First Calorimetric Measurement of OI-line in the Electron Capture Spectrum of 163^{163}Ho

The isotope $^{163}$Ho undergoes an electron capture process with a recommended value for the energy available to the decay, $Q_{\rm EC}$, of about 2.5 keV. According to the present knowledge, this is the lowest $Q_{\rm EC}$ value for electron capture processes. Because of that, $^{163}$Ho is the best candidate to perform experiments to investigate the value of the electron neutrino mass based on the analysis of the calorimetrically measured spectrum. We present for the first time the calorimetric measurement of the atomic de-excitation of the $^{163}$Dy daughter atom upon the capture of an electron from the 5s shell in $^{163}$Ho, OI-line. The measured peak energy is 48 eV. This measurement was performed using low temperature metallic magnetic calorimeters with the $^{163}$Ho ion implanted in the absorber. We demonstrate that the calorimetric spectrum of $^{163}$Ho can be measured with high precision and that the parameters describing the spectrum can be learned from the analysis of the data. Finally, we discuss the implications of this result for the Electron Capture $^{163}$Ho experiment, ECHo, aiming to reach sub-eV sensitivity on the electron neutrino mass by a high precision and high statistics calorimetric measurement of the $^{163}$Ho spectrum.Comment: 5 pages, 3 figure

Firm heterogeneity and wages under different bargaining regimes : does a centralised union care for low-productivity firms?

This paper studies the relationship between wages and the degree of firm heterogeneity in a given industry under different wage setting structures. To derive testable hypotheses, we set up a theoretical model that analyses the sensitivity of wages to the variability in productivity conditions in a unionsised oligopoly framework. The model distinguishes centralised and decentralised wage determination. The theoretical results predict wages to be negatively associated with the degree of firm heterogeneity under centralised wage-setting, as unions internalise negative externalities of a wage increase for low-productivity firms. We test this prediction using a linked employeremployee panel data set from the German mining and manufacturing sector. Consistent with our hypotheses, the empirical results suggest that under industry-level bargaining workers in more heterogeneous sectors receive lower wages than workers in more homogeneous sectors. In contrast, the degree of firm heterogeneity is found to have no negative impact on wages in uncovered firms and under firm-level contracts

Upper limits to interstellar NH^+ and para-NH_2^− abundances. Herschel-HIFI observations towards Sgr B2 (M) and G10.6−0.4 (W31C)

The understanding of interstellar nitrogen chemistry has improved significantly with recent results from the Herschel Space Observatory. To set even better constraints, we report here on deep searches for the NH^+ ground state rotational transition J = 1.5−0.5 of the ^2Π_(1/2) lower spin ladder, with fine-structure transitions at 1013 and 1019 GHz, and the para-NH_2^− 1_(1,1)−0_(0,0) rotational transition at 934 GHz towards Sgr B2 (M) and G10.6−0.4 (W31C) using the Herschel Heterodyne Instrument for the Far-Infrared (HIFI). No clear detections of NH^+ are made and the derived upper limits relative to the total number of hydrogen nuclei are ≲2 × 10^(-12) and ≲7 × 10^(-13) in the Sgr B2 (M) molecular envelope and in the G10.6−0.4 molecular cloud, respectively. The searches are, however, complicated by the fact that the 1 013 GHz transition lies only −2.5 km s^(-1) from a CH_2NH line, which is seen in absorption in Sgr B2 (M), and that the hyperfine structure components in the 1019 GHz transition are spread over 134 km s^(-1). Searches for the so far undetected NH_2^− anion turned out to be unfruitful towards G10.6−0.4, while the para-NH_2^− 1_(1,1)−0_(0,0) transition was tentatively detected towards Sgr B2 (M) at a velocity of 19 km s^(-1). Assuming that the absorption occurs at the nominal source velocity of +64 km s^(-1), the rest frequency would be 933.996 GHz, offset by 141 MHz from our estimated value. Using this feature as an upper limit, we found N(p-NH_2^−) ≲4 × 10^(11) cm^(-2), which implies an abundance of ≲8 × 10^(-13) in the Sgr B2 (M) molecular envelope. The upper limits for both species in the diffuse line-of-sight gas are less than 0.1 to 2% of the values found for NH, NH_2, and NH_3 towards both sources, and the abundance limits are ≲2−4 × 10^(-11). An updated pseudo time-dependent chemical model with constant physical conditions, including both gas-phase and surface chemistry, predicts an NH^+ abundance a few times lower than our present upper limits in diffuse gas and under typical Sgr B2 (M) envelope conditions. The NH_2^− abundance is predicted to be several orders of magnitudes lower than our observed limits, hence not supporting our tentative detection. Thus, while NH_2^− may be very difficult to detect in interstellar space, it could, on the other hand, be possible to detect NH^+ in regions where the ionisation rates of H_2 and N are greatly enhanced

A new view of electrochemistry at highly oriented pyrolytic graphite

Major new insights on electrochemical processes at graphite electrodes are reported, following extensive investigations of two of the most studied redox couples, Fe(CN)64–/3– and Ru(NH3)63+/2+. Experiments have been carried out on five different grades of highly oriented pyrolytic graphite (HOPG) that vary in step-edge height and surface coverage. Significantly, the same electrochemical characteristic is observed on all surfaces, independent of surface quality: initial cyclic voltammetry (CV) is close to reversible on freshly cleaved surfaces (>400 measurements for Fe(CN)64–/3– and >100 for Ru(NH3)63+/2+), in marked contrast to previous studies that have found very slow electron transfer (ET) kinetics, with an interpretation that ET only occurs at step edges. Significantly, high spatial resolution electrochemical imaging with scanning electrochemical cell microscopy, on the highest quality mechanically cleaved HOPG, demonstrates definitively that the pristine basal surface supports fast ET, and that ET is not confined to step edges. However, the history of the HOPG surface strongly influences the electrochemical behavior. Thus, Fe(CN)64–/3– shows markedly diminished ET kinetics with either extended exposure of the HOPG surface to the ambient environment or repeated CV measurements. In situ atomic force microscopy (AFM) reveals that the deterioration in apparent ET kinetics is coupled with the deposition of material on the HOPG electrode, while conducting-AFM highlights that, after cleaving, the local surface conductivity of HOPG deteriorates significantly with time. These observations and new insights are not only important for graphite, but have significant implications for electrochemistry at related carbon materials such as graphene and carbon nanotubes

Spatial organization in cyclic Lotka-Volterra systems

We study the evolution of a system of $N$ interacting species which mimics the dynamics of a cyclic food chain. On a one-dimensional lattice with N<5 species, spatial inhomogeneities develop spontaneously in initially homogeneous systems. The arising spatial patterns form a mosaic of single-species domains with algebraically growing size, $\ell(t)\sim t^\alpha$, where $\alpha=3/4$ (1/2) and 1/3 for N=3 with sequential (parallel) dynamics and N=4, respectively. The domain distribution also exhibits a self-similar spatial structure which is characterized by an additional length scale, ${\cal L}(t)\sim t^\beta$, with $\beta=1$ and 2/3 for N=3 and 4, respectively. For $N\geq 5$, the system quickly reaches a frozen state with non interacting neighboring species. We investigate the time distribution of the number of mutations of a site using scaling arguments as well as an exact solution for N=3. Some possible extensions of the system are analyzed.Comment: 18 pages, 10 figures, revtex, also available from http://arnold.uchicago.edu/~ebn

Temozolomide chemotherapy versus radiotherapy in high-risk low-grade glioma (EORTC 22033-26033): a randomised, open-label, phase 3 intergroup study.

BACKGROUND: Outcome of low-grade glioma (WHO grade II) is highly variable, reflecting molecular heterogeneity of the disease. We compared two different, single-modality treatment strategies of standard radiotherapy versus primary temozolomide chemotherapy in patients with low-grade glioma, and assessed progression-free survival outcomes and identified predictive molecular factors. METHODS: For this randomised, open-label, phase 3 intergroup study (EORTC 22033-26033), undertaken in 78 clinical centres in 19 countries, we included patients aged 18 years or older who had a low-grade (WHO grade II) glioma (astrocytoma, oligoastrocytoma, or oligodendroglioma) with at least one high-risk feature (aged &gt;40 years, progressive disease, tumour size &gt;5 cm, tumour crossing the midline, or neurological symptoms), and without known HIV infection, chronic hepatitis B or C virus infection, or any condition that could interfere with oral drug administration. Eligible patients were randomly assigned (1:1) to receive either conformal radiotherapy (up to 50·4 Gy; 28 doses of 1·8 Gy once daily, 5 days per week for up to 6·5 weeks) or dose-dense oral temozolomide (75 mg/m(2) once daily for 21 days, repeated every 28 days [one cycle], for a maximum of 12 cycles). Random treatment allocation was done online by a minimisation technique with prospective stratification by institution, 1p deletion (absent vs present vs undetermined), contrast enhancement (yes vs no), age (&lt;40 vs ≥40 years), and WHO performance status (0 vs ≥1). Patients, treating physicians, and researchers were aware of the assigned intervention. A planned analysis was done after 216 progression events occurred. Our primary clinical endpoint was progression-free survival, analysed by intention-to-treat; secondary outcomes were overall survival, adverse events, neurocognitive function (will be reported separately), health-related quality of life and neurological function (reported separately), and correlative analyses of progression-free survival by molecular markers (1p/19q co-deletion, MGMT promoter methylation status, and IDH1/IDH2 mutations). This trial is closed to accrual but continuing for follow-up, and is registered at the European Trials Registry, EudraCT 2004-002714-11, and at ClinicalTrials.gov, NCT00182819. FINDINGS: Between Sept 23, 2005, and March 26, 2010, 707 patients were registered for the study. Between Dec 6, 2005, and Dec 21, 2012, we randomly assigned 477 patients to receive either radiotherapy (n=240) or temozolomide chemotherapy (n=237). At a median follow-up of 48 months (IQR 31-56), median progression-free survival was 39 months (95% CI 35-44) in the temozolomide group and 46 months (40-56) in the radiotherapy group (unadjusted hazard ratio [HR] 1·16, 95% CI 0·9-1·5, p=0·22). Median overall survival has not been reached. Exploratory analyses in 318 molecularly-defined patients confirmed the significantly different prognosis for progression-free survival in the three recently defined molecular low-grade glioma subgroups (IDHmt, with or without 1p/19q co-deletion [IDHmt/codel], or IDH wild type [IDHwt]; p=0·013). Patients with IDHmt/non-codel tumours treated with radiotherapy had a longer progression-free survival than those treated with temozolomide (HR 1·86 [95% CI 1·21-2·87], log-rank p=0·0043), whereas there were no significant treatment-dependent differences in progression-free survival for patients with IDHmt/codel and IDHwt tumours. Grade 3-4 haematological adverse events occurred in 32 (14%) of 236 patients treated with temozolomide and in one (&lt;1%) of 228 patients treated with radiotherapy, and grade 3-4 infections occurred in eight (3%) of 236 patients treated with temozolomide and in two (1%) of 228 patients treated with radiotherapy. Moderate to severe fatigue was recorded in eight (3%) patients in the radiotherapy group (grade 2) and 16 (7%) in the temozolomide group. 119 (25%) of all 477 patients had died at database lock. Four patients died due to treatment-related causes: two in the temozolomide group and two in the radiotherapy group. INTERPRETATION: Overall, there was no significant difference in progression-free survival in patients with low-grade glioma when treated with either radiotherapy alone or temozolomide chemotherapy alone. Further data maturation is needed for overall survival analyses and evaluation of the full predictive effects of different molecular subtypes for future individualised treatment choices. FUNDING: Merck Sharpe &amp; Dohme-Merck &amp; Co, Canadian Cancer Society, Swiss Cancer League, UK National Institutes of Health, Australian National Health and Medical Research Council, US National Cancer Institute, European Organisation for Research and Treatment of Cancer Cancer Research Fund

Overall Survival Benefit with Tebentafusp in Metastatic Uveal Melanoma

Background: Uveal melanoma is a disease that is distinct from cutaneous melanoma, with a low tumor mutational burden and a 1-year overall survival of approximately 50% in patients with metastatic uveal melanoma. Data showing a proven overall survival benefit with a systemic treatment are lacking. Tebentafusp is a bispecific protein consisting of an affinity-enhanced T-cell receptor fused to an anti-CD3 effector that can redirect T cells to target glycoprotein 100-positive cells. Methods: In this open-label, phase 3 trial, we randomly assigned previously untreated HLA-A*02:01-positive patients with metastatic uveal melanoma in a 2:1 ratio to receive tebentafusp (tebentafusp group) or the investigator's choice of therapy with single-agent pembrolizumab, ipilimumab, or dacarbazine (control group), stratified according to the lactate dehydrogenase level. The primary end point was overall survival. Results: A total of 378 patients were randomly assigned to either the tebentafusp group (252 patients) or the control group (126 patients). Overall survival at 1 year was 73% in the tebentafusp group and 59% in the control group (hazard ratio for death, 0.51; 95% confidence interval [CI], 0.37 to 0.71; P<0.001) in the intention-to-treat population. Progression-free survival was also significantly higher in the tebentafusp group than in the control group (31% vs. 19% at 6 months; hazard ratio for disease progression or death, 0.73; 95% CI, 0.58 to 0.94; P = 0.01). The most common treatment-related adverse events in the tebentafusp group were cytokine-mediated events (due to T-cell activation) and skin-related events (due to glycoprotein 100-positive melanocytes), including rash (83%), pyrexia (76%), and pruritus (69%). These adverse events decreased in incidence and severity after the first three or four doses and infrequently led to discontinuation of the trial treatment (2%). No treatment-related deaths were reported. Conclusions: Treatment with tebentafusp resulted in longer overall survival than the control therapy among previously untreated patients with metastatic uveal melanoma. (Funded by Immunocore; ClinicalTrials.gov number, NCT03070392; EudraCT number, 2015-003153-18.)

Treatment sequence with tebentafusp and immune checkpoint inhibitors in patients with metastatic uveal melanoma and metastatic GNA11/GNAQ mutant melanocytic tumors.

Metastatic uveal melanoma (mUM) is rare. Immune checkpoint inhibitors (ICIs) have shown modest efficacy in mUM. Tebentafusp prolonged overall survival (OS) in a phase 3 study. We aimed to investigate the efficacy and safety of the sequence of tebentafusp and ICIs. Patients with HLA-A * 02:01 positive mUM, or metastatic GNA11/GNAQ mutant melanocytic tumors treated with tebentafusp followed by ICIs (group 1) or the inverse sequence (group 2) at any treatment line were retrospectively identified. The primary objective was OS rate at 2 years. 131 patients were included; 51 in group 1 and 80 in group 2. 30 % in group 1 % and 40 % in group 2 had normal baseline lactate dehydrogenase (LDH, p = 0.05). 94 % in group 1 % and 77 % in group 2 had multilobular liver disease (p = 0.02). Median OS was 22.4 months (95 % CI 19-24.8) in group 1 and 33.6 months (95 % CI 28.9-43) in group 2 (p = 0.004). Total median PFS was 12 months (95 % CI 10.7-18.8) in group 1 and 20.3 months (95 % CI 17.2-27.3) in group 2 (p = 0.04). The frequency of cytokine release syndrome was higher in group 2 (15 % vs 27 %). Other clinical factors were associated with short total PFS in the multivariable analysis. Both treatment sequences are clinically feasible. A clinical benefit was noted in the sequential combination of ICIs followed by tebentafusp. This observation is limited by the retrospective nature of the study and merits further investigation in prospective clinical trials