Showing papers by "University of Erlangen-Nuremberg published in 2015"

Low-threshold amplified spontaneous emission and lasing from colloidal nanocrystals of caesium lead halide perovskites

Abstract: Metal halide semiconductors with perovskite crystal structures have recently emerged as highly promising optoelectronic materials. Despite the recent surge of reports on microcrystalline, thin-film and bulk single-crystalline metal halides, very little is known about the photophysics of metal halides in the form of uniform, size-tunable nanocrystals. Here we report low-threshold amplified spontaneous emission and lasing from ∼10 nm monodisperse colloidal nanocrystals of caesium lead halide perovskites CsPbX3 (X=Cl, Br or I, or mixed Cl/Br and Br/I systems). We find that room-temperature optical amplification can be obtained in the entire visible spectral range (440–700 nm) with low pump thresholds down to 5±1 μJ cm−2 and high values of modal net gain of at least 450±30 cm−1. Two kinds of lasing modes are successfully observed: whispering-gallery-mode lasing using silica microspheres as high-finesse resonators, conformally coated with CsPbX3 nanocrystals and random lasing in films of CsPbX3 nanocrystals. Lead halide perovskite colloidal nanocrystals have promising optoelectronic properties, such as high photoluminescence quantum yields and narrow emission linewidths. Here, the authors report low-threshold amplified spontaneous emission and two kinds of lasing in nanostructured caesium lead halide perovskites.

Common Genetic Variation In Cellular Transport Genes and Epithelial Ovarian Cancer (EOC) Risk

Abstract: BACKGROUND: Defective cellular transport processes can lead to aberrant accumulation of trace elements, iron, small molecules and hormones in the cell, which in turn may promote the formation of reactive oxygen species, promoting DNA damage and aberrant expression of key regulatory cancer genes. As DNA damage and uncontrolled proliferation are hallmarks of cancer, including epithelial ovarian cancer (EOC), we hypothesized that inherited variation in the cellular transport genes contributes to EOC risk. METHODS: In total, DNA samples were obtained from 14,525 case subjects with invasive EOC and from 23,447 controls from 43 sites in the Ovarian Cancer Association Consortium (OCAC). Two hundred seventy nine SNPs, representing 131 genes, were genotyped using an Illumina Infinium iSelect BeadChip as part of the Collaborative Oncological Gene-environment Study (COGS). SNP analyses were conducted using unconditional logistic regression under a log-additive model, and the FDR q<0.2 was applied to adjust for multiple comparisons. RESULTS: The most significant evidence of an association for all invasive cancers combined and for the serous subtype was observed for SNP rs17216603 in the iron transporter gene HEPH (invasive: OR = 0.85, P = 0.00026; serous: OR = 0.81, P = 0.00020); this SNP was also associated with the borderline/low malignant potential (LMP) tumors (P = 0.021). Other genes significantly associated with EOC histological subtypes (p<0.05) included the UGT1A (endometrioid), SLC25A45 (mucinous), SLC39A11 (low malignant potential), and SERPINA7 (clear cell carcinoma). In addition, 1785 SNPs in six genes (HEPH, MGST1, SERPINA, SLC25A45, SLC39A11 and UGT1A) were imputed from the 1000 Genomes Project and examined for association with INV EOC in white-European subjects. The most significant imputed SNP was rs117729793 in SLC39A11 (per allele, OR = 2.55, 95% CI = 1.5-4.35, p = 5.66x10-4). CONCLUSION: These results, generated on a large cohort of women, revealed associations between inherited cellular transport gene variants and risk of EOC histologic subtypes.

Prospects of Nanoscience with Nanocrystals

Abstract: Colloidal nanocrystals (NCs, i.e., crystalline nanoparticles) have become an important class of materials with great potential for applications ranging from medicine to electronic and optoelectronic devices. Today’s strong research focus on NCs has been prompted by the tremendous progress in their synthesis. Impressively narrow size distributions of just a few percent, rational shape-engineering, compositional modulation, electronic doping, and tailored surface chemistries are now feasible for a broad range of inorganic compounds. The performance of inorganic NC-based photovoltaic and light-emitting devices has become competitive to other state-of-the-art materials. Semiconductor NCs hold unique promise for near- and mid-infrared technologies, where very few semiconductor materials are available. On a purely fundamental side, new insights into NC growth, chemical transformations, and self-organization can be gained from rapidly progressing in situ characterization and direct imaging techniques. New phenom...

European Society of Contact Dermatitis guideline for diagnostic patch testing – recommendations on best practice

Abstract: The present guideline summarizes all aspects of patch testing for the diagnosis of contact allergy in patients suspected of suffering, or having been suffering, from allergic contact dermatitis or other delayed-type hypersensitivity skin and mucosal conditions. Sections with brief descriptions and discussions of different pertinent topics are followed by a highlighted short practical recommendation. Topics comprise, after an introduction with important definitions, materials, technique, modifications of epicutaneous testing, individual factors influencing the patch test outcome or necessitating special considerations, children, patients with occupational contact dermatitis and drug eruptions as special groups, patch testing of materials brought in by the patient, adverse effects of patch testing, and the final evaluation and patient counselling based on this judgement. Finally, short reference is made to aspects of (continuing) medical education and to electronic collection of data for epidemiological surveillance.

Liquid exfoliation of solvent-stabilized few-layer black phosphorus for applications beyond electronics

Abstract: Few-layer black phosphorus (BP) is a new two-dimensional material which is of great interest for applications, mainly in electronics. However, its lack of environmental stability severely limits its synthesis and processing. Here we demonstrate that high-quality, few-layer BP nanosheets, with controllable size and observable photoluminescence, can be produced in large quantities by liquid phase exfoliation under ambient conditions in solvents such as N-cyclohexyl-2-pyrrolidone (CHP). Nanosheets are surprisingly stable in CHP, probably due to the solvation shell protecting the nanosheets from reacting with water or oxygen. Experiments, supported by simulations, show reactions to occur only at the nanosheet edge, with the rate and extent of the reaction dependent on the water/oxygen content. We demonstrate that liquid-exfoliated BP nanosheets are potentially useful in a range of applications from ultrafast saturable absorbers to gas sensors to fillers for composite reinforcement.

Practical Non-Linear Energy Harvesting Model and Resource Allocation for SWIPT Systems

Abstract: In this letter, we propose a practical non-linear energy harvesting model and design a resource allocation algorithm for simultaneous wireless information and power transfer (SWIPT) systems. The algorithm design is formulated as a non-convex optimization problem for the maximization of the total harvested power at energy harvesting receivers subject to minimum required signal-to-interference-plus-noise ratios (SINRs) at multiple information receivers. We transform the considered non-convex objective function from sum-of-ratios form into an equivalent objective function in subtractive form, which enables the derivation of an efficient iterative resource allocation algorithm. In each iteration, a rank-constrained semidefinite program (SDP) is solved optimally by SDP relaxation. Numerical results unveil a substantial performance gain that can be achieved if the resource allocation design is based on the proposed non-linear energy harvesting model instead of the traditional linear model.

Detection of X-ray photons by solution-processed lead halide perovskites

Abstract: The evolution of real-time medical diagnostic tools such as angiography and computer tomography from radiography based on photographic plates was enabled by the development of integrated solid-state X-ray photon detectors, based on conventional solid-state semiconductors. Recently, for optoelectronic devices operating in the visible and near infrared spectral regions, solution-processed organic and inorganic semiconductors have also attracted immense attention. Here we demonstrate a possibility to use such inexpensive semiconductors for sensitive detection of X-ray photons by direct photon-to-current conversion. In particular, methylammonium lead iodide perovskite (CH3NH3PbI3) offers a compelling combination of fast photoresponse and a high absorption cross-section for X-rays, owing to the heavy Pb and I atoms. Solution processed photodiodes as well as photoconductors are presented, exhibiting high values of X-ray sensitivity (up to 25 µC mGyair-1 cm-3) and responsivity (1.9×104 carriers/photon), which are commensurate with those obtained by the current solid-state technology.

Computational Lipidomics with insane: A Versatile Tool for Generating Custom Membranes for Molecular Simulations

Abstract: For simulations of membranes and membrane proteins, the generation of the lipid bilayer is a critical step in the setup of the system. Membranes comprising multiple components pose a particular challenge, because the relative abundances need to be controlled and the equilibration of the system may take several microseconds. Here we present a comprehensive method for building membrane containing systems, characterized by simplicity and versatility. The program uses preset, coarse-grain lipid templates to build the membrane, and also allows on-the-fly generation of simple lipid types by specifying the headgroup, linker, and lipid tails on the command line. The resulting models can be equilibrated, after which a relaxed atomistic model can be obtained by reverse transformation. For multicomponent membranes, this provides an efficient means for generating equilibrated atomistic models. The method is called insane, an acronym for INSert membrANE. The program has been made available, together with the complemen...

Update of EULAR recommendations for the treatment of systemic sclerosis

Abstract: The aim was to update the 2009 European League against Rheumatism (EULAR) recommendations for the treatment of systemic sclerosis (SSc), with attention to new therapeutic questions. Update of the previous treatment recommendations was performed according to EULAR standard operating procedures. The task force consisted of 32 SSc clinical experts from Europe and the USA, 2 patients nominated by the pan-European patient association for SSc (Federation of European Scleroderma Associations (FESCA)), a clinical epidemiologist and 2 research fellows. All centres from the EULAR Scleroderma Trials and Research group were invited to submit and select clinical questions concerning SSc treatment using a Delphi approach. Accordingly, 46 clinical questions addressing 26 different interventions were selected for systematic literature review. The new recommendations were based on the available evidence and developed in a consensus meeting with clinical experts and patients. The procedure resulted in 16 recommendations being developed (instead of 14 in 2009) that address treatment of several SSc-related organ complications: Raynaud's phenomenon (RP), digital ulcers (DUs), pulmonary arterial hypertension (PAH), skin and lung disease, scleroderma renal crisis and gastrointestinal involvement. Compared with the 2009 recommendations, the 2016 recommendations include phosphodiesterase type 5 (PDE-5) inhibitors for the treatment of SSc-related RP and DUs, riociguat, new aspects for endothelin receptor antagonists, prostacyclin analogues and PDE-5 inhibitors for SSc-related PAH. New recommendations regarding the use of fluoxetine for SSc-related RP and haematopoietic stem cell transplantation for selected patients with rapidly progressive SSc were also added. In addition, several comments regarding other treatments addressed in clinical questions and suggestions for the SSc research agenda were formulated. These updated data-derived and consensus-derived recommendations will help rheumatologists to manage patients with SSc in an evidence-based way. These recommendations also give directions for future clinical research in SSc.

The microbiota regulates type 2 immunity through RORγt+ T cells

Abstract: Changes to the symbiotic microbiota early in life, or the absence of it, can lead to exacerbated type 2 immunity and allergic inflammations. Although it is unclear how the microbiota regulates type 2 immunity, it is a strong inducer of proinflammatory T helper 17 (TH17) cells and regulatory T cells (Tregs) in the intestine. Here, we report that microbiota-induced Tregs express the nuclear hormone receptor RORγt and differentiate along a pathway that also leads to TH17 cells. In the absence of RORγt+ Tregs, TH2-driven defense against helminths is more efficient, whereas TH2-associated pathology is exacerbated. Thus, the microbiota regulates type 2 responses through the induction of type 3 RORγt+ Tregs and TH17 cells and acts as a key factor in balancing immune responses at mucosal surfaces.

The Synthesis of Nanostructured Ni5P4 Films and their Use as a Non‐Noble Bifunctional Electrocatalyst for Full Water Splitting

Abstract: The investigation of nickel phosphide (Ni5 P4 ) as a catalyst for the hydrogen (HER) and oxygen evolution reaction (OER) in strong acidic and alkaline environment is described. The catalyst can be grown in a 3D hierarchical structure directly on a nickel substrate, thus making it an ideal candidate for practical water splitting devices. The activity of the catalyst towards the HER, together with its high stability especially in acidic solution, makes it one of the best non-noble materials described to date. Furthermore, Ni5 P4 was investigated in the OER and showed activity superior to pristine nickel or platinum. The practical relevance of Ni5 P4 as a bifunctional catalyst for the overall water splitting reaction was demonstrated, with 10 mA cm(-2) achieved below 1.7 V.

Big Data Meets Quantum Chemistry Approximations: The Δ-Machine Learning Approach.

Abstract: Chemically accurate and comprehensive studies of the virtual space of all possible molecules are severely limited by the computational cost of quantum chemistry. We introduce a composite strategy that adds machine learning corrections to computationally inexpensive approximate legacy quantum methods. After training, highly accurate predictions of enthalpies, free energies, entropies, and electron correlation energies are possible, for significantly larger molecular sets than used for training. For thermochemical properties of up to 16k isomers of C7H10O2 we present numerical evidence that chemical accuracy can be reached. We also predict electron correlation energy in post Hartree-Fock methods, at the computational cost of Hartree-Fock, and we establish a qualitative relationship between molecular entropy and electron correlation. The transferability of our approach is demonstrated, using semiempirical quantum chemistry and machine learning models trained on 1 and 10% of 134k organic molecules, to reproduce enthalpies of all remaining molecules at density functional theory level of accuracy.

Quantitative optical coherence tomography angiography of vascular abnormalities in the living human eye

Abstract: Retinal vascular diseases are important causes of vision loss. A detailed evaluation of the vascular abnormalities facilitates diagnosis and treatment in these diseases. Optical coherence tomography (OCT) angiography using the highly efficient split-spectrum amplitude decorrelation angiography algorithm offers an alternative to conventional dye-based retinal angiography. OCT angiography has several advantages, including 3D visualization of retinal and choroidal circulations (including the choriocapillaris) and avoidance of dye injection-related complications. Results from six illustrative cases are reported. In diabetic retinopathy, OCT angiography can detect neovascularization and quantify ischemia. In age-related macular degeneration, choroidal neovascularization can be observed without the obscuration of details caused by dye leakage in conventional angiography. Choriocapillaris dysfunction can be detected in the nonneovascular form of the disease, furthering our understanding of pathogenesis. In choroideremia, OCT's ability to show choroidal and retinal vascular dysfunction separately may be valuable in predicting progression and assessing treatment response. OCT angiography shows promise as a noninvasive alternative to dye-based angiography for highly detailed, in vivo, 3D, quantitative evaluation of retinal vascular abnormalities.

Oxaliplatin added to fluorouracil-based preoperative chemoradiotherapy and postoperative chemotherapy of locally advanced rectal cancer (the German CAO/ARO/AIO-04 study): final results of the multicentre, open-label, randomised, phase 3 trial

Abstract: Summary Background Preoperative chemoradiotherapy with infusional fluorouracil, total mesorectal excision surgery, and postoperative chemotherapy with fluorouracil was established by the German CAO/ARO/AIO-94 trial as a standard combined modality treatment for locally advanced rectal cancer. Here we compare the previously established regimen with an investigational regimen in which oxaliplatin was added to both preoperative chemoradiotherapy and postoperative chemotherapy. Methods In this multicentre, open-label, randomised, phase 3 study we randomly assigned patients with rectal adenocarcinoma, clinically staged as cT3–4 or any node-positive disease, to two groups: a control group receiving standard fluorouracil-based combined modality treatment, consisting of preoperative radiotherapy of 50·4 Gy in 28 fractions plus infusional fluorouracil (1000 mg/m 2 on days 1–5 and 29–33), followed by surgery and four cycles of bolus fluorouracil (500 mg/m 2 on days 1–5 and 29); or to an investigational group receiving preoperative radiotherapy of 50·4 Gy in 28 fractions plus infusional fluorouracil (250 mg/m 2 on days 1–14 and 22–35) and oxaliplatin (50 mg/m 2 on days 1, 8, 22, and 29), followed by surgery and eight cycles of oxaliplatin (100 mg/m 2 on days 1 and 15), leucovorin (400 mg/m 2 on days 1 and 15), and infusional fluorouracil (2400 mg/m 2 on days 1–2 and 15–16). Randomisation was done with computer-generated block-randomisation codes stratified by centre, clinical T category (cT1–3 vs cT4), and clinical N category (cN0 vs cN1–2) without masking. The primary endpoint was disease-free survival, defined as the time between randomisation and non-radical surgery of the primary tumour (R2 resection), locoregional recurrence after R0/1 resection, metastatic disease or progression, or death from any cause, whichever occurred first. Survival and cumulative incidence of recurrence analyses followed the intention-to-treat principle; toxicity analyses included all patients treated. Enrolment of patients in this trial is completed and follow-up is ongoing. This study is registered with ClinicalTrials.gov, number NCT00349076. Findings Of the 1265 patients initially enrolled, 1236 were assessable (613 in the investigational group and 623 in the control group). With a median follow-up of 50 months (IQR 38–61), disease-free survival at 3 years was 75·9% (95% CI 72·4–79·5) in the investigational group and 71·2% (95% CI 67·6–74·9) in the control group (hazard ratio [HR] 0·79, 95% CI 0·64–0·98; p=0·03). Preoperative grade 3–4 toxic effects occurred in 144 (24%) of 607 patients who actually received fluorouracil and oxaliplatin during chemoradiotherapy and in 128 (20%) of 625 patients who actually received fluorouracil chemoradiotherapy. Of 445 patients who actually received adjuvant fluorouracil and leucovorin and oxaliplatin, 158 (36%) had grade 3–4 toxic effects, as did 170 (36%) of 470 patients who actually received adjuvant fluorouracil. Late grade 3–4 adverse events in patients who received protocol-specified preoperative and postoperative treatment occurred in 112 (25%) of 445 patients in the investigational group, and in 100 (21%) of 470 patients in the control group. Interpretation Adding oxaliplatin to fluorouracil-based neoadjuvant chemoradiotherapy and adjuvant chemotherapy (at the doses and intensities used in this trial) significantly improved disease-free survival of patients with clinically staged cT3–4 or cN1–2 rectal cancer compared with our former fluorouracil-based combined modality regimen (based on CAO/ARO/AIO-94). The regimen established by CAO/ARO/AIO-04 can be deemed a new treatment option for patients with locally advanced rectal cancer. Funding German Cancer Aid (Deutsche Krebshilfe).

Inherited Mutations in 17 Breast Cancer Susceptibility Genes Among a Large Triple-Negative Breast Cancer Cohort Unselected for Family History of Breast Cancer

Abstract: Purpose Recent advances in DNA sequencing have led to the development of breast cancer susceptibility gene panels for germline genetic testing of patients. We assessed the frequency of mutations in 17 predisposition genes, including BRCA1 and BRCA2, in a large cohort of patients with triple-negative breast cancer (TNBC) unselected for family history of breast or ovarian cancer to determine the utility of germline genetic testing for those with TNBC. Patients and Methods Patients with TNBC (N 1,824) unselected for family history of breast or ovarian cancer were recruited through 12 studies, and germline DNA was sequenced to identify mutations. Results Deleterious mutations were identified in 14.6% of all patients. Of these, 11.2% had mutations in the BRCA1 (8.5%) and BRCA2 (2.7%) genes. Deleterious mutations in 15 other predisposition genes were detected in 3.7% of patients, with the majority observed in genes involved in homologous recombination, including PALB2 (1.2%) and BARD1, RAD51D, RAD51C, and BRIP1 (0.3% to 0.5%). Patients with TNBC with mutations were diagnosed at an earlier age (P .001) and had higher-grade tumors (P .01) than those without mutations. Conclusion Deleterious mutations in predisposition genes are present at high frequency in patients with TNBC unselected for family history of cancer. Mutation prevalence estimates suggest that patients with TNBC, regardless of age at diagnosis or family history of cancer, should be considered for germline genetic testing of BRCA1 and BRCA2. Although mutations in other predisposition genes are observed among patients with TNBC, better cancer risk estimates are needed before these mutations are used for clinical risk assessment in relatives. J Clin Oncol 33:304-311. © 2014 by American Society of Clinical Oncology

A Unified in Vitro Evaluation for Apatite-Forming Ability of Bioactive Glasses and Their Variants

Abstract: The aim of this study was to propose and validate a new unified method for testing dissolution rates of bioactive glasses and their variants, and the formation of calcium phosphate layer formation on their surface, which is an indicator of bioactivity At present, comparison in the literature is difficult as many groups use different testing protocols An ISO standard covers the use of simulated body fluid on standard shape materials but it does not take into account that bioactive glasses can have very different specific surface areas, as for glass powders Validation of the proposed modified test was through round robin testing and comparison to the ISO standard where appropriate The proposed test uses fixed mass per solution volume ratio and agitated solution The round robin study showed differences in hydroxyapatite nucleation on glasses of different composition and between glasses of the same composition but different particle size The results were reproducible between research facilities Researchers should use this method when testing new glasses, or their variants, to enable comparison between the literature in the future

Genome-wide association analysis of more than 120,000 individuals identifies 15 new susceptibility loci for breast cancer

Abstract: Genome-wide association studies (GWAS) and large-scale replication studies have identified common variants in 79 loci associated with breast cancer, explaining ∼14% of the familial risk of the disease. To identify new susceptibility loci, we performed a meta-analysis of 11 GWAS, comprising 15,748 breast cancer cases and 18,084 controls together with 46,785 cases and 42,892 controls from 41 studies genotyped on a 211,155-marker custom array (iCOGS). Analyses were restricted to women of European ancestry. We generated genotypes for more than 11 million SNPs by imputation using the 1000 Genomes Project reference panel, and we identified 15 new loci associated with breast cancer at P < 5 × 10(-8). Combining association analysis with ChIP-seq chromatin binding data in mammary cell lines and ChIA-PET chromatin interaction data from ENCODE, we identified likely target genes in two regions: SETBP1 at 18q12.3 and RNF115 and PDZK1 at 1q21.1. One association appears to be driven by an amino acid substitution encoded in EXO1.

Quantum squeezing of motion in a mechanical resonator

Abstract: According to quantum mechanics, a harmonic oscillator can never be completely at rest. Even in the ground state, its position will always have fluctuations, called the zero-point motion. Although the zero-point fluctuations are unavoidable, they can be manipulated. Using microwave frequency radiation pressure, we have manipulated the thermal fluctuations of a micrometer-scale mechanical resonator to produce a stationary quadrature-squeezed state with a minimum variance of 0.80 times that of the ground state. We also performed phase-sensitive, back-action evading measurements of a thermal state squeezed to 1.09 times the zero-point level. Our results are relevant to the quantum engineering of states of matter at large length scales, the study of decoherence of large quantum systems, and for the realization of ultrasensitive sensing of force and motion.

Mechanical properties of gray and white matter brain tissue by indentation.

Abstract: The mammalian brain is composed of an outer layer of gray matter, consisting of cell bodies, dendrites, and unmyelinated axons, and an inner core of white matter, consisting primarily of myelinated axons Recent evidence suggests that microstructural differences between gray and white matter play an important role during neurodevelopment While brain tissue as a whole is rheologically well characterized, the individual features of gray and white matter remain poorly understood Here we quantify the mechanical properties of gray and white matter using a robust, reliable, and repeatable method, flat-punch indentation To systematically characterize gray and white matter moduli for varying indenter diameters, loading rates, holding times, post-mortem times, and locations we performed a series of n = 192 indentation tests We found that indenting thick, intact coronal slices eliminates the common challenges associated with small specimens: it naturally minimizes boundary effects, dehydration, swelling, and structural degradation When kept intact and hydrated, brain slices maintained their mechanical characteristics with standard deviations as low as 5% throughout the entire testing period of five days post mortem White matter, with an average modulus of 1895 kPa±0592 kPa, was on average 39% stiffer than gray matter, p 001 , with an average modulus of 1389 kPa±0289 kPa, and displayed larger regional variations It was also more viscous than gray matter and responded less rapidly to mechanical loading Understanding the rheological differences between gray and white matter may have direct implications on diagnosing and understanding the mechanical environment in neurodevelopment and neurological disorders

From transverse angular momentum to photonic wheels

Abstract: This Progress Article details the latest achievements and underlying principles of light carrying transverse spin.The capabilities and future applications of this young yet already advanced field are highlighted. Scientists have known for more than a century that light possesses both linear and angular momenta along the direction of propagation. However, only recent advances in optics have led to the notion of spinning electromagnetic fields capable of carrying angular momenta transverse to the direction of motion. Such fields enable numerous applications in nano-optics, biosensing and near-field microscopy, including three-dimensional control over atoms, molecules and nanostructures, and allowing for the realization of chiral nanophotonic interfaces and plasmonic devices. Here, we report on recent developments of optics with light carrying transverse spin. We present both the underlying principles and the latest achievements, and also highlight new capabilities and future applications emerging from this young yet already advanced field of research.

A combined maximum-likelihood analysis of the high-energy astrophysical neutrino flux measured with icecube

Abstract: Evidence for an extraterrestrial flux of high-energy neutrinos has now been found in multiple searches with the IceCube detector. The first solid evidence was provided by a search for neutrino events with deposited energies greater than or similar to 30 TeV and interaction vertices inside the instrumented volume. Recent analyses suggest that the extraterrestrial flux extends to lower energies and is also visible with throughgoing, nu(mu)-induced tracks from the Northern Hemisphere. Here, we combine the results from six different IceCube searches for astrophysical neutrinos in a maximum-likelihood analysis. The combined event sample features high-statistics samples of shower-like and track-like events. The data are fit in up to three observables: energy, zenith angle, and event topology. Assuming the astrophysical neutrino flux to be isotropic and to consist of equal flavors at Earth, the all-flavor spectrum with neutrino energies between 25 TeV and 2.8 PeV is well described by an unbroken power law with best-fit spectral index -2.50 +/- 0.09 and a flux at 100 TeV of (6.7(-1.2)(+1.1)) x 10(-18) GeV-1 s(-1) sr(-1) cm(-2). Under the same assumptions, an unbroken power law with index -2 is disfavored with a significance of 3.8 sigma (p = 0.0066%) with respect to the best fit. This significance is reduced to 2.1 sigma (p = 1.7%) if instead we compare the best fit to a spectrum with index -2 that has an exponential cut-off at high energies. Allowing the electron-neutrino flux to deviate from the other two flavors, we find a nu(e) fraction of 0.18 +/- 0.11 at Earth. The sole production of electron neutrinos, which would be characteristic of neutron-decay-dominated sources, is rejected with a significance of 3.6 sigma ( p = 0.014%).

Prediction of Breast Cancer Risk Based on Profiling With Common Genetic Variants

Abstract: Background: Data for multiple common susceptibility alleles for breast cancer may be combined to identify women at different levels of breast cancer risk. Such stratification could guide preventive and screening strategies. However, empirical evidence for genetic risk stratification is lacking. Methods: We investigated the value of using 77 breast cancer-associated single nucleotide polymorphisms (SNPs) for risk stratification, in a study of 33 673 breast cancer cases and 33 381 control women of European origin. We tested all possible pair-wise multiplicative interactions and constructed a 77-SNP polygenic risk score (PRS) for breast cancer overall and by estrogen receptor (ER) status. Absolute risks of breast cancer by PRS were derived from relative risk estimates and UK incidence and mortality rates. Results: There was no strong evidence for departure from a multiplicative model for any SNP pair. Women in the highest 1% of the PRS had a three-fold increased risk of developing breast cancer compared with women in the middle quintile (odds ratio [OR] = 3.36, 95% confidence interval [CI] = 2.95 to 3.83). The ORs for ER-positive and ER-negative disease were 3.73 (95% CI = 3.24 to 4.30) and 2.80 (95% CI = 2.26 to 3.46), respectively. Lifetime risk of breast cancer for women in the lowest and highest quintiles of the PRS were 5.2% and 16.6% for a woman without family history, and 8.6% and 24.4% for a woman with a first-degree family history of breast cancer. Conclusions: The PRS stratifies breast cancer risk in women both with and without a family history of breast cancer. The observed level of risk discrimination could inform targeted screening and prevention strategies. Further discrimination may be achievable through combining the PRS with lifestyle/environmental factors, although these were not considered in this report.

Anticoagulant reversal, blood pressure levels, and anticoagulant resumption in patients with anticoagulation-related intracerebral hemorrhage.

Abstract: RESULTS Hemorrhage enlargement occurred in 307 of 853 patients (36.0%). Reduced rates of hematoma enlargement were associated with reversal of INR levels <1.3 within 4 hours after admission (43/217 [19.8%]) vs INR of1.3 (264/636 [41.5%]; P < .001) and systolic BP <160 mm Hg at 4 hours (167/504 [33.1%]) vs160 mm Hg (98/187 [52.4%]; P < .001). The combination of INR reversal <1.3 within 4 hours and systolic BP of <160 mm Hg at 4 hours was associated with lower rates of hematoma enlargement (35/193 [18.1%] vs 220/498 [44.2%] not achieving these values; OR, 0.28; 95% CI, 0.19-0.42; P < .001) and lower rates of in-hospital mortality (26/193 [13.5%] vs 103/498 [20.7%]; OR, 0.60; 95% CI, 0.37-0.95; P = .03). OAC was resumed in 172 of 719 survivors (23.9%). OAC resumption showed fewer ischemic complications (OAC: 9/172 [5.2%] vs no OAC: 82/547 [15.0%]; P < .001) and not significantly different hemorrhagic complications (OAC: 14/172 [8.1%] vs no OAC: 36/547 [6.6%]; P = .48). Propensity-matched survival analysis in patients with atrial fibrillation who restarted OAC showed a decreased HR of 0.258 (95% CI, 0.125-0.534; P < .001) for long-term mortality. Functional long-term outcome was unfavorable in 786 of 1083 patients (72.6%). CONCLUSIONS AND RELEVANCE Among patients with OAC-associated ICH, reversal of INR <1.3 within 4 hours and systolic BP <160 mm Hg at 4 hours were associated with lower rates of hematoma enlargement, and resumption of OAC therapy was associated with lower risk of ischemic events. These findings require replication and assessment in prospective studies.

Application of smart antenna technologies in simultaneous wireless information and power transfer

Abstract: Simultaneous wireless information and power transfer (SWIPT) is a promising solution to increase the lifetime of wireless nodes and hence alleviate the energy bottleneck of energy constrained wireless networks. As an alternative to conventional energy harvesting techniques, SWIPT relies on the use of radio frequency signals, and is expected to bring some fundamental changes to the design of wireless communication networks. This article focuses on the application of advanced smart antenna technologies to SWIPT, including multiple-input multiple-output and relaying techniques. These smart antenna technologies have the potential to significantly improve the energy efficiency and also the spectral efficiency of SWIPT. Different network topologies with single and multiple users are investigated, along with some promising solutions to achieve a favorable trade-off between system performance and complexity. A detailed discussion of future research challenges for the design of SWIPT systems is also provided.