Toolkit for simulated commissioning of storage-ring light sources and application to the advanced light source upgrade accumulator

We present a new accelerator toolbox (AT)-based toolkit for simulating the commissioning of light-source storage rings. The toolkit provides a framework for supporting high-level scripts to represent with realism the various procedures (e.g., orbit and optics correction, beam-based alignment, etc.) encountered during commissioning and is designed to mirror as closely as possible the reality as seen from the control room. Emphasis is placed on the inclusion of a comprehensive set of error sources and faithful modeling of beam diagnostics. The toolkit capabilities are demonstrated in an application to the recent design and commissioning studies of the Advanced Light Source Upgrade (ALS-U) Accumulator Ring, a short-time successful commissioning of which will be critical to the overall ALS-U project success

Voluntary Exercise Stabilizes Established Angiotensin II-Dependent Atherosclerosis in Mice through Systemic Anti-Inflammatory Effects.

We have previously demonstrated that exercise training prevents the development of Angiotensin (Ang) II-induced atherosclerosis and vulnerable plaques in Apolipoprotein E-deficient (ApoE-/-) mice. In this report, we investigated whether exercise attenuates progression and promotes stability in pre-established vulnerable lesions. To this end, ApoE-/- mice with already established Ang II-mediated advanced and vulnerable lesions (2-kidney, 1-clip [2K1C] renovascular hypertension model), were subjected to sedentary (SED) or voluntary wheel running training (EXE) regimens for 4 weeks. Mean blood pressure and plasma renin activity did not significantly differ between the two groups, while total plasma cholesterol significantly decreased in 2K1C EXE mice. Aortic plaque size was significantly reduced by 63% in 2K1C EXE compared to SED mice. Plaque stability score was significantly higher in 2K1C EXE mice than in SED ones. Aortic ICAM-1 mRNA expression was significantly down-regulated following EXE. Moreover, EXE significantly down-regulated splenic pro-inflammatory cytokines IL-18, and IL-1β mRNA expression while increasing that of anti-inflammatory cytokine IL-4. Reduction in plasma IL-18 levels was also observed in response to EXE. There was no significant difference in aortic and splenic Th1/Th2 and M1/M2 polarization markers mRNA expression between the two groups. Our results indicate that voluntary EXE is effective in slowing progression and promoting stabilization of pre-existing Ang II-dependent vulnerable lesions by ameliorating systemic inflammatory state. Our findings support a therapeutic role for voluntary EXE in patients with established atherosclerosis

Use of Diabetes Data Management Software Reports by Health Care Providers, Patients With Diabetes, and Caregivers Improves Accuracy and Efficiency of Data Analysis and Interpretation Compared With Traditional Logbook Data: First Results of the Accu-Chek C

We assessed users’ proficiency and efficiency in identifying and interpreting self-monitored blood glucose (SMBG), insulin, and carbohydrate intake data using data management software reports compared with standard logbooks. This prospective, self-controlled, randomized study enrolled insulin-treated patients with diabetes (PWDs) (continuous subcutaneous insulin infusion [CSII] and multiple daily insulin injection [MDI] therapy), patient caregivers [CGVs]) and health care providers (HCPs) who were naïve to diabetes data management computer software. Six paired clinical cases (3 CSII, 3 MDI) and associated multiple-choice questions/answers were reviewed by diabetes specialists and presented to participants via a web portal in both software report (SR) and traditional logbook (TL)  formats. Participant response time and accuracy were documented and assessed. Participants completed a preference questionnaire at study completion. All participants (54 PWDs, 24 CGVs, 33 HCPs) completed the cases. Participants achieved greater accuracy (assessed by percentage of accurate answers) using the SR versus TL formats: PWDs, 80.3 (13.2)% versus 63.7 (15.0)%, P < .0001; CGVs, 84.6 (8.9)% versus 63.6 (14.4)%, P <.0001; HCPs, 89.5 (8.0)% versus 66.4 (12.3)%, P < .0001. Participants spent less time (minutes) with each case using the SR versus TL formats: PWDs, 8.6 (4.3) versus 19.9 (12.2), P < .0001; CGVs, 7.0 (3.5) versus 15.5 (11.8), P = .0005; HCPs, 6.7 (2.9) versus 16.0 (12.0), P < .0001. The majority of participants preferred using the software reports versus logbook data. Use of the Accu-Chek Connect Online software reports enabled  PWDs, CGVs, and HCPs, naïve to diabetes data management software, to identify and utilize key diabetes information with significantly greater  accuracy and efficiency compared with traditional logbook information. Use of SRs was preferred over logbooks.Keywords: diabetes software, insulin, self-management, self-monitoring of blood glucose, SMB

Clinical Implementation of DPYD Pharmacogenetic Testing to Prevent Early-Onset Fluoropyrimidine-Related Toxicity in Cancer Patients in Switzerland.

The implementation of pharmacogenetic testing into clinical practice has been a slow process so far. Here, we review the implementation of pre-treatment testing of dihydropyrimidine dehydrogenase gene (DPYD) risk variants to prevent early-onset fluoropyrimidine (FP)-related toxicity in cancer patients in Switzerland based on data of a large Swiss diagnostic center. In January 2017, the Swiss Federal Office of Public Health introduced the reimbursement of DPYD testing by the compulsory health insurance in Switzerland based on evidence for the clinical relevance of DPYD-risk variants and the cost-effectiveness of pre-treatment testing, and on the availability of international guidelines. However, we did not observe a strong increase in DPYD testing at our diagnostic center from 2017 to 2019. Only a low number of DPYD-testing requests (28-42 per year), concerning mostly retrospective investigations of suspected FP-toxicity, were received. In contrast, we observed a 14-fold increase in DPYD testing together with a strong shift from retrospective to pre-treatment test requests upon the release of recommendations for DPYD testing prior to FP-treatment in April 2020 by the European Medicines Agency. This increase was mainly driven by three geographic regions of Switzerland, where partner institutions of previous research collaborations regarding FP-related toxicity are located and who acted as early-adopting institutions of DPYD testing. Our data suggest the important role of early adopters as accelerators of clinical implementation of pharmacogenetic testing by introducing these policies to their working environment and educating health workers from their own and nearby institutions

Response to ranibizumab therapy in neovascular AMD - an evaluation of good and bad responders

Background: Treatment of neovascular age-related macular degeneration (AMD) with Lucentis® shows a broad spectrum regarding the course of visual acuity (VA). While some patients show a good response (increase in VA), others disclose much less promising results. Patients and Methods: A retrospective data analysis of all eyes treated for neovascular AMD at the University Hospital of Zurich, Switzerland for at least 12 months was carried out. The courses of VA between the 90th (good responders, GR) and the 10th (bad responders, BR) percentiles were compared at 3, 12 and 24 months from baseline. An analysis regarding demographic data, lesion type and size as well as injection frequency and visits was done and predictive factors for GR and BR were evaluated. Results: Marked differences in the course of VA between GR (n = 30) and BR (n = 30) are already observed 3 months from baseline. In GR the gains in VA after 3, 12 and 24 were 15.7 ± 9 letters ETDRS, 25.3 ± 7 and 14.0 ± 14. BR showed a deterioration of 8.3 ± 11 letters ETDRS after 3, 22.1 ± 8 after 12 and 23.6 ± 13 after 24 months. The gender distribution was equal with a higher percentage of female patients (64 % in BR and 66 % in GR). The baseline VA was statistically significantly lower in GR (45.7 ± 10 vs. 55.4 ± 11, p < 0.05) than in BR. No other significant differences in baseline data were found, and no predictor for group membership could be identified. Conclusions: Only the course of VA in the first three months seems to be of value for an estimation of the response to treatment. In the future the response to treatment in the early phase may influence the treatment algorithm and the injection frequency

Data on the Number of Somites Compared with Age in the White Rat

Author Institution: Department of Anatomy, University of California and Ohio State Universit

Reaching absent and refusing individuals during home-based HIV testing through self-testing-at what cost?

Introduction: In the HOSENG trial (NCT03598686), the secondary distribution of oral self-tests for persons absent or refusing to test during a home-based HIV testing campaign in rural Lesotho resulted in an increase in testing coverage of 21% compared to a testing campaign without secondary distribution. This study aims to determine the per patient costs of both HOSENG trial arms. Method: We conducted a micro-costing study to estimate the cost of home-based HIV testing with (HOSENG intervention arm) and without (HOSENG control arm) secondary self-test distribution from a provider's perspective. A mixture of top-down and bottom-up costing was used. We estimated both the financial and economic per patient costs of each possible testing cascade scenario. The costs were adjusted to 2018 US$. Results: The overall provider cost for delivering the home-based HIV testing with secondary distribution was US$36,481 among the 4,174 persons enumerated and 3,094 eligible for testing in the intervention villages compared to US$28,620 for 3,642 persons enumerated and 2,727 eligible for testing in the control. The cost per person eligible for testing was US$11.79 in the intervention vs. US$10.50 in the control. This difference was mainly driven by the cost of distributed oral self-tests. The cost per person tested was, however, lower in intervention villages (US$15.70 vs. US$22.15) due to the higher testing coverage achieved through self-test distribution. The cost per person confirmed new HIV+ was US$889.79 in the intervention and US$753.17 in the control. Conclusion: During home-based HIV testing in Lesotho, the secondary distribution of self-tests for persons absent or refusing to test during the visit reduced the costs per person tested and thus presents a promising add-on for such campaigns. Trial Registration:https://ClinicalTrials.gov/, identifier: NCT03598686

Influence of crack history on the stable tearing behavior of a thin-sheet material with multiple cracks

Fracture tests were conducted on 2.3mm thick, 305mm wide sheets of 2024-T3 aluminum alloy with from one to five collinear cracks. The cracks were introduced (crack history) into the specimens by three methods: saw cutting, fatigue precracking at a low stress range, and fatigue precracking at a high stress range. For the single crack tests, the initial crack history influenced the stress required for the onset of stable crack growth and the first 10mm of crack growth. The effect on failure stress was about 4 percent or less. For the multiple crack tests, the initial crack history was shown to cause differences of more than 20 percent in the link-up stress and 13 percent in failure stress. An elastic-plastic finite element analysis employing the CTOA fracture criterion was used to predict the fracture behavior of the single and multiple crack tests. The numerical predictions were within 7 percent of the observed link-up and failure stress in all the tests

Stable tearing behavior of a thin-sheet material with multiple cracks

Fracture tests were conducted on 2.3mm thick, 305mm wide sheets of 2024-T3 aluminum alloy with 1-5 collinear cracks. The cracks were introduced (crack history) into the specimens by three methods: (1) saw cutting; (2) fatigue precracking at a low stress range; and (3) fatigue precracking at a high stress range. For the single crack tests, the initial crack history influenced the stress required for the onset of stable crack growth and the first 10mm of crack growth. The effect on failure stress was about 4 percent or less. For the multiple crack tests, the initial crack history was shown to cause differences of more than 20 percent in the link-up stress and 13 percent in failure stress. An elastic-plastic finite element analysis employing the Crack Tip Opening Angle (CTOA) fracture criterion was used to predict the fracture behavior of the single and multiple crack tests. The numerical predictions were within 7 percent of the observed link-up and failure stress in all the tests