29 research outputs found
Method For Making 2-Electron Response Reduced Density Matrices Approximately N-representable
In methods like geminal-based approaches or coupled cluster that are solved
using the projected Schr\"odinger equation, direct computation of the
2-electron reduced density matrix (2-RDM) is impractical and one falls back to
a 2-RDM based on response theory. However, the 2-RDMs from response theory are
not -representable. That is, the response 2-RDM does not correspond to an
actual physical -electron wave function. We present a new algorithm for
making these non--representable 2-RDMs approximately -representable, i.e.
it has the right symmetry and normalization and it fulfills the -, - and
-conditions. Next to an algorithm which can be applied to any 2-RDM, we have
also developed a 2-RDM optimization procedure specifically for seniority-zero
2-RDMs. We aim to find the 2-RDM with the right properties that is the closest
(in the sense of the Frobenius norm) to the non-N-representable 2-RDM by
minimizing the square norm of the difference between the initial 2-RDM and the
targeted 2-RDM under the constraint that the trace is normalized and the 2-RDM,
- and -matrices are positive semidefinite, i.e. their eigenvalues are
non-negative. Our method is suitable for fixing non-N-respresentable 2-RDMs
which are close to being N-representable. Through the N-representability
optimization algorithm we add a small correction to the initial 2-RDM such that
it fulfills the most important N-representability conditions.Comment: 13 pages, 8 figure
Clinical response correlates with 4-week postinjection ustekinumab concentrations in patients with moderate-to-severe psoriasis
Background: Costâeffective use of biologicals is important. As drug concentrations have been linked to clinical outcomes, monitoring drug concentrations is a valuable tool to guide clinical decisionâmaking. A concentrationâresponse relationship for ustekinumab at trough is uncertain owing to the contradictory results reported.
Objectives: To investigate the relationship between 4âweek postinjection ustekinumab concentrations and clinical response in patients with psoriasis.
Methods: Fortyânine patients with moderateâtoâsevere psoriasis treated with 45 mg or 90 mg ustekinumab every 12 weeks for â„ 16 weeks were included. Ustekinumab serum concentrations and antiâustekinumab antibodies were measured at week 4 after injection and disease severity was assessed by Psoriasis Area and Severity Index (PASI).
Results: At week 4 after injection, a significantly negative correlation was observed between ustekinumab concentrations and absolute PASI score up to 5·9 ÎŒg mLâ1 (Ï = â0·357, P = 0·032). Ustekinumab concentrations were higher in optimal responders (PASI †2) than in suboptimal responders (PASI > 2) (4·0 vs 2·8 ÎŒg mLâ1, P = 0·036). The ustekinumab concentration threshold associated with optimal response was determined to be 3·6 ÎŒg mLâ1 (area under the curve 0·71, sensitivity 86%, specificity 63%). Only one patient (2%) had antiâustekinumab antibodies. Psoriatic arthritis was identified as an independent predictor of higher PASI scores and higher ustekinumab concentrations (P = 0·003 and P = 0·048, respectively).
Conclusions: A concentrationâresponse relationship at week 4 after injection was observed for patients with psoriasis treated with ustekinumab. Monitoring 4âweek postinjection ustekinumab concentrations could timely identify underexposed patients who might benefit from treatment optimization
Optimization of simple sphygmomanometric blood pressure measurement in routine prenatal care
status: publishe
Clinical response correlates with 4-week postinjection ustekinumab concentrations in patients with moderate-to-severe psoriasis
BACKGROUND: Cost-effective use of biologicals is important. As drug concentrations have been linked to clinical outcomes, monitoring drug concentrations is a valuable tool to guide clinical decision-making. A concentration-response relationship for ustekinumab at trough is uncertain owing to the contradictory results reported. OBJECTIVES: To investigate the relationship between 4-week postinjection ustekinumab concentrations and clinical response in patients with psoriasis. METHODS: Forty-nine patients with moderate-to-severe psoriasis treated with 45 mg or 90 mg ustekinumab every 12 weeks for â„ 16 weeks were included. Ustekinumab serum concentrations and anti-ustekinumab antibodies were measured at week 4 after injection and disease severity was assessed by Psoriasis Area and Severity Index (PASI). RESULTS: At week 4 after injection, a significantly negative correlation was observed between ustekinumab concentrations and absolute PASI score up to 5·9 ÎŒg mL-1 (Ï = -0·357, P = 0·032). Ustekinumab concentrations were higher in optimal responders (PASI †2) than in suboptimal responders (PASI > 2) (4·0 vs 2·8 ÎŒg mL-1 , P = 0·036). The ustekinumab concentration threshold associated with optimal response was determined to be 3·6 ÎŒg mL-1 (area under the curve 0·71, sensitivity 86%, specificity 63%). Only one patient (2%) had anti-ustekinumab antibodies. Psoriatic arthritis was identified as an independent predictor of higher PASI scores and higher ustekinumab concentrations (P = 0·003 and P = 0·048, respectively). CONCLUSIONS: A concentration-response relationship at week 4 after injection was observed for patients with psoriasis treated with ustekinumab. Monitoring 4-week postinjection ustekinumab concentrations could timely identify underexposed patients who might benefit from treatment optimization. What's already known about this topic? Monitoring drug concentrations is a valuable tool that can guide clinical decision-making when drug concentrations are linked to clinical outcomes. The presence of a concentration-response relationship for ustekinumab at trough is still debated owing to the contradictory results reported. What does this study add? A concentration-response relationship at week 4 after injection for ustekinumab-treated patients with psoriasis was demonstrated. Monitoring 4-week postinjection ustekinumab concentrations could timely identify underexposed patients who might benefit from treatment optimization. Based on the findings of this study, a treatment algorithm for patients with a suboptimal response is proposed.status: publishe
Dermatoscopy of combined blue nevi: a multicentre study of the International Dermoscopy Society
Background: Combined blue nevi (CBN) may mimic melanoma and are relatively often biopsied for diagnostic reasons. Objective: To better characterize CBN and to compare it with melanoma. Methods: We collected clinical and dermatoscopic images of 111 histologically confirmed CBN and contrasted their dermatoscopic characteristics with 132 partly blue coloured melanomas. Furthermore, we compared the accuracy of human experts using pattern analysis with a computer algorithm based on deep learning. Results: Combined blue nevi are usually flat or slightly elevated and, in comparison with melanoma, more frequent on the head and neck. Dermatoscopically, they are typified by a blue structureless part in combination with either brown clods (n = 52, 46.8%), lines (n = 28, 25.2%) or skin-coloured or brown structureless areas (n = 31, 27.9%). In contrast with melanoma, the blue part of CBN is more often well defined (18.9% vs. 4.5%, P < 0.001) and more often located in the centre (22.5% vs. 5.3%, P < 0.001). Melanomas are more often chaotic (OR: 28.7, 95% CI: 14.8â55.7, P < 0.001), have at least one melanoma clue (OR: 10.8, 95% CI: 5.2â22.2 P < 0.001) in particular white lines (OR: 37.1, 95% CI: 13.4â102.9, P < 0.001). Using simplified pattern analysis (chaos and clues), two raters reached sensitivities of 93.9% (95% CI: 88.4â97.3%) and 92.4% (95% CI: 86.5â96.3%) at corresponding specificities of 59.5% (95% CI: 49.7â68.7%) and 65.8% (95% CI: 56.2â74.5%). The human accuracy with pattern analysis was on par with a state-of-the-art computer algorithm based on deep learning that achieved an area under the curve of (0.92, 95% CI: 0.87â0.96) and a specificity of 85.3% (95% CI: 76.5â91.7%) at a given sensitivity of 83.6% (95% CI: 72.5â91.5%). Conclusion: CBN usually lack melanoma clues, in particular white lines. The accuracy of pattern analysis for combined nevi is acceptable, and histopathologic confirmation may not be necessary in exemplary cases