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1.
Br J Surg ; 108(6): 659-666, 2021 06 22.
Artículo en Inglés | MEDLINE | ID: mdl-34157089

RESUMEN

BACKGROUND: Frailty may explain why some older patients having vascular surgery are at high risk of adverse outcomes. The Hospital Frailty Risk Score (HFRS) has been designed specifically for use with administrative data and has three categories of frailty risk (low, intermediate and high). The aim of this study was to evaluate the HFRS in predicting mortality, and hospital use in older patients undergoing vascular surgery. METHODS: Routinely collected hospital data linked to death records were analysed for all patients aged 75 years or older who had undergone either endovascular or open vascular surgery between 2010 and 2012 in New South Wales, Australia. Multilevel logistic regression models were used to compare outcomes adjusted for patient and procedural factors, with and without frailty. RESULTS: Some 9752 patients were identified, of whom 1719 (17·6 per cent) had a high-risk HFRS. Patients in the high-risk frailty category had an adjusted odds ratio for death by 30 days after surgery of 4·15 (95 per cent c.i. 2·99 to 5·76) compared with those in the low-risk frailty category, and a similarly increased odds of death by 2 years (odds ratio 4·27, 3·69 to 4·95). Adding the HFRS to a model adjusted for age, sex, co-morbidity score, socioeconomic status, previous hospitalization and vascular procedure type improved the prediction of 2-year mortality and prolonged hospital stay, but there was minimal improvement for 30-day mortality and readmission. CONCLUSION: Adjusting for the HFRS in addition to other patient and procedural risk factors provided greater discrimination of outcomes in this cohort of older patients undergoing vascular surgery.


Asunto(s)
Fragilidad/diagnóstico , Procedimientos Quirúrgicos Vasculares/estadística & datos numéricos , Anciano , Procedimientos Endovasculares/efectos adversos , Procedimientos Endovasculares/mortalidad , Procedimientos Endovasculares/estadística & datos numéricos , Femenino , Fragilidad/complicaciones , Fragilidad/mortalidad , Humanos , Modelos Logísticos , Masculino , Pronóstico , Medición de Riesgo , Resultado del Tratamiento , Procedimientos Quirúrgicos Vasculares/efectos adversos , Procedimientos Quirúrgicos Vasculares/mortalidad
2.
Circulation ; 137(4): 354-363, 2018 01 23.
Artículo en Inglés | MEDLINE | ID: mdl-29138293

RESUMEN

BACKGROUND: Efforts to safely reduce length of stay for emergency department patients with symptoms suggestive of acute coronary syndrome (ACS) have had mixed success. Few system-wide efforts affecting multiple hospital emergency departments have ever been evaluated. We evaluated the effectiveness of a nationwide implementation of clinical pathways for potential ACS in disparate hospitals. METHODS: This was a multicenter pragmatic stepped-wedge before-and-after trial in 7 New Zealand acute care hospitals with 31 332 patients investigated for suspected ACS with serial troponin measurements. The implementation was a clinical pathway for the assessment of patients with suspected ACS that included a clinical pathway document in paper or electronic format, structured risk stratification, specified time points for electrocardiographic and serial troponin testing within 3 hours of arrival, and directions for combining risk stratification and electrocardiographic and troponin testing in an accelerated diagnostic protocol. Implementation was monitored for >4 months and compared with usual care over the preceding 6 months. The main outcome measure was the odds of discharge within 6 hours of presentation RESULTS: There were 11 529 participants in the preimplementation phase (range, 284-3465) and 19 803 in the postimplementation phase (range, 395-5039). Overall, the mean 6-hour discharge rate increased from 8.3% (range, 2.7%-37.7%) to 18.4% (6.8%-43.8%). The odds of being discharged within 6 hours increased after clinical pathway implementation. The odds ratio was 2.4 (95% confidence interval, 2.3-2.6). In patients without ACS, the median length of hospital stays decreased by 2.9 hours (95% confidence interval, 2.4-3.4). For patients discharged within 6 hours, there was no change in 30-day major adverse cardiac event rates (0.52% versus 0.44%; P=0.96). In these patients, no adverse event occurred when clinical pathways were correctly followed. CONCLUSIONS: Implementation of clinical pathways for suspected ACS reduced the length of stay and increased the proportions of patients safely discharged within 6 hours. CLINICAL TRIAL REGISTRATION: URL: https://www.anzctr.org.au/ (Australian and New Zealand Clinical Trials Registry). Unique identifier: ACTRN12617000381381.


Asunto(s)
Síndrome Coronario Agudo/diagnóstico , Servicio de Cardiología en Hospital/normas , Vías Clínicas/normas , Servicio de Urgencia en Hospital/normas , Hospitalización , Mejoramiento de la Calidad/normas , Indicadores de Calidad de la Atención de Salud/normas , Síndrome Coronario Agudo/sangre , Síndrome Coronario Agudo/epidemiología , Síndrome Coronario Agudo/terapia , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Toma de Decisiones Clínicas , Electrocardiografía , Femenino , Humanos , Tiempo de Internación , Masculino , Persona de Mediana Edad , Nueva Zelanda/epidemiología , Valor Predictivo de las Pruebas , Prevalencia , Pronóstico , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Troponina/sangre
3.
Osteoporos Int ; 28(3): 1047-1052, 2017 03.
Artículo en Inglés | MEDLINE | ID: mdl-27844134

RESUMEN

Data were gathered with regard to mortality after fractures in 1006 younger patients. Results revealed that major osteoporotic fractures of the hip and humerus and drinking alcohol to excess were related to an increased risk of mortality. INTRODUCTION: Major osteoporotic fractures are known to be associated with increased mortality in older individuals. It is less clear whether this also applies to younger patients. METHODS: Date were gathered regarding patient demographics, fracture pattern, mechanism of injury, as well as smoking and alcohol intake at the time of injury in consecutive patients aged between 40 and 55 who presented to a UK trauma centre over a 12-month period. Mortality data was taken from the electronic patient records and was cross referenced with data from the General Registrar Office of Scotland. Cox regression analysis was used to identify independent predictors of mortality after adjusting for confounding factors. RESULTS: The study cohort consisted of 1006 patients, of which 53% were male. The commonest mechanism of injury was a fall. We obtained complete data regarding mortality for all patients at a median of 5.4 years (inter-quartile range 5.1 to 5.6). During this period, 46 patients were identified as being deceased. The overall standardised mortality ratio for the cohort was substantially increased relative to the age and sex matched general population with a ratio of 3.89 (95% confidence intervals (CI) 1.59 to 6.19). Alcohol excess and fractures involving the humerus and the neck of femur were independent predictors of mortality. CONCLUSIONS: Young individuals with hip and humerus fractures have a significantly increased mortality risk after their injury relative to the general population. The results of our study suggest that this may be in part due to a high prevalence of alcohol excess.


Asunto(s)
Fracturas Osteoporóticas/mortalidad , Accidentes por Caídas/mortalidad , Adulto , Factores de Edad , Alcoholismo/complicaciones , Alcoholismo/mortalidad , Femenino , Fracturas de Cadera/etiología , Fracturas de Cadera/mortalidad , Humanos , Fracturas del Húmero/etiología , Fracturas del Húmero/mortalidad , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Fracturas Osteoporóticas/etiología , Factores de Riesgo , Escocia/epidemiología , Fumar/efectos adversos , Fumar/epidemiología
6.
Vascular ; 24(4): 435-45, 2016 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-26223531

RESUMEN

PURPOSE: This study is a systematic review to determine the types of outcomes reported in abdominal aortic aneurysm (AAA) studies of patients aged 80 and over. Specifically, it determines the types of patient-centered outcomes reported. METHOD: MEDLINE and EMBASE were searched from 2000 to 2014 for studies on AAA surgery with outcome data on patients aged 80 and over. Outcomes were categorized according to Donabedian's framework for health quality indicators, with further classification as procedural, complication, resource or patient-centered outcome indicators. FINDINGS: Forty studies were reviewed. Patient-centered outcomes were infrequently reported (13%, n=5), with limited outcomes specifically relevant to older patients. No studies reported physical function, activities of daily living or cognition using validated assessment methods. Short-term mortality (95%, n=38) and complications (85%, n=34) were reported most frequently. CONCLUSION: Reporting of aortic surgery outcomes in patients aged 80 and over requires a focus upon outcomes of primary importance to people of this age.


Asunto(s)
Aneurisma de la Aorta Abdominal/cirugía , Ensayos Clínicos como Asunto/métodos , Procedimientos Endovasculares , Determinación de Punto Final , Evaluación del Resultado de la Atención al Paciente , Evaluación de Procesos, Atención de Salud , Procedimientos Quirúrgicos Vasculares , Factores de Edad , Anciano de 80 o más Años , Aneurisma de la Aorta Abdominal/diagnóstico por imagen , Aneurisma de la Aorta Abdominal/mortalidad , Procedimientos Endovasculares/efectos adversos , Procedimientos Endovasculares/mortalidad , Femenino , Humanos , Masculino , Factores de Riesgo , Resultado del Tratamiento , Procedimientos Quirúrgicos Vasculares/efectos adversos , Procedimientos Quirúrgicos Vasculares/mortalidad
7.
Heredity (Edinb) ; 115(2): 153-64, 2015 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-25806545

RESUMEN

Hybrid zones provide an opportunity to study the effects of selection and gene flow in natural settings. We employed nuclear microsatellites (single sequence repeat (SSR)) and candidate gene single-nucleotide polymorphism markers (SNPs) to characterize the genetic architecture and patterns of interspecific gene flow in the Picea glauca × P. engelmannii hybrid zone across a broad latitudinal (40-60 degrees) and elevational (350-3500 m) range in western North America. Our results revealed a wide and complex hybrid zone with broad ancestry levels and low interspecific heterozygosity, shaped by asymmetric advanced-generation introgression, and low reproductive barriers between parental species. The clinal variation based on geographic variables, lack of concordance in clines among loci and the width of the hybrid zone points towards the maintenance of species integrity through environmental selection. Congruency between geographic and genomic clines suggests that loci with narrow clines are under strong selection, favoring either one parental species (directional selection) or their hybrids (overdominance) as a result of strong associations with climatic variables such as precipitation as snow and mean annual temperature. Cline movement due to past demographic events (evidenced by allelic richness and heterozygosity shifts from the average cline center) may explain the asymmetry in introgression and predominance of P. engelmannii found in this study. These results provide insights into the genetic architecture and fine-scale patterns of admixture, and identify loci that may be involved in reproductive barriers between the species.


Asunto(s)
Flujo Génico , Hibridación Genética , Picea/genética , Colombia Británica , ADN de Plantas/genética , Evolución Molecular , Sitios Genéticos , Genética de Población , Genotipo , Geografía , Repeticiones de Microsatélite , Modelos Genéticos , Polimorfismo de Nucleótido Simple , Análisis de Secuencia de ADN , Sudoeste de Estados Unidos
9.
Scott Med J ; 58(3): 143-8, 2013 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-23960052

RESUMEN

INTRODUCTION: Undiagnosed and untreated scaphoid fractures have poorer outcomes and many patients are unnecessarily immobilised for prolonged periods of time to avoid missing occult injuries. Magnetic resonance imaging has a high sensitivity and specificity in detecting occult scaphoid fractures, but many units do not routinely use this imaging modality in the diagnostic pathway. We aimed to determine the patterns of suspected scaphoid injuries, report the process of care, and calculate the costs involved in their management. METHODS: We prospectively identified all adult patients referred to fracture clinic at the Royal Infirmary of Edinburgh with a scaphoid-related injury, between October 2007 and September 2008. Clinical notes were examined retrospectively. We defined three injury groups: true fractures, occult fractures, and suspected scaphoid injuries. We analysed patient demographics, treatment timelines, and the treatment costs involved. RESULTS: Fracture clinic received 537 scaphoid-related referrals. There were 87 true fractures, 43 occult fractures, and 407 suspected injuries, incurring average treatment costs of £1,173, £773, and £384 respectively. Occult fractures accounted for 33% of all confirmed scaphoid fractures. The majority of scaphoid-related referrals (76%) were never proven to have a scaphoid fracture, and many were unnecessarily immobilised. The costs involved in the treatment of suspected scaphoid injuries were found to be higher than the cost of magnetic resonance imaging (£97). CONCLUSION: In this group of suspected scaphoid injury, we believe the introduction of an early magnetic resonance imaging protocol would lead to an earlier definitive diagnosis and potentially a more cost-effective service.


Asunto(s)
Servicio de Urgencia en Hospital/economía , Fracturas Óseas/economía , Fracturas Cerradas/economía , Imagen por Resonancia Magnética , Hueso Escafoides/lesiones , Adulto , Análisis Costo-Beneficio , Femenino , Fracturas Óseas/diagnóstico , Fracturas Cerradas/diagnóstico , Humanos , Imagen por Resonancia Magnética/economía , Masculino , Dimensión del Dolor , Estudios Prospectivos , Derivación y Consulta , Escocia/epidemiología
10.
mSystems ; 7(5): e0047622, 2022 10 26.
Artículo en Inglés | MEDLINE | ID: mdl-36036505

RESUMEN

Noncarbapenemase-producing carbapenem-resistant Enterobacterales (non-CP-CRE) are increasingly recognized as important contributors to prevalent carbapenem-resistant Enterobacterales (CRE) infections. However, there is limited understanding of mechanisms underlying non-CP-CRE causing invasive disease. Long- and short-read whole-genome sequencing was used to elucidate carbapenem nonsusceptibility determinants in Enterobacterales bloodstream isolates at MD Anderson Cancer Center in Houston, Texas. We investigated carbapenem nonsusceptible Enterobacterales (CNSE) mechanisms (i.e., isolates with carbapenem intermediate resistance phenotypes or greater) through a combination of phylogenetic analysis, antimicrobial resistance gene detection/copy number quantification, porin assessment, and mobile genetic element (MGE) characterization. Most CNSE isolates sequenced were non-CP-CRE (41/79; 51.9%), whereas 25.3% (20/79) were Enterobacterales with intermediate susceptibility to carbapenems (CIE), and 22.8% (18/79) were carbapenemase-producing Enterobacterales (CPE). Statistically significant copy number variants (CNVs) of extended-spectrum ß-lactamase (ESBL) genes (Wilcoxon Test; P-value < 0.001) were present in both non-CP-CR E. coli (median CNV = 2.6×; n = 17) and K. pneumoniae (median CNV = 3.2×, n = 17). All non-CP-CR E. coli and K. pneumoniae had predicted reduced expression of at least one outer membrane porin gene (i.e., ompC/ompF or ompK36/ompK35). Completely resolved CNSE genomes revealed that IS26 and ISEcp1 structures harboring blaCTX-M variants along with other antimicrobial resistance elements were associated with gene amplification, occurring in mostly IncFIB/IncFII plasmid contexts. MGE-mediated ß-lactamase gene amplifications resulted in either tandem arrays, primarily mediated by IS26 translocatable units, or segmental duplication, typically due to ISEcp1 transposition units. Non-CP-CRE strains were the most common cause of CRE bacteremia with carbapenem nonsusceptibility driven by concurrent porin loss and MGE-mediated amplification of blaCTX-M genes. IMPORTANCE Carbapenem-resistant Enterobacterales (CRE) are considered urgent antimicrobial resistance (AMR) threats. The vast majority of CRE research has focused on carbapenemase-producing Enterobacterales (CPE) even though noncarbapenemase-producing CRE (non-CP-CRE) comprise 50% or more of isolates in some surveillance studies. Thus, carbapenem resistance mechanisms in non-CP-CRE remain poorly characterized. To address this problem, we applied a combination of short- and long-read sequencing technologies to a cohort of CRE bacteremia isolates and used these data to unravel complex mobile genetic element structures mediating ß-lactamase gene amplification. By generating complete genomes of 65 carbapenem nonsusceptible Enterobacterales (CNSE) covering a genetically diverse array of isolates, our findings both generate novel insights into how non-CP-CRE overcome carbapenem treatments and provide researchers scaffolds for characterization of their own non-CP-CRE isolates. Improved recognition of mechanisms driving development of non-CP-CRE could assist with design and implementation of future strategies to mitigate the impact of these increasingly recognized AMR pathogens.


Asunto(s)
Bacteriemia , Sepsis , Humanos , Carbapenémicos/farmacología , Antibacterianos/farmacología , Escherichia coli/genética , Amplificación de Genes , Filogenia , beta-Lactamasas/genética , Klebsiella pneumoniae/genética , Sepsis/genética , Bacteriemia/tratamiento farmacológico , Porinas/genética , Secuencias Repetitivas Esparcidas
11.
Osteoporos Int ; 22(4): 1211-8, 2011 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-20552329

RESUMEN

UNLABELLED: The relationship between fall-related fractures and social deprivation was studied in 3,843 patients. The incidence of fractures correlated with deprivation in all age groups although the spectrum of fractures was not affected by deprivation. The average age and the prevalence of hip fractures decreased with increasing deprivation. INTRODUCTION: This study examines the relationship between social deprivation and fall-related fractures. Social deprivation has been shown to be a predisposing factor in a number of diseases. There is evidence that it is implicated in fractures in children and young adults, but the evidence that it is associated with fragility fractures in older adults is weak. As fragility fractures are becoming progressively more common and increasingly expensive to treat, the association between social deprivation and fractures is important to define. METHODS: All out-patient and in-patient fractures presenting to the Royal Infirmary of Edinburgh over a 1-year period were prospectively recorded. The fractures caused by falls from a standing height were analysed in all patients of at least 15 years of age. Social deprivation was assessed using the Carstairs score and social deprivation deciles, and the 2001 census was used to calculate fracture incidence. The data were used to analyse the relationship between social deprivation and fall-related fractures in all age groups. RESULTS: The incidence of fall-related fractures correlated with social deprivation in all age groups including fragility fractures in the elderly. The overall spectrum of fractures was not affected by social deprivation although the prevalence of proximal femoral fractures decreased with increasing deprivation. The average age of patients with fall-related fractures also decreased with increasing social deprivation as did the requirement for in-patient treatment. CONCLUSIONS: This is the first study to show the relationship between fall-related fractures and social deprivation in older patients. We believe that the decreased incidence of proximal femoral fractures, and the lower average age of patients with fall-related fractures, in the socially deprived relates to the relative life expectancies in the different deprivation deciles.


Asunto(s)
Accidentes por Caídas/estadística & datos numéricos , Fracturas Óseas/etiología , Adolescente , Adulto , Distribución por Edad , Anciano , Anciano de 80 o más Años , Métodos Epidemiológicos , Femenino , Fracturas Óseas/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Fracturas Osteoporóticas/epidemiología , Fracturas Osteoporóticas/etiología , Áreas de Pobreza , Escocia/epidemiología , Distribución por Sexo , Factores Socioeconómicos , Adulto Joven
12.
Clin Radiol ; 66(4): 349-56, 2011 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-21295772

RESUMEN

AIM: To evaluate the diagnostic accuracy of multidetector computed tomography (MDCT) for hepatocellular carcinoma (HCC) in cirrhotic patients undergoing liver transplantation. Secondary aims were to examine the effect of radiologist experience and lesion size on diagnostic accuracy. MATERIALS AND METHODS: Thirty-nine patients (72% male with a mean age of 56.5 years) underwent liver transplantation following preoperative triple-phase MDCT examination of the liver. MDCT examinations were retrospectively independently reviewed by three radiologists for the presence and location of suspected HCCs, with the diagnostic confidence recorded using a five-point confidence scale. MDCT examinations were compared with explant specimens for histopathological correlation. RESULTS: Histopathological results demonstrated 46 HCCs in 29 of the 39 patients. Analysis demonstrated a sensitivity of 65-75% and specificity of 47-88% for detection of HCC lesions. The sensitivity dropped to 48-57% for lesions of size ≤20mm. As the diagnostic confidence increased, there was a further decrease in the sensitivity (4-26%). The radiologist with the greatest number of years experience was found to have a significantly higher accuracy of detection of HCC lesions compared with the least experienced radiologist. CONCLUSION: Larger lesion size of HCC and greater number of years experience of the radiologist resulted in significantly higher accuracy of HCC lesion detection. The overall sensitivity and specificity results for MDCT detection of HCC are comparable to previous helical CT imaging.


Asunto(s)
Carcinoma Hepatocelular/diagnóstico por imagen , Neoplasias Hepáticas/diagnóstico por imagen , Trasplante de Hígado/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodos , Carcinoma Hepatocelular/patología , Femenino , Humanos , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/cirugía , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Carga Tumoral
13.
Emerg Med J ; 28(4): 274-9, 2011 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-20659880

RESUMEN

Mountain biking is increasing in popularity worldwide. The injury patterns associated with elite level and competitive mountain biking are known. This study analysed the incidence, spectrum and risk factors for injuries sustained during recreational mountain biking. The injury rate was 1.54 injuries per 1000 biker exposures. Men were more commonly injured than women, with those aged 30-39 years at highest risk. The commonest types of injury were wounding, skeletal fracture and musculoskeletal soft tissue injury. Joint dislocations occurred more commonly in older mountain bikers. The limbs were more commonly injured than the axial skeleton. The highest hospital admission rates were observed with head, neck and torso injuries. Protective body armour, clip-in pedals and the use of a full-suspension bicycle may confer a protective effect.


Asunto(s)
Traumatismos en Atletas/epidemiología , Ciclismo/lesiones , Adolescente , Adulto , Anciano , Traumatismos en Atletas/clasificación , Distribución de Chi-Cuadrado , Niño , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Admisión del Paciente/estadística & datos numéricos , Estudios Prospectivos , Equipos de Seguridad , Recreación , Factores de Riesgo , Triaje , Reino Unido/epidemiología
14.
Ann Oncol ; 21(6): 1254-1261, 2010 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-19858088

RESUMEN

BACKGROUND: Assessment of receptors [estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2)] is routinely carried out on primary tumour in order to select appropriate adjuvant therapy; the same analysis is not carried out on nodal metastases. Since de novo resistance to therapy is common, we quantified differences in receptor expression between primary and nodal disease in order to assess whether this might contribute to therapeutic resistance. PATIENTS AND METHODS: A total of 385 patients with invasive primary breast carcinomas and paired lymph nodes (n = 211) were assessed for ER, PR and HER2 expression using quantitative immunofluorescence. Cut-points were defined by comparison with tumours scored by immunohistochemistry (IHC) and FISH. Differences in expression for each of the markers and molecular phenotype were analysed. RESULTS: Quantitative receptor expression shows a wide dynamic range compared with IHC. Overall, 46.9% cases had disparate breast/node receptor status of at least one receptor. Many of the differences in expression between primary tumour and node are large magnitude (greater than fivefold) changes. Triple-negative phenotype changes in 23.1% of cases. CONCLUSIONS: A significant number of patients show discordant quantitative expression of molecular markers between primary and nodal disease. Appropriately measured, lymph node receptor status could be a more accurate measurement for guiding adjuvant therapy, which requires testing in a clinical trial.


Asunto(s)
Neoplasias de la Mama/metabolismo , Carcinoma/metabolismo , Ganglios Linfáticos/metabolismo , Receptor ErbB-2/análisis , Receptores de Estrógenos/análisis , Receptores de Progesterona/análisis , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/metabolismo , Neoplasias de la Mama/patología , Carcinoma/patología , Femenino , Técnica del Anticuerpo Fluorescente/métodos , Humanos , Ganglios Linfáticos/patología , Metástasis Linfática , Análisis por Apareamiento , Estadificación de Neoplasias/métodos , Receptor ErbB-2/metabolismo , Receptores de Estrógenos/metabolismo , Receptores de Progesterona/metabolismo , Proyectos de Investigación , Carga Tumoral
15.
Mol Ecol ; 19(18): 3857-64, 2010 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-20738783

RESUMEN

Deviations of the site frequency spectrum of mutations (SFS) from neutral expectations may be caused by natural selection or by demographic processes such as population subdivision or temporal changes in population size. As most widespread temperate and boreal tree species have expanded from glacial refugia in the past 13,000 years, colonization bottlenecks associated with this migration may have left variable demographic signatures among geographic populations corresponding to distance from the refugia. To determine whether the signature of postglacial re-colonization has skewed the SFS in the widely distributed conifer Sitka spruce (Picea sitchensis (Bong.) Carr.), we re-sequenced 153 nuclear genes in six populations from across the species range. We found that while the SFS for the pooled sample produced negative values for Tajima's D and Fay and Wu's H, these statistics exhibited strong clinal variation when populations were analysed separately (R(2) = 0.84, P = 0.007 for Tajima's D and R(2) = 0.65, P = 0.033 for Fay and Wu's H). When historical bottlenecks of varying age were simulated using approximate Bayesian computation, distance of populations from the southern range limit explained most of the variation in bottleneck timing among populations (R(2) = 0.89, P = 0.003). These data suggest that sequential population bottlenecks during postglacial re-colonization have resulted in diverse among-population signatures within the contemporary SFS in Sitka spruce, with rare variants more common in the south, and medium-frequency variants more common in the north. Our results also emphasize the need to consider sampling strategy and to explore population-specific null demographic models in surveys of nucleotide variation in widely distributed species.


Asunto(s)
Genética de Población , Modelos Genéticos , Picea/genética , Teorema de Bayes , Canadá , Simulación por Computador , ADN de Plantas/genética , Variación Genética , Geografía , Noroeste de Estados Unidos , Selección Genética , Análisis de Secuencia de ADN
16.
J Evol Biol ; 23(2): 249-58, 2010 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-20021549

RESUMEN

High-dispersal rates in heterogeneous environments and historical rapid range expansion can hamper local adaptation; however, we often see clinal variation in high-dispersal tree species. To understand the mechanisms of the species' distribution, we investigated local adaptation and adaptive plasticity in a range-wide context in Sitka spruce, a wind-pollinated tree species that has recently expanded its range after glaciations. Phenotypic traits were observed using growth chamber experiments that mimicked temperature and photoperiodic regimes from the limits of the species realized niche. Bud phenology exhibited parallel reaction norms among populations; however, putatively adaptive plasticity and strong divergent selection were seen in bud burst and bud set timing respectively. Natural selection appears to have favoured genotypes that maximize growth rate during available frost-free periods in each environment. We conclude that Sitka spruce has developed local adaptation and adaptive plasticity throughout its range in response to current climatic conditions despite generally high pollen flow and recent range expansion.


Asunto(s)
Adaptación Biológica , Clima , Fenotipo , Picea/genética , Flujo Génico , Fotoperiodo , Plantones/crecimiento & desarrollo , Temperatura
17.
Aust J Gen Pract ; 49(5): 239-244, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-32416650

RESUMEN

BACKGROUND: Patients with lower limb peripheral artery disease (PAD) are at high risk of cardiovascular mortality and morbidity along with limb loss. PAD is underdiagnosed in the community and presents a missed opportunity to prescribe evidence-based secondary prevention therapy. OBJECTIVE: The aim of this article is to summarise key updates in the management of patients with PAD, with particular reference to newly published guidelines. DISCUSSION: PAD continues to be a major contributor to the mortality and morbidity of patients with atherosclerosis in Australia. For patients with chronic limb-threatening ischaemia, revascularisation remains the mainstay of limb salvage, and expedited access to vascular surgery assessment is necessary. Both prescription of, and adherence to, evidence-based secondary prevention therapy is low. A greater emphasis on cardiovascular risk factor modification for all patients with PAD is required to improve long-term outcomes. General practitioners and vascular surgeons can work collaboratively to provide patient-centred, effective care to patients with PAD.


Asunto(s)
Extremidad Inferior/irrigación sanguínea , Enfermedad Arterial Periférica/complicaciones , Pronóstico , Australia , Humanos , Extremidad Inferior/fisiopatología , Enfermedad Arterial Periférica/diagnóstico , Enfermedad Arterial Periférica/terapia , Factores de Riesgo , Prevención Secundaria/métodos , Prevención Secundaria/normas
18.
Bone ; 136: 115329, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32224162

RESUMEN

Pyrophosphate (PPi) serves as a potent and physiologically important regulator of mineralization, with systemic and local concentrations determined by several key regulators, including: tissue-nonspecific alkaline phosphatase (ALPL gene; TNAP protein), the progressive ankylosis protein (ANKH; ANK), and ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1; ENPP1). Results to date have indicated important roles for PPi in cementum formation, and we addressed several gaps in knowledge by employing genetically edited mouse models where PPi metabolism was disrupted and pharmacologically modulating PPi in a PPi-deficient mouse model. We demonstrate that acellular cementum growth is inversely proportional to PPi levels, with reduced cementum in Alpl KO (increased PPi levels) mice and excess cementum in Ank KO mice (decreased PPi levels). Moreover, simultaneous ablation of Alpl and Ank results in reestablishment of functional cementum in dKO mice. Additional reduction of PPi by dual deletion of Ank and Enpp1 does not further increase cementogenesis, and PDL space is maintained in part through bone modeling/remodeling by osteoclasts. Our results provide insights into cementum formation and expand our knowledge of how PPi regulates cementum. We also demonstrate for the first time that pharmacologic manipulation of PPi through an ENPP1-Fc fusion protein can regulate cementum growth, supporting therapeutic interventions targeting PPi metabolism.


Asunto(s)
Cementogénesis , Difosfatos , Animales , Cemento Dental , Ratones , Osteoclastos
19.
Clin Microbiol Infect ; 26(5): 646.e1-646.e8, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-31639470

RESUMEN

OBJECTIVES: The significance of isolating Staphylococus epidermidis from a blood culture is highly heterogeneous, ranging from contamination to an indication of a serious infection. Herein we sought to determine whether there is a relationship between S. epidermidis genotype and clinical severity of bacteraemia. METHODS: S. epidermidis bacteraemias from a prospective, multicentre trial at 15 centres in the United States and one in Spain were classified as simple (including possible contamination), uncomplicated, and complicated. Whole-genome sequencing (WGS) was performed on 161 S. epidermidis isolates, and clinical outcomes were correlated with genotypic information. RESULTS: A total of 49 S. epidermidis sequence types (STs) were identified. Although strains of all 49 STs were isolated from patients with either simple or uncomplicated infection, all strains causing complicated infections were derived from five STs: ST2, ST5, ST7, ST16, and ST32. ST2 and ST5 isolates were significantly more likely to cause uncomplicated and complicated bloodstream infections compared to simple bacteraemia (odds ratio 2.0, 95%CI 1.1-3.9, p 0.04). By multivariate regression analysis, having an ST2 or ST5 S. epidermidis bacteraemia was an independent predictor of complicated bloodstream infection (odds ratio 3.7, 95%CI 1.2-11.0, p 0.02). ST2/ST5 strains carried larger numbers of antimicrobial resistance determinants compared to non-ST2/ST5 isolates (6.34 ± 1.5 versus 4.4 ± 2.5, p < 0.001). CONCLUSION: S. epidermidis bacteraemia was caused by a genetically heterogeneous group of organisms, but only a limited number of STs-particularly multidrug-resistant ST2 and ST5 strains-caused complicated infections.


Asunto(s)
Bacteriemia/microbiología , Bacteriemia/patología , Infecciones Estafilocócicas/microbiología , Infecciones Estafilocócicas/patología , Staphylococcus epidermidis/genética , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Bacteriemia/tratamiento farmacológico , Ensayos Clínicos como Asunto , Farmacorresistencia Bacteriana/efectos de los fármacos , Farmacorresistencia Bacteriana/genética , Femenino , Genoma Bacteriano/genética , Genotipo , Humanos , Masculino , Pruebas de Sensibilidad Microbiana , Estudios Multicéntricos como Asunto , Fenotipo , Filogenia , Infecciones Estafilocócicas/tratamiento farmacológico , Staphylococcus epidermidis/clasificación , Staphylococcus epidermidis/efectos de los fármacos , Staphylococcus epidermidis/aislamiento & purificación
20.
Sex Transm Infect ; 85(2): 102-5, 2009 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-19004866

RESUMEN

OBJECTIVES: The aim of this study was to develop a novel urine transport method to be used in self-collection-based screening for Chlamydia trachomatis. The method needed to be suitable for C trachomatis PCR detection, be economical and suitable for transport by standard envelope mailing. METHODS: An anhydrous gel composed of super-absorbent polymer and buffering agent was used to desiccate urine into a dry granulous state, which could subsequently be reconstituted upon arrival at a laboratory. DNA was then extracted from the reconstituted solution using the Roche MagNA Pure protocol for the detection of C trachomatis by PCR. Collections of urine specimens from three populations with widely differing chlamydia prevalence (100%,n = 56; 47%, n = 70; 3%, n = 97) were used. We determined the gel method's impact on C trachomatis PCR sensitivity and specificity using neat and gel-processed urine specimens. An equine herpes virus PCR was used to test for assay inhibition. RESULTS: Overall, the sensitivity of the gel-based method ranged from 94.6-100% compared with neat urine, with a specificity of 100%. No PCR inhibition or decrease in analytical sensitivity was observed using the gel-processed extracts. CONCLUSIONS: The gel-based method was found to be suitable for the detection of C trachomatis by PCR. In addition, its ease of use, effectiveness at ambient temperature and low cost makes it well-suited for self-collection kits used in population-based C trachomatis screening, particularly for geographically and socially isolated individuals.


Asunto(s)
Infecciones por Chlamydia/diagnóstico , Chlamydia trachomatis/aislamiento & purificación , Juego de Reactivos para Diagnóstico/normas , Manejo de Especímenes/métodos , Infecciones por Chlamydia/orina , ADN Bacteriano/orina , Femenino , Geles , Humanos , Masculino , Reacción en Cadena de la Polimerasa , Estudios Prospectivos , Sensibilidad y Especificidad
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