Applied and laboratory-based autonomic and neurophysiological monitoring during sustained attention tasks

Fluctuations during sustained attention can cause momentary lapses in performance which can have a significant impact on safety and wellbeing. However, it is less clear how unrelated tasks impact current task processes, and whether potential disturbances can be detected by autonomic and central nervous system measures in naturalistic settings. In a series of five experiments, I sought to investigate how prior attentional load impacts semi-naturalistic tasks of sustained attention, and whether neurophysiological and psychophysiological monitoring of continuous task processes and performance could capture attentional lapses. The first experiment explored various non-invasive electrophysiological and subjective methods during multitasking. The second experiment employed a manipulation of multitasking, task switching, to attempt to unravel the negative lasting impacts of multitasking on neural oscillatory activity, while the third experiment employed a similar paradigm in a semi-naturalistic environment of simulated driving. The fourth experiment explored the feasibility of measuring changes in autonomic processing during a naturalistic sustained monitoring task, autonomous driving, while the fifth experiment investigated the visual demands and acceptability of a biological based monitoring system. The results revealed several findings. While the first experiment demonstrated that only self-report ratings were able to successfully disentangle attentional load during multitasking; the second and third experiment revealed deficits in parieto-occipital alpha activity and continuous performance depending on the attentional load of a previous unrelated task. The fourth experiment demonstrated increased sympathetic activity and a smaller distribution of fixations during an unexpected event in autonomous driving, while the fifth experiment revealed the acceptability of a biological based monitoring system although further research is needed to unpick the effects on attention. Overall, the results of this thesis help to provide insight into how autonomic and central processes manifest during semi-naturalistic sustained attention tasks. It also provides support for a neuro- or biofeedback system to improve safety and wellbeing

Spatially and temporally distinct encoding of muscle and kinematic information in rostral and caudal primary motor cortex

The organising principle of human motor cortex does not follow an anatomical body map, but rather a distributed representational structure in which motor primitives are com- bined to produce motor outputs. Electrophysiological recordings in primates and human imaging data suggest that M1 encodes kinematic features of movements, such as joint position and velocity. However, M1 exhibits well-documented sensory responses to cu- taneous and proprioceptive stimuli, raising questions regarding the origins of kinematic motor representations: are they relevant in top-down motor control, or are they an epiphe- nomenon of bottom-up sensory feedback during movement? Here we provide evidence for spatially and temporally distinct encoding of kinematic and muscle information in human M1 during the production of a wide variety of naturalistic hand movements. Using a powerful combination of high-field fMRI and MEG, a spatial and temporal multivariate representational similarity analysis revealed encoding of kinematic information in more caudal regions of M1, over 200 ms before movement onset. In contrast, patterns of muscle activity were encoded in more rostral motor regions much later after movements began. We provide compelling evidence that top-down control of dexterous movement engages kinematic representations in caudal regions of M1 prior to movement production

Asymmetric Oxidation of Enol Derivatives to α-Alkoxy Carbonyls Using Iminium Salt Catalysts: A Synthetic and Computational Study

We report herein the first examples of asymmetric oxidation of enol ether and ester substrates using iminium salt organocatalysis, affording moderate to excellent enantioselectivities of up to 98% ee for tetralone-derived substrates in the α-hydroxyketone products. A comprehensive density functional theory study was undertaken to interpret the competing diastereoisomeric transition states in this example in order to identify the origins of enantioselectivity. The calculations, performed at the B3LYP/6-31G(D) level of theory, gave good agreement with the experimental results, in terms of the magnitude of the effects under the specified reaction conditions, and in terms of the preferential formation of the (R)-enantiomer. Just one of the 30 characterized transition states dominates the enantioselectivity, which is attributed to the adoption of an orientation relative to stereochemical features of the chiral controlling element that combines a CH interaction between a CH 2 group in the substrate and one of the aromatic rings of the biaryl section of the chiral auxiliary with a good alignment of the acetoxy group with the other biaryl ring, and places the smallest substituent on the alkene (a hydrogen atom) in the most sterically hindered position

Investigating the outcome of the initial assessment at a national transgender health service: is it time to review the process?

Background: Globally there is a lack of a standardised assessment process prior to the initiation of gender affirming medical interventions and consequently there is a discrepancy in this process among different transgender health services. Aim: The main objective of this study is to investigate the outcome of the initial assessment process at a national transgender health service. Method: The outcome of people over the age of 17 years, assessed at a large national transgender health service in the United Kingdom during a two year period was categorised into: 1) recommendation for cross-sex hormone treatment, or: 2) no recommendation for cross-sex hormone treatment. In addition, 200 case notes were reviewed in order to investigate the level of agreement between the two clinicians involved in the assessment process. Results: During the study period a total of 617 people completed their assessment at the service. Following assessment 380 (61.6%) patients were recommended for cross-sex hormone treatment, leaving 237 (38.4%) patients who required a longer assessment period or were discharged. The factors associated with being recommended for cross-sex hormone treatment were: having socially transitioned, not smoking, having initiated cross-sex hormones prior to assessment, being older, and assigned male at birth. Out of the 200 case notes reviewed, agreement between assessor 1 and 2 (3 months apart) was found in 88 % (n= 176) of the cases. Discussion: Although the results of the study may not be generalizable to other international centres, questioning the assessment process and the role of the assessors is important to ensure treatment is offered in a timely and efficient manner. The findings from this study suggest that the routine inclusion of two assessors needs to be reviewed

Psychosocial impact of undergoing prostate cancer screening for men with BRCA1 or BRCA2 mutations.

OBJECTIVES: To report the baseline results of a longitudinal psychosocial study that forms part of the IMPACT study, a multi-national investigation of targeted prostate cancer (PCa) screening among men with a known pathogenic germline mutation in the BRCA1 or BRCA2 genes. PARTICPANTS AND METHODS: Men enrolled in the IMPACT study were invited to complete a questionnaire at collaborating sites prior to each annual screening visit. The questionnaire included sociodemographic characteristics and the following measures: the Hospital Anxiety and Depression Scale (HADS), Impact of Event Scale (IES), 36-item short-form health survey (SF-36), Memorial Anxiety Scale for Prostate Cancer, Cancer Worry Scale-Revised, risk perception and knowledge. The results of the baseline questionnaire are presented. RESULTS: A total of 432 men completed questionnaires: 98 and 160 had mutations in BRCA1 and BRCA2 genes, respectively, and 174 were controls (familial mutation negative). Participants' perception of PCa risk was influenced by genetic status. Knowledge levels were high and unrelated to genetic status. Mean scores for the HADS and SF-36 were within reported general population norms and mean IES scores were within normal range. IES mean intrusion and avoidance scores were significantly higher in BRCA1/BRCA2 carriers than in controls and were higher in men with increased PCa risk perception. At the multivariate level, risk perception contributed more significantly to variance in IES scores than genetic status. CONCLUSION: This is the first study to report the psychosocial profile of men with BRCA1/BRCA2 mutations undergoing PCa screening. No clinically concerning levels of general or cancer-specific distress or poor quality of life were detected in the cohort as a whole. A small subset of participants reported higher levels of distress, suggesting the need for healthcare professionals offering PCa screening to identify these risk factors and offer additional information and support to men seeking PCa screening

A population-based investigation into inequalities amongst Indigenous mothers and newborns by place of residence in the Northern Territory, Australia

BACKGROUND: Comparisons of birth outcomes between Australian Indigenous and non-Indigenous populations show marked inequalities. These comparisons obscure Indigenous disparities. There is much variation in terms of culture, language, residence, and access to services amongst Australian Indigenous peoples. We examined outcomes by region and remoteness for Indigenous subgroups and explored data for communities to inform health service delivery and interventions. METHODS: Our population-based study examined maternal and neonatal outcomes for 7,560 mothers with singleton pregnancies from Australia’s Northern Territory Midwives’ Data Collection (2003–2005) using uni- and multivariate analyses. Groupings were by Indigenous status; region (Top End (TE)/Central Australia (CA)); Remote/ Urban residence; and across two large TE communities. RESULTS: Of the sample, 34.1% were Indigenous women, of whom 65.6% were remote-dwelling versus 6.7% of non- Indigenous women. In comparison to CA Urban mothers: TE Remote (adjusted odds ratio [aOR] 1.47, 95%CI: 1.13, 1.90) and TE Urban mothers (aOR 1.36 (95% CI: 1.02, 1.80) were more likely, but CA Remote mothers (aOR 0.43; 95% CI: 0.31, 0.58) less likely to smoke during pregnancy; CA Remote mothers giving birth at >32 weeks gestation were less likely to have attended ≥ five antenatal visits (aOR 0.55; 95%CI: 0.36, 0.86); TE Remote (aOR 0.71; 95%CI: 0.53, 0.95) and CA Remote women (aOR 0.68; 95%CI: 0.49, 0.95) who experienced labour had lower odds of epidural/ spinal/narcotic pain relief; and TE Remote (aOR 0.47; 95%CI: 0.34, 0.66), TE Urban (aOR 0.67; 95%CI: 0.46, 0.96) and CA Remote mothers (aOR 0.52; 95%CI: 0.35, 0.76) all had lower odds of having a ‘normal’ birth. The aOR for preterm birth for TE Remote newborns was 2.09 (95%CI: 1.20, 3.64) and they weighed 137 g (95%CI: -216 g, -59 g) less than CA Urban babies. There were few significant differences for communities, except for smoking prevalence. CONCLUSIONS: This paper is one of few quantifying inequalities between groups of Australian Indigenous women and newborns at a regional level. Indigenous mothers and newborns do worse on some outcomes if they live remotely, especially if they live in the TE. Smoking prevention and high-quality antenatal care is fundamental to addressing many of the adverse outcomes identified in this paper.Malinda Steenkamp, Alice Rumbold, Lesley Barclay and Sue Kilde

Economic impact of screening for X-linked Adrenoleukodystrophy within a newborn blood spot screening programme.

BACKGROUND: A decision tree model was built to estimate the economic impact of introducing screening for X-linked adrenoleukodystrophy (X-ALD) into an existing tandem mass spectrometry based newborn screening programme. The model was based upon the UK National Health Service (NHS) Newborn Blood Spot Screening Programme and a public service perspective was used with a lifetime horizon. The model structure and parameterisation were based upon literature reviews and expert clinical judgment. Outcomes included health, social care and education costs and quality adjusted life years (QALYs). The model assessed screening of boys only and evaluated the impact of improved outcomes from hematopoietic stem cell transplantation in patients with cerebral childhood X-ALD (CCALD). Threshold analyses were used to examine the potential impact of utility decrements for non-CCALD patients identified by screening. RESULTS: It is estimated that screening 780,000 newborns annually will identify 18 (95%CI 12, 27) boys with X-ALD, of whom 10 (95% CI 6, 15) will develop CCALD. It is estimated that screening may detect 7 (95% CI 3, 12) children with other peroxisomal disorders who may also have arisen symptomatically. If results for girls are returned an additional 17 (95% CI 12, 25) cases of X-ALD will be identified. The programme is estimated to cost an additional £402,000 (95% CI £399-407,000) with savings in lifetime health, social care and education costs leading to an overall discounted cost saving of £3.04 (95% CI £5.69, £1.19) million per year. Patients with CCALD are estimated to gain 8.5 discounted QALYs each giving an overall programme benefit of 82 (95% CI 43, 139) QALYs. CONCLUSION: Including screening of boys for X-ALD into an existing tandem mass spectrometry based newborn screening programme is projected to reduce lifetime costs and improve outcomes for those with CCALD. The potential disbenefit to those identified with non-CCALD conditions would need to be substantial in order to outweigh the benefit to those with CCALD. Further evidence is required on the potential QALY impact of early diagnosis both for non-CCALD X-ALD and other peroxisomal disorders. The favourable economic results are driven by estimated reductions in the social care and education costs