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INTRODUCTION: Molecular profiling of NSCLC is essential for optimising treatment decisions, but often incomplete. We assessed the efficacy of protocolised molecular profiling in the current standard-of-care (SoC) in a prospective observational study in the Netherlands and measured the effect of providing standardised diagnostic procedures. We also explored the potential of plasma-based molecular profiling in the primary diagnostic setting. METHODS: This multi-centre prospective study was designed to explore the performance of current clinical practice during the run-in phase using local SoC tissue profiling procedures. The subsequent phase was designed to investigate the extent to which comprehensive molecular profiling (CMP) can be maximized by protocolising tumour profiling. Successful molecular profiling was defined as completion of at least EGFR and ALK testing. Additionally, PD-L1 tumour proportions scores were explored. Lastly, the additional value of centralised plasma-based testing for EGFR and KRAS mutations using droplet digital PCR was evaluated. RESULTS: Total accrual was 878 patients, 22.0% had squamous cell carcinoma and 78.0% had non-squamous NSCLC. Stage I-III was seen in 54.0%, stage IV in 46.0%. Profiling of EGFR and ALK was performed in 69.9% of 136 patients included in the run-in phase, significantly more than real-world data estimates of 55% (p<0.001). Protocolised molecular profiling increased the rate to 77.0% (p = 0.049). EGFR and ALK profiling rates increased from 77.9% to 82.1% in non-squamous NSCLC and from 43.8% to 57.5% in squamous NSCLC. Plasma-based testing was feasible in 98.4% and identified oncogenic driver mutations in 7.1% of patients for whom tissue profiling was unfeasible. CONCLUSION: This study shows a high success rate of tissue-based molecular profiling that was significantly improved by a protocolised approach. Tissue-based profiling remains unfeasible for a substantial proportion of patients. Combined analysis of tumour tissue and circulating tumour DNA is a promising approach to allow adequate molecular profiling of more patients.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/diagnóstico , Feminino , Masculino , Idoso , Pessoa de Meia-Idade , Estudos Prospectivos , Receptores ErbB/genética , Mutação , Quinase do Linfoma Anaplásico/genética , Países Baixos , Proteínas Proto-Oncogênicas p21(ras)/genética , Biomarcadores Tumorais/genética , Adulto , Idoso de 80 Anos ou mais , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Perfilação da Expressão Gênica/métodosRESUMO
Internal herniation (IH) is a common problem after laparoscopic Roux-en-Y gastric bypass surgery (RYGB). Routine closure of the mesenteric defects (MDs) reduces the risk of IH. Only very few articles report on risk factors for IH or describe detailed closing techniques. There is no consensus yet on the best closing method. The objective of this study is to determine the optimal stapling method for closure of MDs after RYGB. All performed RYGB procedures in our high-volume bariatric institute were included. Quality of the closure was scored in the categories poor, sub-optimal, and optimal, to see if the quality of the closure would predict the chance of reopening of the MDs and, therefore, the chance of IH. During any type of laparoscopy in the follow-up of the patient, the conditions of the MDs were stated, for example during diagnostic laparoscopy in symptomatic patients suspicious for IH or during laparoscopic cholecystectomy. Technically well-executed closure of Petersen's space (PS) with two rows of staples had a greater chance of still being closed upon re-inspection compared to closure with one row (odds ratio = 8.1; 95% confidence interval [1.2-53.2], p = 0.029). Optimal closure of the MD at the jejuno-jejunostomy (JJ-space, JJS) resulted in more closed JJSs upon re-inspection compared to sub-optimal closure (odds ratio = 3.6 [CI 95% 0.8-16.1], p = 0.099). Non-optimally closed MDs had higher reopening rates and, therefore, pose an additional risk for IH. Our classification provides a quality assessment of MD closure during RYGB and gives insight into how to optimize surgical technique.
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Derivação Gástrica , Laparoscopia , Mesentério , Grampeamento Cirúrgico , Humanos , Derivação Gástrica/métodos , Derivação Gástrica/efeitos adversos , Laparoscopia/métodos , Grampeamento Cirúrgico/métodos , Mesentério/cirurgia , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Complicações Pós-Operatórias/prevenção & controle , Complicações Pós-Operatórias/etiologia , Hérnia Interna/etiologia , Hérnia Interna/prevenção & controle , Reoperação , Obesidade Mórbida/cirurgia , Estudos RetrospectivosRESUMO
INTRODUCTION: Haemorrhoidal disease (HD) is a common condition with significant epidemiologic and economic implications. While it is possible to treat symptomatic grade 1-2 haemorrhoids with rubber band ligation (RBL) or sclerotherapy (SCL), the effectiveness of these treatments compatible with current standards has not yet been investigated with a randomised controlled trial. The hypothesis is that SCL is not inferior to RBL in terms of symptom reduction (patient-related outcome measures (PROMs)), patient experience, complications or recurrence rate. METHODS AND ANALYSIS: This protocol describes the methodology of a non-inferiority, multicentre, randomised controlled trial comparing rubber band ligation and sclerotherapy for symptomatic grade 1-2 haemorrhoids in adults (> 18 years). Patients are preferably randomised between the two treatment arms. However, patients with a strong preference for one of the treatments and refuse randomisation are eligible for the registration arm. Patients either receive 4 cc Aethoxysklerol 3% SCL or 3 × RBL. The primary outcome measures are symptom reduction by means of PROMs, recurrence and complication rates. Secondary outcome measures are patient experience, number of treatments and days of sick leave from work. Data are collected at 4 different time points. DISCUSSION: The THROS trial is the first large multicentre randomised trial to study the difference in effectivity between RBL and SCL for the treatment of grade 1-2 HD. It will provide information as to which treatment method (RBL or SCL) is the most effective, gives fewer complications and is experienced by the patient as the best option. ETHICS AND DISSEMINATION: The study protocol has been approved by the Medical Ethics Review Committee of the Amsterdam University Medical Centers, location AMC (nr. 2020_053). The gathered data and results will be submitted for publication in peer-reviewed journals and spread to coloproctological associations and guidelines. TRIAL REGISTRATION: Dutch Trial Register NL8377 . Registered on 12-02-2020.
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Hemorroidectomia , Hemorroidas , Adulto , Humanos , Hemorroidas/diagnóstico , Hemorroidas/terapia , Escleroterapia/efeitos adversos , Ligadura/métodos , Protocolos Clínicos , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Multicêntricos como AssuntoRESUMO
AIM: Cardiac diseases remain a leading cause of cardiovascular disease (CVD) related hospitalisation and mortality. That is why research to improve our understanding of pathophysiological processes underlying cardiac diseases is of great importance. There is a strong need for healthy and diseased human cardiac tissue and related clinical data to accomplish this, since currently used animal and in vitro disease models do not fully grasp the pathophysiological processes observed in humans. This design paper describes the initiative of the Netherlands Heart Tissue Bank (NHTB) that aims to boost CVD-related research by providing an open-access biobank. METHODS: The NHTB, founded in June 2020, is a non-profit biobank that collects and stores biomaterial (including but not limited to myocardial tissue and blood samples) and clinical data of individuals with and without previously known cardiac diseases. All individuals aged ≥â¯18 years living in the Netherlands are eligible for inclusion as a potential future donor. The stored samples and clinical data will be available upon request for cardiovascular researchers. CONCLUSION: To improve the availability of cardiac tissue for cardiovascular research, the NHTB will include extensive (cardiac) biosamples, medical images, and clinical data of donors with and without a previously known cardiac disease. As such, the NHTB will function as a translational bridge to boost a wide range of cardiac disease-related fundamental and translational studies.
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BACKGROUND: Current surgical closure techniques for sphincter-sparing treatment of high cryptoglandular fistulas in the Netherlands include the mucosal advancement flap procedure (MAF) and ligation of the intersphincteric fistula tract (LIFT). A relatively novel treatment is the fistula tract laser closure (FiLaC™) method. The aim of this study was to investigate the differences in healing and recurrence rates between FiLaC™ and current standard practices. METHODS: This multicenter retrospective cohort study included both primary and recurrent high cryptoglandular anorectal fistulas, treated with either FiLaC™ or standard methods (MAF or LIFT) between September 2015 and July 2020. Patients with extrasphincteric fistulas, Crohn's disease, multiple fistulas, age < 18 years or missing data regarding healing time or recurrence were excluded. The primary outcomes were the clinical primary and secondary healing and recurrence rates. Primary healing was defined as a closed external opening without fluid discharge within 6 months of treatment on examination, while secondary healing was the same endpoint after secondary treatment. Secondary outcomes included healing time and complaints. RESULTS: A total of 162 high fistulas from 3 Dutch hospitals were included. Ninety-nine high fistulas were treated with FiLaC™ and 63 with either MAF or LIFT. There were no significant differences between FiLaC™ and MAF/LIFT in terms of clinical healing (55.6% versus 58.7%, p = .601), secondary healing (70.0% versus 69.2%, p = .950) or recurrence rates (49.5% versus 54%, p = .420), respectively. Median follow-up duration was 7.1 months in the FiLaC™ group (interquartile range [IQR] 4.1-14.4 months) versus 6 months in the control group (IQR 3.5-8.1 months). CONCLUSIONS: FiLaC™ treatment of high anorectal fistulas does not appear to be inferior to MAF or LIFT. Based on these preliminary results, FiLaC™ can be considered as a worthwhile treatment option for high cryptoglandular fistulas. Prospective studies with a longer follow-up period and well-determined postoperative parameters such as complication rates, magnetic resonance imaging for confirmation of fistula healing, incontinence and quality of life are warranted.
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Canal Anal , Fístula Retal , Adolescente , Canal Anal/cirurgia , Humanos , Ligadura/métodos , Países Baixos , Tratamentos com Preservação do Órgão/efeitos adversos , Estudos Prospectivos , Qualidade de Vida , Fístula Retal/etiologia , Recidiva , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: Management of cryptoglandular fistula-in-ano (FIA) can be challenging. Despite Dutch and international guidelines determining optimal therapy is still quite difficult. The aim of this study was to report current practices in the management of cryptoglandular FIA among gastrointestinal surgeons in the Netherlands. METHODS: Dutch surgeons and residents who are treating FIA regularly were sent a survey invitation by email. The survey was available online from September 19 to December 1 2019. The questionnaire consisted of 28 questions concerning diagnostic and surgical techniques in the treatment of intersphincteric and transsphincteric FIA. RESULTS: In total, 147 (43%) surgeons responded and completed the survey. Magnetic resonance imaging was the preferred diagnostic imaging modality (97%) followed by the endo-anal ultrasound (12%). In case of a high FIA, 86% used a non-cutting seton. Most respondents removed a seton between 6 weeks and 3 months (n = 84, 58%). Fistulotomy was the procedure of preference in low transsphincteric (86%) and low intersphincteric FIA (92%). Mucosal advancement flap (MAF) and ligation of intersphincteric fistula tract (LIFT), with 78% and 46%, respectively, were the procedures that were applied most often in high transsphincteric FIA. In high intersphincteric FIA 67% performed a MAF and 33% a fistulotomy. Thirty-three percent of all respondents stated that they habitually closed the internal fistula opening, half of them used a Z-plasty. For debridement of the fistula tract the preferred method was curettage (78%). CONCLUSIONS: Dutch gastrointestinal surgeons use various techniques in the management of FIA. Novel promising techniques should be investigated adequately in sufficient large trials to increase consensus. A core outcome measurement and a prospective international database would help in comparing results. Until then, treatment should be adjusted to the individual patient, governed by fistula characteristics and patient choice.
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Fístula Retal , Cirurgiões , Canal Anal , Humanos , Ligadura , Países Baixos , Estudos Prospectivos , Fístula Retal/cirurgia , Recidiva , Resultado do TratamentoRESUMO
The distribution of entangled states across the nodes of a future quantum internet will unlock fundamentally new technologies. Here, we report on the realization of a three-node entanglement-based quantum network. We combine remote quantum nodes based on diamond communication qubits into a scalable phase-stabilized architecture, supplemented with a robust memory qubit and local quantum logic. In addition, we achieve real-time communication and feed-forward gate operations across the network. We demonstrate two quantum network protocols without postselection: the distribution of genuine multipartite entangled states across the three nodes and entanglement swapping through an intermediary node. Our work establishes a key platform for exploring, testing, and developing multinode quantum network protocols and a quantum network control stack.
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Vertical farming can produce food in a climate-resilient manner, potentially emitting zero pesticides and fertilizers, and with lower land and water use than conventional agriculture. Vertical farming systems (VFS) can meet daily consumer demands for nutritious fresh products, forming a part of resilient food systems-particularly in and around densely populated areas. VFS currently produce a limited range of crops including fruits, vegetables and herbs, but successful implementation of vertical farming as part of mainstream agriculture will require improvements in profitability, energy efficiency, public policy and consumer acceptance. Here we discuss VFS as multi-layer indoor crop cultivation systems, exploring state-of-the-art vertical farming and future challenges in the fields of plant growth, product quality, automation, robotics, system control and environmental sustainability and how research and development, socio-economic and policy-related institutions must work together to ensure successful upscaling of VFS to future food systems.
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BACKGROUND: Size of fruit is an important issue in determining yield at harvest. Even under controlled conditions, variation between fruit and trusses can be considerable. As an easy to measure indication of size, the diameter of tomatoes growing in trusses was assessed in three experiments with different number of tomatoes per truss, as well as cultivars, and also by varying the level of ions in the recirculated drain water. RESULTS: By applying the von Bertalanffy growth model, more than 99% of the variation present could be explained by the time of fruit set for all tomatoes growing anywhere in the trusses. A linear relationship between time of fruit set and the biological shift factor, an indication of developmental age, was observed. Integrating this linear relationship in the analysis of the diameter data removed one stochastic variable (biological shift factor), effectively halving the number of parameters to be estimated. CONCLUSION: The results of the present study indicate that the major part of the variation present in the diameter of tomatoes growing in trusses is the result of variation in the time of fruit set of individual fruits. The position within the greenhouse (i.e. local differences in assimilates supply) exerted only a minor effect on diameter development. Accordingly, the time of fruit set largely determines fruit size. Likely, growing conditions before fruit set are crucial for final fruit size. The time of fruit set of each tomato in the truss and the local growing conditions within the greenhouse that affect assimilate supply need to be assessed accurately for a reliable size prediction.
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Frutas/química , Solanum lycopersicum/crescimento & desenvolvimento , Biomassa , Produção Agrícola , Frutas/crescimento & desenvolvimento , Solanum lycopersicum/química , Fatores de TempoRESUMO
BACKGROUND: Immune checkpoint inhibitors have improved survival outcome of advanced non-small-cell lung cancer (NSCLC). However, most patients do not benefit. Therefore, biomarkers are needed that accurately predict response. We hypothesized that molecular profiling of exhaled air may capture the inflammatory milieu related to the individual responsiveness to anti-programmed death ligand 1 (PD-1) therapy. This study aimed to determine the accuracy of exhaled breath analysis at baseline for assessing nonresponders versus responders to anti-PD-1 therapy in NSCLC patients. METHODS: This was a prospective observational study in patients receiving checkpoint inhibitor therapy using both a training and validation set of NSCLC patients. At baseline, breath profiles were collected in duplicate by a metal oxide semiconductor electronic nose (eNose) positioned at the rear end of a pneumotachograph. Patients received nivolumab or pembrolizumab of which the efficacy was assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 at 3-month follow-up. Data analysis involved advanced signal-processing and statistics based on independent t-tests followed by linear discriminant and receiver operating characteristic (ROC) analysis. RESULTS: Exhaled breath data of 143 NSCLC patients (training: 92, validation: 51) were available at baseline. ENose sensors contributed significantly (P < 0.05) at baseline in differentiating between patients with different responses at 3 months of anti-PD-1 treatment. The eNose sensors were combined into a single biomarker with an ROC-area under the curve (AUC) of 0.89 [confidence interval (CI) 0.82-0.96]. This AUC was confirmed in the validation set: 0.85 (CI 0.75-0.96). CONCLUSION: ENose assessment was effective in the noninvasive prediction of individual patient responses to immunotherapy. The predictive accuracy and efficacy of the eNose for discrimination of immunotherapy responder types were replicated in an independent validation set op patients. This finding can potentially avoid application of ineffective treatment in identified probable nonresponders.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/análise , Testes Respiratórios/métodos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Nariz Eletrônico , Neoplasias Pulmonares/tratamento farmacológico , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/metabolismo , Adenocarcinoma de Pulmão/patologia , Anticorpos Monoclonais Humanizados/administração & dosagem , Área Sob a Curva , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Expiração , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Nivolumabe/administração & dosagem , Prognóstico , Estudos ProspectivosRESUMO
BACKGROUND: Anti-PD1/PD-L1 directed immune checkpoint inhibitors (ICI) are widely used to treat patients with advanced non-small-cell lung cancer (NSCLC). The activity of ICI across NSCLC harboring oncogenic alterations is poorly characterized. The aim of our study was to address the efficacy of ICI in the context of oncogenic addiction. PATIENTS AND METHODS: We conducted a retrospective study for patients receiving ICI monotherapy for advanced NSCLC with at least one oncogenic driver alteration. Anonymized data were evaluated for clinicopathologic characteristics and outcomes for ICI therapy: best response (RECIST 1.1), progression-free survival (PFS), and overall survival (OS) from ICI initiation. The primary end point was PFS under ICI. Secondary end points were best response (RECIST 1.1) and OS from ICI initiation. RESULTS: We studied 551 patients treated in 24 centers from 10 countries. The molecular alterations involved KRAS (n = 271), EGFR (n = 125), BRAF (n = 43), MET (n = 36), HER2 (n = 29), ALK (n = 23), RET (n = 16), ROS1 (n = 7), and multiple drivers (n = 1). Median age was 60 years, gender ratio was 1 : 1, never/former/current smokers were 28%/51%/21%, respectively, and the majority of tumors were adenocarcinoma. The objective response rate by driver alteration was: KRAS = 26%, BRAF = 24%, ROS1 = 17%, MET = 16%, EGFR = 12%, HER2 = 7%, RET = 6%, and ALK = 0%. In the entire cohort, median PFS was 2.8 months, OS 13.3 months, and the best response rate 19%. In a subgroup analysis, median PFS (in months) was 2.1 for EGFR, 3.2 for KRAS, 2.5 for ALK, 3.1 for BRAF, 2.5 for HER2, 2.1 for RET, and 3.4 for MET. In certain subgroups, PFS was positively associated with PD-L1 expression (KRAS, EGFR) and with smoking status (BRAF, HER2). CONCLUSIONS: : ICI induced regression in some tumors with actionable driver alterations, but clinical activity was lower compared with the KRAS group and the lack of response in the ALK group was notable. Patients with actionable tumor alterations should receive targeted therapies and chemotherapy before considering immunotherapy as a single agent.
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Antineoplásicos Imunológicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Imunológicos/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/imunologia , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/imunologia , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Feminino , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Mutação , Oncogenes/genética , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/imunologia , Intervalo Livre de Progressão , Sistema de Registros/estatística & dados numéricos , Critérios de Avaliação de Resposta em Tumores Sólidos , Estudos RetrospectivosRESUMO
We investigate the magnetic field and temperature dependence of the single-electron spin lifetime in silicon quantum dots and find a lifetime of 2.8 ms at a temperature of 1.1 K. We develop a model based on spin-valley mixing and find that Johnson noise and two-phonon processes limit relaxation at low and high temperature, respectively. We also investigate the effect of temperature on charge noise and find a linear dependence up to 4 K. These results contribute to the understanding of relaxation in silicon quantum dots and are promising for qubit operation at elevated temperatures.
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AIMS: The primary aim of this independent prospective randomised trial was to compare serum metal ion levels for ceramic-on-metal (CoM) and metal-on-metal (MoM) bearing surfaces in total hip arthroplasty (THA). Our one-year results demonstrated elevation in metal ion levels above baseline with no significant difference between the CoM and MoM groups. This paper reviews the five-year data. PATIENTS AND METHODS: The implants used in each patient differed only in respect to the type of femoral head (ceramic or metal). At five-year follow-up of the 83 enrolled patients, data from 67 (36 CoM, 31 MoM) was available for comparison. RESULTS: The mean serum cobalt (Co) and chromium (Cr) ion levels remained above baseline in both groups (CoM: Co 1.16 µg/l (0.41 to 14.67), Cr 1.05 µg/l (0.16 to 12.58); MoM: Co 2.93 µg/l (0.35 to 30.29), Cr 1.85 µg/l (0.36 to 17.00)) but the increase was significantly less in the CoM cohort (Co difference p = 0.001, Cr difference p = 0.002). These medium-term results, coupled with lower revision rates from national joint registries, suggest that the performance of CoM THA may be superior to that of MoM. CONCLUSION: While both bearing combinations have since been withdrawn these results provide useful information for planning clinical surveillance of CoM THAs and warrants continued monitoring. Cite this article: Bone Joint J 2017;99-B:1298-1303.
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Artroplastia de Quadril/métodos , Cerâmica , Prótese de Quadril , Próteses Articulares Metal-Metal , Osteoartrite do Quadril/cirurgia , Adulto , Idoso , Biomarcadores/sangue , Cromo/sangue , Cobalto/sangue , Método Duplo-Cego , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Osteoartrite do Quadril/sangue , Estudos Prospectivos , Desenho de Prótese , Sistema de Registros , Fatores de Tempo , Resultado do TratamentoRESUMO
Superconducting electronic devices have reemerged as contenders for both classical and quantum computing due to their fast operation speeds, low dissipation, and long coherence times. An ultimate demonstration of coherence is lasing. We use one of the fundamental aspects of superconductivity, the ac Josephson effect, to demonstrate a laser made from a Josephson junction strongly coupled to a multimode superconducting cavity. A dc voltage bias applied across the junction provides a source of microwave photons, and the circuit's nonlinearity allows for efficient down-conversion of higher-order Josephson frequencies to the cavity's fundamental mode. The simple fabrication and operation allows for easy integration with a range of quantum devices, allowing for efficient on-chip generation of coherent microwave photons at low temperatures.
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OBJECTIVES: The aim of this study is to evaluate long-term facial growth in adults previously treated for an isolated unilateral complete cleft lip, alveolus and palate by two-stage palatoplasty. MATERIALS AND METHODS: Unilateral cleft lip and palate (UCLP) patients of 17 years and older treated by two-stage palatoplasty were invited for long-term follow-up. During follow-up, lateral cephalograms were obtained (n = 52). Medical history was acquired from their medical files. Outcome was compared to previously published normal values and the Eurocleft study. RESULTS: Soft and hard palate closure were performed at the age of 8 (SD 5.9) months and 3 (SD 2.2) years, respectively. The mean maxillary and mandibular angle (SNA, SNB) were 74.9° (SD 4.2) and 75.8° (SD 3.8). Maxillary and maxillomandibular relationships (SNA, ANB) were comparable to all Eurocleft Centres, except for Centre D. We observed a significantly steeper upper interincisor angle compared to the Eurocleft Centres. CONCLUSIONS: This study describes the long-term craniofacial morphology in adults treated for a UCLP with hard palate closure at a mean age of 3 years. The mean maxillary angle SNA and mandibular angle SNPg were comparable to previous studies both applying early and delayed hard palate closure. The observed upper incisor proclination is likely caused by orthodontic overcorrection in response to the unfavourable jaw relationships. No clear growth benefit of this protocol could be demonstrated. CLINICAL RELEVANCE: The present study shows the long-term craniofacial morphology of UCLP adults after the Utrecht treatment protocol which includes two-stage palate closure.
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Fenda Labial/fisiopatologia , Fenda Labial/cirurgia , Fissura Palatina/fisiopatologia , Fissura Palatina/cirurgia , Desenvolvimento Maxilofacial/fisiologia , Adolescente , Cefalometria , Fenda Labial/diagnóstico por imagem , Fissura Palatina/diagnóstico por imagem , Feminino , Humanos , Masculino , Adulto JovemRESUMO
The recently reported violation of a Bell inequality using entangled electronic spins in diamonds (Hensen et al., Nature 526, 682-686) provided the first loophole-free evidence against local-realist theories of nature. Here we report on data from a second Bell experiment using the same experimental setup with minor modifications. We find a violation of the CHSH-Bell inequality of 2.35 ± 0.18, in agreement with the first run, yielding an overall value of S = 2.38 ± 0.14. We calculate the resulting P-values of the second experiment and of the combined Bell tests. We provide an additional analysis of the distribution of settings choices recorded during the two tests, finding that the observed distributions are consistent with uniform settings for both tests. Finally, we analytically study the effect of particular models of random number generator (RNG) imperfection on our hypothesis test. We find that the winning probability per trial in the CHSH game can be bounded knowing only the mean of the RNG bias. This implies that our experimental result is robust for any model underlying the estimated average RNG bias, for random bits produced up to 690 ns too early by the random number generator.
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More than 50 years ago, John Bell proved that no theory of nature that obeys locality and realism can reproduce all the predictions of quantum theory: in any local-realist theory, the correlations between outcomes of measurements on distant particles satisfy an inequality that can be violated if the particles are entangled. Numerous Bell inequality tests have been reported; however, all experiments reported so far required additional assumptions to obtain a contradiction with local realism, resulting in 'loopholes'. Here we report a Bell experiment that is free of any such additional assumption and thus directly tests the principles underlying Bell's inequality. We use an event-ready scheme that enables the generation of robust entanglement between distant electron spins (estimated state fidelity of 0.92 ± 0.03). Efficient spin read-out avoids the fair-sampling assumption (detection loophole), while the use of fast random-basis selection and spin read-out combined with a spatial separation of 1.3 kilometres ensure the required locality conditions. We performed 245 trials that tested the CHSH-Bell inequality S ≤ 2 and found S = 2.42 ± 0.20 (where S quantifies the correlation between measurement outcomes). A null-hypothesis test yields a probability of at most P = 0.039 that a local-realist model for space-like separated sites could produce data with a violation at least as large as we observe, even when allowing for memory in the devices. Our data hence imply statistically significant rejection of the local-realist null hypothesis. This conclusion may be further consolidated in future experiments; for instance, reaching a value of P = 0.001 would require approximately 700 trials for an observed S = 2.4. With improvements, our experiment could be used for testing less-conventional theories, and for implementing device-independent quantum-secure communication and randomness certification.
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Realizing robust quantum information transfer between long-lived qubit registers is a key challenge for quantum information science and technology. Here we demonstrate unconditional teleportation of arbitrary quantum states between diamond spin qubits separated by 3 meters. We prepare the teleporter through photon-mediated heralded entanglement between two distant electron spins and subsequently encode the source qubit in a single nuclear spin. By realizing a fully deterministic Bell-state measurement combined with real-time feed-forward, quantum teleportation is achieved upon each attempt with an average state fidelity exceeding the classical limit. These results establish diamond spin qubits as a prime candidate for the realization of quantum networks for quantum communication and network-based quantum computing.
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The stochastic evolution of quantum systems during measurement is arguably the most enigmatic feature of quantum mechanics. Measuring a quantum system typically steers it towards a classical state, destroying the coherence of an initial quantum superposition and the entanglement with other quantum systems. Remarkably, the measurement of a shared property between non-interacting quantum systems can generate entanglement, starting from an uncorrelated state. Of special interest in quantum computing is the parity measurement, which projects the state of multiple qubits (quantum bits) to a state with an even or odd number of excited qubits. A parity meter must discern the two qubit-excitation parities with high fidelity while preserving coherence between same-parity states. Despite numerous proposals for atomic, semiconducting and superconducting qubits, realizing a parity meter that creates entanglement for both even and odd measurement results has remained an outstanding challenge. Here we perform a time-resolved, continuous parity measurement of two superconducting qubits using the cavity in a three-dimensional circuit quantum electrodynamics architecture and phase-sensitive parametric amplification. Using postselection, we produce entanglement by parity measurement reaching 88 per cent fidelity to the closest Bell state. Incorporating the parity meter in a feedback-control loop, we transform the entanglement generation from probabilistic to fully deterministic, achieving 66 per cent fidelity to a target Bell state on demand. These realizations of a parity meter and a feedback-enabled deterministic measurement protocol provide key ingredients for active quantum error correction in the solid state.
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BACKGROUND: Opening wedge high tibial osteotomy often requires bone grafting to improve the union rate and avoid instability at the osteotomy site. Autograft and allograft have both been associated with complications and the use of bone substitute wedges has been advocated to improve the outcome. This study investigated the clinical, radiological and histological outcomes of using biphasic calcium phosphate ceramic (Triosite) wedges in opening wedge high tibial osteotomy and determined whether the presence of the graft would compromise the satisfactory conversion to a total knee replacement. METHODS: A consecutive cohort underwent radiological review to determine whether the osteotomy healed and the correction was maintained. Biopsies were performed on those undergoing second procedures. All patients converted to total knee arthroplasty were assessed separately as to any surgical complications attributed to the Triosite wedge. RESULTS: There were 36 osteotomies in 33 patients with a minimum of 4 years follow up. All osteotomies healed. There was an average 90 (5-14) of correction, which was maintained. Histological assessment of 17 cases confirmed adequate bone replacement of the Triosite although some areas of tricalcium phosphate remained visible. Conversion to a total knee arthroplasty occurred in 11 cases with no complications. CONCLUSION: Biphasic calcium phosphate ceramic wedges (Triosite) can be reliably used in opening wedge high tibial osteotomy with a low incidence of complications and satisfactory conversion to total knee arthroplasty.