308 research outputs found

    Equilibration, generalized equipartition, and diffusion in dynamical Lorentz gases

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    We prove approach to thermal equilibrium for the fully Hamiltonian dynamics of a dynamical Lorentz gas, by which we mean an ensemble of particles moving through a dd-dimensional array of fixed soft scatterers that each possess an internal harmonic or anharmonic degree of freedom to which moving particles locally couple. We establish that the momentum distribution of the moving particles approaches a Maxwell-Boltzmann distribution at a certain temperature TT, provided that they are initially fast and the scatterers are in a sufficiently energetic but otherwise arbitrary stationary state of their free dynamics--they need not be in a state of thermal equilibrium. The temperature TT to which the particles equilibrate obeys a generalized equipartition relation, in which the associated thermal energy kBTk_{\mathrm B}T is equal to an appropriately defined average of the scatterers' kinetic energy. In the equilibrated state, particle motion is diffusive

    A pragmatic study exploring the prevention of delirium among hospitalized older hip fracture patients: Applying evidence to routine clinical practice using clinical decision support

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    Delirium occurs in up to 65% of older hip fracture patients. Developing delirium in hospital has been associated with a variety of adverse outcomes. Trials have shown that multi-component preventive interventions can lower delirium rates. The objective of this study was to implement and evaluate the effectiveness of an evidence-based electronic care pathway, which incorporates multi-component delirium strategies, among older hip fracture patients. We conducted a pragmatic study using an interrupted time series design in order to evaluate the use and impact of the intervention. The target population was all consenting patients aged 65 years or older admitted with an acute hip fracture to the orthopedic units at two Calgary, Alberta hospitals. The primary outcome was delirium rates. Secondary outcomes included length of hospital stay, in-hospital falls, in-hospital mortality, new discharges to long-term care, and readmissions. A Durbin Watson test was conducted to test for serial correlation and, because no correlation was found, Chi-square statistics, Wilcoxon test and logistic regression analyses were conducted as appropriate. At study completion, focus groups were conducted at each hospital to explore issues around the use of the order set. During the 40-week study period, 134 patients were enrolled. The intervention had no effect on the overall delirium rate (33% pre versus 31% post; p = 0.84). However, there was a significant interaction between study phase and hospital (p = 0.03). Although one hospital did not experience a decline in delirium rate, the delirium rate at the other hospital declined from 42% to 19% (p = 0.08). This difference by hospital was mirrored in focus group feedback. The hospital that experienced a decline in delirium rates was more supportive of the intervention. Overall, post-intervention there were no significant differences in mean length of stay (12 days post versus 14 days pre; p = 0.74), falls (6% post versus 10% pre; p = 0.43) or discharges to long-term care (6% post versus 13% pre; p = 0.20). Translation of evidence-based multi-component delirium prevention strategies into everyday clinical care, using the electronic medical record, was not found to be effective at decreasing delirium rates among hip facture patients

    Classical motion in force fields with short range correlations

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    We study the long time motion of fast particles moving through time-dependent random force fields with correlations that decay rapidly in space, but not necessarily in time. The time dependence of the averaged kinetic energy and mean-squared displacement is shown to exhibit a large degree of universality; it depends only on whether the force is, or is not, a gradient vector field. When it is, p^{2}(t) ~ t^{2/5} independently of the details of the potential and of the space dimension. Motion is then superballistic in one dimension, with q^{2}(t) ~ t^{12/5}, and ballistic in higher dimensions, with q^{2}(t) ~ t^{2}. These predictions are supported by numerical results in one and two dimensions. For force fields not obtained from a potential field, the power laws are different: p^{2}(t) ~ t^{2/3} and q^{2}(t) ~ t^{8/3} in all dimensions d\geq 1

    A single site in human β-hexosaminidase A binds both 6-sulfate-groups on hexosamines and the sialic acid moiety of GM2 ganglioside

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    AbstractHuman β-hexosaminidase A (Hex A) (αβ) is composed of two subunits whose primary structures are ∼60% identical. Deficiency of either subunit results in severe neurological disease due to the storage of GM2 ganglioside; Tay–Sachs disease, α deficiency, and Sandhoff disease, β deficiency. Whereas both subunits contain active sites only the α-site can efficiently bind negatively charged 6-sulfated hexosamine substrates and GM2 ganglioside. We have recently identified the αArg424 as playing a critical role in the binding of 6-sulfate-containing substrates, and βAsp452 as actively inhibiting their binding. To determine if these same residues affect the binding of the sialic acid moiety of GM2 ganglioside, an αArg424Gln form of Hex A was expressed and its kinetics analyzed using the GM2 activator protein:[3H]-GM2 ganglioside complex as a substrate. The mutant showed a ∼3-fold increase in its Km for the complex. Next a form of Hex B (ββ) containing a double mutation, βAspLeu453AsnArg (duplicating the α-aligning sequences), was expressed. As compared to the wild type (WT), the mutant exhibited a >30-fold increase in its ability to hydrolyze a 6-sulfated substrate and was now able to hydrolyze GM2 ganglioside when the GM2 activator protein was replaced by sodium taurocholate. Thus, this α-site is critical for binding both types of negatively charge substrates

    Characteristics associated with polypharmacy in people with type 2 diabetes:the Dutch Diabetes Pearl cohort

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    Contains fulltext : 232027.pdf (Publisher’s version ) (Open Access)AIM: To describe the prevalence and characteristics of polypharmacy in a Dutch cohort of individuals with type 2 diabetes. METHODS: We included people with type 2 diabetes from the Diabetes Pearl cohort, of whom 3886 were treated in primary care and 2873 in academic care (secondary/tertiary). With multivariable multinomial logistic regression analyses stratified for line of care, we assessed which sociodemographic, lifestyle and cardiometabolic characteristics were associated with moderate (5-9 medications) and severe polypharmacy (≥10 medications) compared with no polypharmacy (0-4 medications). RESULTS: Mean age was 63 ± 10 years, and 40% were women. The median number of daily medications was 5 (IQR 3-7) in primary care and 7 (IQR 5-10) in academic care. The prevalence of moderate and severe polypharmacy was 44% and 10% in primary care, and 53% and 29% in academic care respectively. Glucose-lowering and lipid-modifying medications were most prevalent. People with severe polypharmacy used a relatively large amount of other (i.e. non-cardiovascular and non-glucose-lowering) medication. Moderate and severe polypharmacy across all lines of care were associated with higher age, low educational level, more smoking, longer diabetes duration, higher BMI and more cardiovascular disease. CONCLUSIONS: Severe and moderate polypharmacy are prevalent in over half of people with type 2 diabetes in primary care, and even more in academic care. People with polypharmacy are characterized by poorer cardiometabolic status. These results highlight the significance of polypharmacy in type 2 diabetes

    High prevalence of impaired awareness of hypoglycemia and severe hypoglycemia among people with insulin-treated type 2 diabetes: The Dutch Diabetes Pearl Cohort

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    Objective People with type 2 diabetes on insulin are at risk for hypoglycemia. Recurrent hypoglycemia can cause impaired awareness of hypoglycemia (IAH), and increase the risk for severe hypoglycemia. The aim of this study was to assess the prevalence and determinants of self-reported IAH and severe hypoglycemia in a Dutch nationwide cohort of people with insulin-treated type 2 diabetes. Research design and methods Observational study of The Dutch Diabetes Pearl, a cohort of people with type 2 diabetes treated in primary, secondary and tertiary diabetes care centers. The presence of IAH and the occurrence of severe hypoglycemia in the past year, defined as an event requiring external help to re

    Calorimetric Behavior of Phosphatidylcholine/Phosphatidylethanolamine Bilayers is Compatible with the Superlattice Model

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    Differential scanning calorimetry was used to study the phase behavior of binary lipid bilayers consisting of phosphatidylcholine (PC) and phosphatidylethanolamine (PE) of varying acyl chain length. A two-state transition model was used to resolve the individual transition components, and the two-state transition enthalpy, the relative enthalpy, and the transition temperature of each component were plotted as a function of composition. Intriguingly, abrupt changes in these thermodynamic parameters were observed at or close to many “critical” XPE values predicted by the superlattice model proposing that phospholipids with different headgroups tend to adopt regular rather than random lateral distributions. Statistical analysis indicated that the agreement between the observed and predicted “critical” compositions is highly significant. Accordingly, these data provide strong evidence that the molecules in PC/PE bilayers tend to adopt regular, superlattice-like lateral arrangements, which could be involved in the regulation of the lipid compositions of biological membranes

    The Diabetes Pearl: Diabetes biobanking in The Netherlands

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    Contains fulltext : 109720.pdf (publisher's version ) (Open Access)ABSTRACT: BACKGROUND: Type 2 diabetes is associated with considerable comorbidity and severe complications, which reduce quality of life of the patients and require high levels of healthcare. The Diabetes Pearl is a large cohort of patients diagnosed with type 2 diabetes, covering different geographical areas in the Netherlands. The aim of the study is to create a research infrastructure that will allow the study of risk factors, including biomarkers and genetic determinants for severe diabetes complications. METHODS/DESIGN: Baseline examinations began November 2009 and will continue through 2012. By the end of 2012, it is expected that 7000 patients with type 2 diabetes will be included in the Diabetes Pearl cohort. To ensure quality of the data collected, standard operation procedures were developed and used in all 8 recruitment centers. From all patients who provide informed consent, the following information is collected: personal information, medication use, physical examination (antropometry, blood pressure, electrocardiography (ECG), retina photographs, ankle-brachial index, peripheral vibration perception), self-report questionnaire (socio-economic status, lifestyle, (family) history of disease, and psychosocial well-being), laboratory measurements (glucose, A1c, lipid profile, kidney function), biobank material (storage of urine and blood samples and isolated DNA). All gathered clinical data and biobank information is uploaded to a database for storage on a national level. Biobanks are maintained locally at all recruitment centers. DISCUSSION: The Diabetes Pearl is large-scale cohort of type 2 diabetes patients in the Netherlands aiming to study risk factors, including biomarkers and genetic markers, for disease deterioration and the development of severe diabetes complications. As a result of the well-designed research design and the national coverage, the Diabetes Pearl data can be of great value to national and international researchers with an interest in diabetes related research
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