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Nuclear spins were among the first physical platforms to be considered for quantum information processing1,2, because of their exceptional quantum coherence3 and atomic-scale footprint. However, their full potential for quantum computing has not yet been realized, owing to the lack of methods with which to link nuclear qubits within a scalable device combined with multi-qubit operations with sufficient fidelity to sustain fault-tolerant quantum computation. Here we demonstrate universal quantum logic operations using a pair of ion-implanted 31P donor nuclei in a silicon nanoelectronic device. A nuclear two-qubit controlled-Z gate is obtained by imparting a geometric phase to a shared electron spin4, and used to prepare entangled Bell states with fidelities up to 94.2(2.7)%. The quantum operations are precisely characterized using gate set tomography (GST)5, yielding one-qubit average gate fidelities up to 99.95(2)%, two-qubit average gate fidelity of 99.37(11)% and two-qubit preparation/measurement fidelities of 98.95(4)%. These three metrics indicate that nuclear spins in silicon are approaching the performance demanded in fault-tolerant quantum processors6. We then demonstrate entanglement between the two nuclei and the shared electron by producing a Greenberger-Horne-Zeilinger three-qubit state with 92.5(1.0)% fidelity. Because electron spin qubits in semiconductors can be further coupled to other electrons7-9 or physically shuttled across different locations10,11, these results establish a viable route for scalable quantum information processing using donor nuclear and electron spins.
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Obesity, type 2 diabetes, and heart failure are associated with aberrant cardiac metabolism. We show that the heart regulates systemic energy homeostasis via MED13, a subunit of the Mediator complex, which controls transcription by thyroid hormone and other nuclear hormone receptors. MED13, in turn, is negatively regulated by a heart-specific microRNA, miR-208a. Cardiac-specific overexpression of MED13 or pharmacologic inhibition of miR-208a in mice confers resistance to high-fat diet-induced obesity and improves systemic insulin sensitivity and glucose tolerance. Conversely, genetic deletion of MED13 specifically in cardiomyocytes enhances obesity in response to high-fat diet and exacerbates metabolic syndrome. The metabolic actions of MED13 result from increased energy expenditure and regulation of numerous genes involved in energy balance in the heart. These findings reveal a role of the heart in systemic metabolic control and point to MED13 and miR-208a as potential therapeutic targets for metabolic disorders.
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Metabolismo Energético , Resistência à Insulina , MicroRNAs/metabolismo , Miocárdio/metabolismo , Obesidade/genética , Animais , Diabetes Mellitus Tipo 2 , Feminino , Glucose/metabolismo , Coração/fisiologia , Homeostase , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , MicroRNAs/antagonistas & inibidores , MicroRNAs/genética , Obesidade/prevenção & controleRESUMO
BACKGROUND: Polycystic ovary syndrome (PCOS) is the most common cause of anovulatory infertility. Obesity exacerbates the reproductive complications of PCOS; however, the management of obesity in women with PCOS remains a large unmet clinical need. Observational studies have indicated that bariatric surgery could improve the rates of ovulatory cycles and prospects of fertility; however, the efficacy of surgery on ovulation rates has not yet been compared with behavioural modifications and medical therapy in a randomised trial. The aim of this study was to compare the safety and efficacy of bariatric surgery versus medical care on ovulation rates in women with PCOS, obesity, and oligomenorrhoea or amenorrhoea. METHODS: In this multicentre, open-label, randomised controlled trial, 80 women older than 18 years, with a diagnosis of PCOS based on the 2018 international evidence-based guidelines for assessing and managing PCOS, and a BMI of 35 kg/m2 or higher, were recruited from two specialist obesity management centres and via social media. Participants were randomly assigned at a 1:1 ratio to either vertical sleeve gastrectomy or behavioural interventions and medical therapy using a computer-generated random sequence (PLAN procedure in SAS) by an independent researcher not involved with any other aspect of the clinical trial. The median age of the entire cohort was 31 years and 79% of participants were White. The primary outcome was the number of biochemically confirmed ovulatory events over 52 weeks, and was assessed using weekly serum progesterone measurements. The primary endpoint included the intention-to-treat population and safety analyses were per-protocol population. This study is registered with the ISRCTN registry (ISRCTN16668711). FINDINGS: Participants were recruited from Feb 20, 2020 to Feb 1, 2021. 40 participants were assigned to each group and there were seven dropouts in the medical group and ten dropouts in the surgical group. The median number of ovulations was 6 (IQR 3·5-10·0) in the surgical group and 2 (0·0-4·0) in the medical group. Women in the surgical group had 2.5 times more spontaneous ovulations compared with the medical group (incidence rate ratio 2·5 [95% CI 1·5-4·2], p<0·0007). There were more complications in the surgical group than the medical group, although without long-term sequelae. There were 24 (66·7%) adverse events in the surgical group and 12 (30·0%) in the medical group. There were no treatment-related deaths. INTERPRETATION: Bariatric surgery was more effective than medical care for the induction of spontaneous ovulation in women with PCOS, obesity, and oligomenorrhoea or amenorrhoea. Bariatric surgery could, therefore, enhance the prospects of spontaneous fertility in this group of women. FUNDING: The Jon Moulton Charity Trust.
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Cirurgia Bariátrica , Obesidade , Ovulação , Síndrome do Ovário Policístico , Humanos , Síndrome do Ovário Policístico/complicações , Síndrome do Ovário Policístico/cirurgia , Feminino , Adulto , Cirurgia Bariátrica/efeitos adversos , Cirurgia Bariátrica/métodos , Obesidade/complicações , Obesidade/cirurgia , Oligomenorreia , Resultado do Tratamento , Amenorreia/etiologia , Adulto Jovem , Gastrectomia/métodos , Gastrectomia/efeitos adversos , Infertilidade Feminina/etiologiaRESUMO
The development of devices that exhibit both superconducting and semiconducting properties is an important endeavor for emerging quantum technologies. We investigate superconducting nanowires fabricated on a silicon-on-insulator (SOI) platform. Aluminum from deposited contact electrodes is found to interdiffuse with Si along the entire length of the nanowire, over micrometer length scales and at temperatures well below the Al-Si eutectic. The phase-transformed material is conformal with the predefined device patterns. The superconducting properties of a transformed mesoscopic ring formed on a SOI platform are investigated. Low-temperature magnetoresistance oscillations, quantized in units of the fluxoid, h/2e, are observed.
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Color centers in diamond are promising platforms for quantum technologies. Most color centers in diamond discovered thus far emit in the visible or near-infrared wavelength range, which are incompatible with long-distance fiber communication and unfavorable for imaging in biological tissues. Here, we report the experimental observation of a new color center that emits in the telecom O-band, which we observe in silicon-doped bulk single crystal diamonds and microdiamonds. Combining absorption and photoluminescence measurements, we identify a zero-phonon line at 1221 nm and phonon replicas separated by 42 meV. Using transient absorption spectroscopy, we measure an excited state lifetime of around 270 ps and observe a long-lived baseline that may arise from intersystem crossing to another spin manifold.
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PURPOSE OF REVIEW: The development of endoscopic and minimally invasive techniques has revolutionized the treatment of ureteropelvic junction obstruction (UPJO). Patients can now undergo successful UPJO repair without the morbidity and complications associated with open surgery. Laparoscopic and robotic repair has supplanted open surgery as the gold standard, but percutaneous endoscopic treatment remains a relevant alternative to more invasive surgery. This review will focus on the percutaneous approach for the treatment of UPJO. RECENT FINDINGS: Percutaneous endopyelotomy was popularized during the 1980âs due to advances in the field of endourology, allowing for well tolerated and reliable percutaneous access to the kidney. After percutaneous access to the kidney is achieved, the narrowed ureter at the UPJ is incised in a full thickness fashion in the posterolateral position from the ureteral lumen to the periureteral fat. Success rates for this procedure are nearly 90% at high-volume centres. The ideal patient who has success with percutaneous endopyelotomy has a short segment of narrowing less than 2âcm, no crossing vessel, good ipsilateral renal function and mild hydronephrosis. SUMMARY: Although the development of laparoscopic and robotic approaches to pyeloplasty has produced outcomes that surpass those of percutaneous endopyelotomy, it remains a viable option in the appropriately selected patient, but success rates tend to decrease with longer follow up.
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Laparoscopia , Ureter , Obstrução Ureteral , Humanos , Pelve Renal/cirurgia , Obstrução Ureteral/etiologia , Obstrução Ureteral/cirurgia , Ureter/cirurgia , Laparoscopia/efeitos adversos , Laparoscopia/métodos , RimRESUMO
BACKGROUND: Recidivism after initial sleeve gastrectomy (SG) remains common. Revisional surgery to convert SG to Roux-en-Y gastric bypass (RYGB) or duodenal switch (DS) for additional weight loss is increasing. This study aims to compare the outcomes after conversion of SG to RYGB or DS. METHODS: A retrospective single-institution review was conducted from 2015 to 2021, identifying 75 patients who underwent conversion from prior SG to either RYGB (40) or DS (35). Mean excess body weight loss (EBWL) at 3, 6, 12, and 24 months was assessed and compared. Secondary measures of length of stay (LOS), procedure length, and 30-day readmission rate were also reviewed. RESULTS: Percentage EBWL for RYGB vs DS was 24.0% vs 18.8% at 3 months (N = 36 vs 26; P < 0.0491), 34.8% vs 29.0% at 6 months (N = 29 vs 17; P < 0.2192), 43.0% vs 40.1% at 12 months (N = 28 vs 12; P < 0.6828), and 36.2% vs 41.7% at 24 months (N = 27 vs 7; P < 0.5553). Average LOS was 2.6 days ± 1.4 for RYGB and 2.8 days ± 1.3 for DS (P < 0.6032). Average procedure length was 134.4 min for RYGB and 189.8 min for DS (P < 0.0001). 30-day readmission rate was 27.5% (N = 11) for RYGB and 14.3% (N = 5) for DS (P < 0.1645). Significant weight loss was observed in both subgroups up to 12 months, with no significant weight loss between 12 and 24 months (RYGB N = 21, P < 0.2961; DS N = 5, P < 0.7233). CONCLUSION: Both revisional RYGB and revisional DS procedures had significant and sustained weight loss in the first 12 months. There was no significant excess body weight loss difference between revisional RYGB and revisional DS patients at 6, 12, and 24 months, with only significant greater weight loss for RYGB patients at 3 months. Additionally, procedure length was significantly longer for DS compared to RYGB, with no significant differences in LOS and 30-day readmission rates.
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Derivação Gástrica , Obesidade Mórbida , Humanos , Derivação Gástrica/métodos , Obesidade Mórbida/cirurgia , Estudos Retrospectivos , Hospitais Comunitários , Reoperação/métodos , Gastrectomia/métodos , Redução de Peso , Resultado do TratamentoRESUMO
The detection of charge trap ionization induced by resonant excitation enables spectroscopy on single Er3+ ions in silicon nanotransistors. In this work, a time-resolved detection method is developed to investigate the resonant excitation and relaxation of a single Er3+ ion in silicon. The time-resolved detection is based on a long-lived current signal with a tunable reset and allows the measurement under stronger and shorter resonant excitation in comparison to time-averaged detection. Specifically, the short-pulse study gives an upper bound of 23.7 µs on the decay time of the 4I13/2 state of the Er3+ ion. The fast decay and the tunable reset allow faster repetition of the single-ion detection, which is attractive for implementing this method in large-scale quantum systems of single optical centers. The findings on the detection mechanism and dynamics also provide an important basis for applying this technique to detect other single optical centers in solids.
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Age-related macular degeneration (AMD) is a debilitating eye disease that tends to affect people over the age of 55. Lipofuscins are autofluorescent, toxic byproducts of the visual cycle thought to contribute toward the progression of the disease. Targeting the accumulation of lipofuscin through catabolism may serve as a method for the early treatment of AMD. Thus, an enzymatic approach capable of degrading lipofuscin, cycloretinal (all-trans retinal dimer), was examined. A peroxidase from the organism Marasmius scorodonius (MsP1) has shown capability of degrading this toxic metabolite into nontoxic byproducts. A catalytic triad within MsP1 (D228, H365, and R388) was identified through multiple-sequence alignment and homology modeling and confirmed by kinetic analysis. MsP1-associated cleavage products were detected by gas chromatography-mass spectrometry (GC-MS), high-performance liquid chromatography (HPLC), liquid chromatography-mass spectrometry (LC-MS), and liquid chromatography-tandem mass spectrometry (LC-MSMS). MsP1 degradation byproducts of cycloretinal show reduced cytotoxicity within cell culture (ARPE-19), demonstrating its potential as a gene therapeutic to alleviate the buildup of lipofuscin within AMD.
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Lipofuscina , Degeneração Macular , Humanos , Cromatografia Líquida de Alta Pressão , Cinética , Lipofuscina/química , Degeneração Macular/metabolismo , PeroxidasesRESUMO
Electron-spin qubits have long coherence times suitable for quantum technologies. Spin-orbit coupling promises to greatly improve spin qubit scalability and functionality, allowing qubit coupling via photons, phonons or mutual capacitances, and enabling the realization of engineered hybrid and topological quantum systems. However, despite much recent interest, results to date have yielded short coherence times (from 0.1 to 1 µs). Here we demonstrate ultra-long coherence times of 10 ms for holes where spin-orbit coupling yields quantized total angular momentum. We focus on holes bound to boron acceptors in bulk silicon 28, whose wavefunction symmetry can be controlled through crystal strain, allowing direct control over the longitudinal electric dipole that causes decoherence. The results rival the best electron-spin qubits and are 104 to 105 longer than previous spin-orbit qubits. These results open a pathway to develop new artificial quantum systems and to improve the functionality and scalability of spin-based quantum technologies.
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PURPOSE: The treatment of stones ureteroscopically is associated with postoperative pain, thought to be due largely to the use of ureteral stents. In some, stent removal precipitates renal colic that can last from minutes to hours. We sought to determine if intramuscular ketorolac could reduce post-stent removal renal colic. MATERIALS AND METHODS: We performed a prospective, randomized, double-blind, placebo-controlled trial assessing the effects of ketorolac administered at time of stent removal. Patients were randomized to receive an intramuscular ketorolac 30 mg or placebo immediately prior to stent removal. Patients were contacted 1 and 7 days after stent removal to assess pain, need for opioids, emergency department or clinic visits and the need for surgical/medical interventions. RESULTS: A total of 124 patients (62 patients each in the control and treatment groups) were included in the study. The groups were comparable in demographic/operative characteristics. No difference in mean pain scores or proportion of patients who experienced severe pain at 1 and 7 days post stent removal was detected between groups. However, use of ketorolac resulted in significantly fewer renal colic-related unplanned emergency department/clinic visits in the treatment group (2%) compared with the control group (13%, p=0.032). CONCLUSIONS: Although administration of ketorolac prior to stent removal does not significantly reduce overall subjective pain experienced post stent removal compared to placebo, it does reduce the likelihood of severe renal colic requiring emergency department or office visits. Eligible patients may benefit from routine use of ketorolac injection at the time of stent removal.
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Cetorolaco , Cólica Renal , Anti-Inflamatórios não Esteroides/uso terapêutico , Método Duplo-Cego , Humanos , Cetorolaco/uso terapêutico , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/etiologia , Dor Pós-Operatória/prevenção & controle , Estudos Prospectivos , Cólica Renal/tratamento farmacológico , Cólica Renal/etiologia , Cólica Renal/prevenção & controle , Stents/efeitos adversosRESUMO
RESEARCH QUESTION: Do women receiving corifollitropin alfa with a gonadotrophin-releasing hormone (GnRH) antagonist experience less emotional and/or physical exhaustion than women receiving standard of care gonadotrophin with daily administration of GnRH agonist or antagonist? DESIGN: The CoRifollitropin EvAluation in PracTicE (CREATE) study was a prospective observational study of fertility clinics in 17 countries in Europe and the Asia-Pacific region. Women undergoing IVF were categorized by treatment. Group A received single-dose corifollitropin alfa plus a GnRH antagonist; group B received usual care daily gonadotrophin regimens with a GnRH agonist or antagonist; and group B1i received daily GnRH agonist injections. For the primary analysis, two items from the Controlled Ovarian Stimulation Impact questionnaire were used to assess the level of emotional and physical exhaustion associated with ovarian stimulation. Secondary end-points included the impact of ovarian stimulation-related healthcare resource use. RESULTS: No statistical difference was found between the percentage of participants reporting emotional exhaustion in group A (11.6%) and B (13.1%) or the percentage reporting being 'often' or 'always' physically exhausted. More participants in group B1i (16.4%) reported being emotionally exhausted 'often' or 'always' during ovarian stimulation compared with group A (11.6%; Pâ¯=â¯0.026). Patient questionnaire scores for psychological impact were higher in group A compared with group B, indicating less negative impact (72.7 versus 70.9; Pâ¯=â¯0.004). Group A had fewer clinic visits, physician consultations, nurse contacts and transvaginal ultrasound scans (all P < 0.001) than group B1. CONCLUSIONS: Treatment with corifollitropin alfa resulted in similar or numerically small differences in psychological impact and lower clinic service use compared with daily gonadotrophin regimens.
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Fertilização in vitro , Infertilidade Feminina , Atenção à Saúde , Feminino , Fertilização in vitro/métodos , Hormônio Foliculoestimulante Humano/uso terapêutico , Hormônio Liberador de Gonadotropina , Antagonistas de Hormônios , Humanos , Infertilidade Feminina/tratamento farmacológico , Indução da Ovulação/métodos , Gravidez , Taxa de GravidezRESUMO
PURPOSE OF REVIEW: Artificial intelligence in medicine has allowed for efficient processing of large datasets to perform cognitive tasks that facilitate clinical decision-making, and it is an emerging area of research. This review aims to highlight the most pertinent and recent research in artificial intelligence in endourology, where it has been used to optimize stone diagnosis, support decision-making regarding management, predict stone recurrence, and provide new tools for bioinformatics research within endourology. RECENT FINDINGS: Artificial neural networks (ANN) and machine learning approaches have demonstrated high accuracy in predicting stone diagnoses, stone composition, and outcomes of spontaneous stone passage, shockwave lithotripsy (SWL), or percutaneous nephrolithotomy (PCNL); some of these models outperform more traditional predictive models and existing nomograms. In addition, these approaches have been used to predict stone recurrence, quality of life scores, and provide novel methods of mining the electronic medical record for research. SUMMARY: Artificial intelligence can be used to enhance existing approaches to stone diagnosis, management, and prevention to provide a more individualized approach to endourologic care. Moreover, it may support an emerging area of bioinformatics research within endourology. However, despite high accuracy, many of the published algorithms lack external validity and require further study before they are more widely adopted.
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Cálculos Renais , Litotripsia , Inteligência Artificial , Humanos , Cálculos Renais/terapia , Litotripsia/métodos , Qualidade de Vida , Tecnologia , Resultado do TratamentoRESUMO
OBJECTIVES: Solid renal masses have unknown malignant potential with commonly utilized imaging. Biopsy can offer a diagnosis of cancer but has a high non-diagnostic rate and complications. Reported use of multiparametric magnetic resonance imaging (mpMRI) to diagnose aggressive histology (i.e., clear cell renal cell carcinoma (ccRCC)) via a clear cell likelihood score (ccLS) was based on retrospective review of cT1a tumors. We aim to retrospectively assess the diagnostic performance of ccLS prospectively assigned to renal masses of all stages evaluated with mpMRI prior to histopathologic evaluation. METHODS: In this retrospective cohort study from June 2016 to November 2019, 434 patients with 454 renal masses from 2 institutions with heterogenous patient populations underwent mpMRI with prospective ccLS assignment and had pathologic diagnosis. ccLS performance was assessed by contingency table analysis. The association between ccLS and ccRCC was assessed with logistic regression. RESULTS: Mean age and tumor size were 60 ± 13 years and 5.4 ± 3.8 cm. Characteristics were similar between institutions except for patient age and race (both p < 0.001) and lesion laterality and histology (both p = 0.04). The PPV of ccLS increased with each increment in ccLS (ccLS1 5% [3/55], ccLS2 6% [3/47], ccLS3 35% [20/57], ccLS4 78% [85/109], ccLS5 93% [173/186]). Pooled analysis for ccRCC diagnosis revealed sensitivity 91% (258/284), PPV 87% (258/295) for ccLS ≥ 4, and specificity 56% (96/170), NPV 94% (96/102) for ccLS ≤ 2. Diagnostic performance was similar between institutions. CONCLUSIONS: We confirm the optimal diagnostic performance of mpMRI to identify ccRCC in all clinical stages. High PPV and NPV of ccLS can help inform clinical management decision-making. KEY POINTS: ⢠The positive predictive value of the clear cell likelihood score (ccLS) for detecting clear cell renal cell carcinoma was 5% (ccLS1), 6% (ccLS2), 35% (ccLS3), 78% (ccLS4), and 93% (ccLS5). Sensitivity of ccLS ≥ 4 and specificity of ccLS ≤ 2 were 91% and 56%, respectively. ⢠When controlling for confounding variables, ccLS is an independent risk factor for identifying clear cell renal cell carcinoma. ⢠Utilization of the ccLS can help guide clinical care, including the decision for renal mass biopsy, reducing the morbidity and risk to patients.
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Carcinoma de Células Renais , Neoplasias Renais , Imageamento por Ressonância Magnética Multiparamétrica , Neoplasias da Próstata , Carcinoma de Células Renais/diagnóstico por imagem , Humanos , Neoplasias Renais/diagnóstico por imagem , Imageamento por Ressonância Magnética , Masculino , Estudos Prospectivos , Estudos RetrospectivosRESUMO
Bacterial spot, an important disease of bell and chili peppers grown in Oklahoma, is caused by Xanthomonas euvesicatoria. We evaluated isolates from 1995 to 2015 (n = 72) for avirulence alleles and race by assessing hypersensitive responses (HRs) on differentials with resistance genes Bs1, Bs2, Bs3, or Bs4. Most isolates (96%) expressed AvrBs2 (races 1, 3, 7, 8), and only three were virulent on Bs2 (race 6). Chili cultivars, grown locally for capsaicin production, were susceptible to all races. Copper-based spray programs were evaluated on bell pepper hybrids with and without Bs2 resistance from 2008 to 2010 and on bell and jalapeño hybrids with Bs2 or Bs1-2-3 from 2017 to 2018. Bs2 and Bs1-2-3 hybrids generally had lower disease and higher yields (≤21 t/ha) than susceptible entries. Copper reduced disease by 20 to 40% and increased yield by an average of 4 t/ha, but yield responses were not always significant (P = 0.05). In August 2018, disease increased to >50% on Bs2 hybrids but remained low on the Bs1-2-3 hybrid. Despite the breakdown of Bs2 resistance, yields of the Bs2 hybrids were not reduced. Avirulence alleles and race of isolates from susceptible, Bs2, and Bs1-2-3 hybrids at the end of the 2018 trial depended on source plant genetics. AvrBs2 was expressed in 86% of isolates from a susceptible hybrid but not in any isolates from the Bs2 and Bs1-2-3 hybrids. HR resistances effectively protected yield, but their deployment may not be sustainable without cultural practices such as crop rotation that limit pathogen survival and transmission to subsequent crops.
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Doenças das Plantas , Xanthomonas , Biologia , Oklahoma , Xanthomonas/genéticaRESUMO
We realize a cryogenic wide-field nitrogen-vacancy microscope and use it to image Abrikosov vortices and transport currents in a superconducting Nb film. We observe the disappearance of vortices upon increase of laser power and their clustering about hot spots upon decrease, indicating local quenching of superconductivity by the laser. Resistance measurements confirm the presence of large temperature gradients across the film. We then investigate the effect of such gradients on transport currents where the current path is seen to correlate with the temperature profile even in the fully superconducting phase. In addition to highlighting the role of temperature inhomogeneities in superconductivity phenomena, this work establishes that under sufficiently low laser power conditions wide-field nitrogen-vacancy microscopy enables imaging over mesoscopic scales down to 4 K with submicrometer spatial resolution, providing a new platform for spatially resolved investigations of a range of systems from topological insulators to van der Waals ferromagnets.
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PURPOSE: We aimed to assess failure rates of salvage interventions and changes in split kidney function (SKF) following failed primary repair of ureteropelvic junction obstruction (UPJO). MATERIALS AND METHODS: A retrospective review of adult patients at an academic medical center who underwent salvage intervention following primary treatment for UPJO was performed. Symptomatic failure was defined as significant flank pain. Radiographic failure was defined as no improvement in drainage or a decrease in SKF by ≥7%. Overall failure, the primary outcome, was defined as symptomatic failure, radiographic failure, or both. RESULTS: Between 2008-2017, 34 patients (median age 38 years, 50% men) met study criteria. UPJO management was primary pyeloplasty/secondary endopyelotomy for 21/34 (62%), primary pyeloplasty/secondary pyeloplasty for 6/34 (18%), and primary endopyelotomy/secondary pyeloplasty for 7/34 (21%). Median follow-up was 3.3 years following secondary intervention. Patients undergoing primary pyeloplasty/secondary endopyelotomy had significantly higher overall failure than those undergoing primary pyeloplasty/secondary pyeloplasty (16/21 [76%] vs. 1/6 [17%], p=0.015). Among patients undergoing secondary endopyelotomy, presence of a stricture on retrograde pyelogram, stricture length, and SKF were not associated with symptomatic, radiographic, or overall failure. Serial renography was performed for 28/34 (82%) patients and 2/28 (7%) had a significant decline in SKF. CONCLUSIONS: Following failed primary pyeloplasty, secondary endopyelotomy had a greater overall failure rate than secondary pyeloplasty. No radiographic features assessed were associated with secondary endopyelotomy failure. Secondary intervention overall failure rates were higher than reported in the literature. Unique to this study, serial renography demonstrated that significant functional loss was overall infrequent.
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Laparoscopia , Obstrução Ureteral , Adulto , Feminino , Humanos , Pelve Renal/diagnóstico por imagem , Pelve Renal/cirurgia , Masculino , Estudos Retrospectivos , Obstrução Ureteral/diagnóstico por imagem , Obstrução Ureteral/cirurgia , Procedimentos Cirúrgicos UrológicosRESUMO
INTRODUCTION: There are no effective treatments for gliomas after progression on radiation, temozolomide, and bevacizumab. Microglia activation may be involved in radiation resistance and can be inhibited by the brain penetrating antibiotic minocycline. In this phase 1 trial, we examined the safety and effect on survival, symptom burden, and neurocognitive function of reirradiation, minocycline, and bevacizumab. METHODS: The trial used a 3 + 3 design for dose escalation followed by a ten person dose expansion. Patients received reirradiation with dosing based on radiation oncologist judgment, bevacizumab 10 mg/kg IV every two weeks, and oral minocycline twice a day. Symptom burden was measured using MDASI-BT. Neurocognitive function was measured using the COGSTATE battery. RESULTS: The maximum tolerated dose of minocycline was 400 mg twice a day with no unexpected toxicities. The PFS3 was 64.6%, and median overall survival was 6.4 months. Symptom burden and neurocognitive function did not decline in the interval between treatment completion and tumor progression. CONCLUSIONS: Minocycline 400 mg orally twice a day with bevacizumab and reirradiation is well tolerated by physician and patient reported outcomes in people with gliomas that progress on bevacizumab.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Encefálicas/terapia , Quimiorradioterapia/mortalidade , Glioma/terapia , Adulto , Idoso , Bevacizumab/administração & dosagem , Neoplasias Encefálicas/patologia , Resistencia a Medicamentos Antineoplásicos , Feminino , Seguimentos , Glioma/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Minociclina/administração & dosagem , Gradação de Tumores , Estudos Prospectivos , Retratamento , Taxa de SobrevidaRESUMO
Continued scaling of semiconductor devices has driven information technology into vastly diverse applications. The performance of ultrascaled transistors is strongly influenced by local electric field and strain. As the size of these devices approaches fundamental limits, it is imperative to develop characterization techniques with nanometer resolution and three-dimensional (3D) mapping capabilities for device optimization. Here, we report on the use of single erbium (Er) ions as atomic probes for the electric field and strain in a silicon ultrascaled transistor. Stark shifts on the Er3+ spectra induced by both the overall electric field and the local charge environment are observed. Changes in strain smaller than 3 × 10-6 are detected, which is around 2 orders of magnitude more sensitive than the standard techniques used in the semiconductor industry. These results open new possibilities for 3D mapping of the local strain and electric field in the channel of ultrascaled transistors.