63 research outputs found
Physical Activity, High-Sensitivity C-Reactive Protein, and Total and Cardiovascular Disease Mortality in Type 2 Diabetes
Long-term clinical and economic outcomes in previously untreated paediatric patients with severe haemophilia A : A nationwide real-world study with 700 person-years
AimFor previously untreated patients (PUPs) with severe haemophilia A in Finland for the past 2 decades, the standard practice has been to start early primary prophylaxis. We evaluated the long-term clinical outcomes and costs of treatment with high-dose prophylaxis in PUPs from birth to adolescence, including immune tolerance induction (ITI). MethodsFrom the medical records of all PUPs born between June 1994 and May 2013 in Finland, we retrospectively extracted data on clinical outcomes and healthcare use. Using linear mixed models, we analysed longitudinal clinical outcome data. To analyse skewed cost data, including zero costs, we applied hurdle regression. ResultsAll 62 patients received early regular prophylaxis; totally, they have had treatment for nearly 700 patient-years. The median age of starting home treatment was 1.1years. The mean (SD) annual treatment costs (Europerkg) were 4391Euro (3852). For ages 1-3, ITI comprised over half of the costs; in other groups, prophylactic FVIII treatment dominated. With these high costs, however, clinical outcomes were desirable; median (IQR) ABR was low at 0.19 (0.07-0.46) and so was AJBR at 0.06 (0-0.24). Thirteen (21%) patients developed a clinically significant inhibitor, 10 (16%) with a high titre. All ITIs were successful. The mean costs for ITI were 383448Euro (259085). The expected ITI payback period was 1.81 (95% CI 0.62-12.12) years. ConclusionsEarly high-dose prophylaxis leads to excellent long-term clinical outcomes, and early childhood ITI therapy seems to turn cost-neutral generally already in 2years.Peer reviewe
Mesonic correlation lengths in high-temperature QCD
We consider spatial correlation lengths \xi for various QCD light quark
bilinears at temperatures above a few hundred MeV. Some of the correlation
lengths (such as that related to baryon density) coincide with what has been
measured earlier on from glueball-like states; others do not couple to
glueballs, and have a well-known perturbative leading-order expression as well
as a computable next-to-leading-order correction. We determine the latter
following analogies with the NRQCD effective theory, used for the study of
heavy quarkonia at zero temperature: we find (for the quenched case) \xi^{-1} =
2 \pi T + 0.1408 g^2 T, and compare with lattice results. One manifestation of
U_A(1) symmetry non-restoration is also pointed out.Comment: 25 pages. v2: small clarifications; published versio
Bacterial diversity and predicted enzymatic function in a multipurpose surface water system - from wastewater effluent discharges to drinking water production
Identification of the Allosteric Regulatory Site of Insulysin
Background: Insulin degrading enzyme (IDE) is responsible for the metabolism of insulin and plays a role in clearance of the Ab peptide associated with Alzheimer's disease. Unlike most proteolytic enzymes, IDE, which consists of four structurally related domains and exists primarily as a dimer, exhibits allosteric kinetics, being activated by both small substrate peptides and polyphosphates such as ATP.Principal Findings: the crystal structure of a catalytically compromised mutant of IDE has electron density for peptide ligands bound at the active site in domain 1 and a distal site in domain 2. Mutating residues in the distal site eliminates allosteric kinetics and activation by a small peptide, as well as greatly reducing activation by ATP, demonstrating that this site plays a key role in allostery. Comparison of the peptide bound IDE structure (using a low activity E111F IDE mutant) with unliganded wild type IDE shows a change in the interface between two halves of the clamshell-like molecule, which may enhance enzyme activity by altering the equilibrium between closed and open conformations. in addition, changes in the dimer interface suggest a basis for communication between subunits.Conclusions/Significance: Our findings indicate that a region remote from the active site mediates allosteric activation of insulysin by peptides. Activation may involve a small conformational change that weakens the interface between two halves of the enzyme.United States Public Health ServicesUniv Kentucky, Dept Mol & Cellular Biochem, Lexington, KY 40536 USAUniv Kentucky, Struct Biol Ctr, Lexington, KY USAUniversidade Federal de São Paulo, Dept Biophys, Escola Paulista Med, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Biophys, Escola Paulista Med, São Paulo, BrazilUnited States Public Health Services: NS38041United States Public Health Services: DA02243United States Public Health Services: DA016176United States Public Health Services: P20 RR20171United States Public Health Services: T32 DA016176Web of Scienc
Variability in the life history of the water strider Gerris lacustris (Heteroptera: Gerridae) across small spatial scales
Significance of spring migration and flexibility in flight-muscle histolysis in waterstriders (Heteroptera, Gerridae)
DIFFERENCES IN SURVIVORSHIP, DEVELOPMENT RATE AND FERTILITY BETWEEN THE LONGWINGED AND WINGLESS MORPHS OF THE WATERSTRIDER, LIMNOPORUS CANALICULATUS
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