EEG spectral abnormalities and psychosis as predictors of cognitive and functional decline in probable Alzheimer's disease

We examined whether either psychotic features (e.g., delusions and hallucinations) or EEG abnormalities are associated with more rapid progression of Alzheimer's disease (AD). AD patients with psychosis have exhibited more EEG abnormalities than those without psychosis, and both abnormal EEG and psychosis have been noted to be predictors of functional and cognitive decline in AD. Ninety-five probable AD patients participating in a longitudinal study of dementia had an EEG and a semistructured psychiatric interview at baseline. Using EEG spectral analysis, we classified records as normal/abnormal based on the parasagittal mean frequency. Patients with abnormal EEGs were more functionally (e.g., Blessed Rating Scale for activities of daily living) and cognitively (e.g., Mini-Mental State) impaired than patients with normal EEG. AD patients with psychosis were only more functionally impaired than patients without psychosis. A two-factor analysis showed no interaction between abnormal EEG and psychosis. In addition, using a Cox proportional hazard model adjusted for age and education, the presence of an abnormal EEG or psychotic symptom at study entry was associated with higher risk of reaching severe cognitive and functional impairment during follow-up. Neither abnormal EEG nor the presence of psychosis predicted death. These results indicate that both abnormal EEG and psychosis are independent predictors of disease progression but not of physical survival.     

The ultradian clocks of eukaryotic microbes: timekeeping devices displaying a homeostasis of the period

Ultra-high-sensitivity, biopolymer sequencing is a goal in many fields of molecular biology, and collisionally activated decomposition electrospray mass spectrometry (CAD ES MS/MS) using a triple quadrupole mass spectrometer has become a method of choice for work in the high- to mid-femtomole range. However, when the detection of ions becomes statistical, as it may in that range, the mass assignment of fragment ions is inaccurate and either sequencing becomes impossible or ambiguities result due, for example, to the closeness in amino acid residue masses (I/L, N or K/Q, E). Some ambiguities may be resolved by synthesizing possible sequences, but this is unsatisfactory. In considering the limitations of triple quadrupole MS/MS with respect to scanning ion detection, resolution, transmission, and mass accuracy, we reasoned that a novel geometry quadrupole orthogonal acceleration time-of-flight (Q-TOF) instrument would have special merit for ultra-high-sensitivity MS/MS sequencing, and suggested its construction for this purpose some three years ago. A prototype Q-TOF has now been built by Micromass [Morris et al. (1996), Rapid Commun. Mass Spectrom. 10, 889-896], and in the first research on the instrument, including MHC antigen and filarial nematode glycoprotein studies, we demonstrate low-femtomole- and attomole-range sequencing with mass accuracy of better than 0.1 Da throughout the daughter-ion spectrum, thus removing sequencing ambiguities in some of the most challenging work demanding the highest sensitivity.     

Peer evaluation. A visual picture

To meet the criteria of role accountability, nursing competence and ongoing staff development, an improved peer-evaluation system was designed to continuously monitor these new roles. This peer-evaluation process converts evaluation input into data, giving staff a visual picture of how their performance compares within their peer group. This peer-evaluation process was designed as a tool to assist in staff growth and development, not as a punitive system.     

Epilepsy, retarded growth and onchocerciasis, in two areas of different endemicity of onchocerciasis in Burundi

A high prevalence of epilepsy (up to 1.3%) was observed in an area hyperendemic for onchocerciasis in the province of Bururi, Burundi. Following this observation, epileptics and controls were examined in 2 communes (administrative units) with different endemicity for onchocerciasis. Altogether, onchocerciasis was more frequent in epileptics (81.8%) than in controls from the same households (68.3%; P < 0.05). This difference was more marked in the hyperendemic area. Other possible causes of epilepsy, including cysticercosis, were infrequent (18 possible cases among 110 epileptics). During this survey, 9 epileptics with growth retardation were seen. They showed most characteristics of Nakalanga syndrome, which was described from Uganda. All 9 such cases were suffering from onchocerciasis. These findings give more evidence of a possible association between onchocerciasis and epilepsy, and between onchocerciasis and Nakalanga syndrome.     

Repair of extensive ionizing-radiation DNA damage at 95 degrees C in the hyperthermophilic archaeon Pyrococcus furiosus

We investigated the capacity of the hyperthermophile Pyrococcus furiosus for DNA repair by measuring survival at high levels of 60Co gamma-irradiation. The P. furiosus 2-Mb chromosome was fragmented into pieces ranging from 500 kb to shorter than 30 kb at a dose of 2,500 Gy and was fully restored upon incubation at 95 degrees C. We suggest that recombination repair could be an extremely active repair mechanism in P. furiosus and that it might be an important determinant of survival of hyperthermophiles at high temperatures.     

An EIA method on single donor solubilized HLA antigens for the identification of anti-HLA antibodies

Primary biliary cirrhosis (PBC) is an immunologically mediated disease in which activated T lymphocytes attack and destroy epithelial cells in the small intralobular bile ducts of genetically susceptible patients. This article reviews the results of treatment of PBC with immunomodulatory agents. Results with drugs such as glucocorticoids, azathioprine, and chlorambucil have been disappointing because of either limited efficacy (azathioprine), toxicity (chlorambucil), or both (glucocorticoids). Colchicine improved tests of liver function in three prospective studies and was associated with improved survival for up to 4 years. However, survival benefits were lost at 8 years. Colchicine appears to slow the rate of progression of PBC but not to stop it. Preliminary results suggest that colchicine may have synergistic effects if used together with ursodeoxycholic acid, particularly in patients who are only partially responsive to ursodeoxycholic acid. Results with cyclosporine have been disappointing because of limited efficacy and predictable toxicity. The modest improvement in tests of liver function and survival are counterbalanced by the development of hypertension in some and worsening renal function in most. There is little beneficial effect on symptoms or histology. Results with methotrexate are promising. There are improvements in symptoms and tests of liver function that are equal to those seen with ursodeoxycholic acid and significant improvement in liver histology. Some patients, particularly those with striking inflammation and granulomas in portal triads, appear to have achieved sustained remission while on methotrexate. The effects of methotrexate are additive to those of ursodeoxycholic acid in patients whose blood tests have responded only partially to ursodeoxycholic acid. The most effective treatment of PBC will most likely use a combination of drugs such as ursodeoxycholic acid, colchicine, and methotrexate.     

Certain nonlinear partially observable stochastic optimal controlproblems with explicit control laws equivalent to LEQG/LQG problems

This paper is concerned with partially observed stochastic optimal control problems when nonlinearities enter the dynamics of the unobservable state and the observations as gradients of potential functions. Explicit representations for the information state are derived in terms of a finite number of sufficient statistics. Consequently, the partially observed problem is recast as one of complete information with a new state generated by a modified version of the Kalman filter. When the terminal cost is quadratic in the unobservable state and includes the integral of the nonlinearities, the optimal control laws are explicitly computed, similar to linear-exponential-quadratic-Gaussian (LEQG) and linear-quadratic-Gaussian (LQG) tracking problems. The results are applicable to filtering and control of Hamiltonian systems     

Estimating the viewing parameters of random, noisy projections ofasymmetric objects for tomographic reconstruction

The ability to determine the viewing parameters of objects from their projections has enabled well established tomographic techniques to be employed in the 3D reconstruction of objects from images obtained via modalities where the orientation of the objects cannot be controlled. A method is described for the determination of the viewing parameters of randomly acquired projections of asymmetric objects. It extends upon the common lines algorithm by determining the relative orientation of projections from the location of lines of intersection among the Fourier transforms of the projections in 3D Fourier space. A new technique for finding the lines of intersection in the presence of translational displacement, and for subsequently finding the translational displacement, is presented. The complete algorithm is described and its efficacy is demonstrated using real data. A new technique for dealing with noise is also discussed     

On a large-gain theorem

The aim of this paper is to give a general quantitative requirement which the loop gain must satisfy in order to stabilize a given unstable (possibly nonlinear and time-varying) plant, namely that the gain must exceed one.