Simulation-based determination of systematic errors of flow meters due to uncertain inflow conditions

Computational fluid dynamics (CFD) provides well-established tools for the prediction of the velocity profiles in turbulent pipe flows. As far as industrial pipe and district heating systems are concerned, combinations of elbows are the most common pipe assemblies. Among the different pipe combinations, double elbows out-of-plane are of special interest, since they introduce strong disturbances into the flow profile and have a strong influence on many common types of flow meters. In front of a double elbow there is often another flow-disturbing installation. As a result the upstream conditions are unknown and an investigation of the resulting systematic bias on the measurement of the flow rate and the associated contribution to its measurement uncertainty is necessary. We demonstrate here that this can be achieved by a variation of the inlet profile in terms of swirls and asymmetry components. In particular, an ultrasonic and an electromagnetic flow meter are modeled in order to quantify the systematic errors stemming from uncertain inflow conditions. For this purpose, a generalized non-intrusive polynomial chaos method has been used in conjunction with a commercial CFD code. As the most influential parameters on the measured volume flow, the distance between the double elbow and the flow meter as well as the orientation of the flow meter are considered as random variables in the polynomial chaos approach. This approach allowed us to obtain accurate prediction of the systematic error for the ultrasonic and electromagnetic meter as functions of the distance to the double elbow. The resulting bias in the flow rate has been found to be in the range of 1.5–4.5% (0.1–0.5%) with a systematic uncertainty contribution of 2–2.4% (0.6–0.7%) for the ultrasonic (electromagnetic) flow meter if the distance to the double elbow is smaller than 40 pipe diameters. Moreover, it is demonstrated that placing the flow meters in a Venturi constriction leads to substantial decrease of the bias and the contribution to the measurement uncertainty stemming from the uncertain inflow condition

Comparison of variables measured with a Scheimpflug device for evaluation of progression and detection of keratoconus

Keratoconus is a progressive ectatic corneal disorder, which can result in severe visual impairment. The new ABCD keratoconus classification system allows differentiated description of the disease. Aim of the study was to evaluate the components of this novel staging system (ARC, PRC, thinnest pachymetry) as well as topometric indices, deviation of normality indices, and other parameters in terms of repeatability and reliability. 317 eyes with keratoconus were examined twice with a Scheimpflug device (Pentacam, Oculus). Bland Altman analysis and intraclass correlations were carried out to evaluate the parameters repeatability and reliability. Apart from IHA (ICC=0.730), all parameters showed excellent reliability (ICC>0.900). ARC, PRC, thinnest pachymetry, Kmax, CKI, KI, Rmin, and Progression Avg were the best repeatable parameters with relative repeatability values<2.5%. Other parameters performing well in terms of repeatability were IHD, ISV, IVA, and final D (RR<13%). Regression analysis revealed consistently high repeatability along all stages of keratoconus for PRC, thinnest pachymetry, and CKI. All parameters of the ABCD staging system showed excellent reliability and repeatability, PRC and thinnest pachymetry even at all stages of keratoconus and can consequently be reliably used in the determination of keratoconus progression

Dosing Regimens of Intravitreal Aflibercept for Diabetic Macular Edema Beyond the First Year: VIOLET, a Prospective Randomized Trial.

INTRODUCTION The purpose was to compare two flexible regimens of intravitreal aflibercept (IVT-AFL) with fixed dosing every 8 weeks, beyond the first year of treatment, in patients with diabetic macular edema (DME). VIOLET was a 100-week, randomized, Phase IIIb, non-inferiority study in patients with center-involving DME previously treated with IVT-AFL for ≥ 1 year according to the European label. METHODS Patients received an initial dose of IVT-AFL at study baseline and were randomly assigned (1:1:1) to treat-and-extend (T&E), pro re nata (PRN), or fixed regimens. The primary endpoint was mean change in best-corrected visual acuity (BCVA) from baseline (randomization) to Week 52. RESULTS Full analysis set comprised 458 patients (baseline mean BCVA: 72.5, 71.0, and 72.7 letters in the T&E, PRN, and fixed-dose groups, respectively). Patients received a mean (min-max) of 10.0 (2-14; T&E), 11.5 (1-25; PRN), and 12.3 (3-13; fixed) injections over 100 weeks, with 13.3 (4-23), 25.0 (3-29), and 16.1 (5-25) clinic visits, respectively. At Week 52, mean (± standard deviation) BCVA changes from baseline were + 0.5 ± 6.7 (T&E), + 1.7 ± 6.8 (PRN), and + 0.4 ± 6.7 (fixed-dosing) letters (least squares mean difference [95% confidence interval]: T&E 0.01 [- 1.46, 1.47] and PRN 0.95 (- 0.52, 2.42) letters versus fixed dosing; p < 0.0001 for both non-inferiority tests [4-letter margin]). The IVT-AFL safety profile was consistent with previous studies. CONCLUSION The treatment burden associated with intravitreal injections for DME is lowest with T&E regimens, but there are a range of flexible IVT-AFL dosing regimens, allowing physicians to adopt an individualized treatment plan. TRIAL REGISTRATION ClinicalTrials.gov identifier: NCT02818998

Vision-related quality of life in patients with diabetic macular edema treated with intravitreal aflibercept: The AQUA Study

Purpose: To examine vision-related quality of life in patients with diabetic macular edema (DME) treated with intravitreal aflibercept (EYLEA, Regeneron Pharmaceuticals, Inc, Tarrytown, NY). Design: AQUA was a multicenter, open-label, single-arm, phase 4 study. Participants: Adults 18 years of age or older with type 1 or 2 diabetes mellitus and DME. Methods: Patients received intravitreal aflibercept 2 mg every 8 weeks for 52 weeks, after 5 initial doses every 4 weeks. Main outcome measures: The primary outcome was the change in 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25) total score from baseline to week 52. Secondary outcomes included the change in NEI VFQ-25 near and distant activities subscale scores, best-corrected visual acuity (BCVA; Early Treatment Diabetic Retinopathy Study [ETDRS] letters), and central retinal thickness (CRT) from baseline to week 52. Change in NEI VFQ-25 score at week 52 for better-seeing eyes (BSEs) and worse-seeing eyes (WSEs) also was evaluated. Results: A total of 553 patients comprised the full analysis set, and 560 patients comprised the safety analysis set. At baseline, the mean NEI VFQ-25 total score was 70.12, mean BCVA was 61.5 ETDRS letters, and mean CRT was 464.81 μm. A mean of 8.8 injections were administered over 52 weeks. At week 52, the mean improvement from baseline in the NEI VFQ-25 total score was +6.11 (standard deviation [SD], 11.46); the corresponding improvements in near and distant activities were +11.37 (SD, 18.01) and +7.33 (SD, 17.32), respectively. Similarly, improvements in patients whose BSE and WSE were treated were 7.74 (SD, 13.59) and 5.48 (SD, 9.70), respectively. At week 52, mean change in BCVA was +10.0 ETDRS letters (SD, 8.0 ETDRS letters), and mean change in CRT was -175.38 μm (SD, 132.62 μm). Overall, 53.6% of patients reported treatment-emergent adverse events (TEAEs), of whom 26.8% experienced an ocular TEAE in the study eye. The most common serious ocular TEAE was endophthalmitis (0.5% [n = 3]). Five deaths (0.9%) were reported, but were not considered treatment related. Conclusions: Intravitreal aflibercept was associated with clinically meaningful improvements in NEI VFQ-25 total score over 52 weeks in patients with DME; these were even more pronounced for near than for distant activities. Adverse events were consistent with the known safety profile of intravitreal aflibercept

Gemeindenahe stationäre Psychotherapie – erste Ergebnisse einer multizentrischen Erhebung in bayerischen Bezirkskliniken

Psychotherapeutische Methoden haben einen zunehmenden Stellenwert im Behandlungsangebot der Bayerischen Bezirkskliniken. In der vorliegenden deskriptiven Erhebung konnte gezeigt werden, dass in den entsprechenden Abteilungen der Kliniken vor allem schwer und sehr schwer erkrankte Patienten, die überwiegend im Versorgungsgebiet der Kliniken wohnen, mit nachgewiesen guten Effekten behandelt werden. Dabei finden vorwiegend integrative psychotherapeutische Konzepte Anwendung

The Optimality of Single-group Designs for Certain Mixed Models

Optimal design, Mixed model, Random coefficient regression, Approximate design,

Experimental Design for Mixed Models with Application to Population Pharmacokinetic Studies

doctor rerum naturalium (Dr. rer. nat.) genehmigt durch die Fakultät für Mathematik der Otto-von-Guericke-Universität Magdebur

Efficacy and safety of intravitreal aflibercept using a treat-and-extend regimen for neovascular age-related macular degeneration: the ARIES study

PURPOSE Treating neovascular age-related macular degeneration (nAMD) with intravitreal aflibercept (IVT-AFL) treat-and-extend (T&E) can reduce treatment burden. ARIES assessed whether IVT-AFL early-start T&E was noninferior (NI) to late-start T&E. METHODS A randomized, open-label, Phase 3b/4 study that included treatment-naïve patients aged ≥50 years with best-corrected visual acuity (BCVA) 73-25 Early Treatment Diabetic Retinopathy Study letters and active choroidal neovascularization secondary to AMD. Patients received 2mg IVT-AFL at Week (W)0, W4, W8, and W16. At W16 patients were randomized 1:1 to early-start (2W interval adjustments) or late-start T&E (8W intervals until W48 then 2W interval adjustments). Primary endpoint: BCVA change from randomization to W104. RESULTS 271 patients were randomized. Mean (standard deviation [SD]) BCVA at baseline was 60.2 (12.1; early-T&E) and 61.3 (10.8; late-T&E) letters. Mean (SD) BCVA change (W16-104) was -2.1 (11.4) vs -0.4 (8.4) letters (early- vs late-T&E; least-squares mean difference: -2.0; 95% CI: -4.75 to 0.71; P=0.0162 for NI); +4.3 (13.4) vs +7.9 (11.9) letters (W0-104). Mean (SD) number of injections was 12.0 (2.3) vs 13.0 (1.8). From baseline to W104, 93.4% and 96.2% maintained BCVA; mean (SD) central retinal thickness change was -161.6 (135.6) µm and -158.6 (125.1) µm. Last injection interval (W104) was ≥12W for 47.2% and 51.9% of patients. CONCLUSION Outcomes were similar between patients with nAMD treated with an IVT-AFL early- or late-T&E regimen following initial dosing, with one injection difference over 2 years

The Effect of Age, Parity and Body Mass Index on the Efficacy, Safety, Placement and User Satisfaction Associated With Two Low-Dose Levonorgestrel Intrauterine Contraceptive Systems: Subgroup Analyses of Data From a Phase III Trial

<div><p>Objective</p><p>Two low-dose levonorgestrel intrauterine contraceptive systems (LNG-IUSs; total content 13.5 mg [average approx. 8 μg/24 hours over the first year; LNG-IUS 8] and total content 19.5 mg [average approx. 13 μg/24 hours over the first year; LNG-IUS 13]) have previously been shown to be highly effective (3-year Pearl Indices: 0.33 and 0.31, respectively), safe and well tolerated. The present subgroup analyses evaluated whether or not outcomes were affected by parity, age (18–25 vs 26–35 years), or body mass index (BMI, <30 vs ≥30 kg/m²).</p><p>Methods</p><p>Nulliparous and parous women aged 18‒35 years with regular menstrual cycles (21‒35 days) requesting contraception were randomized to 3 years of LNG-IUS 8 or LNG-IUS 13 use.</p><p>Results</p><p>In the LNG-IUS 8 and LNG-IUS 13 groups, 1432 and 1452 women, respectively, had a placement attempted and were included in the full analysis set; 39.2%, 39.2% and 17.1% were 18–25 years old, nulliparous and had a BMI ≥30 kg/m², respectively. Both systems were similarly effective regardless of age, parity or BMI; the subgroup Pearl Indices had widely overlapping 95% confidence intervals. Placement of LNG-IUS 8 and LNG-IUS 13 was easier (p < 0.0001) and less painful (p < 0.0001) in women who had delivered vaginally than in women who had not. The complete/partial expulsion rate was 2.2–4.2% across all age and parity subgroups and higher in parous than in nulliparous women (p = 0.004). The incidence of pelvic inflammatory disease was 0.1–0.6% across all age and parity subgroups: nulliparous and younger women were not at higher risk than parous and older women, respectively. The ectopic pregnancy rate was 0.3–0.4% across all age and parity subgroups. Across all age and parity subgroups, the 3-year completion rate was 50.9–61.3% for LNG-IUS 8 and 57.9–61.1% for LNG-IUS 13, and was higher (p = 0.0001) among older than younger women in the LNG-IUS 8 group only.</p><p>Conclusions</p><p>LNG-IUS 8 and LNG-IUS 13 were highly effective, safe and well tolerated regardless of age or parity.</p><p>Trial Registration</p><p>Clinical trials.gov <a href="https://clinicaltrials.gov/ct2/show/NCT00528112" target="_blank">NCT00528112</a></p></div