Anticipated discrimination among people with schizophrenia.

OBJECTIVE: The aim of this study was to evaluate the level of anticipated discrimination in people with schizophrenia (n = 732) from 27 countries in the International Study of Discrimination and Stigma Outcomes (INDIGO). METHOD: Anticipated discrimination was assessed through four questions of Discrimination and Stigma Scale. Twenty-five individuals were identified at each site who were reasonably representative of all such treated cases within the local area. RESULTS: Sixty-four per cent of the participants reported that they had stopped themselves from applying for work, training or education because of anticipated discrimination. Seventy-two per cent of them reported that they felt the need to conceal their diagnosis. Expecting to be avoided by others who know about their diagnosis was highly associated with decisions to conceal their diagnosis. Those who concealed their diagnosis were younger and more educated. The participants who perceived discrimination by others were more likely to stop themselves from looking for a close relationship. Anticipated discrimination in finding and keeping work was more common in the absence than in the presence of experienced discrimination, and the similar findings applied to intimate relationships. CONCLUSION: This study shows that anticipated discrimination among people with schizophrenia is common, but is not necessarily associated with experienced discrimination.

Manual interception of moving targets in two dimensions: performance and space-time accuracy.

We report results from four experiments that examined performance of an interceptive task that restricted movement of the hand and moving target to a horizontal plane. The task required accurate control over both where and when interception takes place. Three experiments studied the effects of four independent variables: target speed, target size, manipulandum size and movement amplitude. For small amplitude movements, small, fast targets were hit harder than larger slower ones and targets were hit harder with smaller manipulanda; movement time (MT) was unaffected by target size, but was shorter when the manipulandum was smaller. For larger amplitude movements, smaller, faster targets were also hit harder, but MTs tended to be greater when targets were smaller. The results support the idea that MT and peak movement speed can be independently controlled to some degree in order to meet the accuracy demands of the task. Analysis of the task showed that spatial and temporal accuracy demands are interdependent, indicating that the spatial and temporal variable errors should covary such that increases in one are accompanied by decreases in the other. This can be tested if there is no variation in interception location; which was not the case in the first three experiments. In a final experiment variation in interception location was restricted by requiring that the target be struck through an aperture. Both spatial and temporal variable errors could be estimated. As predicted, it was found that when spatial errors were small, temporal errors were large.

Effects of acoustic startle stimuli on interceptive action.

In reaction time (RT) tasks, presentation of a startling acoustic stimulus (SAS) together with a visual imperative stimulus can dramatically reduce RT while leaving response execution unchanged. It has been suggested that a prepared motor response program is triggered early by the SAS but is not otherwise affected. Movements aimed at intercepting moving targets are usually considered to be similarly governed by a prepared program. This program is triggered when visual stimulus information about the time to arrival of the moving target reaches a specific criterion. We investigated whether a SAS could also trigger such a movement. Human experimental participants were trained to hit moving targets with movements of a specific duration. This permitted an estimate of when movement would begin (expected onset time). Startling and sub-startle threshold acoustic probe stimuli were delivered unexpectedly among control trials: 65, 85, 115 and 135 ms prior to expected onset (10:1 ratio of control to probe trials). Results showed that startling probe stimuli at 85 and 115 ms produced early response onsets but not those at 65 or 135 ms. Sub-threshold stimuli at 115 and 135 ms also produced early onsets. Startle probes led to an increased vigor in the response, but sub-threshold probes had no detectable effects. These data can be explained by a simple model in which preparatory, response-related activation builds up in the circuits responsible for generating motor commands in anticipation of the GO command. If early triggering by the acoustic probes is the mechanism underlying the findings, then the data support the hypothesis that rapid interceptions are governed by a motor program.

Constraints on the spatiotemporal accuracy of interceptive action: effects of target size on hitting a moving target.

Results of two experiments are reported that examined how people respond to rectangular targets of different sizes in simple hitting tasks. If a target moves in a straight line and a person is constrained to move along a linear track oriented perpendicular to the target's motion, then the length of the target along its direction of motion constrains the temporal accuracy and precision required to make the interception. The dimensions of the target perpendicular to its direction of motion place no constraints on performance in such a task. In contrast, if the person is not constrained to move along a straight track, the target's dimensions may constrain the spatial as well as the temporal accuracy and precision. The experiments reported here examined how people responded to targets of different vertical extent (height): the task was to strike targets that moved along a straight, horizontal path. In experiment 1 participants were constrained to move along a horizontal linear track to strike targets and so target height did not constrain performance. Target height, length and speed were co-varied. Movement time (MT) was unaffected by target height but was systematically affected by length (briefer movements to smaller targets) and speed (briefer movements to faster targets). Peak movement speed (Vmax) was influenced by all three independent variables: participants struck shorter, narrower and faster targets harder. In experiment 2, participants were constrained to move in a vertical plane normal to the target's direction of motion. In this task target height constrains the spatial accuracy required to contact the target. Three groups of eight participants struck targets of different height but of constant length and speed, hence constant temporal accuracy demand (different for each group, one group struck stationary targets = no temporal accuracy demand). On average, participants showed little or no systematic response to changes in spatial accuracy demand on any dependent measure (MT, Vmax, spatial variable error). The results are interpreted in relation to previous results on movements aimed at stationary targets in the absence of visual feedback.

Wrist posture during computer pointing device use.

OBJECTIVE: This research examines individual differences in the wrist postures adopted during the use of two pointing devices (mouse and trackball). DESIGN: A multiple case study of twelve participants was employed. BACKGROUND: The use of pointing devices may lead to musculoskeletal discomfort and injury as a consequence of prolonged exposure to postures involving wrist extension and ulnar deviation. METHODS: Wrist flexion/extension and radial/ulnar deviation was measured while twelve participants completed two standardised tasks involving horizontal and vertical cursor movements respectively. RESULTS: Exposure to extreme ulnar deviation and wrist extension was observed in the use of computer mouse and trackball. The trackball involved decreased ulnar deviation and increased wrist extension, however considerable individual differences were observed. CONCLUSIONS: Some users may be placed at risk of injury by prolonged exposure to the use of such devices, while others may not. A trackball may reduce the exposure to extreme ulnar deviation, but in some cases, a trackball may increase exposure to extreme wrist extension.

Gaze angle: a possible mechanism of visual stress in virtual reality headsets.

It is known that some Virtual Reality (VR) head-mounted displays (HMDs) can cause temporary deficits in binocular vision. On the other hand, the precise mechanism by which visual stress occurs is unclear. This paper is concerned with a potential source of visual stress that has not been previously considered with regard to VR systems: inappropriate vertical gaze angle. As vertical gaze angle is raised or lowered the 'effort' required of the binocular system also changes. The extent to which changes in vertical gaze angle alter the demands placed upon the vergence eye movement system was explored. The results suggested that visual stress may depend, in part, on vertical gaze angle. The proximity of the display screens within an HMD means that a VR headset should be in the correct vertical location for any individual user. This factor may explain some previous empirical results and has important implications for headset design. Fortuitously, a reasonably simple solution exists.

The contribution of vision and proprioception to judgements of finger proximity.

We sought to determine whether an increase in judged egocentric distance created by increasing vergence-specified distance would be negated when participants pointed at their own finger. It was found that ocular position dominates limb proprioception in the judgement of finger distance in the sagittal plane when vision is available. In contrast, an increase in perceived egocentric distance was largely attenuated by the presence of limb proprioception in reduced visual cue conditions. We conclude that the relative contribution of vergence to perceived distance depends upon the strength of the vergence effort signal when there are other cues present. Furthermore, if the distance percept includes a major contribution from retinal cues, then the visual component will dominate the limb proprioception component. If the visual component is largely determined by vergence information, limb proprioception will make a significant contribution and actually dominate when the vergence effort signal is weak. The results extend previous studies that have found a similar relationship between ocular position and limb proprioception in the perception of a finger's location in the coronal plane.

The effect of imposed and self-selected computer monitor height on posture and gaze angle.

OBJECTIVE:: The objectives were to determine the postural consequences of varying computer monitor height and to describe self-selected monitor heights and postures. DESIGN:: The design involved experimental manipulation of computer monitor height, description of self-selected heights, and measurement of posture and gaze angles. BACKGROUND: Disagreement exists with regard to the appropriate height of computer monitors. It is known that users alter both head orientation and gaze angle in response to changes in monitor height; however the relative contribution of atlanto-occipital and cervical flexion to the change in head rotation is unknown. No information is available with regard to self-selected monitor heights. METHODS: Twelve students performed a tracking task with the monitor placed at three different heights. The subjects then completed eight trials in which monitor height was first self-selected. Sagittal postural and gaze angle data were determined by digitizing markers defining a two-dimensional three-link model of the trunk, cervical spine and head. RESULTS: The 27 degrees change in monitor height imposed was, on average, accommodated by 18 degrees of head inclination and a 9 degrees change in gaze angle relative to the head. The change in head inclination was achieved by a 6 degrees change in trunk inclination, a 4 degrees change in cervical flexion, and a 7 degrees change in atlanto-occipital flexion. The self-selected height varied depending on the initial monitor height and inclination. CONCLUSIONS: Self-selected monitor heights were lower than current 'eye-level' recommendations. Lower monitor heights are likely to reduce both visual and musculoskeletal discomfort. RELEVANCE: Musculoskeletal and visual discomfort may be reduced by placing computer monitors lower than currently recommended.

Looking at the task in hand: vergence eye movements and perceived size.

A retinal afterimage of the hand changes size when the same unseen hand is moved backwards and forwards in darkness. We demonstrate that arm movements per se are not sufficient to cause a size change and that vergence eye movements are a necessary and sufficient condition for the presence of the illusory size change. We review previous literature to illustrate that changing limb position in the dark alters vergence angle and we explain the illusion via this mechanism. A discussion is provided on why altering limb position causes a change in vergence and we speculate on the underlying mechanisms.

Formation and repair of DNA interstrand cross-links in relation to cytotoxicity and unscheduled DNA synthesis induced in control and mutant human cells treated with cis-diamminedichloroplatinum(II).

A comparative study was performed with a variety of human cell lines on the effects of treatments with cis-diamminedichloroplatinum(II) (cisplatin) on cell survival and the induction of unscheduled DNA synthesis. In addition to control fibroblasts (Han, MB), cell lines defective in DNA repair were used [xeroderma pigmentosum, XP(A) and XP(F), and Fanconi's anemia (FA)], as well as cells deficient in arylsulfatase A (mucolipidosis II, ML1 and ML2). Ultraviolet light and mitomycin C were included in this study as model DNA-damaging agents. Furthermore, induction of DNA interstrand cross-links by cisplatin and their repair were studied. As for survival, only XP cells were abnormally sensitive to ultraviolet light, and only FA cells were abnormally sensitive to mitomycin C. To cisplatin, however, all mutants tested were more sensitive (2 to 5 times) than were normal cells. Unscheduled DNA synthesis induction by ultraviolet light was strong in all but the XP cells; the other two agents did not induce unscheduled DNA synthesis. Induction of DNA interstrand cross-links by cisplatin was linear with dose. Formation continued for up to 18 to 24 h after treatment. During this period, all cells but the ML mutants responded similarly. In ML cells, much fewer cross-links were induced, which were repaired rapidly. In FA cells, accumulation continued for at least 96 h; in the other cells, most of the cross-links had been removed after that period. In the discussion, the cisplatin-induced DNA interstrand cross-links are proposed as an important potentially lethal lesion, in view of their persistence in the highly sensitive FA cells. Furthermore, the possible involvement of certain steps of the long-patch excision repair pathway in the removal of this lesion is considered. The sensitivity of ML cells to cisplatin is attributed to cytoplasmic effects, rather than to chromosomal damage.

Influence of treatment temperature on the genotoxic effects of cisplatin in CHO cells: cytotoxicity, mutagenicity and induction of lesions in DNA.

In cells exposed in vitro to the cytotoxic and mutagenic antitumor drug cisplatin (cis-Pt(NH3)2Cl2), various adducts with nuclear DNA are formed. A comparative study was made of the influence of temperature variation during treatment of cultured Chinese hamster ovary (CHO) cells with cisplatin on cytotoxicity, mutation induction and Pt-DNA adduct formation. Before and after treatment (1 h at 32, 37 or 40 degrees C) cells were kept at 37 degrees C. Cytotoxicity increased with temperature; D0 values were 29.6 +/- 1.6, 21.1 +/- 1.2 and 11.4 +/- 0.6 microM at 32, 37 and 40 degrees C, respectively. Pt-DNA binding to DNA at 40 degrees C was 2.0 (+/- 0.3) times as high as at 32 degrees C. This factor remained practically constant over a 24-h post-treatment incubation of the cells, during which about 60% of DNA-bound Pt were removed. As the increase in cytotoxicity between 32 and 40 degrees C was roughly in proportion to that in Pt binding, no substantial changes in the spectrum of adducts appeared to occur. The induction of DNA interstrand cross-links, studied at 32 and 40 degrees C, varied linearly with dose. Influence of temperature on cross-link formation was comparable to that on total Pt binding. Amounts of cross-links highly increased during 24 h after treatment. Plots of cross-links against survival after treatments at 32 and 40 degrees C almost coincided. Induction of 6-thioguanine-resistant (HGPRT) mutants at various cisplatin concentrations did not show a clear temperature dependency. Consequently, equitoxic treatments were significantly more mutagenic at 32 degrees C than at 40 degrees C, the opposite of what has been reported for E. coli.

The quantitative detection of various Pt-DNA-adducts in Chinese hamster ovary cells treated with cisplatin: application of immunochemical techniques.

With polyclonal antibodies raised against cis-Pt(NH3)2Guo-GMP, small quantities of specific Pt-adducts could be detected in DNA from Chinese hamster ovary (CHO) cells treated with the antitumor agent cisplatin, after the DNA had been digested with nucleases and the degradation products separated by anion-exchange chromatography (FPLC). Directly after treatment with 83 microM cisplatin, resulting in 97 X 10(-6) platinum atoms bound per nucleotide, 35.9 +/- 4.7% of the platinum was recovered as cis-Pt(NH3)2d(pGpG), derived from intrastrand cross-links on two neighboring guanines, 3.1 +/- 1.6% as cis-Pt(NH3)2d(GMP)2, the degradation product of interstrand cross-links on two guanines (0.07%, according to separate studies) and of intrastrand cross-links on two guanines separated by one or more bases. The immunochemical method was not sensitive enough for the detection of monofunctionally bound platinum on guanine residues. The amount of these adducts, present in the digests as Pt(NH3)3dGMP, could be established with atomic absorption spectroscopy (AAS) (38.5% of the total Pt-content of the DNA). After a post-treatment incubation of the cells for 24 h, the total amount of platinum decreased to 59 X 10(-6) atoms per nucleotide, indicating the removal of adducts. In the digests, cis-Pt(NH3)2d(pGpG) accounted for 46.4 +/- 6.8% of the total Pt-content, cis-Pt(NH3)2d(GMP)2 for 3.0 +/- 0.9% (0.34% derived from DNA interstrand cross-links). The amounts of monofunctional adducts had decreased to such an extent that the exact quantities (below 15%) could not be determined. According to AAS-assays, at the elution position of cis-Pt(NH3)2d(pApG) a significant amount of Pt-product was present, both at t = 0 and 24 h, but the signals did not allow quantitative evaluation (however, below 48% and 28%, respectively). The possible role of the individual lesions in the DNA in the biological effects of this platinum compound in CHO cells is discussed.

Induction and repair of DNA cross-links in chinese hamster ovary cells treated with various platinum coordination compounds in relation to platinum binding to DNA, cytotoxicity, mutagenicity, and antitumor activity.

Several effects of four diamminechloroplatinum compounds (II and IV) in Chinese hamster ovary cells were studied. The two cis-compounds [cis-diamminedichloroplatinum(II) and cis-diamminetetrachloroplatinum(IV)] are known to possess antitumor activity, whereas the two trans-stereoisomers [trans-diamminedichloroplatinum(II) and trans-diamminetetrachloroplatinum(IV)] are inactive. When the effects of the cis-and trans-platinum compounds were compared after treatments that resulted in the binding of equal amounts of platinum to the DNA of the cells, the following differences were found: (a) the cis-platinum adducts gave a much higher cytotoxicity; (b) only the cis-platinum-DNA complexes were strongly mutagenic (forward mutations at the hypoxanthine-guanine phosphoribosyltransferase locus); (c) the cis-platinum adducts induced more sister chromatid exchanges; (d) the cis compounds initially induced fewer DNA-protein cross-links (Factors 5 to 8), but these cis-platinum cross-links were much more persistent; (e) for both cis complexes, the amount of DNA interstrand cross-links passed through a maximum between 6 and 12 hr after treatment, and the cross-links were repaired slowly. One trans-compound [trans-diamminetetrachloroplatinum(IV)] resembled the cis complexes with respect to the overall kinetics of formation and disappearance of this type of lesion, but the repair went faster. For the other trans compound [trans-diamminedichloroplatinum(II)], the highest number of cross-links was detected directly after the treatment of the cells, and they were rapidly eliminated. Neither the number of platinum-DNA lesions as such nor the initial amount of DNA interstrand cross-links could be related to the (geno)toxic effects of the compounds. However, as the slow repair of the cis-platinum-induced interstrand and DNA-protein cross-links leads to a certain persistency of these adducts, the unrepaired lesions might be responsible for cytotoxicity, mutagenicity, and antitumor activity. This indicates discriminating properties of the repair systems for certain cis-or trans-platinum-DNA adducts. The sister chromatid exchange induction seems to be related to the persistent DNA interstrand cross-links.

Platinum compounds with anti-tumour activity.

Ten platinum (Pt) coordination complexes with different ligands, comprising both Pt(II) and Pt(IV) complexes of which the cis-compounds all possessed at least some anti-tumour activity and the trans-compounds were inactive, were tested as to their effect on cell survival and the induction and repair of DNA damage in cultured Chinese hamster cells (CHO). The tests used were the determination of cytotoxicity, inhibition of the semi-conservative DNA replication, induction of damage in DNA and mutagenicity. The Pt-compounds could be divided in 3 groups on the basis of their cytotoxicity. The compounds with high cytotoxicity were also active anti-tumour drugs, but a clear correlation between cytotoxicity and anti-tumour activity was not observed. All compounds inhibited semi-conservative DNA synthesis and induced DNA repair replication. No induction of DNA single strand breaks and DNA cross-links was detected. However, the occurrence of alkali labile sites in the DNA of treated CHO cells demonstrated the induction of unidentified DNA base damages. The 4 compounds tested so far, 2 cis- and 2 trans-Pt complexes, induced mutations in CHO cells, leading to resistance to 6-thioguanine; the cis-compounds were more mutagenic than the trans-compounds.