Between roost contact is essential for maintenance of European bat lyssavirus type-2 in Myotis daubentonii bat reservoir: 'The Swarming Hypothesis'.

Many high-consequence human and animal pathogens persist in wildlife reservoirs. An understanding of the dynamics of these pathogens in their reservoir hosts is crucial to inform the risk of spill-over events, yet our understanding of these dynamics is frequently insufficient. Viral persistence in a wild bat population was investigated by combining empirical data and in-silico analyses to test hypotheses on mechanisms for viral persistence. A fatal zoonotic virus, European Bat lyssavirus type 2 (EBLV-2), in Daubenton's bats (Myotis daubentonii) was used as a model system. A total of 1839 M. daubentonii were sampled for evidence of virus exposure and excretion during a prospective nine year serial cross-sectional survey. Multivariable statistical models demonstrated age-related differences in seroprevalence, with significant variation in seropositivity over time and among roosts. An Approximate Bayesian Computation approach was used to model the infection dynamics incorporating the known host ecology. The results demonstrate that EBLV-2 is endemic in the study population, and suggest that mixing between roosts during seasonal swarming events is necessary to maintain EBLV-2 in the population. These findings contribute to understanding how bat viruses can persist despite low prevalence of infection, and why infection is constrained to certain bat species in multispecies roosts and ecosystems.

The evolution of sensory divergence in the context of limited gene flow in the bumblebee bat.

The sensory drive theory of speciation predicts that populations of the same species inhabiting different environments can differ in sensory traits, and that this sensory difference can ultimately drive speciation. However, even in the best-known examples of sensory ecology driven speciation, it is uncertain whether the variation in sensory traits is the cause or the consequence of a reduction in levels of gene flow. Here we show strong genetic differentiation, no gene flow and large echolocation differences between the allopatric Myanmar and Thai populations of the world's smallest mammal, Craseonycteris thonglongyai, and suggest that geographic isolation most likely preceded sensory divergence. Within the geographically continuous Thai population, we show that geographic distance has a primary role in limiting gene flow rather than echolocation divergence. In line with sensory-driven speciation models, we suggest that in C. thonglongyai, limited gene flow creates the suitable conditions that favour the evolution of sensory divergence via local adaptation.

Approximations to complete basis set-extrapolated, highly correlated non-covalent interaction energies.

The first-principles calculation of non-covalent (particularly dispersion) interactions between molecules is a considerable challenge. In this work we studied the binding energies for ten small non-covalently bonded dimers with several combinations of correlation methods (MP2, coupled-cluster single double, coupled-cluster single double (triple) (CCSD(T))), correlation-consistent basis sets (aug-cc-pVXZ, X = D, T, Q), two-point complete basis set energy extrapolations, and counterpoise corrections. For this work, complete basis set results were estimated from averaged counterpoise and non-counterpoise-corrected CCSD(T) binding energies obtained from extrapolations with aug-cc-pVQZ and aug-cc-pVTZ basis sets. It is demonstrated that, in almost all cases, binding energies converge more rapidly to the basis set limit by averaging the counterpoise and non-counterpoise corrected values than by using either counterpoise or non-counterpoise methods alone. Examination of the effect of basis set size and electron correlation shows that the triples contribution to the CCSD(T) binding energies is fairly constant with the basis set size, with a slight underestimation with CCSD(T)∕aug-cc-pVDZ compared to the value at the (estimated) complete basis set limit, and that contributions to the binding energies obtained by MP2 generally overestimate the analogous CCSD(T) contributions. Taking these factors together, we conclude that the binding energies for non-covalently bonded systems can be accurately determined using a composite method that combines CCSD(T)∕aug-cc-pVDZ with energy corrections obtained using basis set extrapolated MP2 (utilizing aug-cc-pVQZ and aug-cc-pVTZ basis sets), if all of the components are obtained by averaging the counterpoise and non-counterpoise energies. With such an approach, binding energies for the set of ten dimers are predicted with a mean absolute deviation of 0.02 kcal/mol, a maximum absolute deviation of 0.05 kcal/mol, and a mean percent absolute deviation of only 1.7%, relative to the (estimated) complete basis set CCSD(T) results. Use of this composite approach to an additional set of eight dimers gave binding energies to within 1% of previously published high-level data. It is also shown that binding within parallel and parallel-crossed conformations of naphthalene dimer is predicted by the composite approach to be 9% greater than that previously reported in the literature. The ability of some recently developed dispersion-corrected density-functional theory methods to predict the binding energies of the set of ten small dimers was also examined.

Ring-opening radical clock reactions: many density functionals have difficulty keeping time.

The ability of several density-functional theory methods to describe the kinetics and energetics of a series of ring-opening reactions of cyclopropyl and cyclobutyl-type radicals was explored. PBE, B971 and B3LYP perform quite well in their ability to replicate experiment, based upon the ring opening of cyclopropylcarbinyl, two α-trialkylsilyloxycyclopropylmethyl radicals, pentamethylcyclopropylcarbinyl, cyclobutylcarbinyl and 1-cyclobutylethylcarbinyl. The other functionals tested, which includes BLYP, CAM-B3LYP, BHandHLYP, B2PLYP and B2PLYP-D, as well as functionals designed for kinetics applications, namely MPW1K, BMK and M06-2X, all perform poorly. The latter of these functionals display some integration grid dependencies.

CO2 adsorption by nitrogen-doped carbon nanotubes predicted by density-functional theory with dispersion-correcting potentials.

The interaction of CO(2) to the interior and exterior walls of pristine and nitrogen-doped single-walled carbon nanotubes (SWNT) has been studied using density-functional theory with dispersion-correcting potentials (DCPs). Our calculations predict Gibbs energies of binding between SWNT and CO(2) of up to 9.1 kcal mol(-1), with strongest binding observed for a zigzag [10,0] nanotube, compared to armchair [6,6] (8.3 kcal mol(-1)) and chiral [8,4] (7.0 kcal mol(-1)). Doping of the [10,0] tube with nitrogen increases the Gibbs energies of binding of CO(2) by ca. 3 kcal mol(-1), but slightly reduced binding is found when [6,6] and [8,4] SWNT are doped in similar fashion. The Gibbs energy of binding of CO(2) to the exterior of the tubes is quite small compared to the binding that occurs inside the tubes. These findings suggest that the zigzag SWNT show greater promise as a means of CO(2) gas-capture.

The role of DNA barcodes in understanding and conservation of mammal diversity in southeast Asia.

BACKGROUND: Southeast Asia is recognized as a region of very high biodiversity, much of which is currently at risk due to habitat loss and other threats. However, many aspects of this diversity, even for relatively well-known groups such as mammals, are poorly known, limiting ability to develop conservation plans. This study examines the value of DNA barcodes, sequences of the mitochondrial COI gene, to enhance understanding of mammalian diversity in the region and hence to aid conservation planning. METHODOLOGY AND PRINCIPAL FINDINGS: DNA barcodes were obtained from nearly 1900 specimens representing 165 recognized species of bats. All morphologically or acoustically distinct species, based on classical taxonomy, could be discriminated with DNA barcodes except four closely allied species pairs. Many currently recognized species contained multiple barcode lineages, often with deep divergence suggesting unrecognized species. In addition, most widespread species showed substantial genetic differentiation across their distributions. Our results suggest that mammal species richness within the region may be underestimated by at least 50%, and there are higher levels of endemism and greater intra-specific population structure than previously recognized. CONCLUSIONS: DNA barcodes can aid conservation and research by assisting field workers in identifying species, by helping taxonomists determine species groups needing more detailed analysis, and by facilitating the recognition of the appropriate units and scales for conservation planning.

Accurate dispersion interactions from standard density-functional theory methods with small basis sets.

B971, PBE and PBE1 density functionals with 6-31G(d) basis sets are shown to accurately describe the binding in dispersion bound dimers. This is achieved through the use of dispersion-correcting potentials (DCPs) in conjunction with counterpoise corrections. DCPs resemble and are applied like conventional effective core potentials that can be used with most computational chemistry programs without code modification. Rather, DCPs are implemented by simple appendage to the input files for these types of programs. Binding energies are predicted to within ca. 11% and monomer separations to within ca. 0.06 A of high-level wavefunction data using B971/6-31G(d)-DCP. Similar results are obtained for PBE and PBE1 with the 6-31G(d) basis sets and DCPs. Although results found using the 3-21G(d) are not as impressive, they never-the-less show promise as a means of initial study for a wide variety of dimers, including those dominated by dispersion, hydrogen-bonding and a mixture of interactions. Notable improvement is found in comparison to M06-2X/6-31G(d) data, e.g., mean absolute deviations for the S22-set of dimers of ca. 13.6 and 16.5% for B971/6-31G(d)-DCP and M06-2X, respectively. However, it should be pointed out that the latter data were obtained using a larger integration grid size since a smaller grid results in different binding energies and geometries for simple dispersion-bound dimers such as methane and ethene.

Molecular phylogenetics and historical biogeography of Rhinolophus bats.

The phylogenetic relationships within the horseshoe bats (genus Rhinolophus) are poorly resolved, particularly at deeper levels within the tree. We present a better-resolved phylogenetic hypothesis for 30 rhinolophid species based on parsimony and Bayesian analyses of the mitochondrial cytochrome b gene and three nuclear introns (TG, THY and PRKC1). Strong support was found for the existence of two geographic clades within the monophyletic Rhinolophidae: an African group and an Oriental assemblage. The relaxed Bayesian clock method indicated that the two rhinolophid clades diverged approximately 35 million years ago and results from Dispersal Vicariance (DIVA) analysis suggest that the horseshoe bats arose in Asia and subsequently dispersed into Europe and Africa.

Binding in thiophene and benzothiophene dimers investigated by density functional theory with dispersion-correcting potentials.

We report the use of a newly developed dispersion-corrected density functional approach to study noncovalent binding in a series of thiophene and benzothiophene dimers. These are of interest in both petrochemistry and molecular electronics. We find increasing influence of dispersion forces over dipole interactions as the number of benzene moieties increases from 0 (thiophene) to 3 (tribenzothiophene). Binding in dimers of thiophene was benchmarked vs previously published CCSD(T) data (J. Am. Chem. Soc. 2002, 124, 12200). We have determined the fully optimized geometries and energies of 15 dimers of thiophene, 26 dimers of benzothiophene, 10 of dibenzothiophene, and 11 of tribenzothiophene using B971/6-31+G(d,p) with dispersion-correcting potentials (DCPs). These represent a mixture of T-shaped, tilted-T-shaped, pi-stacked, and coplanar structures. For thiophene we find the lowest energy T-shaped and pi-stacked dimers to bind by 3.0 and 2.5 kcal/mol, respectively. However, for benzothiophene the lowest energy structure is pi-stacked with binding energy, BE = 5.8 kcal/mol, which compares to the most bound T-shaped dimer, BE = 4.1 kcal/mol. This difference between pi-stacked and T-shaped dimer binding increases further going to dibenzothiophene and tribenzothiophene (difference = ca. 6.0 and 6.7 kcal/mol, respectively). When calculations without dispersion corrections are performed on the dimer structures, many display significant changes in structural motif and reductions in binding energies of up to 80%. Therefore, the inclusion of dispersion corrections, for example, through the use of DCPs, is essential in describing the potential energy landscape of these complexes.

Thermal rearrangements of 2-ethynylbiphenyl: a DFT study of competing reaction mechanisms.

Mechanistic pathways for high-temperature rearrangements of 2-ethynylbiphenyl have been investigated by calculations at the B3LYP/6-31G(d) level of theory, with free energy estimates at 625 degrees C. Two different routes for high temperature thermal rearrangement can lead to phenanthrene, which was the major product observed by Brown and co-workers (J. Chem. Soc. Chem. Commun. 1974, 123). 1,2-Hydrogen shift (Hopf type B mechanism) affords a vinylidene which proceeds to the major product by sequential electrocyclic closure and a 1,2-shift, rather than the expected aryl C-H insertion. Alternatively, insertion of the vinylidene into a ring double bond would lead directly to the observed minor product, benzazulene. Along a competitive pathway, electrocyclic closure to an isophenanthrene is predicted to be nearly isoenergetic. This intermediate should have a planar allene structure, with substantial diradical character. Sequential hydrogen shifts lead to phenanthrene but with higher cumulative barriers than for the vinylidene route. Calculation of 625 degrees C free energies shows that the carbene mechanism is of lower energy, primarily because of the lower entropic cost. Predictions are made for the unusually facile hydrogen atom dissociation from isoaromatics at high temperature, a consequence of aryl radical formation. Isophenanthrene, isobenzene (1,2,4-cyclohexatriene) and several isonaphthalenes are also predicted to have unusually low C-H bond dissociation energies. Potential significance as a source of aryl radicals in high temperature and combustion chemistry is discussed.

Hereditary dentine disorders: dentinogenesis imperfecta and dentine dysplasia.

The hereditary dentine disorders, dentinogenesis imperfecta (DGI) and dentine dysplasia (DD), comprise a group of autosomal dominant genetic conditions characterised by abnormal dentine structure affecting either the primary or both the primary and secondary dentitions. DGI is reported to have an incidence of 1 in 6,000 to 1 in 8,000, whereas that of DD type 1 is 1 in 100,000. Clinically, the teeth are discoloured and show structural defects such as bulbous crowns and small pulp chambers radiographically. The underlying defect of mineralisation often results in shearing of the overlying enamel leaving exposed weakened dentine which is prone to wear. Currently, three sub-types of DGI and two sub-types of DD are recognised but this categorisation may change when other causative mutations are found. DGI type I is inherited with osteogenesis imperfecta and recent genetic studies have shown that mutations in the genes encoding collagen type 1, COL1A1 and COL1A2, underlie this condition. All other forms of DGI and DD, except DD-1, appear to result from mutations in the gene encoding dentine sialophosphoprotein (DSPP), suggesting that these conditions are allelic. Diagnosis is based on family history, pedigree construction and detailed clinical examination, while genetic diagnosis may become useful in the future once sufficient disease-causing mutations have been discovered. Differential diagnoses include hypocalcified forms of amelogenesis imperfecta, congenital erythropoietic porphyria, conditions leading to early tooth loss (Kostmann's disease, cyclic neutropenia, Chediak-Hegashi syndrome, histiocytosis X, Papillon-Lefevre syndrome), permanent teeth discolouration due to tetracyclines, Vitamin D-dependent and vitamin D-resistant rickets. Treatment involves removal of sources of infection or pain, improvement of aesthetics and protection of the posterior teeth from wear. Beginning in infancy, treatment usually continues into adulthood with a number of options including the use of crowns, over-dentures and dental implants depending on the age of the patient and the condition of the dentition. Where diagnosis occurs early in life and treatment follows the outlined recommendations, good aesthetics and function can be obtained.

Reaction of phenols with the 2,2-diphenyl-1-picrylhydrazyl radical. Kinetics and DFT calculations applied to determine ArO-H bond dissociation enthalpies and reaction mechanism.

The formal H-atom abstraction by the 2,2-diphenyl-1-picrylhydrazyl (dpph(*)) radical from 27 phenols and two unsaturated hydrocarbons has been investigated by a combination of kinetic measurements in apolar solvents and density functional theory (DFT). The computed minimum energy structure of dpph(*) shows that the access to its divalent N is strongly hindered by an ortho H atom on each of the phenyl rings and by the o-NO(2) groups of the picryl ring. Remarkably small Arrhenius pre-exponential factors for the phenols [range (1.3-19) x 10(5) M(-1) s(-1)] are attributed to steric effects. Indeed, the entropy barrier accounts for up to ca. 70% of the free-energy barrier to reaction. Nevertheless, rate differences for different phenols are largely due to differences in the activation energy, E(a,1) (range 2 to 10 kcal/mol). In phenols, electronic effects of the substituents and intramolecular H-bonds have a large influence on the activation energies and on the ArO-H BDEs. There is a linear Evans-Polanyi relationship between E(a,1) and the ArO-H BDEs: E(a,1)/kcal x mol(-1) = 0.918 BDE(ArO-H)/kcal x mol(-1) - 70.273. The proportionality constant, 0.918, is large and implies a "late" or "product-like" transition state (TS), a conclusion that is congruent with the small deuterium kinetic isotope effects (range 1.3-3.3). This Evans-Polanyi relationship, though questionable on theoretical grounds, has profitably been used to estimate several ArO-H BDEs. Experimental ArO-H BDEs are generally in good agreement with the DFT calculations. Significant deviations between experimental and DFT calculated ArO-H BDEs were found, however, when an intramolecular H-bond to the O(*) center was present in the phenoxyl radical, e.g., in ortho semiquinone radicals. In these cases, the coupled cluster with single and double excitations correlated wave function technique with complete basis set extrapolation gave excellent results. The TSs for the reactions of dpph(*) with phenol, 3- and 4-methoxyphenol, and 1,4-cyclohexadiene were also computed. Surprisingly, these TS structures for the phenols show that the reactions cannot be described as occurring exclusively by either a HAT or a PCET mechanism, while with 1,4-cyclohexadiene the PCET character in the reaction coordinate is much better defined and shows a strong pi-pi stacking interaction between the incipient cyclohexadienyl radical and a phenyl ring of the dpph(*) radical.

Interactions in large, polyaromatic hydrocarbon dimers: application of density functional theory with dispersion corrections.

The interactions within two models for graphene, coronene and hexabenzocoronene (HBC), and (H 3C(CH 2) 5) 6-HBC, a synthesizable model for asphaltenes, were studied using density functional theory (DFT) with dispersion corrections. The corrections were implemented using carbon atom-centered effective core-type potentials that were designed to correct the erroneous long-range behavior of several DFT methods. The potentials can be used with any computational chemistry program package that can handle standard effective core potential input, without the need for software modification. Testing on a set of common noncovalently bonded dimers shows that the potentials improve calculated binding energies by factors of 2-3 over those obtained without the potentials. Binding energies are predicted to within ca. 15%, and monomer separations to within ca. 0.1 A, of high-level wave function data. The application of the present approach predicts binding energies and structures of the coronene dimer that are in excellent agreement with the results of other DFT methods in which dispersion is taken into account. Dimers of HBC show extensive binding in pi-stacking arrangements, with the largest binding energy, 44.8 kcal/mol, obtained for a parallel-displaced structure. This structure is inline with the published crystal structure. Conformations in which the monomers are perpendicular to one another are much more weakly bound and have binding energies less than 10 kcal/mol. For dimers of (H 3C(CH 2) 5) 6-HBC, which contain 336 atoms, we find that a slipped-parallel structure with C s symmetry has a binding energy of 52.4 kcal/mol, 8.9 kcal/mol lower than that of a bowl-like, C 6 v -symmetric structure.

Schizophrenia-related neural and behavioral phenotypes in transgenic mice expressing truncated Disc1.

Disrupted-in-Schizophrenia-1 (DISC1), identified by positional cloning of a balanced translocation (1;11) with the breakpoint in intron 8 of a large Scottish pedigree, is associated with a range of neuropsychiatric disorders including schizophrenia. To model this mutation in mice, we have generated Disc1(tr) transgenic mice expressing 2 copies of truncated Disc1 encoding the first 8 exons using a bacterial artificial chromosome (BAC). With this partial simulation of the human situation, we have discovered a range of phenotypes including a series of novel features not previously reported. Disc1(tr) transgenic mice display enlarged lateral ventricles, reduced cerebral cortex, partial agenesis of the corpus callosum, and thinning of layers II/III with reduced neural proliferation at midneurogenesis. Parvalbumin GABAergic neurons are reduced in the hippocampus and medial prefrontal cortex, and displaced in the dorsolateral frontal cortex. In culture, transgenic neurons grow fewer and shorter neurites. Behaviorally, transgenic mice exhibit increased immobility and reduced vocalization in depression-related tests, and impairment in conditioning of latent inhibition. These abnormalities in Disc1(tr) transgenic mice are consistent with findings in severe schizophrenia.

Spatial distribution of mitochondrial and microsatellite DNA variation in Daubenton's bat within Scotland.

Daubenton's bat (Myotis daubentonii) is a known reservoir for European bat lyssavirus type 2 (EBLV-2). An appreciation of the potential for epidemiological spread and disease risk requires an understanding of the dispersal of the primary host, and any large-scale geographical barriers that may impede gene flow. The spatial pattern of microsatellite and mitochondrial DNA variation was examined to infer patterns of dispersal of bats among 35 populations across Scotland. DNA sequence variation at the mitochondrial control region and ND1 genes revealed two distinct phylogeographical clades, with generally nonoverlapping geographical distributions except for a small number of populations where both matrilines were found in sympatry. Such discontinuity suggests that Scotland was recolonized twice following the retreat of the Pleistocene ice sheet with little subsequent matrilineal introgression. However, eight microsatellite loci showed low levels of genetic divergence among populations, even between populations from the two distinct mitochondrial DNA clades. An overall, macrogeographical genetic isolation-by-distance pattern was observed, with high levels of gene flow among local populations. Apparently contrasting patterns of mitochondrial and microsatellite divergence at different scales could be explained by sex-specific differences in gene flow at large scales.

Thermochemical and kinetic study of the carbocation ring contraction of cyclohexylium to methylcyclopentylium.

The isomerization of cyclohexylium to methylcyclopentylium is a model for a key step required in sterol and triterpene biosynthesis and is important in catalytic processes associated with ring-opening reactions in upgrading petroleum fractions. Using high-level, correlated wave function techniques based on QCISD, the mechanism for this isomerization was found to be very different from that first proposed more than 35 years ago. On the basis of our mechanism, a first-order rate constant expression was derived and used with complete basis set-extrapolated QCISD(T) energies to obtain Ea = 6.9 kcal/mol and A = 1011.18 s-1, in excellent agreement with values of 7.4 +/- 1 kcal/mol and A = 1012 +/- 1.3 s-1 measured in the gas phase. The B3LYP and MP2 methods, two commonly used computational approaches, were found to predict incorrect mechanisms and, in some cases, poor kinetic parameters. The PBE method, however, produced a reaction profile and kinetic parameters in reasonable agreement with those obtained with the complete basis set-extrapolated QCISD(T) method.

Diagnostic dilemma of an ulcer in a child.

UNLABELLED: Careful history-taking and examination are important in diagnosing self-inflicted injuries, which are often very difficult to diagnose and manage. We describe a case of a misdiagnosed traumatic ulcer in a 9-year-old boy which meant that he went through months of pain and discomfort, missed school, was admitted to hospital and had a series of unnecessary investigations. CLINICAL RELEVANCE: This case highlights the importance of dental referral, careful history and examination in managing unusual oral ulceration.

A comparison of paracetamol, ibuprofen or their combination for pain relief following extractions in children under general anaesthesia: a randomized controlled trial.

OBJECTIVE: This study was designed to compare the effectiveness of different oral analgesics for relieving pain and distress in children following the extraction of teeth under general anaesthesia (GA). The analgesics included paracetamol alone, ibuprofen alone, and paracetamol and ibuprofen in combination. METHODS: Two hundred and one subjects were randomly allocated to one of four groups. Forty-seven children were included in the ibuprofen alone (5 mg kg(-1)) group, 51 in the paracetamol/ibuprofen combination (15/5 mg kg(-1)) group, 48 in the high-dose paracetamol (20 mg kg(-1)) group, and 55 children were included in the usual-dose paracetamol (15 mg kg(-1)) group (control group). Evaluation of distress for children was made immediately pre-operatively, on recovery from anaesthesia and again after 15 min by using a five-point face scale. Furthermore, each child was observed immediately postoperatively and 15 min postoperatively for signs of pain using the Children's Hospital of Eastern Ontario Pain Scale. RESULTS: There were significant decreases in the mean pain and distress scores for both the ibuprofen alone and paracetamol/ibuprofen combination groups compared to the control group (usual-dose paracetamol) at 15 min postoperatively. CONCLUSIONS: This study provides evidence to support the oral administration of ibuprofen alone or in combination with paracetamol for postoperative analgesia in children who are having teeth extracted under GA.

The effects of a long wait for children's dental general anaesthesia.

OBJECTIVES: The purpose of this study was to monitor the effect of an interruption in a service for children who were scheduled to have dental extractions under general anaesthesia (GA). The reasons for offering GA and the treatment given while the service was not available, together with the history of the pain, antibiotic usage and alterations to the number of teeth extracted were recorded. METHODS: When the GA extraction service stopped, the children who were scheduled to have their teeth extracted were placed on a waiting list. When the service recommenced 6 months later, the children were invited to attend a reassessment. Relevant data were collected at this visit using a proforma. RESULTS: A total of 321 children had their extractions delayed. Only 249 of these attended for a reassessment. During the waiting period, 102 parents (41.0%) reported that their children required analgesics, 71 (28.5%) stated that their children's sleep was disturbed and 82 (32.9%) recorded problems with eating. One hundred and twenty-three children (49.4%) had received antibiotics, with 49 (19.6%) having been prescribed two or more courses. The majority of treatment plans (85.5%) remained unchanged. CONCLUSIONS: Many children who had had their extractions delayed suffered further pain and disruption to their life.

Assessing the mini-Clinical Evaluation Exercise in comparison to a national specialty examination.

PURPOSE: To evaluate the reliability and validity of the Mini-Clinical Evaluation Exercise (mini-CEX) for postgraduate year 4 (PGY-4) internal medicine trainees compared to a high-stakes assessment of clinical competence, the Royal College of Physicians and Surgeons of Canada Comprehensive Examination in Internal Medicine (RCPSC IM examination). METHODS: Twenty-two PGY-4 residents at the University of British Columbia and the University of Calgary were evaluated, during the 6 months preceding their 2004 RCPSC IM examination, with a mean of 5.5 mini-CEX encounters (range 3-6). Experienced Royal College examiners from each site travelled to the alternate university to assess the encounters. RESULTS: The mini-CEX encounters assessed a broad range of internal medicine patient problems. The inter-encounter reliability for the residents' mean mini-CEX overall clinical competence score was 0.74. The attenuated correlation between residents' mini-CEX overall clinical competence score and their 2004 RCPSC IM oral examination score was 0.59 (P = 0.01). CONCLUSION: By examining multiple sources of validity evidence, this study suggests that the mini-CEX provides a reliable and valid assessment of clinical competence for PGY-4 trainees in internal medicine.