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Hyperkalemia is a potentially life-threatening condition that patients with heart failure or chronic kidney disease, especially those taking renin-angiotensin-aldosterone system inhibitors, are at high risk of developing. Sodium polystyrene sulfonate (SPS), a current treatment, binds potassium within the gastrointestinal tract to reduce potassium absorption. However, poor palatability limits its long-term use. RDX7675, a novel potassium binder in development for the treatment of hyperkalemia, is a calcium salt of a reengineered polystyrene sulfonate-based resin designed to have enhanced palatability. Here, the physical properties and palatability of RDX7675 and SPS are compared. RDX7675 and SPS particle sizes were measured using wet dispersion laser diffraction. Palatability was assessed in a randomized, crossover, healthy volunteer study with two visits. At visit 1 (open label), volunteers evaluated high-viscosity, intermediate-viscosity, and water-reconstituted formulations of RDX7675 (all vanilla flavor), and an equivalent reconstituted SPS (Resonium A ). At visit 2 (single-blind), volunteers evaluated RDX7675 as a high-viscosity formulation in vanilla, citrus, and mint flavors, and as intermediate-viscosity, low-viscosity, and reconstituted formulations in citrus flavor. Volunteers used a \"sip and spit\" technique to rate overall acceptability and seven individual characteristics from 1 (\"dislike everything\") to 9 (\"like extremely\"). RDX7675 particles were smaller than SPS particles, with a narrower size range (RDX7675, 80%, 14-52 µm; SPS, 11.3-124.2 µm), and had a smooth, spherical shape, in contrast to the shard-like SPS particles. Reconstituted RDX7675 was considered superior to SPS for five of the seven palatability characteristics and for overall acceptability (median, visit 1: reconstituted RDX7675, 5.0; SPS, 4.0). High-viscosity vanilla was the most highly rated RDX7675 formulation (median overall acceptability, visit 2: 7.0). The smaller, more uniformly shaped, spherical particles of RDX7675 resulted in improved palatability over SPS when reconstituted in water. The overall results are promising for future patient acceptability of RDX7675 treatment.

Aberrant growth of blood vessels in the choroid layer of the eye, termed choroidal neovascularization (CNV), is the pathological hallmark of exudative age-related macular degeneration (AMD), causing irreversible blindness among the elderly. Co-localization of proangiogenic factors and hypoxia inducible factors (HIF) in neovascular membranes from AMD eyes suggests the role of hypoxia in pathogenesis of CNV. In order to utilize hypoxic conditions in RPE for therapeutic purposes, we developed an optimized hypoxia regulated, RPE cell-specific gene therapy to inhibit choroidal neovascularization. An adeno-associated virus (AAV2) vector comprising a RPE-specific promoter and HIF-1 response elements (HRE) was designed to regulate production of human endostatin (a powerful angiostatic protein) in RPE. The vector was tested in a mouse model of laser-induced CNV using subretinal delivery. Spectral domain optical coherence tomography (SD-OCT) images from live mice and confocal images from lectin stained RPE flat mount sections demonstrated reduction in CNV areas by 80% compared to untreated eyes. Quantitative real-time polymerase chain reaction (qPCR) confirmed exogenous endostatin mRNA expression from the regulated vector that was significantly elevated 3, 7, and 14 days following laser treatment, but its expression was completely shut off after 45 days. Thus, RPE-specific, hypoxia-regulated delivery of anti-angiogenic proteins could be a valuable therapeutic approach to treat neovascular AMD at the time and in the ocular space where it arises.Key pointsAn optimized gene therapy vector targeting hypoxia and tissue-specific expression has been designed.The inhibitory role of gene therapy vector was tested in a mouse model of laser-induced CNV.An 80% reduction in choroidal neovascularization was achieved by the optimized vector.The expression of endostatin was limited to retinal pigment epithelium and regulated by hypoxia.

The LHCb experiment has been taking data at the Large Hadron Collider (LHC) at CERN since the end of 2009. One of its key detector components is the Ring-Imaging Cherenkov (RICH) system. This provides charged particle identification over a wide momentum range, from 2–100 GeV/ c . The operation and control, software, and online monitoring of the RICH system are described. The particle identification performance is presented, as measured using data from the LHC. Excellent separation of hadronic particle types ( π , K, p) is achieved.

Alzheimer's disease is a dementing disorder of unknown cause in which there is degeneration of neuronal subpopulations in the central nervous system. In postmortem studies, we found widespread axonal degeneration in the optic nerves of 8 of 10 patients with Alzheimer's disease. The retinas of four of the patients were also examined histologically, and three had a reduction in the number of ganglion cells and in the thickness of the nerve-fiber layer. There was no retinal neurofibrillary degeneration or amyloid angiopathy, which are typically seen in the brains of patients with Alzheimer's disease. The changes we observed in the patients with Alzheimer's disease were clearly distinguishable from the findings in 10 age-matched controls and represent a sensory-system degeneration that occurs in Alzheimer's disease. Study of the retina in patients with this disease may be helpful diagnostically, and isolation of the affected ganglion cells may facilitate molecular analysis of the disorder. (N Engl J Med 1986; 315:485–7.) The principal histopathological features of brains of patients with Alzheimer's disease include neuronal loss, neurofibrillary tangles, neuritic plaques, and granulovacuolar degeneration. These changes occur most frequently in the hippocampus and other limbic structures and in neocortical association areas. Primary neocortical areas such as motor and visual cortices are relatively spared. 1 , 2 The clinical diagnosis of Alzheimer's disease cannot always be made with certainty, and the neuropathological features are qualitatively not diagnostic of Alzheimer's disease, because similar histologic changes may occur in elderly patients who do not have dementia. 1 Memory deficits, aphasias, and apraxias are the most common signs of Alzheimer's disease, . . .

Neuronal degeneration is one of the hallmarks of Alzheimer disease (AD). Given the paucity of molecular markers available for the identification of neuronal subtypes, the specificity of neuronal loss within the cerebral cortex has been difficult to evaluate. With a panel of four monoclonal antibodies (mAbs) applied to central nervous system tissues from AD patients, we have immunocytochemically identified a population of vulnerable cortical neurons; a subpopulation of pyramidal neurons is recognized by mAbs 3F12 and 44.1 in the hippocampus and neocortex, and clusters of multipolar neurons in the entorhinal cortex reactive with mAb 44.1 show selective degeneration. Closely adjacent stellate-like neurons in these regions, identified by mAb 6A2, show striking preservation in AD. The neurons recognized by mAbs 3F12 and 44.1, to the best of our knowledge, do not comprise a single known neurotransmitter system. mAb 3A4 identifies a phosphorylated antigen that is undetectable in normal brain but accumulates early in the course of AD in somas of vulnerable neurons. Antigen 3A4 is distinct from material reactive with thioflavin S or antibody generated against paired helical filaments. Initially, antigen 3A4 is localized to neurons in the entorhinal cortex and subiculum, later in the association neocortex, and, ultimately in cases of long duration, in primary sensory cortical regions. mAb 3F12 recognizes multiple bands on immunoblots of homogenates of normal and Ad cortical tissues, whereas mAb 3A4 does not bind to immunoblots containing neurofilament proteins or brain homogenates from AD patients. Ultrastructurally, antigen 3A4 is localized to paired-helical filaments. Using these mAbs, further molecular characterization of the affected cortical neurons is now possible.

The branching fractions of the decay [Formula: see text] for different intermediate states are measured using data, corresponding to an integrated luminosity of 1.0 fb , collected by the LHCb experiment. The total branching fraction, its charmless component [Formula: see text] and the branching fractions via the resonant [Formula: see text] states (1 ) and (2 ) relative to the decay via a / intermediate state are [Formula: see text] Upper limits on the branching fractions into the (2 ) meson and into the charmonium-like states (3872) and (3915) are also obtained.

The differential cross-section for the inclusive production of (2 ) mesons in collisions at [Formula: see text] has been measured with the LHCb detector. The data sample corresponds to an integrated luminosity of 36 pb . The (2 ) mesons are reconstructed in the decay channels (2 )→ and (2 )→ / , with the / meson decaying into two muons. Results are presented both for promptly produced (2 ) mesons and for those originating from -hadron decays. In the kinematic range ( (2 ))≤16 GeV/ and 2< ( (2 ))≤4.5 we measure [Formula: see text] where the last uncertainty on the prompt cross-section is due to the unknown (2 ) polarization. Recent QCD calculations are found to be in good agreement with our measurements. Combining the present result with the LHCb / measurements we determine the inclusive branching fraction [Formula: see text] where the last uncertainty is due to the [Formula: see text], [Formula: see text] and [Formula: see text] branching fraction uncertainties.

ABSTRACT The study was prompted by a long-standing concern how best to educate nurse administrators for work in health service organizations. In the last decade, has been increasingly widespread agreement in that advanced education for clinical specialization may be insufficient. To improve understanding of for nursing administration (NA), the suggestions 3? publications printed between 1976 and 1985 were Inferences were made from these publications curriculum content, program structure, instrucplacement, and practicum experiences. Content most often pertained to health systems, nursing research, and policy. Reference was least often to perspectives in organization theory, ethics, and studies. Suggestions for international NA were in only one publication. Administration majors with clinical nursing emphasis in multidisciplinary programs by schools of nursing were widely recommended, as were administrative practicums of variable length. Few suggestions were made about the epistemological considerations needed to guide the development of interdisciplinnursing administration. In the future, consideration of the overlap - from nursing and management science - of concepts, research problems, and modes of inquiry, will be important for the education of nurse administrators. In the 1960s and early 1970s, clinical specialization was the central focus of graduate nursing education. During this period of time, emphasis on nursing administration (NA) declined, as did the number of NA programs, resulting in a critical shortage of nurse administrators academically prepared to manage health services (Blair, 1976a-b). By 1977, it was estimated that as few as 24% of the nations nurse administrators had master's degrees and that the portion with doctorates was barely .6% (American Nurses' Association [ANA], 1980; Fine, 1983). Knudson (1968), Kramer (1968), Leininger (1974), and Miller (1968) warned the profession of an impending leadership crisis. Responding to the shortage, the threat of non-nurses managing nursing services (Jordan, 1979; Rotkovitch, 1979a), and to nurses being educated for management in disciplines other than nursing (Cleland, 1984), the number of NA programs more than doubled between the mid 1970s and 1982, increasing from 24 to 51. The ascendancy of NA had begun. Recognizing the problem of too few well-educated nurses to manage nursing services, and the need for sound academic programs in NA, the Institute of Medicine (1983) recommended that federal funding be allocated for improvements in NA education. By 1985, an administration component was an element of over 65 nursing programs (National League for Nursing [NLN], 1985). Considerable concern has been expressed, however, about the curriculums and structures of these programs, which in some cases have been developed hurriedly - in a brief period of time - and with relatively few resources (Cleland, 1984; Poulin, 1984; Stevens, 1977a).

Objectives. The Rose K1 lens has been shown to be comfortable and successfully fit in a high percentage of keratoconus patients. The addition of spherical aberration correction in the Rose K2 lens has been claimed to improve visual acuity. The aim of this study is to determine if there is a difference in visual acuity or aberrations in the Rose K1 vs. the Rose K2 lens. Methods. High contrast and low contrast acuity was measured in photopic and mesopic conditions on eleven keratoconic subjects with the Rose K1 and Rose K2 lens. Researcher and subject were masked as to which lens was the Rose K2. Results. A generalized estimating equations model was used to show that visual acuity results were not statistically significant different between the two lenses (p > |z| = 0.283) when controlling for contrast and lighting. Wavefront data of higher order aberrations measured while subjects wore each of the lenses also failed to show any statistical difference in amount of spherical aberration (p > |z| = 0.986). Subjects reported a preference for the Rose K1 lens in vision (67%), comfort (54%), and overall performance (54%). Conclusions. The results of this study can not demonstrate to practitioners that the back surface addition of spherical aberration correction to keratoconic lenses is dramatically beneficial. There may still be potential for visual performance enhancement in keratoconic patients, using well fit custom lenses that optimize multiple parameters.

The LHCb experiment has been taking data at the Large Hadron Collider (LHC) at CERN since the end of 2009. One of its key detector components is the Ring-Imaging Cherenkov (RICH) system. This provides charged particle identification over a wide momentum range, from 2-100 GeV/c. The operation and control software, and online monitoring of the RICH system are described. The particle identification performance is presented, as measured using data from the LHC. Excellent separation of hadronic particle types (pion, kaon and proton) is achieved.