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Biomedical subjects

David R Williams

Publications and source records attributed to David R Williams.

At least 37 records · Page 2Linked to original sources
PubMed2005

1-alkoxyallene as an effective precursor for regio- and stereocontrolled allylation reactions with aliphatic aldehydes via bis-stannylation.

Bis-stannylation of 1-(methoxy)methoxyallene yields (E)-(3-(methoxymethoxy)prop-2-ene-1,2-diyl) bis-tributylstannane (2) as a highly reactive allylation reagent. Stereoselective reactions of functionalized stannane 2 with a variety of aldehydes provide good yields of 1,2-diol derivatives. Reactions with alpha-alkoxyaldehydes proceed with chelation-controlled addition to afford efficient constructions of 3,4-anti-4,5-syn-relationships in stereotriads bearing three differentiated oxygen (alkoxy and hydroxy) substituents. Mechanistic considerations are presented, and derivatives for NMR experiments support the stereochemical assignments. An X-ray diffraction study is included.

Aldehydes↗
PubMed2005

Organization of the human trichromatic cone mosaic.

Using high-resolution adaptive-optics imaging combined with retinal densitometry, we characterized the arrangement of short- (S), middle- (M), and long- (L) wavelength-sensitive cones in eight human foveal mosaics. As suggested by previous studies, we found males with normal color vision that varied in the ratio of L to M cones (from 1.1:1 to 16.5:1). We also found a protan carrier with an even more extreme L:M ratio (0.37:1). All subjects had nearly identical S-cone densities, indicating independence of the developmental mechanism that governs the relative numerosity of L/M and S cones. L:M cone ratio estimates were correlated highly with those obtained in the same eyes using the flicker photometric electroretinogram (ERG), although the comparison indicates that the signal from each M cone makes a larger contribution to the ERG than each L cone. Although all subjects had highly disordered arrangements of L and M cones, three subjects showed evidence for departures from a strictly random rule for assigning the L and M cone photopigments. In two retinas, these departures corresponded to local clumping of cones of like type. In a third retina, the L:M cone ratio differed significantly at two retinal locations on opposite sides of the fovea. These results suggest that the assignment of L and M pigment, although highly irregular, is not a completely random process. Surprisingly, in the protan carrier, in which X-chromosome inactivation would favor L- or M-cone clumping, there was no evidence of clumping, perhaps as a result of cone migration during foveal development.

Color Perception↗
PubMed2005

Efforts toward the total synthesis of (-)-kendomycin.

[structure: see text] The synthesis of an advanced component leading to (-)-kendomycin is described. The synthetic scheme features the application of asymmetric conjugate addition methodology for the early generation of the C13-C14 (E)-trisubstituted olefin, providing an efficient assembly of the ansa chain. Condensation reactions probe two strategies for attachment of the aromatic system.

Aldehydes↗
PubMed2005

The locus of fixation and the foveal cone mosaic.

High-resolution retinal imaging with adaptive optics was used to record the position of a light stimulus on the cone mosaic, with an error at least five times smaller than the diameter of the smallest foveal cones. We discuss the factors that limit the accuracy with which absolute retinal position can be determined. In five subjects, the standard deviation of fixation positions measured in discrete trials ranged from 2.1 to 6.3 arcmin, with an average of 3.4 arcmin (about 17 microm), in agreement with previous studies (R. W. Ditchburn, 1973; R. M. Steinman, G. M. Haddad, A. A. Skavenski, & D. Wyman, 1973). The center of fixation, based on the mean retinal position for each of three subjects, was displaced from the location of highest foveal cone density by an average of about 10 arcmin (about 50 microm), indicating that cone density alone does not drive the location on the retina selected for fixation. This method can be used in psychophysical studies or medical applications requiring submicron registration of stimuli with respect to the retina or in delivering light to retinal features as small as single cells.

Adult↗
PubMed2005

Different sensations from cones with the same photopigment.

We used adaptive optics to study color fluctuation in the appearance of tiny flashes of light. For five subjects, near threshold, monochromatic stimuli with full widths at half maximum of 1/3 arcmin were delivered throughout a patch of retina near 1 deg in which we also determined the locations of L, M, and S cones. Subjects reported a wide variety of color sensations, even for long-wavelength stimuli, and all subjects reported blue or purple sensations at wavelengths for which S cones are insensitive. Subjects with more L cones reported more red sensations, and those with more M cones tended to report more green sensations. White responses increased linearly with the asymmetry in L to M cone ratio. The diversity in the color response could not be completely explained by combined L and M cone excitation, implying that photoreceptors within the same class can elicit more than one color sensation.

Color Perception↗
PubMed2005

Characteristics of two distinct clinical phenotypes in pathologically proven progressive supranuclear palsy: Richardson's syndrome and PSP-parkinsonism.

The clinical diagnosis of progressive supranuclear palsy (PSP) relies on the identification of characteristic signs and symptoms. A proportion of pathologically diagnosed cases do not develop these classic features, prove difficult to diagnose during life and are considered as atypical PSP. The aim of this study was to examine the apparent clinical dichotomy between typical and atypical PSP, and to compare the biochemical and genetic characteristics of these groups. In 103 consecutive cases of pathologically confirmed PSP, we have identified two clinical phenotypes by factor analysis which we have named Richardson's syndrome (RS) and PSP-parkinsonism (PSP-P). Cases of RS syndrome made up 54% of all cases, and were characterized by the early onset of postural instability and falls, supranuclear vertical gaze palsy and cognitive dysfunction. A second group of 33 (32%) were characterized by asymmetric onset, tremor, a moderate initial therapeutic response to levodopa and were frequently confused with Parkinson's disease (PSP-P). Fourteen cases (14%) could not be separated according to these criteria. In RS, two-thirds of cases were men, whereas the sex distribution in PSP-P was even. Disease duration in RS was significantly shorter (5.9 versus 9.1 years, P < 0.001) and age at death earlier (72.1 versus 75.5 years, P = 0.01) than in PSP-P. The isoform composition of insoluble tangle-tau isolated from the basal pons also differed significantly. In RS, the mean four-repeat:three-repeat tau ratio was 2.84 and in PSP-P it was 1.63 (P < 0.003). The effect of the H1,H1 PSP susceptibility genotype appeared stronger in RS than in PSP-P (odds ratio 13.2 versus 4.5). The difference in genotype frequencies between the clinical subgroups was not significant. There were no differences in apolipoprotein E genotypes. The classic clinical description of PSP, which includes supranuclear gaze palsy, early falls and dementia, does not adequately describe one-third of cases in this series of pathologically confirmed cases. We propose that PSP-P represents a second discrete clinical phenotype that needs to be clinically distinguished from classical PSP (RS). The different tau isoform deposition in the basal pons suggests that this may ultimately prove to be a discrete nosological entity.

Age of Onset↗
PubMed2005

Kufor Rakeb disease: autosomal recessive, levodopa-responsive parkinsonism with pyramidal degeneration, supranuclear gaze palsy, and dementia.

Kufor Rakeb disease is an autosomal recessive disorder characterized by subacute, juvenile-onset, levodopa-responsive parkinsonism, pyramidal signs, dementia, and a supranuclear gaze palsy. It was originally described more than a decade ago, and linkage analysis identified a locus on chromosome 1p36 that was previously assigned PARK9. We have further characterized the clinical picture and specifically re-assessed the response to levodopa in the original family, in the northern highlands of Jordan. In the 4 surviving patients, there has been a narrowing of the therapeutic window for levodopa with the emergence of peak-dose dyskinesias with increased spasticity and cognitive decline. Several new features were identified, including facial-faucial-finger mini-myoclonus, visual hallucinations, and oculogyric dystonic spasms.

Adolescent↗
PubMed2005

Cigarette smoking among low-income African Americans: a serious public health problem.

BACKGROUND: This study examines the current prevalence of cigarette smoking and the number of cigarettes smoked in a community-based sample of 1021 low-income African-American men and women. METHODS: Participants were selected using a two-stage, area probability sample design. Data were collected in 2002-2003 in face-to-face interviews and analyzed in 2005. All data and analyses were weighted to account for the complex sampling design. RESULTS: Fifty-nine percent of men and 41% of women were current smokers, with younger individuals apparently initiating smoking at an earlier age than older individuals. CONCLUSIONS: The high prevalence of cigarette use provides further evidence that the excess burden of tobacco-related disease among low-income African-American families may be on the rise. This is of great concern, and if confirmed by further research, indicates an urgent need for preventive intervention.

Adolescent↗
PubMed2005

Causes of spherical aberration induced by laser refractive surgery.

PURPOSE: To develop a corneal model to better explain how refractive surgery procedures induce spherical aberration. SETTING: Department of Ophthalmology and Center for Visual Science, University of Rochester, Rochester, New York, USA. METHODS: The preoperative cornea was modeled as a rotationally symmetric surface with various radii of curvature and asphericities. The postoperative cornea was defined as the difference between the preoperative cornea and an ablation thickness profile computed based on the Munnerlyn equation. A ray-tracing program and Zernike polynomial fitting were used to calculate the induced amount of spherical aberration assuming a fixed ablation depth per pulse or a variable ablation depth depending on the incidence angle of each pulse on the cornea. A biological eye model of the corneal surface change after laser refractive surgery was also developed to explain the induced spherical aberrations after myopic and hyperopic treatments. RESULTS: The clinical data showed that positive spherical aberration was induced after myopic correction and negative spherical aberration increased after hyperopic correction. In contrast, assuming a fixed ablation depth per pulse, the theoretical prediction was that negative spherical aberration with myopic treatment and positive spherical aberration with hyperopic treatment would increase. However, when assuming a variable ablation depth per pulse caused by non-normal incidence of laser spot on the cornea, the theoretically predicted induction of spherical aberration tends to fit better with the myopic and hyperopic clinical data. The effect of a variable ablation depth accounted for approximately half the clinically observed amount of spherical aberration. The biological model of the corneal surface change used to explain this remaining discrepancy showed the magnitude of the biological response in myopic correction is 3 times smaller than in hyperopic correction and that the direction of the biological response in hyperopic treatment is opposite that in myopic treatment. CONCLUSIONS: This nontoric eye model, which separates the effects of differences in ablation efficiency and biological corneal surface change quantitatively, explains how spherical aberration is induced after myopic and hyperopic laser refractive surgery. With the corneal topographic data, this model can be incorporated into the ablation algorithm to decrease induced spherical aberrations, improving the outcomes of conventional and customized treatments.

Computer Simulation↗
PubMed2005

Surgeon offsets and dynamic eye movements in laser refractive surgery.

PURPOSE: To determine the amount of static and dynamic pupil decentrations that occur during laser refractive surgery. SETTING: The Center of Visual Science and the Department of Ophthalmology, University of Rochester, Rochester, New York, USA. METHODS: The surgeon's accuracy in aligning the pupil center with the laser center axis was measured when engaging the eye-tracker in 17 eyes receiving conventional laser in situ keratomileusis (LASIK) procedures (Technolas 217z; Bausch & Lomb). Eye movements were measured subsequently during the treatment in 10 eyes using a pupil camera operating at 50 Hz. Temporal power spectra were calculated from the eye movement measurements. RESULTS: The mean pupil misalignment by the surgeon at the beginning of the procedure was 206.1 microm +/- 80.99 (SD) (with respect to the laser center). The laser center was typically misaligned below (inferiorly) and to the left (nasally and temporally in left and right eyes, respectively) of the pupil [corrected] center. Small amounts of cyclotorsion were observed during the ablation (<2 degrees). The mean magnitude of dynamic pupil decentration from the laser center during treatment was 227.0 +/- 44.07 microm. The mean standard deviation of eye movements was 65.7 +/- 25.64 microm. Temporal power spectra calculated from the horizontal and vertical changes in eye position during the ablation were similar. Ninety-five percent of the total power of the eye movements was contained in temporal frequencies up to 1 Hz, on average, in both directions. CONCLUSIONS: Most eye movements during LASIK are slow drifts in fixation. An eye-tracker with a 1.4 Hz closed-loop bandwidth could compensate for most eye movements in conventional or customized ablations.

Calibration↗
PubMed2005

Impact of socioeconomic status on longitudinal accumulation of cardiovascular risk in young adults: the CARDIA Study (USA).

Our objectives were to describe the trajectories of biological risk factors of cardiovascular disease in young adults, and to study the association of socioeconomic status (SES) with aggregate risk scores that summarize longitudinal risk accumulation from multiple risk factors. We used data from a prospective, bi-racial, cohort study of 18-30-year-old adults in the USA, initiated in 1985, with 10-year follow-up. SES was measured by parental education level, financial hardship during the study, and the participant's education level by the end of the study. We studied growth patterns of seven biological risk factors for cardiovascular disease using a semi-parametric, class-mixture model to identify clusters of individuals with distinct growth trajectories. Risk scores that summarize risk from all seven risk factors were created to reflect risk at baseline, longitudinal risk change over 10 years, and total accumulated risk. Multivariable regression was used to study their associations with SES within each race/gender group. We found tracking of all seven risk factors: in each case, the cluster with the highest baseline value maintained its position as the highest-risk cluster over the next 10 years. After adjustment for age, lifestyle, and healthcare access, SES was associated inversely with baseline risk score in women (black and white), with risk change score in all four race/gender groups, and with accumulated risk score in women (black and white) and in white men. Our findings suggest that individuals with high overall cardiovascular risk in midlife can be identified by their relatively higher values of risk factors in younger ages and that socioeconomic differences in cardiovascular risk start accumulating early in life.

Adolescent↗
PubMed2005

Food insufficiency and women's mental health: findings from a 3-year panel of welfare recipients.

Household food insufficiency is a significant problem in the United States, and has been associated with poor outcomes on mental health indicators among low-income women. However, it is difficult to disentangle the mental health consequences of household food insufficiency from poverty and other shared risk factors. Drawing on theories of the social production of health and disease, research evidence linking food insufficiency with poor mental health, and high rates of food insufficiency among welfare recipients, we examined whether a change in household food insufficiency is associated with a change in women's self-reported mental health in a sample of current and recent welfare recipients over a 3-year period of time, controlling for common risk factors. Data were obtained from a prospective survey of women who were welfare recipients in an urban Michigan county in February 1997 (n=753). We estimated fixed effect models for changes in mental health status that make use of information on household food insufficiency gathered in the fall of 1997, 1998, and 1999. The relationship between household food insufficiency and respondents' meeting the diagnostic screening criteria for major depression remained highly significant even when controlling for factors known to confer increased risk of depression and time invariant unobserved heterogeneity. These findings add to growing evidence that household food insufficiency has potentially serious consequences for low-income women's mental health. If confirmed by further research, they suggest that the public health burden of depression in welfare recipients and other low-income women could be reduced by policy-level interventions to reduce their exposure to household food insufficiency.

Adolescent↗
PubMed2005

Visual hallucinations in the diagnosis of idiopathic Parkinson's disease: a retrospective autopsy study.

BACKGROUND: For many years, visual hallucinations (VH) in idiopathic Parkinson's disease (PD) were thought to be a complication of antiparkinsonian treatment. The cause of VH is now thought to be nerve-cell loss and Lewy-body pathology in the ventral-temporal regions of the brain. However, the use of VH as a clinical sign of PD has not been investigated. METHODS: 788 cases with parkinsonism archived at the Queen Square Brain Bank for Neurological Diseases were identified for study. Patients had not been given standardised antemortem assessments. Clinical records were assessed for reports of VH. The incidence of VH in pathologically diagnosed cases was calculated, and factors affecting onset of VH were investigated. FINDINGS: VH occurred in 50% (221/445) of patients with PD, in 73% (32/44) with dementia with Lewy bodies (DLB), and in only 7% (18/255) of patients with non-Lewy-body parkinsonism. The specificity of VH for Lewy-body parkinsonism (PD and DLB combined) was 92.9% (95% CI 89.1-95.8) and the positive predictive value was 93.4% (89.7-95.8). VH were associated with cognitive dysfunction (hazard ratio 5.62, 3.37-9.35), autonomic dysfunction (3.13, 1.77-5.52), axial rigidity (2.22, 1.26-3.85) within the first 2 years of disease onset and also age of onset (1.05, 1.03-1.07). In PD, the onset of VH typically occurred in the second half of the disease course, and time to onset of VH was only weakly correlated with use of selegiline (Spearman's rho 0.22, p=0.005) and ergot dopamine agonists (0.24, p=0.006) but not correlated with use of levodopa, amantadine, or anticholinergic drugs. INTERPRETATION: The presence of VH is helpful in the differentiation of PD from other non-Lewy-body causes of parkinsonism. We propose that VH be added, as a supportive criterion, to the operational clinical criteria for the diagnosis of PD.

Adult↗
PubMed2005

The health of U.S. racial and ethnic populations.

This article provides an overview of racial and ethnic disparities in health in the United States. It describes limitations linked to the quality and method of presentation of the available data. It also considers the complex ways in which immigrant status, race, and SES combine to affect health and outlines important directions for research that would enhance our understanding of the ways in which social factors can lead to changes in health status.

Emigration and Immigration↗
PubMed2005

Image metrics for predicting subjective image quality.

PURPOSE: Despite the proliferation of wavefront sensors to characterize the optical quality of individual eyes, there is not yet an accurate way to determine from a wave aberration how severely it will impact the patient's vision. Some of the most commonly used metrics, such as RMS wavefront error and the Strehl ratio, predict subjective image quality poorly. Our goal is to establish a better metric to predict subjective image quality from the wave aberration. METHODS: We describe three kinds of experiments designed to compare the effectiveness of different metrics in determining the subjective impact of the wave aberration. Subjects viewed a visual stimulus through a deformable mirror in an adaptive optics system that compensated for the subject's wave aberration. In the first experiment, we show that some Zernike modes such as spherical aberration and defocus interact strongly in determining subjective image quality. In the second experiment, the subject's wave aberration was replaced by the wave aberration corresponding to an individual Zernike mode. The subject then adjusted the coefficient of the Zernike mode to match the blur of a standard stimulus. In the third experiment, the subject viewed the same stimulus through the wave aberration of one of 59 different postoperative patients who had undergone LASIK and matched the blur by adjusting defocus. We then determined which among many image quality metrics best predicted these matching data. RESULTS: RMS wavefront error was a poor predictor of the data, as was the Strehl ratio. CONCLUSIONS: The neural sharpness metric best described the subjective sharpness of images viewed through the wave aberrations of real eyes. This metric can provide a single number that describes the subjective impact of each patient's wave aberration and will also increase the accuracy of refraction estimates from wavefront-based autorefractors and phoropters.

Humans↗
PubMed2005

Neighbourhood characteristics, individual level socioeconomic factors, and depressive symptoms in young adults: the CARDIA study.

STUDY OBJECTIVE: To investigate the relation between neighbourhood socioeconomic and ethnic characteristics with depressive symptoms in a population based sample. DESIGN: Cross sectional data from the CARDIA study, including the Center for Epidemiological Studies depression scale score (CES-D). Neighbourhoods were 1990 US census blocks of 1000 people; six census variables reflecting wealth/income, education, and occupation investigated separately and as a summary score; neighbourhood racial composition (percentage white and black) and individual level income and education were also examined. SETTING: Participants recruited in 1985/86 from community lists in Birmingham, AL; Chicago, IL; Minneapolis MN; from a health plan in Oakland, CA. PARTICIPANTS: 3437 adults aged 28-40 years in 1995/96: 24% white men, 27% white women, 20% black men, 29% black women. MAIN RESULTS: For each race-sex group, CES-D was inversely related to neighbourhood score and individual income and education. Associations of neighbourhood score with CES-D became weak and inconsistent after adjusting for individual level factors; personal income remained strongly and inversely associated with CES-D. Age adjusted mean differences (standard errors) in CES-D between the lowest and highest income categories were 3.41 (0.62) for white men, 4.57 (0.64) for white women, 5.80 (0.87) for black men, and 5.74 (0.83) for black women. For both black and white participants, CES-D was associated negatively with percentage of white people and positively with percentage of black people in their census block, before, but not after, adjustment for individual and neighbourhood socioeconomic variables. CONCLUSIONS: Neither neighbourhood socioeconomic characteristics nor ethnic density were consistently related to depressive symptoms once individual socioeconomic characteristics were taken into account.

Adult↗