Best research: research originating in primary care needs support.
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England↗
Biomedical subjects
Martin Edwards
Publications and source records attributed to Martin Edwards.
The discovery of CCR5 receptor antagonists for the treatment of HIV infection: hit-to-lead studies.
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Anti-HIV Agents↗
From plankton to top predators: bottom-up control of a marine food web across four trophic levels.
1. Abundant mid-trophic pelagic fish often play a central role in marine ecosystems, both as links between zooplankton and top predators and as important fishery targets. In the North Sea, the lesser sandeel occupies this position, being the main prey of many bird, mammal and fish predators and the target of a major industrial fishery. However, since 2003, sandeel landings have decreased by > 50%, and many sandeel-dependent seabirds experienced breeding failures in 2004. 2. Despite the major economic implications, current understanding of the regulation of key constituents of this ecosystem is poor. Sandeel abundance may be regulated 'bottom-up' by food abundance, often thought to be under climatic control, or 'top-down' by natural or fishery predation. We tested predictions from these two hypotheses by combining unique long-term data sets (1973-2003) on seabird breeding productivity from the Isle of May, SE Scotland, and plankton and fish larvae from the Continuous Plankton Recorder survey. We also tested whether seabird breeding productivity was more tightly linked to sandeel biomass or quality (size) of individual fish. 3. The biomass of larval sandeels increased two- to threefold over the study period and was positively associated with proxies of the abundance of their plankton prey. Breeding productivity of four seabirds bringing multiple prey items to their offspring was positively related to sandeel larval biomass with a 1-year lag, indicating dependence on 1-year-old fish, but in one species bringing individual fish it was strongly associated with the size of adult sandeels. 4. These links are consistent with bottom-up ecosystem regulation and, with evidence from previous studies, indicate how climate-driven changes in plankton communities can affect top predators and potentially human fisheries through the dynamics of key mid-trophic fish. However, the failing recruitment to adult sandeel stocks and the exceptionally low seabird breeding productivity in 2004 were not associated with low sandeel larval biomass in 2003, so other mechanisms (e.g. predation, lack of suitable food after metamorphosis) must have been important in this case. Understanding ecosystem regulation is extremely important for predicting the fate of keystone species, such as sandeels, and their predators.
Animals↗
Impact of climate change on marine pelagic phenology and trophic mismatch.
Phenology, the study of annually recurring life cycle events such as the timing of migrations and flowering, can provide particularly sensitive indicators of climate change. Changes in phenology may be important to ecosystem function because the level of response to climate change may vary across functional groups and multiple trophic levels. The decoupling of phenological relationships will have important ramifications for trophic interactions, altering food-web structures and leading to eventual ecosystem-level changes. Temperate marine environments may be particularly vulnerable to these changes because the recruitment success of higher trophic levels is highly dependent on synchronization with pulsed planktonic production. Using long-term data of 66 plankton taxa during the period from 1958 to 2002, we investigated whether climate warming signals are emergent across all trophic levels and functional groups within an ecological community. Here we show that not only is the marine pelagic community responding to climate changes, but also that the level of response differs throughout the community and the seasonal cycle, leading to a mismatch between trophic levels and functional groups.
Animals↗
Effect of the new H1-antagonist ReN1869 on capsaicin-induced hyperalgesia in human skin/Human phase-I trial using somatosensory evoked potentials induced by a CO2 laser.
Extensive pre-clinical investigations have shown that the tricyclic compound ReN1869 ((R)-1-(3-(10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-ylidene)-1-propyl)-3-piperidine carboxylic acid, CAS 170149-99-2) is a potent H1-antagonist with pronounced antinociceptive properties. In this human phase-I trial the effect of different acute and multiple doses of ReN1869 on capsaicin induced neurogenic inflammation and hyperalgesia was investigated. Twenty-one healthy male subjects were enrolled in this randomised, double-blind, three-period, crossover trial design--consisting of acute and one week b.i.d. oral administration of 25 and 50 mg doses of ReN1869 and matching placebo--separated by 3 week washout periods. Capsaicin solution (1%) (INCI: Capsicum frutescens--containing capsaicinoides from Capsicum annuum annuum, CAS 84603-55-4) was applied in an occlusive mode for 30 min on the skin of the back in all three acute and subchronic medication periods to induce neurogenic inflammation. When the nociceptive laser pulses were applied to the capsaicin pre-treated skin, ReN1869 exerted a highly significant reduction of the pain response--as predominantly detected by suppression of the (central) P2-component in the laser-induced somatosensory evoked potentials (LSEPs) from Vertex-EEG. The primary efficacy endpoint, the N1/P2 peak to peak amplitude, was significantly reduced with the administration of ReN1869--primarily by a suppression of the P2-component of the LSEP. This suppression was dose-dependent and was more pronounced after a one week treatment (subchronic mode) with ReN1869 than after the first dose (acute mode). In contrast to the (central) P2-component there was no significant effect on the (peripheral) N1-component of the LSEPs taken from capsaicin-treated skin. As ReN1869 had no significant effect when the laser pulses were applied to normal skin, and the compound's effect was mainly restricted to the (central) P2-component, when LSEPs were taken from capsaicin treated skin, it can be concluded that ReN1869 exerts its positive effect to reduce capsaicin-induced hyperalgesia by a primarily central mechanism.
Adult↗
Good, bad or offal? The evaluation of raw pancreas therapy and the rhetoric of control in the therapeutic trial, 1925.
In 1925 a debate erupted in the correspondence columns of the British Medical Journal concerning the effectiveness of eating raw pancreas as a treatment for diabetes. Enthusiasts were predominantly general practitioners (GPs), who claimed success for the therapy on the basis of their clinical impressions. Their detractors were laboratory-oriented 'biochemist-physicians,' who considered that their own experiments demonstrated that raw pancreas therapy was ineffective. The biochemist-physicians consistently dismissed the GPs' observations as inadequately 'controlled'. They did not define the meaning of 'control' in this context, although it clearly did not have the term's present-day meaning of a trial employing an untreated comparison group of patients. Rather, the physician-biochemists' 'properly controlled' experiments involved careful regulation of their patients' diet and other environmental factors, and evaluation of the therapy's success through biochemical, rather than just clinical, criteria. However, my analysis suggests that these factors alone are inadequate to account for the biochemist-physicians' dismissal of the GPs' work as 'uncontrolled'. I suggest that the biochemist-physicians were deliberately exploiting the powerful rhetorical connotations of the term 'control'. Ultimately, they implied that only a trial which they themselves had conducted could be deemed 'adequately controlled'.
History, 20th Century↗
Patients' responses to delayed antibiotic prescription for acute upper respiratory tract infections.
BACKGROUND: Upper respiratory tract infections (URTIs) account for approximately 50% of antibiotic prescriptions in the United Kingdom. General practitioners (GPs) frequently issue such prescriptions simply because they believe that the patient expects it. Deferred prescribing (issuing a prescription, but with instructions to wait for no spontaneous improvement before deciding whether to use it) might address patients' expectations, while minimising actual antibiotic consumption. Although the technique is quite widely practiced, patients' attitudes and responses to it are unclear. AIMS: To establish the proportion of recipients who claim to consume their delayed antibiotic prescriptions. To elicit factors associated with patients' decisions to consume their antibiotics, and patients' confidence in taking this decision. DESIGN OF STUDY: Postal questionnaire survey. SETTING: Patients from 13 group practices in the south of England. METHODS: Patients who had received a delayed antibiotic prescription for URTI from their GP were posted a questionnaire 2 days after their consultation. RESULTS: Three hundred and seventy-four subjects were recruited of whom 256 (68.4%) returned their questionnaires. Just over half (53.1%) of the responders claimed to have consumed their antibiotics. The majority of patients (87.1%) were confident about taking the decision as to whether to use their antibiotics, and 92.5% would choose to receive a delayed prescription again. Subjects were more likely to take their antibiotics if their presenting symptoms included a fever or sinus pain. CONCLUSION: Most patients are confident in making the decision about whether or not to take their antibiotics when receiving a delayed prescription for URTIs. Antibiotic consumption is associated with presenting symptoms, and this has implications for future practice.
Adolescent↗
Reorganization of North Atlantic marine copepod biodiversity and climate.
We provide evidence of large-scale changes in the biogeography of calanoid copepod crustaceans in the eastern North Atlantic Ocean and European shelf seas. We demonstrate that strong biogeographical shifts in all copepod assemblages have occurred with a northward extension of more than 10 degrees latitude of warm-water species associated with a decrease in the number of colder-water species. These biogeographical shifts are in agreement with recent changes in the spatial distribution and phenology detected for many taxonomic groups in terrestrial European ecosystems and are related to both the increasing trend in Northern Hemisphere temperature and the North Atlantic Oscillation.
Animals↗
Historical keywords: trial.
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Clinical Trials as Topic↗
The asthma trigger inventory: validation of a questionnaire for perceived triggers of asthma.
BACKGROUND: Asthma patients' perceptions of triggers have been explored in a largely unstructured fashion in the past. We therefore developed and validated a questionnaire of commonly perceived asthma triggers. METHODS: Two hundred forty-seven primary care patients with asthma filled in an asthma trigger survey together with questionnaires on demographics, asthma-relevant information, perceived control of asthma, and general health status. Factor structure of the item pool and psychometric properties of trigger subscales were evaluated. We also investigated the relationship between allergen or psychological trigger reports and allergy skin test response or respiratory impedance during emotional film viewing, respectively. RESULTS: Principal component analysis yielded six factors that were thematically associated with psychology, animal allergens, pollen allergens, physical activity, infection, and air pollution/irritants. Subscales showed good internal consistencies and low to moderately positive intercorrelations. Psychological triggers were consistently associated with less favorable health status, a reduced perception of asthma control, and greater medical treatment utilization. Animal allergen scores correlated positively with skin test responses to animal allergens. Respiratory impedance increases during emotional film clips were positively correlated with the psychological trigger subscale. CONCLUSION: The questionnaire is a reliable measure of commonly perceived asthma triggers. Aspects of patients' trigger reports reflect actual reactivity to specific trigger factors.
Adult↗