Timing influenced force directed floorplanning

We present a timing driven floorplanning program for general cell layouts. The approach used combines quality of force directed approach with that of constraint graph approach. A floorplan solution is produced in two steps. First a timing and connectivity driven topological arrangement is obtained using a force directed approach. In the second step, the topological arrangement is transformed into a legal floorplan. The objective of the second step is to minimize the overall area of the floorplan. The floorplanner is validated with circuits of sizes varying from 7 to 125 block

Timing influenced force directed floorplanning

We present a timing driven floorplanning program for general cell layouts. The approach used combines quality of force directed approach with that of constraint graph approach. A floorplan solution is produced in two steps. First a timing and connectivity driven topological arrangement is obtained using a force directed approach. In the second step, the topological arrangement is transformed into a legal floorplan. The objective of the second step is to minimize the overall area of the floorplan. The floorplanner is validated with circuits of sizes varying from 7 to 125 block

Sarilumab in patients admitted to hospital with severe or critical COVID-19: a randomised, double-blind, placebo-controlled, phase 3 trial

Background: Elevated proinflammatory cytokines are associated with greater COVID-19 severity. We aimed to assess safety and efficacy of sarilumab, an interleukin-6 receptor inhibitor, in patients with severe (requiring supplemental oxygen by nasal cannula or face mask) or critical (requiring greater supplemental oxygen, mechanical ventilation, or extracorporeal support) COVID-19. Methods: We did a 60-day, randomised, double-blind, placebo-controlled, multinational phase 3 trial at 45 hospitals in Argentina, Brazil, Canada, Chile, France, Germany, Israel, Italy, Japan, Russia, and Spain. We included adults (≥18 years) admitted to hospital with laboratory-confirmed SARS-CoV-2 infection and pneumonia, who required oxygen supplementation or intensive care. Patients were randomly assigned (2:2:1 with permuted blocks of five) to receive intravenous sarilumab 400 mg, sarilumab 200 mg, or placebo. Patients, care providers, outcome assessors, and investigators remained masked to assigned intervention throughout the course of the study. The primary endpoint was time to clinical improvement of two or more points (seven point scale ranging from 1 [death] to 7 [discharged from hospital]) in the modified intention-to-treat population. The key secondary endpoint was proportion of patients alive at day 29. Safety outcomes included adverse events and laboratory assessments. This study is registered with ClinicalTrials.gov, NCT04327388; EudraCT, 2020-001162-12; and WHO, U1111-1249-6021. Findings: Between March 28 and July 3, 2020, of 431 patients who were screened, 420 patients were randomly assigned and 416 received placebo (n=84 [20%]), sarilumab 200 mg (n=159 [38%]), or sarilumab 400 mg (n=173 [42%]). At day 29, no significant differences were seen in median time to an improvement of two or more points between placebo (12·0 days [95% CI 9·0 to 15·0]) and sarilumab 200 mg (10·0 days [9·0 to 12·0]; hazard ratio [HR] 1·03 [95% CI 0·75 to 1·40]; log-rank p=0·96) or sarilumab 400 mg (10·0 days [9·0 to 13·0]; HR 1·14 [95% CI 0·84 to 1·54]; log-rank p=0·34), or in proportions of patients alive (77 [92%] of 84 patients in the placebo group; 143 [90%] of 159 patients in the sarilumab 200 mg group; difference −1·7 [−9·3 to 5·8]; p=0·63 vs placebo; and 159 [92%] of 173 patients in the sarilumab 400 mg group; difference 0·2 [−6·9 to 7·4]; p=0·85 vs placebo). At day 29, there were numerical, non-significant survival differences between sarilumab 400 mg (88%) and placebo (79%; difference +8·9% [95% CI −7·7 to 25·5]; p=0·25) for patients who had critical disease. No unexpected safety signals were seen. The rates of treatment-emergent adverse events were 65% (55 of 84) in the placebo group, 65% (103 of 159) in the sarilumab 200 mg group, and 70% (121 of 173) in the sarilumab 400 mg group, and of those leading to death 11% (nine of 84) were in the placebo group, 11% (17 of 159) were in the sarilumab 200 mg group, and 10% (18 of 173) were in the sarilumab 400 mg group. Interpretation: This trial did not show efficacy of sarilumab in patients admitted to hospital with COVID-19 and receiving supplemental oxygen. Adequately powered trials of targeted immunomodulatory therapies assessing survival as a primary endpoint are suggested in patients with critical COVID-19. Funding: Sanofi and Regeneron Pharmaceuticals

Attending to women's sexual health in Bahrain: does physician's gender make a difference? ‫ذلك؟‬ ‫عىل‬ ٌّ ‫أثر‬ ‫الطبيب‬ ‫جلنس‬ ‫هل‬ ‫البحرين:‬ ‫يف‬ ‫اجلنسية‬ ‫الصحة‬ ‫ألقسام‬ ‫النساء‬ ‫مراجعة‬

ABSTRACT There is a rising incidence of sexually transmitted infections (STIs) in Bahrain. This study aimed to determine physician practices with regard to sexual and reproductive health in women in the primary care setting in Bahrain, and to ascertain if physician gender affected these. The study included all eligible Ministry of Health family physicians (217) in 2006 and data were collected by a self-completed questionnaire; the response rate was 90.3%. Over half (58%) of the responding physicians were female. Male physicians did not undertake gynaecological examinations nor carry out STI screening procedures for asymptomatic women, and rates for women physicians were low (28.9% and 11.4% respectively). As regards to identification of and counselling for sexual health and STI risk factors, there were no differences between male and female physicians in addressing these issues with less than 25% doing so. All physicians would benefit from continuing education in the area of sexual medicine regardless of their gender

Update and, internal and temporal-validation of the FRANCE-2 and ACC-TAVI early-mortality prediction models for Transcatheter Aortic Valve Implantation (TAVI) using data from the Netherlands heart registration (NHR)

Background: The predictive performance of the models FRANCE-2 and ACC-TAVI for early-mortality after Transcatheter Aortic Valve Implantation (TAVI) can decline over time and can be enhanced by updating them on new populations. We aim to update and internally and temporally validate these models using a recent TAVI-cohort from the Netherlands Heart Registration (NHR). Methods: We used data of TAVI-patients treated in 2013–2017. For each original-model, the best update-method (model-intercept, model-recalibration, or model-revision) was selected by a closed-testing procedure. We internally validated both updated models with 1000 bootstrap samples. We also updated the models on the 2013–2016 dataset and temporally validated them on the 2017-dataset. Performance measures were the Area-Under ROC-curve (AU-ROC), Brier-score, and calibration graphs. Results: We included 6177 TAVI-patients, with 4.5% observed early-mortality. The selected update-method for FRANCE-2 was model-intercept-update. Internal validation showed an AU-ROC of 0.63 (95%CI 0.62–0.66) and Brier-score of 0.04 (0.04–0.05). Calibration graphs show that it overestimates early-mortality. In temporal-validation, the AU-ROC was 0.61 (0.53–0.67). The selected update-method for ACC-TAVI was model-revision. In internal-validation, the AU-ROC was 0.63 (0.63–0.66) and Brier-score was 0.04 (0.04–0.05). The updated ACC-TAVI calibrates well up to a probability of 20%, and subsequently underestimates early-mortality. In temporal-validation the AU-ROC was 0.65 (0.58–0.72). Conclusion: Internal-validation of the updated models FRANCE-2 and ACC-TAVI with data from the NHR demonstrated improved performance, which was better than in external-validation studies and comparable to the original studies. In temporal-validation, ACC-TAVI outperformed FRANCE-2 because it suffered less from changes over time