Congestive heart failure in rats is associated with increased expression and targeting of aquaporin-2 water channel in collecting duct

We tested whether severe congestive heart failure (CHF), a condition associated with excess free-water retention, is accompanied by altered regulation of the vasopressin-regulated water channel, aquaporin-2 (AQP2), in the renal collecting duct. CHF was induced by left coronary artery ligation. Compared with sham-operated animals, rats with CHF had severe heart failure with elevated left ventricular end-diastolic pressures (LVEDP): 26.9 ± 3.4 vs. 4.1 ± 0.3 mmHg, and reduced plasma sodium concentrations (142.2 ± 1.6 vs. 149.1 ± 1.1 mEq/liter). Quantitative immunoblotting of total kidney membrane fractions revealed a significant increase in AQP2 expression in animals with CHF (267 ± 53%, n=12) relative to sham-operated controls (100 ± 13%, n=14). In contrast, immunoblotting demonstrated a lack of an increase in expression of AQP1 and AQP3 water channel expression, indicating that the effect on AQP2 was selective.Furthermore, postinfarction animals without LVEDP elevation or plasma Na reduction showed no increase in AQP2 expression (121 ± 28% of sham levels, n=6). Immunocytochemistry and immunoelectron microscopy demonstrated very abundant labeling of the apical plasma membrane and relatively little labeling of intracellular vesicles in collecting duct cells from rats with severe CHF, consistent with enhanced trafficking of AQP2 to the apical plasma membrane. The selective increase in AQP2 expression and enhanced plasma membrane targeting provide an explanation for the development of water retention and hyponatremia in severe CHF

Early VEGF testing in inflammatory neuropathy avoids POEMS syndrome misdiagnosis and associated costs

BACKGROUND: Prompt diagnosis and early treatment prevents disability in Polyneuropathy Organomegaly Endocrinopathy Monoclonal-protein and Skin Changes (POEMS) syndrome. Delay in diagnosis is common with 55% of patients initially incorrectly diagnosed with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Patients are often treated with intravenous immunoglobulin which is both expensive and ineffective in the treatment of POEMS. Testing patients with acquired demyelinating neuropathy with serum vascular endothelial growth factor (VEGF) more accurately identifies POEMS syndrome than the current standard of care. Incorporating VEGF testing into screening could prevent misdiagnosis and reduce costs. METHODS: We used observed treatment information for patients in the University College London Hospital's POEMS syndrome database (n=100) and from the National Immunoglobulin Database to estimate costs associated with incorrect CIDP diagnoses across our cohort. We conducted a model-based cost-effectiveness analysis to compare the current diagnostic algorithm with an alternative which includes VEGF testing for all patients with an acquired demyelinating neuropathy. RESULTS: Treatment associated with an incorrect CIDP diagnosis led to total wasted healthcare expenditures of between £808 550 and £1 111 756 across our cohort, with an average cost-per-POEMS-patient misdiagnosed of £14 701 to £20 214. Introducing mandatory VEGF testing for patients with acquired demyelinating neuropathy would lead to annual cost-savings of £107 398 for the National Health Service and could prevent misdiagnosis in 16 cases per annum. CONCLUSIONS: Misdiagnosis in POEMS syndrome results in diagnostic delay, disease progression and significant healthcare costs. Introducing mandatory VEGF testing for patients with acquired demyelinating neuropathy is a cost-effective strategy allowing for early POEMS diagnosis and potentially enabling prompt disease-directed therapy

Effects of rf Current on Spin Transfer Torque Induced Dynamics

The impact of radiofrequency (rf) currents on the direct current (dc) driven switching dynamics in current-perpendicular-to-plane nanoscale spin valves is demonstrated. The rf currents dramatically alter the dc driven free layer magnetization reversal dynamics as well as the dc switching level. This occurs when the frequency of the rf current is tuned to a frequency range around the dc driven magnetization precession frequencies. For these frequencies, interactions between the dc driven precession and the injected rf induce frequency locking and frequency pulling effects that lead to a measurable dependence of the critical switching current on the frequency of the injected rf. Based on macrospin simulations, including dc as well as rf spin torque currents, we explain the origin of the observed effects.Comment: 5 pages, 4 figure

Influence of ion irradiation on switching field and switching field distribution in arrays of Co/Pd-based bit pattern media

International audienceWe have used ion irradiation to tune switching field and switching field distribution ͑SFD͒ in polycrystalline Co/Pd multilayer-based bit pattern media. Light He + ion irradiation strongly decreases perpendicular magnetic anisotropy amplitude due to Co/Pd interface intermixing, while the granular structure, i.e., the crystalline anisotropy, remains unchanged. In dot arrays, the anisotropy reduction leads to a decrease in coercivity ͑H C ͒ but also to a strong broadening of the normalized SFD/ H C ͑in percentage͒, since the relative impact of misaligned grains is enhanced. Our experiment thus confirms the major role of misorientated grains in SFD of nanodevice arrays. Today a major research effort in magnetism is targeted toward achieving ultrahigh density data storage with nano-scale magnets. Spin-transfer magnetic random access memory ͑spin-RAM͒ and bit patterned media ͑BPM͒ technologies are currently part of the most promising media. The implementation of both of these technologies relies on achieving in-detail physical understanding and control of the magnetization reversal mechanism in each nanoscopic individual bit to ensure reproducibility of the bit properties in order to avoid write errors. Perpendicular magnetic anisotropy ͑PMA͒ materials, such as polycrystalline Co/Pd, Co/Pt, and Co/Ni multilayers, are believed to be promising materials for both spin-RAM and BPM applications. 1–4 Indeed, they have a well defined high amplitude uniaxial anisotropy that provides good thermal stability while offering low critical current in spin-transfer devices 2 and tunable switching fields in BPM.

Early VEGF testing in inflammatory neuropathy avoids POEMS syndrome misdiagnosis and associated costs.

BACKGROUND: Prompt diagnosis and early treatment prevents disability in Polyneuropathy Organomegaly Endocrinopathy Monoclonal-protein and Skin Changes (POEMS) syndrome. Delay in diagnosis is common with 55% of patients initially incorrectly diagnosed with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Patients are often treated with intravenous immunoglobulin which is both expensive and ineffective in the treatment of POEMS. Testing patients with acquired demyelinating neuropathy with serum vascular endothelial growth factor (VEGF) more accurately identifies POEMS syndrome than the current standard of care. Incorporating VEGF testing into screening could prevent misdiagnosis and reduce costs. METHODS: We used observed treatment information for patients in the University College London Hospital's POEMS syndrome database (n=100) and from the National Immunoglobulin Database to estimate costs associated with incorrect CIDP diagnoses across our cohort. We conducted a model-based cost-effectiveness analysis to compare the current diagnostic algorithm with an alternative which includes VEGF testing for all patients with an acquired demyelinating neuropathy. RESULTS: Treatment associated with an incorrect CIDP diagnosis led to total wasted healthcare expenditures of between £808 550 and £1 111 756 across our cohort, with an average cost-per-POEMS-patient misdiagnosed of £14 701 to £20 214. Introducing mandatory VEGF testing for patients with acquired demyelinating neuropathy would lead to annual cost-savings of £107 398 for the National Health Service and could prevent misdiagnosis in 16 cases per annum. CONCLUSIONS: Misdiagnosis in POEMS syndrome results in diagnostic delay, disease progression and significant healthcare costs. Introducing mandatory VEGF testing for patients with acquired demyelinating neuropathy is a cost-effective strategy allowing for early POEMS diagnosis and potentially enabling prompt disease-directed therapy

Electron optics with magnetic vector potential barriers in graphene

An analysis of electron transport in graphene is presented in the presence of various arrangement of delta-function like magnetic barriers. The motion through one such barrier gives an unusual non specular refraction leading to asymmetric transmission. The symmetry is restored by putting two such barriers in opposite direction side by side. Periodic arrangements of such barriers can be used as Bragg reflectors whose reflectivity has been calculated using a transfer matrix formalism. Such Bragg reflectors can be used to make resonant cavities. We also analyze the associated band structure for the case of infinite periodic structures.Comment: Significant revision and added figure

Reversal of Klein reflection in bilayer graphene

Whereas massless Dirac fermions in monolayer graphene exhibit Klein tunneling when passing through a potential barrier upon normal incidence, such a barrier totally reflects massive Dirac fermions in bilayer graphene due to difference in chirality. We show that, in the presence of magnetic barriers, such massive Dirac fermions can have transmission through even at normal incidence. The general consequence of this behaviour for multilayer graphene consisting of massless and massive modes are mentioned. We also briefly discuss the effect of a bias voltage on such magnetotransport.Comment: 10 double space single column latexed pages, 15 eps files in four figure

Financing essential HIV services: a new economic agenda.

Anna Vassall and colleagues discuss the need for, and challenges facing, innovative and sustainable financing of the HIV response. Please see later in the article for the Editors' Summary