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1.
Proc Natl Acad Sci U S A ; 117(14): 7712-7718, 2020 04 07.
Artigo em Inglês | MEDLINE | ID: mdl-32209670

RESUMO

On a planet experiencing global environmental change, the governance of natural resources depends on sustained collective action by diverse populations. Engaging in such collective action can only build upon the foundation of human cognition in social-ecological settings. To help understand this foundation, we assess the effect of cognitive abilities on the management of a common pool resource. We present evidence that two functionally distinct cognitive abilities, general and social intelligence, improve the ability of groups to manage a common pool resource. Groups high in both forms of intelligence engage in more effective collective action that is also more consistent, despite social or ecological change. This result provides a foundation for integrating the effects of cognitive abilities with other dimensions of cognitive diversity to explain when groups will and will not sustainably govern natural resources.


Assuntos
Comportamento Cooperativo , Inteligência Emocional , Cognição , Humanos , Curva de Aprendizado
2.
Transfusion ; 62(7): 1365-1376, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35748490

RESUMO

BACKGROUND: Platelet transfusion carries risk of transfusion-transmitted infection (TTI). Pathogen reduction of platelet components (PRPC) is designed to reduce TTI. Pulmonary adverse events (AEs), including transfusion-related acute lung injury and acute respiratory distress syndrome (ARDS) occur with platelet transfusion. STUDY DESIGN: An open label, sequential cohort study of transfusion-dependent hematology-oncology patients was conducted to compare pulmonary safety of PRPC with conventional PC (CPC). The primary outcome was the incidence of treatment-emergent assisted mechanical ventilation (TEAMV) by non-inferiority. Secondary outcomes included: time to TEAMV, ARDS, pulmonary AEs, peri-transfusion AE, hemorrhagic AE, transfusion reactions (TRs), PC and red blood cell (RBC) use, and mortality. RESULTS: By modified intent-to-treat (mITT), 1068 patients received 5277 PRPC and 1223 patients received 5487 CPC. The cohorts had similar demographics, primary disease, and primary therapy. PRPC were non-inferior to CPC for TEAMV (treatment difference -1.7%, 95% CI: (-3.3% to -0.1%); odds ratio = 0.53, 95% CI: (0.30, 0.94). The cumulative incidence of TEAMV for PRPC (2.9%) was significantly less than CPC (4.6%, p = .039). The incidence of ARDS was less, but not significantly different, for PRPC (1.0% vs. 1.8%, p = .151; odds ratio = 0.57, 95% CI: (0.27, 1.18). AE, pulmonary AE, and mortality were not different between cohorts. TRs were similar for PRPC and CPC (8.3% vs. 9.7%, p = .256); and allergic TR were significantly less with PRPC (p = .006). PC and RBC use were not increased with PRPC. DISCUSSION: PRPC demonstrated reduced TEAMV with no excess treatment-related pulmonary morbidity.


Assuntos
Síndrome do Desconforto Respiratório , Reação Transfusional , Plaquetas , Transfusão de Sangue , Estudos de Coortes , Humanos , Fármacos Fotossensibilizantes , Transfusão de Plaquetas/efeitos adversos , Síndrome do Desconforto Respiratório/etiologia , Síndrome do Desconforto Respiratório/terapia , Reação Transfusional/epidemiologia , Reação Transfusional/etiologia
3.
Sensors (Basel) ; 19(24)2019 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-31817602

RESUMO

The viability for dry coupling of piezoelectric ultrasonic transducer components was investigated, using a thin foil of annealed silver as a filler material/coupling agent at each component interface. Criteria used for room temperature evaluation were centered on signal-to-noise ratio (SNR) and echo bandwidth, for a Li-Nb based transducer operating in pulse-echo mode. A normal clamping stress of only 25 MPa, applied repeatedly over three loading cycles on a precisely-aligned transducer stack, was sufficient to yield backwall echoes with a SNR greater than 25 dB, and a 3 dB bandwidth of approximately 65%. This compares to a SNR of 32 dB and a 3 dB bandwidth of 65%, achievable when all transducer interfaces were coupled with ultrasonic gel. The respective roles of a soft filler material, alignment of transducer components, cyclic clamping, component roughness, and component flatness were evaluated in achieving this high efficiency dry coupling, with transducer clamping forces far lower than previously reported. Preliminary high temperature tests indicate that this coupling method is suitable for high temperature and achieves signal quality comparable to that at room temperature with ultrasonic gel.

4.
J Biol Chem ; 292(52): 21366-21380, 2017 12 29.
Artigo em Inglês | MEDLINE | ID: mdl-29123034

RESUMO

Studies of virulence determinants in the bacterial phytopathogen Erwinia amylovora, the cause of devastating fire blight disease in apple and pear, have shown that HsvA, a putative amidinotransferase enzyme located in the Hrp pathogenicity island, is required for systemic infection in apple. However, the mechanism by which HsvA contributes to virulence is unclear. To investigate the role of HsvA in virulence, we carried out a series of biochemical and structural studies to characterize the amidinotransferase activity of HsvA. We found that HsvA displays a preference for linear aliphatic polyamines as the amidino acceptor substrate, especially for spermidine and putrescine (Km values of 33 µm and 3.9 mm, respectively). The three-dimensional structure, determined at 2.30 Å resolution using X-ray crystallography, revealed that the overall architecture of HsvA is similar to that of the human arginine-glycine amidinotransferase in the creatine biosynthesis pathway. The active site is located in the core of the protein at the base of a long, narrow substrate access channel. Specific amino acids near the entrance of the channel may serve as major determinants of the substrate specificity, including a glutamate residue at the rim of the channel entrance that appears to be positioned to interact with the distal primary amine in the putrescine substrate as well as the internal and distal amines in the spermidine substrate. These results suggest potential in vivo functions for HsvA as a virulence factor in fire blight and may also provide a basis for strategies to control fire blight by inhibiting HsvA activity.


Assuntos
Amidinotransferases/metabolismo , Erwinia amylovora/metabolismo , Amidinotransferases/fisiologia , Cristalografia por Raios X/métodos , Erwinia amylovora/patogenicidade , Ilhas Genômicas/genética , Ilhas Genômicas/fisiologia , Malus/microbiologia , Doenças das Plantas/microbiologia , Poliaminas/metabolismo , Pyrus/microbiologia , Virulência , Fatores de Virulência/metabolismo
5.
Neuroimage ; 125: 189-197, 2016 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-26499807

RESUMO

Speed with which brain performs information processing influences overall cognition and is dependent on the white matter fibers. To understand genetic influences on processing speed and white matter FA, we assessed processing speed and diffusion imaging fractional anisotropy (FA) in related individuals from two populations. Discovery analyses were performed in 146 individuals from large Old Order Amish (OOA) families and findings were replicated in 485 twins and siblings of the Human Connectome Project (HCP). The heritability of processing speed was h(2)=43% and 49% (both p<0.005), while the heritability of whole brain FA was h(2)=87% and 88% (both p<0.001), in the OOA and HCP, respectively. Whole brain FA was significantly correlated with processing speed in the two cohorts. Quantitative genetic analysis demonstrated a significant degree to which common genes influenced joint variation in FA and brain processing speed. These estimates suggested common sets of genes influencing variation in both phenotypes, consistent with the idea that common genetic variations contributing to white matter may also support their associated cognitive behavior.


Assuntos
Encéfalo/fisiologia , Cognição/fisiologia , Genótipo , Substância Branca/fisiologia , Adolescente , Adulto , Idoso , Amish/genética , Anisotropia , Mapeamento Encefálico , Imagem de Tensor de Difusão , Feminino , Humanos , Interpretação de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Fenótipo , Sistema de Registros , Adulto Jovem
6.
Invest New Drugs ; 33(1): 247-53, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25388940

RESUMO

VEGF signaling through VEGFR-2 is the major factor in glioblastoma angiogenesis. CT-322, a pegylated protein engineered from the 10th type III human fibronectin domain, binds the VEGFR-2 extracellular domain with high specificity and affinity to block VEGF-induced VEGFR-2 signaling. This study evaluated CT-322 in an open-label run-in/phase 2 setting to assess its efficacy and safety in recurrent glioblastoma. Eligible patients had 1st, 2nd or 3rd recurrence of glioblastoma with measurable tumor on MRI and no prior anti-angiogenic therapy. The initial CT-322 dose was 1 mg/kg IV weekly, with plans to escalate subsequent patients to 2 mg/kg weekly if tolerated; within each CT-322 dose cohort, patients were randomized to ±irinotecan IV semiweekly. The primary endpoint was 6-month progression-free survival (PFS-6). Sixty-three patients with a median age of 56 were treated, the majority at first recurrence. One-third experienced serious adverse events, of which four were at least possibly related to study treatment (two intracranial hemorrhages and two infusion reactions). Twenty-nine percent of subjects developed treatment-emergent hypertension. The PFS-6 rate in the CT-322 monotherapy groups was 18.6 and 0.0 % in the 1 and 2 mg/kg treatment groups, respectively; results from the 2 mg/kg group indicated that the null hypothesis that PFS-6 ≤12 % could not be rejected. The study was terminated prior to reaching the planned enrollment for all treatment groups because data from the completed CT-322 2 mg/kg monotherapy treatment arm revealed insufficient efficacy. Despite biological activity and a tolerable side effect profile, CT-322 failed to meet the prespecified threshold for efficacy in recurrent glioblastoma.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Fibronectinas/uso terapêutico , Glioblastoma/tratamento farmacológico , Fragmentos de Peptídeos/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores , Adulto , Idoso , Antineoplásicos/efeitos adversos , Neoplasias Encefálicas/genética , Intervalo Livre de Doença , Feminino , Fibronectinas/efeitos adversos , Glioblastoma/genética , Glucuronosiltransferase/genética , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/genética , Fragmentos de Peptídeos/efeitos adversos , Polimorfismo Genético , Inibidores de Proteínas Quinases/efeitos adversos
7.
Blood Adv ; 8(9): 2290-2299, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38447116

RESUMO

ABSTRACT: Patients treated with antineoplastic therapy often develop thrombocytopenia requiring platelet transfusion, which has potential to exacerbate pulmonary injury. This study tested the hypothesis that amotosalen-UVA pathogen-reduced platelet components (PRPCs) do not potentiate pulmonary dysfunction compared with conventional platelet components (CPCs). A prospective, multicenter, open-label, sequential cohort study evaluated the incidence of treatment-emergent assisted mechanical ventilation initiated for pulmonary dysfunction (TEAMV-PD). The first cohort received CPC. After the CPC cohort, each site enrolled a second cohort transfused with PRPC. Other outcomes included clinically significant pulmonary adverse events (CSPAE) and the incidence of treatment-emergent acute respiratory distress syndrome (TEARDS) diagnosed by blinded expert adjudication. The incidence of TEAMV-PD in all patients (1068 PRPC and 1223 CPC) was less for PRPC (1.7 %) than CPC (3.1%) with a treatment difference of -1.5% (95% confidence interval [CI], -2.7 to -0.2). In patients requiring ≥2 PCs, the incidence of TEAMV-PD was reduced for PRPC recipients compared with CPC recipients (treatment difference, -2.4%; 95% CI, -4.2 to -0.6). CSPAE increased with increasing PC exposure but were not significantly different between the cohorts. For patients receiving ≥2 platelet transfusions, TEARDS occurred in 1.3% PRPC and 2.6% CPC recipients (P = .086). Bayesian analysis demonstrated PRPC may be superior in reducing TEAMV-PD and TEARDS for platelet transfusion recipients compared with CPC recipients, with 99.2% and 88.8% probability, respectively. In this study, PRPC compared with CPC demonstrated high probability of reduced severe pulmonary injury requiring assisted mechanical ventilation in patients with hematology disorders dependent on platelet transfusion. This trial was registered at www.ClinicalTrials.gov as #NCT02549222.


Assuntos
Transfusão de Plaquetas , Humanos , Transfusão de Plaquetas/efeitos adversos , Feminino , Pessoa de Meia-Idade , Masculino , Idoso , Lesão Pulmonar Aguda/etiologia , Plaquetas , Estudos Prospectivos , Adulto , Trombocitopenia/etiologia , Doenças Hematológicas/terapia
8.
J Clin Apher ; 28(5): 356-8, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23720092

RESUMO

INTRODUCTION: Bleeding risk because of thrombocytopenia in patients with thrombotic thrombocytopenic purpura (TTP) often causes concern during placement of the central venous catheter for plasma exchange. This perceived risk of bleeding often triggers prophylactic platelet transfusion; however, the risk of platelet transfusion is unknown. METHODS: Single institution review of bleeding episodes after catheter insertion in patients with suspected TTP. RESULTS: Fifty-five thrombocytopenic patients with presumed TTP underwent a total of 57 catheter insertion attempts. There were no major bleeding complications and no bleeding that required invasive intervention. Fourteen patients with a median platelet count of 12,000/µL were transfused with platelets prior to catheter placement. Five (35%) of the transfused patients had minor bleeding complications that did not require intervention. In the nontransfused group, 12 (28%) patients had minor bleeding that did not require invasive intervention and three patients experienced bleeding episodes that resolved after applying direct pressure. Eight (15%) patients died during admission. Mortality in the transfused group was 43% versus 5% in the nontransfused group. In general, patients receiving platelet transfusion prior to catheter insertion were more acutely ill. CONCLUSION: There were no major bleeding complications associated with plasma exchange catheter insertion in thrombocytopenic patients with presumed TTP. In light of the uncertain risk of platelet transfusion in patients with TTP, it may be reasonable to forgo prophylactic platelet transfusion prior to catheter placement.


Assuntos
Cateterismo Venoso Central/efeitos adversos , Hemorragia/etiologia , Troca Plasmática , Plasmaferese , Transfusão de Plaquetas , Púrpura Trombocitopênica Trombótica/complicações , Púrpura Trombocitopênica Trombótica/terapia , Remoção de Componentes Sanguíneos , Estudos de Coortes , Hematoma/terapia , Humanos , Contagem de Plaquetas , Estudos Retrospectivos , Risco , Trombocitopenia/terapia , Resultado do Tratamento
9.
Int J Prosthodont ; 0(0): 0, 2023 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-37196037

RESUMO

PURPOSE: To evaluate the effect of restoration design on fracture resistance and stress distribution of veneered and monolithic 3-unit zirconia fixed partial dentures (FDPs) using finite element analysis (FEA). MATERIALS AND METHODS: Identical epoxy resin replicas of mandibular second premolar and second molar (to serve as abutment for the 3-unit bridge) were divided into four groups (n = 10): monolithic zirconia (MZ) restorations; conventional layering veneering technique (ZL), heat-pressed technique (ZP), or CAD/CAM lithium disilicate glass ceramic (CAD-on). Specimens were subjected to compressive cyclic loading on the mesio-buccal cusp of the pontic (load range 50 to 600 N; aqueous environment; 500,000 cycles) in a universal testing machine. Data were statistically analyzed at 5% significance level with Fisher exact test and Kaplan-Meier survival analysis. 3D models were constructed in accordance with experimental groups. The stress distribution in each model was analyzed and evaluated according to the location and magnitude of the maximum principal stresses (MPS) using ANSYS software. RESULTS: Specimens from ZL and ZP groups failed at different stages of the 500,000 cycles fatigue, while CAD-on and MZ restorations survived fatigue test. Statistically, there was a significant difference between the groups (P < .001). The MPS were located under the mesial connector in both monolithic and bilayered 3-unit zirconia FDPs. These stresses were found to be higher in monolithic geometries compared to bilayered zirconia FDPs. CONCLUSION: Monolithic 3-unit zirconia and CAD-on zirconia frameworks resulted in superior fracture resistance. Restoration design significantly affected the stress distribution of 3-unit zirconia FDPs.

10.
PLoS One ; 17(8): e0263399, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35947612

RESUMO

Solving complex problems, from biodiversity conservation to reducing inequality, requires large scale collective action among diverse stakeholders to achieve a common goal. Research relevant to meeting this challenge must model the interaction of stakeholders with diverse cognitive capabilities and the complexity of the problem faced by stakeholders to predict the success of collective action in various contexts. Here, we build a model from first principles of cognitive abilities, diversity, and socio-environmental complexity to identify the sets of conditions under which groups most effectively engage in collective action to solve governance problems. We then fit the model to small groups, U.S. states, and countries. Our model illustrates the fundamental importance of understanding the interaction between cognitive abilities, diversity, and the complexity of socio-environmental challenges faced by stakeholders today. Our results shed light on the ability of groups to solve complex problems and open new avenues of research into the interrelationship between cognition, institutions, and the environments in which they co-evolve.


Assuntos
Conservação dos Recursos Naturais , Política Ambiental , Biodiversidade , Cognição
11.
Psychol Sci ; 22(10): 1265-9, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21931154

RESUMO

In the research reported here, we examined whether processing speed mediates the development of general intelligence (g) in adolescence. Using the Armed Services Vocational Aptitude Battery, a battery of 12 diverse cognitive tests, we assessed processing speed and g in a large sample of 13- to 17-year-olds obtained from the National Longitudinal Survey of Youth (N = 6,969). The direct effect of age on g was small compared with the total effect of age on g, which was almost fully mediated through speed. The results suggest that increases in g in adolescence can be attributed to increases in mental speed.


Assuntos
Desenvolvimento do Adolescente/fisiologia , Inteligência/fisiologia , Processos Mentais/fisiologia , Tempo de Reação/fisiologia , Adolescente , Fatores Etários , Cognição/fisiologia , Feminino , Humanos , Estudos Longitudinais , Masculino , Testes Neuropsicológicos/estatística & dados numéricos
12.
J Neurooncol ; 101(1): 155-9, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-20524043

RESUMO

Striae distensae (stretch marks) are a common complication seen in patients on chronic corticosteroid therapy. Under certain circumstances, primary brain tumor patients require chronic corticosteroid therapy and can suffer from striae distensae. Bevacizumab, a humanized monoclonal antibody to vascular endothelial growth factor-A (VEGF-A) is now more widely used for the treatment of primary brain tumors. In this paper, we present four cases of ulcerated striae distensae in primary brain tumor patients on concurrent corticosteroid and bevacizumab therapy. Because of bevacizumab's effects on wound healing and its recent accelerated approval for recurrent glioblastoma multiforme (GBM), the most common malignant primary brain tumor in adults, this novel skin complication should be considered in patients on concurrent corticosteroid and bevacizumab therapy.


Assuntos
Corticosteroides/efeitos adversos , Anticorpos Monoclonais/efeitos adversos , Antineoplásicos/efeitos adversos , Neoplasias Encefálicas/tratamento farmacológico , Glioma/tratamento farmacológico , Estrias de Distensão/induzido quimicamente , Úlcera/induzido quimicamente , Corticosteroides/uso terapêutico , Adulto , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados , Antineoplásicos/uso terapêutico , Bevacizumab , Dexametasona/efeitos adversos , Dexametasona/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estrias de Distensão/patologia , Úlcera/patologia , Adulto Jovem
13.
Pers Individ Dif ; 50(4): 470-474, 2011 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-21562615

RESUMO

This research examined the predictive validity of the SAT (formerly, the Scholastic Aptitude Test) for high and low ability groups. SAT scores and college GPAs were obtained from the 1997 National Longitudinal Survey of Youth. Subjects were classified as high or low ability by g factor scores from the Armed Services Vocational Aptitude Battery. SAT correlations with GPA were higher for high than low ability subjects. SAT g loadings (i.e., SAT correlations with g) were equivalent for both groups. This is the first study to show that the predictive validity of the SAT varies for ability groups that differ in g. The results contradict a presumption, based on Spearman's Law of Diminishing Returns, that a test's predictive validity should be lower for high ability subjects. Further research is needed to identify factors that contribute to the predictive validity of the SAT for groups that differ in g.

14.
Hum Brain Mapp ; 30(8): 2581-94, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19067326

RESUMO

We explored the relationship between structural neuroimaging-based indices of cerebral integrity and executive control function (ECF) in two groups of healthy subjects: A maturing group (33 subjects; 19-29 years) and a senescing group (38 adults; 30-90 years). ECF was assessed using the Executive Interview (EXIT) battery. Cortical indices of cerebral integrity included GM thickness, intergyral span, and sulcal span, each measured for five cortical regions per hemisphere. Subcortical indices included fractional anisotropy (FA), measured using track-based-spatial-statistics (TBSS), and the volume of T2-hyperintense WM (HWM). In the maturing group, no significant relationships between neuroanatomical changes and ECF were found; however, there were hints that late-term maturation of cerebral WM influenced variability in ECF. In the senescing group, the decline in ECF corresponded to atrophic changes in cerebral WM (sulcal and intergyral span) primarily in the superior frontal and anterior cingulate regions. A large fraction of the variability in ECF (62%) can be explained by variability in the structural indices from these two regions.


Assuntos
Envelhecimento , Córtex Cerebral/anatomia & histologia , Processos Mentais , Adulto , Idoso , Idoso de 80 Anos ou mais , Anisotropia , Encéfalo/anatomia & histologia , Imagem de Difusão por Ressonância Magnética , Feminino , Humanos , Imageamento Tridimensional , Modelos Lineares , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Análise de Regressão , Adulto Jovem
15.
Nat Commun ; 10(1): 875, 2019 02 20.
Artigo em Inglês | MEDLINE | ID: mdl-30787277

RESUMO

Cognitive abilities underpin the capacity of individuals to build models of their environment and make decisions about how to govern resources. Here, we test the functional intelligences proposition that functionally diverse cognitive abilities within a group are critical to govern common pool resources. We assess the effect of two cognitive abilities, social and general intelligence, on group performance on a resource harvesting and management game involving either a negative or a positive disturbance to the resource base. Our results indicate that under improving conditions (positive disturbance) groups with higher general intelligence perform better. However, when conditions deteriorate (negative disturbance) groups with high competency in both general and social intelligence are less likely to deplete resources and harvest more. Thus, we propose that a functional diversity of cognitive abilities improves how effectively social groups govern common pool resources, especially when conditions deteriorate and groups need to re-evaluate and change their behaviors.

16.
Transl Stroke Res ; 10(5): 495-508, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-30617992

RESUMO

Active transport of microRNAs (miRNA) in extracellular vesicles (EV) occurs in disease. Circulating EV-packaged miRNAs in the serum of stroke patients were compared to stroke mimics with matched cardio- and cerebrovascular risk factors, with corroboration of results in a pre-clinical model. An unbiased miRNA microarray was performed in stroke vs. stroke mimic patients (n = 39). Results were validated (n = 173 patients) by real-time quantitative polymerase chain reaction. miRNA expression was quantified in total serum/EV (n = 5-7) of naïve adult spontaneously hypertensive stroke-prone rats (SHRSP), their normotensive reference strain (Wistar Kyoto, WKY) and in circulating EV (n = 3), peri-infarct brain (n = 6), or EV derived from this region (n = 3) in SHRSP following transient middle cerebral artery occlusion (tMCAO). Circulating EV concentration did not differ between stroke and stroke mimic patients. The microarray identified many altered EV-packaged miRNAs: levels of miRNA-17-5p, -20b-5p and -93-5p (miRNA-17 family members) and miRNA-27b-3p were significantly (p ≤ 0.05) increased in stroke vs. stroke mimic patients. Patients with small vessel disease (SVD) consistently had the highest miRNA levels. Circulating EV concentration was unaltered between naïve SHRSP and WKY but levels of miRNA-17-5p and -93-5p were significantly increased in SHRSP. tMCAO in SHRSP did not further alter circulating EV miRNA-17 family member expression and nor did it change total miRNA-17 family levels in peri-infarct brain tissue or in EV isolated from this region at 24 h post-tMCAO. Changes in EV packaged miRNA expression was validated in patients with stroke, particularly those with SVD and corroborated pre-clinically. Together, altered circulating EV levels of miRNA-17 family members may reflect the chronic sequelae underlying cerebrovascular SVD rather than the acute ischemic stroke itself.


Assuntos
Isquemia Encefálica/sangue , Doenças de Pequenos Vasos Cerebrais/sangue , Vesículas Extracelulares/metabolismo , MicroRNAs/sangue , Acidente Vascular Cerebral/sangue , Animais , Modelos Animais de Doenças , Masculino , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Acidente Vascular Cerebral/complicações
17.
J Clin Apher ; 23(5): 151-6, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18712712

RESUMO

Idiopathic thrombotic thrombocytopenic purpura (TTP) is caused by the production of autoantibodies against the Von Willebrand factor cleaving enzyme. This provides a rationale for the use of rituximab in this disease. We report a retrospective review of 12 patients treated with rituximab for TTP refractory to plasma exchange. Eleven patients were treated during initial presentation, and one patient was treated for recurrent relapse. Ten patients responded to treatment. Median time to response after first dose of rituximab was 10 days (5-32). Of the 11 patients treated during initial presentation, nine remain free of relapse after a median follow-up of 57+ months (1+-79+). Two patients died during initial treatment. One patient was lost to follow-up 1 month after achieving complete response. The patient treated for recurrent disease during second relapse remained disease free for 2years, relapsed and was treated again with rituximab, and was in remission for 22 months. She relapsed again, was retreated, and has now been in remission for 21+ months. We conclude that rituximab is an useful addition to plasma exchange treatment in TTP, but its exact role and dosing need to be verified in prospective studies.


Assuntos
Anticorpos Monoclonais/administração & dosagem , Fatores Imunológicos/administração & dosagem , Troca Plasmática , Púrpura Trombocitopênica Idiopática/terapia , Proteínas ADAM/sangue , Proteína ADAMTS13 , Adulto , Anticorpos Monoclonais Murinos , Autoanticorpos/sangue , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Púrpura Trombocitopênica Idiopática/sangue , Púrpura Trombocitopênica Idiopática/mortalidade , Estudos Retrospectivos , Rituximab , Fatores de Tempo
18.
J Intell ; 6(3)2018 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-31162470

RESUMO

In a prior issue of the Journal of Intelligence, I argued that the most important scientific issue in intelligence research was to identify specific abilities with validity beyond g (i.e., variance common to mental tests) (Coyle, T.R. Predictive validity of non-g residuals of tests: More than g. Journal of Intelligence 2014, 2, 21-25.). In this Special Issue, I review my research on specific abilities related to non-g factors. The non-g factors include specific math and verbal abilities based on standardized tests (SAT, ACT, PSAT, Armed Services Vocational Aptitude Battery). I focus on two non-g factors: (a) non-g residuals, obtained after removing g from tests, and (b) ability tilt, defined as within-subject differences between math and verbal scores, yielding math tilt (math > verbal) and verbal tilt (verbal > math). In general, math residuals and tilt positively predict STEM criteria (college majors, jobs, GPAs) and negatively predict humanities criteria, whereas verbal residuals and tilt show the opposite pattern. The paper concludes with suggestions for future research, with a focus on theories of non-g factors (e.g., investment theories, Spearman's Law of Diminishing Returns, Cognitive Differentiation-Integration Effort Model) and a magnification model of non-g factors.

19.
J Colloid Interface Sci ; 523: 35-44, 2018 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-29605739

RESUMO

HYPOTHESIS: Superhydrophobic surfaces are often created by fabricating suitable surface structures from low-surface-energy organic materials using processes that are not suitable for large-scale fabrication. Rare earth oxides (REO) exhibit hydrophobic behavior that is unusual among oxides. Solution precursor plasma spray (SPPS) deposition is a rapid, one-step process that can produce ceramic coatings with fine scale columnar structures. Manipulation of the structure of REO coatings through variation in deposition conditions may allow the wetting behavior to be controlled. EXPERIMENTS: Yb2O3 coatings were fabricated via SPPS. Coating structure was investigated by scanning electron microscopy, digital optical microscopy, and x-ray diffraction. The static water contact angle and roll-off angle were measured, and the dynamic impact of water droplets on the coating surface recorded. FINDINGS: Superhydrophobic behavior was observed; the best coating exhibited a water contact angle of ∼163°, a roll-off angle of ∼6°, and complete droplet rebound behavior. All coatings were crystalline Yb2O3, with a nano-scale roughness superimposed on a micron-scale columnar structure. The wetting behaviors of coatings deposited at different standoff distances were correlated with the coating microstructures and surface topographies. The self-cleaning, water flushing and water jetting tests were conducted and further demonstrated the excellent and durable hydrophobicity of the coatings.

20.
Am J Clin Oncol ; 41(2): 159-162, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-26658237

RESUMO

PURPOSE: Efficacy signals but substantial myelosuppression were demonstrated in a single arm phase II study of paclitaxel poliglumex (PPX) in combination with temozolomide (TMZ) and radiation therapy (RT) for first-line treatment of glioblastoma. The objective of this randomized phase II trial was to assess the efficacy and safety of single-agent PPX with RT (PPX/RT) versus TMZ with RT (TMZ/RT) for glioblastoma without O-methylguanine-DNA methyltransferase (MGMT) methylation. MATERIALS AND METHODS: Patients with glioblastoma with unmethylated MGMT without prior chemotherapy or RT were eligible. Patients were randomly assigned 2:1 to PPX, 50 mg/m/wk for 6 weeks, or standard TMZ, with concurrent 60.0 Gy RT. One month after completion of chemoradiation all patients received standard maintenance TMZ. The primary endpoint was progression-free survival (PFS). RESULTS: Of the 164 patients enrolled, 86 were MGMT unmethylated. Of these, 63 patients were randomized (42 to PPX/RT and 21 to TMZ/RT). Fifty-nine patients could be analyzed. The median PFS was 9 months in the PPX/RT group and 9.5 months in the TMZ/RT group (hazard ratio in the PPX/RT group, 1.10; 95% confidence interval, 0.79-2.08; P=0.75). Median overall survival was 16 versus 14.8 months for PPX/RT and TMZ/RT groups, respectively (hazard ratio, 1.44; 95% confidence interval, 0.75-2.77; P=0.27). In the PPX and TMZ groups 44% versus 22% of patients, respectively, experienced one or more grade 3 or higher toxicities during chemoradiation. CONCLUSIONS: PPX/RT did not improve PFS or overall survival. This study provides an effective trial design for screening RT sensitizers in glioblastoma.


Assuntos
Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/terapia , Metilases de Modificação do DNA/metabolismo , Enzimas Reparadoras do DNA/metabolismo , Glioblastoma/mortalidade , Glioblastoma/terapia , Paclitaxel/análogos & derivados , Ácido Poliglutâmico/análogos & derivados , Proteínas Supressoras de Tumor/metabolismo , Centros Médicos Acadêmicos , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/patologia , Metilação de DNA , Intervalo Livre de Doença , Relação Dose-Resposta a Droga , Relação Dose-Resposta à Radiação , Feminino , Seguimentos , Glioblastoma/patologia , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Paclitaxel/administração & dosagem , Ácido Poliglutâmico/administração & dosagem , Radioterapia Adjuvante , Método Simples-Cego , Análise de Sobrevida , Resultado do Tratamento , Estados Unidos
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