Electronic cooling of a submicron-sized metallic beam

We demonstrate electronic cooling of a suspended AuPd island using superconductor-insulator-normal metal tunnel junctions. This was achieved by developing a simple fabrication method for reliably releasing narrow submicron sized metal beams. The process is based on reactive ion etching and uses a conducting substrate to avoid charge-up damage and is compatible with e.g. conventional e-beam lithography, shadow-angle metal deposition and oxide tunnel junctions. The devices function well and exhibit clear cooling; up to factor of two at sub-kelvin temperatures.Comment: 4 pages, 3 figure

Hints of Isocurvature Perturbations in the Cosmic Microwave Background?

The improved data on the cosmic microwave background (CMB) anisotropy allow a better determination of the adiabaticity of the primordial perturbation. Interestingly, we find that recent CMB data seem to favor a contribution of a primordial isocurvature mode where the entropy perturbation is positively correlated with the primordial curvature perturbation and has a large spectral index (niso ~ 3). With 4 additional parameters we obtain a better fit to the CMB data by Delta chi^2 = 9.7 compared to an adiabatic model. For this best-fit model the nonadiabatic contribution to the CMB temperature variance is 4%. According to a Markov Chain Monte Carlo analysis the nonadiabatic contribution is positive at more than 95% C.L. The exact C.L. depends somewhat on the choice of priors, and we discuss the effect of different priors as well as additional cosmological data.Comment: v1&2: 4 pages, 2 figures. v4: 16 pages, 7 figures, iopart style. Revised the 'Other cosmological data' section, added a detailed discussion on the effect of priors, and added many figures. Published versio

Population-based estimates of the relation between breast cancer risk, tumor subtype, and family history.

OBJECTIVE: Many studies that have estimated the breast cancer risk attributable to family history have been based on data collected within family units. Use of this study design has likely overestimated risks for the general population. We provide population-based estimates of breast cancer risk and different tumor subtypes in relation to the degree, number, and age at diagnosis of affected relatives. METHODS: Cox Proportional Hazards to calculate risks (hazard ratios; 95% confidence interval) of breast cancer and tumor subtypes for women with a family history of breast cancer relative to women without a family history among a cohort of 75,189 women age >or=40 years of whom 1,087 were diagnosed with breast cancer from June 1, 2001-December 31, 2005 (median follow-up 3.16 years). RESULTS: Breast cancer risk was highest for women with a first-degree family history (1.54; 1.34-1.77); and did not differ substantially by the affected relative's age at diagnosis or by number of affected first-degree relatives. A second-degree family history only was not associated with a significantly increased breast cancer risk (1.15; 0.98-1.35). There was a suggestion that a positive family history was associated with risk of triple positive (Estrogen+/Progesterone+/HER2+) and HER2-overexpressing tumors. CONCLUSIONS: While a family history of breast cancer in first-degree relatives is an important risk factor for breast cancer, gathering information such as the age at diagnosis of affected relatives or information on second-degree relative history may be unnecessary in assessing personal breast cancer risk among women age >or=40 years

KRAS-G12C Mutation in One Real-Life and Three Population-Based Nordic Cohorts of Metastatic Colorectal Cancer

Background: KRAS mutations, present in over 40% of metastatic colorectal cancer (mCRC), are negative predictive factors for anti-EGFR therapy. Mutations in KRAS-G12C have a cysteine residue for which drugs have been developed. Published data on this specific mutation are conflicting; thus, we studied the frequency and clinical characteristics in a real-world and population-based setting.Methods: Patients from three Nordic population-based cohorts and the real-life RAXO-study were combined. RAS and BRAF tests were performed in routine healthcare, except for one cohort. The dataset consisted of 2,559 patients, of which 1,871 could be accurately classified as KRAS, NRAS, and BRAF-V600E. Demographics, treatments, and outcomes were compared using logistic regression. Overall survival (OS) was estimated with Kaplan-Meier, and differences were compared using Cox regression, adjusted for baseline factors.Results: The KRAS-G12C frequency was 2%-4% of all tested in the seven cohorts (mean 3%) and 4%-8% of KRAS mutated tumors in the cohorts (mean 7%). Metastasectomies and ablations were performed more often (38% vs. 28%, p = 0.040), and bevacizumab was added more often (any line 74% vs. 59%, p = 0.007) for patients with KRAS-G12C- vs. other KRAS-mutated tumors, whereas chemotherapy was given to similar proportions. OS did not differ according to KRAS mutation, neither overall (adjusted hazard ratio (HR) 1.03; 95% CI 0.74-1.42, reference KRAS-G12C) nor within treatment groups defined as "systemic chemotherapy, alone or with biologics", "metastasectomy and/or ablations", or "best supportive care", RAS and BRAF wild-type tumors (n = 548) differed similarly to KRAS-G12C, as to other KRAS- or NRAS-mutated (n = 66) tumors.Conclusions: In these real-life and population-based cohorts, there were no significant differences in patient characteristics and outcomes between patients with KRAS-G12C tumors and those with other KRAS mutations. This contrasts with the results of most previous studies claiming differences in many aspects, often with worse outcomes for those with a KRAS-G12C mutation, although not consistent. When specific drugs are developed, as for this mutation, differences in outcome will hopefully emerge.ill hopefully emerge.</p

Resectability, conversion, metastasectomy and outcome according to RAS and BRAF status for metastatic colorectal cancer in the prospective RAXO study

Background Outcomes after metastasectomy for metastatic colorectal cancer (mCRC) vary with RAS and BRAF mutational status, but their effects on resectability and conversion rates have not been extensively studied. Methods This substudy of the prospective RAXO trial included 906 patients recruited between 2011 and 2018. We evaluated repeated centralised resectability assessment, conversion/resection rates and overall survival (OS), according to RAS and BRAF status. Results Patients included 289 with RAS and BRAF wild-type (RAS and BRAFwt), 529 with RAS mutated (RASmt) and 88 with BRAF mutated (BRAFmt) mCRC. Metastatic prevalence varied between the RAS and BRAFwt/RASmt/BRAFmt groups, for liver (78%/74%/61%), lung (24%/35%/28%) and peritoneal (15%/15%/32%) metastases, respectively. Upfront resectability (32%/29%/15%), conversion (16%/13%/7%) and resection/local ablative therapy (LAT) rates (45%/37%/17%) varied for RASa and BRAFwt/RASmt/BRAFmt, respectively. Median OS for patients treated with resection/LAT (n = 342) was 83/69/30 months, with 5-year OS-rates of 67%/60%/24%, while systemic therapy-only patients (n = 564) had OS of 29/21/15 months with 5-year OS-rates of 11%/6%/2% in RAS and BRAFwt/RASmt/BRAFmt, respectively. Resection/LAT was associated with improved OS in all subgroups. Conclusions There were significant differences in resectability, conversion and resection/LAT rates according to RAS and BRAF status. OS was also significantly longer for RAS and BRAFwt versus either mutant. Patients only receiving systemic therapy had poorer long-term survival, with variation according to molecular status.</p