Evaluating the Differences of Wound Related Complications in Robotically Assisted Radical Cystectomy vs Open Radical Cystectomy.

OBJECTIVE: To determine whether robotic-assisted radical cystectomy (RARC) with intracorporeal urinary diversion (ICUD) compared to open radical cystectomy (ORC) or RARC with extracorporeal urinary diversion (ECUD) would result in a decreased rate of surgical site complications. RARC has been shown to be non-inferior to ORC. Both RARC and ORC are complicated by a high rate of perioperative morbidity, including wound-related complications, which may be decreased by a robotic approach with intracorporeal diversion. METHODS: A retrospective review of our bladder cancer database for patients undergoing radical cystectomy from 2013-2021. Patients were stratified by surgical technique as RARC with ICUD vs ORC vs RARC with ECUD. Surgical site complications were measured at both 30- and 90-day intervals. RESULTS: Of the 269 patients, 127 (47.2%) had RARC with ICUD, 118 (43.7%) had ORC, and 24 (8.9%) had RARC with ECUD (mean ages 71.0, 69.5, and 67.5, respectively). A comparison of the 3 groups demonstrated statistical significance at both the 30-day (P <.001) and 90-day (P <.001) timeframes for total surgical site complications, with RARC with ICUD having the fewest amount of patients experiencing a surgical site complication (0.8%) followed by ORC (25.4%) and RARC with ECUD (29.2%). CONCLUSION: Overall, we observed lower surgical site complication rates among patients undergoing RARC with ICUD compared to patients who underwent ORC or RARC with ECUD. This study suggests that decreased surgical site complications may be one benefit of the minimally invasive approach, particularly in patients at high risk for surgical site complications after radical cystectomy.

Online cognitive monitoring technology for people with Parkinson's disease and REM sleep behavioural disorder.

Automated online cognitive assessments are set to revolutionise clinical research and healthcare. However, their applicability for Parkinson's Disease (PD) and REM Sleep Behavioural Disorder (RBD), a strong PD precursor, is underexplored. Here, we developed an online battery to measure early cognitive changes in PD and RBD. Evaluating 19 candidate tasks showed significant global accuracy deficits in PD (0.65 SD, p = 0.003) and RBD (0.45 SD, p = 0.027), driven by memory, language, attention and executive underperformance, and global reaction time deficits in PD (0.61 SD, p = 0.001). We identified a brief 20-min battery that had sensitivity to deficits across these cognitive domains while being robust to the device used. This battery was more sensitive to early-stage and prodromal deficits than the supervised neuropsychological scales. It also diverged from those scales, capturing additional cognitive factors sensitive to PD and RBD. This technology offers an economical and scalable method for assessing these populations that can complement standard supervised practices.

Human ventromedial prefrontal cortex is necessary for prosocial motivation.

Ventromedial prefrontal cortex (vmPFC) is vital for decision-making. Functional neuroimaging links vmPFC to processing rewards and effort, while parallel work suggests vmPFC involvement in prosocial behaviour. However, the necessity of vmPFC for these functions is unknown. Patients with rare focal vmPFC lesions (n = 25), patients with lesions elsewhere (n = 15) and healthy controls (n = 40) chose between rest and exerting effort to earn rewards for themselves or another person. vmPFC damage decreased prosociality across behavioural and computational measures. vmPFC patients earned less, discounted rewards by effort more, and exerted less force when another person benefited, compared to both control groups. Voxel-based lesion mapping revealed dissociations between vmPFC subregions. While medial damage led to antisocial behaviour, lateral damage increased prosocial behaviour relative to patients with damage elsewhere. vmPFC patients also showed reduced effort sensitivity overall, but reward sensitivity was limited to specific subregions. These results reveal multiple causal contributions of vmPFC to prosocial behaviour, effort and reward.

Goal commitment is supported by vmPFC through selective attention.

When striking a balance between commitment to a goal and flexibility in the face of better options, people often demonstrate strong goal perseveration. Here, using functional MRI (n = 30) and lesion patient (n = 26) studies, we argue that the ventromedial prefrontal cortex (vmPFC) drives goal commitment linked to changes in goal-directed selective attention. Participants performed an incremental goal pursuit task involving sequential decisions between persisting with a goal versus abandoning progress for better alternative options. Individuals with stronger goal perseveration showed higher goal-directed attention in an interleaved attention task. Increasing goal-directed attention also affected abandonment decisions: while pursuing a goal, people lost their sensitivity to valuable alternative goals while remaining more sensitive to changes in the current goal. In a healthy population, individual differences in both commitment biases and goal-oriented attention were predicted by baseline goal-related activity in the vmPFC. Among lesion patients, vmPFC damage reduced goal commitment, leading to a performance benefit.

Dopamine encoding of novelty facilitates efficient uncertainty-driven exploration.

When facing an unfamiliar environment, animals need to explore to gain new knowledge about which actions provide reward, but also put the newly acquired knowledge to use as quickly as possible. Optimal reinforcement learning strategies should therefore assess the uncertainties of these action-reward associations and utilise them to inform decision making. We propose a novel model whereby direct and indirect striatal pathways act together to estimate both the mean and variance of reward distributions, and mesolimbic dopaminergic neurons provide transient novelty signals, facilitating effective uncertainty-driven exploration. We utilised electrophysiological recording data to verify our model of the basal ganglia, and we fitted exploration strategies derived from the neural model to data from behavioural experiments. We also compared the performance of directed exploration strategies inspired by our basal ganglia model with other exploration algorithms including classic variants of upper confidence bound (UCB) strategy in simulation. The exploration strategies inspired by the basal ganglia model can achieve overall superior performance in simulation, and we found qualitatively similar results in fitting model to behavioural data compared with the fitting of more idealised normative models with less implementation level detail. Overall, our results suggest that transient dopamine levels in the basal ganglia that encode novelty could contribute to an uncertainty representation which efficiently drives exploration in reinforcement learning.

Machine learning approach for ambient-light-corrected parameters and the Pupil Reactivity (PuRe) score in smartphone-based pupillometry.

Introduction: The pupillary light reflex (PLR) is the constriction of the pupil in response to light. The PLR in response to a pulse of light follows a complex waveform that can be characterized by several parameters. It is a sensitive marker of acute neurological deterioration, but is also sensitive to the background illumination in the environment in which it is measured. To detect a pathological change in the PLR, it is therefore necessary to separate the contributions of neuro-ophthalmic factors from ambient illumination. Illumination varies over several orders of magnitude and is difficult to control due to diurnal, seasonal, and location variations. Methods and results: We assessed the sensitivity of seven PLR parameters to differences in ambient light, using a smartphone-based pupillometer (AI Pupillometer, Solvemed Inc.). Nine subjects underwent 345 measurements in ambient conditions ranging from complete darkness (<5 lx) to bright lighting (≲10,000 lx). Lighting most strongly affected the initial pupil size, constriction amplitude, and velocity. Nonlinear models were fitted to find the correction function that maximally stabilized PLR parameters across different ambient light levels. Next, we demonstrated that the lighting-corrected parameters still discriminated reactive from unreactive pupils. Ten patients underwent PLR testing in an ophthalmology outpatient clinic setting following the administration of tropicamide eye drops, which rendered the pupils unreactive. The parameters corrected for lighting were combined as predictors in a machine learning model to produce a scalar value, the Pupil Reactivity (PuRe) score, which quantifies Pupil Reactivity on a scale 0-5 (0, non-reactive pupil; 0-3, abnormal/"sluggish" response; 3-5, normal/brisk response). The score discriminated unreactive pupils with 100% accuracy and was stable under changes in ambient illumination across four orders of magnitude. Discussion: This is the first time that a correction method has been proposed to effectively mitigate the confounding influence of ambient light on PLR measurements, which could improve the reliability of pupillometric parameters both in pre-hospital and inpatient care settings. In particular, the PuRe score offers a robust measure of Pupil Reactivity directly applicable to clinical practice. Importantly, the formulae behind the score are openly available for the benefit of the clinical research community.

The role of the human hippocampus in decision-making under uncertainty.

The role of the hippocampus in decision-making is beginning to be more understood. Because of its prospective and inferential functions, we hypothesized that it might be required specifically when decisions involve the evaluation of uncertain values. A group of individuals with autoimmune limbic encephalitis-a condition known to focally affect the hippocampus-were tested on how they evaluate reward against uncertainty compared to reward against another key attribute: physical effort. Across four experiments requiring participants to make trade-offs between reward, uncertainty and effort, patients with acute limbic encephalitis demonstrated blunted sensitivity to reward and effort whenever uncertainty was considered, despite demonstrating intact uncertainty sensitivity. By contrast, the valuation of these two attributes (reward and effort) was intact on uncertainty-free tasks. Reduced sensitivity to changes in reward under uncertainty correlated with the severity of hippocampal damage. Together, these findings provide evidence for a context-sensitive role of the hippocampus in value-based decision-making, apparent specifically under conditions of uncertainty.

The effects of pramipexole on motivational vigour during a saccade task: a placebo-controlled study in healthy adults.

Motivation allows us to energise actions when we expect reward and is reduced in depression. This effect, termed motivational vigour, has been proposed to rely on central dopamine, with dopaminergic agents showing promise in the treatment of depression. This suggests that dopaminergic agents might act to reduce depression by increasing the effects of reward or by helping energise actions. The aim of the current study was to investigate whether the dopamine agonist pramipexole enhanced motivational vigour during a rewarded saccade task. In addition, we asked whether the effects of pramipexole on vigour differ between reward contingent on performance and guaranteed reward. Healthy adult participants were randomised to receive either pramipexole (n = 19) or placebo (controls n = 18) for 18 days. The vigour of saccades was measured twice, once before the administration of study medication (Time 1) and after taking it for 12-15 days (Time 2). To separate motivation by contingency vs. reward, saccadic vigour was separately measured when (1) rewards were contingent on performance (2) delivered randomly with matched frequency, (3) when reward was guaranteed, (4) when reward was not present at all. Motivation increased response vigour, as expected. Relative to placebo, pramipexole also increased response vigour. However, there was no interaction, meaning that the effects of reward were not modulated by drug, and there was no differential drug effect on contingent vs. guaranteed rewards. The effect of pramipexole on vigour could not be explained by a speed/accuracy trade-off, nor by autonomic arousal as indexed by pupillary dilation. Chronic D2 stimulation increases general vigour, energising movements in healthy adults irrespective of extrinsic reward.

Remote digital cognitive assessment reveals cognitive deficits related to hippocampal atrophy in autoimmune limbic encephalitis: a cross-sectional validation study.

Background: Autoimmune limbic encephalitis (ALE) is a neurological disease characterised by inflammation of the limbic regions of the brain, mediated by pathogenic autoantibodies. Because cognitive deficits persist following acute treatment of ALE, the accurate assessment of long-term cognitive outcomes is important for clinical assessments and trials. However, evaluating cognition is costly and an unmet need exists for validated digital methods. Methods: In this cross-sectional validation study, we investigated whether a remote digital platform could identify previously characterised cognitive impairments in patients with chronic ALE and whether digital metrics would correlate with standard neuropsychological assessment and hippocampal volume. Patients with ALE who had a chronic and stable presentation and received a clinical diagnosis of ALE were recruited for this study. The cognitive performance of 21 patients with ALE and 54 age-matched healthy controls - enrolled via the University of Oxford (UK) Cognitive Neurology Lab testing programme - was assessed with a battery of 12 cognitive tasks from the Cognitron online platform. The platform was optimised with National Institute for Health and Care Research (NIHR) support to be deliverable remotely to elderly and patient groups. The primary outcome measure was behavioural performance and corresponding neuroimaging and neuropsychological assessment metrics. Findings: Between February 15, 2021, and April 21, 2022, 21 patients with ALE (mean age 63.01 years, 14 males) and 54 healthy controls (mean age 65.56 years, 23 males) completed the digital cognitive assessment. Patients with ALE performed significantly worse in memory, visuospatial abilities, executive function, and language. No impairments in digit & spatial span, target detection (attention) and emotion discrimination were observed. The global score on the online cognitive tasks correlated significantly with the established Addenbrooke's Cognitive Examination III (ACE) pen-and-paper test. Deficits in visuospatial processing and language were identified in ALE compared to controls using remote digital testing but not using the ACE, highlighting higher sensitivity of computerised testing to residual cognitive impairment. Finally, the hippocampal volumes of patients with ALE and healthy controls correlated with online cognitive scores. Interpretation: These findings demonstrate that subtle cognitive deficits in patients with chronic ALE, who often show full recovery in measures of disability and dependence on daily activities, are detectable using a remote online platform, which also relates to hippocampal atrophy. Such methods may facilitate the characterisation of cognitive profiles in complex neurological diseases. Future longitudinal studies designed to assess the utility of such digital methods for further clinical characterisation are needed. Funding: The Wellcome Trust, Medical Research Council, National Institute for Health Research, Rhodes Scholarship, and the Berrow Foundation Scholarship.

Computer aided therapeutic tripeptide design, in alleviating the pathogenic proclivities of nocuous α-synuclein fibrils.

Parkinson's disorder (PD) exacerbates neuronal degeneration of motor nerves, thereby effectuating uncoordinated movements and tremors. Aberrant alpha-synuclein (α-syn) is culpable of triggering PD, wherein cytotoxic amyloid aggregates of α-syn get deposited in motor neurons to instigate neuro-degeneration. Amyloid aggregates, typically rich in beta sheets are cardinal targets to mitigate their neurotoxic effects. In this analysis, owing to their interaction specificity, we formulated an efficacious tripeptide out of the aggregation-prone region of α-syn protein. With the help of a proficient computational pipeline, systematic peptide shortening and an adept molecular simulation platform, we formulated a tripeptide, VAV from α-syn structure based hexapeptide KISVRV. Indeed, the VAV tripeptide was able to effectively mitigate the α-syn amyloid fibrils' dynamic rate of beta-sheet formation. Additional trajectory analyses of the VAV- α-syn complex indicated that, upon its dynamic interaction, VAV efficiently altered the distinct pathogenic structural dynamics of α-syn, further advocating its potential in alleviating aberrant α-syn's amyloidogenic proclivities. Consistent findings from various computational analyses have led us to surmise that VAV could potentially re-alter the pathogenic conformational orientation of α-syn, essential to mitigate its cytotoxicity. Hence, VAV tripeptide could be an efficacious therapeutic candidate to efficiently ameliorate aberrant α-syn amyloid mediated neurotoxicity, eventually attenuating the nocuous effects of PD.Communicated by Ramaswamy H. Sarma.

A Comparative Evaluation of Collagen in Ameloblastoma and Oral Squamous Cell Carcinoma using Picrosirius Red Staining with Polarizing Microscopy and CD44v6 Immunoreactivity.

Background: Solid multicystic ameloblastoma (SMA) is a locally aggressive, benign odontogenic tumor of odontogenic origin with greater rate of recurrence. Epithelial-mesenchymal interaction plays an important role in tooth morphogenesis that shows complete differentiation of epithelial and ectomesenchymal components to the level of tooth formation. Tumor stroma in ameloblastoma is normal mature collagen that prevents differentiation to the level of tooth formation. Current study evaluates the role of stromal elements in aggressive behavior of SMA using picrosirius red staining with polarizing microscopy and CD44v6 immunohistochemistry (IHC). Objectives: To compare nature of collagen using picrosirius red staining under polarized microscope and IHC expression of CD44v6 marker in SMA and oral squamous cell carcinoma (OSCC). Methods: Thirty blocks were retrieved from departmental archives and subjected to picrosirius red staining and CD44v6 IHC staining. Slides stained with picrosirius red were observed under polarized microscope to report the birefringence pattern. IHC slides were annotated for intensity of staining of tumor cells. Results: In contrast to OSCC's 40% red, 40% yellowish-red, and 20% greenish-yellow birefringence, SMA displayed 87% red, 13% yellowish-red, and 0% greenish-yellow. Compared to OSCC, which had tumor cells stained 9% strongly, 64% moderately, 27% mildly, and 0% negatively, SMA revealed 0% strong, 10% moderate, 60% weak, and 30% negative staining. Conclusion: As opposed to OSCC, which exhibited a greater quantity of greenish-yellow birefringence of immature collagen, SMA showed predominantly red birefringence, which is suggestive of mature collagen with a lack of metastasis. Comparing SMA to OSCC, the lack of significant CD44v6 positivity suggests that there has not been perineural invasion or regional metastases in SMA.

Effects of cholinesterase inhibition on attention and working memory in Lewy body dementias.

Cholinesterase inhibitors are frequently used to treat cognitive symptoms in Lewy body dementias (Parkinson's disease dementia and dementia with Lewy bodies). However, the selectivity of their effects remains unclear. In a novel rivastigmine withdrawal design, Parkinson's disease dementia and dementia with Lewy bodies patients were tested twice: once when taking rivastigmine as usual and once when they had missed one dose. In each session, they performed a suite of tasks (sustained attention, simple short-term recall, distractor resistance and manipulating the focus of attention) that allowed us to investigate the cognitive mechanisms through which rivastigmine affects attentional control. Consistent with previous literature, rivastigmine withdrawal significantly impaired attentional efficacy (quicker response latencies without a change in accuracy). However, it had no effects on cognitive control as assessed by the ability to withhold a response (inhibitory control). Worse short-term memory performance was also observed when patients were OFF rivastigmine, but these effects were delay and load independent, likely due to impaired visual attention. In contrast to previous studies that have examined the effects of dopamine withdrawal, cognitively complex tasks requiring control over the contents of working memory (ignoring, updating or shifting the focus of attention) were not significantly impaired by rivastigmine withdrawal. Cumulatively, these data support that the conclusion that cholinesterase inhibition has relatively specific and circumscribed-rather than global-effects on attention that may also affect performance on simple short-term memory tasks, but not when cognitive control over working memory is required. The results also indicate that the withdrawal of a single dose of rivastigmine is sufficient to reveal these impairments, demonstrating that cholinergic withdrawal can be an informative clinical as well as an investigative tool.

Developing a novel device based on a new technology for non-invasive measurement of blood biomarkers irrespective of skin color.

Background: Human hemoglobin is a tetrameric metalloporphyrin. The heme part contains iron radicle and porphyrin. The globin part consists of two pairs of amino-acid chains. The absorption spectrum of hemoglobin spans from 250 nm to as high as 2,500 nm, with high coefficients reported in blue and green color zone. The visible absorption spectrum of deoxyhemoglobin has one, while the visible absorption spectrum of oxyhemoglobin shows two peaks. Objective: (1) To study absorption spectrometry of hemoglobin in 420 to 600 nm range; (2) to conduct preclinical experiments to validate a new device and technology based on green color absorption by hemoglobin; (3) to use this new technology and device for phase 1 study in healthy human volunteers for confirmation. Design material and methods: (1) Checking absorption spectrometry of hemoglobin in venous blood. We measured absorption spectrometry of 25 mother-baby pairs as an observational study. Readings were plotted from 400 nm to 560 nm. These included peaks, flat lines and deeps. Graph tracings of all samples - cord blood and maternal blood - showed similar patterns. (2) Preclinical experiments were set up (a) to correlate the reflection of green light by hemoglobin and concentration of hemoglobin, (b) to correlate concentration of O2 and reflection of green light related to oxyhemoglobin, (c) to correlate concentration of melanin in upper and the hemoglobin in lower layer of tissue phantom and to check the sensitivity of new device with green light for measuring Hb in presence of high levels of melanin, and lastly (d) to check if the new device can measure changes in oxy-hemoglobin and deoxy-hemoglobin, again in presence of high levels of melanin with normal as well as with low levels of hemoglobin. The experiments using bilayer tissue phantom were conducted with horse blood in lower cup as dermal tissue phantom and synthetic melanin in upper layer as epidermal tissue phantom. (3) Phase 1 observational studies following a protocol approved by the institutional review board (IRB) were done in two cohorts. Readings were taken using our device and a commercially available pulse oximeter. In the comparison arm we had Point of Care (POC) Hb test (HemoCu or iSTAT blood test). We had 127 data points of POC Hb test and 170 data points for our device and pulse oximeters. This device uses two wavelengths from the visible spectrum of light and uses reflected light. Light of specific wavelengths is shone on the skin of the individual, and the reflected light is collected as 'optical signal'. This optical signal - after conversion to electrical signal - is processed and finally analysed with a digital display on the screen. Melanin is accounted using Von Luschan's chromatic scale (VLS) and a specially designed algorithm. Results: In this set of various preclinical experiments using different concentrations of hemoglobin and melanin, we indeed demonstrated good sensitivity of our device. It could pick up signals from hemoglobin despite high levels of melanin. Our device is a non-invasive device to measure hemoglobin like a pulse oximeter. Results of our device and pulse oximeter were compared with those by POC Hb test like HemoCu and iSTAT. Our device showed better trending linearity and concordance than a pulse oximeter. Since the absorption spectrum of hemoglobin is the same is new-borns and adults, we could develop one device for all age groups and for people of all colors. Furthermore, the light is shone on the wrist of the individual and is then measured. So, in future this device has the potential of being incorporated in a wearable or smart watch technology.

Invasive Fungal Infections Associated with COVID-19.

The COVID-19 pandemic caused >6 million deaths worldwide, often from respiratory failure. Complications frequently occurred in hospitalized patients, particularly in the intensive care unit. Among these, fungal infections were a cause of high morbidity and mortality. Invasive aspergillosis, candidiasis and mucormycosis were the most serious of these infections. Risk factors included alterations in immune defense mechanisms by COVID-19 itself, as well as immunosuppression due to various therapies utilized in severely ill patients. Diagnosis was often challenging due to lack of sensitivity of current testing. Outcomes were generally poor, due to significant co-morbidities and delayed diagnosis, with mortality rates >50% in some studies. High index of clinical suspicion is needed to facilitate early diagnosis and initiation of appropriate antifungal therapy.

Countrywide monitoring of absorbed dose rate in air due to outdoor natural gamma radiation in India.

The Indian Environmental Radiation Monitoring Network continuously monitors, throughout India, the absorbed dose rate in air due to outdoor natural gamma radiation, by using Geiger-Mueller detector-based standalone environmental radiation monitors. The network consists of 546 monitors spread across 91 monitoring locations distributed all over the country. In this paper, the countrywide long-term monitoring results are summarised. The measured mean dose rate of the monitoring locations followed a log-normal distribution and ranged from 50 to 535 nGy.h-1 with a median value of 91 nGy.h-1. Due to outdoor natural gamma radiation, the average annual effective dose was estimated to be 0.11 mSv.y-1.

Gambling on an empty stomach: Hunger modulates preferences for learned but not described risks.

INTRODUCTION: We assess risks differently when they are explicitly described, compared to when we learn directly from experience, suggesting dissociable decision-making systems. Our needs, such as hunger, could globally affect our risk preferences, but do they affect described and learned risks equally? On one hand, decision-making from descriptions is often considered flexible and context sensitive, and might therefore be modulated by metabolic needs. On the other hand, preferences learned through reinforcement might be more strongly coupled to biological drives. METHOD: Thirty-two healthy participants (females: 20, mean age: 25.6 ± 6.5 years) with a normal weight (Body Mass Index: 22.9 ± 3.2 kg/m2 ) were tested in a within-subjects counterbalanced, randomized crossover design for the effects of hunger on two separate risk-taking tasks. We asked participants to choose between two options with different risks to obtain monetary outcomes. In one task, the outcome probabilities were described numerically, whereas in a second task, they were learned. RESULT: In agreement with previous studies, we found that rewarding contexts induced risk-aversion when risks were explicitly described (F1,31  = 55.01, p < .0001, ηp 2  = .64), but risk-seeking when they were learned through experience (F1,31  = 10.28, p < .003, ηp 2  = .25). Crucially, hunger attenuated these contextual biases, but only for learned risks (F1,31  = 8.38, p < .007, ηp 2  = .21). CONCLUSION: The results suggest that our metabolic state determines risk-taking biases when we lack explicit descriptions.

Association of infant Rib and Alp1 surface protein N-terminal domain immunoglobulin G and invasive Group B Streptococcal disease in young infants.

BACKGROUND: Vaccine development for Group B Streptococcus (GBS), a common cause of invasive disease in early-infancy and adverse pregnancy outcomes, include exploring widely-expressed GBS surface proteins as vaccine epitopes. We investigated the association between natural infant serum IgG against the RibN and Alp1N domains and risk of invasive GBS disease caused by isolates expressing these proteins. METHODS: We analyzed maternal and infant serum samples from GBS disease cases and infants born to GBS-colonized women controls. Bayesian modelling was used to calculate the GBS homotypic IgG concentration associated with risk reduction of invasive disease in the infant. RESULTS: PCR-based typing of 85 GBS invasive isolates showed 46 and 24 possessing the gene for Rib and Alp1, respectively. These were matched to 46 and 36 infant controls whose mothers were colonized with GBS expressing Rib and Alp1, respectively. RibN IgG geometric mean concentrations (GMC) were lower in cases than controls among infants (0.01; 95 %CI: 0.01-0.02 vs 0.04; 95 %CI: 0.03-0.06; p < 0.001), no significant difference was found between maternal RibN IgG GMC in cases compared to controls. Alp1N IgG GMC was also lower in infant cases (0.02; 95 %CI: 0.01-0.03) than controls (0.05; 95 %CI: 0.04-0.07; p < 0.001); albeit not so in mothers. An infant IgG threshold ≥ 0.428 and ≥ 0.112 µg/mL was associated with 90 % risk reduction of invasive GBS disease due to Rib and Alp1 expressing strains, respectively. DISCUSSION: Lower serum RibN and Alp1N IgG GMC were evident in infants with invasive GBS disease compared with controls born to women colonized with GBS expressing the homotypic protein. These data support the evaluation of Alp family proteins as potential vaccine candidates against invasive GBS disease.

Mechanisms underlying corruption of working memory in Parkinson's disease.

Working memory (WM) impairments are reported to occur in patients with Parkinson's disease (PD). However, the mechanisms are unclear. Here, we investigate several putative factors that might drive poor performance, by examining the precision of recall, the order in which items are recalled and whether memories are corrupted by random guessing (attentional lapses). We used two separate tasks that examined the quality of WM recall under different loads and retention periods, as well as a traditional digit span test. Firstly, on a simple measure of WM recall, where patients were asked to reproduce the orientation of a centrally presented arrow, overall recall was not significantly impaired. However, there was some evidence for increased guessing (attentional lapses). On a new analogue version of the Corsi-span task, where participants had to reproduce on a touchscreen the exact spatial pattern of presented stimuli in the order and locations in which they appeared, there was a reduction in the precision of spatial WM at higher loads. This deficit was due to misremembering item order. At the highest load, there was reduced recall precision, whereas increased guessing was only observed at intermediate set sizes. Finally, PD patients had impaired backward, but not forward, digit spans. Overall, these results reveal the task- and load-dependent nature of WM deficits in PD. On simple low-load tasks, attentional lapses predominate, whereas at higher loads, in the spatial domain, the corruption of mnemonic information-both order item and precision-emerge as the main driver of impairment.

Reward insensitivity is associated with dopaminergic deficit in rapid eye movement sleep behaviour disorder.

Idiopathic rapid eye movement sleep behaviour disorder (iRBD) has now been established as an important marker of the prodromal stage of Parkinson's disease and related synucleinopathies. However, although dopamine transporter single photon emission computed tomography (SPECT) has been used to demonstrate the presence of nigro-striatal deficit in iRBD, quantifiable correlates of this are currently lacking. Sensitivity to rewarding stimuli is reduced in some people with Parkinson's disease, potentially contributing to aspects of the neuropsychiatric phenotype in these individuals. Furthermore, a role for dopaminergic degeneration is suggested by the fact that reward insensitivity can be improved by dopaminergic medications. Patients with iRBD present a unique opportunity to study the relationship between reward sensitivity and early dopaminergic deficit in the unmedicated state. Here, we investigate whether a non-invasive, objective measure of reward sensitivity might be a marker of dopaminergic status in prodromal Parkinson's disease by comparing with SPECT/CT measurement of dopaminergic loss in the basal ganglia. Striatal dopaminergic deficits in iRBD are associated with progression to Parkinsonian disorders. Therefore, identification of a clinically measurable correlate of this degenerative process might provide a basis for the development of novel risk stratification tools. Using a recently developed incentivized eye-tracking task, we quantified reward sensitivity in a cohort of 41 patients with iRBD and compared this with data from 40 patients with Parkinson's disease and 41 healthy controls. Patients with iRBD also underwent neuroimaging with dopamine transporter SPECT/CT. Overall, reward sensitivity, indexed by pupillary response to monetary incentives, was reduced in iRBD cases compared with controls and was not significantly different to that in patients with Parkinson's disease. However, in iRBD patients with normal dopamine transporter SPECT/CT imaging, reward sensitivity was not significantly different from healthy controls. Across all iRBD cases, a positive association was observed between reward sensitivity and dopaminergic SPECT/CT signal in the putamen. These findings demonstrate a direct relationship between dopaminergic deficit and reward sensitivity in patients with iRBD and suggest that measurement of pupillary responses could be of value in models of risk stratification and disease progression in these individuals.

Dissociable behavioural signatures of co-existing impulsivity and apathy in decision-making.

Apathy and impulsivity are expressed in a wide range of neuropsychiatric disorders, and, to a less severe extent, in healthy people too. Although traditionally considered to be opposite extremes of a single motivational spectrum, recent epidemiological questionnaire-based data suggest that both traits can in fact co-exist within the same individual. Here, we sought to investigate the relationship between these constructs in healthy people within a controlled task environment that examines the ability to make a decision under temporal uncertainty and measures the vigour of the response. Sixty participants performed a new version of the Traffic Light Task and completed self-report questionnaire measures of apathy and impulsivity. The task required individuals to make rapid decision-making for time-sensitive reward by squeezing a hand-held dynamometer as quickly as possible after a predictable event occurred (a traffic light turning green). Although apathy and impulsivity were positively correlated in questionnaire assessments, the two traits were associated with distinct behavioural signatures on the task. Impulsivity was expressed as an inflexible tendency to generate rapid anticipatory responses, regardless of cost-benefit information. Apathy, on the other hand, was associated with a blunted effect of reward on response vigour. These findings reveal how apathy and impulsivity are related to distinct dimensions of goal-directed behaviour, explaining how these traits might co-exist in the same individuals.