Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 189
Filtrar
Mais filtros

Tipo de documento
Intervalo de ano de publicação
1.
Sensors (Basel) ; 23(5)2023 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-36904729

RESUMO

Using distributed MEMS pressure sensors to measure small flow rates in high resistance fluidic channels is fraught with challenges far beyond the performance of the pressure sensing element. In a typical core-flood experiment, which may last several months, flow-induced pressure gradients are generated in porous rock core samples wrapped in a polymer sheath. Measuring these pressure gradients along the flow path requires high resolution pressure measurement while contending with difficult test conditions such as large bias pressures (up to 20 bar) and temperatures (up to 125 °C), as well as the presence of corrosive fluids. This work is directed at a system for using passive wireless inductive-capacitive (LC) pressure sensors that are distributed along the flow path to measure the pressure gradient. The sensors are wirelessly interrogated with readout electronics placed exterior to the polymer sheath for continuous monitoring of experiments. Using microfabricated pressure sensors that are smaller than ø15 × 3.0 mm3, an LC sensor design model for minimizing pressure resolution, accounting for sensor packaging and environmental artifacts is investigated and experimentally validated. A test setup, built to provide fluid-flow pressure differentials to LC sensors with conditions that mimic placement of the sensors within the wall of the sheath, is used to test the system. Experimental results show the microsystem operating over full-scale pressure range of 20,700 mbar and temperatures up to 125 °C, while achieving pressure resolution of <1 mbar, and resolving gradients of 10-30 mL/min, which are typical in core-flood experiments.

2.
Econ Model ; 120: 106147, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36570545

RESUMO

We estimate the economic impacts of COVID-19 in the U.S. using a disaster economic consequence analysis framework implemented by a dynamic computable general equilibrium (CGE) model. This facilitates identification of relative influences of several causal factors as "shocks" to the model, including mandatory business closures, disease spread trajectories, behavioral responses, resilience, pent-up demand, and government stimulus packages. The analysis is grounded in primary data on avoidance behavior and healthcare parameters. The decomposition of the influence of various causal factors will help policymakers offset the negative influences and reinforce the positive ones during the remainder of this pandemic and future ones.

3.
Technol Cult ; 64(2): 308-358, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38588231

RESUMO

Many historians, journalists, and media mavens have traced the genealogy of Victorian communications networks backward, beginning with radio after World War I and continuing with personal computing in the 1980s and ending with the internet today. This impulse has accelerated with the rise of electronic commerce, social media, and virtual reality. This essay proposes a different agenda. Drawing on recent historical writing on mythmaking, materiality, and political economy and illustrated with case studies from Europe, North America, Asia, and North Africa, it reenvisions the history of new media by telling the story of Victorian communications networks in relation to the issues of their day, not ours. The essay spans five networks in the period between 1830 and 1914: the landline telegraph, the undersea cable, the telephone, the wireless telegraph, and the mail.


Assuntos
Comunicação , Meios de Comunicação de Massa , Humanos , Ásia , América do Norte , Europa (Continente)
4.
Int Urogynecol J ; 33(5): 1157-1164, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35237854

RESUMO

INTRODUCTION AND HYPOTHESIS: The objective was to systemically review the current literature on the association of gut, vaginal, and urinary dysbiosis in female patients with overactive bladder (OAB). METHODS: We performed a comprehensive literature search following the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) protocols for systematic reviews. In the EMBASE, CINAHL, and Medline databases, a search was conducted using key words such as "microbiome," "microbiota," "microflora," "overactive bladder," "urge," "gut," "vaginal." Articles were screened using the online tool www.covidence.org . Two independent reviewers screened studies at each stage and resolved conflicts together. We excluded papers that discussed pediatric patients and animal studies. In total, 13 articles met this criterion, which included 6 abstracts. RESULTS: After identifying 817 unique references, 13 articles met the criteria for data extraction. Articles were published from 2017 to 2021. No study reported the same microbiota abundance, even in healthy individuals. Overall, there was a loss of bacterial diversity in OAB patients compared with controls. Additionally, the bacterial composition of the controls and OAB patients was not significantly different, especially if the urine was collected midstream. Overall, the composition of the microbiome is dependent on the specimen collection methodology, and the metagenomic sequencing technique utilized. OAB urine microbiome is more predisposed to alteration from the gut or vaginal influences than in controls. CONCLUSIONS: Current evidence suggested a potential relationship among gut, vaginal, and urinary microbiome in OAB patients, but there are very limited studies.


Assuntos
Microbiota , Bexiga Urinária Hiperativa , Sistema Urinário , Bactérias , Criança , Feminino , Humanos , Bexiga Urinária Hiperativa/microbiologia , Sistema Urinário/microbiologia , Vagina
5.
J Cardiothorac Vasc Anesth ; 36(1): 275-285, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34023201

RESUMO

The Fontan circulation is the single-ventricle approach to surgical palliation of complex congenital heart disease wherein biventricular separation and function cannot be safely achieved. Incremental improvements in this surgical technique, along with improvements in the long-term medical management of these patients, have led to greater survival of these patients and a remarkably steady increase in the number of adults living with this unusual circulation and physiology. This has implications for healthcare providers who now have a greater chance of encountering Fontan patients during the course of their practice. This has particularly important implications for anesthesiologists because the effects of their interventions on the finely balanced Fontan circulation may be profound. The American Heart Association and American College of Cardiology recommend that, when possible, elective surgery should be performed in an adult congenital heart disease center, although this may not be feasible in the provision of true emergency care. This review article summarizes the pathophysiology pertinent to the provision of anesthesia in this complex patient group and describes important modifications to anesthetic technique and perioperative management.


Assuntos
Anestesia , Anestésicos , Técnica de Fontan , Cardiopatias Congênitas , Adulto , Cardiopatias Congênitas/cirurgia , Humanos , Cuidados Paliativos
6.
Urol Int ; 106(7): 664-671, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35320799

RESUMO

INTRODUCTION: Knowledge gaps regarding available treatment and social stigmatization are barriers to care in patients with overactive bladder (OAB). We assessed the feasibility of an OAB education program targeting older community-dwelling females. METHODS: Community-dwelling women over 55 years old were recruited. Eligible participants underwent an education program covering continence-promotion strategies. The Overactive Bladder Questionnaire-Short Form and Short Form-12 were completed at baseline, 1 week, 3 months, and 6 months post-intervention to measure symptom bother and condition-specific and general quality of life (QoL). Data were analyzed using a linear mixed-effects model for repeated measures. RESULTS: Thirty-seven female patients with OAB symptoms at baseline were assessed with the majority from Latino/Hispanic or Black/African American ethnic/racial backgrounds. For our youngest subgroup (≤68 years old), significant improvements were observed at 3 and 6 months compared to 1 week post-intervention for symptom bother (3 months, -22.75, p = 0.006; 6 months, -25.76; p = 0.001) and condition-specific and health-related QoL subscale scores for concern (3 months, +23.76, p = 0.006; 6 months, +22.15, p = 0.011) and social interaction (3 months, +21.11, p = 0.017; 6 months, +20.51; p = 0.021). For all age subgroups, improvements in general QoL measures for mental health were seen at 3 and 6 months compared to baseline (3 months, +7.57, p = 0.02; 6 months, +6.70; p = 0.048). CONCLUSIONS: Statistically significant improvements in symptom bother, condition-specific, and general QoL measures were observed following an OAB education program pilot study in a predominantly minority female population. Further studies are needed to support efficacy and optimize program design.


Assuntos
Bexiga Urinária Hiperativa , Idoso , Feminino , Humanos , Lactente , Pessoa de Meia-Idade , Projetos Piloto , Qualidade de Vida , Inquéritos e Questionários , Resultado do Tratamento , Bexiga Urinária Hiperativa/psicologia , Bexiga Urinária Hiperativa/terapia
7.
Proc Natl Acad Sci U S A ; 116(37): 18738-18744, 2019 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-31451660

RESUMO

High-throughput metagenomic sequencing offers an unbiased approach to identify pathogens in clinical samples. Conventional metagenomic sequencing, however, does not integrate information about the host, which is often critical to distinguish infection from infectious disease, and to assess the severity of disease. Here, we explore the utility of high-throughput sequencing of cell-free DNA (cfDNA) after bisulfite conversion to map the tissue and cell types of origin of host-derived cfDNA, and to profile the bacterial and viral metagenome. We applied this assay to 51 urinary cfDNA isolates collected from a cohort of kidney transplant recipients with and without bacterial and viral infection of the urinary tract. We find that the cell and tissue types of origin of urinary cfDNA can be derived from its genome-wide profile of methylation marks, and strongly depend on infection status. We find evidence of kidney and bladder tissue damage due to viral and bacterial infection, respectively, and of the recruitment of neutrophils to the urinary tract during infection. Through direct comparison to conventional metagenomic sequencing as well as clinical tests of infection, we find this assay accurately captures the bacterial and viral composition of the sample. The assay presented here is straightforward to implement, offers a systems view into bacterial and viral infections of the urinary tract, and can find future use as a tool for the differential diagnosis of infection.


Assuntos
Ácidos Nucleicos Livres/isolamento & purificação , Interações Hospedeiro-Patógeno/genética , Metagenoma/genética , Metagenômica/métodos , Complicações Pós-Operatórias/diagnóstico , Infecções Urinárias/diagnóstico , Infecções Bacterianas/diagnóstico , Infecções Bacterianas/microbiologia , Infecções Bacterianas/urina , Biomarcadores/urina , Ácidos Nucleicos Livres/genética , Ácidos Nucleicos Livres/urina , Metilação de DNA/genética , DNA Bacteriano/genética , DNA Bacteriano/isolamento & purificação , DNA Bacteriano/urina , DNA Viral/genética , DNA Viral/isolamento & purificação , DNA Viral/urina , Diagnóstico Diferencial , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Interações Hospedeiro-Patógeno/imunologia , Humanos , Rim/citologia , Rim/imunologia , Rim/microbiologia , Rim/patologia , Falência Renal Crônica/cirurgia , Transplante de Rim/efeitos adversos , Masculino , Infiltração de Neutrófilos/imunologia , Complicações Pós-Operatórias/imunologia , Complicações Pós-Operatórias/microbiologia , Complicações Pós-Operatórias/urina , Transplantados , Bexiga Urinária/citologia , Bexiga Urinária/imunologia , Bexiga Urinária/microbiologia , Bexiga Urinária/patologia , Infecções Urinárias/imunologia , Infecções Urinárias/microbiologia , Infecções Urinárias/urina , Viroses/diagnóstico , Viroses/imunologia , Viroses/urina , Viroses/virologia
8.
Risk Anal ; 42(8): 1704-1727, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-33733476

RESUMO

With the increased use of social media in crisis communication following extreme events, it is important to understand how the public distinguishes between true and false information. A U.S. adult sample (N = 588) was presented 20 actual social media posts following a natural disaster or soft-target terrorist attack in the United States. In this study, social media posts are conceptualized as truth signals with varying strengths, either above or below each individual's threshold for believing the post is true. Optimally, thresholds should be contingent on the (incentivized) error penalties and base-rate of true posts, both of which were manipulated. Separate receiver operating characteristic (ROC) analyses indicate that participants performed slightly better than chance for natural disasters and moderately better than chance for terror attacks. While the pooled thresholds are ordinally consistent with the base-rate and error penalty manipulations, they are underadjusted compared to the optimal thresholds. After accounting for demographic and cognitive variables, the base-rate manipulation significantly predicted sensitivity, specificity, and true response rates in the expected direction for both content domains, while the error penalty manipulation had no significant effect in either domain. Self-identified political conservatives performed worse at classifying false content as false for natural disasters, but better for terror attacks.


Assuntos
Mídias Sociais , Terrorismo , Adulto , Comunicação , Humanos , Estados Unidos
9.
Bioinformatics ; 36(5): 1492-1500, 2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-31591642

RESUMO

MOTIVATION: High-throughput phenomic projects generate complex data from small treatment and large control groups that increase the power of the analyses but introduce variation over time. A method is needed to utlize a set of temporally local controls that maximizes analytic power while minimizing noise from unspecified environmental factors. RESULTS: Here we introduce 'soft windowing', a methodological approach that selects a window of time that includes the most appropriate controls for analysis. Using phenotype data from the International Mouse Phenotyping Consortium (IMPC), adaptive windows were applied such that control data collected proximally to mutants were assigned the maximal weight, while data collected earlier or later had less weight. We applied this method to IMPC data and compared the results with those obtained from a standard non-windowed approach. Validation was performed using a resampling approach in which we demonstrate a 10% reduction of false positives from 2.5 million analyses. We applied the method to our production analysis pipeline that establishes genotype-phenotype associations by comparing mutant versus control data. We report an increase of 30% in significant P-values, as well as linkage to 106 versus 99 disease models via phenotype overlap with the soft-windowed and non-windowed approaches, respectively, from a set of 2082 mutant mouse lines. Our method is generalizable and can benefit large-scale human phenomic projects such as the UK Biobank and the All of Us resources. AVAILABILITY AND IMPLEMENTATION: The method is freely available in the R package SmoothWin, available on CRAN http://CRAN.R-project.org/package=SmoothWin. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.


Assuntos
Saúde da População , Software , Animais , Estudos de Associação Genética , Humanos , Camundongos , Fenótipo
10.
Psychosom Med ; 82(5): 454-460, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32310839

RESUMO

OBJECTIVE: Cardiometabolic risk refers to a set of interconnected factors of vascular and metabolic origin associated with both cardiovascular disease and various brain disorders. Although midlife cardiometabolic risk is associated with future brain dysfunction, emerging evidence suggests that alterations in autonomic and central nervous system function may precede increases in cardiometabolic risk. METHODS: The present study tested whether patterns of cerebral blood flow in brain areas associated with autonomic regulation were associated with increases in overall cardiometabolic risk. A community sample of 109 adults with resting systolic blood pressure between 120 and 139 mm Hg, diastolic blood pressure between 80 and 89 mm Hg, or both underwent pseudocontinuous arterial spin labeling to quantify cerebral blood flow responses to cognitively challenging tasks. Cardiometabolic risk and cerebral blood flow measurements were collected at baseline and at a 2-year follow-up. RESULTS: Regression analyses showed that greater frontostriatal cerebral blood flow responses to cognitive challenge were associated with higher cardiometabolic risk at follow-up (ß = 0.26 [95% confidence interval = 0.07 to 0.44], t = 2.81, p = .006, ΔR = 0.04). These findings were specific to frontostriatal brain regions, as frontoparietal, insular-subcortical, and total cerebral blood flow were not associated with progression of cardiometabolic risk. Moreover, cardiometabolic risk was not associated with frontostriatal cerebral blood flow responses 2 years later. CONCLUSIONS: Frontostriatal brain function may precede and possibly forecast the progression of cardiometabolic risk.


Assuntos
Fatores de Risco Cardiometabólico , Circulação Cerebrovascular/fisiologia , Adulto , Idoso , Pressão Sanguínea , Cognição/fisiologia , Feminino , Humanos , Estudos Longitudinais , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Marcadores de Spin
11.
Risk Anal ; 40(2): 399-407, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31483513

RESUMO

In communicating the risk that terror attacks pose to the public, government agencies and other organizations must understand which characteristics of an attack contribute to the public's perception of its severity. An attack's casualty count is one of the most commonly used metrics of a terror attack's severity, yet it is unclear whether the public responds to information about casualty count when forming affective and cognitive reactions to terror attacks. This study sought to characterize the "psychophysical function" relating terror attack casualty counts to the severity of the affective and cognitive reactions they elicit. We recruited n = 684 Mechanical Turk participants to read a realistic vignette depicting either a biological or radiological terror attack, whose death toll ranged from 20 to 50,000, and rated their levels of fear and anger along with the attack's severity. Even when controlling for the perceived plausibility of the scenarios, participants' severity ratings of each attack were logarithmic with respect to casualty count, while ratings of fear and anger did not significantly depend on casualty count. These results were consistent across attack weapon (biological vs. radiological) and time horizon of the casualties (same-day or anticipated to occur over several years). These results complement past work on life loss valuation and highlight a potential bifurcation between the public's affective and cognitive evaluations of terror attacks.


Assuntos
Medo , Psicofísica , Terrorismo , Adulto , Feminino , Humanos , Masculino , Percepção , Medição de Risco , Inquéritos e Questionários
12.
Risk Anal ; 40(3): 476-493, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31529801

RESUMO

This study examines how exploiting biases in probability judgment can enhance deterrence using a fixed allocation of defensive resources. We investigate attacker anchoring heuristics for conjunctive events with missing information to distort attacker estimates of success for targets with equal defensive resources. We designed and conducted a behavioral experiment functioning as an analog cyber attack with multiple targets requiring three stages of attack to successfully acquire a target. Each stage is associated with a probability of successfully attacking a layer of defense, reflecting the allocation of resources for each layer. There are four types of targets that have nearly equal likelihood of being successfully attacked, including one type with equally distributed success probabilities over every layer and three types with success probabilities that are concentrated to be lowest in the first, second, or third layer. Players are incentivized by a payoff system that offers a reward for successfully attacked targets and a penalty for failed attacks. We collected data from a total of 1,600 separate target selections from 80 players and discovered that the target type with the lowest probability of success on the first layer was least preferred among attackers, providing the greatest deterrent. Targets with equally distributed success probabilities across layers were the next least preferred among attackers, indicating greater deterrence for uniform-layered defenses compared to defenses that are concentrated at the inner (second or third) levels. This finding is consistent with both attacker anchoring and ambiguity biases and an interpretation of failed attacks as near misses.

13.
Risk Anal ; 40(3): 450-475, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31613022

RESUMO

This article describes a methodology for risk-informed benefit-cost analyses of homeland security research products. The methodology is field-tested with 10 research products developed for the U.S. Coast Guard. Risk-informed benefit-cost analysis is a tool for risk management that integrates elements of risk analysis, decision analysis, and benefit-cost analysis. The cost analysis methodology includes a full-cost accounting of research projects, starting with initial fundamental research costs and extending to the costs of implementation of the research products and, where applicable, training, maintenance, and upgrade costs. The benefits analysis methodology is driven by changes in costs and risks leading to five alternative models: cost savings at the same level of security, increased security at the same cost, signal detection improvements, risk reduction by deterrence, and value of information. The U.S. Coast Guard staff selected 10 research projects to test and generalize the methodology. Examples include tools to improve the detection of explosives, reduce the costs of harbor patrols, and provide better predictions of hurricane wind speeds and floods. Benefits models and estimates varied by research project and many input parameters of the benefit estimates were highly uncertain, so risk analysis for sensitivity testing and simulation was important. Aggregating across the 10 research products, we found an overall median net present value of about $385 million, with a range from $54 million (5th percentile) to $877 million (95th percentile). Lessons learned are provided for future applications.

14.
Am J Transplant ; 19(2): 488-500, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-29920927

RESUMO

Posttransplant diarrhea is associated with kidney allograft failure and death, but its etiology remains unknown in the majority of cases. Because altered gut microbial ecology is a potential basis for diarrhea, we investigated whether posttransplant diarrhea is associated with gut dysbiosis. We enrolled 71 kidney allograft recipients for serial fecal specimen collections in the first 3 months of transplantation and profiled the gut microbiota using 16S ribosomal RNA (rRNA) gene V4-V5 deep sequencing. The Shannon diversity index was significantly lower in 28 diarrheal fecal specimens from 25 recipients with posttransplant diarrhea than in 112 fecal specimens from 46 recipients without posttransplant diarrhea. We found a lower relative abundance of 13 commensal genera (Benjamini-Hochberg adjusted P ≤ .15) in the diarrheal fecal specimens including the same 4 genera identified in our prior study. The 28 diarrheal fecal specimens were also evaluated by a multiplexed polymerase chain reaction (PCR) assay for 22 bacterial, viral, and protozoan gastrointestinal pathogens, and 26 specimens were negative for infectious etiologies. Using PICRUSt (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States) to predict metagenomic functions, we found that diarrheal fecal specimens had a lower abundance of metabolic genes. Our findings suggest that posttransplant diarrhea is not associated with common infectious diarrheal pathogens but with a gut dysbiosis.


Assuntos
Bactérias/crescimento & desenvolvimento , Diarreia/etiologia , Disbiose/etiologia , Microbioma Gastrointestinal , Rejeição de Enxerto/etiologia , Falência Renal Crônica/cirurgia , Transplante de Rim/efeitos adversos , Adulto , Bactérias/genética , Bactérias/isolamento & purificação , Estudos de Casos e Controles , Estudos de Coortes , Diarreia/patologia , Disbiose/patologia , Fezes/microbiologia , Feminino , Seguimentos , Taxa de Filtração Glomerular , Rejeição de Enxerto/patologia , Sobrevivência de Enxerto , Humanos , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Prognóstico , RNA Ribossômico 16S/genética , Fatores de Risco
15.
Ann Rheum Dis ; 78(4): 465-472, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30793700

RESUMO

OBJECTIVES: To see if a group course delivered by rheumatology teams using cognitive-behavioural approaches, plus usual care, reduced RA fatigue impact more than usual care alone. METHODS: Multicentre, 2-year randomised controlled trial in RA adults (fatigue severity>6/10, no recent major medication changes). RAFT (Reducing Arthritis Fatigue: clinical Teams using CB approaches) comprises seven sessions, codelivered by pairs of trained rheumatology occupational therapists/nurses. Usual care was Arthritis Research UK fatigue booklet. Primary 26-week outcome fatigue impact (Bristol RA Fatigue Effect Numerical Rating Scale, BRAF-NRS 0-10). Intention-to-treat regression analysis adjusted for baseline scores and centre. RESULTS: 308/333 randomised patients completed 26 week data (156/175 RAFT, 152/158 Control). Mean baseline variables were similar. At 26 weeks, the adjusted difference between arms for fatigue impact change favoured RAFT (BRAF-NRS Effect -0.59, 95% CI -1.11 to -0.06), BRAF Multidimensional Questionnaire (MDQ) Total -3.42 (95% CI -6.44 to -0.39), Living with Fatigue -1.19 (95% CI -2.17 to -0.21), Emotional Fatigue -0.91 (95% CI -1.58 to -0.23); RA Self-Efficacy (RASE, +3.05, 95% CI 0.43 to 5.66) (14 secondary outcomes unchanged). Effects persisted at 2 years: BRAF-NRS Effect -0.49 (95% CI -0.83 to -0.14), BRAF MDQ Total -2.98 (95% CI -5.39 to -0.57), Living with Fatigue -0.93 (95% CI -1.75 to -0.10), Emotional Fatigue -0.90 (95% CI -1.44, to -0.37); BRAF-NRS Coping +0.42 (95% CI 0.08 to 0.77) (relevance of fatigue impact improvement uncertain). RAFT satisfaction: 89% scored > 8/10 vs 54% controls rating usual care booklet (p<0.0001). CONCLUSION: Multiple RA fatigue impacts can be improved for 2 years by rheumatology teams delivering a group programme using cognitive behavioural approaches. TRIAL REGISTRATION NUMBER: ISRCTN52709998.


Assuntos
Artrite Reumatoide/complicações , Terapia Cognitivo-Comportamental/métodos , Fadiga/terapia , Adaptação Psicológica , Adulto , Idoso , Artrite Reumatoide/psicologia , Emoções , Fadiga/etiologia , Fadiga/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Equipe de Assistência ao Paciente , Satisfação do Paciente , Autocuidado/métodos , Índice de Gravidade de Doença , Classe Social , Resultado do Tratamento
16.
Drug Metab Dispos ; 47(3): 194-202, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30598508

RESUMO

Tacrolimus exhibits low and variable drug exposure after oral dosing, but the contributing factors remain unclear. Based on our recent report showing a positive correlation between fecal abundance of Faecalibacterium prausnitzii and oral tacrolimus dose in kidney transplant patients, we tested whether F. prausnitzii and other gut abundant bacteria are capable of metabolizing tacrolimus. Incubation of F. prausnitzii with tacrolimus led to production of two compounds (the major one named M1), which was not observed upon tacrolimus incubation with hepatic microsomes. Isolation, purification, and structure elucidation using mass spectrometry and nuclear magnetic resonance spectroscopy indicated that M1 is a C-9 keto-reduction product of tacrolimus. Pharmacological activity testing using human peripheral blood mononuclear cells demonstrated that M1 is 15-fold less potent than tacrolimus as an immunosuppressant. Screening of 22 gut bacteria species revealed that most Clostridiales bacteria are extensive tacrolimus metabolizers. Tacrolimus conversion to M1 was verified in fresh stool samples from two healthy adults. M1 was also detected in the stool samples from kidney transplant recipients who had been taking tacrolimus orally. Together, this study presents gut bacteria metabolism as a previously unrecognized elimination route of tacrolimus, potentially contributing to the low and variable tacrolimus exposure after oral dosing.


Assuntos
Faecalibacterium prausnitzii/metabolismo , Microbioma Gastrointestinal/fisiologia , Imunossupressores/metabolismo , Tacrolimo/metabolismo , Administração Oral , Adulto , Idoso , Células Cultivadas , Relação Dose-Resposta a Droga , Fezes/química , Feminino , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/prevenção & controle , Voluntários Saudáveis , Humanos , Terapia de Imunossupressão/métodos , Imunossupressores/administração & dosagem , Imunossupressores/análise , Transplante de Rim/efeitos adversos , Leucócitos Mononucleares/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Simbiose , Tacrolimo/administração & dosagem , Tacrolimo/análise
17.
BJU Int ; 124(3): 522-531, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31012513

RESUMO

OBJECTIVE: To describe the frequency, intensity and duration of urological chronic pelvic pain syndrome symptom exacerbations ('flares'), as well as risk factors for these features, in the Multidisciplinary Approach to the Study of Chronic Pelvic Pain Epidemiology and Phenotyping longitudinal study. PARTICIPANTS AND METHODS: Current flare status ('urological or pelvic pain symptoms that are much worse than usual') was ascertained at each bi-weekly assessment. Flare characteristics, including start date, and current intensity of pelvic pain, urgency and frequency (scales of 0-10), were assessed for participants' first three flares and at three randomly selected times when they did not report a flare. Generalized linear and mixed effects models were used to investigate flare risk factors. RESULTS: Of the 385 eligible participants, 24.2% reported no flares, 22.9% reported one flare, 28.3% reported 2-3 flares, and 24.6% reported ≥4 flares, up to a maximum of 18 during the 11-month follow-up (median incidence rate = 0.13/bi-weekly assessment, range = 0.00-1.00). Pelvic pain (mean = 2.63-point increase) and urological symptoms (mean = 1.72) were both significantly worse during most flares (60.6%), with considerable within-participant variability (26.2-37.8%). Flare duration varied from 1 to 150 days (94.3% within-participant variability). In adjusted analyses, flares were more common, symptomatic, and/or longer-lasting in women and in those with worse non-flare symptoms, bladder hypersensitivity, and chronic overlapping pain conditions. CONCLUSION: In this foundational flare study, we found that pelvic pain and urological symptom flares were common, but variable in frequency and manifestation. We also identified subgroups of participants with more frequent, symptomatic, and/or longer-lasting flares for targeted flare management/prevention and further study.


Assuntos
Dor Crônica , Dor Pélvica , Adulto , Dor Crônica/epidemiologia , Dor Crônica/etiologia , Cistite Intersticial/complicações , Cistite Intersticial/epidemiologia , Feminino , Humanos , Estudos Longitudinais , Masculino , Dor Pélvica/epidemiologia , Dor Pélvica/etiologia , Prostatite/complicações , Prostatite/epidemiologia , Fatores de Risco
18.
Med Educ ; 53(8): 778-787, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31012131

RESUMO

CONTEXT: Globally, primary health care is facing workforce shortages. Longer and higher-quality placements in primary care increase the likelihood of medical students choosing this specialty. However, the recruitment and retention of community primary care teachers are challenging. Relevant research was predominantly carried out in the 1990s. We seek to understand contemporary facilitators and barriers to general practitioner (GP) engagement with undergraduate education. Communities of practice (CoP) theory offers a novel conceptualisation, which may be pertinent in other community-based teaching settings. METHODS: Semi-structured interviews were undertaken with 24 GP teachers at four UK medical schools. We purposively sampled GPs new to teaching, established GP teachers and GPs who had recently stopped teaching. We undertook NVivo-assisted deductive and inductive thematic analysis of transcripts. We used CoP theory to interpret data. RESULTS: Communities of practice theory illustrated that teachers negotiate membership of three CoPs: (i) clinical practice; (ii) the medical school, and (iii) teaching. The delivery of clinical care and teaching may be integrated or exist in tension. This can depend upon the positioning of the teaching and teacher as central or peripheral to the clinical CoP. Remuneration, workload, space and the expansion of GP trainee numbers impact on this. Teachers did not identify strongly as members of the medical school or a teaching community. Perceptions of membership were affected by medical school communication and support. The findings demonstrate gaps in medical school recruitment. CONCLUSIONS: This research demonstrates the marginalisation of primary care-based teaching and proposes a novel explanation rooted in CoP theory. Concepts including identity and membership may be pertinent to other community-based teaching settings. We recommend that medical schools review and broaden recruitment methods. Teacher retention may be improved by optimising the interface between medical schools and teachers, fostering a teaching community, increasing professional rewards for teaching involvement and altering medical school expectations of learning in primary care.


Assuntos
Medicina Geral/educação , Clínicos Gerais/provisão & distribuição , Estudantes de Medicina , Ensino , Educação de Graduação em Medicina , Docentes de Medicina/psicologia , Feminino , Humanos , Entrevistas como Assunto , Masculino , Reino Unido
19.
Risk Anal ; 39(3): 535-552, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30290397

RESUMO

Previous research has evaluated public risk perception and response to a natural hazards in various settings; however, most of these studies were conducted either with a single scenario or after a natural disaster struck. To better understand the dynamic relationships among affect, risk perception, and behavioral intentions related to natural disasters, the current study implements a simulation scenario with escalating weather intensity, and includes a natural experiment allowing comparison of public response before and after a severe tornado event with extensive coverage by the national media. The current study also manipulated the display of warning information, and investigated whether the warning system display format influences public response. Results indicate that (1) affect, risk perception, and behavioral intention escalated as weather conditions deteriorated, (2) responses at previous stages predicted responses at subsequent stages of storm progression, and (3) negative affect predicted risk perception. Moreover, risk perception and behavioral intention were heightened after exposure to the media coverage of an actual tornado disaster. However, the display format manipulation did not influence behavioral responses. The current study provides insight regarding public perception of predisaster warnings and the influence of exposure to media coverage of an actual disaster event.

20.
Behav Sci Law ; 37(2): 158-175, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30900348

RESUMO

Empirical studies of sexual offender recidivism have proliferated in recent decades. Virtually all of the studies define recidivism as a new legal charge or conviction for a sexual crime, and these studies tend to find recidivism rates of the order of 5-15% after 5 years and 10-25% after 10+ years. It is uncontroversial that such a definition of recidivism underestimates the true rate of sexual recidivism because most sexual crime is not reported to legal authorities, a principle known as the "dark figure of crime." To estimate the magnitude of the dark figure of sexual recidivism, this paper uses a probabilistic simulation approach in conjunction with the following: (i) victim self-report survey data about the rate of reporting sexual crime to legal authorities; (ii) offender self-report data about the number of victims per offender; and (iii) different assumptions about the chances of being convicted of a new sexual offense given that it is reported. Under any configuration of assumptions, the dark figure is substantial, and as a consequence the disparity between recidivism defined as a new legal charge or conviction for a sex crime and recidivism defined as actually committing a new sexual crime is large. These findings call into question the utility of recidivism studies that rely exclusively on official crime statistics to define sexual recidivism, and highlight the need for additional, long-term studies that use a variety of different measures to assess whether or not sexual recidivism has occurred.


Assuntos
Criminosos/estatística & dados numéricos , Reincidência/estatística & dados numéricos , Delitos Sexuais/estatística & dados numéricos , Vítimas de Crime/estatística & dados numéricos , Feminino , Humanos , Masculino
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA