This book offers an introduction to Chiral Perturbation Theory. Coverage starts with the Lagrangian of the strong interactions and general symmetry principles, then develops the basic concepts of ...Chiral Perturbation Theory in the mesonic and baryonic sectors.
A relation is presented between single-hadron long-range matrix elements defined in a finite Euclidean spacetime and the corresponding infinite-volume Minkowski amplitudes. This relation is valid in ...the kinematic region where any number of two-hadron states can simultaneously go on shell, so that the effects of strongly coupled intermediate channels are included. These channels can consist of nonidentical particles with arbitrary intrinsic spins. The result accommodates general Lorentz structures as well as nonzero momentum transfer for the two external currents inserted between the single-hadron states. The formalism, therefore, generalizes the work by Christ et al. Phys. Rev. D 91, 114510 (2015) and extends the reach of lattice quantum chromodynamics (QCD) to a wide class of new observables beyond meson mixing and rare decays. Applications include Compton scattering of the pion ( π γ ⋆ → π π , K ¯¯¯¯ K → π γ ⋆ ), kaon ( K γ ⋆ → π K , η K → K γ ⋆ ), and nucleon ( N γ ⋆ → N π → N γ ⋆ ), as well as double- β decays, and radiative corrections to the single- β decay, of QCD-stable hadrons. The framework presented will further facilitate generalization of the result to studies of nuclear amplitudes involving two currents from lattice QCD.
Popeye domain containing1 (Popdc1), also named Bves, is an evolutionary conserved membrane protein. Despite its high expression level in the heart little is known about its membrane localization and ...cardiac functions. The study examined the hypothesis that Popdc1 might be associated with the caveolae and play a role in myocardial ischemia tolerance. To address these issues, we analyzed hearts and cardiomyocytes of wild type and Popdc1-null mice. Immunoconfocal microscopy revealed co-localization of Popdc1 with caveolin3 in the sarcolemma, intercalated discs and T-tubules and with costameric vinculin. Popdc1 was co-immunoprecipitated with caveolin3 from cardiomyocytes and from transfected COS7 cells and was co-sedimented with caveolin3 in equilibrium density gradients. Caveolae disruption by methyl-β-cyclodextrin or by ischemia/reperfusion (I/R) abolished the cellular co-localization of Popdc1 with caveolin3 and modified their density co-sedimentation. The caveolin3-rich fractions of Popdc1-null hearts redistributed to fractions of lower buoyant density. Electron microscopy showed a statistically significant 70% reduction in caveolae number and a 12% increase in the average diameter of the remaining caveolae in the mutant hearts. In accordance with these changes, Popdc1-null cardiomyocytes displayed impaired Ca(+2)i transients, increased vulnerability to oxidative stress and no pharmacologic preconditioning. In addition, induction of I/R injury to Langendorff-perfused hearts indicated a significantly lower functional recovery in the mutant compared with wild type hearts while their infarct size was larger. No improvement in functional recovery was observed in Popdc1-null hearts following ischemic preconditioning. The results indicate that Popdc1 is a caveolae-associated protein important for the preservation of caveolae structural and functional integrity and for heart protection.
North American grassland birds have widely declined over the past 50 years, largely due to anthropogenic-driven loss of native prairie habitat. In response to these declines, many conservation ...programs have been implemented to help secure wildlife habitat on private and public lands. The Grasslands Coalition is one such initiative established to advance the conservation of grassland birds in Missouri. The Missouri Department of Conservation conducted annual point count surveys for comparison of grassland bird relative abundance between focal grassland areas and nearby paired (i.e., containing no targeted management) sites. We analyzed 17 years of point count data with a generalized linear mixed model in a Bayesian framework to estimate relative abundance and trends across focal or paired sites for nine bird species of management interest that rely on grasslands: barn swallow (Hirundo rustica), brown-headed cowbird (Molothrus ater), dickcissel (Spiza americana), eastern meadowlark (Sturnella magna), grasshopper sparrow (Ammodramus savannarum), Henslow's sparrow (A. henslowii), horned lark (Eremophila alpestris), northern bobwhite (Colinus virginianus), and red-winged blackbird (Agelaius phoeniceus). Relative abundance of all species except eastern meadowlarks declined regionally. Relative abundance of barn swallows, brown-headed cowbirds, dickcissels, eastern meadowlarks, Henslow's sparrows, and northern bobwhites was higher in focal than paired sites, though relative abundance trends were only improved in focal vs. paired areas for dickcissels and Henslow's sparrows. Relative abundance increased with increasing grassland cover at the local (250-m radius) scale for all species except horned larks and red-winged blackbirds and at the landscape (2,500-m radius) scale for all species except dickcissels, eastern meadowlarks, and northern bobwhites. Our results suggest focal areas contained greater relative abundances of several grassland species of concern, likely due to increased availability of grassland habitat at local and landscape scales. Further efforts to decrease landscape-scale fragmentation and improve habitat quality may be needed to achieve conservation goals.
A large number of promising candidate disease-modifying treatments for Alzheimer disease (AD) continue to advance into phase II and phase III testing. However, most completed trials have failed to ...demonstrate efficacy, and there is growing concern that methodologic difficulties may contribute to these clinical trial failures. The optimal time to intervene with such treatments is probably in the years prior to the onset of dementia, before the neuropathology has progressed to the advanced stage corresponding to clinical dementia.
An international task force of individuals from academia, industry, nonprofit foundations, and regulatory agencies was convened to discuss optimal trial design in early (predementia) AD.
General consensus was reached on key principles involving the scope of the AD diagnosis, the selection of subjects for trials, outcome measures, and analytical methods.
A consensus has been achieved in support of the testing of candidate treatments in the early (predementia) AD population.
Renal function in humans declines with old age. Currently, the normal range for renal function is not differentiated by age but uniformly given, which has evoked criticism. The symptoms of high-grade ...impairment of renal function are nonspecific. The current data situation does not support early initiation of dialysis: on the contrary, initiation of dialysis should be decided from clinical aspects and not according to the values for the glomerular filtration rate (GFR). Elderly patients should be offered peritoneal dialysis (PD) as well as hemodialysis (HD), which can be performed either at home (PD) or at a dialysis center (HD or PD). Patients and their relatives should be presented with all available information on both therapy options but there are also conservative, palliative therapy options for the very old or for those with a high number of comorbidities. The decision for therapy should be individualized and tailored for each patient. The planning of kidney replacement therapy should be carried out well in advance. A multidisciplinary team should discuss possible barriers to one or the other treatment option and provide assistance for implementation of the individual optimal therapy. In some cases a home-based assisted PD can be a sensible option.
We evaluated the performance characteristics of computed tomographic (CT) virtual colonoscopy for the detection of colorectal neoplasia in an average-risk screening population.
A total of 1233 ...asymptomatic adults (mean age, 57.8 years) underwent same-day virtual and optical colonoscopy. Radiologists used the three-dimensional endoluminal display for the initial detection of polyps on CT virtual colonoscopy. For the initial examination of each colonic segment, the colonoscopists were unaware of the findings on virtual colonoscopy, which were revealed to them before any subsequent reexamination. The sensitivity and specificity of virtual colonoscopy and the sensitivity of optical colonoscopy were calculated with the use of the findings of the final, unblinded optical colonoscopy as the reference standard.
The sensitivity of virtual colonoscopy for adenomatous polyps was 93.8 percent for polyps at least 10 mm in diameter, 93.9 percent for polyps at least 8 mm in diameter, and 88.7 percent for polyps at least 6 mm in diameter. The sensitivity of optical colonoscopy for adenomatous polyps was 87.5 percent, 91.5 percent, and 92.3 percent for the three sizes of polyps, respectively. The specificity of virtual colonoscopy for adenomatous polyps was 96.0 percent for polyps at least 10 mm in diameter, 92.2 percent for polyps at least 8 mm in diameter, and 79.6 percent for polyps at least 6 mm in diameter. Two polyps were malignant; both were detected on virtual colonoscopy, and one of them was missed on optical colonoscopy before the results on virtual colonoscopy were revealed.
CT virtual colonoscopy with the use of a three-dimensional approach is an accurate screening method for the detection of colorectal neoplasia in asymptomatic average-risk adults and compares favorably with optical colonoscopy in terms of the detection of clinically relevant lesions.
Summary
Background
Nucleos(t)ide analogues (NUCs) for chronic hepatitis B treatment achieve high rates of viral suppression and are generally well tolerated. Entecavir (ETV) and tenofovir disoproxil ...fumarate (TDF) are the currently preferred first‐line agents. The safety of these agents in clinical practice is particularly relevant since long‐term treatment is usually required.
Aim
To summarise and critically discuss recent real‐world evidence on the safety of treatment with ETV or TDF in hepatitis B virus (HBV)‐monoinfected patients.
Methods
PubMed and conference proceedings up to 15th June 2015 were searched using the terms (((Hepatitis_B) OR HBV) AND ((tenofovir) OR entecavir)) AND (((lactic_acidosis) OR bone) OR renal)).
Results
In selected populations included in registration studies, both ETV and TDF were well tolerated with no clinically significant renal toxicity or lactic acidosis. Growing ‘real‐world’ clinical experience with these agents includes some reports of ETV‐associated lactic acidosis and TDF‐associated renal impairment; however, evidence from cohort studies appears to be conflicting. In the case of ETV‐related lactic acidosis, a small number of cases have been reported, all in patients with decompensated cirrhosis. The degree of association between TDF treatment and changes in markers of renal function varies between studies: discrepancies may result from the use of different definitions and cut‐offs for reporting renal toxicities, and differences in patient populations.
Conclusions
Pre‐treatment and on‐treatment monitoring of eGFR and phosphorus, with prompt appropriate dose adjustment or treatment switch can minimise the impact of NUC renal toxicity. Standardisation of measures of renal impairment and identification of early molecular markers remain an unmet need.
The impacts of the partitioning of potentially toxic metals (PTM) within the estuarine environment is highly complex, but is of key significance owing to increases in populations living within such ...sensitive environments. Although empirical data exist for the partitioning of metals between the dissolved and particulate phases, little is known regarding the impacts of extracellular polymeric substances (EPS) upon the flocculation of particles within such a dynamic system nor the resultant influence on the distribution of metals between the particulate and dissolved phases. This prevents regulators from fully understanding the fate and risks associated with metals in estuaries. This study provides data associated with the simulation of 3 settlings typical of the turbulent mixing found in estuaries and partitioning of copper, cadmium, nickel, arsenic, lead and zinc for 3 salinities (0, 15, 30 PSU) reflecting the full salinity range from freshwater to seawater. Experiments were completed with and without the presence of EPS, using kaolin as the mineral particulate. The results showed significant differences between salinity, PTMs and turbulence for the experiments with and without EPS present. Overall, salinity was the main factor controlling the PTM partitioning to sediment, however the flocculation process did impact on the PTM distribution and with the addition of EPS the impact was more pronounced. The data highlighted the importance of taking account of EPS within any estuarine sediment process modelling, for relying on simple partitioning with corrections for salinity would likely lead to significant bias.
Variations in partitioning coefficient, Kp, for 6 potentially toxic metals (PTMs) at three catchment salinities for slack water at low tide (low turbulent shear stress, τ = 0.10 Pa). Solid bars show Kp for mineral-only sediment (biotic case); Outlined bars show Kp for sediment containing EPS (biotic case). Display omitted
•Turbulence shear stress impacts on trace element partitioning•Naturally occurring biopolymers significantly impact trace element partitioning•Biopolymer increases partition coefficients for some metals by orders of magnitude•Saline waters prone to partitioning changes for elements with biopolymer present•Rate of particulate PTM deposition likely to vary by two orders of magnitude across tidal cycles
The goal of this study was to identify changes in extracellular vesicles (EV) surface proteins specific to traumatic brain injury (TBI), which could be used as a diagnostic and prognostic tool in ...polytrauma patients.
Known serum TBI-specific biomarkers (S100B, NSE, and GFAP), which can predict the severity and outcome of isolated TBI, lose their predictive value in the presence of additional extracranial injuries. Extracellular vesicles (EVs) are released from cells in response to various stimuli and carry specific cargo/surface molecules that could be used for tracking injury-responding cells.
EVs were isolated using size exclusion chromatography (SEC) from the plasma of two groups of patients (with isolated TBI, ISS≥16, AIShead≥4, n=10; and polytraumatized patients without TBI ISS≥16, AIShead=0, n=10) collected in the emergency room and 48 h after trauma. EVs' surface epitope expression was investigated using a neurospecific multiplex flow cytometry assay and compared with healthy controls (n=10). Three enrichments of EV epitopes found to be specific to TBI were validated by western blot.
The expression of 10 EV epitopes differed significantly among the patient and control groups, and five of these epitopes (CD13, CD196, MOG, CD133, and MBP) were TBI-specific. The increased expression of CD196, CD13, and MOG-positive EVs was validated by western blot.
Our data showed that TBI is characterized by a significant increase of CD13, CD196, MOG, CD133, and MBP-positive EVs in patients' plasma. A high level of MOG-positive EVs negatively correlated with the Glasgow Coma Scale score at admission and could be an indicator of poor neurological status.
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