225 research outputs found
What motivates senior clinicians to teach medical students?
BACKGROUND: This study was designed to assess the motivations of senior medical clinicians to teach medical students. This understanding could improve the recruitment and retention of important clinical teachers. METHODS: The study group was 101 senior medical clinicians registered on a teaching list for a medical school teaching hospital (The Canberra Hospital, ACT, Australia). Their motivations to teach medical students were assessed applying Q methodology. RESULTS: Of the 75 participants, 18 (24%) were female and 57 (76%) were male. The age distribution was as follows: 30–40 years = 16 participants (21.3%), 41–55 years = 46 participants (61.3%) and >55 years = 13 participants (17.3%). Most participants (n = 48, 64%) were staff specialists and 27 (36%) were visiting medical officers. Half of the participants were internists (n = 39, 52%), 12 (16%) were surgeons, and 24 (32%) were other sub-specialists. Of the 26 senior clinicians that did not participate, two were women; 15 were visiting medical officers and 11 were staff specialists; 16 were internists, 9 were surgeons and there was one other sub-specialist. The majority of these non-participating clinicians fell in the 41–55 year age group. The participating clinicians were moderately homogenous in their responses. Factor analysis produced 4 factors: one summarising positive motivations for teaching and three capturing impediments for teaching. The main factors influencing motivation to teach medical students were intrinsic issues such as altruism, intellectual satisfaction, personal skills and truth seeking. The reasons for not teaching included no strong involvement in course design, a heavy clinical load or feeling it was a waste of time. CONCLUSION: This study provides some insights into factors that may be utilised in the design of teaching programs that meet teacher motivations and ultimately enhance the effectiveness of the medical teaching workforce
Feasibility of pharmacy-initiated pharmacogenetic screening for CYP2D6 and CYP2C19
PURPOSE: Our purpose was to investigate the feasibility of pharmacy-initiated pharmacogenetic (PGt) screening in primary care with respect to patient willingness to participate, quality of DNA collection with saliva kits, genotyping, and dispensing data retrieved from the pharmacy. METHODS: Polypharmacy patients aged >60 years who used at least one drug with Anatomical Therapeutic Chemical (ATC) code N06AA01-N06AX19 (antidepressants), A02BC01-A02BC05 (proton-pump inhibitors), N05AA01-N05AH04 (antipsychotics), or C07AB02 (metoprolol) in the preceding 2 years were randomly selected. DNA was collected with saliva kits and genotyped for CYP2D6 and CYP2C19 with the AmpliChip. Pharmacy dispensing records were retrieved and screened for drugs interacting with the patient's CYP2D6 and CYP2C19 genotype by using the evidence-based PGt guidelines from the Dutch Pharmacogenetics Working Group. RESULTS: Out of the 93 invited patients, 54 (58.1%) provided informed consent. Nine saliva samples (16.7%) contained too little DNA. Call rates for CYP2D6 and CYP2C19 were 93.3% and 100%, respectively. Frequencies of genotype-predicted phenotype were 2.4%, 38.1%, 54.8%, and 4.8% for CYP2D6 poor metabolizers (PM), intermediate metabolizers (IM), extensive metabolizers (EM), and ultrarapid metabolizers (UM) respectively. For CYP2C19 genotype-predicted phenotype, frequencies were 2.2%, 15.6%, and 82.2% for PM, IM, and EM, respectively. CONCLUSIONS: This study shows that pharmacy-initiated PGt screening is feasible for a primary care setting
Intravenous pharmacokinetics, oral bioavailability, dose proportionality and in situ permeability of anti-malarial lumefantrine in rats
<p>Abstract</p> <p>Background</p> <p>Despite the wide spread use of lumefantrine, there is no study reporting the detailed preclinical pharmacokinetics of lumefantrine. For the development of newer anti-malarial combination(s) and selection of better partner drugs, it is long felt need to understand the detailed preclinical pharmacokinetics of lumefantrine in preclinical experimental animal species. The focus of present study is to report bioavailability, pharmacokinetics, dose linearity and permeability of lumefantrine in rats.</p> <p>Methods</p> <p>A single dose of 10, 20 or 40 mg/kg of lumefantrine was given orally to male rats (N = 5 per dose level) to evaluate dose proportionality. In another study, a single intravenous bolus dose of lumefantrine was given to rats (N = 4) at 0.5 mg/kg dose following administration through the lateral tail vein in order to obtain the absolute oral bioavailability and clearance parameters. Blood samples were drawn at predetermined intervals and the concentration of lumefantrine and its metabolite desbutyl-lumefantrine in plasma were determined by partially validated LC-MS/MS method. <it>In-situ </it>permeability study was carried in anaesthetized rats. The concentration of lumefantrine in permeability samples was determined using RP-HPLC.</p> <p>Results</p> <p>For nominal doses increasing in a 1:2:4 proportion, the C<sub>max </sub>and AUC<sub>0-∞ </sub>values increased in the proportions of 1:0.6:1.5 and 1:0.8:1.8, respectively. For lumefantrine nominal doses increasing in a 1:2:4 proportion, the C<sub>max </sub>and the AUC<sub>0-t </sub>values for desbutyl-lumefantrine increased in the proportions of 1:1.45:2.57 and 1:1.08:1.87, respectively. After intravenous administration the clearance (Cl) and volume of distribution (Vd) of lumefantrine in rats were 0.03 (± 0.02) L/h/kg and 2.40 (± 0.67) L/kg, respectively. Absolute oral bioavailability of lumefantrine across the tested doses ranged between 4.97% and 11.98%. Lumefantrine showed high permeability (4.37 × 10<sup>-5 </sup>cm/s) in permeability study.</p> <p>Conclusions</p> <p>The pharmacokinetic parameters of lumefantrine and its metabolite desbutyl-lumefantrine were successfully determined in rats for the first time. Lumefantrine displayed similar pharmacokinetics in the rat as in humans, with multiphasic disposition, low clearance, and a large volume of distribution resulting in a long terminal elimination half-life. The absolute oral bioavailability of lumefantrine was found to be dose dependent. Lumefantrine displayed high permeability in the <it>in-situ </it>permeability study.</p
Autism as a disorder of neural information processing: directions for research and targets for therapy
The broad variation in phenotypes and severities within autism spectrum disorders suggests the involvement of multiple predisposing factors, interacting in complex ways with normal developmental courses and gradients. Identification of these factors, and the common developmental path into which theyfeed, is hampered bythe large degrees of convergence from causal factors to altered brain development, and divergence from abnormal brain development into altered cognition and behaviour. Genetic, neurochemical, neuroimaging and behavioural findings on autism, as well as studies of normal development and of genetic syndromes that share symptoms with autism, offer hypotheses as to the nature of causal factors and their possible effects on the structure and dynamics of neural systems. Such alterations in neural properties may in turn perturb activity-dependent development, giving rise to a complex behavioural syndrome many steps removed from the root causes. Animal models based on genetic, neurochemical, neurophysiological, and behavioural manipulations offer the possibility of exploring these developmental processes in detail, as do human studies addressing endophenotypes beyond the diagnosis itself
Impairment of Adolescent Hippocampal Plasticity in a Mouse Model for Alzheimer's Disease Precedes Disease Phenotype
The amyloid precursor protein (APP) was assumed to be an important neuron-morphoregulatory protein and plays a central role in Alzheimer's disease (AD) pathology. In the study presented here, we analyzed the APP-transgenic mouse model APP23 using 2-dimensional gel electrophoresis technology in combination with DIGE and mass spectrometry. We investigated cortex and hippocampus of transgenic and wildtype mice at 1, 2, 7 and 15 months of age. Furthermore, cortices of 16 days old embryos were analyzed. When comparing the protein patterns of APP23 with wildtype mice, we detected a relatively large number of altered protein spots at all age stages and brain regions examined which largely preceded the occurrence of amyloid plaques. Interestingly, in hippocampus of adolescent, two-month old mice, a considerable peak in the number of protein changes was observed. Moreover, when protein patterns were compared longitudinally between age stages, we found that a large number of proteins were altered in wildtype mice. Those alterations were largely absent in hippocampus of APP23 mice at two months of age although not in other stages compared. Apparently, the large difference in the hippocampal protein patterns between two-month old APP23 and wildtype mice was caused by the absence of distinct developmental changes in the hippocampal proteome of APP23 mice. In summary, the absence of developmental proteome alterations as well as a down-regulation of proteins related to plasticity suggest the disturption of a normally occurring peak of hippocampal plasticity during adolescence in APP23 mice. Our findings are in line with the observation that AD is preceded by a clinically silent period of several years to decades. We also demonstrate that it is of utmost importance to analyze different brain regions and different age stages to obtain information about disease-causing mechanisms
Natural Distribution of Parasitoids of Larvae of the Fall Armyworm, Spodoptera frugiperda, in Argentina
To develop a better understanding of the natural distribution of the fall armyworm, Spodoptera frugiperda (Smith) (Lepidoptera: Noctuidae), and to update the knowledge of the incidence of its complex of parasitoids. S. frugiperda, samplings in whorl-stage corn were carried out in provinces of Argentina from 1999 to 2003. S. frugiperda larvae were collected from corn in localities of the provinces of Tucumán, Salta, Jujuy, Santiago del Estero, La Rioja, Córdoba, San Luis, Chaco and Misiones. In each locality 30 corn plants were sampled and only larvae located in those plants were collected. The parasitoids that emerged from S. frugiperda larvae were identified and counted. The abundance of the parasitoids and the parasitism rate were estimated. The S. frugiperda parasitoids collected were Campoletis grioti (Blanchard) (Hymenoptera: Ichneumonidae), Chelonus insularis (Cresson) (Hymenoptera: Braconidae), Archytas marmoratus (Townsend) (Diptera Tachinidae) and/or A. incertus (Macquart), Ophion sp. (Hymenoptera: Ichneumonidae), Euplectrus platyhypenae Howard (Hymenoptera: Eulophidae), and Incamyia chilensis (Aldrich) (Diptera Tachinidae). C. grioti was the most abundant and frequent during the five-year survey. Similar diversity of parasitoids was obtained in all the provinces, with the exception of I. chilensis and E. platyhypenae that were recovered only in the province of Salta. In the Northwestern region, in Tucumán, C. grioti and species of Archytas were the most abundant and frequent parasitoids. On the contrary, in Salta and Jujuy Ch. insularis was the parasitoid most abundant and frequently recovered. The parasitism rate obtained in Tucumán, Salta and Jujuy provinces were 21.96%, 17.87% and 6.63% respectively with an average of 18.93%. These results demonstrate that hymenopteran and dipteran parasitoids of S. frugiperda occurred differentially throughout the Argentinian provinces and played an important role on the natural control of the S. frugiperda larval population
Effectiveness and Cost-effectiveness of Outpatient Physiotherapy After Knee Replacement for Osteoarthritis: Study Protocol for a Randomised Controlled Trial
Background: Primary total knee replacement is a common operation that is performed to provide pain relief and restore functional ability. Inpatient physiotherapy is routinely provided after surgery to enhance recovery prior to hospital discharge. However, international variation exists in the provision of outpatient physiotherapy after hospital discharge. While evidence indicates that outpatient physiotherapy can improve short-term function, the longer term benefits are unknown. The aim of this randomised controlled trial is to evaluate the long-term clinical effectiveness and cost-effectiveness of a 6-week group-based outpatient physiotherapy intervention following knee replacement.
Methods/design: Two hundred and fifty-six patients waiting for knee replacement because of osteoarthritis will be recruited from two orthopaedic centres. Participants randomised to the usual-care group (n = 128) will be given a booklet about exercise and referred for physiotherapy if deemed appropriate by the clinical care team. The intervention group (n = 128) will receive the same usual care and additionally be invited to attend a group-based outpatient physiotherapy class starting 6 weeks after surgery. The 1-hour class will be run on a weekly basis over
6 weeks and will involve task-orientated and individualised exercises.
The primary outcome will be the Lower Extremity Functional Scale at 12 months post-operative. Secondary outcomes include: quality of life, knee pain and function, depression, anxiety and satisfaction. Data collection will be by questionnaire prior to surgery and 3, 6 and 12 months after surgery and will include a resource-use questionnaire to enable a trial-based economic evaluation. Trial participation and satisfaction with the classes will be evaluated through structured telephone interviews. The primary statistical and economic analyses will be conducted on an intention-to-treat basis with and without imputation of missing data. The primary economic result will estimate the incremental cost per quality-adjusted life year gained from this intervention from a National Health Services (NHS) and personal social services perspective.
Discussion: This research aims to benefit patients and the NHS by providing evidence on the long-term effectiveness and cost-effectiveness of outpatient physiotherapy after knee replacement. If the intervention is found to be effective and cost-effective, implementation into clinical practice could lead to improvement in patients’ outcomes and improved health care resource efficiency
Integrating ecology and evolutionary theory. A game changer for biodiversity conservation?
Currently, one of the central arguments in favour of biodiversity conservation is that it is essential for the maintenance of ecosystem services, that is, the benefits that people receive from ecosystems. However, the relationship between ecosystem services and biodiversity is contested and needs clarification. The goal of this chapter is to spell out the interaction and reciprocal influences between conservation science, evolutionary biology, and ecology, in order to understand whether a stronger integration of evolutionary and ecological studies might help clarify the interaction between biodiversity and ecosystem functioning as well as influence biodiversity conservation practices. To this end, the eco-evolutionary feedback theory proposed by David Post and Eric Palkovacs is analysed, arguing that it helps operationalise niche construction theory and develop a more sophisticated understanding of the relationship between ecosystem functioning and biodiversity. Finally, it is proposed that by deepening the integration of ecological and evolutionary factors in our understanding of ecosystem functioning, the eco-evolutionary feedback theory is supportive of an “evolutionary-enlightened management” of biodiversity within the ecosystem services approach.info:eu-repo/semantics/publishedVersio
Introduced Mammalian Predators Induce Behavioural Changes in Parental Care in an Endemic New Zealand Bird
The introduction of predatory mammals to oceanic islands has led to the extinction of many endemic birds. Although introduced predators should favour changes that reduce predation risk in surviving bird species, the ability of island birds to respond to such novel changes remains unstudied. We tested whether novel predation risk imposed by introduced mammalian predators has altered the parental behaviour of the endemic New Zealand bellbird (Anthornis melanura). We examined parental behaviour of bellbirds at three woodland sites in New Zealand that differed in predation risk: 1) a mainland site with exotic predators present (high predation risk), 2) a mainland site with exotic predators experimentally removed (low risk recently) and, 3) an off-shore island where exotic predators were never introduced (low risk always). We also compared parental behaviour of bellbirds with two closely related Tasmanian honeyeaters (Phylidonyris spp.) that evolved with native nest predators (high risk always). Increased nest predation risk has been postulated to favour reduced parental activity, and we tested whether island bellbirds responded to variation in predation risk. We found that females spent more time on the nest per incubating bout with increased risk of predation, a strategy that minimised activity at the nest during incubation. Parental activity during the nestling period, measured as number of feeding visits/hr, also decreased with increasing nest predation risk across sites, and was lowest among the honeyeaters in Tasmania that evolved with native predators. These results demonstrate that some island birds are able to respond to increased risk of predation by novel predators in ways that appear adaptive. We suggest that conservation efforts may be more effective if they take advantage of the ability of island birds to respond to novel predators, especially when the elimination of exotic predators is not possible
Out of Their Depth? Isolated Deep Populations of the Cosmopolitan Coral Desmophyllum dianthus May Be Highly Vulnerable to Environmental Change
Deep sea scleractinian corals will be particularly vulnerable to the effects of
climate change, facing loss of up to 70% of their habitat as the
Aragonite Saturation Horizon (below which corals are unable to form calcium
carbonate skeletons) rises. Persistence of deep sea scleractinian corals will
therefore rely on the ability of larvae to disperse to, and colonise, suitable
shallow-water habitat. We used DNA sequence data of the internal transcribed
spacer (ITS), the mitochondrial ribosomal subunit (16S) and mitochondrial
control region (MtC) to determine levels of gene flow both within and among
populations of the deep sea coral Desmophyllum dianthus in SE
Australia, New Zealand and Chile to assess the ability of corals to disperse
into different regions and habitats. We found significant genetic subdivision
among the three widely separated geographic regions consistent with isolation
and limited contemporary gene flow. Furthermore, corals from different depth
strata (shallow <600 m, mid 1000–1500 m, deep >1500 m) even on the
same or nearby seamounts were strongly differentiated, indicating limited
vertical larval dispersal. Genetic differentiation with depth is consistent with
the stratification of the Subantarctic Mode Water, Antarctic Intermediate Water,
the Circumpolar Deep and North Pacific Deep Waters in the Southern Ocean, and we
propose that coral larvae will be retained within, and rarely migrate among,
these water masses. The apparent absence of vertical larval dispersal suggests
deep populations of D. dianthus are unlikely to colonise
shallow water as the aragonite saturation horizon rises and deep waters become
uninhabitable. Similarly, assumptions that deep populations will act as refuges
for shallow populations that are impacted by activities such as fishing or
mining are also unlikely to hold true. Clearly future environmental management
strategies must consider both regional and depth-related isolation of deep-sea
coral populations
- …