Gemcitabine, carboplatin, and Epstein Barr virus-specific autologous cytotoxic T lymphocytes for recurrent or metastatic nasopharyngeal carcinoma: VANCE, an international randomized Phase 3 trial.

BACKGROUND: Epstein-Barr virus-specific cytotoxic T lymphocyte (EBV-CTL) is an autologous adoptive T cell immunotherapy generated from the blood of individuals and manufactured without genetic modification. In a previous Phase 2 trial of locally recurrent or metastatic nasopharyngeal cancer (R/M NPC) patients, first-line gemcitabine and carboplatin (GC) and EBV-CTL combination demonstrated objective anti-tumor EBV-CTL activity and a favorable safety profile. The present study explored whether this combined first-line chemo-immunotherapy strategy would produce superior clinical efficacy and better quality of life compared to conventional chemotherapy treatment. PATIENTS AND METHODS: This multicenter, randomized, Phase 3 trial evaluated the efficacy and safety of GC followed by EBV-CTL vs. GC alone as first-line treatment for R/M NPC patients. Thirty clinical sites in Singapore, Malaysia, Taiwan, Thailand, and the United States (US) were included. Subjects were randomized to first-line GC (4 cycles) and EBV-CTL (6 cycles) or GC (6 cycles) in a 1:1 ratio. The primary outcome was overall survival (OS) and secondary outcomes included progression-free survival, objective response rate, clinical benefit rate, quality of life, and safety. CLINICALTRIALS: gov identifier: NCT02578641. RESULTS: 330 subjects with NPC were enrolled. Most subjects in both treatment arms received ≥4 cycles of chemotherapy and most subjects in the GC+EBV-CTL group received ≥2 infusions of EBV-CTL. The central Good Manufacturing Practices (GMP) facility produced sufficient EBV-CTL for 94% of GC+EBV-CTL subjects. The median OS was 25.0 months in the GC+EBV-CTL group and 24.9 months in the GC group (hazard ratio = 1.19; 95% CI: 0.91, 1.56; P = 0.194). Only 1 subject experienced a Grade 2 serious adverse event related to EBV-CTL. CONCLUSION: GC+EBV-CTL in subjects with R/M NPC demonstrated a favorable safety profile but no overall improvement in OS vs. chemotherapy. This is the largest adoptive T cell therapy trial reported in solid tumors to date.

Proton Shell Gaps in N=28 Nuclei from the First Complete Spectroscopy Study with FRIB Decay Station Initiator.

The first complete measurement of the ß-decay strength distribution of _{17}^{45}Cl_{28} was performed at the Facility for Rare Isotope Beams (FRIB) with the FRIB Decay Station Initiator during the second FRIB experiment. The measurement involved the detection of neutrons and γ rays in two focal planes of the FRIB Decay Station Initiator in a single experiment for the first time. This enabled an analytical consistency in extracting the ß-decay strength distribution over the large range of excitation energies, including neutron unbound states. We observe a rapid increase in the ß-decay strength distribution above the neutron separation energy in _{18}^{45}Ar_{27}. This was interpreted to be caused by the transitioning of neutrons into protons excited across the Z=20 shell gap. The SDPF-MU interaction with reduced shell gap best reproduced the data. The measurement demonstrates a new approach that is sensitive to the proton shell gap in neutron rich nuclei according to SDPF-MU calculations.

Study of the

The ^{22}Mg(α,p)^{25}Al reaction rate has been identified as a major source of uncertainty for understanding the nucleosynthesis flow in Type-I x-ray bursts. We report a direct measurement of the energy- and angle-integrated cross sections of this reaction in a 3.3-6.9 MeV center-of-mass energy range using the MUlti-Sampling Ionization Chamber (MUSIC). The new ^{22}Mg(α,p)^{25}Al reaction rate is a factor of ∼4 higher than the previous direct measurement of this reaction within temperatures relevant for x-ray bursts, resulting in the ^{22}Mg waiting point of x-ray burst nucleosynthesis flow to be significantly bypassed via the (α,p) reaction.

Microsecond Isomer at the N=20 Island of Shape Inversion Observed at FRIB.

Excited-state spectroscopy from the first experiment at the Facility for Rare Isotope Beams (FRIB) is reported. A 24(2)-µs isomer was observed with the FRIB Decay Station initiator (FDSi) through a cascade of 224- and 401-keV γ rays in coincidence with ^{32}Na nuclei. This is the only known microsecond isomer (1 µs≤T_{1/2}<1 ms) in the region. This nucleus is at the heart of the N=20 island of shape inversion and is at the crossroads of the spherical shell-model, deformed shell-model, and ab initio theories. It can be represented as the coupling of a proton hole and neutron particle to ^{32}Mg, ^{32}Mg+π^{-1}+ν^{+1}. This odd-odd coupling and isomer formation provides a sensitive measure of the underlying shape degrees of freedom of ^{32}Mg, where the onset of spherical-to-deformed shape inversion begins with a low-lying deformed 2^{+} state at 885 keV and a low-lying shape-coexisting 0_{2}^{+} state at 1058 keV. We suggest two possible explanations for the 625-keV isomer in ^{32}Na: a 6^{-} spherical shape isomer that decays by E2 or a 0^{+} deformed spin isomer that decays by M2. The present results and calculations are most consistent with the latter, indicating that the low-lying states are dominated by deformation.

First Direct Measurement Constraining the

The rate of the final step in the astrophysical αp process, the ^{34}Ar(α,p)^{37}K reaction, suffers from large uncertainties due to a lack of experimental data, despite having a considerable impact on the observable light curves of x-ray bursts and the composition of the ashes of hydrogen and helium burning on accreting neutron stars. We present the first direct measurement constraining the ^{34}Ar(α,p)^{37}K reaction cross section, using the Jet Experiments in Nuclear Structure and Astrophysics gas jet target. The combined cross section for the ^{34}Ar,Cl(α,p)^{37}K,Ar reaction is found to agree well with Hauser-Feshbach predictions. The ^{34}Ar(α,2p)^{36}Ar cross section, which can be exclusively attributed to the ^{34}Ar beam component, also agrees to within the typical uncertainties quoted for statistical models. This indicates the applicability of the statistical model for predicting astrophysical (α,p) reaction rates in this part of the αp process, in contrast to earlier findings from indirect reaction studies indicating orders-of-magnitude discrepancies. This removes a significant uncertainty in models of hydrogen and helium burning on accreting neutron stars.

Crossing N=28 Toward the Neutron Drip Line: First Measurement of Half-Lives at FRIB.

New half-lives for exotic isotopes approaching the neutron drip-line in the vicinity of N∼28 for Z=12-15 were measured at the Facility for Rare Isotope Beams (FRIB) with the FRIB decay station initiator. The first experimental results are compared to the latest quasiparticle random phase approximation and shell-model calculations. Overall, the measured half-lives are consistent with the available theoretical descriptions and suggest a well-developed region of deformation below ^{48}Ca in the N=28 isotones. The erosion of the Z=14 subshell closure in Si is experimentally confirmed at N=28, and a reduction in the ^{38}Mg half-life is observed as compared with its isotopic neighbors, which does not seem to be predicted well based on the decay energy and deformation trends. This highlights the need for both additional data in this very exotic region, and for more advanced theoretical efforts.

Effects of acidified blanching water and pectinase enzyme pretreatments on physicochemical properties and antioxidant capacity of Carica papaya juice.

The high pectin content in papaya (Carica papaya) causes the juice extraction to be difficult and results in a low yield. This study aims to determine the effect of acidified blanching water and pectinase enzyme pretreatments on the yield, physicochemical properties, and antioxidant activities of the papaya juice. For acidified blanching treatment, papaya cubes (3 cm3 ) were blanched in water containing 0%, 0.5%, 1.5%, and 2.5% w/v citric acid at 95℃ for 2 min. For enzyme treatment, a pectinase enzyme (10, 20, and 30 ppm) was added to the homogenous papaya puree and incubated at 45℃ (200 rpm) for 60 min. The enzyme reaction was stopped by pasteurization at 74℃ for 2 min. The puree was filtered, and the juice was pasteurized at 74℃ for 7 min. All pretreated papaya juice were analyzed for physicochemical properties (color, clarity, viscosity, pH, total soluble solids [TSSs], total carotenoid content, total phenolic content [TPC], and total flavonoid content [TFC]), and antioxidant activities (2,2-diphenyl-1-picrylhydrazyl [DPPH] and ferric reducing antioxidant power [FRAP] assay). Both pretreatments improved the clarity of papaya juice, and was significantly greater after pretreatment with pectinase enzyme. The TPC and antioxidant activities of papaya juice were conserved and maintained by acidified blanching at 1.5% (w/v) citric acid. Increased concentrations of pectinase enzyme significantly reduced the TPC and total carotenoid content. Pretreatment with pectinase enzyme up to 20 ppm does not significantly reduce the TFC and antioxidant activities. Acidified blanching and pectinase enzyme pretreatments have an impact on extraction of papaya fruit juice while retaining the nutritional composition of the juice. PRACTICAL APPLICATION: Papaya (Carica papaya) is a fruit with great nutritional values but is highly perishable and prone to postharvest loss. Juice has become a more cost-effective and convenient option for preserving the fruit. However, since papaya is a pectin-rich fruit, the extraction of juice using mechanical pressing is difficult due to the bonding of juice to the pulp in the form of a jellied mass, which results in juice with low yield. Using acidified blanching and pectinase enzyme to clarify the juice not only increases the yield but also retains the nutrient composition of the juice.

Non-gestational choriocarcinoma of the ovary: A case report.

Non-gestational choriocarcinoma of the ovary is an extremely rare clinical condition. Very few cases of this high-grade malignancy of the ovary are reported in the literature worldwide. Given the rarity of the tumour, this disease is generally overlooked, which leads to delayed diagnosis and management. For the attending clinicians, the non-gestational choriocarcinoma of the ovary poses a diagnostic challenge due to its non-specific clinical presentations. A 16-year-old girl presented with pain in the right iliac fossa and with a positive urine pregnancy test. Despite being sexually inactive, the patient was diagnosed with an ectopic pregnancy and underwent emergency laparoscopic surgery. Six weeks later, the histopathological analysis revealed a diagnosis of non-gestational choriocarcinoma of the ovary. Further evaluations showed that her cancer had already advanced to stage IV. In this case report, the non-specific presentations of the disease, radiological features, current treatments, and possible safety strategies are discussed.

Evolving Practice Pattern of Palliative Radiation Therapy for Bone Metastases from Lung Cancer in Australia.

AIMS: Radiation therapy is an effective treatment for bone metastases. Single-fraction conformal radiation therapy (SF-CRT) is equally effective as multifraction radiation therapy for the management of uncomplicated bone metastases. There has been a rapid development of advanced radiation therapy techniques (ART) in radiation oncology. We evaluated the changing pattern of SF-CRT and ART use for the management of bone metastases in lung cancer. MATERIALS AND METHODS: This was a state-wide population-based cohort of lung cancer patients from Victoria, Australia, who received radiation therapy for bone metastases between 2012 and 2017. The primary outcomes were proportion of radiation therapy courses using: SF-CRT and ART. We identified a subcohort in which radiation therapy was delivered at the end of life (EOL), i.e. within 30 days of death. The Cochran-Armitage test for trend was used to evaluate the change in pattern of SF-CRT and ART use over time. Multivariable analyses were used to identify factors associated with the primary outcomes. RESULTS: Of the 4335 courses of radiation therapy for bone metastases in lung cancer, 20% were SF-CRT - increasing from 19% in 2012 to 26% in 2017 (P-trend = 0.004). In multivariate analyses, treatment to the rib, shoulder, hip or extremities, and treatment in public institutions were independently associated with SF-CRT use, but the effect of year of radiation therapy was no longer significant. Five per cent of radiation therapy was delivered using ART, increasing markedly from 2016 onwards (P-trend < 0.001). In multivariate analyses, treatment in private institutions and more recent years of treatment were independently associated with the use of ART. There were 587 courses of radiation therapy delivered at the EOL, with SF-CRT more commonly used closer to death - 53%, 29% and 25% of radiation therapy within 7 days, 8-14 days and 15-30 days of death, respectively. CONCLUSION: SF-CRT continued to be underutilised for bone metastases in lung cancer in Australia, including at the EOL. We observed an increase in ART use for bone metastases from 2016, which occurred contemporaneously with changes in government funding.

Exploiting Isospin Symmetry to Study the Role of Isomers in Stellar Environments.

Proton capture on the excited isomeric state of ^{26}Al strongly influences the abundance of ^{26}Mg ejected in explosive astronomical events and, as such, plays a critical role in determining the initial content of radiogenic ^{26}Al in presolar grains. This reaction also affects the temperature range for thermal equilibrium between the ground and isomeric levels. We present a novel technique, which exploits the isospin symmetry of the nuclear force, to address the long-standing challenge of determining proton-capture rates on excited nuclear levels. Such a technique has in-built tests that strongly support its veracity and, for the first time, we have experimentally constrained the strengths of resonances that dominate the astrophysical ^{26m}Al(p,γ)^{27}Si reaction. These constraints demonstrate that the rate is at least a factor ∼8 lower than previously expected, indicating an increase in the stellar production of ^{26}Mg and a possible need to reinvestigate sensitivity studies involving the thermal equilibration of ^{26}Al.

Otolaryngology residents' perceptions of endoscopic ear surgery during surgical training.

BACKGROUND: The introduction of endoscopic ear surgery has implications for the training of otolaryngology residents. OBJECTIVES: To report on the status of endoscopic ear surgery and assess the effects of this new technology on otolaryngology training in Singapore, from the residents' perspective. METHODS: An anonymous survey was conducted amongst all Singaporean otolaryngology residents. Residents' exposure to, and perceptions of, endoscopic ear surgery were assessed. RESULTS: Residents from institutions that practise endoscopic ear surgery were more positive regarding its efficacy in various otological surgical procedures. Of residents in programmes with exposure to endoscopic ear surgery, 82.4 per cent felt that its introduction had adversely affected their training, with 88.3 per cent of residents agreeing that faculty members' learning of endoscopic ear surgery had decreased their hands-on surgical load. Both groups expressed desire for more experience with endoscopy. CONCLUSION: The majority of residents view endoscopic ear surgery as an expanding field with a potentially negative impact on their training. Mitigating measures should be implemented to minimise its negative impact on residents' training.

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.

Erratum: High-Precision Mass Measurement of

This corrects the article DOI: 10.1103/PhysRevLett.120.032701.

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.

Effects of mass loading on the viability of assessing the state of healing of a fixated fractured long bone.

INTRODUCTION: This paper aims to evaluate the effects of mass loading on the healing assessment of an internally fixated femur by vibrational means. The presence of soft tissue surrounding a femur increases damping and mass of a system, and hence affects the vibrational response of a mechanical structure by obscuring the coherent modes. This may compromise vibration-based monitoring strategies in identifying modes associated with fracture healing. METHODS: This paper presents a series of experimental works to address this issue. Two osteotomised composite femurs were internally fixated using a plate-screw system and an intramedullary nail. Soft tissue is approximated by surrounding an artificial Sawbone femur with modelling clay. The femur is excited by an instrumented impact hammer and instrumented with two accelerometers to record bending and torsion modes between 0 and 600 Hz. A 30-min epoxy was applied to simulate the healing of the fractured femur in the osteotomised region. The resonant frequencies and its modes are monitored while union is being formed and a healing index is calculated at various times to quantify the degree of healing. RESULTS: The results demonstrate that the effect of modelling clay compressed the natural modes along the frequency axis. It is observed that frequency bandwidth in the vicinity of 150 Hz and 500 Hz is sensitive to the state of healing of the fixated femurs, which is due to the increase in stiffness of the osteotomised region. These findings were used to formulate the healing index which assists in identifying the initial, later and complete healing stages in conjunction with the index derivative. CONCLUSION: In this study, a two-sensor measurement strategy to quantify fixated femur healing is investigated. It is shown that the mass loading effect did not affect this vibrational analysis method ability to assess the state of healing, and both coherent bending and twisting modes associated with healing were easily identified. The proposed healing index, its derivative, and the cross-spectra are a viable tool for quantitative healing assessment.

High-Precision Mass Measurement of

We report the mass measurement of ^{56}Cu, using the LEBIT 9.4 T Penning trap mass spectrometer at the National Superconducting Cyclotron Laboratory at Michigan State University. The mass of ^{56}Cu is critical for constraining the reaction rates of the ^{55}Ni(p,γ) ^{56}Cu(p,γ) ^{57}Zn(ß^{+}) ^{57}Cu bypass around the ^{56}Ni waiting point. Previous recommended mass excess values have disagreed by several hundred keV. Our new value, ME=-38626.7(7.1) keV, is a factor of 30 more precise than the extrapolated value suggested in the 2012 atomic mass evaluation [Chin. Phys. C 36, 1603 (2012)CPCHCQ1674-113710.1088/1674-1137/36/12/003], and more than a factor of 12 more precise than values calculated using local mass extrapolations, while agreeing with the newest 2016 atomic mass evaluation value [Chin. Phys. C 41, 030003 (2017)CPCHCQ1674-113710.1088/1674-1137/41/3/030003]. The new experimental average, using our new mass and the value from AME2016, is used to calculate the astrophysical ^{55}Ni(p,γ) and ^{56}Cu(p,γ) forward and reverse rates and perform reaction network calculations of the rp process. These show that the rp-process flow redirects around the ^{56}Ni waiting point through the ^{55}Ni(p,γ) route, allowing it to proceed to higher masses more quickly and resulting in a reduction in ashes around this waiting point and an enhancement to higher-mass ashes.

Anti-inflammatory effects of Lactobacillus brevis K65 on RAW 264.7 cells and in mice with dextran sulphate sodium-induced ulcerative colitis.

Lactic acid bacteria (LAB) with anti-inflammatory effects may be beneficial to the prevention or treatment for inflammation-related diseases, such as inflammatory bowel diseases. In an in vitro assay, heat-killed Lactobacillus brevis K65 (K65) reduced lipopolysaccharide-induced production of nitric oxide, tumour necrosis factor (TNF)-α and prostaglandin E2 in RAW 264.7 cells. In RAW 264.7 cells stably expressing an ind=ucible nitric oxide synthase (iNOS) reporter, viable K65 showed greater inhibition of iNOS production than its heat-killed form. In order to further examine the in vivo anti-inflammatory effect of K65, viable K65 was orally administered to BALB/c mice before and during the period of dextran sulphate sodium (DSS)-induced ulcerative colitis (UC). K65 improved UC symptoms, including reduced the levels of the pro-inflammatory cytokines, TNF-α, interleukin (IL)-6 and IL-1ß, and lowered the activity of myeloperoxidase. Furthermore, K65 inhibited TNF-α, cyclo-oxygenase 2, forkhead box P3, and Toll-like receptor 4 mRNA expression in the colonic tissue of DSS-induced UC mice. Taken together, K65, a LAB with in vitro anti-inflammatory activity showed preventive effects on mice with DSS-induced UC by lowering the expression of inflammatory molecules.

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.