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"Bernhard, J"
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Fully automated deep learning for knee alignment assessment in lower extremity radiographs: a cross-sectional diagnostic study
ObjectivesAccurate assessment of knee alignment and leg length discrepancy is currently measured manually from standing long-leg radiographs (LLR), a process that is both time consuming and poorly reproducible. The aim was to assess the performance of a commercial available AI software by comparing its outputs with manually performed measurements.Materials and methodsThe AI was trained on over 15,000 radiographs to measure various clinical angles and lengths from LLRs. We performed a retrospective single-center analysis on 295 LLRs obtained between 2015 and 2020 from male and female patients over 18 years. AI and expert measurements were performed independently. Kellgren-Lawrence score and reading time were assessed. All measurements were compared and non-inferiority, mean-absolute-deviation (sMAD), and intra-class-correlation (ICC) were calculated.ResultsA total of 295 LLRs from 284 patients (mean age, 65 years (18; 90); 97 (34.2%) men) were analyzed. The AI model produces outputs on 98.0% of the LLRs. Manually annotations were considered as 100% accurate. For each measurement, its divergence was calculated, resulting in an overall accuracy of 89.2% when comparing the AI outputs to the manually measured. AI vs. mean observer revealed an sMAD between 0.39 and 2.19° for angles and 1.45–5.00 mm for lengths. AI showed good reliability in all lengths and angles (ICC ≥ 0.87). Non-inferiority comparing AI to the mean observer revealed an equivalence-index (γ) between 0.54 and 3.03° for angles and − 0.70–1.95 mm for lengths. On average, AI was 130 s faster than clinicians.ConclusionAutomated measurements of knee alignment and length measurements produced with an AI tool result in reproducible, accurate measures with a time savings compared to manually acquired measurements.
Journal Article
Optimal sequencing of enzalutamide and abiraterone acetate plus prednisone in metastatic castration-resistant prostate cancer: a multicentre, randomised, open-label, phase 2, crossover trial
Abiraterone acetate plus prednisone and enzalutamide are both used for the treatment of metastatic castration-resistant prostate cancer. We aimed to determine the best sequence in which to use both drugs, as well as their second-line efficacy.
In this multicentre, randomised, open-label, phase 2, crossover trial done in six cancer centres in British Columbia, Canada, we recruited patients aged 18 years or older with newly-diagnosed metastatic castration-resistant prostate cancer without neuroendocrine differentiation and Eastern Cooperative Oncology Group performance status 2 or less. Patients were randomly assigned (1:1) using a computer-generated random number table to receive either abiraterone acetate 1000 mg orally once daily plus prednisone 5 mg orally twice daily until PSA progression followed by crossover to enzalutamide 160 mg orally once daily (group A), or the opposite sequence (group B). Treatment was not masked to investigators or participants. Primary endpoints were time to second PSA progression and PSA response (≥30% decline from baseline) on second-line therapy, analysed by intention-to-treat in all randomly assigned patients and in patients who crossed over, respectively. The trial is registered with ClinicalTrials.gov, NCT02125357.
Between Oct 21, 2014, and Dec 13, 2016, 202 patients were enrolled and randomly assigned to either group A (n=101) or group B (n=101). At the time of data cutoff, 73 (72%) patients in group A and 75 (74%) patients in group B had crossed over. Time to second PSA progression was longer in group A than in group B (median 19·3 months [95% CI 16·0–30·5] vs 15·2 months [95% CI 11·9–19·8] months; hazard ratio 0·66, 95% CI 0·45–0·97, p=0·036), at a median follow-up of 22·8 months (IQR 10·3–33·4). PSA responses to second-line therapy were seen in 26 (36%) of 73 patients for enzalutamide and three (4%) of 75 for abiraterone (χ2 p<0·0001). The most common grade 3–4 adverse events throughout the trial were hypertension (27 [27%] of 101 patients in group A vs 18 [18%] of 101 patients in group B) and fatigue (six [10%] vs four [4%]). Serious adverse events were reported in 15 (15%) of 101 patients in group A and 20 (20%) of 101 patients in group B. There were no treatment-related deaths.
Enzalutamide showed activity as a second-line novel androgen receptor pathway inhibitor, whereas abiraterone acetate did not, leading to a longer time to second PSA progression for the sequence of abiraterone followed by enzalutamide than with the opposite treatment sequence. Our data suggest that using a sequencing strategy of abiraterone acetate followed by enzalutamide provides the greatest clinical benefit.
Canadian Cancer Society Research Institute, Prostate Cancer Canada, Movember Foundation, Prostate Cancer Foundation, Terry Fox New Frontiers Program, BC Cancer Foundation, Jane and Aatos Erkko Foundation, Janssen, and Astellas.
Journal Article
Status and Plans for the NA64 Experiment
The NA64 experiment at the CERN North Area searches for dark matter production via both visible and invisible decays of sub-GeV vector mediators, such as the dark photon A ′. In a first data taking period from 2016-2018, A′ generation from the reaction e Z → e Z A ′ and subsequent decays A ′ → χ χ ¯ and A ′ → e + e − was studied with the help of an active dump set-up using 100 GeV/ c and 150 GeV/ c electrons. Recently, an extension of the performed searches was proposed using a 150 GeV/ c muon beam, available at the M2 beamline at CERN. These measurements would allow for additional coverage of parameter space towards higher A ′ masses and would open the possibility for searches for a new gauge boson Z μ that would couple predominantly to the second and third lepton generations. We will present both the analysis of the available NA64 data as well as future plans for searches with muon and electron beams that are proposed within the “Physics Beyond Colliders” framework at CERN, including optimisation of the M2 optics and integration studies for implementing NA64 μ in the EHN2 experimental area.
Journal Article
التداول بعد الحصاد
يتناول الكتاب أهمية معاملات ما بعد الحصاد في تحسين جودة المنتجات البستانية وضمان سلامتها. يركز على تقنيات ما قبل التخزين للحد من التلف وتقليل الفاقد، ويستعرض الطرق الحديثة للكشف عن الكائنات الدقيقة المسببة للفساد والأمراض. يهدف إلى دعم الأمن الغذائي ورفع كفاءة التداول، مما يسهم في توفير غذاء آمن للمستهلك وتعزيز القدرة التصديرية للأسواق العالمية. يقدم مرجعا متكاملا للمهتمين بأنظمة ما بعد الحصاد والابتكار في سلاسل الإمداد الزراعي.
BOOK
Plasma ctDNA is a tumor tissue surrogate and enables clinical-genomic stratification of metastatic bladder cancer
Molecular stratification can improve the management of advanced cancers, but requires relevant tumor samples. Metastatic urothelial carcinoma (mUC) is poised to benefit given a recent expansion of treatment options and its high genomic heterogeneity. We profile minimally-invasive plasma circulating tumor DNA (ctDNA) samples from 104 mUC patients, and compare to same-patient tumor tissue obtained during invasive surgery. Patient ctDNA abundance is independently prognostic for overall survival in patients initiating first-line systemic therapy. Importantly, ctDNA analysis reproduces the somatic driver genome as described from tissue-based cohorts. Furthermore, mutation concordance between ctDNA and matched tumor tissue is 83.4%, enabling benchmarking of proposed clinical biomarkers. While 90% of mutations are identified across serial ctDNA samples, concordance for serial tumor tissue is significantly lower. Overall, our exploratory analysis demonstrates that genomic profiling of ctDNA in mUC is reliable and practical, and mitigates against disease undersampling inherent to studying archival primary tumor foci. We urge the incorporation of cell-free DNA profiling into molecularly-guided clinical trials for mUC.
In metastatic urothelial carcinoma, it has not been established whether circulating tumor DNA (ctDNA) can replace archival primary tissue to assess mutations and biomarkers. Here, the authors show high mutation concordance between ctDNA and tumour tissue, with high consistency in serial samples.
Journal Article