49 research outputs found

    Is Acceleration Used for Ocular Pursuit and Spatial Estimation during Prediction Motion?

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    Here we examined ocular pursuit and spatial estimation in a linear prediction motion task that emphasized extrapolation of occluded accelerative object motion. Results from the ocular response up to occlusion showed that there was evidence in the eye position, velocity and acceleration data that participants were attempting to pursue the moving object in accord with the veridical motion properties. They then attempted to maintain ocular pursuit of the randomly-ordered accelerative object motion during occlusion but this was not ideal, and resulted in undershoot of eye position and velocity at the moment of object reappearance. In spatial estimation there was a general bias, with participants less likely to report object reappearance being behind than ahead of the expected position. In addition, participants’ spatial estimation did not take into account the effects of object acceleration. Logistic regression indicated that spatial estimation was best predicted for the majority of participants by the difference between actual object reappearance position and an extrapolation based on pre-occlusion velocity. In combination, and in light of previous work, we interpret these findings as showing that eye movements are scaled in accord with the effects of object acceleration but do not directly specify information for accurate spatial estimation in prediction motion

    A nucleotide binding rectification Brownian ratchet model for translocation of Y-family DNA polymerases

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    Y-family DNA polymerases are characterized by low-fidelity synthesis on undamaged DNA and ability to catalyze translesion synthesis over the damaged DNA. Their translocation along the DNA template is an important event during processive DNA synthesis. In this work we present a Brownian ratchet model for this translocation, where the directed translocation is rectified by the nucleotide binding to the polymerase. Using the model, different features of the available structures for Dpo4, Dbh and polymerase ι in binary and ternary forms can be easily explained. Other dynamic properties of the Y-family polymerases such as the fast translocation event upon dNTP binding for Dpo4 and the considerable variations of the processivity among the polymerases can also be well explained by using the model. In addition, some predicted results of the DNA synthesis rate versus the external force acting on Dpo4 and Dbh polymerases are presented. Moreover, we compare the effect of the external force on the DNA synthesis rate of the Y-family polymerase with that of the replicative DNA polymerase

    An Active Site Aromatic Triad in Escherichia coli DNA Pol IV Coordinates Cell Survival and Mutagenesis in Different DNA Damaging Agents

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    DinB (DNA Pol IV) is a translesion (TLS) DNA polymerase, which inserts a nucleotide opposite an otherwise replication-stalling N2-dG lesion in vitro, and confers resistance to nitrofurazone (NFZ), a compound that forms these lesions in vivo. DinB is also known to be part of the cellular response to alkylation DNA damage. Yet it is not known if DinB active site residues, in addition to aminoacids involved in DNA synthesis, are critical in alkylation lesion bypass. It is also unclear which active site aminoacids, if any, might modulate DinB's bypass fidelity of distinct lesions. Here we report that along with the classical catalytic residues, an active site “aromatic triad”, namely residues F12, F13, and Y79, is critical for cell survival in the presence of the alkylating agent methyl methanesulfonate (MMS). Strains expressing dinB alleles with single point mutations in the aromatic triad survive poorly in MMS. Remarkably, these strains show fewer MMS- than NFZ-induced mutants, suggesting that the aromatic triad, in addition to its role in TLS, modulates DinB's accuracy in bypassing distinct lesions. The high bypass fidelity of prevalent alkylation lesions is evident even when the DinB active site performs error-prone NFZ-induced lesion bypass. The analyses carried out with the active site aromatic triad suggest that the DinB active site residues are poised to proficiently bypass distinctive DNA lesions, yet they are also malleable so that the accuracy of the bypass is lesion-dependent

    Red Blood Cell Transfusions Impact Pneumonia Rates After Coronary Artery Bypass Grafting

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    BACKGROUND: Pneumonia, a known complication of coronary artery bypass grafting (CABG), significantly increases a patient\u27s risk of morbidity and mortality. Although not well characterized, red blood cell (RBC) transfusions may increase a patient\u27s risk of pneumonia. We describe the relationship between RBC transfusion and postoperative pneumonia after CABG. METHODS: A total of 16,182 consecutive patients underwent isolated CABG between 2011 and 2013 at 1 of 33 hospitals in the state of Michigan. We used multivariable logistic regression to estimate the relative odds of pneumonia associated with the use or number of RBC units (0, 1, 2, 3, 4, 5, and ≥ 6). We adjusted for predicted risk of mortality, preoperative hematocrit values, history of pneumonia, cardiopulmonary bypass duration, and medical center. We confirmed the strength and direction of these relationships among selected clinical subgroups in a secondary analysis. RESULTS: Five hundred seventy-six (3.6%) patients had pneumonia and 6,451 (39.9%) received RBC transfusions. There was a significant association between any RBC transfusion and pneumonia (adjusted odds ratio [ORadj], 3.4; p \u3c 0.001). There was a dose response between number of units and odds of pneumonia, with a ptrend less than 0.001. Patients receiving only 2 units of RBCs had a 2-fold (ORadj, 2.1; p \u3c 0.001) increased odds of developing pneumonia. These findings were consistent across clinical subgroups. CONCLUSIONS: We found a significant volume-dependent association between an increasing number of RBCs and the odds of pneumonia, which persisted after risk adjustment. Clinical teams should explore opportunities for preventing a patient\u27s risk of RBC transfusions, including reducing hemodilution or adopting a lower transfusion threshold in a stable patient

    Prediction of Transfusions After Isolated Coronary Artery Bypass Grafting Surgical Procedures

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    BACKGROUND: Although blood transfusions are common and have been associated with adverse sequelae after cardiac surgical procedures, few contemporaneous models exist to support clinical decision making. This study developed a preoperative clinical decision support tool to predict perioperative red blood cell transfusions in the setting of isolated coronary artery bypass grafting. METHODS: We performed a multicenter, observational study of 20,377 patients undergoing isolated coronary artery bypass grafting among patients at 39 hospitals participating in the Michigan Society of Thoracic and Cardiovascular Surgeons Quality Collaborative\u27s PERFusion measures and outcomes (PERForm) registry between 2011 and 2015. Candidates\u27 preoperative risk factors were identified based on previous work and clinical input. The study population was randomly divided into a 70% development sample and a 30% validation sample. A generalized linear mixed-effect model was developed to predict perioperative red blood cell transfusion. The model\u27s performance was assessed for calibration and discrimination. Sensitivity analysis was performed to assess the robustness of the model in different clinical subgroups. RESULTS: Transfusions occurred in 36.8% of patients. The final regression model included 16 preoperative variables. The correlation between the observed and expected transfusions was 1.0. The risk prediction model discriminated well (receiver operator characteristic [ROC] CONCLUSIONS: Our risk prediction model uses 16 readily obtainable preoperative variables. This model, which provides a patient-specific estimate of the need for transfusion, offers clinicians a guide for decision making and evaluating the effectiveness of blood management strategies

    Prediction of Transfusions After Isolated Coronary Artery Bypass Grafting Surgical Procedures

    No full text
    BACKGROUND: Although blood transfusions are common and have been associated with adverse sequelae after cardiac surgical procedures, few contemporaneous models exist to support clinical decision making. This study developed a preoperative clinical decision support tool to predict perioperative red blood cell transfusions in the setting of isolated coronary artery bypass grafting. METHODS: We performed a multicenter, observational study of 20,377 patients undergoing isolated coronary artery bypass grafting among patients at 39 hospitals participating in the Michigan Society of Thoracic and Cardiovascular Surgeons Quality Collaborative\u27s PERFusion measures and outcomes (PERForm) registry between 2011 and 2015. Candidates\u27 preoperative risk factors were identified based on previous work and clinical input. The study population was randomly divided into a 70% development sample and a 30% validation sample. A generalized linear mixed-effect model was developed to predict perioperative red blood cell transfusion. The model\u27s performance was assessed for calibration and discrimination. Sensitivity analysis was performed to assess the robustness of the model in different clinical subgroups. RESULTS: Transfusions occurred in 36.8% of patients. The final regression model included 16 preoperative variables. The correlation between the observed and expected transfusions was 1.0. The risk prediction model discriminated well (receiver operator characteristic [ROC] CONCLUSIONS: Our risk prediction model uses 16 readily obtainable preoperative variables. This model, which provides a patient-specific estimate of the need for transfusion, offers clinicians a guide for decision making and evaluating the effectiveness of blood management strategies

    People favour imperfect catching by assuming a stable world

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    The visual angle that is projected by an object (e.g. a ball) on the retina depends on the object's size and distance. Without further information, however, the visual angle is ambiguous with respect to size and distance, because equal visual angles can be obtained from a big ball at a longer distance and a smaller one at a correspondingly shorter distance. Failure to recover the true 3D structure of the object (e.g. a ball's physical size) causing the ambiguous retinal image can lead to a timing error when catching the ball. Two opposing views are currently prevailing on how people resolve this ambiguity when estimating time to contact. One explanation challenges any inference about what causes the retinal image (i.e. the necessity to recover this 3D structure), and instead favors a direct analysis of optic flow. In contrast, the second view suggests that action timing could be rather based on obtaining an estimate of the 3D structure of the scene. With the latter, systematic errors will be predicted if our inference of the 3D structure fails to reveal the underlying cause of the retinal image. Here we show that hand closure in catching virtual balls is triggered by visual angle, using an assumption of a constant ball size. As a consequence of this assumption, hand closure starts when the ball is at similar distance across trials. From that distance on, the remaining arrival time, therefore, depends on ball's speed. In order to time the catch successfully, closing time was coupled with ball's speed during the motor phase. This strategy led to an increased precision in catching but at the cost of committing systematic errors

    Testing Whether and When Parent Alcoholism Uniquely Affects Various Forms of Adolescent Substance Use

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    The current study examined the distal, proximal, and time-varying effects of parents’ alcohol-related consequences on adolescents’ substance use. Previous studies show that having a parent with a lifetime diagnosis of alcoholism is a clear risk factor for adolescents’ own substance use. Less clear is whether the timing of a parent’s alcohol-related consequences differentially predicts the adolescent’s own substance involvement. Using a multilevel modeling approach, we tested whether adolescents showed elevated rates of alcohol, heavy alcohol, marijuana and other illegal drug use (a) at the same time that parents showed alcohol-related consequences (time-varying effects), (b) if parents showed greater alcohol-related consequences during the child’s adolescence (proximal effects), and (c) if parents had a lifetime diagnosis of alcoholism that predated the child’s adolescence (distal effects). We tested these effects in a high-risk sample of 451 adolescents assessed over three waves beginning at ages 11–15 from 1988 to 1991 (53 % male, 71 % non-Hispanic Caucasian, 54 % children of alcoholic parents and 46 % matched controls). Strong and consistent distal effects of parent alcoholism on adolescent’s substance use were found, though no additional risk was associated with proximal effects. Limited time-varying effects were also found. The importance of differentiating the timing effects of parent alcoholism in identifying underlying mechanisms of risk for adolescent substance use is discussed
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