Impact of Radiofrequency Exposure From Mobile Phones on the Risk of Developing Brain Tumors in Korean and Japanese Adolescents: A MOBI-Kids Case-control Study.

BACKGROUND: This study aimed to examine the association between risk of brain tumors and radiofrequency (RF) exposure from mobile phones among young people in Korea and Japan. METHODS: This case-control study of brain tumors in young people was conducted in Korea and Japan under the framework of the international MOBI-Kids study. We included 118 patients diagnosed with brain tumors between 2011 and 2015 and 236 matched appendicitis controls aged 10-24 years. Information on mobile phone use was collected through face-to-face interviews. A detailed RF exposure algorithm, based on the MOBI-Kids algorithm and modified to account for the specificities of Japanese and Korean phones and networks, was used to calculate the odds ratios (ORs) for total cumulative specific energy using conditional logistic regression. RESULTS: The adjusted ORs in the highest tertile of cumulative call time at 1 year before the reference date were 1.61 (95% confidence interval [CI], 0.72-3.60) for all brain tumors and 0.70 (95% CI, 0.16-3.03) for gliomas, with no indication of a trend with exposure. The ORs for glioma specifically, were below 1 in the lowest exposure category. CONCLUSION: This study provided no evidence of a causal association between mobile phone use and risk of brain tumors as a whole or of glioma specifically. Further research will be required to evaluate the impact of newer technologies of communication in the future.

[Late toxicity following primary conservative treatment : Dysphagia and xerostomia]. / Spättoxizität nach primär konservativer Therapie : Dysphagie und Xerostomie.

Dysphagia and xerostomia are still among the most important acute and late side effects of radiotherapy. Technical developments over the past two decades have led to improved diagnostics and recognition as well as understanding of the causes of these side effects. Based on these findings and advances in both treatment planning and irradiation techniques, the incidence and severity of treatment-associated radiogenic late sequelae could be clearly reduced by the use of intensity-modulated radiotherapy (IMRT), which could contribute to marked long-term improvements in the quality of life in patients with head and neck cancer. Highly conformal techniques, such as proton therapy have the potential to further reduce treatment-associated side effects in head and neck oncology and are currently being prospectively tested within clinical trial protocols at several centers.

Outcomes with durvalumab by tumour PD-L1 expression in unresectable, stage III non-small-cell lung cancer in the PACIFIC trial.

BACKGROUND: In the PACIFIC trial, durvalumab significantly improved progression-free and overall survival (PFS/OS) versus placebo, with manageable safety, in unresectable, stage III non-small-cell lung cancer (NSCLC) patients without progression after chemoradiotherapy (CRT). We report exploratory analyses of outcomes by tumour cell (TC) programmed death-ligand 1 (PD-L1) expression. PATIENTS AND METHODS: Patients were randomly assigned (2:1) to intravenous durvalumab 10 mg/kg every 2 weeks or placebo ≤12 months, stratified by age, sex, and smoking history, but not PD-L1 status. Where available, pre-CRT samples were tested for PD-L1 expression (immunohistochemistry) and scored at pre-specified (25%) and post hoc (1%) TC cut-offs. Treatment-effect hazard ratios (HRs) were estimated from unstratified Cox proportional hazards models (Kaplan-Meier-estimated medians). RESULTS: In total, 713 patients were randomly assigned, 709 of whom received at least 1 dose of study treatment durvalumab (n = 473) or placebo (n = 236). Some 451 (63%) were PD-L1-assessable: 35%, 65%, 67%, 33%, and 32% had TC ≥25%, <25%, ≥1%, <1%, and 1%-24%, respectively. As of 31 January 2019, median follow-up was 33.3 months. Durvalumab improved PFS versus placebo (primary-analysis data cut-off, 13 February 2017) across all subgroups [HR, 95% confidence interval (CI); medians]: TC ≥25% (0.41, 0.26-0.65; 17.8 versus 3.7 months), <25% (0.59, 0.43-0.82; 16.9 versus 6.9 months), ≥1% (0.46, 0.33-0.64; 17.8 versus 5.6 months), <1% (0.73, 0.48-1.11; 10.7 versus 5.6 months), 1%-24% [0.49, 0.30-0.80; not reached (NR) versus 9.0 months], and unknown (0.59, 0.42-0.83; 14.0 versus 6.4 months). Durvalumab improved OS across most subgroups (31 January 2019 data cut-off; HR, 95% CI; medians): TC ≥ 25% (0.50, 0.30-0.83; NR versus 21.1 months), <25% (0.89, 0.63-1.25; 39.7 versus 37.4 months), ≥1% (0.59, 0.41-0.83; NR versus 29.6 months), 1%-24% (0.67, 0.41-1.10; 43.3 versus 30.5 months), and unknown (0.60, 0.43-0.84; 44.2 versus 23.5 months), but not <1% (1.14, 0.71-1.84; 33.1 versus 45.6 months). Safety was similar across subgroups. CONCLUSIONS: PFS benefit with durvalumab was observed across all subgroups, and OS benefit across all but TC <1%, for which limitations and wide HR CI preclude robust conclusions.

ß Decay of

The interpretation of observations of cooling neutron star crusts in quasipersistent x-ray transients is affected by predictions of the strength of neutrino cooling via crust Urca processes. The strength of crust Urca neutrino cooling depends sensitively on the electron-capture and ß-decay ground-state-to-ground-state transition strengths of neutron-rich rare isotopes. Nuclei with a mass number of A=61 are predicted to be among the most abundant in accreted crusts, and the last remaining experimentally undetermined ground-state-to-ground-state transition strength was the ß decay of ^{61}V. This Letter reports the first experimental determination of this transition strength, a ground-state branching of 8.1_{-3.1}^{+4.0}%, corresponding to a log ft value of 5.5_{-0.2}^{+0.2}. This result was achieved through the measurement of the ß-delayed γ rays using the total absorption spectrometer SuN and the measurement of the ß-delayed neutron branch using the neutron long counter system NERO at the National Superconducting Cyclotron Laboratory at Michigan State University. This method helps to mitigate the impact of the pandemonium effect in extremely neutron-rich nuclei on experimental results. The result implies that A=61 nuclei do not provide the strongest cooling in accreted neutron star crusts as expected by some predictions, but that their cooling is still larger compared to most other mass numbers. Only nuclei with mass numbers 31, 33, and 55 are predicted to be cooling more strongly. However, the theoretical predictions for the transition strengths of these nuclei are not consistently accurate enough to draw conclusions on crust cooling. With the experimental approach developed in this work, all relevant transitions are within reach to be studied in the future.

Constraining the Neutron Star Compactness: Extraction of the

The ^{23}Al(p,γ)^{24}Si reaction is among the most important reactions driving the energy generation in type-I x-ray bursts. However, the present reaction-rate uncertainty limits constraints on neutron star properties that can be achieved with burst model-observation comparisons. Here, we present a novel technique for constraining this important reaction by combining the GRETINA array with the neutron detector LENDA coupled to the S800 spectrograph at the National Superconducting Cyclotron Laboratory. The ^{23}Al(d,n) reaction was used to populate the astrophysically important states in ^{24}Si. This enables a measurement in complete kinematics for extracting all relevant inputs necessary to calculate the reaction rate. For the first time, a predicted close-lying doublet of a 2_{2}^{+} and (4_{1}^{+},0_{2}^{+}) state in ^{24}Si was disentangled, finally resolving conflicting results from two previous measurements. Moreover, it was possible to extract spectroscopic factors using GRETINA and LENDA simultaneously. This new technique may be used to constrain other important reaction rates for various astrophysical scenarios.

Approaching the Gamow Window with Stored Ions: Direct Measurement of

We report the first measurement of low-energy proton-capture cross sections of ^{124}Xe in a heavy-ion storage ring. ^{124}Xe^{54+} ions of five different beam energies between 5.5 and 8 AMeV were stored to collide with a windowless hydrogen target. The ^{125}Cs reaction products were directly detected. The interaction energies are located on the high energy tail of the Gamow window for hot, explosive scenarios such as supernovae and x-ray binaries. The results serve as an important test of predicted astrophysical reaction rates in this mass range. Good agreement in the prediction of the astrophysically important proton width at low energy is found, with only a 30% difference between measurement and theory. Larger deviations are found above the neutron emission threshold, where also neutron and γ widths significantly impact the cross sections. The newly established experimental method is a very powerful tool to investigate nuclear reactions on rare ion beams at low center-of-mass energies.

Predictive biomarkers for response to EGFR-directed monoclonal antibodies for advanced squamous cell lung cancer.

Background: Upregulated expression and aberrant activation of the epidermal growth-factor receptor (EGFR) are found in lung cancer, making EGFR a relevant target for non-small-cell lung cancer (NSCLC). Treatment with anti-EGFR monoclonal antibodies (mAbs) is associated with modest improvement in overall survival in patients with squamous cell lung cancer (SqCLC) who have a significant unmet need for effective treatment options. While there is evidence that using EGFR gene copy number, EGFR mutation, and EGFR protein expression as biomarkers can help select patients who respond to treatment, it is important to consider biomarkers for response in patients treated with combination therapies that include EGFR mAbs. Design: Randomized trials of EGFR-directed mAbs cetuximab and necitumumab in combination with chemotherapy, immunotherapy, or antiangiogenic therapy in patients with advanced NSCLC, including SqCLC, were searched in the literature. Results of associations of potential biomarkers and outcomes were summarized. Results: Data from phase III clinical trials indicate that patients with NSCLC, including SqCLC, whose tumors express high levels of EGFR protein (H-score of ≥200) and/or gene copy numbers of EGFR (e.g. ≥40% cells with ≥4 EGFR copies as detected by fluorescence in situ hybridization; gene amplification in ≥10% of analyzed cells) derive greater therapeutic benefits from EGFR-directed mAbs. Biomarker data are limited for EGFR mAbs used in combination with immunotherapy and are absent when used in combination with antiangiogenic agents. Conclusions: Therapy with EGFR-directed mAbs in combination with chemotherapy is associated with greater clinical benefits in patients with NSCLC, including SqCLC, whose tumors express high levels of EGFR protein and/or have increased EGFR gene copy number. These data support validating the role of these as biomarkers to identify those patients who derive the greatest clinical benefit from EGFR mAb therapy. However, data on biomarkers for EGFR-directed mAbs combined with immunotherapy or antiangiogenic agents remain limited.

Observation of the Isovector Giant Monopole Resonance via the

The (^{10}Be,^{10}B^{*}[1.74 MeV]) charge-exchange reaction at 100 AMeV is presented as a new probe for isolating the isovector (ΔT=1) nonspin-transfer (ΔS=0) response of nuclei, with ^{28}Si being the first nucleus studied. By using a secondary ^{10}Be beam produced by fast fragmentation of ^{18}O nuclei at the NSCL Coupled Cyclotron Facility, applying the dispersion-matching technique with the S800 magnetic spectrometer to determine the excitation energy in ^{28}Al, and performing high-resolution γ-ray tracking with the Gamma-Ray Energy Tracking In-beam Nuclear Array (GRETINA) to identify the 1022-keV γ ray associated with the decay from the 1.74-MeV T=1 isobaric analog state in ^{10}B, a ΔS=0 excitation-energy spectrum in ^{28}Al was extracted. Monopole and dipole contributions were determined through a multipole-decomposition analysis, and the isovector giant dipole resonance and isovector giant monopole resonance (IVGMR) were identified. The results show that this probe is a powerful tool for studying the elusive IVGMR, which is of interest for performing stringent tests of modern density functional theories at high excitation energies and for constraining the bulk properties of nuclei and nuclear matter. The extracted distributions were compared with theoretical calculations based on the normal-modes formalism and the proton-neutron relativistic time-blocking approximation. Calculated cross sections based on these strengths underestimate the data by about a factor of 2, which likely indicates deficiencies in the reaction calculations based on the distorted wave Born approximation.

Isospin Mixing Reveals

The thermonuclear ^{30}P(p,γ)^{31}S reaction rate is critical for modeling the final elemental and isotopic abundances of ONe nova nucleosynthesis, which affect the calibration of proposed nova thermometers and the identification of presolar nova grains, respectively. Unfortunately, the rate of this reaction is essentially unconstrained experimentally, because the strengths of key ^{31}S proton capture resonance states are not known, largely due to uncertainties in their spins and parities. Using the ß decay of ^{31}Cl, we have observed the ß-delayed γ decay of a ^{31}S state at E_{x}=6390.2(7) keV, with a ^{30}P(p,γ)^{31}S resonance energy of E_{r}=259.3(8) keV, in the middle of the ^{30}P(p,γ)^{31}S Gamow window for peak nova temperatures. This state exhibits isospin mixing with the nearby isobaric analog state at E_{x}=6279.0(6) keV, giving it an unambiguous spin and parity of 3/2^{+} and making it an important l=0 resonance for proton capture on ^{30}P.

Survival, quality-adjusted survival, and other clinical end points in older advanced non-small-cell lung cancer patients treated with albumin-bound paclitaxel.

BACKGROUND: This analysis compared the quality-adjusted survival and clinical outcomes of albumin-bound paclitaxel+carboplatin (nab-PC) vs solvent-based paclitaxel+carboplatin (sb-PC) as first-line therapy in advanced non-small-cell lung cancer (NSCLC) in older patients. METHODS: Using age-based subgroup data from a randomised Phase-3 clinical trial, nab-PC and sb-PC were compared with respect to overall response rate (ORR), overall survival (OS), progression-free survival (PFS), quality of life (QoL), safety/toxicity, and quality-adjusted time without symptoms or toxicity (Q-TWiST) with ages ⩾60 and ⩾70 years as cut points. RESULTS: Among patients aged ⩾60 years (N=546), nab-PC (N=265) significantly increased ORR and prolonged OS, despite a non-significant improvement in PFS, vs sb-PC (N=281). Nab-PC improved QoL and was associated with less neuropathy, arthralgia, and myalgia but resulted in more anaemia and thrombocytopenia. Nab-PC yielded significant Q-TWiST benefits (11.1 vs 9.8 months; 95% CI of gain: 0.2-2.6), with a relative Q-TWiST gain of 10.8% (ranging from 6.4% to 15.1% in threshold analysis). In the ⩾70 years age group, nab-PC showed similar, but non-significant, ORR, PFS, and Q-TWiST benefits and significantly improved OS and QoL. CONCLUSION: Nab-PC as first-line therapy in older patients with advanced NSCLC increased ORR, OS, and QoL and resulted in quality-adjusted survival gains compared with standard sb-PC.

Mass Measurement of 56Sc Reveals a Small A = 56 Odd-Even Mass Staggering, Implying a Cooler Accreted Neutron Star Crust.

We present the mass excesses of (52-57)Sc, obtained from recent time-of-flight nuclear mass measurements at the National Superconducting Cyclotron Laboratory at Michigan State University. The masses of 56Sc and 57Sc were determined for the first time with atomic mass excesses of -24.85(59)((-54)(+0)) MeV and -21.0(1.3) MeV, respectively, where the asymmetric uncertainty for 56Sc was included due to possible contamination from a long-lived isomer. The 56Sc mass indicates a small odd-even mass staggering in the A = 56 mass chain towards the neutron drip line, significantly deviating from trends predicted by the global FRDM mass model and favoring trends predicted by the UNEDF0 and UNEDF1 density functional calculations. Together with new shell-model calculations of the electron-capture strength function of 56Sc, our results strongly reduce uncertainties in model calculations of the heating and cooling at the 56Ti electron-capture layer in the outer crust of accreting neutron stars. We find that, in contrast to previous studies, neither strong neutrino cooling nor strong heating occurs in this layer. We conclude that Urca cooling in the outer crusts of accreting neutron stars that exhibit superbursts or high temperature steady-state burning, which are predicted to be rich in A≈56 nuclei, is considerably weaker than predicted. Urca cooling must instead be dominated by electron capture on the small amounts of adjacent odd-A nuclei contained in the superburst and high temperature steady-state burning ashes. This may explain the absence of strong crust Urca cooling inferred from the observed cooling light curve of the transiently accreting x-ray source MAXI J0556-332.

Mass measurements demonstrate a strong N=28 shell gap in argon.

We present results from recent time-of-flight nuclear mass measurements at the National Superconducting Cyclotron Laboratory at Michigan State University. We report the first mass measurements of ^{48}Ar and ^{49}Ar and find atomic mass excesses of -22.28(31) MeV and -17.8(1.1) MeV, respectively. These masses provide strong evidence for the closed shell nature of neutron number N=28 in argon, which is therefore the lowest even-Z element exhibiting the N=28 closed shell. The resulting trend in binding-energy differences, which probes the strength of the N=28 shell, compares favorably with shell-model calculations in the sd-pf shell using SDPF-U and SDPF-MU Hamiltonians.

Longitudinal analysis of 25 sequential sample-pairs using a custom multiple myeloma mutation sequencing panel (M(3)P).

Recent advances in genomic sequencing technologies now allow results from deep next-generation sequencing to be obtained within clinically meaningful timeframes, making this an attractive approach to better guide personalized treatment strategies. No multiple myeloma-specific gene panel has been established so far; we therefore designed a 47-gene-targeting gene panel, containing 39 genes known to be mutated in ≥3 % of multiple myeloma cases and eight genes in pathways therapeutically targeted in multiple myeloma (MM). We performed targeted sequencing on tumor/germline DNA of 25 MM patients in which we also had a sequential sample post treatment. Mutation analysis revealed KRAS as the most commonly mutated gene (36 % in each time point), followed by NRAS (20 and 16 %), TP53 (16 and 16 %), DIS3 (16 and 16 %), FAM46C (12 and 16 %), and SP140 (12 and 12 %). We successfully tracked clonal evolution and identified mutation acquisition and/or loss in FAM46C, FAT1, KRAS, NRAS, SPEN, PRDM1, NEB, and TP53 as well as two mutations in XBP1, a gene associated with bortezomib resistance. Thus, we present the first longitudinal analysis of a MM-specific targeted sequencing gene panel that can be used for individual tumor characterization and for tracking clonal evolution over time.

Electrical transport properties of Ge-doped GaN nanowires.

The conductivity and charge carrier concentration of single GaN nanowires (NWs) doped with different concentrations of Ge were determined by four-point resistivity and temperature-dependent Seebeck coefficient measurements. We observed high carrier concentrations ranging from 9.1 × 10(18) to 5.5 × 10(19) cm(-3), well above the Mott density of 1.6 × 10(18) cm(-3), and conductivities up to 625 S cm(-1) almost independent of the NW diameter. The weak temperature dependence of the conductivity between 2 and 10 K could be assigned to the formation of an impurity band. For the sample with the highest conductivity metallic behaviour was found, indicated by a positive temperature coefficient of the resistivity. The near band edge emission analyzed by micro-photoluminescence spectroscopy showed only a small increase of the peak width up to 70 meV and no spectral shift for carrier concentrations up to 5.5 × 10(19) cm(-3). The latter was attributed to the simultaneous influence of band filling, band gap renormalization, and strain.

Entangled mechanical oscillators.

Hallmarks of quantum mechanics include superposition and entanglement. In the context of large complex systems, these features should lead to situations as envisaged in the 'Schrödinger's cat' thought experiment (where the cat exists in a superposition of alive and dead states entangled with a radioactive nucleus). Such situations are not observed in nature. This may be simply due to our inability to sufficiently isolate the system of interest from the surrounding environment-a technical limitation. Another possibility is some as-yet-undiscovered mechanism that prevents the formation of macroscopic entangled states. Such a limitation might depend on the number of elementary constituents in the system or on the types of degrees of freedom that are entangled. Tests of the latter possibility have been made with photons, atoms and condensed matter devices. One system ubiquitous to nature where entanglement has not been previously demonstrated consists of distinct mechanical oscillators. Here we demonstrate deterministic entanglement of separated mechanical oscillators, consisting of the vibrational states of two pairs of atomic ions held in different locations. We also demonstrate entanglement of the internal states of an atomic ion with a distant mechanical oscillator. These results show quantum entanglement in a degree of freedom that pervades the classical world. Such experiments may lead to the generation of entangled states of larger-scale mechanical oscillators, and offer possibilities for testing non-locality with mesoscopic systems. In addition, the control developed here is an important ingredient for scaling-up quantum information processing with trapped atomic ions.

Epiregulin gene expression as a biomarker of benefit from cetuximab in the treatment of advanced colorectal cancer.

BACKGROUND: Anti-EGFR antibody, cetuximab, improves overall survival (OS) in K-ras wild-type chemotherapy-refractory colorectal cancer. Epidermal growth factor receptor ligand epiregulin (EREG) gene expression may further predict cetuximab benefit. METHODS: Tumour samples from a phase III clinical trial of cetuximab plus best supportive care (BSC) vs BSC alone (CO.17) were analysed for EREG mRNA gene expression. Predictive effects of high vs low EREG on OS and progression-free survival (PFS) were examined for treatment-biomarker interaction. RESULTS: Both EREG and K-ras status were ascertained in 385 (193 cetuximab, 192 BSC) tumour samples. Within the high EREG and K-ras wild-type status ('co-biomarker')-positive group (n=139, 36%), median PFS was 5.4 vs 1.9 months (hazard ratio (HR) 0.31; P<0.0001), and median OS was 9.8 vs 5.1 months (HR 0.43; P<0.001) for cetuximab vs BSC, respectively. In the rest (n=246, 64%), PFS (HR 0.82; P=0.12) and OS (HR 0.90; P=0.45) were not significantly different. Test for treatment interaction showed a larger cetuximab effect on OS (HR 0.52; P=0.007) and PFS (HR 0.49; P=0.001) in the co-biomarker-positive group. CONCLUSION: In pre-treated K-ras wild-type status colorectal cancer, patients with high EREG gene expression appear to benefit more from cetuximab therapy compared with low expression. Epiregulin as a selective biomarker requires further evaluation.

Evolution of collectivity in 72Kr: evidence for rapid shape transition.

The transition rates from the yrast 2+ and 4+ states in the self-conjugate 72Kr nucleus were studied via lifetime measurements employing the GRETINA array with a novel application of the recoil-distance method. The large collectivity observed for the 4+→2+ transition suggests a prolate character of the excited states. The reduced collectivity previously reported for the 2+→0+ transition was confirmed. The irregular behavior of collectivity points to the occurrence of a rapid oblate-prolate shape transition in 72Kr, providing stringent tests for advanced theories to describe the shape coexistence and its evolution.

Determining the rp-process flow through 56Ni: resonances in 57Cu(p,γ)58Zn identified with GRETINA.

An approach is presented to experimentally constrain previously unreachable (p, γ) reaction rates on nuclei far from stability in the astrophysical rp process. Energies of all critical resonances in the (57)Cu(p,γ)(58)Zn reaction are deduced by populating states in (58)Zn with a (d, n) reaction in inverse kinematics at 75 MeV/u, and detecting γ-ray-recoil coincidences with the state-of-the-art γ-ray tracking array GRETINA and the S800 spectrograph at the National Superconducting Cyclotron Laboratory. The results reduce the uncertainty in the (57)Cu(p,γ) reaction rate by several orders of magnitude. The effective lifetime of (56)Ni, an important waiting point in the rp process in x-ray bursts, can now be determined entirely from experimentally constrained reaction rates.

ß+ Gamow-Teller transition strengths from 46Ti and stellar electron-capture rates.

The Gamow-Teller strength in the ß(+) direction to (46)Sc was extracted via the (46)Ti(t,(3)He + γ) reaction at 115 MeV/u. The γ-ray coincidences served to precisely measure the very weak Gamow-Teller transition to a final state at 991 keV. Although this transition is weak, it is crucial for accurately estimating electron-capture rates in astrophysical scenarios with relatively low stellar densities and temperatures, such as presupernova stellar evolution. Shell-model calculations with different effective interactions in the pf shell-model space do not reproduce the experimental Gamow-Teller strengths, which is likely due to sd-shell admixtures. Calculations in the quasiparticle random phase approximation that are often used in astrophysical simulations also fail to reproduce the experimental Gamow-Teller strength distribution, leading to strongly overestimated electron-capture rates. Because reliable theoretical predictions of Gamow-Teller strengths are important for providing astrophysical electron-capture reaction rates for a broad set of nuclei in the lower pf shell, we conclude that further theoretical improvements are required to match astrophysical needs.