Boundary conditions in quasiclassical theory of superconductivity are of crucial importance for describing proximity effects in heterostructures between different materials. Although they have been ...derived for the ballistic case in full generality, corresponding boundary conditions for the diffusive limit, described by Usadel theory, have been lacking for interfaces involving strongly spin-polarized materials, e.g. half-metallic ferromagnets. Given the current intense research in the emerging field of superconducting spintronics, the formulation of appropriate boundary conditions for the Usadel theory of diffusive superconductors in contact with strongly spin-polarized ferromagnets for arbitrary transmission probability and arbitrary spin-dependent interface scattering phases has been a burning open question. Here we close this gap and derive the full boundary conditions for quasiclassical Green functions in the diffusive limit, valid for any value of spin polarization, transmission probability, and spin-mixing angles (spin-dependent scattering phase shifts). Our formulation allows also for complex spin textures across the interface and for channel off-diagonal scattering (a necessary ingredient when the numbers of channels on the two sides of the interface differ). As an example we derive expressions for the proximity effect in diffusive systems involving half-metallic ferromagnets. In a superconductor/half-metal/superconductor Josephson junction we find -junction behavior under certain interface conditions.
The theory of superconductivity developed by Bardeen, Cooper and Schrieffer (BCS) explains the stabilization of electron pairs into a spin-singlet, even frequency, state by the formation of an energy ...gap within which the density of states is zero. At a superconductor interface with an inhomogeneous ferromagnet, a gapless odd frequency superconducting state is predicted, in which the Cooper pairs are in a spin-triplet state. Although indirect evidence for such a state has been obtained, the gap structure and pairing symmetry have not so far been determined. Here we report scanning tunnelling spectroscopy of Nb superconducting films proximity coupled to epitaxial Ho. These measurements reveal pronounced changes to the Nb subgap superconducting density of states on driving the Ho through a metamagnetic transition from a helical antiferromagnetic to a homogeneous ferromagnetic state for which a BCS-like gap is recovered. The results prove odd frequency spin-triplet superconductivity at superconductor/inhomogeneous magnet interfaces.
Objective To evaluate long-term device outcomes following primary artificial urinary sphincter (AUS) implantation. Materials and Methods We identified 1802 male patients with stress urinary ...incontinence that underwent AUS placement from 1983 to 2011. Of these, 1082 (60%) were involving primary implantations and comprise the study cohort. Multiple clinical and surgical variables were evaluated for potential association with treatment failure, defined as any secondary surgery. Patient follow-up was obtained through office examination, operative report, and written or telephone correspondence. Results Patients undergoing AUS implantation had a median age of 71 years (interquartile range 66-76) and median follow-up of 4.1 years (interquartile range 0.8-7.7). Overall, 338 of 1082 patients (31.2%) underwent secondary surgery, including 89 for device infection and/or erosion, 131 for device malfunction, 89 for urethral atrophy, and 29 for pump malposition or tubing complications. No patient-related risk factors were independently associated with an increased risk of secondary surgery on multivariable analysis. Secondary surgery-free survival was 90% at 1 year, 74% at 5 years, 57% at 10 years, and 41% at 15 years. Conclusion Primary AUS implantation is associated with acceptable long-term outcomes. Recognition of long-term success is important for preoperative patient counseling.
Genome-wide studies have defined cell type-specific patterns of DNA methylation that are important for regulating gene expression in both normal development and disease. However, determining the ...functional significance of specific methylation events remains challenging, owing to the lack of methods for removing such modifications in a targeted manner. Here we describe an approach for efficient targeted demethylation of specific CpGs in human cells using fusions of engineered transcription activator-like effector (TALE) repeat arrays and the TET1 hydroxylase catalytic domain. Using these TALE-TET1 fusions, we demonstrate that modification of critical methylated promoter CpG positions can lead to substantial increases in the expression of endogenous human genes. Our results delineate a strategy for understanding the functional significance of specific CpG methylation marks in the context of endogenous gene loci and validate programmable DNA demethylation reagents with potential utility for research and therapeutic applications.
Electron pairing in the vast majority of superconductors follows the Bardeen-Cooper-Schrieffer theory of superconductivity, which describes the condensation of electrons into pairs with antiparallel ...spins in a singlet state with an s-wave symmetry. Unconventional superconductivity was predicted in single-layer graphene (SLG), with the electrons pairing with a p-wave or chiral d-wave symmetry, depending on the position of the Fermi energy with respect to the Dirac point. By placing SLG on an electron-doped (non-chiral) d-wave superconductor and performing local scanning tunnelling microscopy and spectroscopy, here we show evidence for a p-wave triggered superconducting density of states in SLG. The realization of unconventional superconductivity in SLG offers an exciting new route for the development of p-wave superconductivity using two-dimensional materials with transition temperatures above 4.2 K.
The aim of the present study was to review major organizational guidelines on the evaluation and management of asymptomatic microscopic haematuria (AMH). We reviewed the haematuria guidelines from: ...the American Urological Association; the consensus statement by the Canadian Urological Association, Canadian Urologic Oncology Group and Bladder Cancer Canada; the American College of Physicians; the Joint Consensus Statement of the Renal Association and British Association of Urological Surgeons; and the National Institute for Health and Care Excellence. All guidelines reviewed recommend evaluation for AMH in the absence of potential benign aetiologies, with the evaluation including cystoscopy and upper urinary tract imaging. Existing guidelines vary in their definition of AMH (role of urine dipstick vs urine microscopy), the age threshold for recommending evaluation, and the optimal imaging method (computed tomography vs ultrasonography). Of the reviewed guidelines, none recommended the use of urine cytology or urine markers during the initial AMH evaluation. Patients should have ongoing follow‐up after a negative initial AMH evaluation. Significant variation exists among current guidelines for AMH with respect to who should be evaluated and in what manner. Given the patient and health system implications of balancing appropriately focused and effective diagnostic evaluation, AMH represents a valuable future research opportunity.
In 1933, Meissner and Ochsenfeld reported the expulsion of magnetic flux—the diamagnetic Meissner effect—from the interior of superconducting lead. This discovery was crucial in formulating the ...Bardeen-Cooper-Schrieffer (BCS) theory of superconductivity. In exotic superconducting systems BCS theory does not strictly apply. A classical example is a superconductor-magnet hybrid system where magnetic ordering breaks time-reversal symmetry of the superconducting condensate and results in the stabilization of an odd-frequency superconducting state. It has been predicted that under appropriate conditions, odd-frequency superconductivity should manifest in the Meissner state as fluctuations in the sign of the magnetic susceptibility, meaning that the superconductivity can either repel (diamagnetic) or attract (paramagnetic) external magnetic flux. Here, we report local probe measurements of faint magnetic fields in a Au/Ho/Nb trilayer system using low-energy muons, where antiferromagnetic Ho (4.5 nm) breaks time-reversal symmetry of the proximity-induced pair correlations in Au. From depth-resolved measurements below the superconducting transition of Nb, we observe a local enhancement of the magnetic field in Au that exceeds the externally applied field, thus proving the existence of an intrinsic paramagnetic Meissner effect arising from an odd-frequency superconducting state.
Artificial activators designed using transcription activator-like effector (TALE) technology have broad utility, but previous studies suggest that these monomeric proteins often exhibit low ...activities. Here we demonstrate that TALE activators can robustly function individually or in synergistic combinations to increase expression of endogenous human genes over wide dynamic ranges. These findings will encourage applications of TALE activators for research and therapy, and guide design of monomeric TALE-based fusion proteins.
Abstract Background While the receipt of a perioperative blood transfusion (PBT) has been associated with an increased risk of mortality for a number of malignancies, the relationship between PBT and ...survival following radical cystectomy (RC) for bladder cancer (BCa) has not been well established. Objective To evaluate the association of PBT with disease recurrence and mortality following RC. Design, setting, and participants We identified 2060 patients who underwent RC at the Mayo Clinic between 1980 and 2005. PBT was defined as transfusion of allogenic red blood cells during RC or postoperative hospitalization. Outcome measurements and statistical analysis Survival was estimated using the Kaplan-Meier method and was compared with the log-rank test. Cox proportional hazard regression models were used to evaluate the association of PBT with outcome, controlling for clinicopathologic variables. Results and limitations A total of 1279 patients (62%) received PBT. The median number of units transfused was 2 (interquartile range IQR: 2–4). Patients receiving PBT were significantly older (median: 69 yr vs 66 yr; p < 0.0001), had a worse Eastern Cooperative Oncology Group performance status ( p < 0.0001), and were more likely to have muscle-invasive tumors (56% vs 49%; p = 0.004). Median postoperative follow-up was 10.9 yr (IQR: 7.9–15.7). Receipt of PBT was associated with significantly worse 5-yr recurrence-free survival (58% vs 64%; p = 0.01), cancer-specific survival (59% vs 72%; p < 0.001), and overall survival (45% vs 63%; p < 0.001). On multivariate analyses, PBT remained associated with significantly increased risks of postoperative tumor recurrence (hazard ratio HR: 1.20; p = 0.04), death from BCa (HR: 1.31; p = 0.003), and all-cause mortality (HR: 1.27; p = 0.0002). Among patients who received PBT, an increasing number of units transfused was independently associated with increased cancer-specific mortality (HR: 1.07; p < 0.0001) and all-cause mortality (HR: 1.05; p < 0.0001). Limitations include selection bias and lack of standardized transfusion criteria. Conclusions We found that PBT is associated with significantly increased risks of cancer recurrence and mortality following RC. While external validation is required, continued efforts to reduce the use of blood products in these patients are warranted.
Purpose We evaluate the clinical presentation, management and outcomes of patients undergoing cystectomy for refractory hemorrhagic cystitis. Materials and Methods We identified 21 patients with ...refractory hematuria treated with cystectomy at our institution between 2000 and 2012. Clot evacuation, bladder fulguration and bladder irrigation had failed in all patients before cystectomy. In addition, 45% of patients had received prior intravesical therapy (aminocaproic acid, alum or formalin), hyperbaric oxygen therapy (25%), nephrostomy tube placement for attempted urinary diversion (15%) and/or selective bladder angioembolization (5%). Results Median patient age at surgery was 77 years (IQR 72, 80) and 81% (17 of 21) of patients were male. The most common etiology for hemorrhagic cystitis was prior radiation therapy for prostate cancer (17, 81%). Median time from receipt of radiation to cystectomy in these patients was 91 months (IQR 73, 125). Median ASA® (American Society of Anesthesiologists) score at cystectomy was 3 and median preoperative hemoglobin was 10.2 gm/dl. Median length of stay after cystectomy was 10 days (IQR 7, 19). Severe (Clavien grade III to V) complications were noted in 42% of patients (8 of 19) and the 90-day mortality rate in this cohort was 16% (3 of 19). With a median postoperative followup of 13 months (IQR 4, 21), the 1 and 3-year overall survival was 84% and 52%, respectively. Conclusions Cystectomy for hemorrhagic cystitis is associated with a high risk of perioperative complications and mortality, consistent with the baseline clinical status of this patient cohort and, as such, should remain a last resort to control bleeding after failure of conservative measures.
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