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OBJECTIVES: This study aims to systematically review the existing literature and critically appraise the evidence of genome-wide association studies (GWAS) on periodontitis. This study also aims to synthesise the findings of genetic risk variants of periodontitis from included GWAS. METHODS: A systematic search was conducted on PubMed, GWAS Catalog, MEDLINE, GLOBAL HEALTH and EMBASE via Ovid for GWAS on periodontitis. Only studies exploring single-nucleotide polymorphisms(SNPs) associated with periodontitis were eligible for inclusion. The quality of the GWAS was assessed using the Q-genie tool. Information such as study population, ethnicity, genomic data source, phenotypic characteristics(definition of periodontitis), and GWAS methods(quality control, analysis stages) were extracted. SNPs that reached conventional or suggestive GWAS significance level(5e-8 or 5e-06) were extracted and synthesized. RESULTS: A total of 15 good-quality GWAS on periodontitis were included (Q-genie scores ranged from 38-50). There were huge heterogeneities among studies. There were 11 identified risk SNPs (rs242016, rs242014, rs10491972, rs242002, rs2978951, rs2738058, rs4284742, rs729876, rs149133391, rs1537415, rs12461706) at conventional GWAS significant level (p<5x10-8), and 41 at suggestive level (p<5x10-6), but no common SNPs were found between studies. Three SNPs (rs4284742 [G], rs11084095 [A], rs12461706 [T]) from three large studies were from the same gene region-SIGLEC5. CONCLUSION: GWAS of periodontitis showed high heterogeneity of methodology used and provided limited SNPs statistics, making identifying reliable risk SNPs challenging. A clear guidance in dental research with requirement of expectation to make GWAS statistics available to other investigators are needed.
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Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Periodontitis , Polimorfismo de Nucleótido Simple , Humanos , Periodontitis/genéticaRESUMEN
OBJECTIVE: To investigate the bidirectional association between oral diseases and cognitive function comprehensively. SUBJECTS AND METHODS: This cross sectional study utilized data from the National Health and Nutrition Examination Survey. Oral diseases include periodontitis, dental caries, and tooth loss (end point of oral disease resulting in tooth extraction). Cognitive function included three domains: memory, processing speed, and executive function. A global cognitive score was then derived from sum of the three cognitive domains. Oral cognition associations were examined using various statistical models: (1) Regress oral disease on cognitive function; (2) Regress cognitive function on oral disease; and (3) Structural equation modelling treating cognition and oral disease as latent variables. RESULTS: There were 2508 participants aged 60+ who had both oral and cognitive information. Associations between various oral disease and global cognitive score were observed (Odds ratio ORcog->periodontitis 0.95, 95% Confidence Interval [0.92, 0.99]; ßcog->caries -0.13, [-0.23, -0.04]; ßcog->tooth loss -0.03 [-0.04, -0.01]; ßtooth loss->cog -0.04 [-0.06, -0.02]; ßcaries->cog -0.03 [-0.06, -0.01]; ßperiodontitis->cog -0.39 [-0.69, -0.10]). Significant correlation was also found between these oral disease and cognitive function using structural equation model (r -0.22, [-0.34, -0.10]). CONCLUSIONS: This study found robust bidirectional associations between oral disease and cognitive function using various modelling approaches among the aging population.
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Ex vivo shoulder motion simulators are commonly used to study shoulder biomechanics but are often limited to performing simple planar motions at quasi-static speeds using control architectures that do not allow muscles to be deactivated. The purpose of this study was to develop an open-loop tendon excursion controller with iterative learning and independent muscle control to simulate complex multiplanar motion at functional speeds and allow for muscle deactivation. The simulator performed abduction/adduction, faceted circumduction, and abduction/adduction (subscapularis deactivation) using a cadaveric shoulder with an implanted reverse total shoulder prosthesis. Kinematic tracking accuracy and repeatability were assessed using maximum absolute error (MAE), root mean square error (RMSE), and average standard deviation (ASD). During abduction/adduction and faceted circumduction, the RMSE did not exceed 0.3, 0.7, and 0.8 degrees for elevation, plane of elevation, and axial rotation, respectively. During abduction/adduction, the ASD did not exceed 0.2 degrees. Abduction/adduction (subscapularis deactivation) resulted in a loss of internal rotation, which could not be restored at low elevation angles. This study presents a novel control architecture, which can accurately simulate complex glenohumeral motion. This simulator will be used as a testing platform to examine the effect of shoulder pathology, treatment, and rehabilitation on joint biomechanics during functional shoulder movements.
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BACKGROUND: Between 1 June 2012 and 31 December 2020, there were 49 cases considered by the Medical Practitioners Tribunal Service where a doctor's misconduct involved child pornography. The determinations concerning these cases provided the data for analysis. FINDINGS: In 47/49 (96%) the regulatory outcome was erasure from the GMC's Medical Register, ending the doctor's career. 12 doctors had been imprisoned for 1 to 20 years, and 19 given suspended prison sentences. In 33/49 (67%) cases the indecent images of children included one or more video recordings. Some of these were of children (including very young infants) being raped, sometimes for prolonged periods, the video recordings sometimes indicating that the child could be seen to be in extreme pain. INTERPRETATION: The high proportion of erasures reflected the gravity of these cases, coupled with the fundamental incompatibility of sexual misconduct involving children with a career in medicine.
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Literatura Erótica , Médicos , Humanos , Niño , Conducta Sexual , Personal de Salud , Reino Unido , Mala Conducta ProfesionalRESUMEN
In the period 1 January 2012 to 30 June 2020, 76 doctors whose names/entries had been erased from the UK Medical Register by a disciplinary tribunal applied for restoration, and 23 out of 76 (30.3%) applications granted. In 5 of the 53 of those refused restoration, the tribunal suspended indefinitely the right to make further applications. The most frequent reasons for refusal were failure to demonstrate insight (seen in 96%), failure to demonstrate remediation (seen in 79%), and failure to demonstrate that knowledge and skills were up to date (24.5%). Success was more common in UK graduate applications (14/29 - 48.3%) than non-UK graduate applications (9/37 - 24.3%), and in those legally represented (16/29 - 55.2%) than in those without legal representation (7/29 - 24.1%), but the data does not indicate the reasons for these differences. Disciplinary erasure need not necessarily be for life as doctors who learn from their experience, change their ways, and provide evidence of genuine insight and remediation along with up to date knowledge and skills can successfully be reinstated on the register.
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Licencia Médica/legislación & jurisprudencia , Médicos , Mala Conducta Profesional/legislación & jurisprudencia , Práctica Profesional/normas , Sistema de Registros , Humanos , Reino UnidoRESUMEN
Health and social care regulators in their guidance to pre-registration students and registrants emphasise the importance of honesty and integrity. While the term honesty is generally understood, the meaning of integrity is less familiar, and for many years, there has been disagreement as to whether there is any difference between "dishonesty" and "lack of integrity." To explore the possible application of lack of integrity to student behaviour, we present cases that illustrate what might be considered to demonstrate a lack of integrity. As with other allegations, if there is to be a finding of fact then an allegation of lack of integrity and its basis need to be clearly set out in advance of any hearing. If the term lack of integrity is to be useful, guidance from the regulators will need to explain the meaning of the term. If, however, agreement as to the meaning cannot be reached, maybe the term "integrity" should no longer be a standard accompaniment to the term "honesty."
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Conducta , Carácter , Principios Morales , Estudiantes de Medicina/psicología , Decepción , Ética Profesional , Femenino , Humanos , MasculinoRESUMEN
We review selected aeropolitical issues that may impact the international aviation sector post-COVID-19. Consideration regarding ICAO's role in coordinating safety provisions using existing frameworks will be important. Issues relating to national airline bailouts and recapitalisation as well as international ownership are also explored. We offer several further, as yet unanswerable, questions about future aeropolitical issues, including how ICAO will continue to address the crisis, implications for air services capacity restrictions, the impact of deglobalisation and the question of state aid for national carriers and other parts of the aviation system.
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MX2 protein is a dynamin-like GTPase2 that has recently been identified as an interferon-induced restriction factor of HIV-1 and other primate lentiviruses. A single nucleotide polymorphism (SNP), rs45430, in an intron of the MX2 gene, was previously reported as a novel melanoma susceptibility locus in genome-wide association studies. Functionally, however, it is still unclear whether and how MX2 contributes to melanoma susceptibility and tumorigenesis. Here, we show that MX2 is differentially expressed in melanoma tumors and cell lines, with most metastatic cell lines showing lower MX2 expression than primary melanoma cell lines and melanocytes. Furthermore, high expression of MX2 RNA in primary melanoma tumors is associated with better patient survival. Overexpression of MX2 reduces in vivo proliferation partially through inhibition of AKT activation, suggesting that it can act as a tumor suppressor in melanoma. However, we have also identified a subset of melanoma cell lines with high endogenous MX2 expression where downregulation of MX2 leads to reduced proliferation. In these cells, MX2 downregulation interfered with DNA replication and cell cycle processes. Collectively, our data for the first time show that MX2 is functionally involved in the regulation of melanoma proliferation but that its function is context-dependent.
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Ciclo Celular , Melanoma/patología , Proteínas de Resistencia a Mixovirus/metabolismo , Animales , Ciclo Celular/genética , Línea Celular Tumoral , Proliferación Celular , Regulación hacia Abajo/genética , Regulación Neoplásica de la Expresión Génica , Humanos , Estimación de Kaplan-Meier , Melanoma/genética , Ratones Desnudos , Proteínas de Resistencia a Mixovirus/genética , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de SeñalRESUMEN
Background: Inhibitory κB kinases (IKKs) play a key role in modulating proinflammatory and growth stimulating signals through their regulation of the nuclear factor κB (NF-κB) cascade. Therefore, the level of expression of IKKs represents a viable prognostic predictor with regard to various pathological processes. The prognostic value of IKKs expression in gastric cancer remains unclear. Methods: We used the 'Kaplan-Meier plotter' (KM plotter) online database, to explore the predictive prognostic value of individual IKKs members' mRNA expression to overall survival (OS) in different clinical data including pathological staging, histology, and therapies employed. Results: Our results revealed that a higher mRNA expression of inhibitor of NF-κB kinase subunit α (IKKα) was correlated to better OS, whereas higher mRNA expression of IKKß, inhibitor of NF-κB kinase subunit γ (IKKγ), inhibitor of NF-κB kinase subunit ε (IKKε), and suppressor of IKKε (SIKE) were generally correlated to unfavorable OS in gastric cancer. Increased mRNA expression of IKKε also showed better outcomes in stage IV gastric cancer. Further a correlation between elevated levels of mRNA expression of both IKKε and SIKE was found to have favorable OS in diffuse type gastric cancer. It was also revealed that high expression of SIKE had favorable OS when treated with other adjuvant therapies, while worse OS when treated only with 5FU therapy. Conclusion: Our results suggest that mRNA expression of individual IKKs and SIKE are associated with unique prognostic significance and may act as valuable prognostic biomarkers and potential targets for future therapeutic interventions in gastric cancer.
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Biomarcadores de Tumor/genética , Regulación Neoplásica de la Expresión Génica , Quinasa I-kappa B/genética , Péptidos y Proteínas de Señalización Intracelular/genética , Proteínas Serina-Treonina Quinasas/genética , ARN Mensajero/genética , Neoplasias Gástricas/genética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores de Tumor/metabolismo , Bases de Datos Factuales , Progresión de la Enfermedad , Femenino , Humanos , Quinasa I-kappa B/metabolismo , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Isoenzimas/genética , Isoenzimas/metabolismo , Estimación de Kaplan-Meier , Masculino , FN-kappa B/genética , FN-kappa B/metabolismo , Estadificación de Neoplasias , Pronóstico , Proteínas Serina-Treonina Quinasas/metabolismo , ARN Mensajero/metabolismo , Transducción de Señal , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/mortalidad , Quinasa de Factor Nuclear kappa BRESUMEN
Metastasis is the leading cause of death in patients with advanced melanoma, yet the somatic alterations that aid tumour cell dissemination and colonisation are poorly understood. Here, we deploy comparative genomics to identify and validate clinically relevant drivers of melanoma metastasis. To do this, we identified a set of 976 genes whose expression level was associated with a poor outcome in patients from two large melanoma cohorts. Next, we characterised the genomes and transcriptomes of mouse melanoma cell lines defined as weakly metastatic, and their highly metastatic derivatives. By comparing expression data between species, we identified lunatic fringe (LFNG), among 28 genes whose expression level is predictive of poor prognosis and whose altered expression is associated with a prometastatic phenotype in mouse melanoma cells. CRISPR/Cas9-mediated knockout of Lfng dramatically enhanced the capability of weakly metastatic melanoma cells to metastasise in vivo, a phenotype that could be rescued with the Lfng cDNA. Notably, genomic alterations disrupting LFNG are found exclusively in human metastatic melanomas sequenced as part of The Cancer Genome Atlas. Using comparative genomics, we show that LFNG expression plays a functional role in regulating melanoma metastasis.
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Glicosiltransferasas/metabolismo , Melanoma/genética , Melanoma/secundario , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/patología , Animales , Línea Celular Tumoral , Estudios de Cohortes , Genómica , Glicosiltransferasas/genética , Humanos , Neoplasias Pulmonares/secundario , Melanoma/patología , Melanoma Experimental/genética , Melanoma Experimental/patología , Ratones , Ratones Endogámicos C3H , Ratones Endogámicos C57BL , Metástasis de la Neoplasia , TranscriptomaRESUMEN
OBJECTIVE: Since 2012, all community care recipients in New Zealand have undergone a standardised needs assessment using the Home Care International Residential Assessment Instrument (interRAI-HC). This study describes the national interRAI-HC population, assesses its data quality and evaluates its ability to be matched. METHODS: The interRAI-HC instrument elicits information on 236 questions over 20 domains; conducted by 1,800+ trained health professionals. Assessments between 1 July 2012 and 30 June 2014 are reported here. Stratified by age, demographic characteristics were compared to 2013 Census estimates and selected health profiles described. Deterministic matching to the Ministry of Health's mortality database was undertaken. RESULTS: Overall, 51,232 interRAI-HC assessments were conducted, with 47,714 (93.1%) research consent from 47,236 unique individuals; including 2,675 Maori and 1,609 Pacific people. Apart from height and weight, data validity and reliability were high. A 99.8% match to mortality data was achieved. CONCLUSIONS: The interRAI-HC research database is large and ethnically diverse, with high consent rates. Its generally good psychometric properties and ability to be matched enhances its research utility. IMPLICATIONS: This national database provides a remarkable opportunity for researchers to better understand older persons' health and health care, so as to better sustain older people in their own homes.
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Bases de Datos Factuales/estadística & datos numéricos , Evaluación Geriátrica/métodos , Evaluación Geriátrica/estadística & datos numéricos , Características de la Residencia , Actividades Cotidianas , Anciano , Anciano de 80 o más Años , Estudios Transversales , Femenino , Humanos , Masculino , Evaluación de Necesidades , Nueva Zelanda , Psicometría , Reproducibilidad de los ResultadosRESUMEN
Medical students who exhibit severe forms of adverse behaviour (including criminal matters), sometimes accompanied by mental health problems, are likely to be seen by their medical school's fitness to practise committee, a topic explained in this review.
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Crimen/estadística & datos numéricos , Trastornos Mentales/epidemiología , Mala Conducta Profesional/estadística & datos numéricos , Facultades de Medicina/normas , Estudiantes de Medicina/psicología , Humanos , Reino UnidoRESUMEN
In the last five years, 2010-2014, there have been 17 instances when an application for provisional registration by a U.K. medical graduate was refused by the General Medical Council because the Registrar considered that the applicant's fitness to practise was impaired. While this number is small, the fact that this can happen is largely unappreciated by medical students and their teachers, the prevailing false assumption being that passing finals and graduation is the final hurdle before taking up a Foundation Programme post. It is a poorly recognised fact that just because a university fitness to practise committee has concluded that a student is fit to practise there is no guarantee that the General Medical Council will come to the same decision. This paper explains the reasons for these refusals and makes suggestions for students and medical schools.
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Licencia Médica/legislación & jurisprudencia , Competencia Clínica/legislación & jurisprudencia , Competencia Clínica/normas , Conducta Criminal , Fraude/legislación & jurisprudencia , Humanos , Licencia Médica/normas , Inhabilitación Médica/legislación & jurisprudencia , Competencia Profesional/legislación & jurisprudencia , Competencia Profesional/normas , Estudiantes de Medicina , Reino UnidoRESUMEN
Recent studies suggest that normal-hearing listeners maintain robust speech intelligibility despite severe degradations of amplitude-modulation (AM) cues, by using temporal-envelope information recovered from broadband frequency-modulation (FM) speech cues at the output of cochlear filters. This study aimed to assess whether cochlear damage affects this capacity to reconstruct temporal-envelope information from FM. This was achieved by measuring the ability of 40 normal-hearing listeners and 41 listeners with mild-to-moderate hearing loss to identify syllables processed to degrade AM cues while leaving FM cues intact within three broad frequency bands spanning the range 65-3,645 Hz. Stimuli were presented at 65 dB SPL for both normal-hearing listeners and hearing-impaired listeners. They were presented as such or amplified using a modified half-gain rule for hearing-impaired listeners. Hearing-impaired listeners showed significantly poorer identification scores than normal-hearing listeners at both presentation levels. However, the deficit shown by hearing-impaired listeners for amplified stimuli was relatively modest. Overall, hearing-impaired data and the results of a simulation study were consistent with a poorer-than-normal ability to reconstruct temporal-envelope information resulting from a broadening of cochlear filters by a factor ranging from 2 to 4. These results suggest that mild-to-moderate cochlear hearing loss has only a modest detrimental effect on peripheral, temporal-envelope reconstruction mechanisms.
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Pérdida Auditiva Sensorineural/fisiopatología , Percepción del Habla/fisiología , Adulto , Factores de Edad , Anciano , Señales (Psicología) , Humanos , Persona de Mediana Edad , Adulto JovenRESUMEN
Parameter identification methods are used to find optimal parameter values to fit models to measured data. The single integral method was defined as a simple and robust parameter identification method. However, the method did not necessarily converge to optimum parameter values. Thus, the iterative integral method (IIM) was developed. IIM will be compared to a proprietary nonlinear-least-squares-based Levenberg-Marquardt parameter identification algorithm using a range of reasonable starting values. Performance is assessed by the rate and accuracy of convergence for an exemplar two parameters insulin pharmacokinetic model, where true values are known a priori. IIM successfully converged to within 1% of the true values in all cases with a median time of 1.23 s (IQR 0.82-1.55 s; range 0.61-3.91 s). The nonlinear-least-squares method failed to converge in 22% of the cases and had a median (successful) convergence time of 3.29 s (IQR 2.04-4.89 s; range 0.42-44.9 s). IIM is a stable and relatively quick parameter identification method that can be applied in a broad variety of model configurations. In contrast to most established methods, IIM is not susceptible to local minima and is thus, starting point and operator independent.
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Interpretación Estadística de Datos , Hipoglucemiantes/farmacocinética , Insulina/farmacocinética , Algoritmos , Humanos , Resistencia a la Insulina/fisiología , Modelos BiológicosRESUMEN
BACKGROUND: Evidence suggests that doctors and medical students use different strategies to evaluate unprofessional behaviour. Anecdotal evidence suggests that the public and profession may judge misdemeanours differently. AIMS: To explore whether members of the public will judge examples of medical student misconduct more harshly than medical students and doctors. METHODS: This was a pilot cross-sectional survey of the public, medical students and doctors. For 10 hypothetical examples of medical student misconduct and one of appropriate conduct in a questionnaire, participants were asked to (1) indicate the level of acceptability and (2) to choose the sanction they considered most appropriate for each. RESULTS: Overall, doctors were harsher than students and the public were harsher than doctors in their choice of sanctions. The most lenient outcomes were selected by students for deception in an examination, nonattendance and dishonesty. The most punitive were chosen by the public for forgery, criminal conviction, misrepresenting qualifications, alcohol and drug misuse and lack of insight. CONCLUSIONS: The public judge misdemeanours among medical students more harshly than do medical students and medical professionals. This implies that views of lay members should be sought by medical schools when promoting professionalism and considering cases of medical student misconduct.
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Actitud del Personal de Salud , Médicos/psicología , Mala Conducta Profesional , Opinión Pública , Estudiantes de Medicina/psicología , Estudios Transversales , Inglaterra , Humanos , Proyectos PilotoRESUMEN
Nursing students whose behaviour or health raises serious questions about their fitness to enter the profession may have to appear before a fitness to practise committee. One possible outcome could be termination of the student's studies. This article provides guidance on how to support students during fitness to practise hearings.
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Estudiantes de Enfermería , Competencia Clínica , Competencia Profesional , Medidas de Seguridad , Sociedades de Enfermería , Reino UnidoRESUMEN
Since 2009, all schools of nursing have been required to establish a fitness to practise committee to consider any pre-registration student health or character issues (Nursing and Midwifery Council, 2008). In 2009, fitness to practice standards were published (NMC, 2009a). This article outlines how fitness to practise procedures apply to nursing and midwifery students in the U.K. and explains the key differences between how they are applied to trainees and to registered nurses.
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Bachillerato en Enfermería/organización & administración , Competencia Profesional/normas , Mala Conducta Profesional , Comité de Profesionales/organización & administración , Facultades de Enfermería/organización & administración , Estudiantes de Enfermería , Decepción , Humanos , Trastornos Mentales/prevención & control , Plagio , Guías de Práctica Clínica como Asunto , Competencia Profesional/legislación & jurisprudencia , Mala Conducta Profesional/legislación & jurisprudencia , Criterios de Admisión Escolar , Estudiantes de Enfermería/legislación & jurisprudencia , Trastornos Relacionados con Sustancias/prevención & control , Reino UnidoRESUMEN
BACKGROUND: The aim was to explore the structures for managing student fitness to practise hearings in medical schools in the UK. We surveyed by email the named fitness to practise leads of all full members of the UK Medical Schools Council with a medical undergraduate programme. We asked whether student fitness to practise cases were considered by a committee/panel dedicated to medicine, or by one which also considered other undergraduate health and social care students. FINDINGS: All 31 medical schools responded. 19 medical schools had a fitness to practise committee dealing with medical students only. Three had a committee that dealt with students of medicine and dentistry. One had a committee that dealt with students of medicine and veterinary medicine. Eight had a committee that dealt with students of medicine and two or more other programmes, such as dentistry, nursing, midwifery, physiotherapy, dietetics, social work, pharmacy, psychology, audiology, speech therapy, operating department practice, veterinary medicine and education. CONCLUSION: All 31 UK medical schools with undergraduate programmes have a fitness to practise committee to deal with students whose behaviour has given rise to concern about their fitness to practise. The variation in governance structures for student fitness to practise committees/panels can in part be explained by variations in University structures and the extent to which Universities co-manage undergraduate medicine with other courses.