Precision in spatial working memory examined with mouse pointing.

The capacity of visuospatial working memory (VSWM) is limited. However, there is continued debate surrounding the nature of this capacity limitation. The resource model (Bays et al., 2009) proposes that VSWM capacity is limited by the precision with which visuospatial features can be retained. In one of the few studies of spatial working memory, Schneegans and Bays (2016) report that memory guided pointing responses show a monotonic decrease in precision as set size increases, consistent with resource models. Here we report two conceptual replications of this study that use mouse responses rather than pointing responses. Overall results are consistent with the resource model, as there was an exponential increase in localisation error and monotonic increases in the probability of misbinding and guessing with increases in set size. However, an unexpected result of Experiment One was that, unlike Schneegans and Bays (2016), imprecision did not increase between set sizes of 2 and 8. Experiment Two replicated this effect and ruled out the possibility that the invariance of imprecision at set sizes greater than 2 was a product of oculomotor strategies during recall. We speculate that differences in imprecision are related to additional visuomotor transformations required for memory-guided mouse localisation compared to memory-guided manual pointing localisation. These data demonstrate the importance of considering the nature of the response modality when interpreting VSWM data.

A presaccadic perceptual impairment at the postsaccadic location of the blindspot.

Saccadic eye movements are preceded by profound changes in visual perception. These changes have been linked to the phenomenon of 'forward remapping', in which cells begin to respond to stimuli that appear in their post-saccadic receptive field before the eye has moved. Few studies have examined the perceptual consequences of remapping of areas of impaired sensory acuity, such as the blindspot. Understanding the perceptual consequences of remapping of scotomas may produce important insights into why some neurovisual deficits, such as hemianopia are so intractable for rehabilitation. The current study took advantage of a naturally occurring scotoma in healthy participants (the blindspot) to examine pre-saccadic perception at the upcoming location of the blindspot. Participants viewed stimuli monocularly and were required to make stimulus-driven vertical eye-movements. At a variable latency between the onset of saccade target (ST) and saccade execution a discrimination target (DT) was presented at one of 4 possible locations; within the blindspot, contralateral to the blindspot, in post-saccadic location of the blindspot and contralateral to the post-saccadic location of the blindspot. There was a significant perceptual impairment at the post-saccadic location of the blindspot relative to the contralateral post-saccadic location of the blindspot and the post-saccadic location of the blindspot in a no-saccade control condition. These data are consistent with the idea that the visual system includes a representation of the blindspot which is remapped prior to saccade onset.

Dynamic resource allocation in spatial working memory during full and partial report tasks.

Serial position effects are well-documented in working memory literature. Studies of spatial short-term memory that rely on binary response; full report tasks tend to report stronger primacy than recency effects. In contrast, studies that utilize a continuous response, partial report task report stronger recency than primacy effects (Gorgoraptis, Catalao, Bays, & Husain, 2011; Zokaei, Gorgoraptis, Bahrami, Bays, & Husain, 2011). The current study explored the idea that probing spatial working memory using full and partial continuous response tasks would produce different distributions of visuospatial working memory resources across spatial sequences and, therefore, explain the conflicting results in the literature. Experiment 1 demonstrated that primacy effects were observed when memory was probed with a full report task. Experiment 2 confirmed this finding while controlling eye movements. Critically, Experiment 3 demonstrated that switching from a full to a partial report task abolished the primacy effect and produced a recency effect, consistent with the idea that the distribution of resources in visuospatial working memory depends on the type of recall required. It is argued that the primacy effect in the whole report task arose from the accumulation of noise caused by the execution of multiple spatially directed actions during recall, whereas the recency effect in the partial report task reflects the redistribution of preallocated resources when an anticipated item is not presented. These data show that it is possible to reconcile apparently contradictory findings within the resource theory of spatial working memory and the importance of considering how memory is probed when interpreting behavioral data through the lens of resource theories of spatial working memory.

Gaze cueing, mental States, and the effect of autistic traits.

The ability to interpret and follow the gaze of our social partners is an integral skill in human communication. Recent research has demonstrated that gaze following behaviour is influenced by theory of mind (ToM) processes. However, it has yet to be determined whether the modulation of gaze cueing by ToM is affected by individual differences, such as autistic traits. The aim of this experiment was to establish whether autistic traits in neurotypical populations affect the mediation of gaze cueing by ToM processes. This study used a gaze cueing paradigm within a change detection task. Participants' perception of a gaze cue was manipulated such that they only believed the cue to be able to 'see' in one condition. The results revealed that participants in the Low Autistic Traits group were significantly influenced by the mental state of the gaze cue and were more accurate on valid trials when they believed the cue could 'see'. By contrast, participants in the High Autistic Traits group were also more accurate on valid trials, but this was not influenced by the mental state of the gaze cue. This study therefore provides evidence that autistic traits influence the extent to which mental state attributions modulate social attention in neurotypical adults.

Oculomotor rehearsal in visuospatial working memory.

The neural and cognitive mechanisms of spatial working memory are tightly coupled with the systems that control eye movements, but the precise nature of this coupling is not well understood. It has been argued that the oculomotor system is selectively involved in rehearsal of spatial but not visual material in visuospatial working memory. However, few studies have directly compared the effect of saccadic interference on visual and spatial memory, and there is little consensus on how the underlying working memory representation is affected by saccadic interference. In this study we aimed to examine how working memory for visual and spatial features is affected by overt and covert attentional interference across two experiments. Participants were shown a memory array, then asked to either maintain fixation or to overtly or covertly shift attention in a detection task during the delay period. Using the continuous report task we directly examined the precision of visual and spatial working memory representations and fit psychophysical functions to investigate the sources of recall error associated with different types of interference. These data were interpreted in terms of embodied theories of attention and memory and provide new insights into the nature of the interactions between cognitive and motor systems.

Factors associated with declaration of disability in medical students and junior doctors, and the association of declared disability with academic performance: observational study using data from the UK Medical Education Database, 2002-2018 (UKMED54).

OBJECTIVES: To examine factors associated with declaration of disability by medical students and doctors, and the association of declared disability with academic performance. DESIGN: Observational study using record-linked data collected between 2002 and 2018. SETTING: UK Medical Education Database is a repository of data relating to training of medical students and doctors. Disability and other data are record-linked. PARTICIPANTS: All students starting at a UK medical school between 2002 and 2018 (n=135 930). MAIN OUTCOME MEASURES: Declared disability was categorised by the Higher Education Statistics Authority. Outcomes related to undergraduate academic performance included scores in the educational performance measure (EPM), prescribing safety assessment and situational judgement test. Performance in postgraduate examinations was studied, as well as prior attainment in school examinations and aptitude tests. RESULTS: Specific learning disability (SLD) was the most commonly declared disability (3.5% compared with the next most commonly declared disability at 1.0% of n=129 345 all cases in the study), and during the period covered by the data, SLD declarations increased from 1.4% (n=6440 for students starting in 2002) to 4.6% (n=8625 for students starting in 2018). In a logistic regression, the following factors predicted recording of SLD on entry to medical school ((exp(B)±95% CI), p<0.0001 unless otherwise stated): attendance at a fee-paying school (2.306±0.178), graduate status (1.806±0.205), participation of local areas quintile (1.089±0.030), age (1.034±0.012). First year medical students were less likely to declare SLD if they were from a non-white ethnic background (Asian/Asian British 0.324±0.034, black/black British 0.571±0.102, mixed 0.731±0.108, other ethnic groups 0.566±0.120), female (0.913±0.059; p=0.007) or from a low index of multiple deprivation quintile (0.963±0.029); p=0.017. In univariate analysis with Bonferroni corrections applied for multiple tests, no significant difference was observed in the recording of SLD according to socioeconomic class (χ2=5.637, p=1), whether or not a student's parents had a higher education (χ2=0.140, p=1), or whether or not a student had received a United Kingdom Clinical Aptitude Test (UKCAT) bursary (χ2=7.661, p=0.068). Students who declared SLD at some point in medical school (n=4830) had lower EPM normalised deviate values (-0.390) than those who did not (-0.119) (F=189.872, p<0.001). Those for whom SLD was recorded were as likely to complete the course successfully as those who did not declare disability (93.0% successful completion by those for whom SLD declared from year 1 (n=2480), 92.2% by those for whom SLD declared after year 1 (n=2350), 91.6% by those for whom SD not declared at any point (n=85 180)) (χ2=6.905, p=0.032). Of 3580 first year students who declared SLD, 43.1% had not sat the UKCAT Special Educational Needs aptitude test (which gives extra time for those with special educational needs), while 28% of 2400 registrants for whom SLD was recorded as medical students did not declare it at General Medical Council registration. CONCLUSIONS: Substantial increases in declaration of SLD may reflect changes in the social and legal environment during the period of the study. Those who declare SLD are just as likely to gain a primary medical qualification as those who do not. For some individuals, disability declaration appears to depend on context, based on differences in numbers declaring SLD before, during and after medical school.

Situational judgement test performance and subsequent misconduct in medical students.

INTRODUCTION: Situational judgement tests (SJTs) have been widely adopted, internationally, into medical selection. It was hoped that such assessments could identify candidates likely to exhibit future professional behaviours. Understanding how performance on such tests may predict the risk of disciplinary action during medical school would provide evidence for the validity of such SJTs within student selection. It would also inform the implementation of such tests within student recruitment. METHODS: This cohort study used data for 6910 medical students from 36 UK medical schools who sat the University Clinical Aptitude Test (UCAT) SJT in 2013. The relationship between SJT scores at application and the risk of subsequent disciplinary action during their studies was modelled. The incremental ability of the SJT scores to predict the risk of disciplinary action, above that already provided by UCAT cognitive test scores and secondary (high) school achievement, was also evaluated in 5535 of the students with information available on this latter metric. RESULTS: Two hundred and ten (3.05%) of the students in the cohort experienced disciplinary action. The risk of disciplinary action reduced with increasing performance on the admissions SJT (odds ratio (OR) 0.80, 95% confidence interval (CI) 0.69 to 0.92, p = 0.002). This effect remained similar after adjusting for cognitive performance and prior academic attainment (OR 0.77, 95% CI 0.65 to 0.92, p = 0.004). The overall estimated effect-size was small (Cohen's d = 0.08) and no evidence of 'threshold' effects were observed for the SJT scores and risk of disciplinary action. CONCLUSIONS: Performance on admissions SJTs can, at least modestly, incrementally predict the risk of subsequent disciplinary action, supporting their use in this context. However, for this SJT and outcome, there did not seem a distinct threshold score above which the risk of disciplinary action disproportionately increased. This should be considered when using the scores within medical selection.

Predictive validity of A-level grades and teacher-predicted grades in UK medical school applicants: a retrospective analysis of administrative data in a time of COVID-19.

OBJECTIVES: To compare in UK medical students the predictive validity of attained A-level grades and teacher-predicted A levels for undergraduate and postgraduate outcomes. Teacher-predicted A-level grades are a plausible proxy for the teacher-estimated grades that replaced UK examinations in 2020 as a result of the COVID-19 pandemic. The study also models the likely future consequences for UK medical schools of replacing public A-level examination grades with teacher-predicted grades. DESIGN: Longitudinal observational study using UK Medical Education Database data. SETTING: UK medical education and training. PARTICIPANTS: Dataset 1: 81 202 medical school applicants in 2010-2018 with predicted and attained A-level grades. Dataset 2: 22 150 18-year-old medical school applicants in 2010-2014 with predicted and attained A-level grades, of whom 12 600 had medical school assessment outcomes and 1340 had postgraduate outcomes available. OUTCOME MEASURES: Undergraduate and postgraduate medical examination results in relation to attained and teacher-predicted A-level results. RESULTS: Dataset 1: teacher-predicted grades were accurate for 48.8% of A levels, overpredicted in 44.7% of cases and underpredicted in 6.5% of cases. Dataset 2: undergraduate and postgraduate outcomes correlated significantly better with attained than with teacher-predicted A-level grades. Modelling suggests that using teacher-estimated grades instead of attained grades will mean that 2020 entrants are more likely to underattain compared with previous years, 13% more gaining the equivalent of the lowest performance decile and 16% fewer reaching the equivalent of the current top decile, with knock-on effects for postgraduate training. CONCLUSIONS: The replacement of attained A-level examination grades with teacher-estimated grades as a result of the COVID-19 pandemic may result in 2020 medical school entrants having somewhat lower academic performance compared with previous years. Medical schools may need to consider additional teaching for entrants who are struggling or who might need extra support for missed aspects of A-level teaching.

Reduced mood variability is associated with enhanced performance during ultrarunnning.

Ultrarunning requires extraordinary endurance but the psychological factors involved in successful ultrarunning are not well understood. One widely held view is that fluctuations in mood play a pivotal role in performance during endurance events. However, this view is primarily based on comparisons of mood before and after marathons and shorter running events. Indeed, to date no study has explicitly examined mood changes during a competive ultramarathon. To address this issue, we measured mood fluctuations in athletes competing in the Hardmoors 60, a 100 km, single day continuous trail-ultramarathon, and examined how variation in mood related to performance, as measured by completion time. The key finding was that the variability of athletes Total Mood Disturbance (TMD) score was significantly and positively correlated with completion time, consistent with the idea that mood is an important factor in determining race performance. Athletes also experienced a significant increase in tension immediately prior to race onset. This effect was more pronounced in less experienced athletes and significantly attenuated by measurement stage 1 at 35.4 km, which suggests the effect was driven by the release of pre-competition anxiety. Depression, anger and TMD were significantly lower at the pre-race measurement compared to the baseline measurement taken the week before. Consistent with previous studies, there were also significant increases in fatigue, anger and TMD during the race. The data are interpreted in terms of the Psychobiological model of endurance and may have broader implications for the understanding of endurance performance in other domains.

The presence of placeholders modulates the naso-temporal asymmetry in the remote distractor effect.

The remote distractor effect (RDE) is a well-known and robust phenomenon whereby latencies of saccades are increased when a distractor is presented simultaneously along with the saccade target. Studies of the RDE in patients with a loss of vision in one visual field (hemianopia) following damage to primary visual cortex have provided conflicting results. Rafal, Smith, Krantz, Cohen, and Brennan (1990) reported a naso-temporal asymmetry in the RDE in patients with hemianopias, with a greater influence of distractors presented in their blind temporal visual field. This asymmetry was not observed in typically sighted controls. By contrast, Walker, Mannan, Maurer, Pambakian, and Kennard (2000) observed no effect of distractors presented to either the blind nasal or blind temporal hemifield of hemianopes, but the naso-temporal asymmetry was observed in typically sighted controls. The present study addressed one potential methodological differences between the two studies by investigating the inhibitory effect of a distractor on saccade latency in neurotypical participants. Here participants were tested monocularly and the effect of a nasal/temporal hemifield distractor on saccade latency observed in the presence or absence of peripheral placeholders. Our results showed a naso-temporal asymmetry in the magnitude of the RDE in the no placeholder condition, with a greater RDE when the distractor was presented in the temporal visual field. However, in the placeholder condition the opposite asymmetry was observed, that is an increased RDE when the distractor was presented in the nasal visual field. Our results suggest that the presence/absence of a placeholder might be the critical factor explaining the discrepancy between Rafal et al. (1990) and Walker et al. (2000) in participants without visual field loss. The current results can be interpreted in terms of additional inhibitory or attentional processes that bias selection towards stimuli in the nasal hemifield in the presence of placeholders, still, the mechanisms underlying these effects remain unclear.

Scaling up high-throughput phenotyping for abiotic stress selection in the field.

KEY MESSAGE: High-throughput phenotyping (HTP) is in its infancy for deployment in large-scale breeding programmes. With the ability to measure correlated traits associated with physiological ideotypes, in-field phenotyping methods are available for screening of abiotic stress responses. As cropping environments become more hostile and unpredictable due to the effects of climate change, the need to characterise variability across spatial and temporal scales will become increasingly important. The sensor technologies that have enabled HTP from macroscopic through to satellite sensors may also be utilised here to complement spatial characterisation using envirotyping, which can improve estimations of genotypic performance across environments by better accounting for variation at the plot, trial and inter-trial levels. Climate change is leading to increased variation at all physical and temporal scales in the cropping environment. Maintaining yield stability under circumstances with greater levels of abiotic stress while capitalising upon yield potential in good years, requires approaches to plant breeding that target the physiological limitations to crop performance in specific environments. This requires dynamic modelling of conditions within target populations of environments, GxExM predictions, clustering of environments so breeding trajectories can be defined, and the development of screens that enable selection for genetic gain to occur. High-throughput phenotyping (HTP), combined with related technologies used for envirotyping, can help to address these challenges. Non-destructive analysis of the morphological, biochemical and physiological qualities of plant canopies using HTP has great potential to complement whole-genome selection, which is becoming increasingly common in breeding programmes. A range of novel analytic techniques, such as machine learning and deep learning, combined with a widening range of sensors, allow rapid assessment of large breeding populations that are repeatable and objective. Secondary traits underlying radiation use efficiency and water use efficiency can be screened with HTP for selection at the early stages of a breeding programme. HTP and envirotyping technologies can also characterise spatial variability at trial and within-plot levels, which can be used to correct for spatial variations that confound measurements of genotypic values. This review explores HTP for abiotic stress selection through a physiological trait lens and additionally investigates the use of envirotyping and EC to characterise spatial variability at all physical scales in METs.

Maleate salts of bedaquiline.

Bedaquiline is one of two important new drugs for the treatment of drug-resistant tuberculosis (TB). It is marketed in the US as its fumarate salt, but only a few salts of bedaquiline have been structurally described so far. We present here five crystal structures of bedaquilinium maleate {systematic name: [4-(6-bromo-2-meth-oxy-quinolin-3-yl)-3-hy-droxy-3-(naphthalen-1-yl)-4-phenyl-but-yl]di-methyl-aza-nium 3-carb-oxy-prop-2-enoate}, C32H32BrN2O2 +·C4H3O4 -, namely, a hemihydrate, a tetra-hydro-furan (THF) solvate, a mixed acetone/hexane solvate, an ethyl acetate solvate, and a solvate-free structure obtained from the acetone/hexane solvate by in situ single-crystal-to-single-crystal desolvation. All salts exhibit a 1:1 cation-to-anion ratio, with the anion present as monoanionic hydro-maleate and a singly protonated bedaquilinium cation. The maleate exhibits the strong intra-molecular hydrogen bond typical for cis-di-carb-oxy-lic acid anions. The conformations of the cations and packing inter-actions in the maleate salts are compared to those of free base bedaquiline and other bedaquilinium salts.

Interaction of Polymers with Enzalutamide Nanodroplets-Impact on Droplet Properties and Induction Times.

Amorphous solid dispersions (ASDs), which consist of a drug dispersed in a polymeric matrix, are increasingly being applied to improve the in vivo performance of poorly water-soluble drugs delivered orally. The polymer is a critical component, playing several roles including facilitating drug release from the ASD, as well as delaying crystallization from the supersaturated solution generated upon dissolution. Certain ASD formulations dissolve to produce amorphous drug-rich nanodroplets. The interaction of the polymer with these nanodroplets is poorly understood but is thought to be important for inhibiting crystallization in these systems. In this study, the impact of ionic polymers on the crystallization kinetics of enzalutamide from supersaturated solutions containing different amounts of amorphous nanodroplets was evaluated by determination of nucleation induction times. The amount of the polymer associated with the drug nanodroplets was also determined. When comparing two polymers, hydroxypropylmethyl cellulose acetate succinate (HPMCAS) and Eudragit E PO, it was found that the crystallization tendency and physical properties of the drug nanodroplets varied in the presence of these two polymers. Both polymers distributed between the aqueous phase and the drug-rich nanodroplets. A greater amount of Eudragit E PO was associated with the drug-rich nanodroplets. Despite this, Eudragit E PO was a less-effective crystallization inhibitor than HPMCAS in systems containing nanodroplets. In conclusion, in supersaturated solutions containing amorphous nanodroplets, the extent of association of a polymer with the drug nanodroplet does not solely predict crystallization inhibition.

Spatial attention and spatial short term memory in PSP and Parkinson's disease.

Progressive Supranuclear Palsy (PSP) is a neurodegenerative disorder characterised by deterioration in motor, oculomotor and cognitive function. A key clinical feature of PSP is the progressive paralysis of eye movements, most notably for vertical saccades. These oculomotor signs can be subtle, however, and PSP is often misdiagnosed as Parkinson's disease (PD), in its early stages. Although some of the clinical features of PD and PSP overlap, they are distinct disorders with differing underlying pathological processes, responses to treatment and prognoses. One key difference lies in the effects the diseases have on cognition. The oculomotor system is tightly linked to cognitive processes such as spatial attention and spatial short-term memory (sSTM), and previous studies have suggested that PSP and PD experience different deficits in these domains. We therefore hypothesised that people with PSP (N = 15) would experience problems with attention (assessed with feature and conjunction visual search tasks) and sSTM (assessed with the Corsi blocks task) compared to people with PD (N = 16) and Age Matched Controls (N = 15). As predicted, feature and conjunction search were sgnificantly slower in the PSP group compared to the other groups, and this deficit was significantly worse for feature compared to conjunction search. The PD group did not differ from AMC on feature search but were significantly impaired on the conjunction search. The PSP group also had a pronounced vertical sSTM impairment that was not present in PD or AMC groups. It is argued that PSP is associated with specific impairment of visuospatial cognition which is caused by degeneration of the oculomotor structures that support exogenous spatial attention, consistent with oculomotor theories of spatial attention and memory.

The role of the left dorsolateral prefrontal cortex in attentional bias.

The DLPFC is thought to be critically involved in maintaining attention away from behaviourally irrelevant information, and in the establishment of attentional control settings. These play an important role in the phenomenon of top-down bias to features in the visual field - also known as attentional bias. This paper probes the involvement of the left DLPFC in attentional bias by manipulating its cortical excitability via tDCS and then analysing these effects following an induced attentional bias towards the colour green. Although both anodal and cathodal tDCS over the left DLPFC decrease distractibility caused by biased but irrelevant objects, further interrogation of our data reveals theoretically differential mechanisms for each type of stimulation. Anodal tDCS appears to increase cognitive control over attentional bias-related items that are behaviourally irrelevant, allowing for their efficient disregard. In contrast, cathodal tDCS appears to lessen the overall effect of the induced attentional bias, potentially by reducing the influence of top-down modulated attentional control settings thus preventing the implementation of the control setting favouring green items. These results suggest a potential causal role of the left DLPFC in the cognitive mechanism underlying attentional bias.

Exploring UK medical school differences: the MedDifs study of selection, teaching, student and F1 perceptions, postgraduate outcomes and fitness to practise.

BACKGROUND: Medical schools differ, particularly in their teaching, but it is unclear whether such differences matter, although influential claims are often made. The Medical School Differences (MedDifs) study brings together a wide range of measures of UK medical schools, including postgraduate performance, fitness to practise issues, specialty choice, preparedness, satisfaction, teaching styles, entry criteria and institutional factors. METHOD: Aggregated data were collected for 50 measures across 29 UK medical schools. Data include institutional history (e.g. rate of production of hospital and GP specialists in the past), curricular influences (e.g. PBL schools, spend per student, staff-student ratio), selection measures (e.g. entry grades), teaching and assessment (e.g. traditional vs PBL, specialty teaching, self-regulated learning), student satisfaction, Foundation selection scores, Foundation satisfaction, postgraduate examination performance and fitness to practise (postgraduate progression, GMC sanctions). Six specialties (General Practice, Psychiatry, Anaesthetics, Obstetrics and Gynaecology, Internal Medicine, Surgery) were examined in more detail. RESULTS: Medical school differences are stable across time (median alpha = 0.835). The 50 measures were highly correlated, 395 (32.2%) of 1225 correlations being significant with p < 0.05, and 201 (16.4%) reached a Tukey-adjusted criterion of p < 0.0025. Problem-based learning (PBL) schools differ on many measures, including lower performance on postgraduate assessments. While these are in part explained by lower entry grades, a surprising finding is that schools such as PBL schools which reported greater student satisfaction with feedback also showed lower performance at postgraduate examinations. More medical school teaching of psychiatry, surgery and anaesthetics did not result in more specialist trainees. Schools that taught more general practice did have more graduates entering GP training, but those graduates performed less well in MRCGP examinations, the negative correlation resulting from numbers of GP trainees and exam outcomes being affected both by non-traditional teaching and by greater historical production of GPs. Postgraduate exam outcomes were also higher in schools with more self-regulated learning, but lower in larger medical schools. A path model for 29 measures found a complex causal nexus, most measures causing or being caused by other measures. Postgraduate exam performance was influenced by earlier attainment, at entry to Foundation and entry to medical school (the so-called academic backbone), and by self-regulated learning. Foundation measures of satisfaction, including preparedness, had no subsequent influence on outcomes. Fitness to practise issues were more frequent in schools producing more male graduates and more GPs. CONCLUSIONS: Medical schools differ in large numbers of ways that are causally interconnected. Differences between schools in postgraduate examination performance, training problems and GMC sanctions have important implications for the quality of patient care and patient safety.

Physical Barrier Type Abuse-Deterrent Formulations: Mechanistic Understanding of Sintering-Induced Microstructural Changes in Polyethylene Oxide Placebo Tablets.

The main goal of the presented work was to understand changes in the microstructure of tablets, as well as the properties of its main component viz. polyethylene oxide (PEO) as a function of sintering. Key polymer variables and sintering conditions were investigated, and sintering-induced increase in tablet tensile strength was evaluated. For the current study, binary-component placebo tablets comprised of varying ratios of PEO and anhydrous dibasic calcium phosphate (DCP) were prepared at two levels of tablet solid fraction. The prepared tablets were sintered in an oven at 80°C at different time points ranging from 10 to 900 min and were evaluated for pore size, tablet expansion (%), and PEO crystallinity. The results showed that for efficient sintering and a significant increase in the tablet tensile strength, a minimum of 50% w/w PEO was required. Moreover, all microstructural changes in tablets were found to occur within 60 min of sintering, with no significant changes occurring thereafter. Sintering also resulted in a decrease in PEO crystallinity, causing changes in polymer ductility. These changes in PEO ductility resulted in tablets with higher tensile strength. Formulation variables such as PEO level and PEO particle size distribution were found to be important influencers of the sintering process. Additionally, tablets with high initial solid fraction and sintering duration of 60 min were found to be optimal conditions for efficient sintering of PEO-based compacts. Finally, prolonged sintering times were not found to provide any additional benefits in terms of abuse-deterrent properties.

On the link between attentional search and the oculomotor system: Is preattentive search restricted to the range of eye movements?

It has been proposed that covert visual search can be fast, efficient, and stimulus driven, particularly when the target is defined by a salient single feature, or slow, inefficient, and effortful when the target is defined by a nonsalient conjunction of features. This distinction between fast, stimulus-driven orienting and slow, effortful orienting can be related to the distinction between exogenous spatial attention and endogenous spatial attention. Several studies have shown that exogenous, covert orienting is limited to the range of saccadic eye movements, whereas covert endogenous orienting is independent of the range of saccadic eye movements. The current study examined whether covert visual search is affected in a similar way. Experiment 1 showed that covert visual search for feature singletons was impaired when stimuli were presented beyond the range of saccadic eye movements, whereas conjunction search was unaffected by array position. Experiment 2 replicated and extended this effect by measuring search times at 6 eccentricities. The impairment in covert feature search emerged only when stimuli crossed the effective oculomotor range and remained stable for locations further into the periphery, ruling out the possibility that the results of Experiment 1 were due to a failure to fully compensate for the effects of cortical magnification. The findings are interpreted in terms of biased competition and oculomotor theories of spatial attention. It is concluded that, as with covert exogenous orienting, biological constraints on overt orienting in the oculomotor system constrain covert, preattentive search.

Spatial working memory in Progressive Supranuclear Palsy.

The neural and cognitive mechanisms of spatial working memory are tightly coupled with the systems that control eye-movements but the precise nature of this coupling is not well understood. In particular, there are very few neuropsychological studies that explicitly examine how deficits of oculomotor control affect visuospatial working memory. Here, we examined the link between spatial working memory and the oculomotor system in a sample of patients with Progressive Supranuclear Palsy, a degenerative neurological disease characterised by defective vertical eye-movements but relatively preserved horizontal eye-movements. Consistent with the idea that the oculomotor system plays a critical role in spatial working memory performance, people with PSP had significantly shorter spatial spans when stimuli were presented along the vertical axis compared to the horizontal axis. This effect was not observed in age matched controls. We hypothesise that PSP disrupts a colliculo-parietal feedback loop that contributes to the maintenance of activation in a parietal priority map during the delay period. This result is the first direct neuropsychological evidence for an association between oculomotor function and spatial working memory and is broadly consistent with idea that rehearsal in visuospatial working memory is mediated by an 'oculomotor loop', as proposed by Baddeley (1986). We conclude that optimal spatial working memory performance depends on an intact oculomotor system.