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Biomedical subjects

Paul Davis

Publications and source records attributed to Paul Davis.

28 records · Page 2Linked to original sources

Genomic and genetic analysis of Bordetella bacteriophages encoding reverse transcriptase-mediated tropism-switching cassettes.

Liu et al. recently described a group of related temperate bacteriophages that infect Bordetella subspecies and undergo a unique template-dependent, reverse transcriptase-mediated tropism switching phenomenon (Liu et al., Science 295: 2091-2094, 2002). Tropism switching results from the introduction of single nucleotide substitutions at defined locations in the VR1 (variable region 1) segment of the mtd (major tropism determinant) gene, which determines specificity for receptors on host bacteria. In this report, we describe the complete nucleotide sequences of the 42.5- to 42.7-kb double-stranded DNA genomes of three related phage isolates and characterize two additional regions of variability. Forty-nine coding sequences were identified. Of these coding sequences, bbp36 contained VR2 (variable region 2), which is highly dynamic and consists of a variable number of identical 19-bp repeats separated by one of three 5-bp spacers, and bpm encodes a DNA adenine methylase with unusual site specificity and a homopolymer tract that functions as a hotspot for frameshift mutations. Morphological and sequence analysis suggests that these Bordetella phage are genetic hybrids of P22 and T7 family genomes, lending further support to the idea that regions encoding protein domains, single genes, or blocks of genes are readily exchanged between bacterial and phage genomes. Bordetella bacteriophages are capable of transducing genetic markers in vitro, and by using animal models, we demonstrated that lysogenic conversion can take place in the mouse respiratory tract during infection.

Animals↗

Mental health, social inclusion and the green agenda: an evaluation of a land based rehabilitation project designed to promote occupational access and inclusion of service users in North Somerset, UK.

The current debate about social inclusion in the field of mental health reveals a tension between the political and economic objectives of social policy. The former utilises the language of citizen empowerment and rights, whilst the latter is concerned with reducing welfare dependency through labour market activation. A central question here is whether a suitable programme of therapeutic work, training and support will produce better outcomes than those predicted by either a clinical diagnostic assessment or indeed open employment in the labour market. This article evaluates a research project with mental health users designed to develop pathways towards inclusion. The principal means for achieving this was a programme of 'green' land-based activities, training and social support. The researchers employed a mixed method approach, utilising a quasi-experimental design with a hypothetical control and standardised testing. This was followed by interviews with users, staff and focus group discussion. The evaluation produced some unexpected findings; for example, it was found that no strong correlation existed between diagnosis and performance. Many users performed better than had been predicted by their diagnostic assessment. However, the reasons for this remained unclear until the qualitative interviews enabled users to give accounts of the problems they faced, explain what inclusion meant for them, and outline how the project had brought gains in confidence, motivation and self belief. The data gathered during the research derived from different epistemological positions. This can be seen as representing two ways of 'slicing the reality cake' rather than producing one complete view of mental health users reality. One construction related to how 'the system' diagnosed, processed, and 'objectively' managed them. The other was about how users' responded to their situation, utilised the opportunities available, and made 'subjective' sense of their experience.

Agriculture↗

Cenozoic climate change as a possible cause for the rise of the Andes.

Causal links between the rise of a large mountain range and climate have often been considered to work in one direction, with significant uplift provoking climate change. Here we propose a mechanism by which Cenozoic climate change could have caused the rise of the Andes. Based on considerations of the force balance in the South American lithosphere, we suggest that the height of, and tectonics in, the Andes are strongly controlled both by shear stresses along the plate interface in the subduction zone and by buoyancy stress contrasts between the trench and highlands, and shear stresses in the subduction zone depend on the amount of subducted sediments. We propose that the dynamics of subduction and mountain-building in this region are controlled by the processes of erosion and sediment deposition, and ultimately climate. In central South America, climate-controlled sediment starvation would then cause high shear stress, focusing the plate boundary stresses that support the high Andes.

Journal Article↗

Comparative analysis of the genome sequences of Bordetella pertussis, Bordetella parapertussis and Bordetella bronchiseptica.

Bordetella pertussis, Bordetella parapertussis and Bordetella bronchiseptica are closely related Gram-negative beta-proteobacteria that colonize the respiratory tracts of mammals. B. pertussis is a strict human pathogen of recent evolutionary origin and is the primary etiologic agent of whooping cough. B. parapertussis can also cause whooping cough, and B. bronchiseptica causes chronic respiratory infections in a wide range of animals. We sequenced the genomes of B. bronchiseptica RB50 (5,338,400 bp; 5,007 predicted genes), B. parapertussis 12822 (4,773,551 bp; 4,404 genes) and B. pertussis Tohama I (4,086,186 bp; 3,816 genes). Our analysis indicates that B. parapertussis and B. pertussis are independent derivatives of B. bronchiseptica-like ancestors. During the evolution of these two host-restricted species there was large-scale gene loss and inactivation; host adaptation seems to be a consequence of loss, not gain, of function, and differences in virulence may be related to loss of regulatory or control functions.

Base Sequence↗

Reactivity studies, structural characterization, and thermolysis of cubic titanosiloxanes: precursors to titanosilicate materials which catalyze olefin epoxidation.

The cubic titanosiloxane [RSiO(3)Ti(OPr(i))](4) (R = 2,6-Pr(2)(i)C(6)H(3)NSiMe(3)) (1) is found to be relatively inert in its attempted reactions with alcohols and other acidic hydrogen containing compounds. The reaction of 1 with silanol (Bu(t)O)(3)SiOH however proceeds over a period of approximately 3 months to result in the hydrolysis of (Bu(t)O)(3)SiOH and yield the transesterification product [RSiO(3)Ti(OBu(t))](4) (2) rather than the expected [RSiO(3)Ti(OSi(OBu(t))(3))](4). Products 1 and 2 have been characterized by elemental analysis, thermal analysis, and spectroscopic techniques (IR, EI-MS, and NMR). The solid-state structures of both 1 and 2 have been determined by single-crystal X-ray diffraction studies. Compounds 1 and 2 are isomorphous and crystallize in a cubic space group with a central cubic Ti(4)Si(4)O(12) core. Solid state thermolysis of 1 was carried at 450, 600, 800, 900, 1000, and 1200 degrees C in air, and the resulting titanosilicate materials 1a-f were characterized by spectroscopic (IR and DR UV), powder XRD, and electron microscopic methods. While, the presence of Ti-O-Si linkages appears to be dominant in the samples prepared at lower temperatures (450-800 degrees C), phase separation of anatase and rutile forms of TiO(2) occurs at temperatures above 900 degrees C as revealed by IR spectral and PXRD studies. The presence of octahedral titanium centers was observed by DR UV spectroscopy for the samples heated at higher temperatures. The use of new titanosilicate materials as catalysts for olefin epoxidation has been investigated. The titanosilicate materials produced at temperatures below 800 degrees C with a large number of Ti-O-Si linkages (or tetrahedral titanium centers) were found to be more active catalysts compared to the materials produced above 900 degrees C. The observed conversion in the epoxidation reactions was found to be somewhat low although the selectivity of the epoxide formation over the other possible oxidized products was found to be very good.

Journal Article↗

Incorporating dairy foods into low and high fat diets increases the postprandial cholecystokinin response in men and women.

The postprandial period is a dynamic state of hormone and lipoprotein metabolism that can be influenced by dietary composition. The objective of this study was to determine whether the source of dietary fat [dairy (D) vs. nondairy (ND)] would modify the lipemic, insulin and cholecystokinin (CCK) response to high or low fat meals. Men and women (n = 24) consumed 4 test meals with a similar polyunsaturated:saturated (P:S; 0.12:1) fat ratio. The diets were high (38% energy) or low (20% energy) in fat, with or without fat from dairy sources. CCK responses were greater after consumption of meals containing D than ND, and for high compared with low fat meals. Women had higher CCK responses than men and were more sensitive to the differences in dietary treatments. Consumption of low fat meals resulted in greater insulin responses than high fat meals. However, after consumption of the low fat meals, the insulin response of D was about half of the ND response; no differences in insulin response were detected after the high fat meals. Triacylglyceride response was influenced primarily by the fat content of the diet. Consumption of dairy products containing fat was associated with an enhanced CCK response, which may have implications for the regulation of food intake. Blunting glucose and insulin response in low fat meals containing fat from dairy products may be useful for glycemic control.

Adult↗

Cardiorespiratory fitness and C-reactive protein among a tri-ethnic sample of women.

BACKGROUND: Elevated C-reactive protein (CRP) is associated with increased coronary heart disease (CHD) risk. Cardiorespiratory fitness ("fitness") is related with lower CHD risk; however, its relationship with CRP is relatively unknown. METHODS AND RESULTS: Cross-sectional associations between fitness and plasma CRP were examined among 135 African American (AA), Native American (NA), and Caucasian (CA) women (55+/-11 year; 28+/-6 kg/m2). Fitness was assessed with a maximal treadmill exercise test. Plasma CRP concentrations were determined with the Dade Behring high-sensitivity immunoassay. Geometric mean CRP levels were 0.43, 0.25, and 0.23 mg/dL, and average maximal MET levels of fitness were 7.2, 9.1, and 10 METs for AA, NA, and CA, respectively. CRP decreased across tertiles of fitness (P=0.002), increased across tertiles of BMI (P=0.0007), and varied by race (P=0.002). After adjustment for covariates, lower CRP (P<0.05) was observed across tertiles of fitness among NA and CA, but not AA. Among all women, after adjusting for race and covariates, the odds of high-risk CRP (>0.19 mg/dL) were 0.67 (95% CI=0.19 to 2.4) among fit (>6.5 METs) versus unfit women. CONCLUSIONS: The health benefits from enhanced fitness may have an antiinflammatory mechanism.

Black People↗

A six-month randomized, controlled, double-blind, dose-response comparison of intravenous pamidronate (60 mg versus 10 mg) in the treatment of nonsteroidal antiinflammatory drug-refractory ankylosing spondylitis.

OBJECTIVE: To determine the safety and efficacy of intravenous (IV) pamidronate treatment in ankylosing spondylitis (AS) patients who have had a suboptimal response to nonsteroidal antiinflammatory drugs (NSAIDs). METHODS: Pamidronate at 60 mg was compared with pamidronate at 10 mg rather than placebo in view of the high incidence of transient arthralgias upon first IV exposure to the drug. The drug were given monthly for 6 months in a randomized double-blind, controlled trial. The inclusion criterion was active disease (Bath AS Disease Activity Index [BASDAI] of > or = 4 or morning stiffness of > or = 45 minutes) despite stable NSAID therapy. The primary outcome measure was the BASDAI, and secondary outcomes included the Bath AS Functional Index (BASFI), Bath AS Global Index (BASGI), Bath AS Metrology Index (BASMI), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) level, and percentage of patients achieving a reduction of > or = 25% in the BASDAI. Outcome assessments were done at -2, 0, 12, and 24 weeks, and analysis was by intent to treat. RESULTS: Eighty-four AS patients (67 men and 17 women; mean age 39.6 years and mean disease duration 15.1 years) were enrolled. Dosage groups were well matched at baseline for demographics, disease activity, and functional indices. At 6 months, the mean BASDAI had decreased by 2.22 (34.5%) in the 60-mg group and by 0.93 (15%) in the 10-mg group (P = 0.002). Significantly greater reductions in the 60-mg group were also noted for the BASFI (P < 0.001), BASGI (P = 0.01), and BASMI (P = 0.03). Significantly more patients achieved a reduction of > or = 25% in the BASDAI in the 60-mg group versus the 10-mg group (63.4% versus 30.2%; P = 0.004). Differences in ESR/CRP were not significant (NS). Withdrawals included 9 (20.9%) from the 10-mg group and 3 (7.3%) from the 60-mg group (P NS). Adverse events were confined to transient arthralgias/myalgias after the first IV infusion, occurring in 68.3% and 46.5% of patients in the 60-mg and 10-mg groups, respectively (P NS). CONCLUSION: Pamidronate has dose-dependent therapeutic properties in AS.

Adult↗

Restructuring rural continuing medical education through videoconferencing.

We piloted a videoconferencing continuing medical education programme for rural physicians in Alberta and compared its feasibility, acceptability and cost implications with currently existing telephone conferencing and regional conference programmes. Videoconferencing clearly had advantages over telephone conferencing but was not as well appreciated by consumers as the existing regional conference programme. Nonetheless, the videoconferencing programme, although somewhat more costly than telephone conferencing, was associated with considerable cost-savings compared with the regional conference programme. On balance, we concluded that further development of the videoconferencing programme is warranted and we will slowly replace existing telephone conferencing programmes. However, there remains a need for the current regional conference programme.

Alberta↗