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1.
J Public Health Policy ; 44(4): 616-633, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37899483

RESUMO

There is a pressing need to develop and evaluate culturally tailored, community-based interventions that address hypertension management among low-income African American women. We employed a randomized controlled trial to test the effectiveness of the Prime Time Sister Circles® Program in reducing blood pressure and body mass index among low-income African American women ages with hypertension. Study participants (N = 339) were African American women aged 40-75 years who were diagnosed with hypertension and received their primary care at government funded health centers in Washington, D.C. Compared to the usual care group, Prime Time Sister Circles® participation was associated with a reduction in systolic BP by - 2.45 (CI - 6.13, 1.23) mmHg, a reduction in diastolic BP by - 3.66 mmHg (CI - 6.32, - 0.99), and a change in BMI by - 0.26 (CI - 2.00, 1.48) from baseline to 15 months. The results suggest that culturally tailored community-based interventions can improve hypertension management in low-income women.


Assuntos
Negro ou Afro-Americano , Hipertensão , Feminino , Humanos , Pressão Sanguínea , Pobreza , Estados Unidos , Washington , Serviços de Saúde Comunitária
2.
J Biomed Inform ; 145: 104476, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37598737

RESUMO

OBJECTIVE: We developed and evaluated a novel one-shot distributed algorithm for evidence synthesis in distributed research networks with rare outcomes. MATERIALS AND METHODS: Fed-Padé, motivated by a classic mathematical tool, Padé approximants, reconstructs the multi-site data likelihood via Padé approximant whose key parameters can be computed distributively. Thanks to the simplicity of [2,2] Padé approximant, Fed-Padé requests an extremely simple task and low communication cost for data partners. Specifically, each data partner only needs to compute and share the log-likelihood and its first 4 gradients evaluated at an initial estimator. We evaluated the performance of our algorithm with extensive simulation studies and four observational healthcare databases. RESULTS: Our simulation studies revealed that a [2,2]-Padé approximant can well reconstruct the multi-site likelihood so that Fed-Padé produces nearly identical estimates to the pooled analysis. Across all simulation scenarios considered, the median of relative bias and rate of instability of our Fed-Padé are both <0.1%, whereas meta-analysis estimates have bias up to 50% and instability up to 75%. Furthermore, the confidence intervals derived from the Fed-Padé algorithm showed better coverage of the truth than confidence intervals based on the meta-analysis. In real data analysis, the Fed-Padé has a relative bias of <1% for all three comparisons for risks of acute liver injury and decreased libido, whereas the meta-analysis estimates have a substantially higher bias (around 10%). CONCLUSION: The Fed-Padé algorithm is nearly lossless, stable, communication-efficient, and easy to implement for models with rare outcomes. It provides an extremely suitable and convenient approach for synthesizing evidence in distributed research networks with rare outcomes.


Assuntos
Algoritmos , Aprendizado de Máquina , Simulação por Computador , Metanálise como Assunto
3.
J Acoust Soc Am ; 154(2): 721-729, 2023 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-37556564

RESUMO

Acoustic communications often have limited data rates because of the intrinsically low frequencies. Exploring new spatial modes to increase data bandwidth at fixed frequency is a possible solution to this problem. Here, we demonstrate acoustic wave chirality transmission between two reciprocal metamaterial vortex wave antennas, generating and sensing transmitted acoustic wave chirality through the sub-wavelength geometry of the system. By adding an acoustic leaky wave surface to a ring resonator waveguide, acoustic vortex waves with positive or negative integer mode chirality are independently radiated and detected using a small number of microphones. Through computational simulation and experimental verification, using three-dimensional printed waveguides, we show that the vortex mode chirality can be transferred between two opposing acoustic vortex wave antennas across a small unguided air gap. We also show that emission into an external waveguide can provide long distance data transmission. This demonstrates the first use of metamaterial vortex wave antennas as chiral, mode multi-channel data transceivers.

4.
Opt Express ; 30(23): 42276-42282, 2022 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-36366684

RESUMO

We report the dynamics and control of the orientational and positional order of ensembles of gold nanorods suspended in air at standard temperature and pressure using externally applied electric fields, demonstrating an active aerosol. Light filter, valve and gradient responses are shown, establishing active aerosols as a unique type of optical element we term component-less optics.

5.
Biometrics ; 78(2): 660-667, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-33715153

RESUMO

The propensity methodology is widely used in medical research to compare different treatments in designs with a nonrandomized treatment allocation. The inverse probability weighted (IPW) estimators are a primary tool for estimating the average treatment effect but the large variance of these estimators is often a significant concern for their reliable use in practice. Inspired by Rao-Blackwellization, this paper proposes a method to smooth an IPW estimator by replacing the weights in the original estimator by their mean over a distribution of the potential treatment assignment. In our simulation study, the smoothed IPW estimator achieves a substantial variance reduction over its original version with only a small increased bias, for example two-to-sevenfold variance reduction for the three IPW estimators in Lunceford and Davidian [Statistics in Medicine, 23(19), 2937-2960]. In addition, our proposed smoothing can also be applied to the locally efficient and doubly robust estimator for added protection against model misspecification. An implementation in R is provided.


Assuntos
Modelos Estatísticos , Projetos de Pesquisa , Viés , Simulação por Computador , Probabilidade , Pontuação de Propensão
6.
J Acoust Soc Am ; 149(6): 4327, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34241492

RESUMO

Additive manufacturing has expanded greatly in recent years with the promise of being able to create complex and custom structures at will. Enhanced control over the microstructure properties, such as percent porosity, is valuable to the acoustic design of materials. In this work, aluminum foams are fabricated using a modified powder bed fusion method, which enables voxel-by-voxel printing of structures ranging from fully dense to approximately 50% porosity. To understand the acoustic response, samples are measured in an acoustic impedance tube and characterized with the Johnson-Champoux-Allard-Lafarge model for rigid-frame foams. Bayesian statistical inversion of the model parameters is performed to assess the applicability of commonly employed measurement and modeling methods for traditional foams to the additively manufactured, low porosity aluminum foams. This preliminary characterization provides insights into how emerging voxel-by-voxel additive manufacturing approaches could be used to fabricate acoustic metal foams and what could be learned about the microstructure using traditional measurement and analysis techniques.

7.
Sensors (Basel) ; 19(11)2019 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-31212636

RESUMO

Submersible robotics have improved in efficiency and versatility by incorporating features found in aquatic life, ranging from thunniform kinematics to shark skin textures. To fully realize these benefits, sensor systems must be incorporated to aid in object detection and navigation through complex flows. Again, inspiration can be taken from biology, drawing on the lateral line sensor systems and neuromast structures found on fish. To maintain a truly soft-bodied robot, a man-made flow sensor must be developed that is entirely complaint, introducing no rigidity to the artificial "skin." We present a capacitive cupula inspired by superficial neuromasts. Fabricated via lost wax methods and vacuum injection, our 5 mm tall device exhibits a sensitivity of 0.5 pF/mm (capacitance versus tip deflection) and consists of room temperature liquid metal plates embedded in a soft silicone body. In contrast to existing capacitive examples, our sensor incorporates the transducers into the cupula itself rather than at its base. We present a kinematic theory and energy-based approach to approximate capacitance versus flow, resulting in equations that are verified with a combination of experiments and COMSOL simulations.

8.
PLoS One ; 13(12): e0209622, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30586453

RESUMO

INTRODUCTION: A significant population of our wounded veterans suffer long-term functional consequences of visual deficit, disorientation, dizziness, and an impaired ability to read. These symptoms may be related to damage within the otolith pathways that contribute to ocular alignment. The purpose of this study was to compare perception of vertical and torsional ocular alignment between veterans and healthy controls in an upright and supine test position. MATERIALS AND METHODS: Veterans (n = 26) with reports of dizziness were recruited from the East Orange Veterans Administration Hospital. Healthy controls (n = 26) were recruited from both Johns Hopkins University and the East Orange VA. Each subject performed 20 trials each of a novel vertical and torsional binocular alignment perception test. Veterans underwent semicircular canal and otolith pathway function testing. RESULTS: 88% of the Veterans had an absent otolith response. Only the veterans had an abnormally large variability in perception of both vertical and torsional ocular alignment, and in both upright and supine position. Neither post-traumatic stress disorder, nor depression contributed to the misperception in binocular alignment. CONCLUSIONS: Our novel method of measuring vertical and torsional misalignment distinguishes veterans with dizziness from healthy controls. The high prevalence of absent otolith function seems to explain this result. Further studies are needed to better understand the fundamental mechanism responsible for the increased variability of perception of binocular alignment.


Assuntos
Tontura/diagnóstico , Membrana dos Otólitos/fisiopatologia , Transtornos de Estresse Pós-Traumáticos/fisiopatologia , Transtornos da Visão/fisiopatologia , Tontura/fisiopatologia , Olho/fisiopatologia , Movimentos Oculares/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reflexo Vestíbulo-Ocular/fisiologia , Transtornos de Estresse Pós-Traumáticos/diagnóstico , Vertigem/fisiopatologia , Veteranos , Transtornos da Visão/diagnóstico , Visão Binocular/fisiologia
9.
J Appl Gerontol ; 37(2): 177-202, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-27006434

RESUMO

PURPOSE: The purpose of this article was to assess segregation's role on race differences in hypertension among non-Hispanic Blacks and Whites aged 50 and over. METHOD: Hypertension was defined as systolic blood pressure (BP) ≥ 140 mmHg, diastolic BP ≥ 90 mmHg, or self-reported antihypertensive medication use. Segregation measures combined race, neighborhood racial composition, and individual and neighborhood poverty level. Logistic models produced odds ratios and 95% confidence intervals (CIs) for each segregation category, adjusting for health-related factors. RESULTS: Blacks in Black (OR = 2.54, CI = [1.61, 4.00]), White (OR = 2.56, CI = [1.24, 5.31]), and integrated neighborhoods (OR = 3.23, CI = [1.72, 6.03]) had greater odds of hypertension compared with Whites in White neighborhoods. Poor Whites in poor neighborhoods (OR = 1.74, CI = [1.09, 2.76]), nonpoor Blacks in nonpoor (OR = 3.03, CI = [1.79, 5.12]) and poor neighborhoods (OR = 4.08, CI = [2.16, 7.70]), and poor Blacks in nonpoor (OR = 4.35, CI = [2.17, 8.73]) and poor neighborhoods (OR = 2.75, CI = [1.74, 4.36]) had greater odds compared with nonpoor Whites in nonpoor neighborhoods. CONCLUSION: Interventions targeting hypertension among older adults should consider neighborhood compositions.


Assuntos
Exposição Ambiental/efeitos adversos , Exposição Ambiental/estatística & dados numéricos , Hipertensão/epidemiologia , Características de Residência , Segregação Social , Negro ou Afro-Americano/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Anti-Hipertensivos/uso terapêutico , Estudos Transversais , Feminino , Humanos , Hipertensão/tratamento farmacológico , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Prevalência , Meio Social , Estados Unidos , População Branca/estatística & dados numéricos
10.
J Acoust Soc Am ; 139(6): 3251, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-27369149

RESUMO

Acoustic antennas have long been utilized to directionally steer acoustic waves in both air and water. Typically, these antennas are comprised of arrays of active acoustic elements, which are electronically phased to steer the acoustic profile in the desired direction. A new technology, known as an acoustic leaky wave antenna (LWA), has recently been shown to achieve directional steering of acoustic waves using a single active transducer coupled to a transmission line passive aperture. The LWA steers acoustic energy by preferential coupling to an input frequency and can be designed to steer from backfire to endfire, including broadside. This paper provides an analysis of resolution as a function of both input frequency and antenna length. Additionally, the resolution is compared to that achieved using an array of active acoustic elements.

11.
J Acoust Soc Am ; 139(6): 3325, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-27369158

RESUMO

The paper presents a method to design and characterize mechanically robust solid acoustic metamaterials suitable for operation in dense fluids such as water. These structures, also called metafluids, behave acoustically as inertial fluids characterized by anisotropic mass densities and isotropic bulk modulus. The method is illustrated through the design and experimental characterization of a metafluid consisting of perforated steel plates held together by rubber coated magnetic spacers. The spacers are very effective at reducing the effective shear modulus of the structure, and therefore effective at minimizing the ensuing coupling between the shear and pressure waves inside the solid effective medium. Inertial anisotropy together with fluid-like acoustic behavior are key properties that bring transformation acoustics in dense fluids closer to reality.

12.
Eur J Neurosci ; 43(3): 443-50, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26332647

RESUMO

Functional testing has assumed a progressively dominant role in validating the success of experimental nerve repair. Results obtained in one model, however, cannot predict the results in others because they reflect the coordinated interaction of several muscles across multiple joints. As a result, many combinations of topographically correct and incorrect muscle reinnervation could produce the same result. We have developed a binary model in which elbow flexors and extensors are reinnervated, and elbow flexion and extension are the functions tested. The musculocutaneous and radial nerves of Lister-Hooded rats were subjected to axonotmetic injuries that produced increasing degrees of axonal misdirection at the site of injury ranging from simple crush to transection and rotational offset of proximal and distal stumps. Elbow function was tested with a device that requires coordinated elbow extension to reach sugar pellets and flexion to return them to the mouth. After 12 weeks of regeneration, motoneurons projecting to the distal musculocutaneous nerve were retrogradely labelled with WGA-Ruby and scored regarding their location within musculocutaneous or radial motoneuron pools. The severity of axonal misdirection resulting from the initial surgery was mirrored by progressive degrees of inappropriate reinnervation of the musculocutaneous nerve by radial nerve axons. The specificity of reinnervation predicted elbow function (r = 0.72), whereas the number of motoneurons regenerating did not. This model is thus well suited to study the interaction of regeneration specificity and function across a single joint, and to produce data that can be generalized more broadly than those obtained from more complex models.


Assuntos
Regeneração Nervosa , Traumatismos dos Nervos Periféricos/fisiopatologia , Nervo Radial/fisiologia , Recuperação de Função Fisiológica , Animais , Masculino , Músculo Esquelético/inervação , Traumatismos dos Nervos Periféricos/reabilitação , Traumatismos dos Nervos Periféricos/cirurgia , Nervo Radial/cirurgia , Ratos
13.
Sci Rep ; 5: 13175, 2015 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-26282067

RESUMO

We explore an acoustic scattering cancellation shell for buoyant hollow cylinders submersed in a water background. A thin, low-shear, elastic coating is used to cancel the monopole scattering from an air-filled, neutrally buoyant steel shell for all frequencies where the wavelength is larger than the object diameter. By design, the uncoated shell also has an effective density close to the aqueous background, independently canceling its dipole scattering. Due to the significantly reduced monopole and dipole scattering, the compliant coating results in a hollow cylindrical inclusion that is simultaneously impedance and sound speed matched to the water background. We demonstrate the proposed cancellation method with a specific case, using an array of hollow steel cylinders coated with thin silicone rubber shells. These experimental results are matched to finite element modeling predictions, confirming the scattering reduction. Additional calculations explore the optimization of the silicone coating properties. Using this approach, it is found that scattering cross-sections can be reduced by 20 dB for all wavelengths up to k0a = 0.85.

14.
Prev Med ; 58: 33-9, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24161713

RESUMO

BACKGROUND: Food store availability may determine the quality of food consumed by residents. Neighborhood racial residential segregation, poverty, and urbanicity independently affect food store availability, but the interactions among them have not been studied. PURPOSE: To examine availability of supermarkets, grocery stores, and convenience stores in US census tracts according to neighborhood racial/ethnic composition, poverty, and urbanicity. METHODS: Data from 2000 US Census and 2001 InfoUSA food store data were combined and multivariate negative binomial regression models employed. RESULTS: As neighborhood poverty increased, supermarket availability decreased and grocery and convenience stores increased, regardless of race/ethnicity. At equal levels of poverty, Black census tracts had the fewest supermarkets, White tracts had the most, and integrated tracts were intermediate. Hispanic census tracts had the most grocery stores at all levels of poverty. In rural census tracts, neither racial composition nor level of poverty predicted supermarket availability. CONCLUSIONS: Neighborhood racial composition and neighborhood poverty are independently associated with food store availability. Poor predominantly Black neighborhoods face a double jeopardy with the most limited access to quality food and should be prioritized for interventions. These associations are not seen in rural areas which suggest that interventions should not be universal but developed locally.


Assuntos
Comércio/estatística & dados numéricos , Indústria Alimentícia/normas , Áreas de Pobreza , Racismo/estatística & dados numéricos , Características de Residência , População Urbana , Distribuição Binomial , Censos , Indústria Alimentícia/economia , Humanos , Análise Multivariada , Estados Unidos
15.
Am J Public Health ; 104(11): 2147-55, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24228660

RESUMO

OBJECTIVES: We sought to determine the role of neighborhood poverty and racial composition on race disparities in diabetes prevalence. METHODS: We used data from the 1999-2004 National Health and Nutrition Examination Survey and 2000 US Census to estimate the impact of individual race and poverty and neighborhood racial composition and poverty concentration on the odds of having diabetes. RESULTS: We found a race-poverty-place gradient for diabetes prevalence for Blacks and poor Whites. The odds of having diabetes were higher for Blacks than for Whites. Individual poverty increased the odds of having diabetes for both Whites and Blacks. Living in a poor neighborhood increased the odds of having diabetes for Blacks and poor Whites. CONCLUSIONS: To address race disparities in diabetes, policymakers should address problems created by concentrated poverty (e.g., lack of access to reasonably priced fruits and vegetables, recreational facilities, and health care services; high crime rates; and greater exposures to environmental toxins). Housing and development policies in urban areas should avoid creating high-poverty neighborhoods.


Assuntos
Diabetes Mellitus/epidemiologia , Disparidades nos Níveis de Saúde , Pobreza/estatística & dados numéricos , Grupos Raciais/estatística & dados numéricos , Adolescente , Negro ou Afro-Americano/estatística & dados numéricos , Criança , Diabetes Mellitus/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos Nutricionais , Prevalência , Características de Residência/estatística & dados numéricos , Fatores de Risco , População Branca/estatística & dados numéricos , Adulto Jovem
16.
Front Cell Neurosci ; 7: 123, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23966909

RESUMO

Stroke in the neonatal brain frequently results in neurologic impairments including cognitive disability. We investigated the effect of long-term sodium valproate (valproate) and trichostatin A (TSA) treatment upon post-stroke neurogenesis in the dentate gyrus (DG) of stroke-injured immature mice. Decreased or abnormal integration of newborn DG neurons into hippocampal circuits can result in impaired visual-spatial function, abnormal modulation of mood-related behaviors, and the development of post-stroke epilepsy. Unilateral carotid ligation of P12 CD1 mice was followed by treatment with valproate, TSA, or vehicle for 2 weeks, bromodeoxyuridine (BrdU) administration for measurement of neurogenesis, and perfusion at P42 or P60. Behavior testing was conducted from P38-42. No detrimental effects on behavior testing were noted with TSA treatment, but mildly impaired cognitive function was noted with valproate-treated injured animals compared to normal animals. Significant increases in DG neurogenesis with both TSA and valproate treatment were noted with later administration of BrdU. Increased mortality and impaired weight gain was noted in the valproate-treated ligated animals, but not in the TSA-treated animals. In summary, the impact of histone deacetylase (HDAC) inhibition upon post-stroke subgranular zone neurogenesis is likely to depend on the age of the animal at the time point when neurogenesis is assessed, duration of HDAC inhibition before BrdU labeling, and/or the stage in the evolution of the injury.

17.
Pediatr Res ; 72(5): 525-30, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22918523

RESUMO

BACKGROUND: Maternal thyroid autoantibodies during pregnancy have been implicated in neurodevelopmental delays, including early childhood cognitive deficits. We evaluated whether maternal autoantibodies to thyroid peroxidase (TPOaAbs) during late pregnancy were associated with childhood intelligence quotient (IQ) scores in their offspring and how the children's TPOaAb-associated sensorineural hearing loss (HL) might affect the result. METHODS: We evaluated banked third-trimester sera corresponding to 1,733 children for whom childhood cognitive test scores and audiology data were available. The mothers and their children participated in the National Institutes of Health (NIH)-sponsored Collaborative Perinatal Project (CPP) that ran from 1959 to 1974. RESULTS: A modest, statistically significant, effect of TPOaAbs on cognitive performance observed at 4 y of age lessened in both magnitude and P value by the age of 7 y. Children with sensorineural HL (SNHL) had lower IQ scores at both ages. CONCLUSION: Our data suggest that the reported effect of maternal TPOaAbs on IQ may involve early developmental delays or transient effects rather than permanent deficits. Reports associating TPOaAbs directly with IQ may reflect a portion with unexamined TPOaAb-associated SNHL. Whether the TPOaAb-associated SNHL is in the neurodevelopmental pathway of later cognitive delays or is independently associated with IQ requires investigation in other studies.


Assuntos
Autoanticorpos/sangue , Autoantígenos/imunologia , Autoimunidade , Desenvolvimento Infantil , Deficiências do Desenvolvimento/imunologia , Perda Auditiva Neurossensorial/imunologia , Inteligência , Iodeto Peroxidase/imunologia , Proteínas de Ligação ao Ferro/imunologia , Efeitos Tardios da Exposição Pré-Natal , Fatores Etários , Audiometria de Tons Puros , Baltimore/epidemiologia , Criança , Cognição , Deficiências do Desenvolvimento/diagnóstico , Deficiências do Desenvolvimento/epidemiologia , Deficiências do Desenvolvimento/psicologia , Feminino , Perda Auditiva Neurossensorial/diagnóstico , Perda Auditiva Neurossensorial/epidemiologia , Perda Auditiva Neurossensorial/psicologia , Humanos , Testes de Inteligência , Modelos Lineares , Masculino , Análise Multivariada , Gravidez , Terceiro Trimestre da Gravidez , Prevalência , Fatores de Risco
18.
Pediatr Res ; 68(5): 446-51, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-20661168

RESUMO

Rett syndrome (RTT) is an X-linked neurodevelopmental disorder caused by mutations in the MECP2 gene. In 49 female RTT children, aged 1.9-17 y, bone mass was assessed and correlated with clinical parameters and mutations involving the MECP2 gene. We also studied five adult females, aged 20-33 y, and one male child, aged 6 y. Lumbar spine bone mineral content (BMC) and bone mineral density (BMD) were correlated with weight, height, BMI, clinical severity, degree of scoliosis, use of anticonvulsants, and ambulatory status. L1-L4 BMD and BMC showed that 48.9% of them had BMD values >2 SD below age-related norms. BMD values were in the osteoporotic range in the five adult females with RTT. Eleven percent of the children and adults with RTT experienced fractures. Low bone mass was correlated with marginal significance to clinical severity and ambulation but not to scoliosis or anticonvulsant use. Lowest bone mass occurred in patients with T158M or R270X mutations but without statistical significance. Studies in a murine model of RTT confirmed low bone mass as an inherent component of this syndrome. MECP2 mutations and clinical parameters impact bone mass in RTT, but an association with a specific mutation was not demonstrable.


Assuntos
Densidade Óssea/genética , Proteína 2 de Ligação a Metil-CpG/genética , Mutação , Síndrome de Rett/genética , Síndrome de Rett/patologia , Adolescente , Adulto , Animais , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Camundongos , Camundongos Knockout , Síndrome de Rett/fisiopatologia , Adulto Jovem
19.
Eur J Hum Genet ; 18(8): 933-41, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20424645

RESUMO

Investigators performing genetic association studies grapple with how to measure strength of association evidence, choose sample size, and adjust for multiple testing. We apply the evidential paradigm (EP) to genetic association studies, highlighting its strengths. The EP uses likelihood ratios (LRs), as opposed to P-values or Bayes' factors, to measure strength of association evidence. We derive EP methodology to estimate sample size, adjust for multiple testing, and provide informative graphics for drawing inferences, as illustrated with a Rolandic Epilepsy (RE) fine-mapping study. We focus on controlling the probability of observing weak evidence for or against association (W) rather than type I errors (M). For example, for LR> or =32 representing strong evidence, at one locus with n=200 cases, n=200 controls, W=0.134, whereas M=0.005. For n=300 cases and controls, W=0.039 and M=0.004. These calculations are based on detecting an OR=1.5. Despite the common misconception, one is not tied to this planning value for analysis; rather one calculates the likelihood at all possible values to assess evidence for association. We provide methodology to adjust for multiple tests across m loci, which adjusts M and W for m. We do so for (a) single-stage designs, (b) two-stage designs, and (c) simultaneously controlling family-wise error rate (FWER) and W. Method (c) chooses larger sample sizes than (a) or (b), whereas (b) has smaller bounds on the FWER than (a). The EP, using our innovative graphical display, identifies important SNPs in elongator protein complex 4 (ELP4) associated with RE that may not have been identified using standard approaches.


Assuntos
Mapeamento Cromossômico/estatística & dados numéricos , Epilepsia Rolândica/genética , Estudo de Associação Genômica Ampla/estatística & dados numéricos , Funções Verossimilhança , Modelos Genéticos , Teorema de Bayes , Canadá , Estudos de Casos e Controles , Interpretação Estatística de Dados , Estudo de Associação Genômica Ampla/métodos , Humanos , Probabilidade
20.
Exp Neurol ; 223(1): 112-8, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-19464291

RESUMO

The role of pathway-derived growth factors in the support of peripheral axon regeneration remains elusive. Few appropriate knock-out mice are available, and gene silencing techniques are rarely 100% effective. To overcome these difficulties, we have developed an in vitro organotypic co-culture system that accurately models peripheral nerve repair in the adult mammal. Spinal cord sections from P4 mice that express YFP in their neurons are used to innervate segments of P4 peripheral nerve. This reconstructed ventral root is then transected and joined to a nerve graft. Growth of axons across the nerve repair and into the graft can be imaged repeatedly with fluorescence microscopy to define regeneration speed, and parent neurons can be labeled in retrograde fashion to identify contributing neurons. Nerve graft harvested from adult mice remains viable in culture by both morphologic and functional criteria. Motoneurons are supported with GDNF for the first week in culture, after which they survive axotomy, and are thus functionally adult. This platform can be modified by using motoneurons from any genetically modified mouse that can be bred to express XFP, by harvesting nerve graft from any source, or by treating the culture systemically with antibodies, growth factors, or pathway inhibitors. The regeneration environment is controlled to a degree not possible in vivo, and the use of experimental animals is reduced substantially. The flexibility and control offered by this technique should thus make it a useful tool for the study of regeneration biology.


Assuntos
Modelos Animais , Neurônios Motores/fisiologia , Regeneração Nervosa/fisiologia , Animais , Animais Recém-Nascidos , Técnicas de Cocultura/métodos , Dextranos , Fator Neurotrófico Derivado de Linhagem de Célula Glial/farmacologia , Fator de Crescimento Insulin-Like I/farmacologia , Proteínas Luminescentes/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Microscopia Eletrônica de Transmissão/métodos , Neurônios Motores/efeitos dos fármacos , Fator de Crescimento Neural/farmacologia , Regeneração Nervosa/efeitos dos fármacos , Regeneração Nervosa/genética , Técnicas de Cultura de Órgãos/métodos , Nervos Periféricos/fisiologia , Nervos Periféricos/ultraestrutura , Rodaminas , Medula Espinal/citologia
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