The LHCb experiment at CERN has decided to optimise its physics reach by removing the first level hardware trigger for 2020 and beyond. In addition to requiring fully redesigned front-end electronics ...this design creates interesting challenges for the data-acquisition and the rest of the online computing system. Such a system can only be realized within realistic cost using as much off-the-shelf hardware as possible. Relevant technologies evolve very quickly and thus the system design is architecture-centred and tries to avoid to depend too much on specific technologies. In this paper we describe the design, the motivations for various choices and the current favoured options for the implementation, and the status of the R&D. We will cover the back-end readout, which contains the only custom-made component, the event-building, the event-filter infrastructure, and storage.
Objectives
To determine i) whether cases of elderly fallers had lower serum 25-hydroxyvitamin D (25OHD) concentration than controls without history of falls; and ii) whether serum 25OHD concentration ...was associated with specific mechanisms, circumstances and consequences of falls.
Design
Case-control study with a 1:2 ratio.
Setting
Geriatric ward of the University Hospital of Angers, France, between February 2012 and March 2014.
Participants
216 inpatients (72 cases and 144 age- and gender-matched controls).
Measurement
Falls were defined as involuntary events causing the person to the ground or other lower level. The main mechanisms, circumstances and consequences of falls were identified using standardized questionnaires. Vitamin D deficiency was defined as serum 25OHD concentration ≤25nmol/L. Age, gender, body mass index, polypharmacy, use antihypertensive drugs, use psychoactive drugs, disability, cognitive performance, serum concentrations of parathyroid hormone, creatinine and albumin, and season of evaluation were used as potential confounders.
Results
216 participants (72 cases and 144 controls) were included in the study. There was no between-group difference in the prevalence of vitamin D deficiency (P=0.176). After adjusting for confounding factors, vitamin D deficiency was positively associated with falls (OR=4.03, P=0.014). Finally, the fallers with vitamin D deficiency exhibited more often orthostatic hypotension (68.8% against 33.3%, P=0.039) and a history of recurrent falls (85% against 50%, P=0.002) than those without vitamin D deficiency.
Conclusion
This casecontrol study reported that vitamin D deficiency was associated with falls in older inpatients. There was a greater prevalence of orthostatic hypotension and of the reccurrence of falls among fallers with vitamin D deficiency, suggesting that vitamin D may influence the conditions predisposing to falls rather than the fall by itself.
Abstract
STUDY QUESTION
Can artificial intelligence (AI) algorithms developed to assist embryologists in evaluating embryo morphokinetics be enriched with multi-centric clinical data to better ...predict clinical pregnancy outcome?
SUMMARY ANSWER
Training algorithms on multi-centric clinical data significantly increased AUC compared to algorithms that only analyzed the time-lapse system (TLS) videos.
WHAT IS KNOWN ALREADY
Several AI-based algorithms have been developed to predict pregnancy, most of them based only on analysis of the time-lapse recording of embryo development. It remains unclear, however, whether considering numerous clinical features can improve the predictive performances of time-lapse based embryo evaluation.
STUDY DESIGN, SIZE, DURATION
A dataset of 9986 embryos (95.60% known clinical pregnancy outcome, 32.47% frozen transfers) from 5226 patients from 14 European fertility centers (in two countries) recorded with three different TLS was used to train and validate the algorithms. A total of 31 clinical factors were collected. A separate test set (447 videos) was used to compare performances between embryologists and the algorithm.
PARTICIPANTS/MATERIALS, SETTING, METHODS
Clinical pregnancy (defined as a pregnancy leading to a fetal heartbeat) outcome was first predicted using a 3D convolutional neural network that analyzed videos of the embryonic development up to 2 or 3 days of development (33% of the database) or up to 5 or 6 days of development (67% of the database). The output video score was then fed as input alongside clinical features to a gradient boosting algorithm that generated a second score corresponding to the hybrid model. AUC was computed across 7-fold of the validation dataset for both models. These predictions were compared to those of 13 senior embryologists made on the test dataset.
MAIN RESULTS AND THE ROLE OF CHANCE
The average AUC of the hybrid model across all 7-fold was significantly higher than that of the video model (0.727 versus 0.684, respectively, P = 0.015; Wilcoxon test). A SHapley Additive exPlanations (SHAP) analysis of the hybrid model showed that the six first most important features to predict pregnancy were morphokinetics of the embryo (video score), oocyte age, total gonadotrophin dose intake, number of embryos generated, number of oocytes retrieved, and endometrium thickness. The hybrid model was shown to be superior to embryologists with respect to different metrics, including the balanced accuracy (P ≤ 0.003; Wilcoxon test). The likelihood of pregnancy was linearly linked to the hybrid score, with increasing odds ratio (maximum P-value = 0.001), demonstrating the ranking capacity of the model. Training individual hybrid models did not improve predictive performance. A clinic hold-out experiment was conducted and resulted in AUCs ranging between 0.63 and 0.73. Performance of the hybrid model did not vary between TLS or between subgroups of embryos transferred at different days of embryonic development. The hybrid model did fare better for patients older than 35 years (P < 0.001; Mann–Whitney test), and for fresh transfers (P < 0.001; Mann–Whitney test).
LIMITATIONS, REASONS FOR CAUTION
Participant centers were located in two countries, thus limiting the generalization of our conclusion to wider subpopulations of patients. Not all clinical features were available for all embryos, thus limiting the performances of the hybrid model in some instances.
WIDER IMPLICATIONS OF THE FINDINGS
Our study suggests that considering clinical data improves pregnancy predictive performances and that there is no need to retrain algorithms at the clinic level unless they follow strikingly different practices. This study characterizes a versatile AI algorithm with similar performance on different time-lapse microscopes and on embryos transferred at different development stages. It can also help with patients of different ages and protocols used but with varying performances, presumably because the task of predicting fetal heartbeat becomes more or less hard depending on the clinical context. This AI model can be made widely available and can help embryologists in a wide range of clinical scenarios to standardize their practices.
STUDY FUNDING/COMPETING INTEREST(S)
Funding for the study was provided by ImVitro with grant funding received in part from BPIFrance (Bourse French Tech Emergence (DOS0106572/00), Paris Innovation Amorçage (DOS0132841/00), and Aide au Développement DeepTech (DOS0152872/00)). A.B.-C. is a co-owner of, and holds stocks in, ImVitro SAS. A.B.-C. and F.D.M. hold a patent for ‘Devices and processes for machine learning prediction of in vitro fertilization’ (EP20305914.2). A.D., N.D., M.M.F., and F.D.M. are or have been employees of ImVitro and have been granted stock options. X.P.-V. has been paid as a consultant to ImVitro and has been granted stocks options of ImVitro. L.C.-D. and C.G.-S. have undertaken paid consultancy for ImVitro SAS. The remaining authors have no conflicts to declare.
TRIAL REGISTRATION NUMBER
N/A.
Introduction
Late‐onset Pompe disease (LOPD) is characterized by a progressive myopathy resulting from a deficiency of acid α‐glucosidase enzyme activity. Enzyme replacement therapy has been shown to ...be effective, but long‐term treatment results vary. Avalglucosidase alfa demonstrated non‐inferiority to alglucosidase alfa in a phase 3 study, allowing in France compassionate access for advanced LOPD patients unresponsive to alglucosidase alfa.
Methods
Data from the French Pompe registry were analyzed for patients who benefited from a switch to avalglucosidase alfa with at least 1 year of follow‐up. Respiratory (forced vital capacity FVC) and motor functions (Six‐Minute Walk Test 6MWT) were assessed before and 1 year after switching. Individual changes in FVC and 6MWT were expressed as slopes and statistical analyses were performed to compare values.
Results
Twenty‐nine patients were included (mean age 56 years, 11 years of prior treatment). The FVC and 6MWT values remained stable. The individual analyses showed a stabilization of motor worsening: –1 m/year on the 6MWT after the switch versus –63 m/year the year before the switch (i.e., a worsening of 33%/year before vs. an improvement of 3%/year later). Respiratory data were not statistically different.
Discussion
At the group level, gait parameters improved slightly with a stabilization of previous worsening, but respiratory parameters showed limited changes. At the individual level, results were discordant, with some patients with a good motor or respiratory response and some with further worsening.
Conclusion
Switching to avalglucosidase alfa demonstrated varied responses in advanced LOPD patients with failing alglucosidase alfa therapy, with a general improvement in motor stabilization.
Symptomatic neurological complications (NC) are a major cause of mortality in infective endocarditis (IE) but the impact of asymptomatic complications is unknown. We aimed to assess the impact of ...asymptomatic NC (AsNC) on the management and prognosis of IE.
From the database of cases collected for a population-based study on IE, we selected 283 patients with definite left-sided IE who had undergone at least one neuroimaging procedure (cerebral CT scan and/or MRI) performed as part of initial evaluation.
Among those 283 patients, 100 had symptomatic neurological complications (SNC) prior to the investigation, 35 had an asymptomatic neurological complications (AsNC), and 148 had a normal cerebral imaging (NoNC). The rate of valve surgery was 43% in the 100 patients with SNC, 77% in the 35 with AsNC, and 54% in the 148 with NoNC (p<0.001). In-hospital mortality was 42% in patients with SNC, 8.6% in patients with AsNC, and 16.9% in patients with NoNC (p<0.001). Among the 135 patients with NC, 95 had an indication for valve surgery (71%), which was performed in 70 of them (mortality 20%) and not performed in 25 (mortality 68%). In a multivariate adjusted analysis of the 135 patients with NC, age, renal failure, septic shock, and IE caused by S. aureus were independently associated with in-hospital and 1-year mortality. In addition SNC was an independent predictor of 1-year mortality.
The presence of NC was associated with a poorer prognosis when symptomatic. Patients with AsNC had the highest rate of valve surgery and the lowest mortality rate, which suggests a protective role of surgery guided by systematic neuroimaging results.
To assess the rate of complications of radical lymph node dissection following sentinel lymph node biopsy in patients with malignant melanoma.
A single-centre retrospective study was performed ...between 2001 and 2009. All melanoma patients who first had a sentinel node biopsy followed by a radical lymph node dissection were included.
Seventy-four patients had radical lymph node dissection after confirmation of metastasis in a sentinel node. The sites of the lymphadenectomy were axillary in 51% of patients, groin in 43%, neck in 5% and popliteal in 1%. A nodal metastasis was observed in 12 of 74 lymph node dissections. Median follow-up time was 41.5 months (3-135 months). At least one complication was seen in 47 patients (64%). Early complications were: postoperative infection (n=9; 12%), lymphocele (n=22; 30%), chronic seroma (n=9; 12%), postoperative haematoma (n=6; 8%), and wound separation (n=7; 9%). Late complications were: lymphoedema (n=30; 41%), joint complications (n=10; 14%), fibrous scar (n=11; 15%), chronic pain (n=6; 8%) and hyposensitivity (n=6; 8%). Two patients were rehospitalised for a complication. The complication rate was 53% for axillary location and 81% for inguinal location (P=0.02).
Radical lymph node dissection performed after positive sentinel node biopsy in melanoma patients is associated with significant morbidity.
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