discharge.

A new method for the comparative verification of electron density measurements obtained with a tangential interferometer and a polarimeter during a discharge is proposed. The possible errors associated with the interferometer and polarimeter are classified by the time required for their identification. Based on the characteristics of the errors, the fringe shift error of the interferometer and the low-frequency noise of the polarimeter were identified and corrected for the JT-60U tangential interferometer∕polarimeter system.

International consensus on (ICON) pediatric asthma.

Asthma is the most common chronic lower respiratory disease in childhood throughout the world. Several guidelines and/or consensus documents are available to support medical decisions on pediatric asthma. Although there is no doubt that the use of common systematic approaches for management can considerably improve outcomes, dissemination and implementation of these are still major challenges. Consequently, the International Collaboration in Asthma, Allergy and Immunology (iCAALL), recently formed by the EAACI, AAAAI, ACAAI, and WAO, has decided to propose an International Consensus on (ICON) Pediatric Asthma. The purpose of this document is to highlight the key messages that are common to many of the existing guidelines, while critically reviewing and commenting on any differences, thus providing a concise reference. The principles of pediatric asthma management are generally accepted. Overall, the treatment goal is disease control. To achieve this, patients and their parents should be educated to optimally manage the disease, in collaboration with healthcare professionals. Identification and avoidance of triggers is also of significant importance. Assessment and monitoring should be performed regularly to re-evaluate and fine-tune treatment. Pharmacotherapy is the cornerstone of treatment. The optimal use of medication can, in most cases, help patients control symptoms and reduce the risk for future morbidity. The management of exacerbations is a major consideration, independent of chronic treatment. There is a trend toward considering phenotype-specific treatment choices; however, this goal has not yet been achieved.

Response shift in oral health-related quality of life measurement in patients with partial edentulism.

The purposes of this study were to determine whether a response shift was observable after partial denture treatment and to identify the predictors that influenced the response shift magnitude and direction. A total of 173 consecutive patients with no more than eight missing teeth who received implant-supported, fixed or removable partial dentures at Okayama University Dental Hospital were asked to complete a full-version Oral Health-Related Quality of Life (OHRQoL) questionnaire before (pre-test) and after treatment (post-test). Additionally, a short form (then-test) consisting of seven questions selected from the full version had its reliability verified and was utilised to retrospectively assess the pre-treatment OHRQoL status. The difference between the summary scores of the then-test and the pre-test determined the response shift magnitude and direction. The then-test mean score (22·9 ± 6·6) was significantly lower (worse OHRQoL) than that of the pre-test (26·4 ± 5·2). The response shift effect size was of moderate magnitude and negative direction (d = -0·78). A multiple regression analysis showed that age (younger patients) (P < 0·01), number of replaced teeth (fewer) (P < 0·01) and pre-test scores (lower) (P < 0·01) were the significant predictors for response shift. In conclusion, a response shift phenomenon with negative and moderate effect size was observed after partial denture treatment. The significant predictor variables were young age, fewer numbers of replaced teeth and lower pre-test scores.

Observation of long-distance radial correlation in toroidal plasma turbulence.

This Letter presents the discovery of macroscale electron temperature fluctuations with a long radial correlation length comparable to the plasma minor radius in a toroidal plasma. Their spatiotemporal structure is characterized by a low frequency of ∼1-3 kHz, ballistic radial propagation, a poloidal or toroidal mode number of m/n=1/1 (or 2/1), and an amplitude of ∼2% at maximum. Nonlinear coupling between the long-range fluctuations and the microscopic fluctuations is identified. A change of the amplitude of the long-range fluctuation is transmitted across the plasma radius at the velocity which is of the order of the drift velocity.