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PURPOSE: Undergraduate medical education (UGME) has to prepare students to do safety-critical work (notably, to prescribe) immediately after qualifying. Despite hospitals depending on them, medical graduates consistently report feeling unprepared to prescribe and they sometimes harm patients. Research clarifying how to prepare students better could improve healthcare safety. Our aim was to explore how students experienced preparing for one of their commonest prescribing tasks: intravenous fluid therapy (IVFT). METHODS: Complexity assumptions guided the research, which used a qualitative methodology oriented towards hermeneutic phenomenology. The study design was an uncontrolled and unplanned complex intervention: judicial review of the iatrogenic death of five children due to hyponatraemia in our region had resulted in the recommendation that students' education in 'the implementation of important clinical guidelines' relevant to fluid and electrolyte balance should be intensified. An opportunity sample of 40 final-year medical students drew and gave audio-recorded commentaries on rich pictures. We completed two template analyses: one of participants' transcribed commentaries on the pictures and one using a novel heuristic to analyse the pictures themselves. We then reconciled the two analyses into a single template. RESULTS: There were four themes: affects, teaching and learning, contradictions, and the curriculum as a journey. To explore interconnections between themes, we chose the picture best exemplifying each of the four themes and interpreted the curriculum journey depicted in each of them. These interpretations were grounded in each participant's picture, verbal account of the picture, and the aggregate findings of the template analysis. Participants' experiences were influenced by the situated complexity of IVFT. Layered on top of that, contradictions, overlaps, and gaps within the curriculum introduced extraneous complexity. Confusion and apprehension resulted. CONCLUSIONS: After spending five years preparing to prescribe IVFT, participants felt unprepared to do so. We conclude that intensive teaching had not achieved its avowed goal of improving students' preparedness for safe practice. Merton's seminal work on the 'unanticipated consequences of purposive social action' suggests that intensive teaching may even have contributed to their unpreparedness.
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BACKGROUND: Advance Care Planning is recommended for people with end-stage kidney disease but evidence is limited. Robust clinical trials are needed to investigate the impact of advance care planning in this population. There is little available data on cost-effectiveness to guide decision makers in allocating resources for advance care planning. Therefore we sought to determine the feasibility of a randomised controlled trial and to test methods for assessing cost-effectiveness. METHODS: A deferred entry, randomised controlled feasibility trial, incorporating economic and process evaluations, with people with end-stage kidney disease, aged 65 years or older, receiving haemodialysis, in two renal haemodialysis units in Northern Ireland, UK. A nurse facilitator helped the patient make an advance care plan identifying: a surrogate decision-maker; what the participant would like to happen in the future; any advance decision to refuse treatment; preferred place of care at end-of-life. RESULTS: Recruitment lasted 189 days; intervention and data collection 443 days. Of the 67 patients invited to participate 30 (45%) declined and 36 were randomised to immediate or deferred advance care plan groups. Twenty-two (61%) made an advance care plan and completed data collection at 12 weeks; 17 (47.2%) were able to identify a surrogate willing to be named in the advance care plan document. The intervention was well-received and encouraged end-of-life conversations, but did not succeed in helping patients to fully clarify their values or consider specific treatment choices. There was no significant difference in health system costs between the immediate and deferred groups. CONCLUSIONS: A trial of advance care planning with participants receiving haemodialysis is feasible and acceptable to patients, but challenging. A full trial would require a pool of potential participants five times larger than the number required to complete data collection at 3 months. Widening eligibility criteria to include younger (under 65 years of age) and less frail patients, together with special efforts to engage and retain surrogates may improve recruitment and retention. Traditional advance care planning outcomes may need to be supplemented with those that are defined by patients, helping them to participate with clinicians in making medical decisions. TRIAL REGISTRATION: Registered December 16, 2015. ClinicalTrials.gov Identifier: NCT02631200 .
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Planificación Anticipada de Atención , Fallo Renal Crónico , Enfermeras y Enfermeros , Anciano , Actitud del Personal de Salud , Actitud Frente a la Salud , Análisis Costo-Beneficio , Estudios de Factibilidad , Humanos , Fallo Renal Crónico/terapia , Diálisis RenalRESUMEN
Biphenyl is a prototype molecule, the study of which is important for a proper understanding of stereo-electronic effects. In the gas phase it has an equilibrium central torsion angle of ~ 45° and shows both a planar (0°) and a perpendicular (90°) torsional energy barrier. The latter is analysed for the first time. We use the newly proposed REG method, which is an exhaustive procedure that automatically ranks atomic energy contributions according to their importance in explaining the energy profile of a total system. Here, the REG method operates on energy contributions computed by the interacting quantum atoms method. This method is minimal in architecture and provides a crisp picture of well-defined and well-separated electrostatic, steric and exchange (covalent) energies at atomistic level. It is shown that the bond critical point occurring between the ortho-hydrogens in the planar geometry has been wrongly interpreted as a sign of repulsive interaction. A convenient metaphor of analysing football matches is introduced to clarify the role of a REG analysis.
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Improvements in immunosuppression have modified short-term survival of deceased-donor allografts, but not their rate of long-term failure. Mismatches between donor and recipient HLA play an important role in the acute and chronic allogeneic immune response against the graft. Perfect matching at clinically relevant HLA loci does not obviate the need for immunosuppression, suggesting that additional genetic variation plays a critical role in both short- and long-term graft outcomes. By combining patient data and samples from supranational cohorts across the United Kingdom and European Union, we performed the first large-scale genome-wide association study analyzing both donor and recipient DNA in 2094 complete renal transplant-pairs with replication in 5866 complete pairs. We studied deceased-donor grafts allocated on the basis of preferential HLA matching, which provided some control for HLA genetic effects. No strong donor or recipient genetic effects contributing to long- or short-term allograft survival were found outside the HLA region. We discuss the implications for future research and clinical application.
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Estudio de Asociación del Genoma Completo , Trasplante de Riñón , Donantes de Tejidos , Receptores de Trasplantes , Adulto , Replicación del ADN , Femenino , Genotipo , Supervivencia de Injerto/inmunología , Prueba de Histocompatibilidad , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Trasplante HomólogoRESUMEN
Accurate description of the intrinsic preferences of amino acids is important to consider when developing a biomolecular force field. In this study, we use a modern energy partitioning approach called Interacting Quantum Atoms to inspect the cause of the φ and ψ torsional preferences of three dipeptides (Gly, Val, and Ile). Repeating energy trends at each of the molecular, functional group, and atomic levels are observed across both (1) the three amino acids and (2) the φ/ψ scans in Ramachandran plots. At the molecular level, it is surprisingly electrostatic destabilization that causes the high-energy regions in the Ramachandran plot, not molecular steric hindrance (related to the intra-atomic energy). At the functional group and atomic levels, the importance of key peptide atoms (Oi-1 , Ci , Ni , Ni+1 ) and some sidechain hydrogen atoms (Hγ ) are identified as responsible for the destabilization seen in the energetically disfavored Ramachandran regions. Consistently, the Oi-1 atoms are particularly important for the explanation of dipeptide intrinsic behavior, where electrostatic and steric destabilization unusually complement one another. The findings suggest that, at least for these dipeptides, it is the peptide group atoms that dominate the intrinsic behavior, more so than the sidechain atoms. © 2017 The Authors. Journal of Computational Chemistry Published by Wiley Periodicals, Inc.
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The Interacting Quantum Atoms (IQA) energy partitioning scheme has been applied to a set of liquid water largely spherical clusters (henceforth called spheres) of up to 9 Å radius, with a maximum cluster size of 113 molecules. This constitutes half of the commonly used 216 molecules in a typical simulation box of a liquid water box, and to our knowledge is the largest analysis of this kind ever undertaken. As well as demonstrating the topological analysis of large systems, which has only recently become computationally feasible, important long range properties of liquid water are obtained. The full topological partitioning of each sphere into atomic basins is used to consider the long-range convergence of the energetic and multipolar properties of the water molecule at the centre of each sphere. It is found that the total molecular energy converges to its 9 Å value after 7 Å, which corresponds to approximately the first three solvation shells, while the molecular dipole and quadrupole moments approximately converge after 5.5 Å, which corresponds to approximately the first two solvation shells. The effect of water molecule flexibility is also considered.
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BACKGROUND: Only a paucity of studies have addressed clinician perspectives on patient decisional conflict, in making complex decisions between dialysis and conservative management (renal supportive and palliative care). AIM: To explore clinician views on decisional conflict in patients with end-stage kidney disease. DESIGN: Interpretive, qualitative study. SETTING AND PARTICIPANTS: As part of the wider National Institute for Health Research, PAlliative Care in chronic Kidney diSease study, semi-structured interviews were conducted with clinicians (nephrologists n = 12; 7 female and clinical nurse specialists n = 15; 15 female) across 10 renal centres in the United Kingdom. Interviews took place between April 2015 and October 2016 and a thematic analysis of the interview data was undertaken. RESULTS: Three major themes with associated subthemes were identified. The first, 'Frequent changing of mind regarding treatment options', revealed how patients frequently altered their treatment decisions, some refusing to make a decision until deterioration occurred. The second theme, 'Obligatory beneficence', included clinicians helping patients to make informed decisions where outcomes were uncertain. In weighing up risks and benefits, and the impact on patients, clinicians sometimes withheld information they thought might cause concern. Finally, 'Intricacy of the decision' uncovered clinicians' views on the momentous and brave decision to be made. They also acknowledged the risks associated with this complex decision in giving prognostic information which might be inaccurate. LIMITATIONS: Relies on interpretative description which uncovers constructed truths and does not include interviews with patients. CONCLUSION: Findings identify decisional conflict in patient decision-making and a tension between the prerequisite for shared decision-making and current clinical practice. Clinicians also face conflict when discussing treatment options due to uncertainty in equipoise between treatments and how much information should be shared. The findings are likely to resonate across countries outside the United Kingdom.
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Actitud del Personal de Salud , Conflicto Psicológico , Tratamiento Conservador , Toma de Decisiones , Diálisis Renal , Insuficiencia Renal Crónica/terapia , Adulto , Tratamiento Conservador/psicología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Investigación Cualitativa , Diálisis Renal/psicologíaRESUMEN
UNLABELLED: The prediction of hydrogen-bond (H-bond) acceptor ability is crucial in drug design. This important property is quantified in a large pKBHX database of consistently measured values. We aim to expand the chemical diversity of the studied H-bond acceptors and to increase the range of H-bond strength considered. Two quantum chemical descriptors are contrasted, called ΔE(H) (the change in the energy of a topological hydrogen atom upon complexation) and Vmin (the local minimum in the electrostatic potential on the H-bond accepting site). We performed a systematic analysis of the correlations between pKBHX and Vmin for an initial set of 106 compounds (including O- and N-containing subsets, as well as compounds including sulfur, chlorine, and π-bases). Correlations improve for family dependent subsets, and after outlier treatment, a set of 90 compounds was used to set up a linear equation to predict pKBHX from Vmin. This equation and a previously published equation [Green and Popelier J. Chem. Inf. MODEL: 2014, 54 (2), 553-561], to predict pKBHX from ΔE(H), were used to predict the pKBHX values for 22 potentially biologically active heteroaromatic ring compounds, [Pitt et al. J. Med. Chem. 2009, 52 (9), 2952-2963], among which several structures still remain experimentally unavailable. H-Bond basicity of sp(2) nitrogen sites were consistently predicted with both descriptors. A worse agreement was found with carbonyl acceptor sites, with the stronger deviations observed for the lactam groups. It was shown that secondary interactions involving the neighboring NH group were influencing the results. Substitution of the NH group with an NMe group resulted in an improved consistency from both Vmin and ΔE(H) predictions, the latter being more prominently affected by the methyl substitution. Both approaches appear as efficient procedures for the H-bond ability prediction of novel heteroaromatic rings. Nevertheless, the ΔE(H) parameter presents slight chemical structure limitations and requires more detailed H-bond structure investigations.
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Hidrocarburos/química , Modelos Teóricos , Ciclización , Enlace de HidrógenoRESUMEN
An interaction between two atoms, bonded or non-bonded, consists of interatomic contributions: electrostatic energy, exchange energy and electronic correlation energy. Together with the intra-atomic energy of an atom, these contributions are the basic components of the Interacting Quantum Atom (IQA) energy decomposition scheme. Here, we investigate IQA's proper use in conjunction with an explicit implementation of the B3LYP functional. The recovery of the total molecular energy from the IQA components is emphasised, for the first time. A systematic study of three model systems of biological relevance, N-methylacetamide (NMA), the doubly capped tripeptide GlyGlyGly and an alloxan dimer, shows the stabilization effect of B3LYP on most of the interatomic exchange energies (V) compared to their Hartree-Fock values. Diagrams of exchange energies versus interatomic distance show the clustering of interactions, one cluster for each 1,n (n = 1 to 6 where the atoms are separated by n - 1 bonds). The positioning of some V values outside their expected cluster marks interesting interactions.
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In this study, we aimed to develop a theoretical framework for a multimodal, integrative, exercise, anti-inflammatory and dietary counselling (MMIEAD) intervention for patients with renal cachexia with reference to how this addresses the underlying causal pathways for renal cachexia, the outcomes anticipated, and how these will be evaluated. We used a Theory of Change (ToC) approach to guide six steps. Step 1 included inputs from a workshop to obtain key stakeholder views on the potential development of a multimodal intervention for renal cachexia. Step 2 included the findings of a mixed-methods study with Health Care Practitioners (HCPs) caring for individuals with End Stage Kidney Disease (ESKD) and cachexia. Step 3 included the results from our systematic literature review on multimodal interventions for cachexia management. In step 4, we used the body of our research team's cachexia research and wider relevant research to gather evidence on the specific components of the multimodal intervention with reference to how this addresses the underlying causal pathways for renal cachexia. In steps 5 and 6 we developed and refined the ToC map in consultation with the core research team and key stakeholders which illustrates how the intervention components of MMIEAD interact to achieve the intended long-term outcomes and anticipated impact. The results of this study provide a theoretical framework for the forthcoming MMIEAD intervention for those with renal cachexia and in subsequent phases will be used to determine whether this intervention is effective. To the best of our knowledge no other multimodal intervention trials for cachexia management have reported a ToC. Therefore, this research may provide a useful framework and contribute to the ongoing development of interventions for cachexia management.
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Renal cachexia is an important consideration in the person-centred care that is needed in end-stage renal disease (ESRD). However, given that clinical guidelines relating to renal cachexia are largely absent, this is an unmet care need. To inform guidelines and future renal service planning, there is an urgency to understand individuals' experiences of renal cachexia and the interrelated experiences of the carers in their lives. We report here the protocol for an interpretative phenomenological study which will explore this lived experience. A purposive sampling strategy will recruit individuals living with ESRD who have cachexia and their carers. A maximum of 30 participants (15 per group) dependent on saturation will be recruited across two nephrology directorates, within two healthcare trusts in the United Kingdom. Individuals with renal cachexia undergoing haemodialysis will be recruited via clinical gatekeepers and their carers will subsequently be invited to participate in the study. Participants will be offered the opportunity to have a face-to-face, virtual or telephone interview. Interviews will be audio-recorded, transcribed verbatim and analysed using interpretative phenomenological analysis. NVivo, will be used for data management. Ethical approval for this study was granted by the Office for Research Ethics Committees Northern Ireland (REC Reference: 22/NI/0107). Scientific evidence tends to focus on measurable psychological, social and quality of life outcomes but there is limited research providing in-depth meaning and understanding of the views of individuals with renal disease who are experiencing renal cachexia. This information is urgently needed to better prepare healthcare providers and in turn support individuals with ESRD and their carers. This study will help healthcare providers understand what challenges individuals with ESRD, and their carers face in relation to cachexia and aims to inform future clinical practice guidelines and develop supportive interventions which recognise and respond to the needs of this population.
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Cuidadores , Fallo Renal Crónico , Humanos , Cuidadores/psicología , Caquexia/etiología , Caquexia/epidemiología , Calidad de Vida/psicología , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/psicología , Diálisis Renal/psicología , Investigación CualitativaRESUMEN
Currently, there are no standardized treatments for cachexia or severe wasting. There is a growing consensus advocating multimodal interventions to address the complex pathogenesis and metabolic alterations in these conditions. This review examined multimodal treatments intended to alleviate and/or stabilize cachexia and severe wasting. The objectives of this review were to 1) identify multimodal interventions for the treatment of cachexia or associated wasting syndromes in patients with a chronic illness, 2) assess the quality of these studies, and 3) assess the effectiveness of multimodal interventions. Electronic databases including PubMed, MEDLINE, EMBASE, Scopus, Web of Science, Cochrane Library, CINAHL, PEDro, OpenGrey, and clinicaltrials.org were systematically searched using both text words and MeSH (medical subject heading) terms. The literature revealed a dearth of large, well-conducted trials in this area. Fourteen trials (n = 5 cancer, n = 5 chronic obstructive pulmonary disease, n = 4 chronic kidney disease) were included in this review. A total of 1026 patients were included across all studies; sample size ranged between 21 and 138 patients. Baseline and follow-up data were collected between 6 wk and 24 mo. All demonstrated some improvement in favor of the treatment groups, in relevant measures of body composition, nutrition, biomarkers, and functionality; however, caution should be applied due to the heterogenous nature of the interventions and small sample sizes. Overall, the evidence from this review supports the role of multimodal interventions in the treatment of severe wasting. However, randomized controlled trials with a powered sample size and sufficiently lengthy interaction period are necessary to assess if multimodal interventions are effective forms of therapy for improving body composition and nutritional and physical status in patients with cachexia and wasting. The protocol for this review is registered with Prospero (ID: CRD42019124374).
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Caquexia , Neoplasias , Caquexia/terapia , Enfermedad Crónica , Terapia Combinada , Humanos , Neoplasias/complicaciones , Neoplasias/terapiaRESUMEN
This study evaluated the clinical and histopathological responses of vulval lichen sclerosus (LS) and squamous hyperplasia (SH) to photodynamic therapy (PDT). A novel bioadhesive patch containing aminolevulinic acid (ALA) at a dose of (38 mg/cm(2)) was used to treat 10 patients before irradiation with light of 630 nm. Clinical, histopathological and pathological responses to treatment were assessed at 6 weeks post-treatment. After 17 cycles of PDT, six patients reported significant symptomatic relief and no cutaneous photosensitivity. Histopathological differences were not demonstrated, but statistically significant induction of apoptosis was seen. It can be concluded that ALA-PDT patch-based formulation is pragmatic and primarily offers symptomatic management of vulval LS and SH.
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Ácido Aminolevulínico/administración & dosificación , Ácido Aminolevulínico/uso terapéutico , Fotoquimioterapia , Fármacos Fotosensibilizantes/administración & dosificación , Fármacos Fotosensibilizantes/uso terapéutico , Liquen Escleroso Vulvar/terapia , Adhesividad , Administración Cutánea , Ácido Aminolevulínico/farmacología , Femenino , Humanos , Hiperplasia/patología , Hiperplasia/terapia , Fármacos Fotosensibilizantes/farmacología , Liquen Escleroso Vulvar/patologíaRESUMEN
Cnidarians are among the simplest extant animals; however EST analyses reveal that they have a remarkably high level of genetic complexity. In this article, we show that the full diversity of metazoan signaling pathways is represented in this phylum, as are antagonists previously known only in chordates. Many of the cnidarian ESTs match genes previously known only in non-animal kingdoms. At least some of these represent ancient genes lost by all bilaterians examined so far, rather than genes gained by recent lateral gene transfer.
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Antozoos/genética , Genética de Población , Animales , Proteínas Bacterianas/genética , Genes Duplicados , Proteínas de Choque Térmico/genética , Humanos , FilogeniaRESUMEN
CONTEXT: Patients with end-stage kidney disease have a high mortality rate and disease burden. Despite this, many do not speak with health care professionals about end-of-life issues. Advance care planning is recommended in this context but is complex and challenging. We carried out a realist review to identify factors affecting its implementation. OBJECTIVES: The objectives of this study are 1) to identify implementation theories; 2) to identify factors that help or hinder implementation; and 3) to develop theory on how the intervention may work. METHODS: We carried out a systematic realist review, searching seven electronic databases: Medline, Embase, CINAHL, PsycINFO, Cochrane Library, Google Scholar, and ScienceDirect. RESULTS: Sixty-two papers were included in the review. CONCLUSION: We identified two intervention stages-1) training for health care professionals that addresses concerns, optimizes skills, and clarifies processes and 2) use of documentation and processes that are simple, individually tailored, culturally appropriate, and involve surrogates. These processes work as patients develop trust in professionals, participate in discussions, and clarify values and beliefs about their condition. This leads to greater congruence between patients and surrogates; increased quality of communication between patients and professionals; and increased completion of advance directives. Advance care planning is hindered by lack of training; administrative complexities; pressures of routine care; patients overestimating life expectancy; and when patients, family, and/or clinical staff are reluctant to initiate discussions. It is more likely to succeed where organizations treat it as core business; when the process is culturally appropriate and takes account of patient perceptions; and when patients are willing to consider death and dying with suitably trained staff.
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Planificación Anticipada de Atención , Fallo Renal Crónico , Humanos , Fallo Renal Crónico/terapiaRESUMEN
OBJECTIVE: Patients with chronic kidney disease (CKD) benefit from specialist interventions to retard progression of renal failure and prevent cardiovascular events. Certain patient groups have poor access to specialist renal services when dialysis is required. This study used a population-based laboratory database to investigate access to and timeliness of referral to renal specialists relatively early in the course of the disease. METHODS: All tests for serum creatinine and haemoglobin (Hb) A(1)c in Northern Ireland in a two-year period (2001 and 2002) were retrieved for 345,441 adults. Of these, 16,856 patients had at least one serum creatinine level above 150 micromol/L in 2001 not deemed to be due to acute renal failure (crude prevalence 1.42%). This cohort was followed until the end of 2002 and the differences in the time to referral to a specialist were assessed using Cox's proportional hazards regression. RESULTS: Diabetic patients, older patients and those living in deprived areas were significantly more likely to have serum creatinine testing, compared with non-diabetic, younger and those living in more affluent areas. Delays in referral to renal specialists for patients with raised serum creatinine levels were significantly shorter among diabetic patients, women, younger individuals, those living in rural areas, those living close to renal centres and those living in deprived areas. Overall, only 19% of diabetic patients and 6% of non-diabetic patients who had CKD had seen a renal specialist within 12 months of their index creatinine test. CONCLUSION: Contrary to other diseases, disadvantaged patients do not seem to be under-investigated for renal disease compared with their more affluent neighbours and are generally referred earlier for specialist assessment. However, the absolute rate of timely specialist assessment is low. Recent changes in referral criteria for CKD will result in more referrals and will have serious resource implications. Opportunities for health gain among patients with declining renal function are being missed, particularly among the old and those living furthest from specialist centres.
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Accesibilidad a los Servicios de Salud , Fallo Renal Crónico/prevención & control , Medicina , Derivación y Consulta , Justicia Social , Especialización , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Auditoría Médica , Persona de Mediana Edad , Irlanda del Norte , PobrezaRESUMEN
The geometry optimization of a water molecule with a novel type of energy function called FFLUX is presented, which bypasses the traditional bonded potentials. Instead, topologically-partitioned atomic energies are trained by the machine learning method kriging to predict their IQA atomic energies for a previously unseen molecular geometry. Proof-of-concept that FFLUX's architecture is suitable for geometry optimization is rigorously demonstrated. It is found that accurate kriging models can optimize 2000 distorted geometries to within 0.28 kJ mol-1 of the corresponding ab initio energy, and 50% of those to within 0.05 kJ mol-1. Kriging models are robust enough to optimize the molecular geometry to sub-noise accuracy, when two thirds of the geometric inputs are outside the training range of that model. Finally, the individual components of the potential energy are analyzed, and chemical intuition is reflected in the independent behavior of the three energy terms [Formula: see text](intra-atomic), [Formula: see text] (electrostatic) and [Formula: see text] (exchange), in contrast to standard force fields.
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BACKGROUND: Phylogenetic footprinting is the identification of functional regions of DNA by their evolutionary conservation. This is achieved by comparing orthologous regions from multiple species and identifying the DNA regions that have diverged less than neutral DNA. Vestige is a phylogenetic footprinting package built on the PyEvolve toolkit that uses probabilistic molecular evolutionary modelling to represent aspects of sequence evolution, including the conventional divergence measure employed by other footprinting approaches. In addition to measuring the divergence, Vestige allows the expansion of the definition of a phylogenetic footprint to include variation in the distribution of any molecular evolutionary processes. This is achieved by displaying the distribution of model parameters that represent partitions of molecular evolutionary substitutions. Examination of the spatial incidence of these effects across regions of the genome can identify DNA segments that differ in the nature of the evolutionary process. RESULTS: Vestige was applied to a reference dataset of the SCL locus from four species and provided clear identification of the known conserved regions in this dataset. To demonstrate the flexibility to use diverse models of molecular evolution and dissect the nature of the evolutionary process Vestige was used to footprint the Ka/Ks ratio in primate BRCA1 with a codon model of evolution. Two regions of putative adaptive evolution were identified illustrating the ability of Vestige to represent the spatial distribution of distinct molecular evolutionary processes. CONCLUSION: Vestige provides a flexible, open platform for phylogenetic footprinting. Underpinned by the PyEvolve toolkit, Vestige provides a framework for visualising the signatures of evolutionary processes across the genome of numerous organisms simultaneously. By exploiting the maximum-likelihood statistical framework, the complex interplay between mutational processes, DNA repair and selection can be evaluated both spatially (along a sequence alignment) and temporally (for each branch of the tree) providing visual indicators to the attributes and functions of DNA sequences.
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Biología Computacional/métodos , Interpretación Estadística de Datos , Algoritmos , Animales , Proteína BRCA1/genética , Secuencia de Bases , Codón , Simulación por Computador , ADN/química , Reparación del ADN , Evolución Molecular , Genoma , Humanos , Funciones de Verosimilitud , Modelos Biológicos , Modelos Estadísticos , Filogenia , Lenguajes de Programación , Secuencias Reguladoras de Ácidos Nucleicos , Alineación de Secuencia , Análisis de Secuencia de ADN , Análisis de Secuencia de Proteína , Programas Informáticos , Especificidad de la Especie , Factores de TiempoRESUMEN
BACKGROUND: It is well recognised that medical students and junior doctors find fluid prescription a challenging topic. This study was designed to gain a greater understanding of the experiences that medical students face related to learning about fluid prescribing. METHODS: A qualitative approach, using focus groups, was employed in this research. Final-year medical students in academic year 2011-12 at Queen's University Belfast were invited to participate during their 'Assistantship' placement in March 2012. Discussions in focus groups, consisting of between six and eight students, were recorded and transcribed verbatim. The research team, consisting of three separate investigators, conducted thematic analysis independently. A final consensus regarding emerging themes was reached by discussion within the whole research team. Medical students and junior doctors find fluid prescription a challenging topic RESULTS: Five prominent themes emerged: 'Teaching experience: a disruptive variation'; 'Curricular disconnections'; 'The driving test: Theory-practice transformation'; 'Role modelling: which standard to aspire to?'; and finally 'Reconciling the perceived risk'. DISCUSSION: This re search provided insights into medical students' opinions of the teaching practices and learning experiences related to fluid prescribing. The learning of prescribing skills is complex and contextual. In the development of such skills, medical students are often exposed to conflicting educational experiences that challenge the novice learner in making judgements on best prescribing practice. This study adds to the body of evidence that fluid prescription is a difficult topic, and has generated a number of multifaceted and strategic recommendations to potentially improve fluid prescription teaching.