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1.
Phys Rev Lett ; 132(1): 017001, 2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-38242669

RESUMO

The ideal superconductor provides a pristine environment for the delicate states of a quantum computer: because there is an energy gap to excitations, there are no spurious modes with which the qubits can interact, causing irreversible decay of the quantum state. As a practical matter, however, there exists a high density of excitations out of the superconducting ground state even at ultralow temperature; these are known as quasiparticles. Observed quasiparticle densities are of order 1 µm^{-3}, tens of orders of magnitude greater than the equilibrium density expected from theory. Nonequilibrium quasiparticles extract energy from the qubit mode and can induce dephasing. Here we show that a dominant mechanism for quasiparticle poisoning is direct absorption of high-energy photons at the qubit junction. We use a Josephson junction-based photon source to controllably dose qubit circuits with millimeter-wave radiation, and we use an interferometric quantum gate sequence to reconstruct the charge parity of the qubit. We find that the structure of the qubit itself acts as a resonant antenna for millimeter-wave radiation, providing an efficient path for photons to generate quasiparticles. A deep understanding of this physics will pave the way to realization of next-generation superconducting qubits that are robust against quasiparticle poisoning.

2.
Phys Rev Lett ; 131(15): 150602, 2023 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-37897769

RESUMO

Stabilizer operations are at the heart of quantum error correction and are typically implemented in software-controlled entangling gates and measurements of groups of qubits. Alternatively, qubits can be designed so that the Hamiltonian corresponds directly to a stabilizer for protecting quantum information. We demonstrate such a hardware implementation of stabilizers in a superconducting circuit composed of chains of π-periodic Josephson elements. With local on-chip flux and charge biasing, we observe a progressive softening of the energy band dispersion with respect to flux as the number of frustrated plaquette elements is increased, in close agreement with our numerical modeling.

3.
ESMO Open ; 8(2): 101199, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-37018874

RESUMO

BACKGROUND: Fluoropyrimidines (FPs) are an essential part of the majority of systemic regimens in the treatment of metastatic colorectal cancer (CRC). The use of the oral FP S-1 has been approved by the European Medicines Agency as monotherapy or in combination with oxaliplatin or irinotecan, with or without bevacizumab, for the treatment of patients with metastatic CRC in whom it is not possible to continue treatment with another FP due to hand-foot syndrome (HFS) or cardiovascular toxicity (CVT). Subsequently, this indication has been included in the 2022 ESMO guidelines for metastatic CRC. Recommendations for use in daily practice are not available. PATIENTS AND METHODS: Based on peer-reviewed published data on the use of S-1 in Western patients with metastatic CRC who switched from infusional 5-fluorouracil (5-FU) or capecitabine to S-1 for reasons of HFS or CVT, recommendations for its use were formulated by an international group of medical oncologists with expertise in the treatment of metastatic CRC and a cardio-oncologist. RESULTS: In patients who experience pain and/or functional impairment due to HFS during treatment with capecitabine or infusional 5-FU, a switch to S-1 is recommended without prior dose reduction of capecitabine/5-FU. S-1 should preferably be initiated at full dose when HFS has decreased to grade ≤1. In patients with cardiac complaints, in whom an association with capecitabine or infusional 5-FU treatment cannot be excluded, capecitabine/5-FU should be discontinued and a switch to S-1 is recommended. CONCLUSIONS: These recommendations should guide clinicians in daily practice in the treatment of patients with metastatic CRC with FP-containing regimens.


Assuntos
Neoplasias do Colo , Neoplasias Colorretais , Síndrome Mão-Pé , Humanos , Capecitabina/efeitos adversos , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Síndrome Mão-Pé/etiologia , Síndrome Mão-Pé/tratamento farmacológico , Fluoruracila/efeitos adversos , Irinotecano/uso terapêutico , Neoplasias do Colo/tratamento farmacológico , Fatores Imunológicos/uso terapêutico
4.
Nat Commun ; 13(1): 6425, 2022 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-36307415

RESUMO

Quantum error correction can preserve quantum information in the presence of local errors, but correlated errors are fatal. For superconducting qubits, high-energy particle impacts from background radioactivity produce energetic phonons that travel throughout the substrate and create excitations above the superconducting ground state, known as quasiparticles, which can poison all qubits on the chip. We use normal metal reservoirs on the chip back side to downconvert phonons to low energies where they can no longer poison qubits. We introduce a pump-probe scheme involving controlled injection of pair-breaking phonons into the qubit chips. We examine quasiparticle poisoning on chips with and without back-side metallization and demonstrate a reduction in the flux of pair-breaking phonons by over a factor of 20. We use a Ramsey interferometer scheme to simultaneously monitor quasiparticle parity on three qubits for each chip and observe a two-order of magnitude reduction in correlated poisoning due to background radiation.

5.
ESMO Open ; 7(3): 100427, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35798468

RESUMO

BACKGROUND: Capecitabine- or 5-fluorouracil (5-FU)-based chemotherapy is widely used in many solid tumours, but is associated with cardiotoxicity. S-1 is a fluoropyrimidine with low rates of cardiotoxicity, but evidence regarding the safety of switching to S-1 after 5-FU- or capecitabine-associated cardiotoxicity is scarce. PATIENTS AND METHODS: This retrospective study (NCT04260269) was conducted at 13 centres in 6 countries. The primary endpoint was recurrence of cardiotoxicity after switch to S-1-based treatment due to 5-FU- or capecitabine-related cardiotoxicity: clinically meaningful if the upper boundary of the 95% confidence interval (CI; by competing risk) is not including 15%. Secondary endpoints included cardiac risk factors, diagnostic work-up, treatments, outcomes, and timelines of cardiotoxicity. RESULTS: Per protocol, 200 patients, treated between 2011 and 2020 [median age 66 years (range 19-86); 118 (59%) males], were included. Treatment intent was curative in 145 (73%). Initial cardiotoxicity was due to capecitabine (n = 170), continuous infusion 5-FU (n = 22), or bolus 5-FU (n = 8), which was administered in combination with other chemotherapy, targeted agents, or radiotherapy in 133 patients. Previous cardiovascular comorbidities were present in 99 (50%) patients. Cardiotoxic events (n = 228/200) included chest pain (n = 125), coronary syndrome/infarction (n = 69), arrhythmia (n = 22), heart failure/cardiomyopathy (n = 7), cardiac arrest (n = 4), and malignant hypertension (n = 1). Cardiotoxicity was severe or life-threatening in 112 (56%) patients and led to permanent capecitabine/5-FU discontinuation in 192 (96%). After switch to S-1, recurrent cardiotoxicity was observed in eight (4%) patients (95% CI 2.02-7.89, primary endpoint met). Events were limited to grade 1-2 and occurred at a median of 16 days (interquartile range 7-67) from therapy switch. Baseline ischemic heart disease was a risk factor for recurrent cardiotoxicity (odds ratio 6.18, 95% CI 1.36-28.11). CONCLUSION: Switching to S-1-based therapy is safe and feasible after development of cardiotoxicity on 5-FU- or capecitabine-based therapy and allows patients to continue their pivotal fluoropyrimidine-based treatment.


Assuntos
Fluoruracila , Neoplasias , Adulto , Idoso , Idoso de 80 Anos ou mais , Capecitabina/efeitos adversos , Cardiotoxicidade/etiologia , Feminino , Fluoruracila/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/tratamento farmacológico , Estudos Retrospectivos , Adulto Jovem
6.
Ann Oncol ; 33(10): 1052-1060, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35764271

RESUMO

BACKGROUND: In the phase II multicohort CheckMate 142 study, nivolumab plus low-dose (1 mg/kg) ipilimumab provided robust and durable clinical benefit with a manageable safety profile in previously treated patients with microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) metastatic colorectal cancer (mCRC) at 13.4- and 25.4-month median follow-up (Overman MJ, Lonardi S, Wong KYM et al. Durable clinical benefit with nivolumab plus ipilimumab in DNA mismatch repair-deficient/microsatellite instability-high metastatic colorectal cancer. J Clin Oncol. 2018;36:773-779. Overman MJ, Lonardi S, Wong KYM, et al. Nivolumab plus low-dose ipilimumab in previously treated patients with microsatellite instability-high/mismatch repair deficient metastatic colorectal cancer: long-term follow-up. J Clin Oncol. 2019;37:635). Here, we present results from the 4-year follow-up of these patients. PATIENTS AND METHODS: Patients received nivolumab (3 mg/kg) plus low-dose (1 mg/kg) ipilimumab every 3 weeks (four doses) followed by nivolumab (3 mg/kg) every 2 weeks until disease progression. Primary endpoint was investigator-assessed objective response rate (ORR; as per RECIST version 1.1). RESULTS: A total of 119 patients were treated; 76% had ≥2 prior lines of therapy. Median follow-up was 50.9 months (range 46.9-62.7 months). Median duration of therapy was 24.9 months [95% confidence interval (CI) 15.8-33.2 months]. Investigator-assessed ORR increased from 55% (95% CI 45% to 64%) at 13.4 months to 65% (95% CI 55% to 73%) at 50.9 months with a disease control rate of 81% (95% CI 72% to 87%). The complete response rate increased from 3% at 13.4 months to 13% at 50.9 months. Partial responses were observed in 52% of patients; 21% had stable disease, and 12% had progressive disease. Median time to response was 2.8 months (range 1.1-37.1 months), and median duration of response was not reached (range 1.4+ to 58.0+ months). At data cut-off, 37 (48%) patients had ongoing responses. Median progression-free survival was not reached [95% CI 38.4 months-not estimable (NE)], and median overall survival was not reached (95% CI NE). Grade 3-4 treatment-related adverse events (TRAEs) were observed in 32% of patients; 13% of patients had any-grade TRAEs leading to discontinuation. CONCLUSIONS: The results confirm long-term benefit of nivolumab plus low-dose ipilimumab for previously treated patients with MSI-H/dMMR mCRC. The safety profile was manageable with no new safety signals.


Assuntos
Neoplasias do Colo , Neoplasias Colorretais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias do Colo/tratamento farmacológico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Reparo de Erro de Pareamento de DNA/genética , Seguimentos , Humanos , Ipilimumab , Instabilidade de Microssatélites , Nivolumabe/uso terapêutico
7.
Ir Med J ; (4): 588, 2022 04 29.
Artigo em Inglês | MEDLINE | ID: mdl-35695828

RESUMO

Presentation Tick borne encephalitis (TBE) is not endemic in Ireland and diagnostic tests are seldom requested. We describe the first notified case in Ireland. A 50-year-old female returned from Lithuania and presented with fever and new neurologic signs. Diagnosis TBE was diagnosed by detection of TBE virus specific antibodies in serum and cerebrospinal fluid (CSF). Treatment The patient was managed with observation and supportive care consisting of intravenous fluids and analgesia. Discussion The case highlights the importance of awareness of TBE among physicians and travellers to guide appropriate testing and vaccination. TBE is being recognised in non-endemic countries posing an emerging risk to public health.


Assuntos
Vírus da Encefalite Transmitidos por Carrapatos , Encefalite Transmitida por Carrapatos , Encefalite Transmitida por Carrapatos/diagnóstico , Encefalite Transmitida por Carrapatos/epidemiologia , Encefalite Transmitida por Carrapatos/terapia , Feminino , Humanos , Irlanda/epidemiologia , Pessoa de Meia-Idade , Vacinação
8.
J Prev Alzheimers Dis ; 8(4): 457-461, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34585220

RESUMO

BACKGROUND: Although studies have examined the geographic distribution of dementia among the general population in order to develop geographically targeted interventions, no studies have examined the geographic distribution of subjective cognitive decline (SCD) among military veterans specifically. OBJECTIVES: To map the geographic distribution of subjective cognitive decline from 2011-2019 in the United States among military veterans. DESIGN: Cross-sectional. SETTING: United States. PARTICIPANTS: Individuals reporting previous service in the United States Armed Forces. MEASUREMENTS: Using 2011 Behavioral Risk Factor Surveillance System (BRFSS) data, which is last year for which geocoded SCD data is publicly available, we estimated the survey-weighted county-level prevalence of veteran SCD for counties with >30 veterans (43 counties in 7 states). We then developed a Fay-Herriot small area estimation linear model using auxiliary data from the Census, with county-level veteran-specific covariates including % >65 years old, % female, % college educated, and median income. Following model validation, we created beta-weighted predictions of veteran SCD for all USA counties for 2011-2019 using relevant time-specific Census auxiliary data. We provide choropleth maps of our predictions. RESULTS: Results of our model on 43 counties showed that county-level rates of SCD were significantly associated with all auxiliary variables except annual income (F = 1.49, df = 4, 38). Direct survey-weighted rates were correlated with model-predicted rates in 43 counties (Pearson r = 0.32). Regarding predicted rates for the entire USA, the average county-level prevalence rate of veteran SCD in 2011 was 13.83% (SD = 7.35), but 29.13% in 2019 (SD = 14.71) - although variation in these rates were evident across counties. CONCLUSIONS: SCD has increased since 2011 among veterans. Veterans Affairs hospitals should implement plans that include cognitive assessments, referral to resources, and monitoring patient progress, especially in rural areas.


Assuntos
Sistema de Vigilância de Fator de Risco Comportamental , Disfunção Cognitiva/epidemiologia , Modelos Estatísticos , Autorrelato , Veteranos/estatística & dados numéricos , Adulto , Idoso , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Estados Unidos
9.
J Phys Condens Matter ; 33(49)2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34521077

RESUMO

Decoherence in quantum bits (qubits) is a major challenge for realizing scalable quantum computing. One of the primary causes of decoherence in qubits and quantum circuits based on superconducting Josephson junctions is the critical current fluctuation. Many efforts have been devoted to suppressing the critical current fluctuation in Josephson junctions. Nonetheless, the efforts have been hindered by the defect-induced trapping states in oxide-based tunnel barriers and the interfaces with superconductors in the traditional Josephson junctions. Motivated by this, along with the recent demonstration of 2D insulatorh-BN with exceptional crystallinity and low defect density, we fabricated a vertical NbSe2/h-BN/Nb Josephson junction consisting of a bottom NbSe2superconductor thin layer and a top Nb superconductor spaced by an atomically thinh-BN layer. We further characterized the superconducting current and voltage (I-V) relationships and Fraunhofer pattern of the NbSe2/h-BN/Nb junction. Notably, we demonstrated the critical current noise (1/fnoise power) in theh-BN-based Josephson device is at least a factor of four lower than that of the previously studied aluminum oxide-based Josephson junctions. Our work offers a strong promise ofh-BN as a novel tunnel barrier for high-quality Josephson junctions and qubit applications.

10.
Nature ; 594(7863): 369-373, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34135523

RESUMO

The central challenge in building a quantum computer is error correction. Unlike classical bits, which are susceptible to only one type of error, quantum bits (qubits) are susceptible to two types of error, corresponding to flips of the qubit state about the X and Z directions. Although the Heisenberg uncertainty principle precludes simultaneous monitoring of X- and Z-flips on a single qubit, it is possible to encode quantum information in large arrays of entangled qubits that enable accurate monitoring of all errors in the system, provided that the error rate is low1. Another crucial requirement is that errors cannot be correlated. Here we characterize a superconducting multiqubit circuit and find that charge noise in the chip is highly correlated on a length scale over 600 micrometres; moreover, discrete charge jumps are accompanied by a strong transient reduction of qubit energy relaxation time across the millimetre-scale chip. The resulting correlated errors are explained in terms of the charging event and phonon-mediated quasiparticle generation associated with absorption of γ-rays and cosmic-ray muons in the qubit substrate. Robust quantum error correction will require the development of mitigation strategies to protect multiqubit arrays from correlated errors due to particle impacts.

11.
Clin Oncol (R Coll Radiol) ; 33(5): 292-299, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33309479

RESUMO

AIMS: Stereotactic ablative radiation therapy (SABR) is a standard of care for medically inoperable early stage non-small cell lung carcinoma. Tumours greater than 5 cm have been excluded from randomised trials using SABR and, hence, it is not used as a standard for larger lung tumours. However, improvements in radiation therapy techniques and the success of SABR in treatment of early stage disease may allow safe delivery of ablative doses to larger tumours. We analysed our experience with tumours ≥5 cm to determine the efficacy and toxicity profile of SABR in this setting. MATERIALS AND METHODS: We evaluated survival, control rates, patterns of failure and toxicity in patients with a tumour diameter larger than 5 cm that had no nodal or distant metastases treated with SABR technology. Patients had been treated in two centres since 2009 and were retrospectively analysed. All patients had positron emission tomography staging, were discussed at a tumour board and were documented to have no nodal or distant metastatic disease. Treatment outcomes were analysed using Kaplan-Meier estimates and compared using the Log-rank test. Cox regression was used to investigate the association between the survival outcomes and predictor variables. RESULTS: In total, 86 patients were identified. Six patients had no follow-up imaging. Therefore, 80 patients were available for analysis. All patients were reclassified according to the updated AJCC eighth edition. The median follow-up was 19.6 months. No patients received neoadjuvant or concurrent systemic therapy. One patient received adjuvant systemic therapy. The median age at treatment was 77 years (range 58-91). Eighty-four per cent were stage T3N0M0 and 16% were staged T4N0M0. The median tumour diameter was 5.8 cm (range 5.0-9.3 cm). The median gross tumour volume, measured on a single phase of the respiratory cycle, was 45.7 cm3 (range 12.1-203.3 cm3). The median overall survival was 20.9 months (95% confidence interval 12.6-29.1 months). One-, 2- and 3-year overall survival was 71%, 48% and 32%, respectively. The median local failure-free survival was 19.5 months (95% confidence interval 14.4-24.6). The median disease-free survival was 15.1 months (95% confidence interval 9.9-20.4 months). Local control at 1, 2 and 3 years was 85% (95% confidence interval 76-94%), 71% (95% confidence interval 58-84%) and 57% (95% confidence interval 40-74%), respectively. Forty-four patients (55%) had any treatment failure (local, mediastinal, intrapulmonary or distant metastases). Out-of-field intrapulmonary disease progression was the most common mode of failure, occurring in 21 patients (26%). Local failure occurred in 19 patients (24%) - alone or in combination with other progression. Distant metastases occurred in 20 patients (25%). Neither histological subtype, tumour size nor gross tumour volume had a statistically significant effect on local failure-free survival. Two patients experienced grade 3 late dyspnoea. There were no other reported grade 3 or higher acute or late toxicities. CONCLUSION: SABR for larger lung tumours ≥5 cm results in high local control and acceptable survival in patients with medically inoperable large non-small cell lung carcinoma treated with radiation alone. Such patients should be considered for SABR owing to fewer treatment fractions and acceptable toxicity. Local control analysis reveals a sustained pattern of local failure emphasising the need for long-term follow-up. Improvements in technical strategies are required to further improve local control.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Radiocirurgia , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Humanos , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/cirurgia , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
13.
BMC Health Serv Res ; 20(1): 814, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32867837

RESUMO

BACKGROUND: Many women with hyperglycaemia in pregnancy do not receive care during and after pregnancy according to standards recommended in international guidelines. The burden of hyperglycaemia in pregnancy falls disproportionately upon Indigenous peoples worldwide, including Aboriginal and Torres Strait Islander women in Australia. The remote and regional Australian context poses additional barriers to delivering healthcare, including high staff turnover and a socially disadvantaged population with a high prevalence of diabetes. METHODS: A complex health systems intervention to improve care for women during and after a pregnancy complicated by hyperglycaemia will be implemented in remote and regional Australia (the Northern Territory and Far North Queensland). The Theoretical Domains Framework was used during formative work with stakeholders to identify intervention components: (1) increasing workforce capacity, skills and knowledge and improving health literacy of health professionals and women; (2) improving access to healthcare through culturally and clinically appropriate pathways; (3) improving information management and communication; (4) enhancing policies and guidelines; (5) embedding use of a clinical register as a quality improvement tool. The intervention will be evaluated utilising the RE-AIM framework at two timepoints: firstly, a qualitative interim evaluation involving interviews with stakeholders (health professionals, champions and project implementers); and subsequently a mixed-methods final evaluation of outcomes and processes: interviews with stakeholders; survey of health professionals; an audit of electronic health records and clinical register; and a review of operational documents. Outcome measures include changes between pre- and post-intervention in: proportion of high risk women receiving recommended glucose screening in early pregnancy; diabetes-related birth outcomes; proportion of women receiving recommended postpartum care including glucose testing; health practitioner confidence in providing care, knowledge and use of relevant guidelines and referral pathways, and perception of care coordination and communication systems; changes to health systems including referral pathways and clinical guidelines. DISCUSSION: This study will provide insights into the impact of health systems changes in improving care for women with hyperglycaemia during and after pregnancy in a challenging setting. It will also provide detailed information on process measures in the implementation of such health system changes.


Assuntos
Serviços de Saúde do Indígena/organização & administração , Hiperglicemia/terapia , Complicações na Gravidez/terapia , Cuidado Pré-Natal/organização & administração , Adulto , Feminino , Programas Governamentais , Pessoal de Saúde , Humanos , Hiperglicemia/diagnóstico , Programas de Rastreamento , Serviços de Saúde Materna , Assistência Médica , Havaiano Nativo ou Outro Ilhéu do Pacífico , Northern Territory , Gravidez , Gravidez em Diabéticas/diagnóstico , Gravidez em Diabéticas/epidemiologia , Melhoria de Qualidade , Queensland , Encaminhamento e Consulta
14.
Rev Sci Instrum ; 91(2): 023507, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-32113444

RESUMO

The Charge Exchange Recombination Spectroscopy (CXRS) diagnostic has become a routine diagnostic on almost all major high temperature fusion experimental devices. For the optimized stellarator Wendelstein 7-X (W7-X), a highly flexible and extensive CXRS diagnostic has been built to provide high-resolution local measurements of several important plasma parameters using the recently commissioned neutral beam heating. This paper outlines the design specifics of the W7-X CXRS system and gives examples of the initial results obtained, including typical ion temperature profiles for several common heating scenarios, toroidal flow and radial electric field derived from velocity measurements, beam attenuation via beam emission spectra, and normalized impurity density profiles under some typical plasma conditions.

15.
BJS Open ; 2(6): 456-463, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30511046

RESUMO

BACKGROUND: Caudal-related homeobox transcription factor 2 (CDX2) is an intestine-specific transcription factor implicated in tumour differentiation, proliferation, cell adhesion and migration. Negative CDX2 status (CDX2-) is associated with worse prognosis in colorectal cancer and may identify high-risk stage II disease that benefits from adjuvant chemotherapy. This observational study investigated whether CDX2- is associated with prognosis or response to chemotherapy in the mismatch repair-deficient (dMMR) phenotype of colorectal cancer. METHODS: Patients with resectable dMMR colorectal cancer were eligible for inclusion. The prognostic and predictive value of CDX2 expression on the presence of lymph node metastasis (LNM) and survival was investigated. CDX2 status was determined via immunohistochemistry using the Leica Bond™ CDX2 (clone EP25) ready-to-use primary antibody. RESULTS: Some 235 of 238 consecutive dMMR tumours were assessed for CDX2 status. CDX2- was observed in 15·7 per cent of colorectal cancer. Interobserver agreement was excellent (κ = 0·863; P < 0·001). CDX2- was significantly associated with female sex, increased size, advanced stage, worse conventional and poorly differentiated cluster (PDC) grade, mucinous morphology, perineural and lymphovascular invasion, and pN status (all P ≤ 0·038). CDX2- was not associated with LNM or survival in multivariable analysis. Independent predictors of LNM were PDC grade (odds ratio (OR) 4·12, 95 per cent c.i. 1·76 to 9·63; P = 0·001) and extramural venous invasion (OR 3·79, 1·62 to 8·85; P = 0·002). Budding (hazard ratio (HR) 2·79, 95 per cent c.i. 1·60 to 4·87; P < 0·001), pT status (HR 3·59, 1·29 to 10·01; P = 0·015) and adjuvant chemotherapy (HR 2·07, 1·15 to 3·74; P = 0·016) were independently associated with worse disease-free survival. CONCLUSION: CDX2- does not confer a worse prognosis in the dMMR phenotype of colorectal cancer. The MMR status of patients with colorectal cancer should be determined before assessing CDX2 status.

16.
Ir Med J ; 111(7): 786, 2018 08 13.
Artigo em Inglês | MEDLINE | ID: mdl-30450890

RESUMO

Introduction There is little published research evaluating attitudes towards patient safety culture and working conditions in neonatal units. This study aimed to explore this within a Level III Irish neonatal unit setting. Methods This was a quantitative, cross-sectional study performed in the Rotunda Hospital, Dublin. A 30-item safety attitudes questionnaire (SAQ) was utilized to analyze staff perceptions in areas including job satisfaction, working conditions and stress recognition. Results The 'Stress Recognition' domain received the highest score (75.3) followed by 'Job Satisfaction' domain with a mean score of 74.4. The lowest mean scale score in the neonatal unit was for 'Perceptions of Management', with a mean score of 50.7. Collaboration and Communication scores were high across all disciplines. Conclusion This SAQ has highlighted a number of important areas for quality improvement and staff satisfaction in our neonatal unit.


Assuntos
Atitude do Pessoal de Saúde , Hospitais Universitários/normas , Berçários Hospitalares/normas , Segurança do Paciente , Gestão da Segurança , Centros de Atenção Terciária/normas , Estudos Transversais , Feminino , Humanos , Satisfação no Emprego , Masculino , Equipe de Assistência ao Paciente/normas , Estresse Psicológico
17.
Science ; 361(6408): 1239-1242, 2018 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-30237353

RESUMO

Fast, high-fidelity measurement is a key ingredient for quantum error correction. Conventional approaches to the measurement of superconducting qubits, involving linear amplification of a microwave probe tone followed by heterodyne detection at room temperature, do not scale well to large system sizes. We introduce an approach to measurement based on a microwave photon counter demonstrating raw single-shot measurement fidelity of 92%. Moreover, the intrinsic damping of the photon counter is used to extract the energy released by the measurement process, allowing repeated high-fidelity quantum nondemolition measurements. Our scheme provides access to the classical outcome of projective quantum measurement at the millikelvin stage and could form the basis for a scalable quantum-to-classical interface.

18.
Ir J Med Sci ; 187(2): 333-336, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-28852961

RESUMO

BACKGROUND: Bevacizumab is the first angiogenesis inhibitor to be approved for metastatic colorectal cancer. Unfortunately, bevacizumab treatment has been associated with a variety of complications including haemorrhage, poor wound healing and gastrointestinal perforation. Late anastomotic breakdown related to bevacizumab therapy however has rarely been described. CASE REPORT: Here, we present the case of a 56-year-old woman who had a bevacizumab-related anastomotic breakdown 17 months following her primary anastomosis. She initially underwent an emergency Hartmann's procedure and two further laparotomies for significant intra-abdominal haemorrhage. Despite the best efforts of the surgical and intensive care teams, ultimately, the patient passed away. DISCUSSION: There is a small but growing body of literature relating to bevacizumab use and late anastomotic breakdown. It would seem prudent to take extra caution when using bevacizumab in those patients with previous pelvic irradiation, who have a rectal site of anastomosis or have experienced a previous anastomotic leak.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Bevacizumab/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Inibidores da Angiogênese/farmacologia , Bevacizumab/administração & dosagem , Bevacizumab/farmacologia , Feminino , Humanos , Pessoa de Meia-Idade
19.
Fire Saf J ; 1012018.
Artigo em Inglês | MEDLINE | ID: mdl-30983690

RESUMO

This paper provides a report of the discussions held at the first workshop on Measurement and Computation of Fire Phenomena (MaCFP) on June 10-11 2017. The first MaCFP work-shop was both a technical meeting for the gas phase subgroup and a planning meeting for the condensed phase subgroup. The gas phase subgroup reported on a first suite of experimental- computational comparisons corresponding to an initial list of target experiments. The initial list of target experiments identifies a series of benchmark configurations with databases deemed suitable for validation of fire models based on a Computational Fluid Dynamics approach. The simulations presented at the first MaCFP workshop feature fine grid resolution at the millimeter- or centimeter- scale: these simulations allow an evaluation of the performance of fire models under high-resolution conditions in which the impact of numerical errors is reduced and many of the discrepancies between experimental data and computational results may be attributed to modeling errors. The experimental-computational comparisons are archived on the MaCFP repository [1]. Furthermore, the condensed phase subgroup presented a review of the main issues associated with measurements and modeling of pyrolysis phenomena. Overall, the first workshop provided an illustration of the potential of MaCFP in providing a response to the general need for greater levels of integration and coordination in fire research, and specifically to the particular needs of model validation.

20.
Rev Sci Instrum ; 88(7): 073508, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28764552

RESUMO

A new core charge exchange recombination spectroscopy diagnostic has been installed in the ASDEX Upgrade tokamak that is capable of measuring the impurity ion temperature, toroidal rotation, and density on both the low field side (LFS) and high field side (HFS) of the plasma. The new system features 48 lines-of-sight (LOS) with a radial resolution that varies from ±2 cm on the LFS down to ±0.75 cm on the HFS and has sufficient signal to run routinely at 10 ms and for special circumstances down to 2.5 ms integration time. The LFS-HFS ion temperature profiles provide an additional constraint on the magnetic equilibrium reconstruction, and the toroidal rotation frequency profiles are of sufficiently high quality that information on the poloidal velocity can be extracted from the LFS-HFS asymmetry. The diagnostic LOS are coupled to two flexible-wavelength spectrometers such that complete LFS-HFS profiles from two separate impurities can be imaged simultaneously, albeit with reduced radial coverage. More frequently, the systems measure the same impurity providing very detailed information on the chosen species. Care has been taken to calibrate the systems as accurately as possible and to include in the data analysis any effects that could lead to spurious temperatures or rotations.

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