Natural versus 'artificial' sweeteners: regulatory aspects.
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Biomedical subjects
Publications and source records attributed to R Walker.
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One of the key problems in theoretical biology is the identification of the mechanisms underlying the evolution of complexity. This paper suggests that some difficulties in current models could be avoided by taking account of"niche selection"as proposed by Waddington [21] and subsequent authors [2]. Computer simulations, in which an evolving population of artificial organisms"selects"the niche(s) that maximize their fitness, are compared with a Control Model in which"Niche Selection"is absent. In the simulations the Niche Selection Model consistently produced a greater number of"fit"organisms than the Control Model; although the Niche Selection Model tended, in general, to produce organisms occupying simple niches, it was nonetheless more effective than the Control Model in producing well-adapted organisms inhabiting complex niches. It is shown that the production of these organisms is critically dependent on the rate of environmental change: Slow change leads to fit but undifferentiated populations, dominated by organisms occupying simple niches; differentiated populations, including well-adapted organisms living in complex niches, require rates of environmental change lying just beyond a mathematically well-defined critical value. In simulation"Niche Selection,"unlike conventional"Natural Selection,"provides a permanent selective bias in favor of simplicity. This tendency is counterbalanced by statistical forces favoring shifts from rare"simple niches"to commoner niches of greater complexity. Fit organisms inhabiting complex niches only emerge in conditions where the rate of environmental change is high enough to avoid the concentration of the population in very simple niches, but slow enough to permit step-by-step adaptation to niches of gradually increasing complexity. This result appears to be robust to changes in simulation parameters and assumptions, and leads to interesting conjectures about the real world behavior of biological organisms (and other complex adaptive systems). It is suggested that some of these conjectures might be relatively easy to test.
The effective management of risk in clinical practice includes steps to limit harm to clients resulting from ethical violations or professional misconduct. Boundary problems constitute some of the most damaging ethical violations. The authors propose an active use of clinical supervision to anticipate and head off possible ethical violations by intervening when signs of boundary problems appear. The authors encourage a facilitative, Socratic method, rather than directive approaches, to help supervisees maximize their learning about ethical complexities. Building on the idea of a slippery slope, in which seemingly insignificant acts can lead to unethical patterns of behavior, the authors discuss ten cues to potential boundary problems, including strong feelings about a client; extended sessions with clients; gift giving between clinician and client; loans, barter, and sale of goods; clinician self-disclosures; and touching and sex. The authors outline supervisory interventions to be made when the cues are detected.
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The Labour Government came to power in Britain in 1997 on a platform to reform welfare that owed a great deal to the social policy views of the Clinton administration. In the subsequent months major reforms were implemented and more announced. Yet by July 1998 the key politicians entrusted with reform either had been sacked or had resigned. This article compares and contrasts welfare policy in Britain and the United States and discusses Labour's welfare reforms, then considers whether the current impasse is due to the failure of U.S. policies to travel well.
OBJECTIVE: To investigate the allele frequencies of 6 polymorphic sites spanning the region of the genome close to the tumor necrosis factor (TNF) gene in a group of HLA-B27 positive patients with ankylosing spondylitis (AS) in the West of Scotland. METHODS: One hundred sixty-seven patients with AS, 93 healthy controls, and 88 HLA-B27 positive healthy controls, all from the West of Scotland, were typed by polymerase chain reaction (PCR) for 3 restriction fragment length polymorphisms (RFLP) and 3 microsatellite polymorphic sites spanning the TNF gene cluster. The distribution of these alleles was correlated with the presence of extraspinal manifestations such as peripheral joint disease and uveitis. RESULTS: The frequency of the Nco-1.2 allele was significantly reduced in patients compared to the genetically unselected control population (p < 0.05), but was no different from the HLA-B27 positive controls. However, the -308.1 allele was significantly increased in the patients compared to the HLA-B27 positive controls (p < 0.03). CONCLUSION: This study confirms the importance of correct matching in genetic analysis in disease association studies, and provides further evidence supporting the involvement of genes other than the MHC class I locus in the pathogenesis and features of AS.
Whole-body MR imaging is in evolution, and although accepting and recognizing limitations, it is likely that both technique and incurred acquisition times will shorten over the next decade. Although the development of dedicated whole-body MR scanners appears to offer the greatest promise for the future, the development of moving table tops, optimized pulse sequences, and advances in gradient technology now facilitate practical whole-body MR imaging using existing clinical systems.
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A Thoroughbred-Quarter Horse crossbred foal developed hemorrhagic enteritis and died < 48 hours after birth. Gross and histologic findings were suggestive of Clostridium perfringens type C infection, and large numbers of C perfringens were isolated from intestinal contents. However, genotyping of isolates indicated that they were enterotoxigenic C perfringens type A, and isolates were found to produce C perfringens enterotoxin in vitro. This case suggests that enterotoxigenic C perfringens type A may cause enteric disease in horses.
The Escherichia coli DNA repair proteins UvrA, UvrB and UvrC work together to recognize and incise DNA damage during the process of nucleotide excision repair (NER). To gain an understanding of the damage recognition properties of UvrA, we have used fluorescence spectroscopy to study the thermodynamics of its interaction with a defined DNA substrate containing a benzo[a]pyrene diol epoxide (BPDE) adduct. Oligonucleotides containing a single site-specifically modified N2-guanine (+)-trans-, (-)-trans-, (+)-cis-, or (-)-cis-BPDE adducts were ligated into 50-base-pair DNA fragments. All four stereoisomers of DNA-BPDE adducts show an excitation maximum at 350 nm and an emission maximum around 380 to 385 nm. Binding of UvrA to the BPDE-DNA adducts results in a five to sevenfold fluorescence enhancement. Titration of the BPDE-adducted DNA with UvrA was used to generate binding isotherms. The equilibrium dissociation constants for UvrA binding to (+)-trans-, (-)-trans-, (+)-cis-, and (-)-cis- BPDE adduct were: 7.4+/-1.9, 15. 8+/-5.4, 11.3+/-2.7 and 22.4+/-2.0 nM, respectively. There was a large negative change in heat capacity DeltaCpo,obs, (-3.3 kcal mol-1 K-1) accompanied by a relatively unchanged DeltaGoobs with temperature. Furthermore, varying the concentration of KCl showed that the number of ions released upon formation of UvrA-DNA complex is about 3.4, a relatively small value compared to the contact size of UvrA with the substrate. These data suggest that hydrophobic interactions are an important driving force for UvrA binding to BPDE-damaged DNA.
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A patient with a lesion confined largely to the right inferior frontal gyrus was found to be impaired on tests of spatial working memory and executive functioning. By contrast, his pattern recognition was good. The patient's selective impairments are consistent with the view that prefrontal cortex contributes to processes involved in spatial working memory. The patient was also tested on a range of oculomotor paradigms, some of which required the temporary suppression of a saccadic response. He was unable to suppress making contra- or ipsilesional reflexive glances to peripheral stimuli on the "anti-saccade" paradigm, but his performance improved on delayed saccade, memory-guided saccade and fixation tasks. Although reflexive glances were observed under these conditions they occurred more frequently in response to contralesional stimuli than ipsilesional ones. Furthermore, the patient had no difficulty in performing anti-point movements with his ipsilesional hand. Thus, his inability to suppress reflexive glances on the anti-saccade task is not due to a generalised problem of "distractibility". The patient's deficits are discussed in terms of models of anti-saccade generation and are related to recent findings regarding the role of prefrontal cortex in working memory and visual attention.
The objectives of the study were to evaluate the effect of baking and freeze-drying on the direct and indirect mutagenicity in the Ames test of ethanolic extracts from the edible mushroom Agaricus bisporus. Direct mutagenicity was not influenced by baking for 10 min at 225 degrees C, but more prolonged baking, for example 4 hr at 100 degrees C reduced mutagenicity. Hepatic cytosol from Aroclor 1254-induced rats and mushroom tyrosinase potentiated the mutagenic response elicited by the mushroom extracts. Baking did not influence either of these processes. Finally, freeze-drying influenced neither the direct nor the indirect mutagenicity of the mushroom extracts. It is concluded that mutagenic and premutagenic compounds present in mushroom are generally not heat labile.
Aqueous extracts of green tea, at concentrations of 2.5. 5.0 and 7.5%, were administered to rats as the sole drinking fluid for 4 weeks. Hepatic glutathione S-transferase (GST) activity, determined using 1-chloro-2,4-dinitrobenzene (CDNB) and 3,4-dichloronitrobenzene (DCNB) as substrates, and UDP-glucuronosyl transferase activity, determined using 2-aminophenol as substrate, were induced but the effect was not always dose dependent. At the two highest doses, hepatic catalase activity was inhibited. In a second study, animals were exposed for 4 weeks to aqueous extracts (2.5%, v/v) of green tea, black tea (which has a much lower content of flavanols compared with green tea) and decaffeinated black tea. Treatment with the black tea enhanced GST activity, whether monitored using CDNB or DCNB, and the glucuronidation of 2-aminophenol. Treatment with decaffeinated black tea failed to modulate any of these activities, whereas treatment with green tea only enhanced the glucuronidation of 2-aminophenol. Finally, at this concentration of tea extract administration, black and decaffeinated black tea, but not green tea, suppressed catalase activity. It is concluded that neither flavanols nor caffeine are responsible for the induction of hepatic Phase II activities and inhibition of catalase activity in the rat.
The purpose of this study was to describe the life of survivors after successful resuscitation and to see if there was an association with the type of emergency cardiac care. The 'Utstein-style' data of patients surviving non-traumatic cardiac arrest 24 (14-32) months were prospectively collected. The everyday activities and psychological concerns of patients with a cerebral performance category (CPC) of 1 and 2 using a questionnaire were analyzed. The chi2-square test was used for statistical analysis. The questionnaires of 92 patients (median age 59, IQR 51-68; females 36) were evaluated. Patients enjoy life (84%; n=73), have depression (36%; n=31), consider their survival a 'second chance' (84%; n=73) and fear that they may suffer cardiac arrest again (56%; n = 45). The average quality of life is 7 on a scale from 0 (worst) to 10 (perfect). The majority of cardiac arrest survivors have a satisfactory life. No significant correlation between the type of emergency cardiac care and post cardiac arrest life was found. The fact that there was no association with the type of emergency cardiac care may be due to the narrow selection of patients (CPC 1 and 2), the small number of patients or factors contributing to post cardiac arrest life other than emergency treatment.
A range of isolation procedures including washing, sonication and incubation in nutrient broth were used separately and in combination to obtain potential bacterial antagonists to Botrytis cinerea and Pythium mamillatum from the testae and cotyledons of peas and dwarf French beans. Heat treatment was also used to bias this selection towards spore-forming bacteria. Ninety-two bacterial isolates were obtained, 72 of which were provisionally characterized as species of Bacillus. Four of these Bacillus isolates (B3, C1, D4 and J7) displayed distinct antagonism in vitro against Botrytis cinerea and P. mamillatum when screened using dual culture analysis. Further characterization of these antagonists using API 50CHB biochemical profiling identified isolate D4 as Bacillus polymyxa and isolates B3, C1 and J7 as strains of B. subtilis. In vitro screening techniques, using cell-free and heat-killed extracts of liquid cultures against Botrytis cinerea, demonstrated the production of antifungal compounds by these four Bacillus antagonists. With each isolate the antifungal activity was found not to be either exclusively spore-bound nor released entirely into the medium but present in both fractions. The antifungal compounds produced by these isolates were shown to be heat-stable. Their identification, production and release require further study for exploitation as biocontrol systems.
This article reports on a national study of collaborative relationships between general practitioners and other health care providers in 20 Division of General Practice projects. It argues that health care organisations will need to collaborate with others in the future and that much can be learnt from the literature on collaborative networks in business and community organisations. Successful collaborations between general practitioners and others were found to be consistent with a model of collaboration in 'under-organised domains', where pre-existing links between organisations are weak. Lessons are identified from the study to assist future collaborative ventures involving general practitioners.