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Urban stormwater runoff is considered a key component of future water supply portfolios for water-stressed cities. Beneficial use of runoff, such as capture for recharge of drinking water aquifers, relies on improved stormwater treatment. Many dissolved constituents, including metals and trace organic contaminants (TrOCs) such as hydrophilic pesticides and poly- and perfluoroalkyl substances (PFASs), are of concern due to their toxicity, persistence, prevalence in stormwater runoff, and poor removal in conventional stormwater control measures. This study explores the operational flow rate limitations of black carbon (BC)-amended engineered media filters for removal of a wide suite of dissolved metals and TrOCs and provides validation for a previously developed predictive TrOC transport model. Column experiments were conducted with face velocities of 40 and 60 cm h -1 to assess Douglas Fir-based biochar and regenerated activated carbon (RAC) filter performance in light of media-contaminant removal kinetic limitations. This study found that increasing the face velocity in BC-amended filters to 40 and 60 cm h -1 , which are representative of field conditions, decreased the removal of total suspended solids, turbidity, dissolved hydrophilic TrOCs, and PFASs when expressed as volume treated relative to previous studies conducted at 20 cm h -1 . Dissolved metals and hydrophobic TrOCs removal were not substantially affected by the increased flow rates. A predictive 1-d intraparticle pore diffusion-limited sorption model with sorption and effective tortuosity parameters determined previously from experiments conducted at 20 cm h -1 was validated for these higher flow rates. This work provides insights to the kinetic limitations of contaminant removal within biochar and RAC filters and implications for stormwater filter design and operation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Improved stormwater treatment is needed to prevent toxic and mobile contaminant transport into receiving waters and allow beneficial use of stormwater runoff. In particular, safe capture of stormwater runoff to augment drinking water supplies is contingent upon removing dissolved trace organic contaminants (TrOCs) not captured by conventional stormwater control measures. This study builds upon a prior laboratory-based column study investigating biochar and regenerated activated carbon (RAC) amendment for removing hydrophilic trace organic contaminants (HiTrOCs) and poly- and perfluoroalkyl substances (PFASs) from stormwater runoff. A robust contaminant transport model framework incorporating time-dependent flow and influent concentration is developed and validated to predict HiTrOC and PFAS transport in biochar- and RAC-amended stormwater filters. Specifically, parameters fit using a sorption-retarded intraparticle pore diffusion transport model were validated using data further along the depth of the column and compared to equilibrium batch isotherms. The transport model and fitted parameters were then used to estimate the lifetime of a hypothetical stormwater filter in Seal Beach, CA, to be 35 ± 6 years for biochar- and 51 ± 17 years for RAC-amended filters, under ideal conditions with no filter clogging. This work offers insights on the kinetics of HiTrOC and PFAS transport within biochar and RAC filters and on the impact of filter design on contaminant removal performance and longevity.

Introduction: Visuomotor impairments have been demonstrated in preclinical AD in individuals with a positive family history of dementia and APOE e4 carriers. Previous behavioral findings have also reported sex-differences in performance of visuomotor tasks involving a visual feedback reversal. The current study investigated the relationship between grey and white matter changes and non-standard visuomotor performance, as well as the effects of APOE status, family history of dementia, and sex on these brain-behavior relationships., Methods: Older adults ( n  = 49) with no cognitive impairments completed non-standard visuomotor tasks involving a visual feedback reversal, plane-change, or combination of the two. Participants with a family history of dementia or who were APOE e4 carriers were considered at an increased risk for AD. T1-weighted anatomical scans were used to quantify grey matter volume and thickness, and diffusion tensor imaging measures were used to quantify white matter integrity., Results: In APOE e4 carriers, grey and white matter structural measures were associated with visuomotor performance. Regression analyses showed that visuomotor deficits were predicted by lower grey matter thickness and volume in areas of the medial temporal lobe previously implicated in visuomotor control (entorhinal and parahippocampal cortices). This finding was replicated in the diffusion data, where regression analyses revealed that lower white matter integrity (lower FA, higher MD, higher RD, higher AxD) was a significant predictor of worse visuomotor performance in the forceps minor, forceps major, cingulum, inferior fronto-occipital fasciculus (IFOF), inferior longitudinal fasciculus (ILF), superior longitudinal fasciculus (SLF), and uncinate fasciculus (UF). Some of these tracts overlap with those important for visuomotor integration, namely the forceps minor, forceps major, SLF, IFOF, and ILF., Conclusion: These findings suggest that measuring the dysfunction of brain networks underlying visuomotor control in early-stage AD may provide a novel behavioral target for dementia risk detection that is easily accessible, non-invasive, and cost-effective. The results also provide insight into the structural differences in inferior parietal lobule that may underlie previously reported sex-differences in performance of the visual feedback reversal task., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Rogojin, Gorbet, Hawkins and Sergio.)

Introduction: Non-standard visuomotor integration requires the interaction of large networks in the brain. Previous findings have shown that non-standard visuomotor performance is impaired in individuals with specific dementia risk factors (family history of dementia and presence of the APOE ε4 allele) in advance of any cognitive impairments. These findings suggest that visuomotor impairments are associated with early dementia-related brain changes. The current study examined the underlying resting state functional connectivity (RSFC) associated with impaired non-standard visuomotor performance, as well as the impacts of dementia family history, sex, and APOE status., Methods: Cognitively healthy older adults ( n  = 48) were tested on four visuomotor tasks where reach and gaze were increasingly spatially dissociated. Participants who had a family history of dementia or the APOE ε4 allele were considered to be at an increased risk for AD. To quantify RSFC within networks of interest, an EPI sequence sensitive to BOLD contrast was collected. The networks of interest were the default mode network (DMN), somatomotor network (SMN), dorsal attention network (DAN), ventral attention network (VAN), and frontoparietal control network (FPN)., Results: Individuals with the ε4 allele showed abnormalities in RSFC between posterior DMN nodes that predicted poorer non-standard visuomotor performance. Specifically, multiple linear regression analyses revealed lower RSFC between the precuneus/posterior cingulate cortex and the left inferior parietal lobule as well as the left parahippocampal cortex. Presence of the APOE ε4 allele also modified the relationship between mean DAN RSFC and visuomotor control, where lower mean RSFC in the DAN predicted worse non-standard visuomotor performance only in APOE ε4 carriers. There were otherwise no effects of family history, APOE ε4 status, or sex on the relationship between RSFC and visuomotor performance for any of the other resting networks., Conclusion: The preliminary findings provide insight into the impact of APOE ε4-related genetic risk on neural networks underlying complex visuomotor transformations, and demonstrate that the non-standard visuomotor task paradigm discussed in this study may be used as a non-invasive, easily accessible assessment tool for dementia risk., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Rogojin, Gorbet, Hawkins and Sergio.)

Urban stormwater runoff is a significant driver of surface water quality impairment. Recently, attention has been drawn to potential beneficial use of urban stormwater runoff, including augmenting drinking water supply in water-stressed areas. However, beneficial use relies on improved treatment of stormwater runoff to remove mobile dissolved metals and trace organic contaminants (TrOCs). This study assesses six engineered media mixtures consisting of sand, zeolite, high-temperature gasification biochar, and regenerated activated carbon (RAC) for removing a suite of co-contaminants comprising five metals, three herbicides, four pesticides, a corrosion inhibitor, six per- and polyfluoroalkyl substances (PFASs), five polychlorinated biphenyls (PCBs), and six polycyclic aromatic hydrocarbons (PAHs). This long-term laboratory-scale column study uses a novel approach to generate reproducible synthetic stormwater that incorporates catch basin material and straw-derived dissolved organic carbon. Higher flow conditions (20 cm hr -1 ), larger sized media (0.42-1.68 mm), and downflow configuration with outlet control increase the relevance of this study to better enable implementation in the field. Biochar- and RAC-amended engineered media filters removed nearly all of the TrOCs in the effluent over the course of three months of continuous flow (480 empty bed volumes), while sample ports spaced at 25% and 50% along the column depth provide windows to observe contaminant transport. Biochar provided greater benefit to TrOC removal than RAC on a mass basis. This study used relatively high concentrations of contaminants and low biochar and RAC content to observe contaminant transport. Performance in the field is likely to be significantly better with higher biochar- and RAC-content filters and lower ambient stormwater contaminant concentrations. This study provides proof-of-concept for biochar- and RAC-amended engineered media filters operated at a flow rate of 20 cm hr -1 for removing dissolved TrOCs and metals and offers insights on the performance of biochar and RAC for improved stormwater treatment and field trials., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Background/objective: In anterior cruciate ligament ​reconstruction, a tendon graft, anchored by interference screws (IFSs), is frequently used as a replacement for the damaged ligament. Generally, IFSs are classified as being either metallic or polymeric. Metallic screws have sharp threads that lacerate the graft, preventing solid fixation. These constructs are difficult to image ​and can limit bone--screw integration because of the higher stiffness of the screw. Polymeric materials are often a better match to bone's material properties, but lack the strength needed to hold grafts in place. Magnesium (Mg) is a material of great promise for orthopaedic applications. Mg has mechanical properties similar to bone, ability to be seen on magnetic resonance imagings, and promotes bone healing. However, questions still remain regarding the strength of Mg-based screws. Previous ex vivo  ​animal experiments found stripping of the screw drive when the full torque was applied to Mg screws during surgery, preventing full insertion and poor graft fixation. The similar design of the Mg screw led to questions regarding the relationship between material properties and design, and the ultimate impact on mechanical behaviour. Thus, the objective of this study was to analyze the stresses in the screw head, a key factor in the stripping mechanism of IFS, then use that information to improve screw design, for this material., Methods: Using finite element analysis, a comparison study of six drive designs (hexagonal, quadrangle, torx, trigonal, trilobe, and turbine) was performed. This was followed by a parametric analysis to determine appropriate drive depth and drive width., Results: It was observed that with a typical torque (2 ​Nm) used for screw insertion during anterior cruciate ligament reconstruction, the maximum von Mises and shear stress values were concentrated in the corners or turns of the drive, which could lead to stripping if the values were greater than the yield stress of Mg (193 ​MPa). With a four-time ​increase in drive depth to be fully driven and a 30% greater drive width, these maximum stress values were significantly decreased by more than 75%., Conclusion: It was concluded that improving the design of a Mg-based screw may increase surgical success rates, by decreasing device failure at insertion., The Translational Potential of This Article: The results of this work have the potential to improve designs of degradable IFSs, allowing for greater torque to be applied and thus greater screw fixation between host bone and the graft. Such a fixation will allow greater integration, better patient healing, and ultimately improved patient outcomes., (© 2019 The Authors.)

Background: Cognitive-motor integration (CMI) involves concurrent thought and action which requires the interaction of large brain networks. Given that early-stage dementia involves neural network dysfunction, deficits in CMI may prove useful for early dementia detection., Objective: Our research objective was to investigate sex-related differences in the ability to integrate rules into action., Methods: Based on family medical history, we recruited male and female participants both with and without dementia risk factors. Participants did not demonstrate cognitive impairment at the time of testing. Participants were tested on four increasingly dissociated visuomotor tasks (eye and hand movements were made in different spatial planes and/or visual feedback was reversed)., Results: We observed significantly greater hand movement endpoint error scores and corrective path lengths in at-risk females compared to at-risk males in the most complex CMI condition (plane-change + feedback reversal). Multiple regression analyses revealed both sex and family history as significant predictors of worse performance in a CMI condition requiring visual feedback reversal. Further, the regression analyses provided preliminary evidence that having an APOEɛ4 allele was a significant predictor of poorer CMI performance in the two plane-change CMI conditions., Conclusion: These data suggest that underlying brain networks controlling simultaneous thought and action may differ between the sexes in ways that may be clinically relevant in dementia progression. Preliminary data also suggest an important connection between APOE variant and CMI performance in individuals at risk of developing dementia.

Despite the interwoven nature of platelet activation and the coagulation system in thrombosis, few studies relate both analysis of protein and cellular parts of coagulation in the same population. In the present study, we use matched ex vivo samples to determine the influences of standard antiplatelet therapies on platelet function and use advanced rheological analyses to assess clot formation. Healthy volunteers were recruited following fully informed consent then treated for 7 days with single antiplatelet therapy of aspirin (75 mg) or prasugrel (10 mg) or with dual antiplatelet therapy (DAPT) using aspirin (75 mg) plus prasugrel (10 mg) or aspirin (75 mg) plus ticagrelor (90 mg). Blood samples were taken at day 0 before treatment and at day 7 following treatment. We found that aspirin plus prasugrel or aspirin plus ticagrelor inhibited platelet responses to multiple agonists and reduced P-selectin expression. Significant platelet inhibition was coupled with a reduction in fractal dimension corresponding to reductions in mean relative mass both for aspirin plus prasugrel (-35 ± 16% change, p = 0.04) and for aspirin plus ticagrelor (-45 ± 14% change, p = 0.04). Aspirin alone had no effect upon measures of clot structure, whereas prasugrel reduced fractal dimension and mean relative mass. These data demonstrate that platelets are important determinants of clot structure as assessed by fractal dimension (d f ) and that effective platelet inhibition is associated with a weaker, more permeable fibrin network. This indicates a strong association between the therapeutic benefits of antiplatelet therapies and their abilities to reduce thrombus density that may be useful in individual patients to determine the functional relationship between platelet reactivity, eventual clot quality, and clinical outcome. d f could represent a novel risk stratification biomarker useful in individualizing antiplatelet therapies.

Our brain's ability to flexibly control the communication between the eyes and the hand allows for our successful interaction with the objects located within our environment. This flexibility has been observed in the pattern of neural responses within key regions of the frontoparietal reach network. More specifically, our group has shown how single-unit and oscillatory activity within the dorsal premotor cortex (PMd) and the superior parietal lobule (SPL) change contingent on the level of visuomotor compatibility between the eyes and hand. Reaches that involve a coupling between the eyes and hand toward a common spatial target display a pattern of neural responses that differ from reaches that require eye-hand decoupling. Although previous work examined the altered spiking and oscillatory activity that occurs during different types of eye-hand compatibilities, they did not address how each of these measures of neurological activity interacts with one another. Thus, in an effort to fully characterize the relationship between oscillatory and single-unit activity during different types of eye-hand coordination, we measured the spike-field coherence (SFC) within regions of macaque SPL and PMd. We observed stronger SFC within PMdr and superficial regions of SPL (areas 5/PEc) during decoupled reaches, whereas PMdc and regions within SPL surrounding medial intrapareital sulcus had stronger SFC during coupled reaches. These results were supported by meta-analysis on human fMRI data. Our results support the proposal of altered cortical control during complex eye-hand coordination and highlight the necessity to account for the different eye-hand compatibilities in motor control research.

Isoprenoids are used in many commercial applications and much work has gone into engineering microbial hosts for their production. Isoprenoids are produced either from acetyl-CoA via the mevalonate pathway or from pyruvate and glyceraldehyde 3-phosphate via the 1-deoxy-D-xylulose 5-phosphate (DXP) pathway. Saccharomyces cerevisiae exclusively utilizes the mevalonate pathway to synthesize native isoprenoids and in fact the alternative DXP pathway has never been found or successfully reconstructed in the eukaryotic cytosol. There are, however, several advantages to isoprenoid synthesis via the DXP pathway, such as a higher theoretical yield, and it has long been a goal to transplant the pathway into yeast. In this work, we investigate and address barriers to DXP pathway functionality in S. cerevisiae using a combination of synthetic biology, biochemistry and metabolomics. We report, for the first time, functional expression of the DXP pathway in S. cerevisiae. Under low aeration conditions, an engineered strain relying solely on the DXP pathway for isoprenoid biosynthesis achieved an endpoint biomass 80% of that of the same strain using the mevalonate pathway., (Copyright © 2016 International Metabolic Engineering Society. All rights reserved.)

The current study quantified lumbar loading while carrying an anterior load mass and navigating an obstacle. Eight healthy male participants walked down a walkway and crossed an obstacle under three randomised LOAD conditions; empty-box (2 KG), five kilogram (5 KG) and ten kilogram (10 KG). Each walk was assessed at two events: left foot mid-stance (LMS) and right toe-crossing (TC) to characterise any changes from approach to crossing. Measures of interest included: trunk pitch, L4/L5 joint moment, compression, joint anterior-posterior shear and erector spinae activation. Findings demonstrate that obstacle crossing extended posture by 50, 41, 44%, respectively for each carried load magnitude. Further, these results indicate that shear rather than compressive loading may be an important consideration during crossing due to increase by 8, 9, 22% from LMS to TC for each load magnitude tested. These results provide insight into sagittal lumbar loading when navigating an obstacle while carrying a load. Practitioner Summary: The risk of carrying while navigating obstacles on the lumbar spine is not completely understood. The forces at the lumbar spine while simultaneously carrying and obstacle crossing were analysed. Data indicate that carrying and obstacle crossing influence lumbar shear loads, thereby moderately increasing the relative risk at lumbar spine.

A bio-based economy has the potential to provide sustainable substitutes for petroleum-based products and new chemical building blocks for advanced materials. We previously engineered Saccharomyces cerevisiae for industrial production of the isoprenoid artemisinic acid for use in antimalarial treatments. Adapting these strains for biosynthesis of other isoprenoids such as β-farnesene (C 15 H 24 ), a plant sesquiterpene with versatile industrial applications, is straightforward. However, S. cerevisiae uses a chemically inefficient pathway for isoprenoid biosynthesis, resulting in yield and productivity limitations incompatible with commodity-scale production. Here we use four non-native metabolic reactions to rewire central carbon metabolism in S. cerevisiae, enabling biosynthesis of cytosolic acetyl coenzyme A (acetyl-CoA, the two-carbon isoprenoid precursor) with a reduced ATP requirement, reduced loss of carbon to CO 2 -emitting reactions, and improved pathway redox balance. We show that strains with rewired central metabolism can devote an identical quantity of sugar to farnesene production as control strains, yet produce 25% more farnesene with that sugar while requiring 75% less oxygen. These changes lower feedstock costs and dramatically increase productivity in industrial fermentations which are by necessity oxygen-constrained. Despite altering key regulatory nodes, engineered strains grow robustly under taxing industrial conditions, maintaining stable yield for two weeks in broth that reaches >15% farnesene by volume. This illustrates that rewiring yeast central metabolism is a viable strategy for cost-effective, large-scale production of acetyl-CoA-derived molecules.

Background: Many neuroimaging parameters have demonstrated utility as biomarkers in preclinical AD, including resting-state functional connectivity in the default mode network. However, neuroimaging is not a practical, cost effective screening instrument., Objective: Here we investigate the relationship between performance on a cognitive-motor integration assessment and alterations in resting-state functional connectivity in an at-risk population., Methods: Three groups of ten adults (young: mean age = 26.6 ± 2.7, low AD risk: mean age = 58.7 ± 5.6, and high AD risk: mean age = 58.5 ± 6.9) performed a simple cognitive-motor integration task using a dual-touchscreen laptop and also underwent functional magnetic resonance imaging at rest., Results: We found poorer cognitive-motor integration performance in high AD risk participants, as well as an association with lower resting-state functional connectivity in this group., Conclusion: These findings provide novel insight into underlying AD-related brain alterations associated with a behavioral assessment that can be easily administered clinically.

Venous thromboembolism (VTE) is common in cancer patients, and is the second commonest cause of death associated with the disease. Patients with chronic inflammation, such as cancer, have been shown to have pathological clot structures with modulated mechanical properties. Fractal dimension (df) is a new technique which has been shown to act as a marker of the microstructure and mechanical properties of blood clots, and can be performed more readily than current methods such as scanning electron microscopy (SEM). We measured df in 87 consecutive patients with newly diagnosed lung cancer prior to treatment and 47 matched-controls. Mean group values were compared for all patients with lung cancer vs controls and for limited disease vs extensive disease. Results were compared with conventional markers of coagulation, fibrinolysis and SEM images. Significantly higher values of df were observed in lung cancer patients compared with controls and patients with extensive disease had higher values than those with limited disease (p< 0.05), whilst conventional markers failed to distinguish between these groups. The relationship between df of the incipient clot and mature clot microstructure was confirmed by SEM and computational modelling: higher df was associated with highly dense clots formed of smaller fibrin fibres in lung cancer patients compared to controls. This study demonstrates that df is a sensitive technique which quantifies the structure and mechanical properties of blood clots in patients with lung cancer. Our data suggests that df has the potential to identify patients with an abnormal clot microstructure and greatest VTE risk.

Implantable ventricular assist devices (VADs) have proven efficient in advanced heart failure patients as a bridge-to-transplant or destination therapy. However, VAD usage often leads to infection, bleeding, and thrombosis, side effects attributable to the damage to blood cells and plasma proteins. Measuring hemolysis alone does not provide sufficient information to understand total blood damage, and research exploring the impact of currently available pumps on a wider range of blood cell types and plasma proteins such as von Willebrand factor (vWF) is required to further our understanding of safer pump design. The extracorporeal CentriMag (Thoratec Corporation, Pleasanton, CA, USA) has a hemolysis profile within published standards of normalized index of hemolysis levels of less than 0.01 g/100 L at 100 mm Hg but the effect on leukocytes, vWF multimers, and platelets is unknown. Here, the CentriMag was tested using bovine blood (n = 15) under constant hemodynamic conditions in comparison with a static control for total blood cell counts, hemolysis, leukocyte death, vWF multimers, microparticles, platelet activation, and apoptosis. The CentriMag decreased the levels of healthy leukocytes (P < 0.006), induced leukocyte microparticles (P < 10(-5) ), and the level of high molecular weight of vWF multimers was significantly reduced in the CentriMag (P < 10(-5) ) all compared with the static treatment after 6 h in vitro testing. Despite the leukocyte damage, microparticle formation, and cleavage of vWF multimers, these results show that the CentriMag is a hemocompatible pump which could be used as a standard in blood damage assays to inform the design of new implantable blood pumps., (© 2014 The Authors. Artificial Organs published by Wiley Periodicals, Inc. on behalf of International Center for Artificial Organs and Transplantation (ICAOT).)

Alzheimer's disease (AD) is typically associated with impairments in memory and other aspects of cognition, while deficits in complex movements are commonly observed later in the course of the disease. Recent studies, however, have indicated that subtle deteriorations in visuomotor control under cognitively demanding conditions may in fact be an early identifying feature of AD. Our previous work has shown that the ability to perform visuomotor tasks that rely on visual-spatial and rule-based transformations is disrupted in prodromal and preclinical AD. Here, in a sample of 30 female participants (10 young: mean age = 26.6 ± 2.7, 10 low AD risk: mean age = 58.7 ± 5.6, and 10 high AD risk: mean age = 58.5 ± 6.9), we test the hypothesis that these cognitive-motor impairments are associated with early AD-related brain alterations. Using diffusion-weighted magnetic resonance imaging, we examined changes in white matter (WM) integrity associated with normal aging and increased AD risk, and assessed the relationship between these underlying WM alterations and cognitive-motor performance. Our whole-brain analysis revealed significant age-related declines in WM integrity, which were more widespread in high relative to low AD risk participants. Furthermore, analysis of mean diffusivity measures within isolated WM clusters revealed a stepwise decline in WM integrity across young, low AD risk, and high AD risk groups. In support of our hypothesis, we also observed that lower WM integrity was associated with poorer cognitive-motor performance. These results are the first to demonstrate a relationship between AD-related WM alterations and impaired cognitive-motor control. The application of these findings may provide a novel clinical strategy for the early detection of individuals at increased AD risk.

Eye-hand coordination is crucial for our ability to interact with the world around us. However, much of the visually guided reaches that we perform require a spatial decoupling between gaze direction and hand orientation. These complex decoupled reaching movements are in contrast to more standard eye and hand reaching movements in which the eyes and the hand are coupled. The superior parietal lobule (SPL) receives converging eye and hand signals; however, what is yet to be understood is how the activity within this region is modulated during decoupled eye and hand reaches. To address this, we recorded local field potentials within SPL from two rhesus macaques during coupled vs. decoupled eye and hand movements. Overall we observed a distinct separation in synchrony within the lower 10- to 20-Hz beta range from that in the higher 30- to 40-Hz gamma range. Specifically, within the early planning phase, beta synchrony dominated; however, the onset of this sustained beta oscillation occurred later during eye-hand decoupled vs. coupled reaches. As the task progressed, there was a switch to low-frequency and gamma-dominated responses, specifically for decoupled reaches. More importantly, we observed local field potential activity to be a stronger task (coupled vs. decoupled) and state (planning vs. execution) predictor than that of single units alone. Our results provide further insight into the computations of SPL for visuomotor transformations and highlight the necessity of accounting for the decoupled eye-hand nature of a motor task when interpreting movement control research data., (Copyright © 2014 the American Physiological Society.)

Background and Objective: Recent evidence suggests that visuomotor behaviors may be disrupted in the very early stages of Alzheimer's disease (AD). Here we propose that using kinematic measures under conditions that place demands on visual-spatial and cognitive-motor processing may provide an effective behavioral means to detect subtle changes associated with AD risk., Methods: To this end, we have tested 22 young adults (mean age = 26.4 ± 4.1) and 22 older adults (mean age = 64.3 ± 10.1) at low AD, and 22 older adults (mean age = 67.7 ± 11.3) at high AD risk (i.e., strong family history or diagnosis of mild cognitive impairment). Kinematic measures were acquired on four visuomotor transformation tasks (standard, feedback reversal, plane dissociated, and plane dissociated + feedback reversal) using a dual-touchscreen tablet., Results: Comparing participants at increased AD risk with both young and old healthy control groups revealed significant performance disruptions in at-risk individuals as task demands increased. Furthermore, we were able to discriminate between individuals at high and low AD risk with a classification accuracy of 86.4% (sensitivity: 81.8%, specificity: 90.9%)., Conclusion: We suggest that the impairments observed in individuals at increased AD risk may reflect inherent brain alteration and/or early neuropathology disrupting the reciprocal communication between hippocampal, parietal, and frontal brain regions required to successfully prepare and update complex reaching movements. Such impairment has the potential to affect activities of daily living, and may serve as a sensitive measure of functional ability in at-risk adults.

Infection is a clinically relevant adverse event in patients with ventricular assist device (VAD) support. The risk of infection could be linked to a reduced immune response resulting from damage to leukocytes during VAD support. The purpose of this study was to develop an understanding of leukocyte responses during the in vitro testing of VADs by analyzing the changes to their morphology and biochemistry. The VentrAssist implantable rotary blood pump (IRBP) and RotaFlow centrifugal pump (CP) were tested in vitro under constant hemodynamic conditions. Automated hematology analysis of samples collected regularly over 25-h tests was undertaken. A new flow cytometric assay was employed to measure biochemical alteration, necrosis (7-AAD) and morphological alteration (CD45 expression) of the circulating leukocytes during the pumping process. The results of hematology analysis show the total leukocyte number and subset counts decreased over the period of in vitro tests dependent on different blood pumps. The percentage of leukocytes damaged during 6-h tests was 40.8 ± 5.7% for the VentrAssist IRBP, 17.6 ± 5.4% for the RotaFlow CP, and 2.7 ± 1.8% for the static control (all n=5). Flow cytometric monitoring of CD45 expression and forward/side scatter characteristics revealed leukocytes that were fragmented into smaller pieces (microparticles). Scanning electron microscopy and imaging flow cytometry were used to confirm this. Device developers could use these robust cellular assays to gain a better understanding of leukocyte-specific VAD performance., (© 2013 Wiley Periodicals, Inc. and International Center for Artificial Organs and Transplantation.)

The aim of this research was to understand how the brain controls voluntary movement when not directly interacting with the object of interest. In the present study, we examined the role of premotor cortex in this behavior. The goal of this study was to characterize the oscillatory activity within the caudal and rostral subdivisions of dorsal premotor cortex (PMdc and PMdr) with a change from the most basic reaching movement to one that involves a simple dissociation between the actions of the eyes and hand. We were specifically interested in how PMdr and PMdc respond when the eyes and hand are decoupled by moving along different spatial planes. We recorded single-unit activity and local field potentials within PMdr and PMdc from two rhesus macaques during performance of two types of visually guided reaches. During the standard condition, a visually guided reach was performed whereby the visual stimulus guiding the movement was the target of the reach itself. During the nonstandard condition, the visual stimulus provided information about the direction of the required movement but was not the target of the motor output. We observed distinct task-related and topographical differences between PMdr and PMdc. Our results support functional differences between PMdr and PMdc during visually guided reaching. PMdr activity appears more involved in integrating the rule-based aspects of a visually guided reach, whereas PMdc is more involved in the online updating of the decoupled reach. More broadly, our results highlight the necessity of accounting for the nonstandard nature of a motor task when interpreting movement control research data.

Cognition allows for the use of different rule-based sensorimotor strategies, but the neural underpinnings of such strategies are poorly understood. The purpose of this study was to compare neural activity in the superior parietal lobule during a standard (direct interaction) reaching task, with two nonstandard (gaze and reach spatially incongruent) reaching tasks requiring the integration of rule-based information. Specifically, these nonstandard tasks involved dissociating the planes of reach and vision or rotating visual feedback by 180°. Single unit activity, gaze, and reach trajectories were recorded from two female Macaca mulattas. In all three conditions, we observed a temporal discharge pattern at the population level reflecting early reach planning and on-line reach monitoring. In the plane-dissociated task, we found a significant overall attenuation in the discharge rate of cells from deep recording sites, relative to standard reaching. We also found that cells modulated by reach direction tended to be significantly tuned either during the standard or the plane-dissociated task but rarely during both. In the standard versus feedback reversal comparison, we observed some cells that shifted their preferred direction by 180° between conditions, reflecting maintenance of directional tuning with respect to the reach goal. Our findings suggest that the superior parietal lobule plays an important role in processing information about the nonstandard nature of a task, which, through reciprocal connections with precentral motor areas, contributes to the accurate transformation of incongruent sensory inputs into an appropriate motor output. Such processing is crucial for the integration of rule-based information into a motor act.

The extent to which different locomotor tasks require cognitive control is not well characterized. In this article, the authors consider the potential increase in attentional demands associated with carrying an anterior load while clearing an obstacle. Nine healthy male volunteers participated in 80 walking trials, 20 in each of 4 conditions: 1 no load condition (NL) and 3 carrying conditions (2KG, 5KG, and 10KG). Of the 20 trials in each condition, 12 included a probe reaction time (PRT) test during lead limb obstacle crossing, which was used to measure cognitive load. A load-dependent increase in PRT was observed, with PRT in the 2KG condition being significantly greater than in the NL condition, and PRT in the 5KG and 10KG conditions being significantly greater than in the 2KG condition. These results suggested that cognitive load was increased when: (a) the obstacle was occluded from vision by the load, and (b) the magnitude of load was increased.

The purpose of this study was to assess the effect of anterior load carriage on obstacle-crossing behaviour, with a focus on lower limb gait parameters. Nine male participants (age 23+/-1.8 years, height 176+/-5.0cm) volunteered. Participants either walked without a load (No Load), or carried a load (2KG (empty box), 5KG, 10KG), and stepped over a 20cm obstacle. Vision of the obstacle was obscured 1.0m to 1.3m prior to the obstacle. Significant correlations were found between trail limb toe distance and lead limb toe clearance, in the 2KG, 5KG, and 10KG conditions. Toe clearance increased with load (No Load, 147.3+/-13.9mm; 2KG, 162.5+/-15.6mm; 5KG, 167.6+/-17.6mm; 10KG, 173.9+/-17.5mm; p<0.0001). Trail limb toe distance, trail limb toe distance variability, lead heel distance variability, and lead limb toe clearance variability were greater in the 2KG, 5KG, and 10KG conditions, compared with the No Load condition. Participants adopted a conservative gait pattern during obstacle crossing when carrying a load, evidenced by increasing toe clearance, which may have been influenced by availability of visual information regarding obstacle position. In contrast with previous literature, increased lead limb toe clearance may have been associated with absence of relative surface height difference pre- and post-obstacle crossing., (Copyright 2010 Elsevier B.V. All rights reserved.)

The benzylisoquinoline alkaloids (BIAs) are a diverse class of metabolites that exhibit a broad range of pharmacological activities and are synthesized through plant biosynthetic pathways comprised of complex enzyme activities and regulatory strategies. We have engineered yeast to produce the key intermediate reticuline and downstream BIA metabolites from a commercially available substrate. An enzyme tuning strategy was implemented that identified activity differences between variants from different plants and determined optimal expression levels. By synthesizing both stereoisomer forms of reticuline and integrating enzyme activities from three plant sources and humans, we demonstrated the synthesis of metabolites in the sanguinarine/berberine and morphinan branches. We also demonstrated that a human P450 enzyme exhibits a novel activity in the conversion of (R)-reticuline to the morphinan alkaloid salutaridine. Our engineered microbial hosts offer access to a rich group of BIA molecules and associated activities that will be further expanded through synthetic chemistry and biology approaches.

Objective: To investigate whether attending a six-week stress management course in a rural adult education centre is effective in reducing participants' levels of stress, anxiety and depression., Design: Repeated measures design using self-report measures of stress, anxiety and depression at commencement and completion of a six-week stress management course, and six months post-completion follow up., Setting and Participants: One hundred and thirty-two adults (age range 18-73 years) living in a rural community who self-enrolled in the stress management course at adult education centres., Intervention: The course consisted of six weekly group sessions. Each two-hour session conducted by mental health professionals, included teaching cognitive behavioural strategies targeted at reducing individual symptoms of stress., Main Outcome Measures: Comparative analysis of pre- and post-test and six-month follow up on measures of stress (Stress Symptom Checklist), anxiety and depression (Hospital Anxiety and Depression Scale)., Results: RESULTS indicated a significant reduction in stress symptoms (F(7,90) = 34.92, P < 0.001), anxiety and depression (F(3,95) = 87.92, P < 0.001) from course commencement to course completion. These improvements were sustained six months after course completion for stress symptoms (F(11,65) = 22.40, P < 0.001), anxiety and depression (F(5,73) = 41.78, P < 0.001)., Conclusion: Findings demonstrate the stress management course is an effective community intervention in a rural community. Challenges for future implementation of the program are discussed.

The GAL genetic switch of Saccharomyces cerevisiae exhibits an ultrasensitive response to the inducer galactose as well as the "all-or-none" behavior characteristic of many eukaryotic regulatory networks. We have constructed a strain that allows intermediate levels of gene expression from a tunable GAL1 promoter at both the population and the single cell level by altering the regulation of the galactose permease Gal2p. Similar modifications to other feedback loops regulating the Gal80p repressor and the Gal3p signaling protein did not result in similarly tuned responses, indicating that the level of inducer transport is unique in its ability to control the switch response of the network. In addition, removal of the Gal1p galactokinase from the network resulted in a regimed response due to the dual role of this enzyme in galactose catabolism and transport. These two activities have competing effects on the response of the network to galactose such that the transport effects of Gal1p are dominant at low galactose concentrations, whereas its catabolic effects are dominant at high galactose concentrations. In addition, flow cytometry analysis revealed the unexpected phenomenon of multiple populations in the gal1delta strains, which were not present in the isogenic GAL1 background. This result indicates that Gal1p may play a previously undescribed role in the stability of the GAL network response.

Utilizing polypeptide secondary structure as a means for controlling oxide pore architectures is explored. Poly-L-lysine is used as a model polypeptide as its folding behavior is well understood and compatible with the sol-gel chemistry of silica. Here, we show that silicas synthesized with poly-L-lysine in a alpha-helix conformation possess cylindrical pores that are approximately 1.5 nm in size, whereas silicas synthesized with poly-L-lysine in a beta-sheet conformation possess larger pores, the size of which are a function of the poly-L-lysine concentration, or in other words the size of the aggregate. In both cases, highly porous materials are obtained. In-situ circular dichroism measurements of the synthesis mixtures show that the poly-L-lysine secondary structure is not perturbed during synthesis. Infrared spectroscopy of the as-synthesized materials is consistent with the poly-L-lysine retaining its secondary structure. Grand canonical Monte Carlo simulations were also performed to validate the interpretation of the experimental adsorption results. The experimental isotherms are consistent with simulated isotherms of cylindrical pores 1.3-1.7 nm in size, in good agreement with expected values. Our results suggest a new avenue for synthesizing porous oxides with highly tuneable pore sizes and shapes under mild conditions.