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Search Results: 1 - 10 of 118648 matches for " Brandon T. Nokes "
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In Vitro Assessment of the Inflammatory Breast Cancer Cell Line SUM 149: Discovery of 2 Single Nucleotide Polymorphisms in the RNase L Gene
Brandon T. Nokes, Heather E. Cunliffe, Bonnie LaFleur, David W. Mount, Robert B. Livingston, Bernard W. Futscher, Julie E. Lang
Journal of Cancer , 2013,
Abstract: Background: Inflammatory breast cancer (IBC) is a rare, highly aggressive form of breast cancer. The mechanism of IBC carcinogenesis remains unknown. We sought to evaluate potential genetic risk factors for IBC and whether or not the IBC cell lines SUM149 and SUM190 demonstrated evidence of viral infection. Methods: We performed single nucleotide polymorphism (SNP) genotyping for 2 variants of the ribonuclease (RNase) L gene that have been correlated with the risk of prostate cancer due to a possible viral etiology. We evaluated dose-response to treatment with interferon-alpha (IFN-α); and assayed for evidence of the putative human mammary tumor virus (HMTV, which has been implicated in IBC) in SUM149 cells. A bioinformatic analysis was performed to evaluate expression of RNase L in IBC and non-IBC. Results: 2 of 2 IBC cell lines were homozygous for RNase L common missense variants 462 and 541; whereas 2 of 10 non-IBC cell lines were homozygous positive for the 462 variant (p= 0.09) and 0 of 10 non-IBC cell lines were homozygous positive for the 541 variant (p = 0.015). Our real-time polymerase chain reaction (RT-PCR) and Southern blot analysis for sequences of HMTV revealed no evidence of the putative viral genome. Conclusion: We discovered 2 SNPs in the RNase L gene that were homozygously present in IBC cell lines. The 462 variant was absent in non-IBC lines. Our discovery of these SNPs present in IBC cell lines suggests a possible biomarker for risk of IBC. We found no evidence of HMTV in SUM149 cells. A query of a panel of human IBC and non-IBC samples showed no difference in RNase L expression. Further studies of the RNase L 462 and 541 variants in IBC tissues are warranted to validate our in vitro findings.
Biomechanical Investigation of Locked Plate Fixation with Suture Augmentation in a Comminuted Three-Part Proximal Humerus Fracture Model  [PDF]
Brian T. Palumbo, Sergio Gutierrez, Brandon Santoni, Mark Mighell
Open Journal of Orthopedics (OJO) , 2017, DOI: 10.4236/ojo.2017.77020
Abstract: Background: Locked plating of displaced proximal humerus fractures is a reliable fixation method. Greater tuberosity (GT) failure is a known complication that may occur in the early post-operative period. Despite postoperative immobilization, the rotator cuff continues to exert significant forces on fracture fragments. Our hypothesis is that suture augmentation will provide greater stability of the GT than locked plating alone. To prove this we developed a three-part proximal humerus fracture model to test fracture fixation. Methods: A biomechanical study was performed on nine fresh frozen cadaveric humeri, simulating a three-part proximal humerus fracture (Neer Classification). Rotator cuff tendon insertions were preserved to physiologically load the proximal humerus. The fracture was reduced and fixed with a locked plate alone or a locked plate with suture augmentation of the GT to the rotator cuff tendons. Biomechanical testing utilized a materials testing machine and a three-dimensional motion capture system to quantify interfragmentary motion under torsional loading as a function of fixation type. Results: Greater torsional stability was observed in the suture-augmented group compared to the plate only group (p = 0.0012). There were two catastrophic failures in the plate only group while none of the suture reinforced constructs failed. Conclusions: In our model, suture-augmentation of the GT to the rotator cuff provided greater stability than locked plating alone. The current study provides a biome-chanical basis for reinforcing locked plate constructs with sutures. The added stability afforded by suture-augmentation may mitigate rotator cuff forces in the clinical setting, avoiding fracture displacement in the early postoperative rehabilitation period.
Challenges confronting road freight transport and the use of vehicle-pavement interaction analysis in addressing these challenges
W J vd M Steyn,C L Monismith,W A Nokes,J T Harvey
Journal of the South African Institution of Civil Engineering , 2012,
Abstract: Traditional arguments for maintaining riding quality of pavement are expanded in this paper to examine the effects of deteriorating riding quality on vehicle operating costs, freight damage and logistics. The objectives of this paper are to analyse the effects of different levels of riding quality on a truck and its freight, and to discuss potential applications of the analysis in terms of effectiveness of the freight transport system. The paper discusses needs and drivers influencing freight transport costs, vehicle-pavement interaction concepts, and the potential physical effects and costs from roads with deteriorating riding quality. A case study is presented analysing vehicle-pavement interaction for selected roadways in California. It is concluded that investments in pavement and freight transport industry improvements can be investigated by applying vehicle-pavement interaction analysis to evaluate damage to pavement, vehicle and freight that would result from alternative levels of pavement riding quality. The paper recommends that existing concepts, tools and resources such as dedicated truck lanes and vehicle-pavement interaction analysis can help to improve the freight transport system. A framework is proposed to better understand the scale of potential impacts of riding quality from localised effects to larger-scale influences, including costs to customers and global competitiveness.
The Submm and mm Excess of the SMC: Magnetic Dipole Emission from Magnetic Nanoparticles?
B. T. Draine,Brandon Hensley
Physics , 2012, DOI: 10.1088/0004-637X/757/1/103
Abstract: The Small Magellanic Cloud (SMC) has surprisingly strong submm and mm-wavelength emission that is inconsistent with standard dust models, including those with emission from spinning dust. Here we show that the emission from the SMC may be understood if the interstellar dust mixture includes magnetic nanoparticles, emitting magnetic dipole radiation resulting from thermal fluctuations in the magnetization. The magnetic grains can be metallic iron, magnetite Fe3O4, or maghemite gamma-Fe2O3. The required mass of iron is consistent with elemental abundance constraints. The magnetic dipole emission is predicted to be polarized orthogonally to the normal electric dipole radiation if the nanoparticles are inclusions in larger grains. We speculate that other low-metallicity galaxies may also have a large fraction of the interstellar Fe in magnetic materials.
Magnetic Nanoparticles in the Interstellar Medium: Emission Spectrum and Polarization
B. T. Draine,Brandon Hensley
Physics , 2012, DOI: 10.1088/0004-637X/765/2/159
Abstract: The presence of ferromagnetic or ferrimagnetic nanoparticles in the interstellar medium would give rise to magnetic dipole radiation at microwave and submm frequencies. Such grains may account for the strong mm-wavelength emission observed from a number of low-metallicity galaxies, including the Small Magellanic Cloud. We show how to calculate the absorption and scattering cross sections for such grains, with particular attention to metallic Fe, magnetite Fe3O4, and maghemite gamma-Fe2O3, all potentially present in the interstellar medium. The rate of Davis-Greenstein alignment by magnetic dissipation is also estimated. We determine the temperature of free-flying magnetic grains heated by starlight and we calculate the polarization of the magnetic dipole emission from both free-fliers and inclusions. For inclusions, the magnetic dipole emission is expected to be polarized orthogonally relative to the normal electric dipole radiation. Finally, we present self-consistent dielectric functions for metallic Fe, magnetite Fe3O4, and maghemite gamma-Fe2O3, enabling calculation of absorption and scattering cross sections from microwave to X-ray wavelengths.
Enhanced Response of T Cells from Murine Gammaherpesvirus 68-Infected Mice Lacking the Suppressor of T Cell Receptor Signaling Molecules Sts-1 and Sts-2
Brandon Cieniewicz, Nicholas Carpino, Laurie T. Krug
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0090196
Abstract: The human gammaherpesviruses establish life-long infections that are associated with the development of lymphomas and neoplasms, especially in immunocompromised individuals. T cells play a crucial role in the control of gammaherpesvirus infection through multiple functions, including the direct killing of infected cells, production of cytokines such as interferon-γ (IFN-γ), and costimulation of B cells. Impaired T cell function in mice infected with murine gammaherpesvirus 68 (MHV68) leads to increased reactivation and pathologies, including a higher incidence of lymphoid hyperplasia. Here we report that the absence of Suppressor of TCR signaling ?1 and ?2 (Sts-1-/-/2-/-) during MHV68 infection leads to the generation of T cells with significantly heightened responses. Transient differences in the T and B cell response of infected Sts-1-/-/2-/- (Sts dKO) mice were also observed when compared to WT mice. However, these alterations in the immune response and the overall absence of Sts-1 and Sts-2 did not impact viral pathogenesis or lead to pathology. Acute lytic replication in the lungs, establishment of latency in the spleen and reactivation from latency in the spleen in the Sts dKO mice were comparable to WT mice. Our studies indicate that Sts-1 and Sts-2 are not required for the immune control of MHV68 in a normal course of gammaherpesvirus infection, but suggest that interference with negative regulators of T cell responses might be further explored as a safe and efficacious strategy to improve adoptive T cell therapy.
Prothrombin complex concentrate (Beriplex P/N) in severe bleeding: experience in a large tertiary hospital
David Bruce, Tim JC Nokes
Critical Care , 2008, DOI: 10.1186/cc6987
Abstract: Thirty consecutive patients who had received PCC were identified from blood transfusion records. For cardiac surgery and warfarin reversal, PCC was administered in accordance with hospital protocols. PCC was administered to cardiac and other surgical patients responding poorly to recognized blood products, whereas it was administered first-line to patients with life-threatening bleeds and requiring warfarin reversal, in accordance with British Committee for Standards in Haematology guidelines. We conducted a retrospective analysis of patient records in order to ascertain PCC dose, use of other blood products and response to PCC (clotting screen results before and after PCC administration, haemostasis achievement, and survival).Six patients (20%) were excluded because of inadequate documentation (n = 5) or acquired haemophilia (n = 1). Therefore, 24 patients were included in the analysis: coronary artery bypass graft (n = 5), mitral/aortic valve replacement (n = 2), other surgery (n = 9) and warfarin reversal (n = 8). Most patients (83.3%) received no more than 1500 IU of Beriplex P/N 500. Considerable reduction in administration of other blood products was seen during the 24 hours after PCC administration. Partial or complete haemostasis was achieved in 14 out of 18 cases (77.8%). In total, 12 out of 24 patients (50%) died during the study; two-thirds of the deaths were considered unrelated to bleeding. No thrombotic complications or adverse drug reactions were observed.This study emphasizes the value of PCC in reversing the effects of oral anticoagulant therapy in bleeding patients. It also demonstrates the potential value of PCC in controlling bleeding in patients undergoing cardiac and other surgical procedures. The use of PCC in bleeding patients without hereditary or anticoagulation-related coagulopathy is novel, and further investigation is warranted. In the future, it may be possible to use PCC as a substitute for fresh frozen plasma in this setting; adequate
Has oral fluid the potential to replace serum for the evaluation of population immunity levels?: a study of measles, rubella and hepatitis B in rural Ethiopia
Nokes,D. James; Enquselassie,Fikre; Nigatu,Wondatir; Vyse,Andrew J.; Cohen,Bernard J.; Brown,David W.G.; Cutts,Felicity T.;
Bulletin of the World Health Organization , 2001, DOI: 10.1590/S0042-96862001000700003
Abstract: objective: to assess the suitability of using oral-fluid samples for determining the prevalence of immunity to vaccine-preventable infections. methods: paired blood and oral-fluid samples were obtained from 853 individuals of all ages from a rural ethiopian community. oral fluid around the gums was screened for measles- and rubella-specific antibodies using enhanced igg antibody capture (gac) enzyme-linked immunosorbent assays (elisas), and for anti-hbc antibodies using a prototype gacelisa. igg antibodies in serum to measles, rubella and hbc were determined using commercial elisas. findings: relative to serum, oral fluid assay sensitivity and specificity were as follows: 98% and 87% for measles, 79% and 90% for rubella, and 43% and 87% for anti-hbc. these assay characteristics yielded population prevalence estimates from oral fluid with a precision equal to that of serum for measles (all ages) and rubella (ages <20 years). conclusion: our results suggest that oral fluid could have the potential to replace serum in igg antibody prevalence surveys. further progress requires assessment of variation in assay performance between populations as well as the availability of standardized, easy to use assays.
Power Law versus Exponential State Transition Dynamics: Application to Sleep-Wake Architecture
Jesse Chu-Shore,M. Brandon Westover,Matt T. Bianchi
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0014204
Abstract: Despite the common experience that interrupted sleep has a negative impact on waking function, the features of human sleep-wake architecture that best distinguish sleep continuity versus fragmentation remain elusive. In this regard, there is growing interest in characterizing sleep architecture using models of the temporal dynamics of sleep-wake stage transitions. In humans and other mammals, the state transitions defining sleep and wake bout durations have been described with exponential and power law models, respectively. However, sleep-wake stage distributions are often complex, and distinguishing between exponential and power law processes is not always straightforward. Although mono-exponential distributions are distinct from power law distributions, multi-exponential distributions may in fact resemble power laws by appearing linear on a log-log plot.
Significance testing as perverse probabilistic reasoning
M Brandon Westover, Kenneth D Westover, Matt T Bianchi
BMC Medicine , 2011, DOI: 10.1186/1741-7015-9-20
Abstract: Medicine is a science of uncertainty and an art of probability. - Sir William Osler [1]While probabilistic considerations have always been fundamental to medical reasoning, formal probabilistic arguments have only become ubiquitous in the medical literature in recent decades [2,3]. Meanwhile, many have voiced concerns that physicians generally misunderstand probabilistic concepts, with potential serious negative implications for the quality of medical science and ultimately public health [3-12]. This problem has been demonstrated previously by surveys similar to the following quiz [13], which we administered to a group of 246 physicians at three major US teaching hospitals (Barnes Jewish Hospital, Brigham and Women's Hospital, and Massachusetts General Hospital). The reader is likewise invited to answer before proceeding.Consider a typical medical research study, for example designed to test the efficacy of a drug, in which a null hypothesis H0 ('no effect') is tested against an alternative hypothesis H1 ('some effect'). Suppose that the study results pass a test of statistical significance (that is P-value <0.05) in favor of H1. What has been shown?1. H0 is false.2. H1 is true.3. H0 is probably false.4. H1 is probably true.5. Both (1) and (2).6. Both (3) and (4).7. None of the above.The answer profile for our participants is shown in Table 1. This essay is for readers who, like 93% of our respondents, did not confidently select the correct answer, (7), 'None of the above'. We hasten to assure the reader that this is not a trick question. Rather, it is a matter of elementary probabilistic logic. As will be clear by the end of this essay answers (1) to (6) involve 'leaping to conclusions', in violation of the basic law of probabilistic inference, Bayes' rule. We will see that Bayes' rule is an essential principle governing all reasoning in the face of uncertainty. Moreover, understanding Bayes' rule serves as a potent prophylaxis against statistical fallacies such as
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