We describe a fully GPU-based implementation of the first level trigger for the upgrade of the LHCb detector, due to start data taking in 2021. We demonstrate that our implementation, named Allen, ...can process the 40 Tbit/s data rate of the upgraded LHCb detector and perform a wide variety of pattern recognition tasks. These include finding the trajectories of charged particles, finding proton–proton collision points, identifying particles as hadrons or muons, and finding the displaced decay vertices of long-lived particles. We further demonstrate that Allen can be implemented in around 500 scientific or consumer GPU cards, that it is not I/O bound, and can be operated at the full LHC collision rate of 30 MHz. Allen is the first complete high-throughput GPU trigger proposed for a HEP experiment.
We describe a fully GPU-based implementation of the first level trigger for the upgrade of the LHCb detector, due to start data taking in 2021. We demonstrate that our implementation, named Allen, ...can process the 40 Tbit/s data rate of the upgraded LHCb detector and perform a wide variety of pattern recognition tasks. These include finding the trajectories of charged particles, finding proton-proton collision points, identifying particles as hadrons or muons, and finding the displaced decay vertices of long-lived particles. We further demonstrate that Allen can be implemented in around 500 scientific or consumer GPU cards, that it is not I/O bound, and can be operated at the full LHC collision rate of 30 MHz. Allen is the first complete high-throughput GPU trigger proposed for a HEP experiment.
The calibration and performance of the LHCb Calorimeter system in Run 1 and 2 at the LHC are described. After a brief description of the sub-detectors and of their role in the trigger, the ...calibration methods used for each part of the system are reviewed. The changes which occurred with the increase of beam energy in Run 2 are explained. The performances of the calorimetry for \(\gamma\) and \(\pi^0\) are detailed. A few results from collisions recorded at \(\sqrt {s}\) = 7, 8 and 13 TeV are shown.
Point-of-care ultrasound (POCUS) is nowadays an essential tool in critical care. Its role seems more important in neonates and children where other monitoring techniques may be unavailable. POCUS ...Working Group of the European Society of Paediatric and Neonatal Intensive Care (ESPNIC) aimed to provide evidence-based clinical guidelines for the use of POCUS in critically ill neonates and children.
Creation of an international Euro-American panel of paediatric and neonatal intensivists expert in POCUS and systematic review of relevant literature. A literature search was performed, and the level of evidence was assessed according to a GRADE method. Recommendations were developed through discussions managed following a Quaker-based consensus technique and evaluating appropriateness using a modified blind RAND/UCLA voting method. AGREE statement was followed to prepare this document.
Panellists agreed on 39 out of 41 recommendations for the use of cardiac, lung, vascular, cerebral and abdominal POCUS in critically ill neonates and children. Recommendations were mostly (28 out of 39) based on moderate quality of evidence (B and C).
Evidence-based guidelines for the use of POCUS in critically ill neonates and children are now available. They will be useful to optimise the use of POCUS, training programs and further research, which are urgently needed given the weak quality of evidence available.
Background Taxanes are among the most active drugs for the treatment of metastatic breast cancer, and, as a consequence, they have also been studied in the adjuvant setting. Methods After breast ...cancer surgery, women with lymph node–positive disease were randomly assigned to treatment with fluorouracil, epirubicin, and cyclophosphamide (FEC) or with FEC followed by weekly paclitaxel (FEC-P). The primary endpoint of study—5-year disease-free survival (DFS)—was assessed by Kaplan–Meier analysis. Secondary endpoints included overall survival and analysis of the prognostic and predictive value of clinical and molecular (hormone receptors by immunohistochemistry and HER2 by fluorescence in situ hybridization) markers. Associations and interactions were assessed with a multivariable Cox proportional hazards model for DFS for the following covariates: age, menopausal status, tumor size, lymph node status, type of chemotherapy, tumor size, positive lymph nodes, HER2 status, and hormone receptor status. All statistical tests were two-sided. Results Among the 1246 eligible patients, estimated rates of DFS at 5 years were 78.5% in the FEC-P arm and 72.1% in the FEC arm (difference = 6.4%, 95% confidence interval CI = 1.6% to 11.2%; P = .006). FEC-P treatment was associated with a 23% reduction in the risk of relapse compared with FEC treatment (146 relapses in the 614 patients in the FEC-P arm vs 193 relapses in the 632 patients in the FEC arm, hazard ratio HR = 0.77, 95% CI = 0.62 to 0.95; P = .022) and a 22% reduction in the risk of death (73 and 95 deaths, respectively, HR = 0.78, 95% CI = 0.57 to 1.06; P = .110). Among the 928 patients for whom tumor samples were centrally analyzed, type of chemotherapy (FEC vs FEC-P) (P = .017), number of involved axillary lymph nodes (P < .001), tumor size (P = .020), hormone receptor status (P = .004), and HER2 status (P = .006) were all associated with DFS. We found no statistically significant interaction between HER2 status and paclitaxel treatment or between hormone receptor status and paclitaxel treatment. Conclusions Among patients with operable breast cancer, FEC-P treatment statistically significantly reduced the risk of relapse compared with FEC as adjuvant therapy.
Background and Objective
Caregiver burden in Parkinson's disease (PD) has been studied in many cross‐sectional studies but poorly in longitudinal ones. The aim of the present study was to analyze the ...change in burden, strain, mood, and quality of life (QoL) after a 2‐year follow‐up in a cohort of caregivers of patients with PD and also to identify predictors of these changes.
Patients and Methods
PD patients and their caregivers who were recruited from January/2016 to November/2017 from 35 centers of Spain from the COPPADIS cohort were included in the study. They were evaluated again at 2‐year follow‐up. Caregivers completed the Zarit Caregiver Burden Inventory (ZCBI), Caregiver Strain Index (CSI), Beck Depression Inventory‐II (BDI‐II), and EUROHIS‐QOL 8‐item index (EUROHIS‐QOL8) at baseline (V0) and at 2‐year follow‐up (V2). General linear model repeated measure and lineal regression models were applied.
Results
Significant changes, indicating an impairment, were detected on the total score of the ZCBI (p < 0.0001), CSI (p < 0.0001), BDI‐II (p = 0.024), and EUROHIS‐QOL8 (p = 0.002) in 192 PD caregivers (58.82 ± 11.71 years old; 69.3% were females). Mood impairment (BDI‐II; β = 0.652; p < 0.0001) in patients from V0 to V2 was the strongest factor associated with caregiver's mood impairment after the 2‐year follow‐up. Caregiver's mood impairment was the strongest factor associated with an increase from V0 to V2 on the total score of the ZCBI (β = 0.416; p < 0.0001), CSI (β = 0.277; p = 0.001), and EUROHIS‐QOL (β = 0.397; p = 0.002).
Conclusion
Burden, strain, mood, and QoL were impaired in caregivers of PD patients after a 2‐year follow‐up. Mood changes in both the patient and the caregiver are key aspects related to caregiver burden increase.
Key points
The present study is, to date, the largest prospective longitudinal study conducted for analyzing how burden, strain, mood, and quality of life change (QoL) in the principal caregiver of a patient with Parkinson's disease (PD).
After 2 years of follow‐up, the status of the principal caregiver of a patient with PD worsens as a whole with an increase in burden and stress and a worsening in mood and QoL.
Mood changes in the patient and in the caregiver as well are key aspects related to increase in caregiver burden.
These findings suggest that it could be essential to detect depressive symptoms both in the patient and in the caregiver too.
Three genome-wide association studies in Europe and the USA have reported eight urinary bladder cancer (UBC) susceptibility loci. Using extended case and control series and 1000 Genomes imputations ...of 5 340 737 single-nucleotide polymorphisms (SNPs), we searched for additional loci in the European GWAS. The discovery sample set consisted of 1631 cases and 3822 controls from the Netherlands and 603 cases and 37 781 controls from Iceland. For follow-up, we used 3790 cases and 7507 controls from 13 sample sets of European and Iranian ancestry. Based on the discovery analysis, we followed up signals in the urea transporter (UT) gene SLC14A. The strongest signal at this locus was represented by a SNP in intron 3, rs17674580, that reached genome-wide significance in the overall analysis of the discovery and follow-up groups: odds ratio = 1.17, P = 7.6 × 10−11. SLC14A1 codes for UTs that define the Kidd blood group and are crucial for the maintenance of a constant urea concentration gradient in the renal medulla and, through this, the kidney's ability to concentrate urine. It is speculated that rs17674580, or other sequence variants in LD with it, indirectly modifies UBC risk by affecting urine production. If confirmed, this would support the 'urogenous contact hypothesis' that urine production and voiding frequency modify the risk of UBC.
Previously, we reported germline DNA variants associated with risk of urinary bladder cancer (UBC) in Dutch and Icelandic subjects. Here we expanded the Icelandic sample set and tested the top 20 ...markers from the combined analysis in several European case-control sample sets, with a total of 4,739 cases and 45,549 controls. The T allele of rs798766 on 4p16.3 was found to associate with UBC (odds ratio = 1.24, P = 9.9 x 10(-12)). rs798766 is located in an intron of TACC3, 70 kb from FGFR3, which often harbors activating somatic mutations in low-grade, noninvasive UBC. Notably, rs798766T shows stronger association with low-grade and low-stage UBC than with more aggressive forms of the disease and is associated with higher risk of recurrence in low-grade stage Ta tumors. The frequency of rs798766T is higher in Ta tumors that carry an activating mutation in FGFR3 than in Ta tumors with wild-type FGFR3. Our results show a link between germline variants, somatic mutations of FGFR3 and risk of UBC.
A good response to levodopa is a key factor to indicate device-aided therapies in people with Parkinson's disease (PwPD). The aim of the present study was to analyze the response to levodopa in PwPD ...with motor fluctuations followed for 4 years.
PwPD with motor fluctuations recruited from January 2016 to November 2017 from the COPPADIS cohort and assessed annually (from baseline to 4-year follow-up) during the OFF and ON states were included in this analysis. At each visit, the Unified Parkinson's Disease Rating Scale – part III (UPDRS-III) was applied during the OFF state (without medication during the last 12 h) and during the ON state. General linear model repeated measures were used to test for changes in the mean UPDRS–III–OFF, UPDRS–III–ON, and ΔUPDRS-III (UPDRS–III–OFF – UPDRS–III–ON) between visits. Levodopa equivalent daily dose (LEDD) was included as covariate.
Sixty-three patients (63.94 ± 8.42 years old; 68.3% males) were included. Mean disease duration was 7.81 ± 3.64 years. From baseline to 4-year follow-up visit, a significant increase in both the UPDRS–III–OFF (from 27.98 ± 9.58 to 31.75 ± 12.39; p = 0.003) and the UPDRS–III–ON (from 15.92 ± 7.93 to 18.84 ± 8.17; p = 0.006) was observed despite the significant increase in the LEDD (from 896.35 ± 355.65 to 1085.51 ± 488.29; p = 0.003). However, no significant differences were detected between visits in the ΔUPDRS-III.
In this cohort of PwPD with motor fluctuations, the response to levodopa did not weaken after a 4-year follow-up.
•A good response to levodopa is a key factor to indicate device-aided or on-demand therapies in Parkinson's disease.•Response to levodopa did not weaken after a 4-year follow-up in 63 fluctuators PD patients.•On and off scores worsen at the expense of axial symptoms and in parallel with conservation of the levodopa response.•There were no differences by motor phenotype.
Motor phenotype (MP) can be associated with a different prognosis in Parkinson's disease (PD), but it is not fixed and can change over time.
Our aim was to analyze how the MP changed over time and to ...identify factors associated with the changes in PD patients from a multicenter Spanish PD cohort.
PD patients who were recruited from January-2016 to November-2017 (baseline visit; V0) and evaluated again at a 2-year±30 days follow-up (V2) from 35 centers of Spain from the COPPADIS cohort, were included in this study.MP was calculated at both visits based on Jankovic classification in TD (tremor dominant), IND (indeterminate), or PIGD (postural instability and gait difficulty). Sociodemographic and clinical data were collected, including serum biomarkers.
Five hundred eleven patients (62.57±8.59 years old; 59.2%males) were included in the study. At V0, MP was: 47.4%(242/511) TD; 36.6%(187/511) PIGD; 16%(82/511) IND. Up to 38%(194/511) of the patients changed their phenotype from V0 to V2, being the most frequent from TD to IND (8.4%) and from TD to PIGD (6.7%). A worse cognitive status (OR = 0.966) and less autonomy for activities of daily living (OR = 0.937) at V0 and a greater increase in the globalNMS burden (OR = 1.011) from V0 to V2 were associated with changing from TD to another phenotype after 2-year follow-up.
The MP in PD can change over time. With disease progression, the percentage of cases with non-tremoric MP increases. PD patients who changed from TD to postural instability and gait difficulty increased NMS burden significantly.
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