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1.
Nature ; 557(7706): 503-509, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29769716

RESUMO

One-third of all protein-coding genes from bacterial genomes cannot be annotated with a function. Here, to investigate the functions of these genes, we present genome-wide mutant fitness data from 32 diverse bacteria across dozens of growth conditions. We identified mutant phenotypes for 11,779 protein-coding genes that had not been annotated with a specific function. Many genes could be associated with a specific condition because the gene affected fitness only in that condition, or with another gene in the same bacterium because they had similar mutant phenotypes. Of the poorly annotated genes, 2,316 had associations that have high confidence because they are conserved in other bacteria. By combining these conserved associations with comparative genomics, we identified putative DNA repair proteins; in addition, we propose specific functions for poorly annotated enzymes and transporters and for uncharacterized protein families. Our study demonstrates the scalability of microbial genetics and its utility for improving gene annotations.


Assuntos
Bactérias/genética , Genes Bacterianos/genética , Anotação de Sequência Molecular , Mutação , Fenótipo , Incerteza , Bactérias/citologia , Proteínas de Bactérias/classificação , Proteínas de Bactérias/genética , Proteínas de Bactérias/fisiologia , Sequência Conservada , Reparo do DNA/genética , Aptidão Genética , Genoma Bacteriano/genética , Proteínas Mutantes/classificação , Proteínas Mutantes/genética , Proteínas Mutantes/fisiologia
2.
BMC Geriatr ; 23(1): 436, 2023 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-37454100

RESUMO

BACKGROUND: Post-operative delirium (POD) is an acute brain failure which may occur following major surgery, with serious implications for participants and caregivers. Evidence regarding optimal anaesthetic management for older participants at higher risk of POD is conflicting. We conducted a feasibility study of our protocol in 5 centres to guide sample size estimation and inform future recruitment strategies for a larger cohort study. METHODS: Participants aged over 65 and scheduled for major surgery were recruited. They were assessed pre-operatively for delirium, cognitive impairment, depression, comorbidity, activity levels and alcohol use. Details of management during surgery, all medications and complications were recorded by a trainee-led research team. Participants were assessed for delirium in the immediate recovery period and then on post-operative days 1-4 using the 4 question attention test (4AT) with complications assessed at day 4 using the post-operative morbidity survey (POMS). Primary outcomes were the incident rates of POD. Secondary outcomes were number of eligible patients, recruitment rates and retention rates throughout the study, time required for data collection, preoperative risk factors assessment and daily postoperative delirium assessments. Also to assess the added value of employing the regional trainee research network (INCARNNET) to deliver the study. Specifically, what proportion of patient consent, data collection and post-operative testing is performed by anaesthesia trainees from this group, especially the success of weekend delirium assessment by trainees? A survey was completed at the end of the study by the trainees involved regarding their involvement in the study. RESULTS: Ninety-five participants were recruited, of whom 93 completed the study. Overall, POD occurred in 9 patients. Of these, three were detected in recovery and six on post-op days 1-4. Median length of stay was 6 days. Recruitment rates were high in all but one site. 59 (62%) participants were consented by trainees and 189 (63%) of post op delirium assessments were performed by trainees. A total of six patients declined the study (in a follow up survey of trainees). Pre-existing cognitive impairment, depression and problem drinking were detected in 4(4.3%), 3(3.2%) and 5(5.37%) participants, respectively. Co-morbidity was common with 55(59%) in class three or four of the geriatric index of morbidity. Overall, from a total of 641 data points, levels of missing data were as follows, site A = 9.3%, B = 13.5%, C = 15.4%, D = 10.9%, E = 11.1% (data could not be completed retrospectively). CONCLUSIONS: A multi-centre observational cohort study of delirium carried out by UK trainee anaesthetists is feasible. Patients are content to undergo day of surgery consent and multiple short questionnaires pre-operatively. Proposed data, especially pharmacological, should be carefully considered for their relevance to modifiable mechanisms that can lead to POD. Future research to enable prognostic modelling of POD should involve large scale cohort studies of enriched populations to capture a higher POD incidence. POD remains a common complication in older persons undergoing major surgery in the UK and studies of interventions are urgently needed. TRIAL REGISTRATION: All methods were carried out in accordance with relevant guidelines and regulations. The study was retrospectively registered with ISRCTN94663125 on 07/02/2018.


Assuntos
Delírio , Delírio do Despertar , Humanos , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Delírio/diagnóstico , Delírio/epidemiologia , Delírio/etiologia , Estudos de Viabilidade , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Fatores de Risco , Inquéritos e Questionários
3.
J Environ Manage ; 210: 263-272, 2018 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-29367139

RESUMO

While performance assessments of constructed wetlands sites around the world have appraised their capacity for effective removal of organics, a large variance remains in these sites' reported ability to retain nutrients, which appears to depend on differences in design, operation and climate factors. Nutrient retention is a very important objective for constructed wetlands, to avoid eutrophication of aquatic environments receiving their effluents. This study assessed the performance of constructed wetlands in terms of nutrient retention and associated parameters under the humid conditions of Ireland's temperate maritime climate. A review of the performance of 52 constructed wetland sites from 17 local authorities aimed to identify the best performing types of constructed wetlands and the treatment factors determining successful compliance with environmental standards. Data analysis compared effluent results from constructed wetlands with secondary free surface flow or tertiary horizontal subsurface flow, hybrid systems and integrated constructed wetlands with those from small-scale mechanical wastewater treatment plants of the same size class. Nutrient concentrations in effluents of constructed wetlands were negatively correlated (p < .01) with specific area, i.e. the ratio of surface area and population equivalents. The latest generation of integrated constructed wetlands, which had applied design guidelines issued by the Department of the Environment, performed best. Storm management design features improved treatment performance of constructed wetlands significantly (p < .05) for total suspended solids concentrations and exceedance frequency of limit values for total nitrogen. Mechanical wastewater treatment plants, secondary free surface water and tertiary horizontal subsurface flow wetlands showed a very large variance in effluent concentrations for organic and nutrient parameters. E. coli numbers in effluents were lowest for integrated constructed wetlands with an arithmetic mean of 89 MPN/100 ml. Despite Ireland's humid climate, some constructed wetland sites achieved long or frequent periods of zero effluent discharge and thus did not transfer any waterborne pollution to their receptors during these periods.


Assuntos
Eutrofização , Eliminação de Resíduos Líquidos , Áreas Alagadas , Escherichia coli , Irlanda , Nitrogênio , Águas Residuárias , Microbiologia da Água
4.
Nat Commun ; 10(1): 308, 2019 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-30659179

RESUMO

A major challenge in genomics is the knowledge gap between sequence and its encoded function. Gain-of-function methods based on gene overexpression are attractive avenues for phenotype-based functional screens, but are not easily applied in high-throughput across many experimental conditions. Here, we present Dual Barcoded Shotgun Expression Library Sequencing (Dub-seq), a method that uses random DNA barcodes to greatly increase experimental throughput. As a demonstration of this approach, we construct a Dub-seq library with Escherichia coli genomic DNA, performed 155 genome-wide fitness assays in 52 experimental conditions, and identified overexpression phenotypes for 813 genes. We show that Dub-seq data is reproducible, accurately recapitulates known biology, and identifies hundreds of novel gain-of-function phenotypes for E. coli genes, a subset of which we verified with assays of individual strains. Dub-seq provides complementary information to loss-of-function approaches and will facilitate rapid and systematic functional characterization of microbial genomes.


Assuntos
DNA Bacteriano/genética , Escherichia coli/genética , Genoma Bacteriano , Código de Barras de DNA Taxonômico , Biblioteca Gênica , Aptidão Genética , Reprodutibilidade dos Testes
5.
ISME J ; 13(4): 937-949, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30523276

RESUMO

In many environments, toxic compounds restrict which microorganisms persist. However, in complex mixtures of inhibitory compounds, it is challenging to determine which specific compounds cause changes in abundance and prevent some microorganisms from growing. We focused on a contaminated aquifer in Oak Ridge, Tennessee, USA that has large gradients of pH and widely varying concentrations of uranium, nitrate, and many other inorganic ions. In the most contaminated wells, the microbial community is enriched in the Rhodanobacter genus. Rhodanobacter abundance is positively correlated with low pH and high concentrations of uranium and 13 other ions and we sought to determine which of these ions are selective pressures that favor the growth of Rhodanobacter over other taxa. Of these ions, low pH and high UO22+, Mn2+, Al3+, Cd2+, Zn2+, Co2+, and Ni2+ are both (a) selectively inhibitory of a Pseudomonas isolate from an uncontaminated well vs. a Rhodanobacter isolate from a contaminated well, and (b) reach toxic concentrations (for the Pseudomonas isolate) in the Rhodanobacter-dominated wells. We used mixtures of ions to simulate the groundwater conditions in the most contaminated wells and verified that few isolates aside from Rhodanobacter can tolerate these eight ions. These results clarify which ions are likely causal factors that impact the microbial community at this field site and are not merely correlated with taxonomic shifts. Furthermore, our general high-throughput approach can be applied to other environments, isolates, and conditions to systematically help identify selective pressures on microbial communities.


Assuntos
Gammaproteobacteria/metabolismo , Água Subterrânea/microbiologia , Metais/toxicidade , Microbiota , Pseudomonas/metabolismo , Biodegradação Ambiental , Gammaproteobacteria/classificação , Gammaproteobacteria/crescimento & desenvolvimento , Gammaproteobacteria/isolamento & purificação , Água Subterrânea/química , Metais/metabolismo , Nitratos/análise , Pseudomonas/classificação , Pseudomonas/crescimento & desenvolvimento , Pseudomonas/isolamento & purificação , Urânio/análise
6.
J Neuroimaging ; 16(2): 176-8, 2006 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-16629743

RESUMO

Hemodynamic factors may play a role in the seeding and subsequent growth of cerebral metastasis. The authors present a case with 2 foci of cerebral metastasis in the same vascular territory ipsilateral to an occluded internal carotid artery. A 65-year-old man with chronic left frontal lobe infarct and left internal carotid artery occlusion was diagnosed with 2 large hemorrhagic metastases in the left middle cerebral artery territory. Diminished flow signals were seen in the trunk and branches of the left middle cerebral artery on magnetic resonance angiography. This case illustrates preferential seeding and growth of cerebral metastases in a region of the brain with diminished blood flow.


Assuntos
Neoplasias Encefálicas/secundário , Carcinoma de Células Renais/secundário , Estenose das Carótidas , Neoplasias Renais/patologia , Idoso , Neoplasias Encefálicas/radioterapia , Carcinoma de Células Renais/radioterapia , Artéria Carótida Interna , Humanos , Angiografia por Ressonância Magnética , Masculino
7.
Phys Rev E ; 94(1-1): 012120, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27575090

RESUMO

The equilibrium properties of a single quantum particle (qp) interacting with a classical gas for a wide range of temperatures that explore the system's behavior in the classical as well as in the quantum regime is investigated. Both the qp and the atoms are restricted to sites on a one-dimensional lattice. A path integral formalism developed within the context of the canonical ensemble is utilized, where the qp is represented by a closed, variable-step random walk on the lattice. Monte Carlo methods are employed to determine the system's properties. To test the usefulness of the path integral formalism, the Metropolis algorithm is employed to determine the equilibrium properties of the qp in the context of a square well potential, forcing the qp to occupy bound states. We consider a one-dimensional square well potential where all atoms on the lattice are occupied with one atom with an on-site potential except for a contiguous set of sites of various lengths centered at the middle of the lattice. Comparison of the potential energy, the energy fluctuations, and the correlation function are made between the results of the Monte Carlo simulations and the numerical calculations.

8.
Am J Obstet Gynecol ; 193(4): 1554-60, 2005 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-16202756

RESUMO

OBJECTIVE: To investigate how gestational age and prior vaginal birth affect cervical anatomy on magnetic resonance imaging during pregnancy. STUDY DESIGN: Magnetic resonance images of the cervix were obtained in consecutive patients referred for a suspected fetal abnormality. We used an image processing protocol to measure cervical dimensions, orientation, and signal intensity. We determined how outcome variables were affected by gestational age and prior vaginal birth. RESULTS: Adequate images were obtained in 53 of 57 patients at 17 to 36 weeks. As gestational age increased by 12 weeks, the mean cross-sectional area of the cervical canal and cervical stroma increased 31% (95% confidence interval 0% to 73%) and 31% (95% confidence interval 11% to 55%), respectively. The normalized signal intensity of the stroma increased from 0.83 (95% confidence interval 0.81 to 0.85) at 20 weeks to 0.91 (95% confidence interval 0.88 to 0.94) at 32 weeks. None of the outcome variables were affected by prior vaginal birth. CONCLUSION: Magnetic resonance imaging revealed that cross-sectional area and signal intensity of the cervical stroma increase with increasing gestational age.


Assuntos
Colo do Útero/anatomia & histologia , Parto Obstétrico , Imageamento por Ressonância Magnética , Adulto , Feminino , Humanos , Gravidez , Segundo Trimestre da Gravidez , Terceiro Trimestre da Gravidez
9.
Eur J Cancer ; 51(9): 1131-43, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24569102

RESUMO

Population-based cancer registries provide indispensable information on cancer incidence and survival, which cannot be obtained by any other means. It is clear that complete and effective use of these data is essential for cancer control, but sharing this information in a uniform, timely and user-friendly manner has been somewhat limited up to now. The European Cancer Observatory (ECO, http://eco.iarc.fr) has been developed in the framework of the EUROCOURSE project (EUROpe against Cancer: Optimisation of Use of Registries for Scientific Excellence in Research) as a comprehensive resource combining all the information currently available in Europe on cancer incidence, mortality, survival and prevalence. The website provides analytical and presentation tools to examine national estimates for 2012 in 40 European countries (EUCAN), data for 130 national or sub-national areas covered by cancer registries for up to 60 years, until 2011 (EUREG) and a planned mechanism for data download (European Cancer Incidence and Mortality (EUROCIM)). The generated statistics outline the considerable variability across Europe in the rates of all major cancer types and help identify key concerns that need to be addressed by public health policies e.g. the unprecedented rise of lung cancer incidence in women with its full impact expected within a decade or so. The support, maintenance and further development of the ECO website should be a high priority for European cancer policymakers, to continue providing this unique information to health professionals, researchers and the general public in Europe and beyond.


Assuntos
Bases de Dados Factuais/provisão & distribuição , Neoplasias/epidemiologia , Sistema de Registros , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Bases de Dados Factuais/normas , Europa (Continente)/epidemiologia , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Mortalidade , Sistema de Registros/estatística & dados numéricos , Interface Usuário-Computador , Adulto Jovem
10.
Artigo em Inglês | MEDLINE | ID: mdl-24827210

RESUMO

The equilibrium properties of a single quantum particle (qp) interacting with a classical gas for a wide range of temperatures that explore the system's behavior in the classical as well as in the quantum regime is investigated. Both the qp and atoms are restricted to the sites of a one-dimensional lattice. A path integral formalism is developed within the context of the canonical ensemble in which the qp is represented by a closed, variable-step random walk on the lattice. Monte Carlo methods are employed to determine the system's properties. For the case of a free particle, analytical expressions for the energy, its fluctuations, and the qp-qp correlation function are derived and compared with the Monte Carlo simulations. To test the usefulness of the path integral formalism, the Metropolis algorithm is employed to determine the equilibrium properties of the qp for a periodic interaction potential, forcing the qp to occupy extended states. We consider a striped potential in one dimension, where every other lattice site is occupied by an atom with potential ε, and every other lattice site is empty. This potential serves as a stress test for the path integral formalism because of its rapid site-to-site variation. An analytical solution was determined in this case by utilizing Bloch's theorem due to the periodicity of the potential. Comparisons of the potential energy, the total energy, the energy fluctuations, and the correlation function are made between the results of the Monte Carlo simulations and the analytical calculations.

12.
J Neuroimaging ; 18(4): 375-80, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19012736

RESUMO

PURPOSE: Our purpose was to study the association between atherosclerosis measured by arterial calcium on computed tomography (CT) and cerebral atrophy demonstrated by brain magnetic resonance imaging (MRI). MATERIALS AND METHODS: IRB approved this prospective study. Twenty-one consecutive patients with acute stroke-like symptoms who are scheduled to have brain MRI were recruited on a voluntary basis. electrocardiogram (ECG)-gated helical CT scans were used to determine the arterial calcium as a reliable index of underlying atherosclerosis. Extracranial arterial calcium content was measured quantitatively by special software available in our CT scanner. Intracranial calcium was graded qualitatively. Brain MRI was independently evaluated to identify cortical, central atrophy, and ischemic changes. Relationship between CT demonstrated atherosclerosis and cerebral ischemic changes, brain atrophy patterns were evaluated both without and with adjustment for age and hypertension. RESULTS: Out of 21 patients 20 were included in final study group. There was no correlation between atherosclerotic calcium measures and cortical atrophy, ischemic findings. Both intracranial and extracranial atherosclerosis had partial correlation with central atrophy (R= 0.43 and 0.52, respectively). After adjustment for age, only intracranial atherosclerosis maintained a partial correlation with central atrophy (R= 0.41). However, this correlation did not reach a statistically significant level (P= .10). CONCLUSIONS: Intracranial atherosclerosis demonstrated a possible correlation with central atrophy.


Assuntos
Angiografia Cerebral , Córtex Cerebral/patologia , Infarto Cerebral/diagnóstico , Processamento de Imagem Assistida por Computador , Arteriosclerose Intracraniana/diagnóstico , Imageamento por Ressonância Magnética , Tomografia Computadorizada Espiral , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Atrofia , Calcinose/diagnóstico , Estenose das Carótidas/diagnóstico , Doença da Artéria Coronariana/diagnóstico , Dominância Cerebral/fisiologia , Feminino , Humanos , Hipertensão/diagnóstico , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Estatística como Assunto
13.
Neuroradiology ; 48(1): 26-30, 2006 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-16237547

RESUMO

Treatment with gamma knife radiosurgery (GKRS) provides adequate short-term pain control in about 70% of the patients with intractable trigeminal neuralgia (TN). The purpose of our study was to evaluate whether the presence of neurovascular contact (NVC) at the root entry zone of the trigeminal nerve on pre-gamma knife MR imaging predicts an increased likelihood of an adequate response to GKRS. We studied 40 consecutive patients who underwent GKRS for treatment of intractable TN. Two neuroradiologists blinded to the side of symptoms analyzed pre-treatment constructive interference in steady state (CISS) images to determine the presence of NVC by consensus. An adequate response was defined as freedom from pain with or without reduced need for medical therapy. Adequate short-term response to GKRS was seen in 29 (72.5%) of 40 patients. NVC was seen in 30 of the 40 patients. Twenty-five (83.3%) of 30 patients with NVC had adequate short-term response to GKRS. Only four (40%) of the 10 patients without NVC had adequate response to GKRS (X2=7.06; P<0.01). Patients with NVC were seven times more likely to have an adequate response to GKRS than those without NVC (odds ratio =7.5).The presence of NVC on pre-treatment MR imaging predicts an increased likelihood of an adequate response to GKRS.


Assuntos
Imageamento por Ressonância Magnética/métodos , Radiocirurgia/instrumentação , Neuralgia do Trigêmeo/diagnóstico , Neuralgia do Trigêmeo/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Distribuição de Qui-Quadrado , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
14.
Radiology ; 238(2): 689-92, 2006 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-16436823

RESUMO

PURPOSE: To retrospectively evaluate the size of the trigeminal nerve on magnetic resonance (MR) images of patients with unilateral trigeminal neuralgia. MATERIALS AND METHODS: Institutional review board approval was obtained and informed consent was waived for this HIPAA-compliant study. The sizes of the trigeminal nerves in 31 patients (18 men and 13 women; mean age, 68 years; age range, 44-84 years) with clinically confirmed intractable unilateral trigeminal neuralgia were measured before treatment with gamma knife radiosurgery. Images were analyzed separately by two neuroradiologists who were blinded to the side of the face with symptoms. Coronal projection images were used to determine the diameter and cross-sectional area of the trigeminal nerves at 5 mm from the entry point of the nerve into the pons. Comparisons were made by using a paired t test. Interobserver variability was assessed by using the Pearson correlation coefficient. RESULTS: The mean diameter of the trigeminal nerve on the symptomatic side was significantly smaller than the mean diameter on the asymptomatic side in 30 of 31 patients (2.11 mm +/- 0.40 [standard deviation] and 2.62 mm +/- 0.56, P < .001, 95% confidence interval: -0.35, -0.67 mm). The mean cross-sectional area on the symptomatic side was significantly smaller than the area on the asymptomatic side in 27 of 31 patients (4.50 mm(2) +/- 1.75 and 6.28 mm(2) +/- 2.19, P < .001, 95% confidence interval: -2.41, -1.16 mm(2)). CONCLUSION: The results indicate that trigeminal nerve atrophy can be depicted noninvasively in patients with trigeminal neuralgia.


Assuntos
Imageamento por Ressonância Magnética , Nervo Trigêmeo/patologia , Neuralgia do Trigêmeo/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Atrofia , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Índice de Gravidade de Doença
15.
J Comput Assist Tomogr ; 29(1): 130-2, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-15665699

RESUMO

A case of fetal rhabdomyoma (myxoid type) of the head and neck demonstrated on prenatal magnetic resonance imaging (MRI) is presented. This benign tumor of skeletal muscle is uncommon and should not be confused with its malignant counterpart-rhabdomyosarcoma. With the increasing use of ultrafast MRI, the radiologist is more likely to encounter head and neck masses in the fetus.


Assuntos
Doenças Fetais/diagnóstico , Neoplasias de Cabeça e Pescoço/diagnóstico , Imageamento por Ressonância Magnética , Diagnóstico Pré-Natal , Rabdomioma/diagnóstico , Adulto , Feminino , Seguimentos , Idade Gestacional , Humanos , Recém-Nascido , Recidiva Local de Neoplasia/patologia , Gravidez , Ultrassonografia Pré-Natal
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