Cursor movements to targets labelled "stop": a kinematic analysis.

The label 'Stop' potentially generates conflict-signifying important corrective action, or a warning not to touch. To examine potential conflict between an incongruent label (i.e. STOP) and an imperative command (i.e. MOVE!), 18 participants used a computer mouse to move a crosshair cursor to targets with superimposed labels. Trials systematically varied Imperative (blank or MOVE!), Label (+GO + or STOP) and movement Distance. Kinematic analyses examined response latency, movement duration and accuracy. Incongruent labels had little impact upon response latencies, but they affected cursor deceleration and the variability of cursor placement. Although reading is assumed to be obligatory, the impact of written labels is not immediate, instead affecting cursor deceleration. Indeed, responses to controls labelled STOP were less accurate than those labelled + GO+. As labelled interfaces can create error versus command confusions, enhancing the discriminability of controls to afford more obvious visible cues as to method of use is recommended. Practitioner summary: Emergency stop and shutdown controls can cause response conflict as their labels signify both urgent corrective actions and 'don't touch'. Response conflict caused by confusing superimposed labels is resolved as cursors near the target control and may result in reduced movement accuracy. Prior warnings may influence resolution of response conflict. Abbreviations: Hz: Hertz; M: Mean; ms: millisecond; mm: millimetre; S: second; SD: Standard Deviation; SE: Standard Error; USB: Universal Serial Bus.

Effect of high-pressure processing on reduction of Listeria monocytogenes in packaged Queso Fresco.

The effect of high-hydrostatic-pressure processing (HPP) on the survival of a 5-strain rifampicin-resistant cocktail of Listeria monocytogenes in Queso Fresco (QF) was evaluated as a postpackaging intervention. Queso Fresco was made using pasteurized, homogenized milk, and was starter-free and not pressed. In phase 1, QF slices (12.7 × 7.6 × 1 cm), weighing from 52 to 66 g, were surface inoculated with L. monocytogenes (ca. 5.0 log10 cfu/g) and individually double vacuum packaged. The slices were then warmed to either 20 or 40°C and HPP treated at 200, 400, and 600 MPa for hold times of 5, 10, 15, or 20 min. Treatment at 600 MPa was most effective in reducing L. monocytogenes to below the detection level of 0.91 log10 cfu/g at all hold times and temperatures. High-hydrostatic-pressure processing at 40°C, 400 MPa, and hold time ≥ 15 min was effective but resulted in wheying-off and textural changes. In phase 2, L. monocytogenes was inoculated either on the slices (ca. 5.0 log10 cfu/g; ON) or in the curds (ca. 7.0 log10 cfu/g; IN) before the cheese block was formed and sliced. The slices were treated at 20°C and 600 MPa at hold times of 3, 10, and 20 min, and then stored at 4 and 10°C for 60 d. For both treatments, L. monocytogenes became less resistant to pressure as hold time increased, with greater percentages of injured cells at 3 and 10 min than at 20 min, at which the lethality of the process increased. For the IN treatment, with hold times of 3 and 10 min, growth of L. monocytogenes increased the first week of storage, but was delayed for 1 wk, with a hold time of 20 min. Longer lag times in growth of L. monocytogenes during storage at 4°C were observed for the ON treatment at hold times of 10 and 20 min, indicating that the IN treatment may have provided a more protective environment with less injury to the cells than the ON treatment. Similarly, HPP treatment for 10 min followed by storage at 4°C was the best method for suppressing the growth of the endogenous microflora with bacterial counts remaining below the level of detection for 2 out of the 3 QF samples for up to 84 d. Lag times in growth were not observed during storage of QF at 10°C. Although HPP reduced L. monocytogenes immediately after processing, a second preservation technique is necessary to control growth of L. monocytogenes during cold storage. However, the results also showed that HPP would be effective for slowing the growth of microorganisms that can shorten the shelf life of QF.

Improved prediction of meat and bone meal metabolizable energy content for ducks through in vitro methods.

Apparent metabolizable energy (AME) of meat and bone meal (MBM) for poultry is highly variable, but impractical to measure routinely. Previous efforts at developing an in vitro method for predicting AME have had limited success. The present study uses data from a previous publication on the AME of 12 MBM samples, determined using 288 White Pekin ducks, as well as composition data on these samples. Here, we investigate the hypothesis that 2 noncompositional attributes of MBM, particle size and protease resistance, will have utility in improving predictions of AME based on in vitro measurements. Using the same MBM samples as the previous study, 2 measurements of particle size were recorded and protease resistance was determined using a modified pepsin digestibility assay. Analysis of the results using a stepwise construction of multiple linear regression models revealed that the measurements of particle size were useful in building models for AME, but the measure of protease resistance was not. Relatively simple (4-term) and complex (7-term) models for both AME and nitrogen-corrected AME were constructed, with R-squared values ranging from 0.959 to 0.996. The rather minor analytical effort required to conduct the measurements involved is discussed. Although the generality of the results are limited by the number of samples involved and the species used, they suggest that AME for poultry can be accurately predicted through simple and inexpensive in vitro methods.

Decisional style, mood and work communication: email diaries.

To understand the use of technology to support interpersonal interaction, a theory of decisional style was applied to email use within the workplace. Previous research has used self-report and rating scales to address employee email behaviours, but this falls short of management's capability to monitor the actual behaviour. Thirty-nine employed individuals completed a five-day communication diary recording their actual behaviour upon receiving personal and work-related emails as well as the Melbourne Decision Making Questionnaire and the Depression Anxiety Stress Scales. It was found that vigilant individuals were more likely to use email in an efficient manner by deleting personal email and being less likely to open email later. Procrastinators, buckpassers and people experiencing high levels of negative affect were all more likely to delay dealing with email, which could be viewed as dealing with email in a less efficient manner. STATEMENT OF RELEVANCE: This work offers insights as to how people receive and process emails and is thus relevant to the development and implementation of collaborative technologies. Whilst other studies use individual's self-reports, this study uses a more accurate communication diary. Decisional style can predict the monitoring and response to electronic communication.

Utilization of Soil Solarization for Eliminating Viable Tilletia indica Teliospores from Arizona Wheat Fields.

Studies were conducted in Arizona to determine the efficacy of soil solarization for killing teliospores of the soilborne fungal wheat pathogen Tilletia indica. In a replicated study conducted in each of 3 years, T. indica teliospores and bunted wheat kernels were buried in a Karnal bunt-infested wheat field at depths of 5, 10, and 20 cm. Replicate samples were removed from under a clear plastic solarization cover at 7-day intervals and the number of viable teliospores determined. A rapid decline in teliospore viability occurred at all treatment depths over 38 days, with efficacy comparable with methyl bromide protocols using clear plastic sheeting. Initial viability rates of 43, 71, and 82% germination were reduced to 0.1, 7.7, and 0.2% after 38 days (across all depths) in 2003, 2005, and 2006, respectively. Mean daily maximum soil temperatures at 5 and 20 cm under clear plastic in 2003, 2005, and 2006 were 67, 53 and 60°C and 43, 38, and 43°C, respectively. Under current United States Department of Agriculture disease management strategies, the method may be useful for the rapid deregulation of Karnal bunt-affected fields.

Automatic behaviour: efficient not mindless.

Automaticity is a core construct underpinning theoretical accounts of human performance and cognition. In spite of this, its current conceptualisation is plagued by circularity - automaticity is typically defined in terms of the very behaviour it seeks to explain - and a lack of internal consistency-defining features of automaticity do not reliably co-occur. Furthermore, invoking automaticity tends to be post hoc as it is used to explain violations of dominant theories of attention. Prevailing models of automaticity explain automatic processing as merely faster processing than controlled processing. We present an alternative conceptualisation of automaticity as efficient, elegant and economical but not fast. This is supported by functional imaging studies, which reveal a pattern of reduced global activation as well as a shift in activation from cortical to subcortical areas once automaticity has been achieved. Were automaticity to be faster processing, functional imaging would indicate greater activation when an automatic task is performed. We propose possible circuitry of automaticity incorporating the direct pathways of the basal ganglia.

Lack of ranitidine effects on cyclophosphamide bone marrow toxicity or metabolism: a placebo-controlled clinical trial.

We previously reported that cimetidine but not ranitidine significantly enhances cyclophosphamide-induced bone marrow toxic effects and the appearance of cyclophosphamide alkylating species in a murine leukemia mouse model, and we advised caution in the use of cimetidine with microsomally metabolized anticancer drugs. Both drugs have been used for the treatment of gastric complications of chemotherapy. Using a randomized, double-blind, crossover study design, we have now evaluated the potential interaction of ranitidine with cyclophosphamide in seven cancer patients, who received two courses of cyclophosphamide, one with ranitidine and one with placebo. Four patients received ranitidine in the first course, and three received placebo. Ranitidine or placebo was started 3 days before a single dose of cyclophosphamide and given for 17 consecutive days. Ranitidine or placebo was given orally (300 mg/d), and cyclophosphamide (600 mg/m2) was given intravenously with [3H]cyclophosphamide (1000 muCi). Cyclophosphamide treatment was repeated at 4 weeks plus or minus 4 days. Blood samples were collected at intervals from 5 minutes to 24 hours after cyclophosphamide treatment and analyzed by thin-layer chromatography and radioassay for the drug and its metabolites. On days 0, 7, 14, and 21 after cyclophosphamide administration, complete blood cell counts, white blood cell differential counts, platelet counts, and SMA-17 were determined. The differences in mean nadir white blood cell counts, granulocyte counts, hemoglobin levels, and hematocrit values during ranitidine versus placebo treatment were not statistically significant. In a statistical but not a clinical sense, mean nadir platelet counts were significantly lower with ranitidine. There was a statistically significant increase in area under the curve for drug concentration in plasma x time (AUC) with ranitidine as well as a statistically significant decrease in the total-body clearance rate of the cyclophosphamide molecule. However, the effect on AUC for the major oncolytic metabolites 4-hydroxycyclophosphamide and phosphoramide mustard was not statistically significant. The lack of toxicologic or metabolic interaction between ranitidine and cyclophosphamide suggests that ranitidine can be used safely with cyclophosphamide.

Plasma pharmacokinetics of cyclophosphamide and its cytotoxic metabolites after intravenous versus oral administration in a randomized, crossover trial.

Since cyclophosphamide is used by both oral and i.v. routes in the treatment of hematological and solid malignancies, we designed a randomized, crossover clinical trial to evaluate the pharmacokinetics of this anticancer agent after either administration route. Plasma levels of cyclophosphamide and its two cytotoxic metabolites, 4-hydroxycyclophosphamide and phosphoramide mustard, were determined in seven cancer patients randomly assigned to treatment initially with either orally or i.v. administered cyclophosphamide with a 30-day interim between alternate therapy courses. Oral treatment was used initially in five patients and i.v. treatment in two patients, and the pharmacokinetic parameter, area under the plasma disappearance curve, was determined for each metabolite in each patient for both routes of drug administration. Statistical comparison of area under the plasma disappearance curve values for this set of patients indicated no significant differences for either metabolite for oral versus i.v. drug treatment, suggesting equal efficacy for these two routes of cyclophosphamide administration.

Identification of Ezrin-Radixin-Moesin proteins as novel regulators of pathogenic B-cell receptor signaling and tumor growth in diffuse large B-cell lymphoma.

Diffuse large B-cell lymphoma (DLBCL) is a hematological cancer associated with an aggressive clinical course. The predominant subtypes of DLBCL display features of chronic or tonic B-cell antigen receptor (BCR) signaling. However, it is not known whether the spatial organization of the BCR contributes to the regulation of pro-survival signaling pathways and cell growth. Here, we show that primary DLBCL tumors and patient-derived DLBCL cell lines contain high levels of phosphorylated Ezrin-Radixin-Moesin (ERM) proteins. The surface BCRs in both activated B cell and germinal B cell subtype DLBCL cells co-segregate with phosphoERM suggesting that the cytoskeletal network may support localized BCR signaling and contribute to pathogenesis. Indeed, ablation of membrane-cytoskeletal linkages by dominant-negative mutants, pharmacological inhibition and knockdown of ERM proteins disrupted cell surface BCR organization, inhibited proximal and distal BCR signaling, and reduced the growth of DLBCL cell lines. In vivo administration of the ezrin inhibitor retarded the growth of DLBCL tumor xenografts, concomitant with reduction in intratumor phosphoERM levels, dampened pro-survival signaling and induction of apoptosis. Our results reveal a novel ERM-based spatial mechanism that is coopted by DLBCL cells to sustain tumor cell growth and survival.

Impaired movement sequencing in patients with Huntington's disease: a kinematic analysis.

This experiment asked whether Huntington's disease, like Parkinson's disease, another disorder of the basal ganglia, causes a specific progressive deficit in the performance of sequential movement. Ten patients with Huntington's disease and their age-matched controls wrote the lower-case letter "l" four times in a linked cursive script, upon a graphics tablet which sampled pen position at 200 Hz. Kinematic features of sequential movement (stroke length, stroke duration, peak velocity, time to peak velocity and time from peak to zero velocity) were examined in a Group by Stroke Position (2 x 8) design, to identify which aspects of movement might show progressive disturbances. Unlike Agostino et al. [Brain 115, 1481-1495, 1992], this experiment did in fact find progressive changes in the performance of sequential movements. Kinematic analysis indicated a progressive increase in movement duration during sequential movement, that was associated with the accelerative phase of movement.

Impairments of movement execution in unilateral neglect: a kinematic analysis of directional bradykinesia.

A kinematic analysis was performed on goal-directed movements made by 14 patients with right hemisphere damage and left unilateral neglect (seven mild, seven severe), and 14 healthy controls. Leftward and rightward pen strokes of varying extents were made to targets of varying size on a centrally located digitising tablet. While mild unilateral neglect patients performed like controls, patients with severe unilateral neglect were slower to initiate leftward than rightward strokes and were slow and inefficient in movement execution. Leftward strokes made by severe unilateral neglect patients were characterised by prolonged movement time, lower peak velocity and departed from optimal bell-shaped velocity profiles. Their leftward strokes also showed prolonged accelerative phases, implying difficulties in force production, while the high proportion of their total movement time spent in decelerating with rightward strokes suggested an abnormal emphasis on terminal visual guidance. Leftward strokes made by these patients also contained more submovements than rightward strokes, suggesting poor force control. An impaired internal representation of the location of left-sided targets and desired movement trajectories in severe unilateral neglect causes breakdown in the temporal control of goal-directed movements.

The effect of Huntington's disease and Gilles de la Tourette's syndrome on the ability to hold and shift attention.

Huntington's disease (HD) and Tourette's syndrome (TS) are two basal ganglia (BG) disorders, associated not simply with hyperkinetic movements but also with attentional impairments. The purpose of this experiment was to evaluate the attention deficits reported in HD and TS via the use of a vibrotactile choice reaction time (CRT) procedure involving biased probabilities of event occurrence. We attempted to ascertain whether HD and TS patients are impaired in their ability to shift their attention to an unexpected location, or when they have to hold attention to an expected location. The results demonstrate that HD patients, as compared to controls, experience difficulties in shifting their attention from expected to unexpected spatial locations; this effect was exacerbated with the adoption of a crossed arm configuration. On the other hand, TS patients' performance, although slower overall, was not qualitatively greatly different from that of the controls. We had previously found, with a similar paradigm, that Parkinson's disease patients instead manifest problems in holding or maintaining attention to an expected locus. We conclude that HD patients experience considerable difficulties in allocating attentional resources between expected and unexpected event occurrences. Perhaps due to pervasive subcortical damage and dysfunction in the circuits linking the frontal lobes with the BG. In TS, a similar if milder functional rather than structural deficit may be reflected in a pattern of responses which resembles a weaker version of the HD response pattern.

Parkinsonian patients without dementia or depression do not suffer from bradyphrenia as indexed by performance in mental rotation tasks with and without advance information.

A predominant symptom of Parkinson's disease is akinesia and bradykinesia, slowing in the initiation and execution of voluntary movement. There has long been speculation as to whether cognitive processes undergo similar processes, but findings may be confounded by the frequent co-occurrence of dementia and/or depression. Mental rotation provides an internal or cognitive analogue of real movement, and enables us to determine the speed of such mental processes independent of any concurrent motor slowing in response initiation and execution. Medicated patients with Parkinson's disease who were free of dementia and depression were found to be able to mentally rotate alphanumeric or figural stimuli, with and without advance information as to the view (front or back) of a stick figure shortly to be shown, as rapidly as normal healthy controls. We conclude that cognitive processes involved in mental rotation are not necessarily slowed in Parkinson's disease.

Visuo-spatial processing in parkinsonians.

It has been suggested that patients with Parkinson's disease (PDs) may have problems processing visuo-spatial information and that this deficiency may contribute to the motor control problems observed in PD. However, most studies reporting visuo-spatial deficits are equivocal; they confound perceptual and motor processes. To address this issue, the present experiment systematically compared the relative contributions of several cognitive processes to performance: perception, stimulus-response translation, movement preparation and execution. Seven non-demented PDs and seven age-matched controls performed visual RT tasks, based upon judgements of spatial displacements. Both the RT and MT data suggested that PDs do not prepare movements as adequately as normals, and that PD deficits are associated with problems controlling movement execution. On the other hand, PDs were not slower in judging distances and linking perception to action, suggesting that previous findings of visuo-spatial deficits may be due in part to motor impairments.

Attentional asymmetries following ECT in patients with major depression.

Neuropsychological abnormalities of lateralization have been reported after right unilateral electroconvulsive therapy (ECT), that may reflect temporary disruption of the treated hemisphere. A visuospatial task sensitive to lateralization of spatial attention was administered in a test-retest design to patients with unipolar major depression and a group of age and gender matched controls. The patient group underwent right unilateral ECT between the two test sessions. The patient and control groups did not differ significantly at the initial baseline testing. After ECT, the patient group showed a significant shift of attentional bias toward the left, while the control group showed no significant shift in the second session relative to the first. The results suggest that approximately 1 h after termination of ictus there is a leftward attentional bias, possibly reflecting a change in right hemisphere cerebral activity.

Contingent and non-contingent auditory cueing in Parkinson's disease.

Parkinson's disease (PD) patients and their normal controls performed two experiments involving a sequential movement task, depressing a series of buttons at choice points along a response board. Visual or auditory cues were presented prior to each move according to various contingencies. PD, a disorder characterised by degeneration of the basal ganglia (BG), typically manifests with poor execution of motor sequences. We found that external cueing facilitated motor sequencing in PD patients. In particular, auditory cues which occurred late in the movement cycle maximally facilitated switching between subcomponents of a sequence. Based on physiological findings reported in the primate literature [Brotchie et al., Brain 114, 1685-1702, 1978; Schultz and Romo, Exp. Brain Res. 1, 363-384, 1992], it is suggested that external cues enhance performance by replacing defective, internally generated cues (discharges) of the BG. This has implications for the use of physical training strategies in the treatment of PD.

To see or not to see: the effects of visible and invisible cues on line bisection judgements in unilateral neglect.

Patients with left unilateral neglect and matched controls were tested in two experiments to examine the effects of lateralized cues on line bisection judgements. Unlike previous studies in which letter or number cues were placed beyond the endpoint(s) of each line, we adopted a procedure which maintained the perceptual point of balance in the horizontal axis of each line. We also related the cueing task more closely to the act of bisection by requiring subjects to place a small mark in direct alignment with the endpoint(s) of each line. In the first experiment, it was found that, for controls, the presence or absence of visible lateralized cues did not differentially affect the magnitude of bisection errors. However, the magnitude of bisection errors made by neglect patients was significantly reduced (and reversed) in the presence of a visible left-sided cue, but remained well to the right of the midpoint in the absence of such cues. In a second experiment, subjects engaged in an otherwise identical cueing procedure, except that no visible marks appeared on the stimulus lines. Neither subject group was affected by the presence or absence of right-sided cues. However, the presence of left-sided cues again reduced the magnitude of bisection errors in neglect patients, but not in controls. These results indicate that the extent of the attentional bias exhibited by neglect patients can be ameliorated even in the absence of lateralized visible cues.

Bradykinesia and movement precision in Huntington's disease.

To determine whether bradykinesia in patients with Huntington's disease (HD) reflects impaired force production or an increased requirement for terminal visual guidance, 11 HD patients and matched controls performed drawing movements with varying precision requirements. Participants used an electronic pen upon a WACOM SD420 graphics tablet to join targets of either 10 or 20 mm diameter which were separated by a distance of 62.5 or 125 mm. While HD patients had slower movements, exhibiting more cycles of acceleration and deceleration, patients were not disproportionately affected by variations in target size or separation. Bradykinesia did not seem to be a product of impaired force production or increased reliance upon terminal visual guidance, since neither accelerative or decelerative phases were specifically affected by HD. However, movements of HD patients were of less consistent duration, implying variability associated with internal cues regulating movement.

Response programming in patients with schizophrenia: a kinematic analysis.

Schizophrenia may involve disturbed subcortical mechanisms or anomalous functional asymmetries. We therefore examined any anomalies of functional asymmetry in a kinematic analysis of a cued sequential movement task previously found to be sensitive to basal ganglia dysfunction. Twenty patients with schizophrenia and 20 matched controls used preferred or non-preferred hand to connect a series of targets on a WACOM SD420 graphics tablet, in response to the pattern of illumination of light emitting diodes (LEDs). Movements were to be initiated with or without an external cue as to target location. Patients with schizophrenia exhibited relatively normal functional asymmetries, but had programming deficits, taking longer to initiate (i.e. self generate) movements in the absence of an external cue. The movements of patients with schizophrenia were more variable and less efficient, resembling those seen in Huntington's disease. Results supported a hypothesis of disturbance at some level in fronto-subcortical circuitry in schizophrenia.

Response programming in dementia of the Alzheimer type: a kinematic analysis.

Although planning is important for the functioning of patients with dementia of the Alzheimer Type (DAT), little is known about response programming in DAT. This study used a cueing paradigm coupled with quantitative kinematic analysis to document the preparation and execution of movements made by a group of 12 DAT patients and their age and sex matched controls. Participants connected a series of targets placed upon a WACOM SD420 graphics tablet, in response to the pattern of illumination of a set of light emitting diodes (LEDs). In one condition, participants could programme the upcoming movement, whilst in another they were forced to reprogramme this movement on-line (i.e. they were not provided with advance information about the location of the upcoming target). DAT patients were found to have programming deficits, taking longer to initiate movements, particularly in the absence of cues. While problems spontaneously programming a movement might cause a greater reliance upon on-line guidance, when both groups were required to guide the movement on-line, DAT patients continued to show slower and less efficient movements implying declining sensori-motor function; these differences were not simply due to strategy or medication status.