Objective: To determine the type of cognitive deficits occurring 3 to 6 years before onset of dementia in a population sample.
Design: A prospective study in which cognitive deficits in participants ...who had incident dementia at the 6‐year follow‐up were examined at baseline and 3 years.
Setting: Honolulu, Hawaii.
Participants: Three thousand seven hundred thirty‐four Japanese‐American men aged 71 to 93 at baseline. At the 6‐year follow‐up, there were 52 incident cases of dementia, and 1,559 controls.
Measurements: The Cognitive Abilities Screening Instrument (CASI) and a questionnaire on subjective memory problems were administered at baseline. Dementia was assessed at baseline and at 3‐year and 6‐year follow‐ups.
Results: Subjects who had incident dementia at 6‐year follow‐up, had showed deficits 3 to 6 years earlier in the CASI domain of episodic memory and in the questionnaire covering subjective memory problems. Up to 3 years before onset, there was worsening of the episodic memory deficit from baseline and new deficits in language, verbal fluency, and orientation.
Conclusion: Cognitive deficits and awareness of memory problems are frequently present several years before dementia onset. The predictive value of these deficits is not large enough to allow earlier diagnosis of dementia, but information about such deficits may be useful as criteria for mild cognitive impairment.
Nitrous oxide (N2O) and methane (CH4) were measured in the upper troposphere and lower stratosphere by multiple instruments aboard the NASA ER‐2 aircraft during the 1995–1996 Stratospheric Tracers of ...Atmospheric Transport (STRAT) and 1997 Photochemistry of Ozone Loss in the Arctic Region in Summer (POLARIS) campaigns. Differences between coincidental, in situ measurements are examined to evaluate the agreement and variability in the agreement between these instruments during each flight. Mean N2O measurement differences for each flight were much smaller than limits calculated from quoted values of N2O measurement accuracy and for all but two flights were ≤8.7 ppb (3.5%). Mean CH4 measurement differences for flights were similarly much smaller than calculated limits and for all but three flights were ≤65 ppb (4.4%). Typical agreement between instruments during flights averaged 6.2 ppb (2.5%) for N2O and 43 ppb (2.9%) for CH4. In contrast, for about half of the flights, the variability of N2O and CH4 measurement differences exceeded limits calculated from quoted values of measurement precision. The typical measurement difference variability (1σ) during a flight averaged ±8.0 ppb (3.2%) for N2O and ±43 ppb (2.9%) for CH4. For some flights, large differences or variations in differences are attributable to the poor measurement accuracy or precision of one instrument. It is demonstrated that small offsets between the computer clocks of these instruments can result in significant differences between their “coincidental” N2O and CH4 data, especially when there is high spatial variability in tracer abundance along a flight track.
Cell swelling stimulates phosphoinositide 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) in hepatocytes, and the PI3K signaling pathway is involved in cAMP-mediated translocation of ...sinusoidal Na+/taurocholate (TC) cotransporter (Ntcp) to the plasma membrane. We determined whether cell swelling also stimulates TC uptake and Ntcp translocation via the PI3K and/or MAPK signaling pathway. All studies were conducted in isolated rat hepatocytes. Hepatocyte swelling induced by hypotonic media resulted in: 1) time- and medium osmolarity-dependent increases in TC uptake, 2) an increase in the Vmax of Na+/TC cotransport, and 3) wortmannin-sensitive increases in TC uptake and plasma membrane Ntcp mass. Hepatocyte swelling also induced wortmannin-sensitive activation of PI3K, protein kinase B, and p70S6K. Rapamycin, an inhibitor of p70S6K, inhibited cell swelling-induced activation of p70S6K but failed to inhibit cell swelling-induced stimulation of TC uptake. Because PD98095, an inhibitor of MAPK, did not inhibit cell swelling-induced increases in TC uptake, it is unlikely that the effect of cell swelling on TC uptake is mediated via the MAPK signaling pathway. Taken together, these results indicate that 1) cell swelling stimulates TC uptake by translocating Ntcp to the plasma membrane, 2) this effect is mediated via the PI3K, but not MAPK, signaling pathway, and 3) protein kinase B, but not p70S6K, is a likely downstream effector of PI3K.
Adsorption of water-soluble, zwitterionic n-hexadecylphosphorylcholine (C16PC) amphiphiles has been examined at the hexadecane−aqueous solution interface using neutron reflectivity (NR) and ...interfacial tension measurements. The results of both methods indicate that the limiting area per surfactant molecule at the interface at the critical micelle concentration (cmc) is 40 ± 5 Å2. In the NR measurements, two isotopic contrasts have been employed to determine the adsorption isotherm and to explore the structure of the interfacial region. Single-layer model fitting to both isotopic contrasts was only possible for the single sub-cmc concentration studied, where a film thickness of 60 ± 5 Å was obtained; consistent single-layer model fits to both contrasts for concentrations greater than the cmc were not possible, leading to the requirement of a two-layer model with an overall film thickness close to 60 ± 2 Å. This film thickness is appreciably greater than the fully extended C16PC molecular length and cannot be explained purely in terms of thermal broadening. A further result is that the reflectivity data indicate that, as the C16PC concentration increases, the amount of water on the hexadecane side of the interfacial region increases, in contrast to intuitive expectation. These findings are interpreted by conjecturing a structural model in which a trilayer of C16PC molecules is formed at the interface with the water concentrated in the region occupied by the headgroups.
To investigate the association between idiopathic Parkinson disease (IPD) and reduced frequency of prior cigarette smoking, the authors compared the 29-year follow-up mortality rates and IPD ...incidence rates of men who were either cigarette smokers or nonsmokers at the time of enrollment in the Honolulu Heart Study (1965–1968). Based on IPD cases detected up to June 30, 1994, the age-adjusted incidence rate in smokers was less than half that in nonsmokers: 34.4 versus 94.2 cases per 100, 000 person-years of pre-illness follow-up, respectively. When data were stratified by 5-year age group, lower IPD incidence in smokers was observed at all ages between 50 and 90 years. Age-specific mortality trends for smokers and nonsmokers with and without IPD suggested that increased mortality in IPD patients was mostly associated with IPD itself and not with smoking. The slight excess mortality in smokers without IPD, versus nonsmokers without IPD, appeared insufficient to account for the “missing” incident IPD cases in smokers. These IPD incidence and mortality data are not highly consistent with the “selective mortality” hypothesis, which attributes reduced prior smoking frequency, typically reported by persons with IPD, to accelerated mortality in undiagnosed IPD-affected persons who smoke. The “protective” association of cigarette smoking with IPD occurrence may thus be real, suggesting the need for further study of biologic mechanisms of protection. Am J Epidemiol 1996; 144: 400–4.
We report on a search for low-frequency radio variability in 944 bright (> 4Jy at 154 MHz) unresolved, extragalactic radio sources monitored monthly for several years with the Murchison Widefield ...Array. In the majority of sources we find very low levels of variability with typical modulation indices < 5%. We detect 15 candidate low frequency variables that show significant long term variability (>2.8 years) with time-averaged modulation indices M = 3.1 - 7.1%. With 7/15 of these variable sources having peaked spectral energy distributions, and only 5.7% of the overall sample having peaked spectra, we find an increase in the prevalence of variability in this spectral class. We conclude that the variability seen in this survey is most probably a consequence of refractive interstellar scintillation and that these objects must have the majority of their flux density contained within angular diameters less than 50 milli-arcsec (which we support with multi-wavelength data). At 154 MHz we demonstrate that interstellar scintillation time-scales become long (~decades) and have low modulation indices, whilst synchrotron driven variability can only produce dynamic changes on time-scales of hundreds of years, with flux density changes less than one milli-jansky (without relativistic boosting). From this work we infer that the low frequency extra-galactic southern sky, as seen by SKA-Low, will be non-variable on time-scales shorter than one year.
A rating instrument is described that can be used to assess the results of stuttering treatments. The instrument yields a comprehensive and detailed description of speech quality in terms of ...articulation, phonation, pitch, and loudness, as well as naturalness. Psychometric characteristics of the instrument are analyzed, and methodological problems with evaluating stuttering instruments are discussed. (Author/PB)
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