An Approach to Flexible Multilevel Modelling

Multilevel modelling approaches tackle issues related to lack of flexibility and mixed levels of abstraction by providing features like deep modelling and linguistic extension. However, the lack of a clear consensus on fundamental concepts of the paradigm has in turn led to lack of common focus in current multilevel modelling tools and their adoption. In this paper, we propose a formal framework, together with its corresponding tools, to tackle these challenges. The approach facilitates definition of flexible multilevel modelling hierarchies by allowing addition and deletion of intermediate abstraction levels in the hierarchies. Moreover, it facilitates separation of concerns by allowing integration of different multilevel modelling hierarchies as different aspects of the system to be modelled. In addition, our approach facilitates reusability of concepts and their behaviour by allowing definition of flexible transformation rules which are applicable to different hierarchies with a variable number of levels. As a proof of concept, a prototype tool and a domain-specific language for the definition of these rules is provided.publishedVersio

The development of nutrient contents on a new conservation area in the far North of Germany concerning different types of use. A proposal for a sustainable development in nature conservation practice

The present study analyzes a short-term observation of a newly created nature conservation area. The aim was to investigate different effects of grazing by cattle and, otherwise, the frequent mowing on the development of nutrient contents of soils. The results are typical for the strong sandy Weichselian outwash plain in the north of Central Europe (Schleswig-Holstein, Germany). Two neighboring testing areas of different use and sowed with an agricultural grass were observed for more than two years. The first area had been grazed intensively by cattle and the other one had been mowed twice a year. During this time, several nutrients and other soil parameters have been analyzed at regular intervals. Furthermore, we made observations about soil compaction and the succession of vegetation. The results show a stronger reduction especially of nitrogenous nutrients on the mowing area (-25%). In contrast, on the grazing area, the contents of nitrogen doubled during two growing seasons (+125%). However, a high atmospheric input of nitrogen strengthened the result. Less conclusive were the results about the contents of potassium, phosphorus and SOM. Therefore, mowing could be advised, if quick results are required concerning the impoverishment of soils. Furthermore, the development of succession vegetation was quite different on both areas with the number of plant species 12% higher on the grazing area. However, long-term but non-intensive cattle-grazing must still be rated as an excellent method of maintenance for this type of cultural landscape. It corresponds with the centuries-old land-use practice in this type of landscape and promotes high level of biodiversity. Therefore, there is nothing that speaks against non-intensive grazing from the beginning on a newly created nature-protection area within a long-term conception of nature conservation. The removal of A horizons should be avoided as it damages Holocene soil profies and has only short-term effects

Development of a novel sports medicine rotation for emergency medicine residents

Musculoskeletal complaints are the most common reason for patients to visit a physician, yet competency in musculoskeletal medicine is invariably reported as a deficiency in medical education in the USA. Sports medicine clinical rotations improve both medical students' and residents' musculoskeletal knowledge. Despite the importance of this knowledge, a standardized sports medicine curriculum in emergency medicine (EM) does not exist. Hence, we developed a novel sports medicine rotation for EM residents to improve their musculoskeletal educational experience and to improve their knowledge in musculoskeletal medicine by teaching the evaluation and management of many common musculoskeletal disorders and injuries that are encountered in the emergency department. The University of Arizona has two distinct EM residency programs, South Campus (SC) and University Campus (UC). The UC curriculum includes a traditional 4-week orthopedic rotation, which consistently rated poorly on evaluations by residents. Therefore, with the initiation of a new EM residency at SC, we replaced the standard orthopedic rotation with a novel sports medicine rotation for EM interns. This rotation includes attendance at sports medicine clinics with primary care and orthopedic sports medicine physicians, involvement in sport event coverage, assigned reading materials, didactic experiences, and an on-call schedule to assist with reductions in the emergency department. We analyzed postrotation surveys completed by residents, postrotation evaluations of the residents completed by primary care sports medicine faculty and orthopedic chief residents, as well as the total number of dislocation reductions performed by each graduating resident at both programs over the last 5 years. While all residents in both programs exceeded the ten dislocation reductions required for graduation, residents on the sports medicine rotation had a statistically significant higher rate of satisfaction of their educational experience when compared to the traditional orthopedics rotation. All SC residents successfully completed their sports medicine rotation, had completed postrotation evaluations by attending physicians, and had no duty hour violations while on sports medicine. In our experience, a sports medicine rotation is an effective alternative to the traditional orthopedics rotation for EM residents.This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Predicting At-Risk Opioid Use Three Months After Ed Visit for Trauma: Results from the AURORA Study

OBJECTIVE: Whether short-term, low-potency opioid prescriptions for acute pain lead to future at-risk opioid use remains controversial and inadequately characterized. Our objective was to measure the association between emergency department (ED) opioid analgesic exposure after a physical, trauma-related event and subsequent opioid use. We hypothesized ED opioid analgesic exposure is associated with subsequent at-risk opioid use. METHODS: Participants were enrolled in AURORA, a prospective cohort study of adult patients in 29 U.S., urban EDs receiving care for a traumatic event. Exclusion criteria were hospital admission, persons reporting any non-medical opioid use (e.g., opioids without prescription or taking more than prescribed for euphoria) in the 30 days before enrollment, and missing or incomplete data regarding opioid exposure or pain. We used multivariable logistic regression to assess the relationship between ED opioid exposure and at-risk opioid use, defined as any self-reported non-medical opioid use after initial ED encounter or prescription opioid use at 3-months. RESULTS: Of 1441 subjects completing 3-month follow-up, 872 participants were included for analysis. At-risk opioid use occurred within 3 months in 33/620 (5.3%, CI: 3.7,7.4) participants without ED opioid analgesic exposure; 4/16 (25.0%, CI: 8.3, 52.6) with ED opioid prescription only; 17/146 (11.6%, CI: 7.1, 18.3) with ED opioid administration only; 12/90 (13.3%, CI: 7.4, 22.5) with both. Controlling for clinical factors, adjusted odds ratios (aORs) for at-risk opioid use after ED opioid exposure were: ED prescription only: 4.9 (95% CI 1.4, 17.4); ED administration for analgesia only: 2.0 (CI 1.0, 3.8); both: 2.8 (CI 1.2, 6.5). CONCLUSIONS: ED opioids were associated with subsequent at-risk opioid use within three months in a geographically diverse cohort of adult trauma patients. This supports need for prospective studies focused on the long-term consequences of ED opioid analgesic exposure to estimate individual risk and guide therapeutic decision-making

Autophagy in major human diseases

Abstract: Autophagy is a core molecular pathway for the preservation of cellular and organismal homeostasis. Pharmacological and genetic interventions impairing autophagy responses promote or aggravate disease in a plethora of experimental models. Consistently, mutations in autophagy‐related processes cause severe human pathologies. Here, we review and discuss preclinical data linking autophagy dysfunction to the pathogenesis of major human disorders including cancer as well as cardiovascular, neurodegenerative, metabolic, pulmonary, renal, infectious, musculoskeletal, and ocular disorders

Mutation of conserved active-site threonine residues in creatine kinase affects autophosphorylation and enzyme kinetics.

Muscle-type creatine kinase (MM-CK) is a member of an isoenzyme family with key functions in cellular energetics. It has become a matter of debate whether the enzyme is autophosphorylated, as reported earlier [Hemmer, Furter-Graves, Frank, Wallimann and Furter (1995) Biochim. Biophys. Acta 1251, 81-90], or exclusively nucleotidylated. In the present paper, we demonstrate unambiguously that CK is indeed autophosphorylated. However, this autophosphorylation is not solely responsible for the observed microheterogeneity of MM-CK on two-dimensional isoelectric focusing gels. Using phosphoamino-acid analysis of (32)P-labelled CK isoforms, phosphothreonine (P-Thr) residues were identified as the only product of autophosphorylation for all CK isoenzymes. The phosphorylated residues in chicken MM-CK were allocated to a region in the vicinity of the active site, where five putative phosphorylation sites were identified. Site-directed threonine-valine-replacement mutants reveal that autophosphorylation is not specific for one particular residue but occurs at all examined threonine residues. The enzyme kinetic parameters indicate that the autophosphorylation of CK exerts a modulatory effect on substrate binding and the equilibrium constant, rather than on the catalytic mechanism itself

A conserved negatively charged cluster in the active site of creatine kinase is critical for enzymatic activity.

International audienceCreatine kinase catalyzes the reversible transphosphorylation of creatine by MgATP. From the sequence homology and the molecular structure of creatine kinase isoenzymes, we have identified several highly conserved residues with a potential function in the active site: a negatively charged cluster (Glu(226), Glu(227), Asp(228)) and a serine (Ser(280)). Mutant proteins E226Q, E226L, E227Q, E227L, D228N, and S280A/S280D of human sarcomeric mitochondrial creatine kinase were generated by in vitro mutagenesis, expressed in Escherichia coli, and purified to homogeneity. Their overall structural integrity was confirmed by CD spectroscopy and gel filtration chromatography. The enzymatic activity of all proteins mutated in the negatively charged cluster was extremely low (0.002-0.4% of wild type) and showed apparent Michaelis constants (K(m)) similar to wild type, suggesting that most of the residual activity may be attributed to wild-type revertants. Mutations of Ser(280) led to higher residual activities and altered K(m) values; S280A showed an increase of K(m) for phosphocreatine (65-fold), creatine (6-fold), and ATP (6-fold); S280D showed a decrease of K(m) for creatine (6-fold). These results, together with the transition state structure of the homologous arginine kinase (Zhou, G., Somasundaram, T., Blanc, E., Parthasarathy G., Ellington, W. R., and Chapman, M. S. (1998) Proc. Natl. Acad. Sci. U. S. A. 95, 8449-8454), strongly suggest a critical role of Glu(226), Glu(227), and Asp(228) in substrate binding and catalysis and point to Glu(227) as a catalytic base

Clinical and historical features of emergency department patients with pericardial effusions

BACKGROUND: Diagnosing pericardial effusion is critical for optimal patient care. Typically, clinicians use physical examination findings and historical features suggesting pericardial effusion to determine which patients require echocardiography. The diagnostic characteristics of these tools are not well described. The objective of this study is to determine the prevalence of historical features and sensitivity of clinical signs to inform clinicians when to proceed with echocardiogram. METHODS: A retrospective review of point-of-care echocardiograms performed over a two and a half year period in two emergency departments were reviewed for the presence of a pericardial effusion. Patient charts were reviewed and abstracted for presenting symptoms, historical features and clinical findings. The prevalence of presenting symptoms and historical features and the sensitivity of classic physical examination findings associated with pericardial effusion and tamponade were determined. RESULTS: One hundred and fifty-three patients with pericardial effusion were identified. Of these patients, the most common presenting complaint was chest pain and shortness of breath. Patients had no historical features that would suggest pericardial effusion in 37.5% of cases. None of the patients with pericardial effusion or pericardial tamponade had all of the elements of Beck's triad. The sensitivity of Beck's triad was found to be 0 (0%-19.4%). The sensitivity for one finding of Beck's triad to diagnose pericardial tamponade was 50% (28.0%-72.0%). CONCLUSION: History and physical examination findings perform poorly as tests for the diagnosis of pericardial effusion or pericardial tamponade. Clinicians must liberally evaluate patients suspected of having a pericardial effusion with echocardiography.Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Clinical and historical features of emergency department patients with pericardial effusions

BACKGROUND: Diagnosing pericardial effusion is critical for optimal patient care. Typically, clinicians use physical examination findings and historical features suggesting pericardial effusion to determine which patients require echocardiography. The diagnostic characteristics of these tools are not well described. The objective of this study is to determine the prevalence of historical features and sensitivity of clinical signs to inform clinicians when to proceed with echocardiogram. METHODS: A retrospective review of point-of-care echocardiograms performed over a two and a half year period in two emergency departments were reviewed for the presence of a pericardial effusion. Patient charts were reviewed and abstracted for presenting symptoms, historical features and clinical findings. The prevalence of presenting symptoms and historical features and the sensitivity of classic physical examination findings associated with pericardial effusion and tamponade were determined. RESULTS: One hundred and fifty-three patients with pericardial effusion were identified. Of these patients, the most common presenting complaint was chest pain and shortness of breath. Patients had no historical features that would suggest pericardial effusion in 37.5% of cases. None of the patients with pericardial effusion or pericardial tamponade had all of the elements of Beck’s triad. The sensitivity of Beck’s triad was found to be 0 (0%–19.4%). The sensitivity for one finding of Beck’s triad to diagnose pericardial tamponade was 50% (28.0%–72.0%). CONCLUSION: History and physical examination findings perform poorly as tests for the diagnosis of pericardial effusion or pericardial tamponade. Clinicians must liberally evaluate patients suspected of having a pericardial effusion with echocardiography