263 research outputs found
Two-dimensional superconductivity at the (111) LaAlO3/SrTiO3 interface
No full textWe report on the discovery and transport study of the superconducting ground state present at the (111)LaAlO3/SrTiO3 (LAO/STO) interface. The superconducting transition is consistent with a Berezinskii-Kosterlitz-Thouless transition and its two-dimensional nature is further corroborated by the anisotropy of the critical magnetic field, as calculated by Tinkham. The estimated superconducting layer thickness and coherence length are 10 and 60nm, respectively. The results of this work provide insight to clarify the microscopic details of superconductivity in LAO/STO interfaces, in particular in what concerns the link with orbital symmetry.QN/Caviglia LabQN/van der Zant La
Impact of Epithelial Histological Types, Subtypes, and Growth Patterns on Oncological Outcomes for Patients with Nonmetastatic Prostate Cancer Treated with Curative Intent: A Systematic Review.
No full textCONTEXT
The optimal management for men with prostate cancer (PCa) with unconventional histology (UH) is unknown. The outcome for these cancers might be worse than for conventional PCa and so different approaches may be needed.
OBJECTIVE
To compare oncological outcomes for conventional and UH PCa in men with localized disease treated with curative intent.
EVIDENCE ACQUISITION
A systematic review adhering to the Referred Reporting Items for Systematic Reviews and Meta-Analyses was prospectively registered on PROSPERO (CRD42022296013) was performed in July 2021.
EVIDENCE SYNTHESIS
We screened 3651 manuscripts and identified 46 eligible studies (reporting on 1 871 814 men with conventional PCa and 6929 men with 10 different PCa UHs). Extraprostatic extension and lymph node metastases, but not positive margin rates, were more common with UH PCa than with conventional tumors. PCa cases with cribriform pattern, intraductal carcinoma, or ductal adenocarcinoma had higher rates of biochemical recurrence and metastases after radical prostatectomy than for conventional PCa cases. Lower cancer-specific survival rates were observed for mixed cribriform/intraductal and cribriform PCa. By contrast, pathological findings and oncological outcomes for mucinous and prostatic intraepithelial neoplasia (PIN)-like PCa were similar to those for conventional PCa. Limitations of this review include low-quality studies, a risk of reporting bias, and a scarcity of studies that included radiotherapy.
CONCLUSIONS
Intraductal, cribriform, and ductal UHs may have worse oncological outcomes than for conventional and mucinous or PIN-like PCa. Alternative treatment approaches need to be evaluated in men with these cancers.
PATIENT SUMMARY
We reviewed the literature to explore whether prostate cancers with unconventional growth patterns behave differently to conventional prostate cancers. We found that some unconventional growth patterns have worse outcomes, so we need to investigate if they need different treatments. Urologists should be aware of these growth patterns and their clinical impact
Beyond the Bosphorus? Comparing German, French and British Discourses on Turkey’s Application to Join the European Union
No full textThis article examines the impact of national borders on public discourses, based on a case study of the struggle surrounding Turkey’s application to join the European Union (EU). Comparing opinions, reasons and interpretation patterns in press commentaries about enlarging the EU beyond the Bosphorus, the findings confirm the paramount importance and robustness of national cleavages between the German and the French public sphere on the one hand, and the British on the other. Whereas Turkish membership was predominantly re-jected on the continent, the British commentators strongly and almost unanimously sup-ported Ankara’s request to open doors. These similarities and divergences, I argue, are first and foremost the result of, and linked with, competing visions of Europe’s finality, especially regarding various constitutional ideas and cultural principles. Against this background, the Turkey question was partly exploited as an instrument supporting or repressing different conceptions of the European Union’s future
Can we expand active surveillance criteria to include biopsy Gleason 3+4 prostate cancer? A multi-institutional study of 2,323 patients
No full textItem does not contain fulltextOBJECTIVE: To test the expandability of active surveillance (AS) to Gleason score 3+4 cancers by assessing the unfavorable disease risk in a large multi-institutional cohort. MATERIALS AND METHODS: We performed a retrospective analysis including 2,323 patients with localized Gleason score 3+4 prostate cancer who underwent a radical prostatectomy between 2005 and 2013 from 6 academic centers. We analyzed the rates of biopsy downgrading/upgrading and advanced stage in the overall cohort by employing standardized AS criteria (using biopsy Gleason score 3+4). RESULTS: The final pathologic Gleason score was 3+3 = 6 in 8%, 3+4 = 7 in 67%, 4+3 = 7 in 20%, and 8 to 10 in 5% cases. The overall rate of unfavorable disease (upgrading or advanced stage or both) was 46%. In multivariable analysis, prostate-specific antigen (PSA) level>10ng/ml, PSA density (PSAD) >0.15ng/ml/g, clinical stage >T1, and>2 positive cores were predictors of unfavorable disease. According to the AS criteria used, the risk of unfavorable disease ranged from 30% to 42%. In patients without any risk factor (PSA level</=10ng/ml, PSAD </=0.15ng/ml/g, T1c, and</=2 positive cores), the unfavorable disease rate was 19%. The main limitations of this study are the retrospective design and nonstandardization of pathologic assessment between centers. CONCLUSIONS: Approximately half of patients with biopsy Gleason score 3+4 cancer have unfavorable disease at final pathology. Nevertheless, expanding AS eligibility to these patients may be acceptable provided adherence to strict selection criteria leading to a<20% risk of unfavorable disease. Future tools for selection such as magnetic resonance imaging, early rebiopsy, and serum markers may be especially beneficial in this group of patients
"Electro-physical" methods to stop rising damp: Assessment of the effectiveness in two case studies
No full textRising damp is a recurrent hazard to ancient buildings and its relevance is expected to increase in future, due to climate changes. In spite of the large diffusion of methods and products to stop rising damp, scientific literature on their effectiveness in the field is often scarce and not conclusive. This is particularly true for recent solutions; examples are the “electro-physical” methods, which are currently flourishing in many countries. These methods are often lacking a scientifically based proof of their working principles and effectiveness. Within the JPI-CH project EMERISDA, the effectiveness of two different commercial electro-physical devices was investigated in two case-studies. The devices were positioned in such a way as to include humid walls under the influence of the device as well as humid walls, comparable in orientation and structure, out of its reach, to be used as reference. The effectiveness of the devices was assessed by collection of samples at different heights and depths in the walls and gravimetric determination of their moisture content. Conclusions are drawn on the effectiveness of the methods by comparing the moisture content before and one year after the intervention, taking into account the variation in moisture content in the reference walls.Heritage & Technolog
The Observational Method for building pits in soft-soil conditions: A study on measurement-processing and feasibility of the Observational method Ab Initio approach.
No full textIn the Observational Method Ab Initio approach a flexible design and construction plan is established to allow anticipation to observational feedback during the construction phase. This way, the structural design can be optimized to the in-situ conditions which is beneficial from both safety and economic point of view. In the application of building pits in the soft-soil conditions of the Netherlands the method has the additional value to verify SLS criteria and timely detect unforeseen events. So far limited building pits have been executed via this design strategy. The main reasons for this are the lack of a design procedure and the problematic quantification of safety of the flexible retaining wall design. A strategy for the execution of the Observational Method Ab Initio approach to retaining wall design is described by the CIRIA guideline C760. In this study, the suitability of this 5 step-strategy has been investigated by means of a benchmark. This investigation indicated that, although the CIRIA guideline C760 contains a valuable design strategy, only a qualitative description of safety is provided. Therefore, this study introduces a methodology for real-time measurement-processing with the use of a Bayesian update. The Bayesian update combines the information of the predictive computer model with the information obtained from measurement sets during construction. By describing this information via probability density functions different uncertainties in both the design and construction phase can be weighted in the outcome of the Bayesian update. Consequently, the retaining wall behavior can be re-assessed throughout construction. This methodology is applied to measurement sets gathered at the construction of two different building pits in the Netherlands. Both case studies showed that with the Bayesian update and consequential calibration new parametric distributions can be found. Those parametric distributions describe the retaining wall behavior from which safety definitions in term of a reliability index can be derived. The performance of this methodology for measurement-processing depends on the accuracy of the calculation model and the measurement interpretation. Especially in the case of unexpectedly high and/or fast progressing retaining wall displacements, measurement interpretation is necessary to select the best strategy to redirect the structure. Although this measurement interpretation is a challenge, it is believed that the Observational Method Ab Initio approach complemented with the Bayesian update is a promising design strategy. Its application to the construction of building pits definitely has economic potential and would be favorable for risk management.Geo-Engineerin
The Contemporary Use of Radium-223 in Metastatic Castration-resistant Prostate Cancer.
No full textRadium-223 dichloride (radium-223) was approved for the treatment of patients with castration-resistant prostate cancer (CRPC) and symptomatic bone metastases in the United States and Europe in 2013. This followed a reported overall survival benefit for patients treated with radium-223 and best standard of care (BSoC) when compared with placebo and BSoC in the ALpharadin in SYMptomatic Prostate CAncer (ALSYMPCA) trial. At that time, docetaxel was the standard first-line choice for patients with metastatic CRPC (mCRPC). Since then, the treatment landscape has changed dramatically with new hormonal agents (abiraterone and enzalutamide) considered to be the first-line choice for many patients. The optimal patient profile for radium-223 in the modern setting, and its best use either in sequence or in combination with other approved agents are unclear, with few definitive guidelines available. This article reports on the views of a group of urologists and medical oncologists experienced in treating patients with mCRPC with radium-223 in routine clinical practice. The aim is to provide an overview of the current use of radium-223 in the treatment of patients with mCRPC, and to discuss best practices for patient selection and on-treatment monitoring. Where agreement was reached, guidance on the optimal use of radium-223 is provided
Preferences in the management of high-risk prostate cancer among urologists in Europe: results of a web-based survey.
No full textOBJECTIVE: To explore preferences in the management of patients with newly diagnosed high-risk prostate cancer (PCa) among urologists in Europe through a web-based survey. MATERIALS AND METHODS: A web-based survey was conducted between 15 August and 15 September 2013 by members of the Prostate Cancer Working Group of the Young Academic Urologists Working Party of the European Association of Urology (EAU). A specific, 29-item multiple-choice questionnaire covering the whole spectrum of diagnosis, staging and treatment of high-risk PCa was e-mailed to all urologists included in the mailing list of EAU members. Europe was divided into four geographical regions: Central-Eastern Europe (CEE), Northern Europe (NE), Southern Europe (SE) and Western Europe (WE). Descriptive statistics were used. Differences among sample segments were obtained from a z-test compared with the total sample. RESULTS: Of the 12 850 invited EAU members, 585 urologists practising in Europe completed the survey. High-risk PCa was defined as serum PSA ≥20 ng/mL or clinical stage ≥ T3 or biopsy Gleason score ≥ 8 by 67% of responders, without significant geographical variations. The preferred single-imaging examinations for staging were bone scan (74%, 81% in WE and 70% in SE; P = 0.02 for both), magnetic resonance imaging (53%, 72% in WE and 40% in SE; P = 0.02 and P = 0.01, respectively) and computed tomography (45%, 60% in SE and 23% in WE; P = 0.01 for both). Pre-treatment predictive tools were routinely used by 62% of the urologists, without significant geographical variations. The preferred treatment was radical prostatectomy as the initial step of a multiple-treatment approach (60%, 40% in NE and 70% in CEE; P = 0.02 and P < 0.01, respectively), followed by external beam radiation therapy with androgen deprivation therapy (29%, 45% in NE and 20% in CEE; P = 0.01 and P = 0.02, respectively), and radical prostatectomy as monotherapy (4%, 7% in WE; P = 0.04). When surgery was performed, the open retropubic approach was the most popular (58%, 74% in CEE, 37% in NE; P < 0.01 for both). Pelvic lymph node dissection was performed by 96% of urologists, equally split between a standard and extended template. There was no consensus on the definition of disease recurrence after primary treatment, and much heterogeneity in the administration of adjuvant and salvage treatments. CONCLUSION: With the limitation of a low response rate, the present study is the first survey evaluating preferences in the management of high-risk PCa among urologists in Europe. Although the definition of high-risk PCa was fairly uniform, wide variations in patterns of primary and adjuvant/salvage treatments were observed. These differences might translate into variations in quality of care with a possible impact on ultimate oncological outcome
Phenotypic spectrum of the first Belgian MYBPC3 founder: a large multi-exon deletion with a varying phenotype
No full textBackground: Variants in the MYBPC3 gene are a frequent cause of hypertrophic cardiomyopathy (HCM) but display a large phenotypic heterogeneity. Founder mutations are often believed to be more benign as they prevailed despite potential negative selection pressure. We detected a pathogenic variant in MYBPC3 (del exon 23-26) in several probands. We aimed to assess the presence of a common haplotype and to describe the cardiac characteristics, disease severity and long-term outcome of mutation carriers. Methods: Probands with HCM caused by a pathogenic deletion of exon 23-26 of MYBPC3 were identified through genetic screening using a gene panel encompassing 59 genes associated with cardiomyopathies in a single genetic center in Belgium. Cascade screening of first-degree relatives was performed, and genotype positive relatives were further phenotyped. Clinical characteristics were collected from probands and relatives. Cardiac outcomes included death, heart transplantation, life-threatening arrhythmia, heart failure hospitalization or septal reduction therapy. Haplotype analysis, using microsatellite markers surrounding MYBPC3, was performed in all index patients to identify a common haplotype. The age of the founder variant was estimated based on the size of the shared haplotype using a linkage-disequilibrium based approach. Results: We identified 24 probands with HCM harbouring the MYBPC3 exon 23-26 deletion. Probands were on average 51 +/- 16 years old at time of clinical HCM diagnosis and 62 +/- 10 years old at time of genetic diagnosis. A common haplotype of 1.19 Mb was identified in all 24 probands, with 19 of the probands sharing a 13.8 Mb haplotype. The founder event was estimated to have happened five generations, or 175-200 years ago, around the year 1830 in central Flanders. Through cascade screening, 59 first-degree relatives were genetically tested, of whom 37 (62.7%) were genotype positive (G+) and 22 (37.3%) genotype negative (G-). They were on average 38 +/- 19 years old at time of genetic testing. Subsequent clinical assessment revealed a HCM phenotype in 19 (51.4%) G+ relatives. Probands were older (63 +/- 10 vs. 42 +/- 21 years; p = 50 years. Overall, 20.3% of all variant carriers developed one of the predefined cardiac outcomes after a median follow-up of 5.5 years with an average age of 50 (+/- 21) years. Conclusion: A Belgian founder variant, an exon 23-26 deletion in MYBPC3, was identified in 24 probands and 37 family members. The variant is characterized by a high penetrance of 78.6% at the age of 50 years but has variable phenotypic expression. Adverse outcomes were observed in 20.3% of patients during follow-up.The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This work was supported by the Flanders Research Foundation- FWO (research grant G055821N, doctoral research grant 1192420N to HB and senior clinical investigator grant 1804320N to EC). BL holds a consolidator grant from the European Research Council (Genomia–ERC-COG-2017-771945)
A Systematic Review of the Efficacy and Toxicity of Brachytherapy Boost Combined with External Beam Radiotherapy for Nonmetastatic Prostate Cancer
No full textContext
The optimum use of brachytherapy (BT) combined with external beam radiotherapy (EBRT) for localised/locally advanced prostate cancer (PCa) remains uncertain.
Objective
To perform a systematic review to determine the benefits and harms of EBRT-BT.
Evidence acquisition
Ovid MEDLINE, Embase, and EBM Reviews—Cochrane Central Register of Controlled Trials databases were systematically searched for studies published between January 1, 2000 and June 7, 2022, according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. Eligible studies compared low- or high-dose-rate EBRT-BT against EBRT ± androgen deprivation therapy (ADT) and/or radical prostatectomy (RP) ± postoperative radiotherapy (RP ± EBRT). The main outcomes were biochemical progression-free survival (bPFS), severe late genitourinary (GU)/gastrointestinal toxicity, metastasis-free survival (MFS), cancer-specific survival (CSS), and overall survival (OS), at/beyond 5 yr. Risk of bias was assessed and confounding assessment was performed. A meta-analysis was performed for randomised controlled trials (RCTs).
Evidence synthesis
Seventy-three studies were included (two RCTs, seven prospective studies, and 64 retrospective studies). Most studies included participants with intermediate-or high-risk PCa. Most studies, including both RCTs, used ADT with EBRT-BT. Generally, EBRT-BT was associated with improved bPFS compared with EBRT, but similar MFS, CSS, and OS. A meta-analysis of the two RCTs showed superior bPFS with EBRT-BT (estimated fixed-effect hazard ratio [HR] 0.54 [95% confidence interval {CI} 0.40–0.72], p < 0.001), with absolute improvements in bPFS at 5–6 yr of 4.9–16%. However, no difference was seen for MFS (HR 0.84 [95% CI 0.53–1.28], p = 0.4) or OS (HR 0.87 [95% CI 0.63–1.19], p = 0.4). Fewer studies examined RP ± EBRT. There is an increased risk of severe late GU toxicity, especially with low-dose-rate EBRT-BT, with some evidence of increased prevalence of severe GU toxicity at 5–6 yr of 6.4–7% across the two RCTs.
Conclusions
EBRT-BT can be considered for unfavourable intermediate/high-risk localised/locally advanced PCa in patients with good urinary function, although the strength of this recommendation based on the European Association of Urology guideline methodology is weak given that it is based on improvements in biochemical control.
Patient summary
We found good evidence that radiotherapy combined with brachytherapy keeps prostate cancer controlled for longer, but it could lead to worse urinary side effects than radiotherapy without brachytherapy, and its impact on cancer spread and patient survival is less clear
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