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Biomedical subjects

David Watson

Publications and source records attributed to David Watson.

At least 19 recordsLinked to original sources

Impact of a collaborative shared antenatal care program for urban Indigenous women: a prospective cohort study.

OBJECTIVES: To evaluate the impact of a community-based, collaborative, shared antenatal care intervention (the Mums and Babies program) for Indigenous women in Townsville. DESIGN AND PARTICIPANTS: Prospective cohort study of women attending Townsville Aboriginal and Islander Health Service (TAIHS) for shared antenatal care with a singleton Indigenous birth between 1 January 2000 and 31 December 2003 (456 women; the MB group), compared with a historical control group of 84 women who attended TAIHS for antenatal care before the intervention between 1 January 1998 and 30 June1999, and a contemporary control group of 540 women who had a singleton birth at Townsville Hospital between 1 January 2000 and 30 June 2003, but did not attend TAIHS for antenatal care. INTERVENTION: Integration of previously autonomous service providers delivering shared antenatal care from TAIHS. MAIN OUTCOME MEASURES: Patterns of antenatal visits, proportion of women undertaking key antenatal screening, and perinatal outcomes. RESULTS: The number of Indigenous women who entered the MB program and gave birth at Townsville Hospital rose from 23.8% in 2000 to 61.2% in 2003. The number of antenatal care visits per pregnancy increased from three (interquartile [IQ] range, 2-6) in the historical control group to seven (IQ range, 4-10) in the MB group (P < 0.001). 88% of women in the MB group had at least one ultrasound. About 90% of all women attending for antenatal care were screened for sexually transmitted infections. In the MB group, there was a significant reduction in preterm births compared with the contemporary control group (8.7% v 14.3%, P < 0.01). There was no significant reduction in the prevalence of low birthweight births or perinatal mortality. CONCLUSION: A community-based collaborative approach to shared antenatal care services increased access to antenatal care and was associated with fewer preterm births among Indigenous women in Townsville. The model may be adaptable in other urban centres with multiple antenatal care providers and significant numbers of Indigenous people across Australia.

Adult↗

Identification and characterization of the unique N-linked glycan common to the flagellins and S-layer glycoprotein of Methanococcus voltae.

The flagellum of Methanococcus voltae is composed of four structural flagellin proteins FlaA, FlaB1, FlaB2, and FlaB3. These proteins possess a total of 15 potential N-linked sequons (NX(S/T)) and show a mass shift on an SDS-polyacrylamide gel indicating significant post-translational modification. We describe here the structural characterization of the flagellin glycan from M. voltae using mass spectrometry to examine the proteolytic digests of the flagellin proteins in combination with NMR analysis of the purified glycan using a sensitive, cryogenically cooled probe. Nano-liquid chromatography-tandem mass spectrometry analysis of the proteolytic digests of the flagellin proteins revealed that they are post-translationally modified with a novel N-linked trisaccharide of mass 779 Da that is composed of three sugar residues with masses of 318, 258, and 203 Da, respectively. In every instance the glycan is attached to the peptide through the asparagine residue of a typical N-linked sequon. The glycan modification has been observed on 14 of the 15 sequon sites present on the four flagellin structural proteins. The novel glycan structure elucidated by NMR analysis was shown to be a trisaccharide composed of beta-ManpNAcA6Thr-(1-4)-beta-Glc-pNAc3NAcA-(1-3)-beta-GlcpNAc linked to Asn. In addition, the same trisaccharide was identified on a tryptic peptide of the S-layer protein from this organism implicating a common N-linked glycosylation pathway.

Amino Acid Sequence↗

Hoarding and its relation to obsessive-compulsive disorder.

Although hoarding is observed in some patients with obsessive-compulsive disorder (OCD), it has not been shown to share a specific relation with OCD. Across two studies, we found that (a) whereas the classic OCD symptoms of checking, rituals, and contamination intercorrelated consistently strongly with one another, hoarding related only moderately to both these OCD symptoms and to depression; (b) OCD patients were distinguished from both other patients and non-patients by classic OCD symptoms, but not by hoarding; and (c) whereas OCD symptoms showed consistent relations with Negative Affect, hoarding largely was uncorrelated with this dimension. These results do not support a specific OCD-hoarding relation but rather call into question the trend of considering it a specific symptom of OCD.

Adolescent↗

Delineating the structure of normal and abnormal personality: an integrative hierarchical approach.

Increasing evidence indicates that normal and abnormal personality can be treated within a single structural framework. However, identification of a single integrated structure of normal and abnormal personality has remained elusive. Here, a constructive replication approach was used to delineate an integrative hierarchical account of the structure of normal and abnormal personality. This hierarchical structure, which integrates many Big Trait models proposed in the literature, replicated across a meta-analysis as well as an empirical study, and across samples of participants as well as measures. The proposed structure resembles previously suggested accounts of personality hierarchy and provides insight into the nature of personality hierarchy more generally. Potential directions for future research on personality and psychopathology are discussed.

Factor Analysis, Statistical↗

Assessment of the hypochondriasis domain: the multidimensional inventory of hypochondriacal traits (MIHT).

Although hypochondriasis is associated with the costly use of unnecessary medical resources, this mental health problem remains largely neglected. A lack of clear conceptual models and valid measures has impeded accurate assessment and hindered progress. The Multidimensional Inventory of Hypochondriacal Traits (MIHT) addresses these deficiencies with scales that correspond to a 4-factor model. The MIHT was built with construct validity as a guiding principle and began with an item pool that broadly assessed dimensions identified in the literature. The items were administered to large samples; factor analyses of the responses led to item pool revisions and scale refinements. Multiple studies validated the final MIHT scales and 4-factor model; these findings suggest that the MIHT will contribute to theory and research.

Adolescent↗

Development and validation of the Schedule of Compulsions, Obsessions, and Pathological Impulses (SCOPI).

This article describes a factor analytically derived, self-report instrument-the Schedule of Compulsions, Obsessions, and Pathological Impulses (SCOPI)-using data from college students, adults, psychiatric outpatients, and patients with obsessive-compulsive disorder (OCD). The five SCOPI scales all are internally consistent (with coefficient alphas of .80 and higher) and are strongly stable across a 2-month interval (with retest correlations ranging from .79 to .82). They also show good convergent and adequate discriminant validity (a) when correlated with other OCD measures and (b) in analyses of self-ratings versus spouse ratings. Additional analyses indicate that three scales-Obsessive Checking, Obsessive Cleanliness, and Compulsive Rituals-assess core symptoms of OCD. The two remaining scales-Hoarding and Pathological Impulses-appear to tap different (but related) constructs.

Adult↗

Highly active antiretroviral therapy improves neurocognitive functioning.

Although the effects of highly active antiretroviral therapy (HAART) have resulted in substantial improvements in the systemic health of patients with HIV infection, concerns remain that these medications, which cross the blood-brain barrier poorly, may have a less beneficial effect on nervous system function. This raises the possibility that there may be a progressive long-term decline in neurologic function in patients with adequate systemic response. In a prospective longitudinal study, subjects were evaluated immediately before instituting HAART. Forty-eight subjects underwent ultrasensitive HIV RNA quantitative evaluation of both plasma and cerebrospinal fluid as well as neurologic and neuropsychological examinations. They were reevaluated 6 months after treatment initiation while receiving stable HAART. Both plasma and cerebrospinal fluid viral levels significantly declined after treatment. There was significant improvement in neurologic and neuropsychological functioning after HAART. These results indicate that despite the poor central nervous system penetration of most of these agents, there is satisfactory short-term improvement in both central nervous system viral burden and nervous system function with HAART. However, because treatment failure is increasingly likely over time, continued longitudinal evaluation of this group of subjects is required.

AIDS Dementia Complex↗

Health care resource use after acute stroke in the Glycine Antagonist in Neuroprotection (GAIN) Americas trial.

BACKGROUND AND PURPOSE: To compare 3-month stroke outcomes and stroke-related health care resource use between the US and Canada in the Glycine Antagonist in Neuroprotection (GAIN) Americas study. Delivery of medical care for stroke patients, often driven by efforts to curb costs, varies substantially between countries. Data on the potential impact of these variations on clinical outcomes are sparse. METHODS: The analysis of health care resource included total length of stay (LOS) in hospital, intensive care unit (ICU), and acute-care ward or rehabilitation unit, or both; number of outpatient rehabilitation sessions and visits to a physician; place of residence after discharge; and employment status. Cox proportional hazards models and logistic regression were used to calculate survival hazards and predictors of favorable functional outcome (Barthel Index of 95 to 100). RESULTS: One thousand six hundred four patients who were independent before stroke (mean age: 69.9+/-12.7 years, 53% men, 85% ischemic stroke, 69% in the US) were included. Three-month survival and functional outcome did not differ between the US and Canada. Survival rate was 80% in both countries. Favorable functional outcome was achieved in 43% of Canadian and 47% of US patients. Fewer Canadian patients received treatment in ICU (19% versus 63% in the US), and Canadians had longer stays in hospital or rehabilitation facility (median: 33 days versus 16 days in the US). CONCLUSIONS: Despite similar 3-month survival and functional outcome, patterns of health care resource varied substantially between the US and Canada. US patients had more intensive early care; Canadian patients had longer hospitalizations and rehabilitation care. Further research is required to determine the most cost-effective treatment and rehabilitation plan for people who have a stroke.

Acute Disease↗

The phobic stimuli response scales: a new self-report measure of fear.

Data from two large undergraduate samples were used to develop the phobic stimuli response scales (PSRS). Factor analyses of data from the first sample (N = 380) led to the creation of several scales, two of which (Social and Blood-Injection Fears) demonstrated good reliability and convergent validity. Analyses of data from a second sample (N = 330) were used to modify the three remaining scales (Animal, Bodily Harm, and Physical Confinement Fears), which also showed sound psychometric properties. As predicted, the PSRS were differentially correlated with neuroticism and extraversion, which may represent predisposing factors for these phobic responses. These new scales improve our understanding of the individual differences that are associated with various fears.

Adolescent↗

Symptom subtypes of obsessive-compulsive disorder and their relation to dissociation.

We examined relations between obsessive-compulsive disorder (OCD) symptoms and dissociation in three studies. Studies 1 and 2 established a strong level of convergence between our two OCD symptom measures. Specific types of symptoms showed a clear convergent/discriminant pattern, indicating that they can be meaningfully distinguished from one another. In both studies, dissociation correlated more strongly with checking and obsessive intrusions than with cleaning, ordering, and hoarding. Moreover, these associations remained substantial even after controlling for neuroticism (Study 1) and other types of anxiety (Study 2). In Study 3, we replicated our key findings in a psychiatric outpatient sample, indicating that they are generalizable to clinical participants. Taken together, our results (a) establish a strong link between dissociation and OCD, and (b) illustrate the importance of analyzing different types of OCD symptoms separately.

Adult↗

The role of person versus situation in life satisfaction: a critical examination.

Two main theoretical approaches have been put forward to explain individual differences in life satisfaction: top-down (i.e., personological) and bottom-up (i.e., situational). The authors examine the relative merit of these 2 approaches and the psychological processes underlying top-down models. Consistent with a top-down approach, meta-analytic findings indicate that Neuroticism, Extraversion, Agreeableness, and Conscientiousness are related to both various domain satisfactions and life satisfaction; however, consistent with a bottom-up approach, domain satisfactions are strongly linked to life satisfaction but only weakly linked to each other. Path analyses based on meta-analytic estimates did not support a simple "direct-effects" top-down model but supported both (a) a temperament-based top-down model and (b) an integrative model that incorporates the direct influence of domain satisfactions on life satisfaction.

Humans↗

Cardiovascular effects of the nitric oxide synthase inhibitor NG-methyl-L-arginine hydrochloride (546C88) in patients with septic shock: results of a randomized, double-blind, placebo-controlled multicenter study (study no. 144-002).

OBJECTIVE: To assess the hemodynamic effects of the nitric oxide synthase inhibitor 546C88 in patients with septic shock, although this was not a stated aim of the protocol. The predefined primary efficacy objective of the protocol was resolution of shock determined at the end of a 72-hr treatment period. DESIGN: Multicentered, randomized, placebo-controlled, safety and efficacy study. SETTING: Forty-eight intensive care units in Europe, North America, and Australia. PATIENTS: A total of 312 patients with septic shock diagnosed within 24 hr before randomization. INTERVENTIONS: Patients were randomly allocated to receive either 546C88 or placebo (5% dextrose) by intravenous infusion for up to 72 hrs. Conventional vasoactive therapy was restricted to norepinephrine, dopamine, and dobutamine. Study drug was initiated at 0.1 mL/kg/hr (5 mg/kg/hr 546C88) and titrated according to response up to a maximum rate of 0.4 mL/kg/hr with the objective to maintain mean arterial pressure at 70 mm Hg while attempting to withdraw any concurrent vasopressor(s). MEASUREMENTS AND MAIN RESULTS: Requirement for vasopressors, systemic and pulmonary hemodynamics, indices of oxygen transport, and plasma concentrations of arginine and nitrate were assessed over time. The median mean arterial pressure for both groups was maintained > or =70 mm Hg. There was an early increase in systemic and pulmonary vascular tone and oxygen extraction, whereas both cardiac index and oxygen delivery decreased for patients in the 546C88 cohort. Although these parameters subsequently returned toward baseline values, the observed differences between the treatment groups, except for pulmonary vascular resistance and oxygen extraction, persisted throughout the treatment period, despite a reduced requirement for vasopressors in the 546C88 cohort. These changes were associated with a reduction in plasma nitrate concentrations, which were elevated in both groups before the start of therapy. CONCLUSIONS: The nitric oxide synthase inhibitor 546C88 can reduce the elevated plasma nitrate concentrations observed in patients with septic shock. In this study, treatment with 546C88 for up to 72 hrs was associated with an increase in vascular tone and a reduction in both cardiac index and oxygen delivery. The successful maintenance of a target mean arterial blood pressure > or =70 mm Hg was achieved with a reduction in the requirement for, or withdrawal of, conventional inotropic vasoconstrictor agents (i.e., dopamine and norepinephrine). There were no substantive untoward consequences accompanying these hemodynamic effects. An international, randomized, double-blind, placebo-controlled phase III study has since been conducted in patients with septic shock. Recruitment into the study was discontinued due to the emergence of increased mortality in the 546C88-treated group.

Adult↗

Administration of the nitric oxide synthase inhibitor NG-methyl-L-arginine hydrochloride (546C88) by intravenous infusion for up to 72 hours can promote the resolution of shock in patients with severe sepsis: results of a randomized, double-blind, placebo-controlled multicenter study (study no. 144-002).

OBJECTIVE: To assess the safety and efficacy of the nitric oxide synthase inhibitor 546C88 in patients with septic shock. The predefined primary efficacy objective was resolution of shock, defined as a mean arterial pressure > or =70 mm Hg in the absence of both conventional vasopressors and study drug, determined at the end of the 72-hr treatment period. DESIGN: Multicentered, randomized, placebo-controlled, safety and efficacy study. SETTING: Forty-eight intensive care units in Europe, North America, and Australia. PATIENTS: A total of 312 patients with septic shock diagnosed within 24 hr before randomization. INTERVENTIONS: Patients were randomly allocated to receive either 546C88 or placebo (5% dextrose) by intravenous infusion for up to 72 hrs. Conventional vasoactive therapy was restricted to norepinephrine, dopamine, and dobutamine. Study drug was initiated at 0.1 mL/kg/hr (5 mg/kg/hr 546C88) and titrated according to response up to a maximum rate of 0.4 mL/kg/hr with the objective to maintain mean arterial pressure at 70 mm Hg while attempting to withdraw any concurrent vasopressor(s). MEASUREMENTS AND MAIN RESULTS: Requirement for vasopressors, systemic hemodynamics, indices of organ function and safety (including survival up to day 28) were assessed. The median mean arterial pressure for both groups was maintained >70 mm Hg. Administration of 546C88 was associated with a decrease in cardiac index while stroke index was maintained. Resolution of shock at 72 hr was achieved by 40% and 24% of the patients in the 546C88 and placebo cohorts, respectively (p =.004). There was no evidence that treatment with 546C88 had any major adverse effect on pulmonary, hepatic, or renal function. Day 28 survival was similar for both groups. CONCLUSIONS: In this study, treatment with the nitric oxide synthase inhibitor 546C88 promoted the resolution of shock in patients with severe sepsis. This was associated with an acceptable overall safety profile.

Adult↗

Match makers and deal breakers: analyses of assortative mating in newlywed couples.

We conducted a comprehensive analysis of assortative mating (i.e., the similarity between wives and husbands on a given characteristic) in a newlywed sample. These newlyweds showed (a) strong similarity in age, religiousness, and political orientation; (b) moderate similarity in education and verbal intelligence; (c) modest similarity in values; and (d) little similarity in matrix reasoning, self- and spouse-rated personality, emotional experience and expression, and attachment. Further analyses established that similarity was not simply due to background variables such as age and education and reflected initial assortment (i.e., similarity at the time of marriage) rather than convergence (i.e., increasing similarity with time). Finally, marital satisfaction primarily was a function of the rater's own traits and showed little relation to spousal similarity.

Adult↗

A comparative developmental study of impulsivity in rats and humans: the role of reward sensitivity.

The present study was conducted to test the hypothesis that differences in reward sensitivity between adolescents and adults account for differences in impulsivity. In a comparative study, we examined preferences for various concentrations of sucrose solutions as an operational measure of reward sensitivity in adolescent and adult rats and humans. Humans also completed self-report measures of impulsivity and reward sensitivity. There was some indication that adolescents preferred sweeter solutions compared to adults. Also, adolescents scored substantially higher on impulsivity. However, adolescents and adults did not differ in self-ratings of reward sensitivity and personality scores were not consistently related to sucrose preferences. The data highlight some of the benefits and issues that arise with developing comparative measures in humans and animals. Future comparative research using alternative behavioral paradigms is necessary to determine if and how changes in reward sensitivity influence developmental shifts in impulsivity.

Adolescent↗

Towards more chemically robust polymer-supported chiral catalysts: alpha,alpha-diphenyl-L-prolinol based catalysts for the reduction of prochiral ketones with borane.

alpha,alpha-Diphenyl-L-prolinol derivatives with para-bromo substituents in either one or both of the phenyl rings are easily bound to crosslinked polystyrene beads containing phenylboronic acid residues by Suzuki couplings. By using extended reaction periods boronic acid residues that do not take part in the couplings are simply lost by hydrolysis. The polymer-supported (PS) alpha,alpha-diphenyl-L-prolinols were used to catalyse reductions of several prochiral ketones with borane in tetrahydrofuran at 22 degrees C. The expected secondary alcohols were obtained in high chemical yields and ees were generally in the range 79-97%. One PS catalyst was recycled 14 times without loss of stereochemical performance.

Boranes↗

Direct detection of deletion mutations in the yeast DEL assay using quantitative PCR (TaqMan).

Established mutagenesis assays measure mutant frequencies at selectable loci. These assays work by encouraging the growth of mutants to form visible colonies while suppressing the growth of non-mutants. An alternative strategy is to detect DNA alterations directly. We present an example of this latter strategy using TaqMan to quantify deletion mutants in mixed cultures of Saccharomyces cerevisiae strain RS112. The RS112 strain contains two heteroallelic his3 sequences that share approximately 400bp homology and are separated by approximately 7 kb of plasmid DNA. Spontaneous and chemical-induced strand breaks that occur in this region are repaired by intrachromosomal recombination, resulting in the loss of the plasmid DNA and creation of a His prototroph. Ordinarily, these prototrophs are detected by growth on His- medium over 2-3 days. In this case, we used TaqMan to selectively detect the DNA of deletion mutants in the presence of a large excess of DNA from non-mutants. This was accomplished using primers whose annealing sites were outside the region of DNA lost due to recombination. Thus, the primers were too far apart to produce PCR products using DNA from non-mutants, but produced a robust TaqMan signal using DNA from deletion mutants. Spontaneous and chemical-induced recombination frequencies (RF) were measured in a series of time-course and dose-response experiments with direct-acting mutagens. Interestingly, chemical-induced increases in RF were observed within a few hours of initiation of exposure, demonstrating that deletion mutations in RS112 can be fixed soon after DNA damage occurs. The ability to measure RF at any time during treatment will be useful for additional mechanistic studies. Chemical-induced increases in RF were also observed in the absence of selective growth conditions. As such, detection of deletion mutations with TaqMan may be applicable to measurements of RFs at non-selectable loci in yeast and other species. Finally, chemical-induced RFs after 17 h exposure were similar to those observed after 3 days growth on selective medium. The TaqMan assay may therefore be used to screen compounds more quickly for their ability to cause deletion mutations than is currently done by plating on selective medium.

Base Sequence↗

Measuring fatigue severity in primary care patients.

OBJECTIVE: We developed a new instrument to measure fatigue that synthesized information from existing instruments. METHODS: 35 candidate items and 4 formats for a new fatigue scale were obtained from 15 previously developed instruments. A new scale was developed using factor analysis on a data set of 409 primary care patients and validated on a sample of 816 additional subjects. RESULTS: Different formats for obtaining information about a given fatigue item gave similar results. The new 11 item scale contained four subscales: cognitive, fatigue, energy and productivity. Correlations between the four subscales ranged from.49 to.66. Patients with a higher fatigue score were much more likely to have lower health status, greater depression and more somatic symptoms. CONCLUSION: This new instrument may be useful in primary care and epidemiological studies to screen and monitor patients for fatigue severity and type.

Adolescent↗