Preferences of German and Swiss melanoma patients for toxicities versus melanoma recurrence during adjuvant treatment (GERMELATOX-A-trial).

PURPOSE: Adjuvant treatment with immune checkpoint inhibitors like PD1-antibodies (ICI) ± CTLA4-antibodies (cICI) or targeted therapy with BRAF/MEK inhibitors (TT) in high-risk melanoma patients demonstrate a significant improvement in disease-free survival (DFS). Due to specific side effects, the choice of treatment is very often driven by the risk for toxicity. This study addressed for the first time in a multicenter setting the attitudes and preferences of melanoma patients for adjuvant treatment with (c)ICI and TT. METHODS: In this study ("GERMELATOX-A"), 136 low-risk melanoma patients from 11 skin cancer centers were asked to rate side effect scenarios typical for each (c)ICI and TT with mild-to-moderate or severe toxicity and melanoma recurrence leading to cancer death. We asked patients about the reduction in melanoma relapse and the survival increase at 5 years they would require to tolerate defined side-effects. RESULTS: By VAS, patients on average valued melanoma relapse worse than all scenarios of side-effects during treatment with (c)ICI or TT. In case of severe side effects, patients required a 15% higher rate of DFS at 5 years for (c)ICI (80%) compared to TT (65%). For survival, patients required an increase of 5-10% for melanoma survival during (c)ICI (85%/80%) compared to TT (75%). CONCLUSION: Our study demonstrated a pronounced variation of patient preferences for toxicity and outcomes and a clear preference for TT. As adjuvant melanoma treatment with (c)ICI and TT will be increasingly implemented in earlier stages, precise knowledge of the patient perspective can be helpful for decision making.

A repeating fast radio burst source in a globular cluster.

Fast radio bursts (FRBs) are flashes of unknown physical origin1. The majority of FRBs have been seen only once, although some are known to generate multiple flashes2,3. Many models invoke magnetically powered neutron stars (magnetars) as the source of the emission4,5. Recently, the discovery6 of another repeater (FRB 20200120E) was announced, in the direction of the nearby galaxy M81, with four potential counterparts at other wavelengths6. Here we report observations that localized the FRB to a globular cluster associated with M81, where it is 2 parsecs away from the optical centre of the cluster. Globular clusters host old stellar populations, challenging FRB models that invoke young magnetars formed in a core-collapse supernova. We propose instead that FRB 20200120E originates from a highly magnetized neutron star formed either through the accretion-induced collapse of a white dwarf, or the merger of compact stars in a binary system7. Compact binaries are efficiently formed inside globular clusters, so a model invoking them could also be responsible for the observed bursts.

New

Precise antineutrino measurements are very sensitive to proper background characterization. We present an improved measurement of the ^{13}C(α,n)^{16}O reaction cross section which constitutes significant background for large ν[over ¯] detectors. We greatly improve the precision and accuracy by utilizing a setup that is sensitive to the neutron energies while making measurements of the excited state transitions via secondary γ-ray detection. Our results shows a 54% reduction in the background contributions from the ^{16}O(3^{-},6.13 MeV) state used in the KamLAND analysis.

Comparing Rates of Diagnosis Using DSM-IV-TR Versus DSM-5 Criteria for Autism Spectrum Disorder.

With the publication of DSM-5, many changes were introduced regarding how Autism Spectrum Disorder (ASD) would be diagnosed. Changes from DSM-IV-TR were controversial, with many arguing that individuals would lose their diagnosis with the new criteria. The purpose of this study was to examine differences in the application of diagnostic criteria across both recent versions in a sample of infants and toddlers. Fewer individuals met criteria according to DSM-5; however, a larger proportion of individuals met criteria for both. Additionally, individuals with higher levels of symptoms were more likely to meet criteria for both versions as compared to either alone. Overall, results suggest that there are meaningful differences in how DSM criteria may apply to individuals with an ASD.

Towards Neutron Capture on Exotic Nuclei: Demonstrating (d,pγ) as a Surrogate Reaction for (n,γ).

The neutron-capture reaction plays a critical role in the synthesis of the elements in stars and is important for societal applications including nuclear power generation and stockpile-stewardship science. However, it is difficult-if not impossible-to directly measure neutron capture cross sections for the exotic, short-lived nuclei that participate in these processes. In this Letter we demonstrate a new technique which can be used to indirectly determine neutron-capture cross sections for exotic systems. This technique makes use of the (d,p) transfer reaction, which has long been used as a tool to study the structure of nuclei. Recent advances in reaction theory, together with data collected using this reaction, enable the determination of neutron-capture cross sections for short-lived nuclei. A benchmark study of the ^{95}Mo(d,p) reaction is presented, which illustrates the approach and provides guidance for future applications of the method with short-lived isotopes produced at rare isotope accelerators.

A radio counterpart to a neutron star merger.

Gravitational waves have been detected from a binary neutron star merger event, GW170817. The detection of electromagnetic radiation from the same source has shown that the merger occurred in the outskirts of the galaxy NGC 4993, at a distance of 40 megaparsecs from Earth. We report the detection of a counterpart radio source that appears 16 days after the event, allowing us to diagnose the energetics and environment of the merger. The observed radio emission can be explained by either a collimated ultrarelativistic jet, viewed off-axis, or a cocoon of mildly relativistic ejecta. Within 100 days of the merger, the radio light curves will enable observers to distinguish between these models, and the angular velocity and geometry of the debris will be directly measurable by very long baseline interferometry.

Factors related to parental age of first concern in toddlers with autism spectrum disorder.

PURPOSE: The age of first concern (AOC) of parents of children with autism spectrum disorders (ASD) has substantial implications for early diagnosis and intervention. The current study sought to determine the average AOC, what types of first concerns are most common, and what factors predict earlier AOC in toddlers with ASD. METHODS: This study analyzed the predictive influence of the type of concern, symptom severity, medical diagnoses, and other independent variables on AOC among toddlers with ASD using multiple regressions. RESULTS: The mean AOC was found to be 13.97 months (SD = 7.86). The most commonly reported first concern was speech/language. First concerns related to communication, speech/language predicted later AOC, while motor concerns predicted earlier AOC. CONCLUSIONS: Concerns that are more closely related to social communication deficits characteristic of ASD predicted later AOC. The implications of these findings on screening/assessment and intervention are discussed.

An abbreviated scoring algorithm for the baby and infant screen for children with autism traits.

PURPOSE: Autism spectrum disorder (ASD) screening is recommended for all children aged 18-24 months. However, healthcare providers may be burdened with the responsibility of conducting these screens in addition to necessary services. Therefore, developing a time-efficient screener with sound psychometric properties is essential. METHODS: This study sought to update the abbreviated scoring algorithm of the Baby and Infant Screen for Children with aUtIsm Traits (BISCUIT) and increase its clinical utility. Six thousand and three children with ASD or atypical development enrolled in an early intervention program participated. RESULTS: A 6-item algorithm with a cutoff score of 3 was found to be optimal and yielded a sensitivity of 0.960 and a specificity of 0.864. CONCLUSION: Sensitivity and specificity estimates were similar to that of the complete BISCUIT-Part 1; thus, the 6-item algorithm can reliably differentiate children at-risk for ASD requiring further assessment. The algorithm appears to be a promising tool for early identification.

Evidence for Gamow-Teller Decay of

The ß-delayed neutron emission of ^{83,84}Ga isotopes was studied using the neutron time-of-flight technique. The measured neutron energy spectra showed emission from states at excitation energies high above the neutron separation energy and previously not observed in the ß decay of midmass nuclei. The large decay strength deduced from the observed intense neutron emission is a signature of Gamow-Teller transformation. This observation was interpreted as evidence for allowed ß decay to ^{78}Ni core-excited states in ^{83,84}Ge favored by shell effects. We developed shell model calculations in the proton fpg_{9/2} and neutron extended fpg_{9/2}+d_{5/2} valence space using realistic interactions that were used to understand measured ß-decay lifetimes. We conclude that enhanced, concentrated ß-decay strength for neutron-unbound states may be common for very neutron-rich nuclei. This leads to intense ß-delayed high-energy neutron and strong multineutron emission probabilities that in turn affect astrophysical nucleosynthesis models.

Autism spectrum disorders: management over the lifespan.

INTRODUCTION: For the majority of the autism spectrum disorder (ASD) population, symptoms begin within the first years of life and associated difficulties continue throughout the lifespan. Currently, the research literature focuses more heavily on problems in childhood. However, given that adulthood accounts for the majority of life, more focus should be placed on evidence-based, lifelong treatment and management strategies for ASD. Areas covered: This paper reviews the topic of lifelong ASD management, primarily emphasizing issues in adolescence and adulthood. Among the topics discussed are timing and methods of treatment across the lifespan, and specific intervention targets that emerge or are more relevant to this older cohort. Expert commentary: Several advances have been made in the treatment of adolescent and adult specific issues. However, research should continue to focus on these areas. Greater focus on coordination of care across disciplines and policy regarding ASD management over the lifespan is also required.

Top-down assessment of the Asian carbon budget since the mid 1990s.

Increasing atmospheric carbon dioxide (CO2) is the principal driver of anthropogenic climate change. Asia is an important region for the global carbon budget, with 4 of the world's 10 largest national emitters of CO2. Using an ensemble of seven atmospheric inverse systems, we estimated land biosphere fluxes (natural, land-use change and fires) based on atmospheric observations of CO2 concentration. The Asian land biosphere was a net sink of -0.46 (-0.70-0.24) PgC per year (median and range) for 1996-2012 and was mostly located in East Asia, while in South and Southeast Asia the land biosphere was close to carbon neutral. In East Asia, the annual CO2 sink increased between 1996-2001 and 2008-2012 by 0.56 (0.30-0.81) PgC, accounting for ∼35% of the increase in the global land biosphere sink. Uncertainty in the fossil fuel emissions contributes significantly (32%) to the uncertainty in land biosphere sink change.

Quality of life of patients with chronic lymphocytic leukaemia in the Netherlands: results of a longitudinal multicentre study.

PURPOSE: To describe the health-related quality of life (HRQoL) of an unselected population of patients with chronic lymphocytic leukaemia (CLL) including untreated patients. METHODS: HRQoL was measured by the EORTC QLQ-C30 including the CLL16 module, EQ-5D, and VAS in an observational study over multiple years. All HRQoL measurements per patient were connected and analysed using area under the curve analysis over the entire study duration. The total patient group was compared with the general population, and three groups of CLL patients were described separately, i.e. patients without any active treatment ("watch and wait"), chlorambucil treatment only, and patients with other treatment(s). RESULTS: HRQoL in the total group of CLL patients was compromised when compared with age- and gender-matched norm scores of the general population. CLL patients scored statistically worse on the VAS and utility score of the EQ-5D, all functioning scales of the EORTC QLQ-C30, and the symptoms of fatigue, dyspnoea, sleeping disturbance, appetite loss, and financial difficulties. In untreated patients, the HRQoL was slightly reduced. In all treatment stages, HRQoL was compromised considerably. Patients treated with chlorambucil only scored worse on the EORTC QLQ-C30 than patients who were treated with other treatments with regard to emotional functioning, cognitive functioning, bruises, uncomfortable stomach, and apathy. CONCLUSIONS: CLL patients differ most from the general population on role functioning, fatigue, concerns about future health, and having not enough energy. Once treatment is indicated, HRQoL becomes considerably compromised. This applies to all treatments, including chlorambucil, which is considered to be a mild treatment.

Constraint of the astrophysical

The Galactic 1.809-MeV γ-ray signature from the ß decay of ^{26g}Al is a dominant target of γ-ray astronomy, of which a significant component is understood to originate from massive stars. The ^{26g}Al(p,γ)^{27}Si reaction is a major destruction pathway for ^{26g}Al at stellar temperatures, but the reaction rate is poorly constrained due to uncertainties in the strengths of low-lying resonances in ^{27}Si. The ^{26g}Al(d,p)^{27}Al reaction has been employed in inverse kinematics to determine the spectroscopic factors, and hence resonance strengths, of proton resonances in ^{27}Si via mirror symmetry. The strength of the 127-keV resonance is found to be a factor of 4 higher than the previously adopted upper limit, and the upper limit for the 68-keV resonance has been reduced by an order of magnitude, considerably constraining the ^{26g}Al destruction rate at stellar temperatures.

The standardised mortality ratio: the proper quality indicator in acute leukaemia?

BACKGROUND: The standardised mortality ratio (SMR) is a quality indicator used to measure quality of care in the Netherlands. It is subject to much criticism, which was the reason to study the value of the SMR as a quality indicator for the treatment of acute leukaemia. METHODS: A retrospective analysis was performed in patients with acute leukaemia admitted to a Santeon hospital during the period 2005-2009. SMR values were calculated and compared with the overall survival (OS). RESULTS: During the study period, 455 unique patients were admitted with acute leukaemia. SMR calculation was based on 992 admissions. SMR analysis yielded a high mortality ratio in hospital 1, 2, 3 and 4 in comparison with the national average (100), significant for hospital 1 and 4 (180 [CI 95% 126-257] and 187 [CI 95% 134-261], respectively) OS analysis also showed a significantly different outcome between hospitals. However, using OS as outcome parameter, hospital 2 and 6 showed the lowest performance as compared with hospital 1 and 4 using SMR as parameter. After multivariate analysis, age (HR 1.04; CI 95% 1.03-1.05; p < 0.001) and hospital (hospital 5 compared with 6: HR 0.54; CI 95% 0.30- .98; p = 0.043; hospital 2 compared with 1: HR 1.51; CI 95% 1.02-2.23; p = 0.039) were the only significant variables that influenced OS. CONCLUSION: Outcome according to SMR is not equivalent to outcome according to OS. This study shows that the use of the SMR as a quality indicator for the treatment of acute leukaemia does not appear to be justified.

Double-magic nature of 132Sn and 208Pb through lifetime and cross-section measurements.

Single-neutron states in (133)Sn and (209)Pb, which are analogous to single-electron states outside of closed atomic shells in alkali metals, were populated by the ((9)Be, (8)Be) one-neutron transfer reaction in inverse kinematics using particle-γ coincidence spectroscopy. In addition, the s(1/2) single-neutron hole-state candidate in (131)Sn was populated by ((9)Be, (10)Be). Doubly closed-shell (132)Sn (radioactive) and (208)Pb (stable) beams were used at sub-Coulomb barrier energies of 3 MeV per nucleon. Level energies, γ-ray transitions, absolute cross sections, spectroscopic factors, asymptotic normalization coefficients, and excited-state lifetimes are reported and compared with shell-model expectations. The results include a new transition and precise level energy for the 3p(1/2) candidate in (133)Sn, new absolute cross sections for the 1h(9/2) candidate in (133)Sn and 3s(1/2) candidate in (131)Sn, and new lifetimes for excited states in (133)Sn and (209)Pb. This is the first report on excited-state lifetimes of (133)Sn, which allow for a unique test of the nuclear shell model and (132)Sn double-shell closure.

Real-world costs of chronic lymphocytic leukaemia in the Netherlands.

We performed a comprehensive cost calculation identifying the main cost drivers of treatment of chronic lymphocytic leukaemia in daily practice. In our observational study 160 patient charts were reviewed repeatedly to assess the treatment strategies from diagnosis till the study end. Ninety-seven patients (61%) received ≥1 treatment lines during an average follow-up time of 6.4 years. The average total costs per patient were €41,417 (€539 per month). The costs varied considerably between treatment groups and between treatment lines. Although patients were treated with expensive chemo(immuno-)therapy, the main cost driver was inpatient days for other reasons than administration of chemo(immuno-)therapy.

Hypogonadism in a patient with mild hereditary haemochromatosis.

Hypogonadism is a potential complication of haemochromatosis, usually seen in patients with severe iron overload and liver cirrhosis. We describe the diagnostic workup of a patient with an early stage of hereditary haemochromatosis, presenting with only mildly elevated liver enzymes and central hypogonadism in the absence of cirrhosis or diabetes, but with concurrent sarcoidosis.

Serum anti-müllerian hormone levels in healthy females: a nomogram ranging from infancy to adulthood.

CONTEXT: Anti-müllerian hormone (AMH) is an accurate marker of ovarian reserve. However, sufficiently large sets of normative data from infancy to the end of reproductive life are scarce. OBJECTIVE: This study was an assessment of serum AMH levels in healthy females. SUBJECTS: In 804 healthy females ranging from infancy until the end of the reproductive period, serum AMH levels were measured with an enzyme-linked immunometric assay. All adults had regular menstrual cycles. The majority was proven fertile and none of them had used oral contraceptive pills prior to study inclusion. RESULTS: In the total cohort, AMH was inversely correlated with age (r = -0.24; P < 0.001). The age at which the maximum AMH value was attained was at 15.8 yr. In girls younger than 15.8 yr, serum AMH and age were positively correlated (r = +0.18; P = 0.007). Thereafter AMH levels remained stable (r = -0.33; P = 0.66), whereas from the age of 25.0 yr onward, an inverse correlation between AMH and age (r = -0.47; P < 0.001) was observed. At any given age, considerable interindividual differences in serum AMH levels were observed. CONCLUSION: During infancy AMH levels increase, whereas during adolescence, a plateau until the age of 25 yr was observed. From the age of 25 yr onward, serum AMH levels correlate inversely with age, implying that AMH is applicable as a marker of ovarian reserve only in women of 25 yr old and older. Our nomogram may facilitate counseling women on their reproductive potential.