Characterization of Trypanosoma brucei isolated from lymph nodes of rats

Forms of Trypanosoma brucei isolated from lymph nodes of cyclically or intravenously infected rats, at different stages of infection, were morphologically compared with the corresponding bloodstream forms. Unlike the pleomorphic bloodstream trypanosome population, the lymph node trypanosome population was essentially monomorphic and resembled the slender forms of the bloodstream. Values for the morphometric parameters indicated a position between the slender and the stumpy forms. The number of trypanosomes/ml of blood showed the well-known periodic fluctuations while the number of trypanosomes/g of lymph node remained fairly constant. Serology revealed that lymph node trypanosome populations differed antigenically from the trypanosome populations isolated simultaneously from the bloodstrea

The effects of donepezil in Alzheimer's disease - Results from a multinational trial

Donepezil has been shown to be well tolerated and to improve cognition and global function in patients with mild to moderately severe Alzheimer's disease (AD). The current trial was undertaken to investigate further the efficacy and safety of donepezil, in a multinational setting, in patients with mild to moderately severe AD. This 30-week, placebo-controlled, parallel-group study consisted of a 24-week, double-blind treatment phase followed by a 6-week, single-blind, placebo washout. Eight hundred and eighteen patients with mild to moderately severe AD were randomly allocated to treatment with single, daily doses of 5 or 10 mg donepezil, or placebo. The two primary efficacy measures were: a cognitive performance test, the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) and a global evaluation, the Clinician's Interview-Based Impression of Change with caregiver input (CIBIC plus). Secondary outcome measures included the Sum of the Boxes of the Clinical Dementia Rating Scale (CDR-SB), a modified Interview for Deterioration in Daily living activities in Dementia (IDDD) and a patient-rated quality of life assessment. Statistically significant improvements in cognitive and global function were observed, as evaluated by ADAS-cog and CIBIC plus, respectively, in both the 5 and 10 mg/day donepezil groups, compared with placebo. Treatment-associated changes were also observed in functional skills, as shown by improved scores on the CDR-SB and the complex-tasks component of the IDDD. A dose-response effect was evident, with the 10 mg/day donepezil group demonstrating greater benefits in all outcome measures than the 5 mg/day group. Donepezil was well tolerated by this patient population and did not produce any clinically significant laboratory test abnormalities. The results of this study confirm that donepezil is effective and well tolerated in treating the symptoms of mild to moderately severe AD

Speech Communication

Contains reports on six research projects.U. S. Air Force Command and Control Development Division under Contract AF19(604)-6102National Science Foundatio

Speech Communication

Contains research objectives and reports on two research projects.U.S. Air Force (Electronic Systems Division) under Contract AF19(604)-6102National Science Foundation (Grant G-10800)National Science Foundation (Grant G-7364)National Science Foundation (Grant G-16526)National Institutes of Health (Grant MP-4737

Fractal Conductance Fluctuations in Gold--Nanowires

A detailed analysis of magneto-conductance fluctuations of quasiballistic gold-nanowires of various lengths is presented. We find that the variance $=$ when analyzed for $\Delta B$ much smaller than the correlation field $B_c$ varies according to $<(\Delta G)^2>\propto \Delta B^{\gamma}$ with $\gamma < 2$ indicating that the graph of $G$ vs. $B$ is fractal. We attribute this behavior to the existence of long-lived states arising from chaotic trajectories trapped close to regular classical orbits. We find that $\gamma$ decreases with increasing length of the wires.Comment: 5 pages, Revtex with epsf, 4 Postscript figures, final version accepted as Phys. Rev. Let

Speech Communication

Contains research objectives and reports on three research projects.U.S. Air Force (Air Force Cambridge Research Center, Air Research and Development Command) under Contract AF19(604)-6102National Science Foundatio

Patient engagement with antibiotic messaging in secondary care: a qualitative feasibility study of the ‘review & revise’ experience

Background: We aimed to investigate and optimise the acceptability and usefulness of a patient leaflet about antibiotic prescribing decisions made during hospitalisation, and to explore individual patient experiences and preferences regarding the process of antibiotic prescription ‘review & revise’ which is a key strategy to minimise antibiotic overuse in hospitals. Methods: In this qualitative study, run within the feasibility study of a large, cluster-randomised stepped wedge trial of 36 hospital organisations, a series of semi-structured, think-aloud telephone interviews were conducted and data were analysed using thematic analysis. Fifteen adult patients who had experienced a recent acute medical hospital admission during which they had been prescribed antimicrobials and offered a patient leaflet about antibiotic prescribing were recruited to the study. Results: Participants reacted positively to the leaflet, reporting that it was both an accessible and important source of information which struck the appropriate balance between informing and reassuring. Participants all valued open communication with clinicians, and were keen to be involved in antibiotic prescribing decisions, with individuals reporting positive experiences regarding antibiotic prescription changes or stopping. Many participants had prior experience or knowledge of antibiotics and resistance, and generally welcomed efforts to reduce antibiotic usage. Overall, there was a feeling that healthcare professionals (HCPs) are trusted experts providing the most appropriate treatment for individual patient conditions. Conclusions: This study offers novel insights into how patients within secondary care are likely to respond to messages advocating a reduction in the use of antibiotics through the ‘review & revise’ approach. Due to the level of trust that patients place in their care provider, encouraging HCPs within secondary care to engage patients with greater communication and information provision could provide great advantages in the drive to reduce antibiotic use. It may also be beneficial for HCPs to view patient experiences as cumulative events that have the potential to impact future behaviour around antibiotic use. Finally, pre-testing messages about antibiotic prescribing and resistance is vital to dispelling any misconceptions either around effectiveness of treatment for patients, or perceptions of how messages may be received

Photoassociation of sodium in a Bose-Einstein condensate

We report on the formation of ultra-cold Na$_2$ molecules using single-photon photoassociation of a Bose-Einstein condensate. The photoassociation rate, linewidth and light shift of the J=1, $v=135$ vibrational level of the \mterm{A}{1}{+}{u} molecular bound state have been measured. We find that the photoassociation rate constant increases linearly with intensity, even where it is predicted that many-body effects might limit the rate. Our observations are everywhere in good agreement with a two-body theory having no free parameters.Comment: Fixes to the figures and references. Just the normal human stupidity type stuff, nothing Earth-shatterin

19F Electron-nuclear double resonance reveals interaction between redox-active tyrosines across the α/β interface of E. coli ribonucleotide reductase

Ribonucleotide reductases (RNRs) catalyze the reduction of ribonucleotides to deoxyribonucleotides, thereby playing a key role in DNA replication and repair. Escherichia coli class Ia RNR is an α2β2 enzyme complex that uses a reversible multistep radical transfer (RT) over 32 Å across its two subunits, α and β, to initiate, using its metallo-cofactor in β2, nucleotide reduction in α2. Each step is proposed to involve a distinct proton-coupled electron-transfer (PCET) process. An unresolved step is the RT involving Y356(β) and Y731(α) across the α/β interface. Using 2,3,5-F3Y122-β2 with 3,5-F2Y731-α2, GDP (substrate) and TTP (allosteric effector), a Y356• intermediate was trapped and its identity was verified by 263 GHz electron paramagnetic resonance (EPR) and 34 GHz pulse electron–electron double resonance spectroscopies. 94 GHz 19F electron-nuclear double resonance spectroscopy allowed measuring the interspin distances between Y356• and the 19F nuclei of 3,5-F2Y731 in this RNR mutant. Similar experiments with the double mutant E52Q/F3Y122-β2 were carried out for comparison to the recently published cryo-EM structure of a holo RNR complex. For both mutant combinations, the distance measurements reveal two conformations of 3,5-F2Y731. Remarkably, one conformation is consistent with 3,5-F2Y731 within the H-bond distance to Y356•, whereas the second one is consistent with the conformation observed in the cryo-EM structure. The observations unexpectedly suggest the possibility of a colinear PCET, in which electron and proton are transferred from the same donor to the same acceptor between Y356 and Y731. The results highlight the important role of state-of-the-art EPR spectroscopy to decipher this mechanism

Strong electron-phonon coupling in delta-phase stabilized Pu

Heat capacity measurements of the delta-phase stabilized alloy Pu-Al suggest that strong electron-phonon coupling is required to explain the moderate renormalization of the electronic density of states near the Fermi energy. We calculate the heat capacity contributions from the lattice and electronic degrees of freedom as well as from the electron-lattice coupling term and find good overall agreement between experiment and theory assuming a dimensionless electron-phonon coupling parameter of order unity, lambda ~ 0.8. This large electron-phonon coupling parameter is comparable to reported values in other superconducting metals with face-centered cubic crystal structure, for example, Pd (lambda ~ 0.7) and Pb (lambda ~ 1.5). Further, our analysis shows evidence of a sizable residual low-temperature entropy contribution, S_{res} ~ 0.4 k_B (per atom). We can fit the residual specific heat to a two-level system. Therefore, we speculate that the observed residual entropy originates from crystal-electric field effects of the Pu atoms or from self-irradiation induced defects frozen in at low temperatures.Comment: 9 pages, 11 figures, to appear in Phys. Rev.