Patient-centered interventions to improve medication management and adherence: A qualitative review of research findings

Patient-centered approaches to improving medication adherence hold promise, but evidence of their effectiveness is unclear. This review reports the current state of scientific research around interventions to improve medication management through four patient-centered domains: shared decision-making, methods to enhance effective prescribing, systems for eliciting and acting on patient feedback about medication use and treatment goals, and medication-taking behavior

Amyloid Precursor Protein Is Trafficked and Secreted via Synaptic Vesicles

A large body of evidence has implicated amyloid precursor protein (APP) and its proteolytic derivatives as key players in the physiological context of neuronal synaptogenesis and synapse maintenance, as well as in the pathology of Alzheimer's Disease (AD). Although APP processing and release are known to occur in response to neuronal stimulation, the exact mechanism by which APP reaches the neuronal surface is unclear. We now demonstrate that a small but relevant number of synaptic vesicles contain APP, which can be released during neuronal activity, and most likely represent the major exocytic pathway of APP. This novel finding leads us to propose a revised model of presynaptic APP trafficking that reconciles existing knowledge on APP with our present understanding of vesicular release and recycling

Modeling nitrous oxide emission from rivers: a global assessment

Estimates of global riverine nitrous oxide (N2 O) emissions contain great uncertainty. We conducted a meta-analysis incorporating 169 observations from published literature to estimate global riverine N2 O emission rates and emission factors. Riverine N2 O flux was significantly correlated with NH4 , NO3 and DIN (NH4  + NO3 ) concentrations, loads and yields. The emission factors EF(a) (i.e., the ratio of N2 O emission rate and DIN load) and EF(b) (i.e., the ratio of N2 O and DIN concentrations) values were comparable and showed negative correlations with nitrogen concentration, load and yield and water discharge, but positive correlations with the dissolved organic carbon : DIN ratio. After individually evaluating 82 potential regression models based on EF(a) or EF(b) for global, temperate zone and subtropical zone datasets, a power function of DIN yield multiplied by watershed area was determined to provide the best fit between modeled and observed riverine N2 O emission rates (EF(a): R2  = 0.92 for both global and climatic zone models, n = 70; EF(b): R2  = 0.91 for global model and R2  = 0.90 for climatic zone models, n = 70). Using recent estimates of DIN loads for 6400 rivers, models estimated global riverine N2 O emission rates of 29.6-35.3 (mean = 32.2) Gg N2 O-N yr-1 and emission factors of 0.16-0.19% (mean = 0.17%). Global riverine N2 O emission rates are forecasted to increase by 35%, 25%, 18% and 3% in 2050 compared to the 2000s under the Millennium Ecosystem Assessment's Global Orchestration, Order from Strength, Technogarden, and Adapting Mosaic scenarios, respectively. Previous studies may overestimate global riverine N2 O emission rates (300-2100 Gg N2 O-N yr-1 ) because they ignore declining emission factor values with increasing nitrogen levels and channel size, as well as neglect differences in emission factors corresponding to different nitrogen forms. Riverine N2 O emission estimates will be further enhanced through refining emission factor estimates, extending measurements longitudinally along entire river networks and improving estimates of global riverine nitrogen loads

ADAMTS-13 glycans and conformation-dependent activity.

Background: ADAMTS-13 activity can be regulated by its conformation, whereby interactions between the C-terminal CUB domains and the spacer domain maintain ADAMTS-13 in a closed conformation. ADAMTS-13 contains 10 N-linked glycans, with four sites present in theTSP2 through to CUB domains that may contribute to its conformation. Objectives/Methods: We hypothesized that glycosylation contributes to ADAMTS-13 conformation and function. The proteolytic activity of glycan-modified ADAMTS-13 was assessed under static and shear stress conditions. Results: Enzymatic removal of terminal silaic acid or entire N-linked glycan chains decreased activity against FRETS-VWF73 at pH 7.4 and against full-length von Willebrand factor (VWF) under shear stress. Using truncated ADAMTS-13, we demonstrated that this was attributable to loss of sialic acid from the glycans in the metalloprotease domain and an effect of N-linked glycosylation in the TSP2 through to CUB domains. Mutation of the N-linked glycan sites in the MDTCS domains reduced or abolished protein expression. However, the N707Q, N828Q, N1235Q and N1354Q (TSP2, TSP4, CUB1, and CUB2 domains, respectively) variants were expressed normally. Interestingly, the N707Q and N828Q variants showed reduced activity against FRETS-VWF73, but normal activity under flow conditions. In contrast, the N1235Q and N1354Q variants had enhanced activity against FRETS-VWF73 and VWF under shear stress. Immunoprecipitation experiments confirmed that loss of N-linked glycans in the CUB domains significantly reduced the interaction with the spacer domain and enhanced binding to the 6A6 anti-ADAMTS-13 antibody, which recognizes a cryptic epitope in the metalloprotease domain. Conclusions: Together, these data demonstrate that the N-linked glycans of ADAMTS-13 play a crucial role in regulating ADAMTS-13 activity

From Beveridge to Turner: demography, distribution and the future of pensions in the UK

The paper outlines the recommendations of the UK Pensions Commission, and the data and analysis on which they were based, including projections of demographic change, trends in private pension saving and evolution of the State pension system. The Commission concluded that, without reform, structural problems with UK pensions would lead to increasingly inadequate and inequitable provision by 2020-2025. It recommended reforms which would lead to a more generous, more universal and less means-tested State system than would otherwise evolve, and the establishment of a low cost national pension savings scheme, into which employees without good employer provision would automatically be enrolled. The proposals, which have now largely been adopted by the UK Government, imply eventual increases both in state spending on pensions as a share of national income and in State pension age, but accompanied by measures to facilitate later and more flexible retirement

Blocking von Willebrand factor free thiols inhibits binding to collagen under high and pathological shear stress

Background Von Willebrand factor (VWF) contains a number of free thiols, the majority of which are located in its C‐domains, and these have been shown to alter VWF function, However, the impact of free thiols on function following acute exposure of VWF to collagen under high and pathological shear stress has not been determined. Methods VWF free thiols were blocked with N‐ethylmaleimide and flow assays performed under high and pathological shear rates to determine the impact on platelet capture and collagen binding function. Atomic force microscopy (AFM) was used to probe the interaction of VWF with collagen and molecular simulations conducted to determine the effect of free thiols on the flexibility of the VWF‐C4 domain. Results Blockade of VWF free thiols reduced VWF‐mediated platelet capture to collagen in a shear‐dependent manner, with platelet capture virtually abolished above 5000 s−1 and in regions of stenosis in microfluidic channels. Direct visualization of VWF fibers formed under extreme pathological shear rates and analysis of collagen‐bound VWF attributed the effect to altered binding of VWF to collagen. AFM measurements showed that thiol‐blockade reduced the lifetime and strength of the VWF‐collagen bond. Pulling simulations of the VWF‐C4 domain demonstrated that with one or two reduced disulphide bonds the C4 domain has increased flexibility and the propensity to undergo free‐thiol exchange. Conclusions We conclude that free thiols in the C‐domains of VWF enhance the flexibility of the molecule and enable it to withstand high shear forces following collagen binding, demonstrating a previously unrecognized role for VWF free thiols

Solar Thermionic-Thermoelectric Generator (ST 2

The thermionic-thermoelectric solid-state technology, characterized by solar-to-electric conversion efficiency feasibly > 40%, is comprehensively proposed and discussed for conversion of concentrating solar power. For the first time, the related solar generator prototype is designed and fabricated by developing advanced materials functionalized for the specific application, such as thermally resistant hafnium carbide-based radiation absorbers, surface-textured at the nanoscale to obtain a solar absorptance > 90%, and chemical vapor deposition diamond films, acting as low- work-function (2.06 eV) thermionic emitters. Commercial thermoelectric generators and encapsulation vacuum components complete the prototype. The conversion efficiency is here evaluated under outdoor concentrated sunlight, demonstrating thermionic stage output power of 130 mW at 756 °C, combined to the maximum thermoelectric output power of 290 mW. The related solar-to-electric conversion efficiency is found to be 0.4%, but, once the net thermal flux fed to the conversion stages is considered, a thermal-to-electric efficiency of 6% is revealed. Factors affecting the performance of the present prototype are analyzed and discussed, as well as a strategy to rapidly overcome limitations, in order to prepare an efficient and highly competitive solid-state conversion alternative for future concentrating solar plant