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To evaluate how hysterectomy performed for benign gynecologic pathologies affects the quality of life and sexual function of patients aged 35 years or younger, and if outcomes differ according to the surgical technique.Seventy-three patients who underwent total laparoscopic hysterectomy (TLH), supracervical laparoscopic hysterectomy (SLH), or vaginal hysterectomy (VH) for benign uterine disorders between April 2014 and June 2020 at the Department of Gynecology and Obstetrics, Saarland University Hospital, Homburg, Germany, were enrolled in this prospective observational cohort study. Quality of life and sexual function were assessed preoperatively and 6 months postoperatively using standardized validated questionnaires: the European Quality of Life Five-Dimension Scale (EQ-5D) and the Female Sexual Function Index (FSFI).Thirty-three (45%) patients underwent TLH, 25 (34%) underwent SLH, and 15 (21%) patients underwent VH. The median preoperative EQ-5D score, FSFI score, and EQ-5D visual analog scale were 0.9 (range 0.62-1), 19.25 (range 2.4-27.4), and 50 (range 0-100); postoperative scores were 1 (range 0.61-1), 24.15 (range 3.9-29.3), and 90 (range 30-100), respectively (P ≤ 0.001). Postoperative scores were significantly higher than preoperative scores, with no significant difference according to the surgical technique.Hysterectomy for benign indication in women aged 35 years or less significantly improved the patients' quality of life and sexual function with no differences regarding the surgical technique.The study was registered in the German trial registry (no. DRKS00005622).

Flowering in day-neutral tobacco (Nicotiana tabacum) plants requires the photoperiod-dependent expression of members of the FLOWERING LOCUS T (FT)-like clade of phosphatidylethanolamine-binding proteins. FT-like floral activators and inhibitors compete for interaction with FD proteins to shift from vegetative to reproductive growth. In the short-day (SD) cultivar Maryland Mammoth (MM), vegetative growth persists under long-day (LD) conditions, generating unusually tall plants. We found that the major floral inducer under long-days (NtFT5) was expressed in MM and that NtFT5 overexpression induced flowering in MM plants under LD conditions. However, sequence analysis revealed a 2-bp deletion near the 3′ end of NtFT5 in MM plants resulting in a truncated C-terminus with an altered amino acid sequence. We found that the truncated NtFT5MM protein was still able to interact with tobacco FD proteins. However, constitutive overexpression under LD conditions in SD-specific flowering tobacco plants showed that NtFT5MM is a weaker floral inducer than NtFT5. Our data indicate that the truncation does not impair the stability of the NtFT5MM protein but affects its binding affinity for NtFD1, probably resulting in the weaker expression of target genes. Our results therefore provide a potential explanation for the MM gigantism phenotype first observed more than 100 years ago.HighlightThe previously unexplained gigantism of Maryland Mammoth tobacco is caused by a truncated major floral activator protein that results in weaker activation and the inability to flower under long-day conditions.

Background: It would be ideal for a non-hyperaemic index to predict fractional flow reserve (FFR) more accurately, given FFR's extensive validation in a multitude of clinical settings. Aims: The aim of this study was to derive a novel non-hyperaemic algorithm based on deep learning and to validate it in an internal validation cohort against FFR. Methods: The ARTIST study is a post hoc analysis of three previously published studies. In a derivation cohort (random 80% sample of the total cohort) a deep neural network was trained (deep learning) with paired examples of resting coronary pressure curves and their FFR values. The resulting algorithm was validated against unseen resting pressure curves from a random 20% sample of the total cohort. The primary endpoint was diagnostic accuracy of the deep learning-derived algorithms against binary FFR ≤0.8. To reduce the variance in the precision, we used a fivefold cross-validation procedure. Results: A total of 1,666 patients with 1,718 coronary lesions and 2,928 coronary pressure tracings were included. The diagnostic accuracy of our convolutional neural network (CNN) and recurrent neural networks (RNN) against binary FFR ≤0.80 was 79.6±1.9% and 77.6±2.3%, respectively. There was no statistically significant difference between the accuracy of our neural networks to predict binary FFR and the most accurate non-hyperaemic pressure ratio (NHPR). Conclusions: Compared to standard derivation of resting pressure ratios, we did not find a significant improvement in FFR prediction when resting data are analysed using artificial intelligence approaches. Our findings strongly suggest that a larger class of hidden information within resting pressure traces is not the main cause of the known disagreement between resting indices and FFR. Therefore, if clinicians want to use FFR for clinical decision making, hyperaemia induction should remain the standard practice.

Zusammenfassung Die fortschreitende Digitalisierung stellt auch die Verbraucherpolitik und den Verbraucherschutz vor Herausforderungen. Gegenstand des vorliegenden Beitrags ist es, diese Herausforderungen zu strukturieren und anhand dreier aktueller Problembereiche zu diskutieren. Ein übergreifendes Ergebnis der Diskussion ist, dass eine zukunftsgerichtete Verbraucherpolitik über den klassischen Verbraucherschutz hinausgehen und eine Perspektivenerweiterung erfahren sollte. Ein wesentliches Element einer in diesem Sinne modernen Verbraucherpolitik wäre es, die Verbraucherinnen und Verbraucher stärker noch als bisher als aktive Akteure des Wirtschaftslebens zu verstehen.

Objective To evaluate family and maternity leave policies and examine the social and professional impacts on female ophthalmologists Participants Participants were recruited through the Women in Ophthalmology online list-serv to complete a survey evaluating maternity leave policies and their impacts. Survey questions were repeated for each birth event after medical school for up to five birth events. Results The survey was accessed 198 times, and 169 responses were unique. Most participants were practicing ophthalmologists (92%), with a minority in residency (5%), in fellowship (1.2%), on disability/leave (0.6%), or retired (0.6%). Most participants (78%) were within their first ten years of practice. Experiences were recorded for each leave event, with 169 responses for the first leave, 120 for the second, 28 for the third, and 2 for the fourth. Nearly half of participants reported the information they received about maternity leave to be somewhat or extremely inadequate (first: 50%; second: 42%; third: 41%). Many reported a greater sense of burnout after returning to work (first: 61%, second: 58%, third: 46%). A minority of participants received full pay during the first through third maternity leave events, 39%, 27%, and 33%, respectively. About a third of participants reported being somewhat or very dissatisfied with their maternity leave experience (first: 42%, second: 35%; third: 27%). Conclusions Female ophthalmologists have varying experiences with maternity leave, but many encounter similar challenges. This study demonstrates that many women receive inadequate information about family leave, desire more weeks of leave, experience a wide variation in pay practices, and lack support for breastfeeding. Understanding the shared experiences of women in ophthalmology identifies areas where improvements are needed in maternity leave practices within the field to create a more supportive environment for physician mothers.

Beauchamp and Childress' definition of autonomous decision-making includes the conditions of intentionality, understanding, and non-control. In genetics, however, a relational conception of autonomy has been increasingly recognized. This article aims to empirically assess aspects of social influence in genetic testing decision-making and to connect these with principlist and relational theories of autonomy. We interviewed 18 adult genetic counsellees without capacity issues considering predictive genetic testing for cancer predisposition for themselves and two counselling physicians in Switzerland. We conducted a qualitative analysis, building on a grounded theory study about predictive genetic testing decision-making. We found that some participants agreed to predictive genetic testing predominantly because relatives wanted them to do it, with some even acting contrary to their own convictions. Others, in contrast, based their decision on purely individualistic reasons but expressed difficulties in explaining their decision to their social environment. Healthcare professionals had a critical influence on decision-making in many cases without being manipulative, as perceived by counsellees. Still, cases of coercion and social pressure occurred within social relationships. In conclusion, predictive genetic testing decision-making includes relational and individualistic aspects, and both are compatible with autonomous decision-making. While the principlist and relational notions of autonomy compete on a theoretical level, they are two sides of the same coin when used as analytical lenses for genetic testing decision-making. Social acceptance of refusal of testing should be improved to mitigate social pressure. Individuals should be encouraged to decide for themselves how much their social environment influences their decision regarding predictive genetic testing.

Background: Newly diagnosed patients with inflammatory bowel disease (IBD) encounter many physical, mental, and social uncertainties. In other chronic diseases, patients having access to disease-specific information and psychological support adhere better to medical regimens. Currently, there is a paucity of data on how newly diagnosed patients with IBD interact with their medical providers. Methods: Patients diagnosed with IBD within 5 years completed a series of questionnaires related to heath-related quality of life (HRQoL), disease activity, health education resources, medical provider relationship, and psychological support. Results: A total of 89 patients were included in the study. IBD activity correlated with disease-specific quality of life (r=−0.69, p

Can imaging provide sufficient risk stratification to warrant revascularization of a stable plaque with negative fractional flow reserve (FFR)? Prophylactic stenting could at best be applied selectively since the composite group of FFR-negative lesions has a death or myocardial infarction rate of approximately 1%/year or less but modern stents have a rate of 2% to 3.5%/year. Because vulnerable features exist in a minority of lesions, at least 9,000 patients must be screened in order to enroll a cohort with sufficient risk. While several ongoing randomized trials are testing the concept of plaque sealing in FFR-negative lesions, preventive stenting depends on such a small effect that sample sizes to validate or refute its benefit become prohibitive. Since FFR provides a quantitative, straightforward, and reproducible metric of plaque vulnerability and burden without the need for or expense of additional catheter devices, intracoronary imaging cannot meaningfully guide prophylactic stenting when faced with a negative FFR.

Background Many patients with glioma suffer from deficits in executive functioning (EF), regardless of tumor location and size. While some patients experience improving EF after tumor resection, others deteriorate over time. This variability in cognitive trajectories is still poorly understood, but neuroscientific approaches that view the brain as a network may bear correlative and predictive value in this respect. Particularly integrative network connectivity of the fronto-parietal network are crucial for EF, but studies so far have only investigated isolated neural frequency bands of interest. Here, we synergize fronto-parietal network connectivity across frequency bands and test its explanatory power for EF at diagnosis and 1 year after tumor resection. Material and Methods Patients with diffuse glioma (n=37) underwent neuropsychological assessments, including three tests for EF, and resting-state magnetoencephalography (MEG) at both time points. Patients’ EF performance was standardized to z-scores using validated norm scores, adjusting for age, sex and education. MEG was source-reconstructed using patients’ MRI in combination with a beamformer approach and time series were filtered into six classical frequency bands. Band-specific functional connectivity between 78 cortical regions was estimated, after which an interconnected multilayer, multi-frequency network was created per patient. Multilayer centrality was then calculated as a measure of integrative network connectivity per region, and averaged over all fronto-parietal network regions to yield a single value reflecting integrative, multi-frequency network connectivity per patient at each time point. Results At diagnosis, eight patients had z-scores Conclusion Our results establish a significant relationship between poorer and decreasing EF with lower and decreasing multilayer, multi-frequency integrative connectivity of the fronto-parietal network in glioma patients. Studies with larger and more homogeneous samples may further explore the relevance of this multilayer approach in understanding and particularly predicting postoperative decline in EF in these patients, as our sample was characterized by large heterogeneity in cognitively relevant patient and tumor characteristics.

The design of service robots is typically treated as a mechatronic design problem aimed at implementation of its core technical functionalities. Intuitive operation and usability are ignored. We developed a trash-picking service robot with a strong focus on human-robot interaction (HRI) using the double diamond framework. The HRI-focussed hardware features were successfully implemented and tested. The results were shown to satisfy the ease of operation and usability requirements set as development goals for the robot.

ObjectiveThe prognostic importance of a coronary stenosis depends on its functional severity and its depending myocardial mass. Functional severity can be assessed by fractional flow reserve (FFR), estimated non-invasively by a specific validated CT algorithm (FFRCT). Calculation of myocardial mass at risk by that same set of CT data (CTmass), however, has not been prospectively validated so far. The aim of the present study was to compare relative territorial-based CTmass assessment with relative flow distribution, which is closely linked to true myocardial mass.MethodsIn this exploratory study, 35 patients with (near) normal coronary arteries underwent CT scanning for computed flow-based CTmass assessment and underwent invasive myocardial perfusion measurement in all 3 major coronary arteries by continuous thermodilution. Next, the mass and flows were calculated as relative percentages of total mass and perfusion.ResultsThe mean difference between CTmass per territory and invasively measured myocardial perfusion, both expressed as percentage of total mass and perfusion, was 5.3±6.2% for the left anterior descending territory, −2.0±7.4% for the left circumflex territory and −3.2±3.4% for the right coronary artery territory. The intraclass correlation between the two techniques was 0.90.ConclusionsOur study shows a close relationship between the relative mass of the perfusion territory calculated by the specific CT algorithm and invasively measured myocardial perfusion. As such, these data support the use of CTmass to estimate territorial myocardium-at-risk in proximal coronary arteries.

Novel phospholipid (PL)-cyclosporine conjugates were prepared and studied as potential prodrugs for inflammatory bowel disease (IBD). Our approach relies on phospholipase A2 (PLA2 ), which is overexpressed in the inflamed intestinal tissues, as the prodrug activator to potentially release cyclosporine at the site of inflammation. PL-cyclosporine prodrug conjugates with methylene linkers of various lengths between the sn-2 position of the PL and cyclosporine were synthesized and evaluated for in vitro activation. Surprisingly, despite previous work indicating that conjugates with six methylene linkers between the lipid and drug would suffer rapid enzymatic hydrolysis, with cyclosporine this was not observed. However, compounds with longer linkers (n=10, 12 methylene units) display complete release of the drug by PLA2 -catalyzed hydrolysis, thus demonstrating the importance and profound impact of structural fine-tuning. This study represents a proof-of-concept for our hypothesis and a first step towards a truly targeted IBD treatment with cyclosporine that could be administered throughout the GI tract.

Introduction: The social impact of inflammatory bowel disease (IBD) on student transition to college is significant, yet poorly understood. Methods: Two 90-min focus groups (FGs) were conducted with eight student-patients with IBD. Reflective journals were used to corroborate, elaborate, or challenge emergent FG findings. Results: Six themes emerged: (1) transitioning to college, (2) interacting with physicians, (3) affecting social life, (4) managing the disease by yourself and through support, (5) coping strategies, and (6) facing disease challenges. These themes remained relevant in the reflective writings. Analysis of serial journal entries showed that students' social life and engagement in coursework was affected 66% and 54% of the time, respectively. Conclusion: Our findings offer guidance for improving students' college success, quality of care, and enhancing physician–patient interactions. Students with IBD have a disability that may not be obvious or visible. They require specific support to help them transition and succeed in college.

Objectives We conducted a review and meta-analysis of published data to compare revascularization to deferral strategy for coronary lesions with grey zone fractional flow reserve (FFR). Background Optimal treatment for coronary stenoses with FFR values between 0.75 and 0.80, the so-called grey zone, remains a matter of debate. Methods We included all studies evaluating revascularization versus deferral for lesions with grey zone FFR. The primary outcome was study-defined major adverse cardiac events (MACE). Secondary outcomes were the composite of death or MI and target vessel revascularization (TVR). A total of 2362 patients were included, of whom 1181 underwent revascularization (revascularization group) and 1181 received medical treatment only (deferral group). Results After a mean follow-up period of 2.4 years, no difference was found for the primary outcome of the study-defined MACE between the two groups [RR = 1.33 (0.73–2.44), p = 0.35]. In addition, there was no difference for the secondary outcomes of death or MI and TVR between the two groups [RR = 1.39 (0.56–3.47), p = 0.48 and RR = 1.49 (0.89–2.51), p = 0.13, respectively]. Conclusions In this meta-analysis revascularization of coronary stenoses with grey zone FFR showed no advantage over a deferral strategy in terms of study-defined MACE. Case by case judgment should be implemented to guide treatment in this special subset of patients.

Objectives: This study aimed to prospectively investigate intra-aortic balloon pump counterpulsation (IABP) support in large myocardial infarction complicated by persistent ischemia after primary percutaneous coronary intervention (PCI). Background: Use of IABP is suggested to be effective by increasing diastolic aortic pressure, thereby improving coronary blood flow. This can only be expected with exhausted coronary autoregulation, typical in acute myocardial infarction complicated by persistent ischemia. In this situation, augmented diastolic pressure is expected to increase myocardial oxygenation. Methods: One hundred patients with large STEMI complicated by persistent ischemia after primary PCI were randomized to treatment with or without IABP therapy on top of standard care. IABP support was initiated following primary PCI, immediately after inclusion. Primary end point was all-cause mortality, need for (additional) mechanical hemodynamic support, or readmission for heart failure within 6 months. Results: Mean age was 63 ± 10 years, 76% were male. Mean systolic and diastolic blood pressure were 120 ± 25 mmHg and 73 ± 17 mmHg. Mean heart rate was 75 ± 18 mmHg. Before PCI, mean summed ST-deviation was 21 ± 8 mm with only minimal ST-resolution after PCI. One patient in the IABP group reached the primary end point versus four patients in the control group (2% vs. 8%; p = 0.16). After primary PCI, resolution of ST-deviation was significantly more pronounced in the IABP group (73 ± 17%) compared to the control group (56 ± 26%; p < 0.01). Conclusions: In this pilot study, in patients with large STEMI and persistent ischemia after primary PCI, use of IABP showed a nonsignificant decrease in mortality, necessity for (additional) mechanical hemodynamic support or readmission for heart failure at 6 months, and resulted in more rapid ST-resolution.

Purpose This study seeks to identify the characteristics and attitudes of faculty in US medical colleges who are at risk of leaving their institution. Methods This research leverages data from the AAMC StandPoint Faculty Engagement Survey administered to 37,779 faculty representing 36 institutions participating during 2013-2016. Univariate and multivariable robust logistic regression models were used to assess predictors of the intent to leave based on the question: "Do you plan to leave this medical school in the next 1-2 years?". Results Thirty percent (n=5559/18,475) of faculty responded that they were considering leaving their institution. Thirty-one percent of female faculty vs 29% of male faculty expressed an intent to leave. At-risk faculty were likely to be at junior faculty rank and at their institutions for 6-15 years vs other time periods (OR=1.16; p≤0.001). Having an administrative title (OR=0.72; p≤0.001) and receiving formal mentorship (OR=0.65; p≤0.001) were protective. Finally, faculty answering "disagree" or "strongly disagree" to any one of these StandPoint Survey questions were at > 6 fold risk of expressing an intent to leave: 1) I am satisfied with my opportunities for professional development, 2) I feel appreciated by my supervisor, 3) My day-to-day activities give me a sense of accomplishment. Conclusion Faculty expressing an intent to leave their institution have an identifiable profile. Top concerns of at-risk faculty relate to supervisory relationships and growth opportunities rather than compensation or governance. Institutional leaders should consider these factors in the development of a proactive strategy to retain talented faculty.

The timely revascularization of an occluded coronary artery is the cornerstone of treatment in patients with ST-elevation myocardial infarction (STEMI). As essential as this treatment is, it can also cause additional damage to cardiomyocytes that were still viable before reperfusion, increasing infarct size. This has been termed “myocardial reperfusion injury”. To date, there is still no effective treatment for myocardial reperfusion injury in patients with STEMI. While numerous attempts have been made to overcome this hurdle with various experimental therapies, the common denominator of these therapies is that, although they often work in the preclinical setting, they fail to demonstrate the same results in human trials. Hypothermia is an example of such a therapy. Although promising results were derived from experimental studies, multiple randomized controlled trials failed to do the same. This review includes a discussion of hypothermia as a potential treatment for myocardial reperfusion injury, including lessons learned from previous (negative) trials, advanced techniques and materials in current hypothermic treatment, and the possible future of hypothermia for cardioprotection in patients with STEMI.

Oral medication with activity specifically at the inflamed sites throughout the gastrointestinal tract and limited systemic exposure would be a major advance in our therapeutic approach to inflammatory bowel disease (IBD). For this purpose, we have designed a prodrug by linking active drug moiety to phospholipid (PL), the substrate of phospholipase A

Since the beginning of the COVID-19 pandemic, research has explored various aspects of face mask use. While most of the research explores their effectiveness to prevent the spread of the virus, a growing body of literature has found that using face masks also has social meaning. But what social meaning does it have, and how does this meaning express itself in people's practice? Based on 413 qualitative interviews with residents in five European countries (Austria, Belgium, Germany, Ireland, and Switzerland), we found that the meanings of face masks have changed drastically during the first months of the pandemic. While in spring 2020 people wearing them had to fear stigmatization, in autumn of 2020 not wearing masks was more likely to be stigmatized. Throughout the first year of the pandemic, we found that mask wearing had multiple and partly seemingly contradictory meanings for people. They were perceived as obstacles for non-verbal communication, but also a way to affirm friendships and maintain social contacts. They also signaled specific moral or political stances on the side of face mask wearers and non-wearers alike, expressed their belonging to certain communities, or articulated concern. In sum, our findings show how face masks serve as scripts for people to navigate their lives during the COVID-19 pandemic. We conclude that public and political discussions concerning face masks should include not only evidence on the epidemiological and infectiological effects of face masks, but also on their social meanings and their social effects. ispartof: FRONTIERS IN PUBLIC HEALTH vol:10 ispartof: location:Switzerland status: published

Background: In contrast to neighboring countries, German and Swiss authorities refrained from general curfews during the first pandemic wave in spring 2020, calling for solidarity and personal responsibility instead. Using a qualitative methodology, this study aims to explore why people in Germany and Switzerland were motivated to comply with policy measures during the first wave of the coronavirus disease 2019 (COVID-19) pandemic, and what factors hindered or limited their motivation. While quantitative surveys can measure the level of compliance, or broadly ask what motives people had for compliance, we here strive to explain why and how these motives lead to compliance. Methods: This publication has been made possible by the joint work of the members of the "Solidarity in times of pandemics" (SolPan) research commons. Seventy-seven semi-structured qualitative interviews were conducted with members of the general public in Germany (n = 46) and the German-speaking part of Switzerland (n = 31) in April 2020. Interviews were transcribed and analyzed following a grounded theory approach. Results: Three themes were identified that summarize factors contributing to compliant or noncompliant behavior. (1) Social cohesion was, on the one hand, an important motivator for compliance, but at the same time related to conflicting needs, illustrating the limits of compliance. (2) Consequences were considered on both the individual level (eg, consequences of individual infection) and societal level (eg, the societal and economic consequences of restrictions). (3) While for some participants following the rules was perceived as a matter of principle, others stressed the importance of making their own risk assessment, which was often associated with with a need for evidence on the effectiveness and reasons behind measures. Conclusion: A variety of motives contribute to COVID-19 related compliance. Authorities should seek to address these multi-faceted aspects to support motivation for compliance in a large proportion of the population.

An alternative method is presented to numerically compute interior elastic transmission eigenvalues for various domains in two dimensions. This is achieved by discretizing the resulting system of boundary integral equations in combination with a non-linear eigenvalue solver. Numerical results are given to show that this new approach can provide better results than the finite element method when dealing with general domains.

Purpose Recent data suggest that individual morphologic factors should be respected to restore preoperative patellofemoral alignment and thus reduce the likelihood of anterior knee pain. The goal of this study was to investigate the effect of excessive femoral torsion (FT) on clinical outcome of TKA. Methods Patients who underwent TKA and complete preoperative radiographic evaluation including a long-leg radiograph and CT scan were included. 51 patients showed increased FT of > 20° and were matched for age/sex to 51 controls (FT Results There was no significant difference between clinical scores two years after surgery between patients with normal and excessive FT (n.s.). Kujala score was 64.3 ± 16.7 versus 64.8 ± 14.4 (n.s.), and patellofemoral score for TKA was 74.3 ± 21 versus 78.5 ± 20.7 (n.s.) for increased FT group and control group, respectively. There was no correlation between preoperative FT and clinical scores. Other radiographic parameters were similar between both groups. No correlations between clinical outcomes and preoperative/postoperative frontal leg axis or total leg axis correction were found (n.s.). Conclusion If the leg axis deformity is corrected to a roughly neutral alignment during cemented TKA, including patellar denervation, then excessive FT was not associated with patellofemoral pain or instability. Level of evidence. Prospective comparative study, level II.

BACKGROUND: Patients with three-vessel coronary artery disease have been found to have better outcomes with coronary-artery bypass grafting (CABG) than with percutaneous coronary intervention (PCI), but studies in which PCI is guided by measurement of fractional flow reserve (FFR) have been lacking.METHODS: In this multicenter, international, noninferiority trial, patients with three-vessel coronary artery disease were randomly assigned to undergo CABG or FFR-guided PCI with current-generation zotarolimus-eluting stents. The primary end point was the occurrence within 1 year of a major adverse cardiac or cerebrovascular event, defined as death from any cause, myocardial infarction, stroke, or repeat revascularization. Noninferiority of FFR-guided PCI to CABG was prespecified as an upper boundary of less than 1.65 for the 95% confidence interval of the hazard ratio. Secondary end points included a composite of death, myocardial infarction, or stroke; safety was also assessed.RESULTS: A total of 1500 patients underwent randomization at 48 centers. Patients assigned to undergo PCI received a mean (±SD) of 3.7±1.9 stents, and those assigned to undergo CABG received 3.4±1.0 distal anastomoses. The 1-year incidence of the composite primary end point was 10.6% among patients randomly assigned to undergo FFR-guided PCI and 6.9% among those assigned to undergo CABG (hazard ratio, 1.5; 95% confidence interval [CI], 1.1 to 2.2), findings that were not consistent with noninferiority of FFR-guided PCI (P = 0.35 for noninferiority). The incidence of death, myocardial infarction, or stroke was 7.3% in the FFR-guided PCI group and 5.2% in the CABG group (hazard ratio, 1.4; 95% CI, 0.9 to 2.1). The incidences of major bleeding, arrhythmia, and acute kidney injury were higher in the CABG group than in the FFR-guided PCI group.CONCLUSIONS: In patients with three-vessel coronary artery disease, FFR-guided PCI was not found to be noninferior to CABG with respect to the incidence of a composite of death, myocardial infarction, stroke, or repeat revascularization at 1 year. (Funded by Medtronic and Abbott Vascular; FAME 3 ClinicalTrials.gov number, NCT02100722.).

Laser-based direct energy deposition (L-DED) with blown powder enables the simultaneous or sequential processing of different powder materials within one component and, thus, offers the possibility of additive multimaterial manufacturing. Therefore, the process allows a spatially resolved material allocation and fabrication of sharp or even graded material transitions. Within this contribution, the latest results from two major research fields in multimaterial L-DED—(I) automation and (II) rapid alloy development of high entropy alloys (HEAs) by in situ synthesis—shall be presented. First, an automated multimaterial deposition process was developed, which enables the automated manufacturing of three-dimensionally graded specimens. For this, a characterization of the deposition system regarding powder feeding dynamics and resulting powder mixtures in the process zone was conducted. The obtained system characteristics were used to achieve a three-dimensional deposition of specified powder mixtures. The fabricated specimens were analyzed by energy-dispersive x-ray spectroscopy, scanning electron microscopy, and micro hardness measurement. The research demonstrates the increasing readiness of L-DED for the fabrication of multimaterial components. Second, the latest results from rapid alloy development for HEAs by DED are presented. By the simultaneous usage of up to four powder feeders, a vast range of alloy compositions within the Al–Ti–Co–Cr–Fe–Ni HEA system was investigated. For this, tailored measurement systems such as an in-house developed powder sensor were beneficially used. The study shows the influence of a variation of Al on the phase formation and resulting mechanical properties and demonstrates the potential of L-DED for reducing development times for new alloys. Validerad;2023;Nivå 2;2023-01-23 (joosat);Funder: Sächsische Aufbaubank—Förderbank—(SAB);Licens fulltext: CC BY License

To improve oral reading fluency rate and promote its generalization to unpracticed texts, this study investigated a Varied Practice approach that involved passages with a high proportion of overlapping words (M = 85% unique word overlap). Fourth graders were randomly assigned either to the Varied Practice treatment (n = 405), where they read three different passages one time each, or the Repeated Reading comparison (n = 422), in which they read the same passage three times each. Both groups read with a partner for about 20 min, 3–4 times per week, over an average 12 weeks (30 total sessions). Results indicated that students in Varied Practice demonstrated significantly better fluency outcomes than students in Repeated Reading, but both groups demonstrated growth near the 90th percentile. Results of a quantile regression revealed that low-to-middle achievers benefited from Varied Practice the most. Overall, the findings suggest fluency approaches rooted in statistical learning hold promise as an alternative to approaches focused on practicing words in redundant contexts.

Anterior knee pain (AKP) is common following total knee arthroplasty. The tibial tuberosity trochlear groove distance (TTTG) influences patellofemoral joint loading in the native knee. Increased TTTG may lead to maltracking of the patella and anterior knee pain. The purpose of this study was to investigate potential changes in TTTG following total knee arthroplasty (TKA).TTTG was measured on preoperative CT data on a consecutive series of patients scheduled to receive TKA with patient-specific instrumentation, and compared to a computer simulation of the postoperative TTTG. Preoperative TTTG was measured with a 3D planning software in 250 knees. The postoperative result was simulated and TTTG measured within the software. Three different groups were analysed: neutral (180° ± 3) (n = 50), valgus ( 190°) (n = 100), and varus ( 170°) (n = 100).Median preoperative to simulated postoperative TTTG decreased from 15.0 [interquartile range (IQR) 6.0] mm to 6.5 (IQR 5.0) mm for all axes combined. A significant postoperative reduction of TTTG was found in each group (p 0.001). The mean change in TTTG did not differ significantly between the groups [- 8.8 (IQR 5.5) mm neutral, - 8.3 (IQR 7.0) mm valgus, - 7.5 (IQR 5.8) mm varus, p = 0.223].This computer-based study suggests that mechanically aligned TKA significantly decreases TTTG distance in neutral, valgus and varus knees, assuming that the postoperative result coincides with the preoperative planning. Further study is warranted to evaluate the clinical relevance of this finding.

Therapeutics with activity specifically at the inflamed sites throughout the gastrointestinal tract (GIT) would be a major advance in our therapeutic approach to inflammatory bowel disease (IBD). We aimed to develop the prodrug approach that can allow such site-specific drug delivery. Currently, using cyclosporine as a drug of choice in IBD is limited to the most severe cases due to substantial systemic toxicities and narrow therapeutic index of this drug. Previously, we synthesized a series of a phospholipid-linker-cyclosporine (PLC) prodrugs designed to exploit the overexpression of phospholipase A

In acute myocardial infarction (AMI), myocardial reperfusion injury may undo part of the recovery after revascularization of the occluded coronary artery. Selective intracoronary hypothermia is a novel method aimed at reducing myocardial reperfusion injury, but its presumed protective effects in AMI still await further elucidation. This proof-of-concept study assesses the potential protective effects of selective intracoronary hypothermia in an ex-vivo, isolated beating heart model of AMI. In four isolated Langendorff perfused beating pig hearts, an anterior wall myocardial infarction was created by inflating a balloon in the mid segment of the left anterior descending (LAD) artery. After one hour, two hearts were treated with selective intracoronary hypothermia followed by normal reperfusion (cooled hearts). In the other two hearts, the balloon was deflated after one hour, allowing normal reperfusion (control hearts). Biopsies for histologic and electron microscopic evaluation were taken from the myocardium at risk at different time points: before occlusion (t = BO); 5 minutes before reperfusion (t = BR); and 10 minutes after reperfusion (t = AR). Electron microscopic analysis was performed to evaluate the condition of the mitochondria. Histological analyses included evaluation of sarcomeric collapse and intramyocardial hematoma. Electron microscopic analysis revealed intact mitochondria in the hypothermia treated hearts compared to the control hearts where mitochondria were more frequently damaged. No differences in the prespecified histological parameters were observed between cooled and control hearts at t = AR. In the isolated beating porcine heart model of AMI, reperfusion was associated with additional myocardial injury beyond ischemic injury. Selective intracoronary hypothermia preserved mitochondrial integrity compared to nontreated controls.

A Técnica do Inseto Estéril (TIE) utiliza métodos que permitem o emprego de uma espécie predadora para o controle da praga alvo. Para tanto, ocorre a multiplicação em massa de determinada praga em meio artificial, esterilização e liberação dos insetos tratados em dado ambiente. Desta forma, ao cruzarem com indivíduos selvagens se obtém gerações estéreis comprometendo o potencial produtivo da praga. Para o sucesso da técnica é importante a adoção de métodos de esterilização que sejam eficientes e não provoquem alterações nos parâmetros biológicos dos organismos. O objetivo desta revisão consistiu em apresentar informações sobre o uso da TIE, especialmente os principais métodos de esterilização utilizados. Com base na análise das publicações, observou-se que os métodos químicos e por radiação ionizante se destacam. No primeiro caso são empregados compostos químicos diretamente no inseto ou incorporados ao alimento. Já a radiação ionizante consiste na aplicação, na maioria dos casos, de raio-X ou radiação gama para indução de mutações letais dominantes capazes de comprometer a capacidade de reprodução dos insetos. O desenvolvimento da técnica, embora não seja passível de aplicação para todos os insetos, representa uma excelente ferramenta para programas de controle de determinadas pragas em diversos países, entre eles o Brasil. Diante da relevância da técnica e da complexidade envolvida, considera-se, após o desenvolvimento da presente revisão, que a TIE no Brasil requer maiores estudos e investimentos, a fim de que os benefícios já obtidos se estenda para um maior número de espécies causadoras de danos.

No cultivo do morangueiro o uso de mudas de qualidade representa a obtenção de plantas mais responsivas as práticas de manejo adotados ao longo do cultivo, mais produtivas e de melhor estado fitossanitário. A produção de mudas ocorre a partir do enraizamento de estolões, podendo ser produzidas mudas de raiz nua ou de torrão. Neste último caso, o substrato é fundamental para o bom desenvolvimento das plantas, gerando mudas com adequado enraizamento e elevado acúmulo de reservas na coroa e na raiz. Este trabalho teve o objetivo de analisar o crescimento de mudas de morangueiro cultivar Pircinque cultivados nos substratos de casca de arroz e Pindstrup®, isolados ou combinados em diferentes proporções. Para tanto, foi conduzido um experimento em casa de vegetação com os seguintes tratamentos: T1) 100% casca de arroz; T2) 75% casca de arroz e 25 % Pindstrup®; T3) 50% casca de arroz e 50% Pindstrup®; T4) 25% casca de arroz e 75% Pindstrup® e T5) 100% Pindstrup®. Foram avaliados os atributos de diâmetro de coroa (mm), número (und), comprimento (cm) e massa fresca de raiz (g) aos 14, 21 e 28 dias após a implantação do experimento. Os resultados obtidos demostraram que a combinação de 25% de casca de arroz e 75% de Pindstrup® possibilitou uma proporção mais adequada entre os substratos, pois, de modo geral, a mistura apresentou os melhores resultados considerando as variáveis analisadas, não diferindo estatisticamente, no entanto, do substrato com 75% casca de arroz e 25 % Pindstrup® para o atributo de comprimento de raiz.

A reason for the slow adoption of digital twins in industry is a lack of trust in the concept and between the stakeholders involved. This paper presents a Trust Framework for Digital Twins based on a literature review and an interview study, including seven recommendations: (1) explain your twin, (2) create a common incentive, (3) make only one step at a time, (4) ensure IP protection and IT security, (5) prove your quality, (6) ensure a uniform environment, and (7) document thoroughly. Together with 20 concrete measures it supports practitioners in improving trust in their Digital Twin.

In top-down design, optimal component requirements are difficult to derive, as the feasible components that satisfy these requirements are yet to be designed and hence unknown. Meta models that provide feasibility and mass estimates for component performance are used for optimal requirement decomposition in an existing approach. This paper (1) extends its applicability adapting it to varying design domains, and (2) increases its efficiency by active-learning. Applying it to the design of a robot arm produces a result that is 1% heavier than the reference obtained by monolithic optimization.

A sophisticated bifunctional catalyst bearing a copper(I)/N-heterocyclic carbene and a guanidine organocatalyst has been prepared by a mechanochemical synthesis in a ball mill. This approach circumvents commonly employed silver(I) complexes which are associated with significant and undesired waste formation. Due to the bifunctional nature of the desired complex, earlier mechanochemical conditions were not applicable and a new protocol based on cheap and readily available K3PO4 as base has been developed. The resulting complex has been shown to be active in a variety of reduction/hydrogenation transformations employing dihydrogen as terminal reducing agent.

Employing a bifunctional catalyst based on a copper(I)/NHC complex and a guanidine organocatalyst, catalytic ester reductions to alcohols with H