To evaluate the dose–response relationship between cigarette smoking and pancreatic cancer and to examine the effects of temporal variables.
We analyzed data from 12 case–control studies within the ...International Pancreatic Cancer Case–Control Consortium (PanC4), including 6507 pancreatic cases and 12 890 controls. We estimated summary odds ratios (ORs) by pooling study-specific ORs using random-effects models.
Compared with never smokers, the OR was 1.2 (95% confidence interval CI 1.0–1.3) for former smokers and 2.2 (95% CI 1.7–2.8) for current cigarette smokers, with a significant increasing trend in risk with increasing number of cigarettes among current smokers (OR = 3.4 for ≥35 cigarettes per day, P for trend <0.0001). Risk increased in relation to duration of cigarette smoking up to 40 years of smoking (OR = 2.4). No trend in risk was observed for age at starting cigarette smoking, whereas risk decreased with increasing time since cigarette cessation, the OR being 0.98 after 20 years.
This uniquely large pooled analysis confirms that current cigarette smoking is associated with a twofold increased risk of pancreatic cancer and that the risk increases with the number of cigarettes smoked and duration of smoking. Risk of pancreatic cancer reaches the level of never smokers ∼20 years after quitting.
In superconducting quantum circuits, aluminum is one of the most widely used materials. It is currently also the superconductor of choice for the development of topological qubits. However, ...aluminum‐based devices suffer from poor magnetic field compatibility. Herein, this limitation is resolved by showing that adatoms of heavy elements (e.g., platinum) increase the critical field of thin aluminum films by more than a factor of two. Using tunnel junctions, it is shown that the increased field resilience originates from spin‐orbit scattering introduced by Pt. This property is exploited in the context of the superconducting proximity effect in semiconductor–superconductor hybrids, where it is shown that InSb nanowires strongly coupled to Al/Pt films can maintain superconductivity up to 7 T. The two‐electron charging effect is shown to be robust against the presence of heavy adatoms. Additionally, non‐local spectroscopy is used in a three‐terminal geometry to probe the bulk of hybrid devices, showing that it remains free of sub‐gap states. Finally, it is demonstrated that proximitized semiconductor states maintain their ability to Zeeman‐split in an applied magnetic field. Combined with the chemical stability and well‐known fabrication routes of aluminum, Al/Pt emerges as the natural successor to Al‐based systems and is a compelling alternative to other superconductors, whenever high‐field resilience is required.
In superconducting quantum circuits, aluminum is one of the most widely used materials. Aluminum‐based devices suffer from poor magnetic field compatibility. In this article, this limitation is resolved by showing that adatoms of heavy elements (e.g., platinum) increase the critical field of thin aluminum films by more than a factor of two.
Abstract
Massive stars (∼8–25
M
⊙
) stripped of their hydrogen-rich envelopes via binary interaction are thought to be the main progenitors for merging neutron stars and stripped-envelope supernovae. ...We recently presented the discovery of the first set of such stripped stars in a companion paper. Here, we fit the spectra of 10 stars with new atmosphere models in order to constrain their stellar properties precisely. We find that the stellar properties align well with the theoretical expectations from binary evolution models for helium-core burning envelope-stripped stars. The fits confirm that the stars have high effective temperatures (
T
eff
∼ 50–100 kK), high surface gravities (
log
g
∼
5), and hydrogen-poor/helium-rich surfaces (
X
H,surf
∼ 0–0.4) while showing for the first time a range of bolometric luminosities (10
3
–10
5
L
⊙
), small radii (∼0.5–1
R
⊙
), and low Eddington factors (Γ
e
∼ 0.006–0.4). Using these properties, we derive intermediate current masses (∼1–8
M
⊙
), which suggest that their progenitors were massive stars (∼5–25
M
⊙
) and that a subset will reach core-collapse, leaving behind neutron stars or black holes. Using the model fits, we also estimate the emission rates of ionizing photons for these stars, which agree well with previous model expectations. Further, by computing models for a range of mass-loss rates, we find that the stellar winds are weaker than predicted by any existing scheme (
M
̇
wind
≲
10
−
9
M
⊙
yr
−1
). The properties of this first sample of intermediate-mass helium stars suggest they both contain progenitors of type Ib and IIb supernovae, and provide important benchmarks for binary evolution and population synthesis models.
Heavy alcohol drinking has been related to pancreatic cancer, but the issue is still unsolved.
To evaluate the role of alcohol consumption in relation to pancreatic cancer, we conducted a pooled ...analysis of 10 case–control studies (5585 cases and 11 827 controls) participating in the International Pancreatic Cancer Case–Control Consortium. We computed pooled odds ratios (ORs) by estimating study-specific ORs adjusted for selected covariates and pooling them using random effects models.
Compared with abstainers and occasional drinkers (<1 drink per day), we observed no association for light-to-moderate alcohol consumption (≤4 drinks per day) and pancreatic cancer risk; however, associations were above unity for higher consumption levels (OR = 1.6, 95% confidence interval 1.2–2.2 for subjects drinking ≥9 drinks per day). Results did not change substantially when we evaluated associations by tobacco smoking status, or when we excluded participants who reported a history of pancreatitis, or participants whose data were based upon proxy responses. Further, no notable differences in pooled risk estimates emerged across strata of sex, age, race, study type, and study area.
This collaborative-pooled analysis provides additional evidence for a positive association between heavy alcohol consumption and the risk of pancreatic cancer.
On 17 August 2017, Swope Supernova Survey 2017a (SSS17a) was discovered as the optical counterpart of the binary neutron star gravitational wave event GW170817. We report time-series spectroscopy of ...SSS17a from 11.75 hours until 8.5 days after the merger. Over the first hour of observations, the ejecta rapidly expanded and cooled. Applying blackbody fits to the spectra, we measured the photosphere cooling from
11,000
−
900
+
3400
to
9300
−
300
+
300
kelvin, and determined a photospheric velocity of roughly 30% of the speed of light. The spectra of SSS17a began displaying broad features after 1.46 days and evolved qualitatively over each subsequent day, with distinct blue (early-time) and red (late-time) components. The late-time component is consistent with theoretical models of r-process–enriched neutron star ejecta, whereas the blue component requires high-velocity, lanthanide-free material.
The proximity effect in semiconductor-superconductor nanowires is expected to generate an induced gap in the semiconductor. The magnitude of this induced gap, together with the semiconductor ...properties like spin-orbit coupling and g-factor, depends on the coupling between the materials. It is predicted that this coupling can be adjusted through the use of electric fields. We study this phenomenon in InSb/Al/Pt hybrids using nonlocal spectroscopy. We show that these hybrids can be tuned such that the semiconductor and superconductor are strongly coupled. In this case, the induced gap is similar to the superconducting gap in the Al/Pt shell and closes only at high magnetic fields. In contrast, the coupling can be suppressed which leads to a strong reduction of the induced gap and critical magnetic field. At the crossover between the strong-coupling and weak-coupling regimes, we observe the closing and reopening of the induced gap in the bulk of a nanowire. Contrary to expectations, it is not accompanied by the formation of zero-bias peaks in the local conductance spectra. As a result, this cannot be attributed conclusively to the anticipated topological phase transition and we discuss possible alternative explanations.
Semiconducting–superconducting hybrids are vital components for the realization of high‐performance nanoscale devices. In particular, semiconducting–superconducting nanowires attract widespread ...interest owing to the possible presence of non‐abelian Majorana zero modes, which are quasiparticles that hold promise for topological quantum computing. However, systematic search for Majoranas signatures is challenging because it requires reproducible hybrid devices and reliable fabrication methods. This work introduces a fabrication concept based on shadow walls that enables the in situ, selective, and consecutive depositions of superconductors and normal metals to form normal‐superconducting junctions. Crucially, this method allows to realize devices in a single shot, eliminating fabrication steps after the synthesis of the fragile semiconductor/superconductor interface. At the atomic level, all investigated devices reveal a sharp and defect‐free semiconducting–superconducting interface and, correspondingly, a hard induced superconducting gap resilient up to 2 T is measured electrically. While the cleanliness of the technique enables systematic studies of topological superconductivity in nanowires, it also allows for the synthesis of advanced nano‐devices based on a wide range of material combinations and geometries while maintaining an exceptionally high interface quality.
Semiconducting–superconducting hybrids are vital components for the realization of nanoscale devices such as topological qubits. Here, a fabrication concept is introduced, enabling the in situ, selective, and consecutive depositions of superconducting and metallic layers on semiconducting nanowires forming hybrid junctions in a single shot. By eliminating conventional nanofabrication steps, all devices reveal sharp interfaces and hard gap induced superconductivity.
Ribociclib plus fulvestrant demonstrated significant progression-free survival (PFS) and overall survival (OS) benefits in patients with hormone receptor-positive, human epidermal growth factor ...receptor 2-negative (HR+/HER2−) advanced breast cancer (ABC). Here we present a new landmark in survival follow-up for a phase III cyclin-dependent kinases 4 and 6 inhibitor clinical trial in patients with ABC (median, 56.3 months).
This phase III, randomized, double-blind, placebo-controlled trial was conducted at 174 sites (30 countries). Patients were men and postmenopausal women (age ≥18 years) with histologically/cytologically confirmed HR+/HER2− ABC. Patients could have received ≤1 line of endocrine therapy (ET) but no chemotherapy for ABC. Patients, assigned 2:1, were stratified by the presence/absence of liver/lung metastases and previous ET. Patients received intramuscular fulvestrant (500 mg, day 1 of each 28-day cycle plus day 15 of cycle 1) with oral ribociclib (600 mg/day, 3 weeks on, 1 week off) or placebo. Efficacy analyses were by intention to treat. Safety was assessed in patients receiving ≥1 dose study treatment. OS was a secondary endpoint. MONALEESA-3 is registered with ClinicalTrials.gov (NCT02422615; no longer enrolling).
Between 18 June 2015 and 10 June 2016, 726 patients were randomly assigned (484, ribociclib; 242, placebo). At data cut-off (30 October 2020), median OS (mOS) was 53.7 months (ribociclib) versus 41.5 months (placebo) hazard ratio (HR), 0.73; 95% confidence interval (CI) 0.59-0.90. Subgroup analyses were consistent with overall population. In the first-line setting, most patients in the ribociclib arm (∼60%) lived longer than median follow-up; mOS was 51.8 months in the placebo arm (HR, 0.64; 95% CI 0.46-0.88). In the second-line setting, mOS was 39.7 months (ribociclib) versus 33.7 months (placebo) (HR, 0.78; 95% CI 0.59-1.04). No apparent drug–drug interaction between ribociclib and fulvestrant or new safety signals were observed.
This analysis reported extended OS follow-up in MONALEESA-3. mOS was ∼12 months longer in patients with HR+/HER2− ABC treated with ribociclib plus fulvestrant compared with fulvestrant monotherapy.
•We report an extended OS follow-up to the MONALEESA-3 trial (median, 56.3 months).•mOS was longer for the ribociclib arm versus the placebo arm: 53.7 versus 41.5 months (HR, 0.73; 95% CI 0.59-0.90).•OS benefit was observed with ribociclib in the first- and second-line settings.•No apparent drug–drug interaction between ribociclib and fulvestrant or new safety signals were observed.
Somatic cell nuclear transfer and transcription-factor-based reprogramming revert adult cells to an embryonic state, and yield pluripotent stem cells that can generate all tissues. Through different ...mechanisms and kinetics, these two reprogramming methods reset genomic methylation, an epigenetic modification of DNA that influences gene expression, leading us to hypothesize that the resulting pluripotent stem cells might have different properties. Here we observe that low-passage induced pluripotent stem cells (iPSCs) derived by factor-based reprogramming of adult murine tissues harbour residual DNA methylation signatures characteristic of their somatic tissue of origin, which favours their differentiation along lineages related to the donor cell, while restricting alternative cell fates. Such an 'epigenetic memory' of the donor tissue could be reset by differentiation and serial reprogramming, or by treatment of iPSCs with chromatin-modifying drugs. In contrast, the differentiation and methylation of nuclear-transfer-derived pluripotent stem cells were more similar to classical embryonic stem cells than were iPSCs. Our data indicate that nuclear transfer is more effective at establishing the ground state of pluripotency than factor-based reprogramming, which can leave an epigenetic memory of the tissue of origin that may influence efforts at directed differentiation for applications in disease modelling or treatment.
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