Biomedical subjects
Publications and source records attributed to David R Williams.
The conjugate addition reactions of allylic stannanes have been investigated utilizing nonracemic N-enoyl-4-phenyl-1,3-oxazolidinones with Lewis acid precomplexation.
[reaction: see text] An enantioselective total synthesis of (-)-stemonine (1) is reported via a convergent assembly of the acyclic precursor 2. Key transformations include a Staudinger-aza-Wittig reaction to form the central perhydroazepine ring system and an iodine-induced tandem cyclization to construct the pyrrolidino-butyrolactone framework.
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The first total synthesis of the marine dolabellane diterpene (+)-4,5-deoxyneodolabelline (1) has been accomplished. The highly efficient approach is characterized by the convergent assembly of dihydropyrans 2ab and cyclopentylsilanes 3ab. Allylic silane 3a was prepared from 2-methyl-2-cyclopentenone via a copper-catalyzed 1,4-addition followed by diastereoselective alkylation of the resulting enolate. A chemical resolution of racemic cyclopentanone 8 was effected by (S)-CBS-catalyzed borohydride reduction. Direct hydroxymethylation of the enantioenriched ketone 8 to form allylic alcohol 14 was achieved by a Stille palladium-catalyzed cross-coupling from the cyclopentenyl triflate 13. Treatment of the corresponding allylic phosphate 15 with trimethylsilylcopper reagent provided for displacement with allylic transposition yielding the exocyclic allylsilane 3a with excellent diastereoselectivity. Dihydropyrans 2a and 2b were prepared from optically pure acyclic acetals via ring-closing metathesis. Coupling of 3a and 2a or 2b via the carbon-Ferrier protocol gave trans-2,6-disubstituted dihydropyrans 30 and 35 with complete stereoselectivity. Vanadium-based pinacol coupling reactions were explored for closure of the medium-sized carbocycle to yield syn-diol 33. X-ray diffraction studies of the monobenzoate 34 have provided unambiguous stereochemical assignments. Substantial ring strain accounted for the lack of alkene products typical of reductive elimination using TiCl(3) and zinc-copper couple (McMurry) conditions leading to 37. Finally, the natural product 1 was obtained via Swern oxidation of the diol 37.
PURPOSE: To study the optical changes induced by the microkeratome cut, the subsequent laser ablation, and the biomechanical healing response of the cornea in normal laser in situ keratomileusis (LASIK) eyes. DESIGN: Prospective randomized clinical trial. METHODS: A Hansatome microkeratome was used to cut a corneal flap in one eye (study eye) of 17 normal myopic patients and a subsequent laser ablation was performed 2 months after this initial microkeratome incision. Control eyes received conventional LASIK treatments at the latter time point. The wave aberration of both the study and contralateral control eyes were measured over a 6-mm pupil with a Shack-Hartmann wavefront sensor for all preoperative, postflap cut, and postablation visits. RESULTS: The eye's higher order aberrations had a small, but significant increase (P =.03) of approximately 30% 2 months after cutting a flap. No systematic changes were observed in nearly all Zernike coefficients from their preoperative levels at 2 months postflap cut. A significant difference between the study and control eyes was observed for one trefoil mode, Z(3)(3) (P =.04). CONCLUSIONS: There was a wide variation in the response of individual Zernike modes across patients after cutting a flap. The majority of spherical aberration induced by the LASIK procedure seems to be due to the laser ablation and not the microkeratome cut. In addition, the total and higher order root mean square of wavefront errors were nearly identical for both the study and control eyes 3-months after the laser ablation, indicating that a procedure in which the incision and the ablation are separated in time to better control aberrations does not compromise the outcome of a conventional LASIK treatment.
The study reported in this article examined the prevalence of mental health disorders and the sociodemographic factors associated with having a mental health disorder in a probability sample of 185 African American and white single mothers. Logistic regression analyses revealed that race (being white) and being on welfare were associated with increased risk of having a mental health disorder, when controlling for other sociodemographic variables. The association of welfare status and psychiatric disorders highlights the need for access to mental health services for this population. Implications for low-income women making the transition from welfare to employment are discussed.
This article provides an overview of the evidence on the ways racism can affect the disproportionate rates of cardiovascular disease (CVD) in African Americans. It describes the significant health disparities in CVD for blacks and whites and suggests that racial disparities should be understood within the context of persistent inequities in societal institutions and relations. Evidence and potential pathways for exploring effects of 3 levels of racism on cardiovascular health risk factors and outcomes are reviewed. First, institutional racism can lead to limited opportunities for socioeconomic mobility, differential access to goods and resources, and poor living conditions that can adversely affect cardiovascular health. Second, perceived/personally mediated racism acts as a stressor and can induce psychophysiological reactions that negatively affect cardiovascular health. Third, in race-conscious societies, such as the United States, the negative self-evaluations of accepting negative cultural stereotypes as true (internalized racism) can have deleterious effects on cardiovascular health. Few population-based studies have examined the relationship between racism and CVD. The findings, though suggestive of a positive association, are neither consistent nor clear. The research agenda of the Jackson Heart Study in addressing the role of racism in CVD is presented.
We explored the impact of the eye's higher-order aberrations on subjective refraction comparing two classes of methods for estimating refractive state, one based directly on the wave aberration defined in the pupil plane and another based on the retinal image plane. The method defined in the pupil plane chose the sphere and cylinder that either minimized the wave aberration root mean square or minimized the sum of all the spherical and cylindrical components in the wave aberration. The method defined in the image plane chose the sphere and cylinder that optimized an image-quality metric such as the Strehl intensity ratio, the entropy and the intensity variance of the point-spread function, the volume under the modulation transfer function, or the volume under the contrast-sensitivity function. All these methods were compared in a population of six eyes for which we measured both the wave aberration with a Shack-Hartmann wavefront sensor and the subjective refraction under identical conditions. Pupil plane methods predicted subjective refraction poorly. The mean absolute error of the prediction, in spherical equivalent, was about 0.5 D (range, 0.1 to 0.8 D) and increased with increases in higher-order aberrations. However, for all the retinal image plane methods, the mean error between predicted and subjective refraction was about 0.1 D (range, 0 to 0.25 D). The reliability of the method based on the image-quality optimization was further confirmed in a large population of 146 eyes. In conclusion, higher-order aberrations influence the amount of sphere and cylinder required to correct vision. The results indicate that subjective refraction can be predicted from the eye's optics alone by optimizing computed retinal image quality.
OBJECTIVE: Little is currently known about the pastoral counseling work of pastors of African-American churches. The authors interviewed the pastors of nearly all African-American churches in a metropolitan area about their pastoral counseling work and related aspects of their ministry. METHODS: Of 121 African-American pastors identified, 99 completed a semistructured interview describing their backgrounds, attitudes, concerns, and work. The interview included detailed queries about how they understood and carried out any pastoral counseling work. RESULTS: The respondents averaged more than six hours of counseling work weekly and often addressed serious problems similar to those seen by secular mental health professionals, with whom they reported readily exchanging referrals. Many of the respondents reported having and maintaining specialized education for their counseling work, which they described as including both spiritual and psychological dimensions. Most of the pastors reported that they observe and address severe mental illness and substance abuse in their congregations and that they also counsel individuals outside their own denominations. CONCLUSIONS: African-American urban ministers functioning as pastoral counselors constitute an engaging and useful group with experiences and skills that can be tapped by interested secular professionals. Their work represents a significant mental health resource for persons who lack sufficient access to needed care.
The authors review the available empirical evidence from population-based studies of the association between perceptions of racial/ethnic discrimination and health. This research indicates that discrimination is associated with multiple indicators of poorer physical and, especially, mental health status. However, the extant research does not adequately address whether and how exposure to discrimination leads to increased risk of disease. Gaps in the literature include limitations linked to measurement of discrimination, research designs, and inattention to the way in which the association between discrimination and health unfolds over the life course. Research on stress points to important directions for the future assessment of discrimination and the testing of the underlying processes and mechanisms by which discrimination can lead to changes in health.
I have summarized in this article data on the magnitude of health challenges faced by men in the United States. Across a broad range of indicators, men report poorer health than women. Although men in all socioeconomic groups are doing poorly in terms of health, some especially high-risk groups include men of low socioeconomic status (SES) of all racial/ethnic backgrounds, low-SES minority men, and middle-class Black men. Multiple factors contribute to the elevated health risks of men. These include economic marginality, adverse working conditions, and gendered coping responses to stress, each of which can lead to high levels of substance use, other health-damaging behaviors, and an aversion to health-protective behaviors. The forces that adversely affect men's health are interrelated, unfold over the life course, and are amenable to change.
An intensely debated issue concerning visual-experience-dependent neural plasticity is whether experience is required only to maintain function or whether information from experience is used actively, relieving the necessity to hard-wire all connections and allowing adaptive adjustments. Here, an active role for experience is demonstrated in circuits for color vision. Chromatic experience was altered using colored filters. Over days there was a shift in color perception, as measured by the wavelength of unique yellow, which persisted 1-2 weeks after the filters were discontinued. Moreover, color-deficient adults were shown to have altered weightings of inputs to chromatic channels, demonstrating a large neural adjustment to their inherited photopigment defect. Thus, a neural normalization mechanism for color perception, determined by visual experience, operates to compensate for large genetic differences in retinal architecture and for changes in chromatic environment.
BACKGROUND: Results of previous studies have suggested that involvement in religious activities may be associated with lower rates of smoking. We sought to determine whether frequent attendance at religious services is associated with less smoking among young adults. METHODS: This prospective cohort study of 4569 adults aged 20 to 32 years included approximately equal numbers of blacks and whites and men and women from 4 cities in the United States who attended the 1987/1988 examination of the Coronary Artery Risk Development in Young Adults (CARDIA) study. Frequency of attendance at religious services and denominational affiliation were determined by self-report questionnaire in 1987/1988. Cigarette smoking was determined by interview at this time and again 3 years later. RESULTS: Of 4544 participants who completed the tobacco questionnaire in 1987/1988, 34% (891/2598) who attended religious services less than once per month or never and 23% (451/1946) who attended religious services at least once per month reported current smoking (odds ratio [OR], 1.7; 95% confidence interval [CI], 1.5-2.0; P<.001). This association between less frequent attendance at religious services and current smoking was found in most denominations and remained significant after adjusting for potential confounding variables (OR, 1.5; 95% CI, 1.3-1.8; P<.001). During 3-year follow-up, nonsmokers who reported little or no religious involvement had an increased risk of smoking initiation (adjusted OR, 1.9; 95% CI, 1.3-2.7; P<.001). CONCLUSIONS: Young adults who attend religious services have lower rates of current and subsequent cigarette smoking. The potential health benefits associated with religious involvement deserve further study.
A strategic use of resources is essential to achieving long-duration space travel and understanding the human physiological changes in space, including the roles of food and nutrition in space. To effectively address the challenges of space flight, the Bioastronautics Initiative, undertaken in 2001, expands extramural collaboration and leverages unique capabilities of the scientific community and the federal government, all the while applying this integrated knowledge to Earth-based problems. Integral to the National Aeronautics and Space Administration's missions in space is the reduction of risk of medical complications, particularly during missions of long duration. Cumulative medical experience and research provide the ability to develop evidence-based medicine for prevention, countermeasures, and treatment modalities for space flight. The early approach applied terrestrial clinical judgment to predict medical problems in space. Space medicine has evolved to an evidence-based approach with the use of biomedical data gathered and lessons learned from previous space flight missions to systematically aid in decision making. This approach led, for example, to the determination of preliminary nutritional requirements for space flight, and it aids in the development of nutrition itself as a countermeasure to support nutritional mitigation of adaptation to space.
A model simulating the human duodenal contents under physiologically realistic, fasting conditions was developed using the joint expert speciation system (JESS) computer program and database and used to investigate the chemical speciation of caesium, uranium(VI) and neptunium(V). Over the pH range 5.0-9.0, and the concentration range 5 x 10(-15) x 10(-5) mol dm(-3), caesium was predicted to occur predominantly as the absorbable free monovalent cation Cs+ (approximately 95%) with species such as CsHPO4- and CsCl representing the remainder. The presence or absence of sulphate at 2.1 x 10(-3) mol dm(-3) did not influence the predicted speciation. Uranium was predicted to be present entirely as a soluble, highly charged species, both in the absence and in the presence of sulphate. Between pH 5.0 and approximately 6.5 the UO2H2(PO4)2(2-) predominated, above this pH carbonate species, either UO2(CO3)4(6-) or, possibly, UO2(CO3)5(8-). At pH 8.0, and in the presence of sulphate, neptunium(V) was predicted to exist solely as the tetrasulphate species, whilst in the absence of sulphate, an array of negatively charged soluble carbonate species predominated. Studies over the pH range 5.0-9.0 predicted the formation of a spectrum of negatively charged carbonate and phosphate species, approximately 40% of the total neptunium was predicted to be present as the electrically net-neutral species NpO2HCO3 at pH6.0, approximately 20% at pH 7.0, approximately 10% at pH 7.5 and approximately 1% at pH 8.0. The observed speciation patterns of uranium and neptunium did not change over the concentration range 5 x 10(-15) - 5 x 10(-5) mol dm(-3) and no solid species were predicted to occur under the conditions simulated. Whether the predicted electrically net-neutral neptunium species or the uranium pentacarbonate species do actually occur under true physiological conditions remains to be established. The observed speciation patterns for caesium and uranium are consistent with the observed absorption of these elements by humans; however, the observations for neptunium appear to be equivocal.
BACKGROUND: Ultrasound is of proven accuracy in abdominal and thoracic trauma and may be useful for diagnosing extremity injury in situations where radiography is not available such as military and space applications. We prospectively evaluated the utility of extremity ultrasound performed by trained, nonphysician personnel in patients with extremity trauma to simulate remote aerospace or military applications. METHODS: Patients with extremity trauma were identified by history, physical examination, and radiographic studies. Ultrasound examination was performed bilaterally by nonphysician personnel, blinded to radiographic results, with a portable ultrasound device using a 10- to 5-MHz linear probe. Images were videorecorded for later analysis against radiography by Fisher's exact test. RESULTS: There were 158 examinations performed in 95 patients. The average time of examination was 4 minutes. Ultrasound accurately diagnosed extremity injury in 94% of patients with no false-positive examinations; accuracy was greater in midshaft locations and least in the metacarpal/metatarsals. Soft tissue/tendon injury was readily visualized. CONCLUSION: Extremity ultrasound can be performed quickly and accurately by nonphysician personnel with excellent accuracy. Pulmonary ultrasound appears promising; blinded verification of the utility of ultrasound in patients with extremity injury should be performed to determine whether extremity and respiratory evaluation should be added to the FAST examination (the FASTER examination) and to verify the technique in remote locations such as military and aerospace applications.
African Americans in the United States have a higher than average risk of morbidity and mortality, despite declining mortality rates for many causes of death for the general population. This article examines race-based residential segregation as a fundamental cause of racial disparities, shaping differences in exposure to, and experiences of, diseases and risk factors. The spatial distribution of racial groups, specifically the residential segregation of African Americans in aging urban areas, contributes to disparities in health by influencing access to economic, social, and physical resources essential to health. Using the Detroit metropolitan area as a case study, this article looks at the influences of the distribution of African American and white residents on access to these resources and discusses the implications for urban policies to reduce racial disparities in health status.