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Background Data on the prognostic value of left ventricular (LV) morphological and functional parameters including LV rotation in patients with dilated cardiomyopathy (DCM) using cardiovascular magnetic resonance (CMR) are currently scarce. In this study, we assessed the prognostic value of global longitudinal strain (GLS), global circumferential strain (GCS), global radial strain (GRS) and LV torsion using CMR feature tracking (FT). Methods CMR was performed in 350 DCM patients and 70 healthy subjects across 5 different European CMR Centers. Myocardial strain parameters were retrospectively assessed from conventional balanced steady-state free precession cine images applying FT. A combined primary endpoint (cardiac death, heart transplantation, aborted sudden cardiac death) was defined for the assessment of clinical outcome. Results GLS, GCS, GRS and LV torsion were significantly lower in DCM patients than in healthy subjects (all p Conclusion LV strain assessed with CMR FT has a high prognostic value in patients with DCM, surpassing routine and dedicated functional parameters. Thus, CMR strain imaging may contribute to the improvement of risk stratification in DCM.

Objectives The purpose of this study was to evaluate the diagnostic accuracy of a fast, needle-free test for myocardial ischemia using fast Strain-ENCoded (fSENC) cardiovascular MR (CMR) after a hyperventilation/breath-hold maneuver (HVBH). Background Myocardial stress testing is one of the most frequent diagnostic tests performed. Recent data indicate that CMR first-pass perfusion outperforms other modalities. Its use, however, is limited by the need for both, a vasodilatory stress and the intravenous application of gadolinium. Both are associated with added cost, safety concerns, and patient inconvenience. The combination of 2 novel CMR approaches, fSENC, an ultrafast technique to visualize myocardial strain, and HVBH, a physiological vasodilator, may overcome these limitations. Methods Patients referred for CMR stress testing underwent an extended protocol to evaluate 3 different tests: 1) adenosine-perfusion; 2) adenosine-strain; and 3) HVBH-strain. Diagnostic accuracy was assessed using quantitative coronary angiography as reference. Results A total of 122 patients (age 66 ± 11years; 80% men) suspected of obstructive coronary artery disease were enrolled. All participants completed the protocol without significant adverse events. Adenosine-strain and HVBH-strain provided significantly better diagnostic accuracy than adenosine-perfusion, both on a patient level (adenosine-strain: sensitivity 82%, specificity 83%; HVBH-strain: sensitivity 81%, specificity 86% vs. adenosine-perfusion: sensitivity 67%, specificity 92%; p Conclusions HVBH-strain has a high diagnostic accuracy in detecting significant coronary artery stenosis. It is not only significantly faster than any other method but also neither requires contrast agents nor pharmacological stressors.

Background Older, compared with younger, patients with treatment-resistant depression (TRD) typically have lower response and remission rates with poorer tolerability to antidepressant treatment. This post-hoc analysis compared outcomes following treatment with esketamine nasal spray (ESK) between younger (18-64 years) and older (≥65 years) patients with TRD. Methods SUSTAIN-2, an up to 1-year open-label safety and efficacy study of ESK plus an oral antidepressant, included patients with TRD either directly enrolled (≥18-year) or transferred from a phase 3 double-blind study, TRANSFORM-3 (≥65-year). Patients were treated in two phases: 4-week induction and 48-week optimization/maintenance. Results Younger (n = 624) and older (n = 178) patients had similar baseline characteristics except for hypertension history (21.5% versus 48.3%, respectively). Patients (younger versus older) had similar mean baseline Montgomery-Asberg Depression Rating Scale (MADRS) total scores and mean (SD) reductions in MADRS total scores for induction (-18.0 [7.19] versus -18.1 [9.37]; p = 0.492 [t = 0.69, df = 701]) and optimization/maintenance (week 12) (-19.9 [7.03] versus -22.2 [9.50]; p = 0.265 [t = -1.12, df = 3470]) phases. Treatment-emergent adverse events (TEAEs) reported in younger versus older patients, respectively, were: induction, 86.1% versus 74.8%; optimization/maintenance, 86.8% versus 81.0%; serious TEAEs: induction, 2.2% versus 1.9%; optimization/maintenance, 6.7% versus 4.8%; TEAEs of increased blood pressure: induction, 6.9% versus 6.5%; optimization/maintenance, 7.1% versus 9.5%; and falls: induction, 0.3% versus 0.6%; optimization/maintenance, 0.2% versus 0.8%. Cognitive tests did not show clinically meaningful differences between the age groups. Conclusions Although limited by the open-label design of SUSTAIN-2, this post-hoc analysis showed generally comparable improvement in depression between ESK-treated younger and older adult patients with TRD, with consistent safety outcomes.

Background: Plasma proteins are critical mediators of cardiovascular processes and are the targets of many drugs. Previous efforts to characterize the genetic architecture of the plasma proteome have been limited by a focus on individuals of European descent and leveraged genotyping arrays and imputation. Here we describe whole genome sequence analysis of the plasma proteome in individuals with greater African ancestry, increasing our power to identify novel genetic determinants. Methods: Proteomic profiling of 1301 proteins was performed in 1852 Black adults from the Jackson Heart Study using aptamer-based proteomics (SomaScan). Whole genome sequencing association analysis was ascertained for all variants with minor allele count ≥5. Results were validated using an alternative, antibody-based, proteomic platform (Olink) as well as replicated in the Multi-Ethnic Study of Atherosclerosis and the HERITAGE Family Study (Health, Risk Factors, Exercise Training and Genetics). Results: We identify 569 genetic associations between 479 proteins and 438 unique genetic regions at a Bonferroni-adjusted significance level of 3.8×10 -11 . These associations include 114 novel locus-protein relationships and an additional 217 novel sentinel variant-protein relationships. Novel cardiovascular findings include new protein associations at the APOE gene locus including ZAP70 (sentinel single nucleotide polymorphism [SNP] rs7412-T, β=0.61±0.05, P =3.27×10 -30 ) and MMP-3 (β=-0.60±0.05, P =1.67×10 -32 ), as well as a completely novel pleiotropic locus at the HPX gene, associated with 9 proteins. Further, the associations suggest new mechanisms of genetically mediated cardiovascular disease linked to African ancestry; we identify a novel association between variants linked to APOL1-associated chronic kidney and heart disease and the protein CKAP2 (rs73885319-G, β=0.34±0.04, P =1.34×10 -17 ) as well as an association between ATTR amyloidosis and RBP4 levels in community-dwelling individuals without heart failure. Conclusions: Taken together, these results provide evidence for the functional importance of variants in non-European populations, and suggest new biological mechanisms for ancestry-specific determinants of lipids, coagulation, and myocardial function.

Large-scale thermal energy storage (TES) emerges as key for the expansion of renewables-based district heating (R-DH) as it is able to bridge the seasonal gap between the heating demand and the availability of renewable energy resources (e.g. solar energy). This work develops a framework for techno-economic analysis considering several key performance indicators (e.g. energy efficiency, exergy efficiency). As TES systems integrated in DH are typically stratified, the work also examines the TES by means of stratification number and efficiency. The economic feasibility of the TES options is examined via the TES specific investment cost. Then, the work recommends the levelized cost of stored heat (LCOS) as a practical measure for the TES techno-economic feasibility. The outcomes show that the tank has higher performance in terms of efficiency indicators (energy and exergy) and stratification measures, but it is characterized with high specific cost. Yet, the tank LCOS is lower compared to that of the shallow pit due to its low performance and despite its low specific cost. Thus, in order to take advantage of the tank's better performance and shallow pit's lower specific cost, the work proposes a third TES geometry called as hybrid TES that combines both tank and shallow pit. The results reveal the potential of this geometry as it arises as a promising option. Furthermore, the results indicate that the transition to low-temperature R-DH brings technical and economic advantages as the LCOS tends to be lower compared to that of TES installed in high-temperature R-DH. Moreover, the work reveals that due to the importance of increasing the economic feasibility for large-scale TES, it is of crucial to develop new materials and construction methods to ensure cost-efficient insulation of the buried TES.

OBJECTIVES: Urinary neutrophil gelatinase-associated lipocalin (uNGAL) appears highly accurate to identify urinary tract infections (UTIs) when obtained via catheterization. Our primary aim was to determine the agreement in uNGAL levels between paired catheter and bag urine specimens. Our secondary aim was to compare the diagnostic test characteristics of quantitative uNGAL, dipstick uNGAL (a potential point-of-care test), and urinalysis (UA). METHODS: This was a prospective study of febrile children < 24 months evaluated for UTIs. We evaluated quantitative uNGAL at a previously identified threshold of 39.1 ng/mL, dipstick uNGAL at its built-in threshold of >50 ng/mL, and UA at standard thresholds for leukocyte esterase (LE). A positive urine culture was defined as >100,000 CFUs/mL of a pathogen. RESULTS: A total of 211 patients were included (10% with positive urine cultures); 116 had paired catheterized and bagged samples. The agreement between catheterized and bagged samples at a quantitative uNGAL cutoff of ≥39.1 ng/mL was 0.76 (95% confidence interval [CI] = 0.67 to 0.83) and 0.77 (95% CI = 0.68 to 0.84) at a uNGAL dipstick threshold of >50 ng/mL. The area under the receiver operating characteristic curve for uNGAL from a catheterized sample was 0.96 (95% CI = 0.89 to 1.00) compared to 0.93 (95% CI = 0.87 to −0.99) from a bagged sample. The sensitivities of catheterized sample quantitative and dipstick uNGAL (90.5%) were higher than UA at a LE threshold of ≥1+ (57.1%). Bagged-sample uNGAL had lower quantitative and dipstick specificities (both 73.8%) than from catheterized samples (94.3% and 95.3% respectively), similar to UA. CONCLUSIONS: uNGAL from bagged and catheterized samples showed insufficient agreement to be used interchangeably. The low specificity of uNGAL from bagged samples suggests that sampling technique affects uNGAL levels.

Summary Background Owing to increasing remission rates, the management of patients with rheumatoid arthritis in sustained remission is of growing interest. The Rheumatoid Arthritis in Ongoing Remission (RETRO) study investigated tapering and withdrawal of disease-modifying antirheumatic drugs (DMARDs) in patients with rheumatoid arthritis in stable remission to test whether remission could be retained without the need to take DMARD therapy despite an absence of symptoms. Methods RETRO was an investigator-initiated, multicentre, prospective, randomised, controlled, open-label, parallel-group phase 3 trial in patients aged at least 18 years with rheumatoid arthritis for at least 12 months before randomisation who were in sustained Disease Activity Score using 28 joints with erythrocyte sedimentation rate (ESR) remission (score ClinicalTrials.gov ( NCT02779114 ). Findings Between May 26, 2010, and May 29, 2018, 303 patients were enrolled and allocated to continue (n=100), taper (n=102), or stop DMARDs (n=101). 282 (93%) of 303 patients were analysed (93 [93%] of 100 for continue, 93 [91%] of 102 for taper, and 96 [95%] of 101 for stop). Remission was maintained at 12 months by 81·2% (95% CI 73·3–90·0) in the continue group, 58·6% (49·2–70·0) in the taper group, and 43·3% (34·6–55·5) in the stop group (p=0·0005 with log-rank test for trend). Hazard ratios for relapse were 3·02 (1·69–5·40; p=0.0003) for the taper group and 4·34 (2·48–7·60; p Interpretation Reducing antirheumatic drugs in patients with rheumatoid arthritis in stable remission is feasible, with maintenance of remission occurring in about half of the patients. Because relapse rates were significantly higher in patients who tapered or stopped antirheumatic drugs than in patients who continued with a 100% dose, such approaches will require tight monitoring of disease activity. However, remission was regained after reintroduction of antirheumatic treatments in most of those who relapsed in this study. These results might help to prevent overtreatment in a substantial number of patients with rheumatoid arthritis. Funding None.

Bronchopulmonary dysplasia (BPD) is a complex condition frequently occurring in preterm newborns, and different animal models are currently used to mimic the pathophysiology of BPD. The comparability of animal models depends on the availability of quantitative data obtained by minimally biased methods. Therefore, the aim of this study was to provide the first design-based stereological analysis of the lungs in the hyperoxia-based model of BPD in the preterm rabbit. Rabbit pups were obtained on gestation day 28 (three days before term) by cesarean section and exposed to normoxic (21% O2, n = 8 ) or hyperoxic (95% O2, n = 8 ) conditions. After seven days of exposure, lung function testing was performed, and lungs were taken for stereological analysis. In addition, the ratio between pulmonary arterial acceleration and ejection time (PAAT/PAET) was measured. Inspiratory capacity and static compliance were reduced whereas tissue elastance and resistance were increased in hyperoxic animals compared with normoxic controls. Hyperoxic animals showed signs of pulmonary hypertension indicated by the decreased PAAT/PAET ratio. In hyperoxic animals, the number of alveoli and the alveolar surface area were reduced by one-third or by approximately 50% of control values, respectively. However, neither the mean linear intercept length nor the mean alveolar volume was significantly different between both groups. Hyperoxic pups had thickened alveolar septa and intra-alveolar accumulation of edema fluid and inflammatory cells. Nonparenchymal blood vessels had thickened walls, enlarged perivascular space, and smaller lumen in hyperoxic rabbits in comparison with normoxic ones. In conclusion, the findings are in line with the pathological features of human BPD. The stereological data may serve as a reference to compare this model with BPD models in other species or future therapeutic interventions.

Within the elderly population, psychogeriatric patients may be particularly susceptible to negative mental health effects of the coronavirus crisis. Detailed information about the psychosocial well-being of psychogeriatric patients during the pandemic is still sparse. Here we examined which aspects of subjective experience of the COVID-19 pandemic especially affect levels of depression, anxiety and quality of life in psychogeriatric patients with and without cognitive impairment. A cross-sectional paper survey was conducted during the first German lockdown among patients with a diagnosed psychiatric disorder (≥ 60 years) or a diagnosed neurodegenerative disease (regardless of their age) from the department for neurodegenerative diseases and geriatric psychiatry at the University of Bonn. The WHO-5-, GAD-7- and WHOQOL-old score were used to determine levels of depression, anxiety and quality of life. The second part obtained information about the subjective experience of the COVID-19 pandemic. Statistical analysis included among others principal component analysis and multiple linear regression analysis. COVID-19-related, immediate distress was a strong predictor of elevated symptoms of depression, anxiety and a reduced quality of life. COVID-19-related concerns regarding health and financial security, however, were not significantly associated with negative mental health outcomes. The overall prevalence of symptoms of depression (50.8% [95% CI 43.8–57.6%]) and anxiety (32.7% [95% CI 26.4–39.2%]) among psychogeriatric patients was high. Our findings indicate that psychogeriatric patients are not significantly affected by COVID-19-related concerns but are primarily suffering from emotional consequences resulting from changed living conditions due to the pandemic. Supplementary Information The online version contains supplementary material available at 10.1007/s00406-021-01340-1.

Policy researchers have difficulty understanding stratification in enrollment in US higher education when race and ethnicity data are plagued by missing values. Students who decline to ethnoracially self-identify become part of a “race unknown” reporting category. In undergraduate enrollment, “race unknown” students are not randomly distributed and are highest among the most selective universities. In this “Policy Research Note,” we investigate these patterns at US law schools to understand if they are driven by selectivity. We find that the most competitive law schools, on average, report 8% of their students are race unknown, double the rate of other law schools. We argue that race unknown enrollment cannot be ignored when studying ethnoracial enrollments in higher education because it varies systematically by institutional type and may mask actual rates of ethnoracial diversity. We posit that the race unknown category is likely produced by a combination of individual and institutional processes. Individual applicants may resist disclosing their ethnoracial identities, perhaps because of a perceived threat to their chances of admission. Additionally, institutional actors may willfully ignore race unknown students (not following up upon enrollment) because this category may enhance the appearance of campus diversity by diminishing the percentages of students in over-represented ethnoracial groups. In this way, high rates of race unknown students may be a product of prestigious and highly competitive educational processes.

Introduction As endpoint of a prospective multicenter 10-year documentation using the Columbus system, this evaluation carried out results of clinical scores (Knee Society Score and Oxford Knee Score), an evaluation of radiological imaging, survival rates and a collection of complication statistics. Materials and methods There was a multicenter prospective recruitment of consecutive patients with the indication for total knee replacement (TKR). Preoperatively and 10 years after implantation, clinical scores, range of motion and radiological imaging was performed. During this period, a detailed documentation of complications was made. Results A total of 210 patients were recruited in 5 centers. 140 patients were available for endpoint examination 10 years after surgery. A survival rate of 96.6% (CI 95%) for the implanted Columbus prostheses after 10 years was demonstrated. Cumulative KSS showed an improvement of 75.3 (± 38.1) points and was highly significant (p t test). The average functional improvement in the Oxford score was 20.6 (± 9.5) points and was also highly significant (p p t test). There were no implant-related complications as well as no new complication documented between 5- and 10-year follow-up. Conclusions The endpoint analysis after an observation period of 10 years provided good clinical and radiographic results. In particular, an excellent survival rate of 96.6% after 10 years was demonstrated. The data published in this study are the first to be available in a prospective multicenter study on this system, which leads to a high level of clinical significance.

Background Performance validity and test-retest reliability of ReVeRe.D, an iPad-administered cognitive test battery in major depressive disorder (MDD) were analyzed. Methods Participants aged 18-59 years had DSM-5 diagnosis of MDD with adequate visual and hearing acuity. All had responded to oral antidepressant treatment for a major depressive episode within the most recent 24-months and were stable with no greater than mild depressive symptoms as evidenced by Montgomery Asberg Depression Rating Scale total score 17. Participants were randomly assigned to 1 of 2 test sequences (AABB or BBAA; A=ReVeRe.D; B=examiner-administered tests) in a crossover design. Results 244 randomized participants (AABB: n=123; BBAA: n=121) had mean age of 38.3 years; 54.9% had a college, baccalaureate, or higher education. At first administration, Pearson correlation coefficients (PCC) for 6/10 pairs of corresponding ReVeRe.D vs examiner-administered tests exceeded the pre-specified acceptance criterion (PCC=0.53) for the primary analysis; 8 test score pairs had PCC exceeding 0.40. At second administration, PCC for 9/10 test scores pairs exceeded PCC=0.53. Together, the series of PCCs supports the concurrent validity for ReVeRe.D. Test-retest reliability for ReVeRe.D test scores was generally moderate to high. Limitations The study included stable participants with MDD who had responded to oral antidepressant treatment, with most in at least partial remission. The sample was limited to English-speaking participants, and skewed towards white, college-educated women. Further studies in acutely ill MDD patients who represent a broader demographic, are warranted. Conclusions iPad-administered ReVeRe.D is a valid and reliable computerized test battery for assessment of cognitive performance in MDD.

We examined the association between self-reported sleep quality, sleep duration, and dietary patterns among police officers in the Buffalo Cardio-Metabolic Occupational Stress (BCOPS) study.422 police officers aged 21-74 (2004-2009).We used a cross-sectional study design and obtained sleep quality and duration from responses to the 19-item Pittsburgh Sleep Quality Index. Using 46 energy-adjusted food groups derived from a 125-item food frequency questionnaire, we identified dietary patterns using exploratory factor analysis. Multiple linear regression analysis was used to examine the associations of sleep quality and duration with the derived dietary patterns.We identified major dietary patterns: fruits and vegetables (FV), dairy products, starches and fried foods, and meat and eggs. Individuals with poor sleep quality had a lower average FV score than those with optimal sleep (β [SE] = -0.32 [0.13]; p = .01). Significant interactions were observed between sex and the FV and dairy products dietary patterns, where women with poor sleep quality had a lower mean FV score compared to women with optimal sleep quality (β [SE] = -0.81 [0.29]; p = .01). Women with < 6 hours sleep duration had a lower mean dairy score compared to women with ≥ 7 hours sleep duration (β [SE] = -0.69 [0.29]; p = .02). We did not observe these associations among men.Among women, good sleep quality and long sleep duration were associated with a dietary pattern high in consumption of both fruits and vegetables and dairy products.Abbreviations: BCOPS: Buffalo Cardio-Metabolic Occupational Stress study; BMI: body mass index; FFQ: food frequency questionnaire; FV: fruits and vegetables; KMO: Kaiser-Meyer-Olkin test; MET: metabolic equivalent of task score; PSQI: Pittsburgh Sleep Quality Index questionnaire.

Background Intranasal drug delivery offers a non-invasive and convenient dosing option for patients and physicians, especially for conditions requiring chronic/repeated-treatment administration. However, in some cases such delivery may be harmful to nasal and olfactory epithelia. Objective The aim of this study was to assess the potential impact of long-term intermittent treatment with esketamine nasal spray, taken in conjunction with an oral antidepressant (AD), on olfactory function and nasal tolerability in patients with treatment-resistant depression (TRD). Methods A total of 1142 patients with TRD participated from four multicenter, randomized, double-blind, phase III studies: three short-term studies (two in patients aged 18–64 years, one in patients ≥65 years), and one long-term maintenance study of esketamine nasal spray + AD versus placebo nasal spray + AD. Across the four studies, assessments were performed at 208 sites in 21 countries. Olfactory function was measured using the 40-item University of Pennsylvania Smell Identification Test (UPSIT®) and the single-staircase Snap & Sniff® Odor Detection Threshold Test (S&S-T). Nasal tolerability, including nasal examinations and a quantitative, self-administered nasal symptom questionnaire (NSQ), was also assessed. Data were analyzed using analyses of covariance. Results Of 1142 participants, 734 were women (64.3%). The mean age of all participants ranged from 45.7 to 70.0 years across the studies. Overall, 855 patients received esketamine nasal spray + AD and 432 received placebo nasal spray + AD. Objective evaluation of nasal function showed no evidence of an adverse impact following esketamine administration. Based on the UPSIT® and S&S-T results, intranasal administration of esketamine had no effect on the odor identification or threshold test scores compared with placebo nasal spray + oral AD. Similarly, repeated administration with esketamine nasal spray had no meaningful impact on assessments of nasal function. No dose–response relationship was observed between esketamine doses and the olfactory test scores. Esketamine nasal spray was well tolerated, as indicated by responses on the NSQ and negative nasal examination findings. Conclusion Findings from this analysis indicate that there was no evidence of adverse effect on either olfactory or nasal health measures with repeated intermittent administration of esketamine nasal spray at any dose over the course of short-term (4 weeks) or long-term (16–100 weeks) studies. Clinical trial registration TRANSFORM-1: NCT02417064, date of registration: 15/04/2015; TRANSFORM-2: NCT02418585, date of registration: 16/04/2015; TRANSFORM-3: NCT02422186, date of registration: 21/04/2015; SUSTAIN-1: NCT02493868, date of registration: 10/07/2015. Supplementary Information The online version contains supplementary material available at 10.1007/s40263-021-00826-9.

With increasing numbers of patients recovering from COVID-19, there is increasing evidence for persistent symptoms and the need for follow-up studies. This retrospective study included patients without comorbidities, who recovered from COVID-19 and attended an outpatient clinic at a university hospital for follow-up care and potential convalescent plasma donation. Network analysis was applied to visualize symptom combinations and persistent symptoms. Comprehensive lab-testing was ascertained at each follow-up to analyze differences regarding patients with vs without persistent symptoms. 116 patients were included, age range was 18–69 years (median: 41) with follow-ups ranging from 22 to 102 days. The three most frequent persistent symptoms were Fatigue (54%), Dyspnea (29%) and Anosmia (25%). Lymphopenia was present in 13 of 112 (12%) cases. Five of 35 cases (14%) had Lymphopenia in the later follow-up range of 80–102 days. Serum IgA concentration was the only lab parameter with significant difference between patients with vs without persistent symptoms with reduced serum IgA concentrations in the patient cohort of persistent symptoms (p = 0.0219). Moreover, subgroup analyses showed that patients with lymphopenia experienced more frequently persistent symptoms. In conclusion, lymphopenia persisted in a noticeable percentage of recovered patients. Patients with persistent symptoms had significantly lower serum IgA levels. Furthermore, our data provides evidence that lymphopenia is associated with persistence of COVID-19 symptoms.

The Wiskott–Aldrich syndrome (WAS) is an X-linked disorder caused by mutations in the WAS gene resulting in congenital thrombocytopenia, eczema, recurrent infections and an increased incidence of autoimmune diseases and malignancies. Without curative therapies, affected patients have diminished life expectancy and reduced quality of life. Since WAS protein (WASP) is constitutively expressed only in hematopoietic stem cell-derived lineages, hematopoietic stem cell transplantation (HSCT) and gene therapy (GT) are well suited to correct the hematologic and immunologic defects. Advances in high-resolution HLA typing, new techniques to prevent GvHD allowing the use of haploidentical donors, and the introduction of reduced intensity conditioning regimens with myeloablative features have increased overall survival (OS) to over 90%. The development of GT for WAS has provided basic knowledge into vector selection and random integration of various viral vectors into the genome, with the possibility of inducing leukemogenesis. After trials and errors, inactivating lentiviral vectors carrying the WAS gene were successfully evaluated in clinical trials, demonstrating cure of the disease except for insufficient resolution of the platelet defect. Thus, 50 years of clinical evaluation, genetic exploration and extensive clinical trials, a lethal syndrome has turned into a curable disorder.

The potential in treating chronic and life-threatening diseases by stem cell therapies can greatly be exploited via the efficient automation of stem cell production. Working with living material though poses severe challenges to automation. Recently, production platforms has been developed and tested worldwide with the aim to increase the reproducibility, quality and throughput of the process, to minimize human errors, and to reduce costs of production. A distinctive feature of this domain is the symbiotic co-existence and co-evolution of the technical, information and communication, as well as biological ingredients in production structures. A challenging way to overcome the issues of automated production is the use of biologically inspired control algorithms. In the paper an approach is described which combines digital, agent-based simulation and reinforcement learning for this purpose. The modelling of the cell growth behaviour, which is an important prerequisite of the simulation, is also introduced, together with an appropriate model fitting procedure. The applicability of the proposed approach is demonstrated by the results of a comprehensive investigation.

Do successful local nudge interventions maintain efficacy when scaled state or nationwide? We investigate, through two randomized controlled trials, the impact of a national and state-level campaign encouraging students to apply for financial aid for college. The campaigns collectively reached over 800,000 students, with multiple treatment arms patterned after prior local interventions in order to explore potential mechanisms. We find no impacts on aid receipt or college enrollment overall or for any subgroups. We find no evidence that different approaches to message framing, delivery, or timing, or access to one-on-one advising affected campaign efficacy. We discuss why nudge strategies that work locally may be hard to scale effectively.

Background: Cardiac magnetic resonance (CMR) pharmacological stress-testing is a well-established technique for detecting myocardial ischemia. Although stressors and contrast agents seem relatively safe, contraindications and side effects must be considered. Substantial costs are further limiting its applicability. Dynamic handgrip exercise (DHE) may have the potential to address these shortcomings as a physiological stressor. We therefore evaluated the feasibility and physiologic stress response of DHE in relation to pharmacological dobutamine-stimulation within the context of CMR examinations.Methods: Two groups were prospectively enrolled: (I) volunteers without relevant disease and (II) patients with known CAD referred for stress-testing. A both-handed, metronome-guided DHE was performed over 2 min continuously with 80 contractions/minute by all participants, whereas dobutamine stress-testing was only performed in group (II). Short axis strain by fast-Strain-ENCoded imaging was acquired at rest, immediately after DHE and during dobutamine infusion.Results: Eighty middle-aged individuals (age 56 ± 17 years, 48 men) were enrolled. DHE triggered significant positive chronotropic (HRrest: 68 ± 10 bpm, HRDHE: 91 ± 13 bpm, p < 0.001) and inotropic stress response (GLSrest: −19.4 ± 1.9%, GLSDHE: −20.6 ± 2.1%, p < 0.001). Exercise-induced increase of longitudinal strain was present in healthy volunteers and patients with CAD to the same extent, but in general more pronounced in the midventricular and apical layers (p < 0.01). DHE was aborted by a minor portion (7%) due to peripheral fatigue. The inotropic effect of DHE appears to be non-inferior to intermediate dobutamine-stimulation (GLSDHE= −19.5 ± 2.3%, GLSDob= −19.1 ± 3.1%, p = n.s.), whereas its chronotropic effect was superior (HRDHE= 89 ± 14 bpm, HRDob= 78 ± 15 bpm, p < 0.001).Conclusions: DHE causes positive ino- and chronotropic effects superior to intermediate dobutamine-stimulation, suggesting a relevant increase of myocardial oxygen demand. DHE appears to be safe and timesaving with broad applicability. The data encourages further studies to determine its potential to detect obstructive CAD.

Family history (FH) of ovarian cancer and breast cancer are well-established risk factors for ovarian cancer, but few studies have examined this association in African American (AA) and white women by histotype. We assessed first- and second-degree FH of ovarian and breast cancer and risk of epithelial ovarian cancer in the Ovarian Cancer in Women of African Ancestry Consortium. Analyses included 1052 AA cases, 2328 AA controls, 2380 white cases and 3982 white controls. Race-specific odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using multilevel logistic regression with adjustment for covariates. Analyses were stratified by histotype (high-grade serous vs others). First-degree FH of ovarian cancer was associated with high-grade serous carcinoma in AA (OR = 2.32, 95% CI: 1.50, 3.59) and white women (OR = 2.48, 95% CI: 1.82, 3.38). First-degree FH of breast cancer increased risk irrespective of histotype in AAs, but with high-grade serous carcinoma only in white women. Associations with second-degree FH of ovarian cancer were observed for overall ovarian cancer in white women and with high-grade serous carcinoma in both groups. First-degree FH of ovarian cancer and of breast cancer, and second-degree FH of ovarian cancer is strongly associated with high-grade serous ovarian carcinoma in AA and white women. The association of FH of breast cancer with high-grade serous ovarian carcinoma is similar in white women and AA women, but may differ for other histotypes.

Most U.S. universities have made explicit commitments to educating economically diverse student bodies; however, the higher education system is highly stratified. In this paper, we seek to understand stratification in the wake of the Great Recession by examining enrollment among students from differing income backgrounds by institutional type. Two theoretical frameworks suggest different conclusions. A Disaster Capitalism framework suggests that in places where the recession was most severe, enrollment by income would become more stratified than in places where the downturn was less severe. In contrast, Effectively Maintained Inequality would suggest that enrollments were already effectively stratified by income and would not necessarily be sensitive to exposure to an economic shock. Employing fixed effects modeling and novel data based on the tax records of 30 million Americans, we examine income composition by institutional type from 2004 to 2012. We find that although stratification by institutional type worsened during the recession and subsequent recovery, patterns of economic stratification were not more intense for institutions that enrolled students from states hardest hit by the recession. We conclude that these patterns are consistent with an Effectively Maintained Inequality framework. During the recession, the top quintiles continued to enjoy their longstanding disproportionate enrollment in the most selective institutions. For the bottom quintiles, the longstanding marginalization from 4-year college going persisted through the recession. These stratification patterns, however, were not more pronounced in places hardest hit by the recession.

Globally, the highest cervical cancer mortality rates are found in East Africa. Visual inspection with acetic acid (VIA)-based screening in resource-poor settings has been shown to decrease the proportion of women presenting with late-stage cervical cancer, a process known as clinical downstaging. The only cancer treatment center in Tanzania, Ocean Road Cancer Institute (ORCI) in Dar es Salaam, opened a VIA-based cervical cancer screening program in 2002. We reviewed 6,676 medical records of cervical cancer patients at the ORCI from 2002–2011 to 2014–2018 for stage at diagnosis and screening status, among other variables. We investigated whether clinical downstaging occurred in this period among women screened at the ORCI, when compared to unscreened women. Our results indicated that the proportion of women presenting with late-stage cervical cancer among women screened at the ORCI decreased by 27.7% over the 16-year period (χ2 = 16.99; p = 0.0002). Among unscreened women, a non-significant 13.2% decrease in late-stage disease was observed (χ2 = 1.74; p = 0.4179). Our results suggest clinical downstaging occurred among women screened at the ORCI over the 16-year period, and this difference may be attributed to the screening program as the same decrease in stage was not observed among unscreened women during the same time period. At present, less than one percent of Tanzanian women receive yearly cervical cancer screenings. Access to screening through expansion of the ORCI screening clinic and the creation of more clinics should be prioritized.

ZusammenfassungEngleiste Blutzuckerspiegel können in der perioperativen Phase gefährlich werden für Patienten mit Diabetes – insbesondere, wenn der Blutzucker 250 mg/dl überschreitet oder der aktuelle HbA1c-Wert über 8,5 – 9% liegt. Dieser Beitrag bietet eine Hilfestellung im perioperativen Umgang mit Patienten mit Diabetes und zeigt praktische Handlungsempfehlungen für eine optimale Blutzuckerkontrolle durch orale Antidiabetika und Insulin.

Background African American and Hispanic postmenopausal women have the highest risk for heart failure compared with other races, but heart failure prevalence is lower than expected in some national cohorts. It is unknown whether psychosocial factors are associated with lower risk of incident heart failure hospitalization among high-risk postmenopausal minority women. Methods and Results Using the Women's Health Initiative Study, African American and US Hispanic women were classified as high-risk for incident heart failure hospitalization with 1 or more traditional heart failure risk factors and the highest tertile heart failure genetic risk scores. Positive psychosocial factors (optimism, social support, religion) and negative psychosocial factors (living alone, social strain, depressive symptoms) were measured using validated survey instruments at baseline. Adjusted subdistribution hazard ratios of developing heart failure hospitalization were determined with death as a competing risk. Positive deviance indicated not developing incident heart failure hospitalization with 1 or more risk factors and the highest tertile for genetic risk. Among 7986 African American women (mean follow-up of 16 years), 27.0% demonstrated positive deviance. Among high-risk African American women, optimism was associated with modestly reduced risk of heart failure hospitalization (subdistribution hazard ratio 0.94, 95% confidence interval 0.91–0.99), and social strain was associated with modestly increased risk of heart failure hospitalization (subdistribution hazard ratio 1.07, 95% confidence interval 1.02–1.12) in the initial models; however, no psychosocial factors were associated with heart failure hospitalization in fully adjusted analyses. Among 3341 Hispanic women, 25.1% demonstrated positive deviance. Among high-risk Hispanic women, living alone was associated with increased risk of heart failure hospitalization (subdistribution hazard ratio 1.97, 95% confidence interval 1.06–3.63) in unadjusted analyses; however, no psychosocial factors were associated with heart failure hospitalization in fully adjusted analyses. Conclusions Among postmenopausal African American and Hispanic women, a significant proportion remained free from heart failure hospitalization despite having the highest genetic risk profile and 1 or more traditional risk factors. No observed psychosocial factors were associated with incident heart failure hospitalization in high-risk African Americans and Hispanics. Additional investigation is needed to understand protective factors among high-risk African American and Hispanic women.

Background The D3-creatine (D3Cr) dilution method provides a direct measure of skeletal muscle. The aim of this study was to compare the association of D3Cr muscle mass with lean body mass (LBM) measured by dual-energy x-ray absorptiometry (DXA) and examine its relation with physical function in postmenopausal women. Methods Seventy-four community-dwelling women (mean age 82.3 ± 5.4) participated in this pilot study from the Buffalo, New York clinical site of the Women’s Health Initiative (WHI). Participants attended a clinic visit which included anthropometric measures, blood draw, DXA scan, measures of physical function, and initiated the D3Cr protocol. Physical function was evaluated using hand grip strength, short physical performance battery (SPPB), and RAND-36 physical function scale. Descriptive statistics and logistic regression models were used to examine the associations of D3Cr muscle mass with functional outcomes. Results D3-creatine muscle mass was moderately correlated with DXA LBM (r = 0.50) and DXA appendicular lean mass (ALM) (r = 0.50). Individuals with high D3Cr muscle mass (%) had higher physical function compared to individuals with low muscle mass (%), indicated by high scores on SPPB (odds ratio [OR] = 5.24; 95% confidence interval [CI]: 1.40, 19.58). We observed stronger relationships between high D3Cr and physical function than either DXA LBM (OR = 3.40; 95% CI: 0.88, 13.11) or DXA ALM (OR = 4.15; 95% CI: 1.10, 15.68) and physical function. Conclusions Our findings provide strong preliminary data for the associations of D3Cr muscle mass with measures of physical function in older women. These findings support and extend prior work on D3Cr muscle mass in older men.

Production companies are getting more and more aware of the relevancy of energy costs and the environmental impact of their manufactured products. Hence, the knowledge about the energy intensity of new process technologies as metal printing becomes increasingly crucial. Therefore, data about the energy intensity of entire process chains allow a detailed assessment of the life cycle costs and environmental impact of metal printed parts. As metal printing with Laser Powder Bed Fusion (LPBF) is applied from rapid prototyping to serial manufacturing processes more and more, sustainability data are useful to support a valid scale-up scenario and energetic improvements of the 3D-printing machinery as well as peripheral aggregates used in the process chain. The contribution aims to increase the transparency of the LPBF process chain in terms of its energy consumption. Therefore a generalized model to assess sustainability aspects of metal printed parts is derived. For this purpose, the LPBF process chain with the essential pre-, main- and post-processes is evaluated regarding its energy intensity. Here, the sub-processes, for example wet and dry cleaning of the printer, sieving of the metal powder or sand-blasting of the part are analyzed as well as the main printing process. Based on the derived experimental data from an installed, industry-like process chain, a model is created, which tends to generalize the experimental findings to evaluate other metal printed parts and process chain variants in terms of their energy intensity.

Introduction: Visceral adipose tissue (VAT) is a hypothesized driver of chronic disease. Dual-energy X-ray absorptiometry (DXA) potentially offers a lower cost and more available alternative compared to gold-standard magnetic resonance imaging (MRI) for quantification of abdominal fat sub-compartments, VAT and subcutaneous adipose tissue (SAT). We sought to validate VAT and SAT area (cm2) from historical DXA scans against MRI. Methodology: Participants (n = 69) from the Women's Health Initiative (WHI) completed a 3 T MRI scan and a whole body DXA scan (Hologic QDR2000 or QDR4500; 2004-2005). A subset of 43 participants were scanned on both DXA devices. DXA-derived VAT and SAT at the 4th lumbar vertebrae (5 cm wide) were analyzed using APEX software (v4.0, Hologic, Inc., Marlborough, MA). MRI VAT and SAT areas for the corresponding DXA region of interest were quantified using sliceOmatic software (v5.0, Tomovision, Magog, Canada). Pearson correlations between MRI and DXA-derived VAT and SAT were computed, and a Bland-Altman analysis was performed. Results: Participants were primarily non-Hispanic white (86%) with a mean age of 70.51 ± 5.79 years and a mean BMI of 27.33 ± 5.40 kg/m2. Correlations between MRI and DXA measured VAT and SAT were 0.90 and 0.92, respectively (p ≤ 0.001). Bland-Altman plots showed that DXA-VAT slightly overestimated VAT on the QDR4500 (-3.31 cm2); this bias was greater in the smaller subset measured on the older DXA model (QDR2000; -30.71 cm2). The overestimation of DXA-SAT was large (-85.16 to -118.66 cm2), but differences were relatively uniform for the QDR4500. Conclusions: New software applied to historic Hologic DXA scans provide estimates of VAT and SAT that are well-correlated with criterion MRI among postmenopausal women.

Purpose: CMR pharmacological stress-testing is well-established to detect myocardial ischemia. Despite stressor and contrast agents appear rather save, contraindications and side effects have to be considered. Substantial costs are further limiting its applicability. Dynamic handgrip exercise(DHE) may have the potential to address these shortcomings as a physiological stressor. We therefore evaluated the feasibility and physiologic stress response of DHE in relation to pharmacological dobutamine-stimulation by cardiac magnetic resonance(CMR).Methods: Two subgroups were prospectively enrolled: (i)volunteers without relevant disease and (ii)patients with known CAD referred for stress-testing. A both-handed, metronome-guided DHE was performed over 2 minutes continuously with 80 contractions/minute by all participants, whereas dobutamine stress-testing was only performed in group(ii). Short axis strain by fast-Strain-ENCoded imaging was acquired at rest, immediately after DHE and during dobutamine infusion. Results: Eighty middle-aged individuals(age 56±17years, 48males) were enrolled. DHE triggered significant positive chronotropic(HRrest:68±10bpm, HRDHE:91±13bpm, prest:-19.4±1.9%, GLSDHE:-20.6±2.1%, pDHE=-19.5±2.3%, GLSDob=-19.1±3.1%, p=n.s.), whereas its chronotropic effect was superior (HRDHE=89±14bpm, HRDOB=78±15bpm, pConclusions: DHE causes positive ino- and chronotropic effects superior to intermediate dobutamine-stimulation, suggesting a relevant increase of myocardial oxygen demand. DHE appears safe and timesaving with broad applicability. The data encourages further studies to determine its potential to detect obstructive CAD.

Funding Acknowledgements Type of funding sources: None. Background Premature ventricular complexes (PVCs) in the absence of underlying structural heart disease are considered to be benign. However, cardiac dysfunction has been observed in patients with a high PVC burden. The characterization of a PVC-induced cardiomyopathy with structural remodeling including myocardial fibrosis and the determination of a specific PVC burden leading to subclinical cardiac dysfunction remains to be determined. Objectives We aimed to evaluate cardiac function, remodeling and myocardial fibrosis patterns in patients with PVCs using cardiac magnetic resonance imaging (CMR). Additionally, we aimed to determine a PVC cut-off value leading to subclinical cardiac dysfunction. Methods Patients who underwent CMR and 24-hour, 12-lead ECG monitoring (Holter ECG) within six months were retrospectively studied. Patients with evidence of structural heart disease were excluded. The cohort was subdivided based on the number of PVCs in Holter ECG; Group-1 = 0-100, Group-2 = 100-5000 and Group-3 > 5000 PVCs. CMR parameters were extracted from our local databank. Myocardial strain was measured using feature tracking. For quantification of myocardial fibrosis, T1 mapping and late gadolinium enhancement (LGE) were investigated. Z-scores were calculated in order to combine T1 values from a 1.5 and 3Tesla CMR vendor. Results 443 patients (52 ± 20 years, 45% females) were included in the study. Compared to Group-1, Group-3 revealed a significantly reduced LV-EF, an increased indexed LV-EDV and increased indexed LV-ESV, indicating cardiac dysfunction and LV enlargement. PVCs frequency was inversely correlated with LV-EF (r=-0.23, p Conclusion CMR revealed cardiac dysfunction, left ventricular enlargement and diffuse myocardial fibrosis in patients with PVC in the absence of structural heart disease. These changes indicate the development of a PVC-induced cardiomyopathy depending on the PVC burden. Interestingly, subclinical myocardial dysfunction was determined at already low PVC frequencies. Further investigations are necessary in order to examine the influence of different origins of PVCs and the development of structural remodeling.

Background Systemic effects of altered serum copper processing in Wilson Disease (WD) might induce myocardial copper deposition and consequently myocardial dysfunction and structural remodeling. This study sought to investigate the prevalence, manifestation and predictors of myocardial tissue abnormalities in WD patients. Methods We prospectively enrolled WD patients and an age-matched group of healthy individuals. We applied cardiovascular magnetic resonance (CMR) to analyze myocardial function, strain, and tissue characteristics. A subgroup analysis of WD patients with predominant neurological (WD-neuro+) or hepatic manifestation only (WD-neuro−) was performed. Results Seventy-six patients (37 years (27–49), 47% women) with known WD and 76 age-matched healthy control subjects were studied. The prevalence of atrial fibrillation in WD patients was 5% and the prevalence of symptomatic heart failure was 2.6%. Compared to healthy controls, patients with WD had a reduced left ventricular global circumferential strain (LV-GCS), and also showed abnormalities consistent with global and regional myocardial fibrosis. WD-neuro+ patients presented with more severe structural remodeling and functional impairment when compared to WD-neuro− patients. Conclusions In a large cohort, WD was not linked to a distinct cardiac phenotype except CMR indexes of myocardial fibrosis. More research is warranted to assess the prognostic implications of these findings. Trial registration: This trial is registered at the local institutional ethics committee (S-188/2018).

In this paper a numerical analysis of the effect of heat emitter characteristics on the local indoor thermal comfort condition in a room is presented. A dynamic model, able to evaluate the 3D distribution of the mean radiant temperature in the whole volume of a thermal zone is developed. The model allows a fast evaluation, in terms of computational time, of the view factors associated to the inner points of a room thanks to the use of the MATLAB Contour Double Integral Formula (CDIF) routine. The new tool has been used in order to obtain, by means of a series of dynamic yearly simulations, a comparison among different heat emitters (i.e. in-slab radiant floor, in-slab radiant ceiling, lightweight radiant ceiling, radiator, radiant vertical wall and all-air systems) in terms of 3D distribution of the local operative temperature in a room. The knowledge of the 3D distribution of the operative temperature enables the local analysis of the indoor thermal comfort conditions established in the room during the year. The local Predicted Mean Vote (PMV) distribution within the room is calculated for each considered configuration. The results allow to quantify how the reduction of the maximum surface temperature of the emitters, which can be experienced when the envelope thermal insulation is increased, can create more uniform indoor thermal conditions by reducing the differences existing among the heat emitters.

Background The causes of racial disparities in epithelial ovarian cancer (EOC) incidence remain unclear. Differences in the prevalence of ovarian cancer risk factors may explain disparities in EOC incidence among African American (AA) and White women. Methods We used data from 4 case-control studies and 3 case-control studies nested within prospective cohorts in the Ovarian Cancer in Women of African Ancestry Consortium to estimate race-specific associations of 10 known or suspected EOC risk factors using logistic regression. Using the Bruzzi method, race-specific population attributable risks (PAR) were estimated for each risk factor individually and collectively, including groupings of exposures (reproductive factors and modifiable factors). All statistical tests were 2-sided. Results Among 3244 White EOC cases and 9638 controls and 1052 AA EOC cases and 2410 controls, AA women had a statistically significantly higher PAR (false discovery rate [FDR] P Conclusions Collectively, the selected risk factors accounted for slightly more of the risk among AA than White women, and interventions to reduce EOC incidence that are focused on multiple modifiable risk factors may be slightly more beneficial to AA women than White women at risk for EOC.

Many postsecondary datasets collect gender data in ways that are not inclusive of all students. Many trans* students, those who identify as trans women, trans men, genderqueer, among other gender identities, are excluded when surveys collect gender data using only two categories. The American Bar Association recently became the first sector of higher education to collect and report enrollment data using three gender categories for all U.S. law schools. Between 2014 and 2019, there was a steady rise in the number of law schools that reported enrolling students in the “other” gender category. We interpret this growth to signify that law schools are beginning to collect data on students who were already there, not a reflection of exponential growth in trans* enrollment in law school. A more inclusive approach to gender data collection is necessary to better understand the educational trajectories of trans* students. However, data collection alone is not sufficient and may in fact be problematic. Importantly, we encourage quantitative researchers to consider their role in processes of administrative violence—that is, the ways in which the use of discrete identity categories (such as male, female and/or other) can create barriers for trans* students as they access healthcare, student housing and campus services.

Acute abdomen is a common and sometimes dramatic clinical condition, which can be fatal if diagnosis is not made in time. A large number of diseases can cause an acute abdomen which makes a targeted and rapid diagnostic approach utterly important. The initial diagnostic approach is based on the clinical assessment (including medical history and physical examination) which allows doctors to quickly establish a suspected diagnosis with a relatively high sensitivity but a rather low specificity. Further diagnostics, including laboratory markers, imaging and - if necessary - interventional diagnostics should be initiated quickly after the first clinical assessment in order to confirm the suspected diagnosis or to further classify unclear cases. The clinical assessment is the leading diagnostic tool that determines further diagnostic approaches for patients with an acute abdomen and thus enables adequate and timely therapy.

This systematic synthesis examines the intended and unintended consequences of performance-based funding (PBF) policies in higher education. Within this synthesis, we focus particularly on evidence from research studies with strong causal inference designs in an effort to understand the impacts of these policies. PBF adoption is generally associated with null or modest positive effects on the intended outcomes of retention and graduation, but there is also compelling evidence that PBF policies lead to unintended outcomes related to restricting access, gaming of the PBF system, and disadvantages for underserved student groups and under-resourced institution types. PBF policies including equity provisions for colleges that enroll or graduate underserved student groups have been found to offset some of these unintended consequences. Based on this synthesis, we offer policy recommendations and directions for future research on PBF policies, including the need to consider variation in policy design and the broader state policy context.

Experience mining is considered a substantial extension of opinion mining. Experience mining covers the description of all events that are related to the user's perception in the interaction with the object. There is information about the user`s experience that cannot be obtained with polarity analysis or sentiment analysis. The information obtained from those analyses is the positive or negative evaluation of a product/service. But in opinion analysis there is more useful information for other users. In this work we propose a method to obtain expressions of user experiences that are difficult to obtain by some of the current methods. The contributions of this work are: 1) Classification of information of user experiences according to the intention of communication: the categories are: "Evaluation", "Sensation" "Recommendation" and “ Target Users". 2) A rule-based method: rules take into account the lexical classification of words to classify sentences based on communicative intention. The results obtained show that the method based on classification rules can provide useful information about the user experience to other users

Obesity is associated with lung function impairment and respiratory diseases; however, the underlying pathophysiological mechanisms are still elusive, and therapeutic options are limited. This study examined the effects of prolonged excess fat intake on lung mechanics and microstructure and tested spermidine supplementation and physical activity as intervention strategies. C57BL/6N mice fed control diet (10% fat) or high-fat diet (HFD; 60% fat) were left untreated or were supplemented with 3 mM spermidine, had access to running wheels for voluntary activity, or a combination of both. After 30 wk, lung mechanics was assessed, and left lungs were analyzed by design-based stereology. HFD exerted minor effects on lung mechanics and resulted in higher body weight and elevated lung, air, and septal volumes. The number of alveoli was higher in HFD-fed animals. This was accompanied by an increase in epithelial, but not endothelial, surface area. Moreover, air-blood barrier and endothelium were significantly thicker. Neither treatment affected HFD-related body weights. Spermidine lowered lung volumes as well as endothelial and air-blood barrier thicknesses toward control levels and substantially increased the endothelial surface area under HFD. Activity resulted in decreased volumes of lung, septa, and septal compartments but did not affect vascular changes in HFD-fed mice. The combination treatment showed no additive effect. In conclusion, excess fat consumption induced alveolar capillary remodeling indicative of impaired perfusion and gas diffusion. Spermidine alleviated obesity-related endothelial alterations, indicating a beneficial effect, whereas physical activity reduced lung volumes apparently by other, possibly systemic effects.

Family history and body mass index (BMI) are well-known risk factors for colorectal cancer (CRC), however, their joint effects are not well described. Using linked data for genealogy, self-reported height and weight from driver's licenses, and the Utah Surveillance, Epidemiology, and End-Results cancer registry, we found that an increasing number of first-degree relatives (FDR) with CRC is associated with higher standardized incidence ratio (SIR) for overweight/obese probands but not for under/normal weight probands. For probands with two CRC-affected FDRs, the SIR = 1.91 (95% CI [0.52, 4.89]) for under/normal weight probands and SIR = 4.31 (95% CI [2.46, 7.00]) for overweight/obese probands. In the absence of CRC-affected FDRs, any number of CRC-affected SDRs did not significantly increase CRC risk for under/normal weight probands, but for overweight/obese probands with at least three CRC-affected SDRs the SIR = 2.68 (95% CI [1.29, 4.93]). In the absence of CRC-affected FDRs and SDRs, any number of CRC-affected third-degree relatives (TDRs) did not increase risk in under/normal weight probands, but significantly elevated risk for overweight/obese probands with at least two CRC-affected TDRs was observed; SIR = 1.32 (95% CI [1.04, 1.65]). For nonsyndromic CRC, maximum midlife BMI affects risk based on family history and should be taken into account for CRC risk communication when possible.

In light of persistent workforce shortages, school psychologists must support the professional growth and well-being of graduate students and early career professionals (ECPs) in their field. This exploratory study examined the self-reported needs, interests, and challenges of doctoral-level ECPs and graduate students in school psychology. Participants were 87 ECP members (n = 55) and student affiliates (SAs; n = 32) of Division 16 of the American Psychological Association (APA D16). A brief online survey assessed their interest in a variety of professional development topics, conference programming formats, and other resources (e.g., webinars and Internet articles). Participants also responded to open-ended items assessing professional challenges as well as organizations accessed outside of APA D16. Whereas ECPs in faculty positions expressed the most interest in research-related professional development, ECPs in practice and SAs expressed the greatest interest in practice-oriented programming. Both ECPs and SAs valued symposia, informal sessions, brief Internet articles, and webinars as forums for professional support. Finally, ECPs and SAs noted challenges related to interpersonal relations in the workplace, diversity and multiculturalism, and pre-doctoral and post-doctoral training. The results of this study suggest that school psychology professional organizations have a significant role in supporting ECPs and SAs with a range of developmental tasks and professional challenges. Moreover, these organizations can support ECPs and graduate students by providing concise and time-efficient conferencing programming (

Research on privacy practices in digital environments has oftentimes discovered a paradoxical relationship between users’ discursive appraisal of privacy and their actual practices: the “privacy paradox.” The emergence of this paradox prompts us to conduct ethnography of a health and fitness platform in order to flesh out the structural mechanisms generating this paradox. We provide an ethnographic analysis of surveillance capitalism in action that relates front-end practices empirically to the data economy’s back-end operations to show how this material-semiotic setup elicits users’ desire to become self-determined subjects in a way that makes them amenable as objects of behavioral engineering. We combine different ethnographic methods and materials (situational mapping: network overview; discourse analysis: interpellations; autoethnography: practices; technical app analysis: data flow; business model canvas: revenue information) to specify how different types of values are produced and translated on the investigated platform. The latter offers users the values of self-mastery and social visibility. However, the data generated in this process serve to translate these values into the value of economic amenability and thereupon ultimately into economic profit. What gets lost in translation, though, is the front-end promise of self-mastery. It is these structural mechanisms that generate the privacy paradox in the first place.

ObjectiveTo determine the interobserver agreement of history and physical examination findings in children undergoing evaluation in the emergency department (ED) for headaches.Study designWe conducted a prospective, cross-sectional study of children aged 2-17years evaluated at 3 tertiary-care pediatric EDs for non-traumatic headaches. Two clinicians independently completed a standardized assessment of each child and documented the presence or absence of history and physical examination variables. Unweighted κ statistics were determined for 68 history and 24 physical examination variables.ResultsWe analyzed 191 paired observations; median age was 12years, with 19 (9.9%) children younger than 7years. Interrater reliability was at least moderate (κ≥0.41) for 41 (60.3%) patient history variables. Eleven (61.1%) of 18 physical examination variables for which κ statistics could be calculated had a κ that was at least moderate.ConclusionsA substantial number of history and physical examination findings demonstrated at least moderate κ statistic values when assessed in children with headaches in the ED. These variables may be generalizable across different types of clinicians for evaluation of children with headaches. If also found to predict the presence or absence of emergent intracranial abnormalities, the more reliable clinical findings may be helpful in the development of clinical prediction rules or risk stratification models that could be used across settings for children with headaches.

One ethnoracial reporting category perplexes higher education researchers: “race and ethnicity unknown.” Using the Integrated Postsecondary Education Data System (IPEDS), we constructed a 28-year panel of 4,401 institutions. We find that the for-profit sector ranges from 5% to 18% “race unknown” students. In addition, almost 10% of students attending the most selective institutions were reported as “race unknown” in 2009 before dropping off precipitously. The size of the “race unknown” category can be attributed to some combination of student responses and data collection practices. We suggest researchers refrain from dropping “race unknown” from their studies as doing so may bias findings for the other ethnoracial categories, especially when comparing rates of student enrollment across institutional types.

Seasonal thermal energy storage (TES) is envisioned as a major player in the future district heating (DH) systems where large shares of renewables are being integrated. Therefore, in order to fulfill the seasonal tasks, such storage systems are characterized with large volumes. Yet, the integration of such large-scale storage technologies is not easily planned and realized. There exist numerous challenges e.g. TES type, volume and ground conditions, need to be tackled in order to obtain an optimal planning solution for TES integration. Given their promising applications, the scope of this work is limited to tank and pit thermal energy storage. Accordingly, this contribution firstly discusses the modeling of seasonal TES in finite element tools. Then, it examines the influence of a list of parameters i.e. TES construction type, geometry, volume and DH characteristics, on TES performance. Later, the work develops a methodology for construction techno-economic analysis of such technologies. It is revealed that the tank TES has always better performance than pit, but on the other hand it is always characterized with higher capital cost. As TES volume increases, the performance difference between tank and pit starts to vanish. Further, the DH characteristics play a major role in TES performance. It is depicted that lowering DH temperatures will ultimately lead to lower thermal losses from TES. Another important finding is the applicability of the suggested performance indicator for techno-economic analysis as it relates the technology capital cost to the effective volume of TES. The contribution also investigates the influence of insulation level on TES performance and it is found that for volumes larger than 500,000 m3, there is no major performance difference between the tank or the pit in case of insulation enclosing TES envelope. However, it is also revealed that insulation is needed only and solely to preserve the ground quality when large volumes are realized.

Osteoporosis is a frequent comorbidity in rheumatoid arthritis (RA). Due to the improved treatment options for RA, we expect a long-term decrease in osteoporosis as an accompanying disease. Data from the German National Database (NDB) were used to investigate whether the frequency of osteoporosis has changed in the last 10 years. From 2007 to 2017, approximately 4000 patients were documented annually with data on therapy and comorbidity. The cross-sectional data were summarised descriptively. Age, sex, disease duration, disease activity and glucocorticoids were considered as influencing factors. The Cochrane-Armitage test for trend was used to test whether the frequency of osteoporosis at the first visit changed from 2007 to 2017. Osteoporosis frequency in RA patients (mean age 63 years, 75% female) decreased from 20% in 2007 to 6% in 2017 (p 10-year disease duration: 28% to 20%). Patients with high disease activity and patients who took glucocorticoids (GC) were more often affected by osteoporosis than patients in remission or without GC. Drug prophylaxis in patients without osteoporosis increased (20% to 41% without GC, 48% to 55% with GC). Men with GC received less prophylactic treatment than women (48% vs. 57% in 2017). In this cohort, osteoporosis in patients with RA is less frequently observed compared to former years. RA-specific risk factors for osteoporosis such as disease activity and GC therapy have declined but long-term GC use is still present. Assessment of osteoporosis in RA patients should be investigated more consistently by bone density measurement. Male RA patients still need to be given greater consideration regarding osteoporosis drug prophylaxis, especially when GC therapy is needed.

Idiopathic pulmonary fibrosis (IPF) is a chronic progressive interstitial lung disease characterized by patchy scarring of the distal lung with limited therapeutic options and poor prognosis. Here, we show that conditional deletion of the ubiquitin ligase Nedd4-2 (Nedd4l) in lung epithelial cells in adult mice produces chronic lung disease sharing key features with IPF including progressive fibrosis and bronchiolization with increased expression of Muc5b in peripheral airways, honeycombing and characteristic alterations in the lung proteome. NEDD4-2 is implicated in the regulation of the epithelial Na+ channel critical for proper airway surface hydration and mucus clearance and the regulation of TGFβ signaling, which promotes fibrotic remodeling. Our data support a role of mucociliary dysfunction and aberrant epithelial pro-fibrotic response in the multifactorial disease pathogenesis. Further, treatment with the anti-fibrotic drug pirfenidone reduced pulmonary fibrosis in this model. This model may therefore aid studies of the pathogenesis and therapy of IPF., Idiopathic pulmonary fibrosis (IPF) is a devastating disease with poor prognosis. Here, the authors show that deficiency of the E3 ubiqutin-protein ligase Nedd4-2 in airway epithelial cells causes IPF-like disease in adult mice. This model may aid studies of the pathogenesis and therapy of IPF.

In a more and more digital world, the protection of sensitive data is an essential challenge. Current cryptographic methods rely on one-way functions based on computationally challenging problems. However, there are several candidates for runtime efficient computing that might require new methods for data security. Among them are Universal Memcomputing Machines (UMM) for which a memristive circuit realization exists, where the eponymous element is a resistor with memory called memristor. While the original concept of UMMs is purely theoretical, we extend the state of the art by providing a thorough circuit theoretical analysis, utilizing models of real memristors and derive a highly flexible software emulator. The deployed memristor is an RRAM-cell which is known to have a rapid transition behavior, making it a suitable choice for runtime critical applications like UMMs. To obtain the emulator, we exploit the wave digital concept which is known to preserve passivity in a signal processing sense. The proper functioning is verified by solving an NP-complete subset sum problem.

Background The concerns of the highly contagious and morbid nature of Coronavirus Disease-2019 (COVID-2019) have prompted healthcare workers to implement strict droplet and contact isolation precautions. Unfortunately, some patients who may be or presumptively or confirmed as infected with COVID-2019 may also require emergent surgical procedures. As such, given the high-risk for exposure of many healthcare workers involved the complex requirements for appropriate isolation must be adhered to. Case presentation We present our experience with a 77-year-old who required emergency cardiac surgery for a presumed acute aortic syndrome in the setting of a presumed, and eventually confirmed, COVID-2019 infection. We outline the necessary steps to maintain strict isolation precautions to limit potential exposure to the surgical Team. Conclusions We hereby provide our algorithm for emergent surgical procedures in critically-ill patients with presumptive or confirmed infection with COVID-2019. The insights from this case report can potentially be templated to other facilities in order to uphold high standards of infection prevention and patient safety in surgery during the current COVID-19 pandemic.