Conscious but not thinking-Mind-blanks during visuomotor tracking: An fMRI study of endogenous attention lapses.

Attention lapses (ALs) are complete lapses of responsiveness in which performance is briefly but completely disrupted and during which, as opposed to microsleeps, the eyes remain open. Although the phenomenon of ALs has been investigated by behavioural and physiological means, the underlying cause of an AL has largely remained elusive. This study aimed to investigate the underlying physiological substrates of behaviourally identified endogenous ALs during a continuous visuomotor task, primarily to answer the question: Were the ALs during this task due to extreme mind-wandering or mind-blanks? The data from two studies were combined, resulting in data from 40 healthy non-sleep-deprived subjects (20M/20F; mean age 27.1 years, 20-45). Only 17 of the 40 subjects were used in the analysis due to a need for a minimum of two ALs per subject. Subjects performed a random 2-D continuous visuomotor tracking task for 50 and 20 min in Studies 1 and 2, respectively. Tracking performance, eye-video, and functional magnetic resonance imaging (fMRI) were recorded simultaneously. A human expert visually inspected the tracking performance and eye-video recordings to identify and categorise lapses of responsiveness as microsleeps or ALs. Changes in neural activity during 85 ALs (17 subjects) relative to responsive tracking were estimated by whole-brain voxel-wise fMRI and by haemodynamic response (HR) analysis in regions of interest (ROIs) from seven key networks to reveal the neural signature of ALs. Changes in functional connectivity (FC) within and between the key ROIs were also estimated. Networks explored were the default mode network, dorsal attention network, frontoparietal network, sensorimotor network, salience network, visual network, and working memory network. Voxel-wise analysis revealed a significant increase in blood-oxygen-level-dependent activity in the overlapping dorsal anterior cingulate cortex and supplementary motor area region but no significant decreases in activity; the increased activity is considered to represent a recovery-of-responsiveness process following an AL. This increased activity was also seen in the HR of the corresponding ROI. Importantly, HR analysis revealed no trend of increased activity in the posterior cingulate of the default mode network, which has been repeatedly demonstrated to be a strong biomarker of mind-wandering. FC analysis showed decoupling of external attention, which supports the involuntary nature of ALs, in addition to the neural recovery processes. Other findings were a decrease in HR in the frontoparietal network before the onset of ALs, and a decrease in FC between default mode network and working memory network. These findings converge to our conclusion that the ALs observed during our task were involuntary mind-blanks. This is further supported behaviourally by the short duration of the ALs (mean 1.7 s), which is considered too brief to be instances of extreme mind-wandering. This is the first study to demonstrate that at least the majority of complete losses of responsiveness on a continuous visuomotor task are, if not due to microsleeps, due to involuntary mind-blanks.

Cerebral perfusion is not impaired in persons with moderate obstructive sleep apnoea when awake.

PURPOSE: It is well established that, together with a multitude of other adverse effects on health, severe obstructive sleep apnoea causes reduced cerebral perfusion and, in turn, reduced cerebral function. Less clear is the impact of moderate obstructive sleep apnoea (OSA). Our aim was to determine if cerebral blood flow is impaired in people diagnosed with moderate OSA. METHODS: Twenty-four patients diagnosed with moderate OSA (15 ≤ apnoea-hypopnea index (AHI) < 30) were recruited (aged 32-72, median 59 years, 10 female). Seven controls (aged 42-73 years, median 62 years, 4 female) with an AHI < 5 were also recruited. The OSA status of all participants was confirmed at baseline by unattended polysomnography and they had an MRI arterial-spin-labelling scan of cerebral perfusion. RESULTS: Neither global perfusion nor voxel-wise perfusion differed significantly between the moderate-OSA and control groups. We also compared the average perfusion across three regional clusters, which had been found in a previous study to have significant perfusion differences with moderate-severe OSA versus control, and found no significant difference in perfusion between the two groups. The perfusions were also very close, with means of 50.2 and 51.8 mL/100 g/min for the moderate-OSAs and controls, respectively, with a negligible effect size (Cohen's d = 0.10). CONCLUSION: We conclude that cerebral perfusion is not impaired in people with moderate OSA and that cerebral flow regulatory mechanisms can cope with the adverse effects which occur in moderate OSA. This is an important factor in clinical decisions for prescription of continuous positive airway pressure therapy (CPAP).

Predicting regression of cervical intraepithelial neoplasia grade 2 in women under 25 years.

BACKGROUND: A number of retrospective and prospective studies have documented substantial rates of regression in cervical intraepithelial neoplasia grade 2 lesions in young women. Initial observational management of cervical intraepithelial neoplasia grade 2 is increasingly accepted as appropriate for women under 25 years of age with screen-detected abnormalities and is included in a number of clinical guidelines. However, there has been a paucity of large prospective studies on observational management with strict inclusion criteria. A number of important questions remain, specifically regarding the clinical variables that are associated with the risk of progression or persistence of disease. To investigate these factors and to ensure that young women with cervical intraepithelial neoplasia grade 2 undergoing observational management were being managed in a well-monitored and an appropriately informed fashion, we conducted a large, multicenter prospective study on observational management of cervical intraepithelial neoplasia grade 2 in women under 25 years. OBJECTIVE: This study aimed to determine the regression rates and clinical, cytologic, and pathologic predictors of regression of cervical intraepithelial neoplasia grade 2 in women under 25 years undergoing observational management over 24 months. STUDY DESIGN: This study was a multicenter prospective study on observational management of cervical intraepithelial neoplasia grade 2 (ie, repeat colposcopy, cytology, and cervical biopsy every 6 months) for up to 24 months. A total of 615 consenting women under 25 years with newly-diagnosed, biopsy-proven cervical intraepithelial neoplasia grade 2 were recruited (from 2010 to 2016) through 16 hospital-based colposcopy units in New Zealand and Australia. RESULTS: At completion, 326 women had confirmed regression, 156 had persistent high-grade cervical intraepithelial neoplasia grade 2 or 3 or adenocarcinoma in situ, and 24 had unconfirmed regression (ie, first regression at the 24-month follow-up). A total of 109 women did not complete the protocol (41 because of delayed follow-up, 41 lost to follow-up, 22 elected treatment, 4 refused a biopsy, and 1 died of an unrelated cause). Confirmed regression was observed in 53% (326 of 615) of all women enrolled in the study and, when missing data were imputed, it was estimated that 64% of women (95% confidence interval, 60%-68%) would have experienced regression. Similarly, lesions regressed in 64% (326 of 506) of women who completed the observational protocol. Based on a multivariable analysis, detection of human papillomavirus 16 in a liquid-based cytology sample at the time of initial colposcopy decreased the chance of regression by 31% (risk ratio, 0.69; 95% confidence interval, 0.56-0.86; P<.001). In addition, at initial colposcopy, low-grade or normal colposcopic impression, later year of diagnosis, low-grade or normal cytology, and being a nonsmoker were all independently associated with an increased chance of regression. CONCLUSION: More than half of women under 25 years with cervical intraepithelial neoplasia grade 2 will regress to cervical intraepithelial neoplasia grade 1 or normal within 24 months without destructive treatment. The absence of human papillomavirus 16 is the most important predictor of regression.

Evaluation of guidelines for observational management of cervical intraepithelial neoplasia 2 in young women.

BACKGROUND: A high rate of regression in young women with cervical intraepithelial neoplasia grade 2 has been recorded. However, there are few prospective data by which to evaluate management guidelines. OBJECTIVE: This study evaluates the American Society for Colposcopy and Cervical Pathology recommendations for follow-up of young women with cervical intraepithelial neoplasia 2 using data created by a large prospective multicenter study of observational management. MATERIALS AND METHODS: Participants were 616 women under 25 years with biopsy-diagnosed cervical intraepithelial neoplasia 2 following a referral to colposcopy for an abnormal smear with no previous high-grade abnormality. The protocol included colposcopy, cytology, and colposcopically directed biopsy at the initial visit and at 6- and 12-month follow-ups visits, and these data were analyzed. Histology from the corresponding cervical biopsy was treated as the reference diagnostic test. For young women with cervical intraepithelial neoplasia 2, we aimed to determine the following: (1) the ability of colposcopy to identify women with cervical intraepithelial neoplasia 3 or worse at 6 months; and (2) the ability of colposcopy, cytology, and a combination of cytology and colposcopy to identify residual high-grade abnormalities at 12 months. In addition, although not specified in the guidelines, we investigated the ability of high-risk human papillomavirus positivity alone or with cytology as a co-test to identify residual high-grade abnormalities at 12 months. RESULTS: At 6 months, cervical intraepithelial neoplasia 3+ colposcopic appearance identified only 28% (95% confidence interval, 18-40%) of women diagnosed with cervical intraepithelial neoplasia 3. At 12 months, a high-grade colposcopic appearance identified only 58% (95% confidence interval, 48-68%) of women with residual histological cervical intraepithelial neoplasia 2 or 3. At 12 months, high-grade cytology identified only 58% (95% confidence interval, 48-68%) of women with cervical intraepithelial neoplasia 2 or 3. However, the combination of either high-grade cytology or colposcopic appearance proved substantially more sensitive (81%; 95% confidence interval, 72-88%). High-risk human papillomavirus positivity at 12 months was a sensitive (96%; 95% confidence interval, 89-99%) indicator of persisting high-grade histology. However, this sensitivity came at the expense of specificity (52%; 95% confidence interval, 45-58%). A co-test of high-risk human papillomavirus positivity or high-grade cytology at 12 months provided a high sensitivity (97%; 95% confidence interval, 90-99%) but low specificity (51%; 95% confidence interval, 45%-58%). CONCLUSION: Colposcopy and cytology are limited in their ability to exclude persistent high-grade abnormality for young women undergoing observational management for cervical intraepithelial neoplasia 2. We recommend biopsy for all women at 12 months. High-risk human papillomavirus positivity is a sensitive indicator of persistent abnormality and should be considered in those not having a biopsy.

Pathological process has a crucial role in sentinel node biopsy for vulvar cancer.

OBJECTIVES: To report the interim findings of an audit of the outcomes of sentinel node (SN) biopsy performed as a replacement for groin node dissection in women with early stage vulvar cancer in routine clinical practice in Australia and New Zealand. METHODS: A prospective multi-center study in 8 participating centers. Eligible patients had squamous cell carcinomas clinically restricted to the vulva <4 cm in diameter. SN procedures and pathological assessment were to be performed in accordance with the methods published by the GROINSS-V collaboration [1]. RESULTS: 130 women with apparent early stage vulvar cancer were enrolled. Seventeen women subsequently did not meet the eligibility criteria and were excluded. SNs were identified in 111/113 of the remaining women. Twenty-two women had positive nodes. Sixteen of these women had at least 12 months follow up and 7 (44%) had recurrent disease. Eighty-nine women had only negative nodes. Seventy-four of these women had at least 12 months follow up and 6 (8%) had recurrent disease (including 2 [2.7%] with recurrence in the groin). On subsequent review of the two women with negative SNs who had groin recurrences, it was found that the recommended pathology protocol had not been followed. In both cases, SN metastases were identified following serial sectioning of the nodes. CONCLUSIONS: SN biopsy is feasible in routine clinical practice. However, undetected metastases in a removed SN may be associated with groin recurrence. To ensure patient safety, strict adherence to the pathology protocol is an essential component in the utilization of the sentinel lymph node technique in vulvar cancer.

Trends in the overall survival rates in women with advanced ovarian cancer in a single tertiary centre in New Zealand.

BACKGROUND: Survival rates for women diagnosed with ovarian cancer are much poorer than other gynaecological cancers and greatly depend on stage at diagnosis. A recent publication showed that unlike some other developed countries, there has been no improvement in the five-year survival rate for those diagnosed with ovarian cancer in New Zealand. AIM: To compare the five-year survival rate of women diagnosed with advanced ovarian cancer in a single tertiary hospital during two 36-month time periods 10 years apart. MATERIALS AND METHODS: An observational retrospective review of patient clinical notes, including all women diagnosed with stage three or four ovarian cancer between 2000 and 2002 (Cohort 1) and 2010-2012 (Cohort 2). Eligible patients were identified through the Regional Gynaecology Oncology database. Clinical notes were reviewed to compare the five-year survival rate between these two time periods and look at changes in patterns of care over time. RESULTS: Eighty-three women were diagnosed in 2000-2002 and 125 women in 2010-2012. There was no difference in five-year survival between cohorts (21.7% vs 23.2%, P = 0.80). Mean age at diagnosis did not differ between cohorts (62.1 years vs 63.5 years, P = 0.43); however, there were more women with stage four cancer in Cohort 2 (14% vs 30%, P = 0.01). In Cohort 2, more women were treated with neoadjuvant chemotherapy (20% vs 34%, P = 0.04) or chemotherapy only (6% vs 18%, P = 0.01). CONCLUSION: Five-year overall survival in women diagnosed with advanced ovarian cancer in our centre has not changed over the last 10 years.

Temporal evolution of neural activity and connectivity during microsleeps when rested and following sleep restriction.

Even when it is critical to stay awake, such as when driving, sleep deprivation weakens one's ability to do so by substantially increasing the propensity for microsleeps. Microsleeps are complete lapses of consciousness but, paradoxically, are associated with transient increases in cortical activity. But do microsleeps provide a benefit in terms of attenuating the need for sleep? And is the neural response to microsleeps altered by the degree of homeostatic drive to sleep? In this study, we continuously monitored eye-video, visuomotor responsiveness, and brain activity via fMRI in 20 healthy subjects during a 20-min visuomotor tracking task following a normally-rested night and a sleep-restricted (4-h) night. As expected, sleep restriction led to an increased number of microsleeps and an increased variability in tracking error. Microsleeps exhibited transient increases in regional activity in the fronto-parietal and parahippocampal area. Network analyses revealed divergent transient changes in the right fronto-parietal, dorsal-attention, default-mode, and thalamo-cortical functional networks. In all subjects, tracking error immediately following microsleeps was improved compared to before the microsleeps. Importantly, post-microsleep recovery in tracking response speed was associated with hyperactivation in the thalamo-cortical network. The temporal evolution of functional connectivity within the frontal and posterior nodes of the default-mode network and between the right fronto-parietal and default-mode networks was associated with temporal changes in visuomotor responsiveness. These findings demonstrate distinct brain-network-level changes in brain activity during microsleeps and suggest that neural activity in the thalamo-cortical network may facilitate the transient recovery from microsleeps. The temporal pattern of evolution in brain activity and performance is indicative of dynamic changes in vigilance during the struggle to stay awake following sleep loss.

Initial observation of CIN2 does not appear to reduce quality of life in women under 25 years of age.

BACKGROUND: Although the patient perspective is implicit in the practice of medicine, research evaluating this remains scarce. In a climate where clinicians and policy-makers constantly strive to achieve more patient-centred models of care, this omission warrants attention. AIM: To assess health-related quality of life (HrQoL) in women under 25 years of age with cervical intra-epithelial neoplasia grade 2 (CIN2) receiving conservative management (colposcopy follow-up, with treatment if necessary) compared with those receiving immediate excisional treatment with large loop excision of the transformation zone (LLETZ). METHODS: An observational study evaluating HrQoL was conducted at Christchurch Women's Hospital, New Zealand. Women undergoing conservative management for CIN2 were compared with those undergoing immediate excisional treatment in an age-matched sample. The Short Form Health Survey 12 version 2 (SF-12v2) was used to evaluate HrQoL. Secondary outcomes of anxiety and sexual function were also assessed. RESULTS: One hundred and four women with CIN2 participated in the study. Of these, 63 (60%) received conservative management and 41 (40%) received immediate excisional treatment with LLETZ. We found no significant difference in HrQoL between the groups in a multivariate regression analysis adjusted for parity, smoking and socioeconomic status. There were also no significant differences in sexual function or anxiety. CONCLUSION: We found no difference in HrQoL by management strategy. Conservative management of CIN2 in women under 25 is unlikely to have an adverse impact on self-reported HrQoL, anxiety or sexual functioning compared with conventional management.

Time-varying effective connectivity of the cortical neuroelectric activity associated with behavioural microsleeps.

An episode of complete failure to respond during an attentive task accompanied by behavioural signs of sleep is called a behavioural microsleep. We proposed a combination of high-resolution EEG and an advanced method for time-varying effective connectivity estimation for reconstructing the temporal evolution of the causal relations between cortical regions when microsleeps occur during a continuous visuomotor task. We found connectivity patterns involving left-right frontal, left-right parietal, and left-frontal/right-parietal connections commencing in the interval [-500; -250] ms prior to the onset of microsleeps and disappearing at the end of the microsleeps. Our results from global graph indices derived from effective connectivity analysis have revealed EEG-based biomarkers of all stages of microsleeps (preceding, onset, pre-recovery, recovery). In particular, this raises the possibility of being able to predict microsleeps in real-world tasks and initiate a 'wake-up' intervention to avert the microsleeps and, hence, prevent injurious and even multi-fatality accidents.

Attention lapses and behavioural microsleeps during tracking, psychomotor vigilance, and dual tasks.

This study examined the incidence of attention lapses and microsleeps under contrasting levels of task complexity during three tasks: PVT, 2-D tracking and a dual task combining the two. More attention lapses per participant (median 15vs. 3; range 1-74vs. 0-76, p=0.001), with the greatest increase with time spent-on-task (p=0.002), were evident on the more cognitively-demanding dual task than on the PVT. Conversely, fewer microsleeps (median 0vs. 0; range 0-1vs. 0-18, p=0.022) occurred during the more complex task compared to the tracking task. An increase in microsleep rate with time spent-on-task (p=0.035) was evident during the tracking task but not the dual task. These results indicate that the higher cognitive load, associated with an increase in task complexity, increased the likelihood of attention lapses, while a reduction in task complexity increased the likelihood of microsleeps.

Observational Management of CIN 2 in Young Women: A Prospective Multicenter Trial.

OBJECTIVES: We present the rationale and methods for PRINCess-a multicenter prospective trial-which aims to determine outcome and predictors of regression in a large cohort of women younger than 25 years with cervical intraepithelial neoplasia grade 2 (CIN 2) undergoing observational management. MATERIALS AND METHODS: Six hundred women younger than 25 years with newly diagnosed biopsy-proven CIN 2 are being recruited to observational management (i.e., repeat colposcopy, cytology, and cervical biopsy every 6 months for 2 years). Five hundred fifty-two women from throughout New Zealand and 1 site in Australia have been recruited so far. Measures include histology, cytology, human papillomavirus genotyping, and immunohistochemical staining. Women who develop CIN 3 will be treated with large loop excision of the transformation zone. The primary outcomes are rates of clinical regression of CIN 2 (i.e., 2 consecutive colposcopy follow-ups showing CIN 1 or normal), loss to follow-up, and progression to invasion. CONCLUSIONS: The optimal treatment for young women with a diagnosis of CIN 2 is controversial. Although many undergo surgical treatment, observational management is increasingly recommended. However, there is little evidence from large clinical trials of the safety and practicality of observational management of young women with CIN 2. When completed, we will have adequate evidence by which to counsel women regarding their likely outcomes and to offer advice on clinical follow-up protocols.

Source-space ICA for EEG source separation, localization, and time-course reconstruction.

We propose source-space independent component analysis (ICA) for separation, tomography, and time-course reconstruction of EEG and MEG source signals. Source-space ICA is based on the application of singular value decomposition and ICA on the neuroelectrical signals from all brain voxels obtained post minimum-variance beamforming of sensor-space EEG or MEG. We describe the theoretical background and equations, then evaluate the performance of this technique in several different situations, including weak sources, bilateral correlated sources, multiple sources, and cluster sources. In this approach, tomographic maps of sources are obtained by back-projection of the ICA mixing coefficients into the source-space (3-D brain template). The advantages of source-space ICA over the popular alternative approaches of sensor-space ICA together with dipole fitting and power mapping via minimum-variance beamforming are demonstrated. Simulated EEG data were produced by forward head modeling to project the simulated sources onto scalp sensors, then superimposed on real EEG background. To illustrate the application of source-space ICA to real EEG source reconstruction, we show the localization and time-course reconstruction of visual evoked potentials. Source-space ICA is superior to the minimum-variance beamforming in the reconstruction of multiple weak and strong sources, as ICA allows weak sources to be identified and reconstructed in the presence of stronger sources. Source-space ICA is also superior to sensor-space ICA on accuracy of localization of sources, as source-space ICA applies ICA to the time-courses of voxels reconstructed from minimum-variance beamforming on a 3D scanning grid and these time-courses are optimally unmixed via the beamformer. Each component identified by source-space ICA has its own tomographic map which shows the extent to which each voxel has contributed to that component.

Losing the struggle to stay awake: divergent thalamic and cortical activity during microsleeps.

Maintaining alertness is critical for safe and successful performance of most human activities. Consequently, microsleeps during continuous visuomotor tasks, such as driving, can be very serious, not only disrupting performance but sometimes leading to injury or death due to accidents. We have investigated the neural activity underlying behavioral microsleeps--brief (0.5-15 s) episodes of complete failure to respond accompanied by slow eye-closures--and EEG theta activity during drowsiness in a continuous task. Twenty healthy normally-rested participants performed a 50-min continuous tracking task while fMRI, EEG, eye-video, and responses were simultaneously recorded. Visual rating of performance and eye-video revealed that 70% of the participants had frequent microsleeps. fMRI analysis revealed a transient decrease in thalamic, posterior cingulate, and occipital cortex activity and an increase in frontal, posterior parietal, and parahippocampal activity during microsleeps. The transient activity was modulated by the duration of the microsleep. In subjects with frequent microsleeps, power in the post-central EEG theta was positively correlated with the BOLD signal in the thalamus, basal forebrain, and visual, posterior parietal, and prefrontal cortices. These results provide evidence for distinct neural changes associated with microsleeps and with EEG theta activity during drowsiness in a continuous task. They also suggest that the occurrence of microsleeps during an active task is not a global deactivation process but involves localized activation of fronto-parietal cortex, which, despite a transient loss of arousal, may constitute a mechanism by which these regions try to restore responsiveness.

Perceived barriers to self-collected HPV testing for cervical cancer screening, and knowledge of HPV: a survey of primary healthcare smear-takers across Aotearoa New Zealand.

AIMS: Cervical cancer remains a burden within Aotearoa New Zealand, with 2022 screening rates sitting 12.7% below target. The National Cervical Screening Programme has changed to primary human papillomavirus (HPV) testing for all screen-eligible people, with the aim for home self-testing. Little is known about the readiness of primary care for the change to self-testing and its associated challenges. A pilot HPV cervical cancer screening programme is being conducted in 17 practice centres. The aim of this study is to explore smear-taker knowledge at these centres about the use of primary HPV testing for cervical cancer screening. METHODS: This is an ethically approved questionnaire study, with data from a structured web-based questionnaire sent to all smear-takers at the pilot centres. RESULTS: We achieved a total completion rate of 57.8%. The average score for "Knowledge of HPV" was 56.5% (range=20-100%). The challenges to patient home HPV self-testing were felt to be overall "not at all" to "mildly challenging". Up to 73.3% of participants identified ongoing needs for further education. CONCLUSIONS: The findings indicate knowledge deficits regarding HPV testing for cervical cancer screening and a desire for the provision of further education. Overall, respondents felt that no major barriers to implementing HPV self-testing would occur.

Distinct neural correlates of time-on-task and transient errors during a visuomotor tracking task after sleep restriction.

Sleep loss leads to both time-on-task slowing of responsiveness and increased frequency of transient response errors. The consequences of such errors during real-world visuomotor tasks, such as driving, are serious and life threatening. To investigate the neuronal underpinning of time-on-task and transient errors during a visuomotor tracking task following sleep restriction, we performed fMRI on 20 healthy individuals when well-rested and when sleep-restricted while they performed a 2-D pursuit-tracking task. Sleep restriction to 4-h time-in-bed was associated with significant time-on-task decline in tracking performance and an increased number of transient tracking errors. Sleep restriction was associated with time-on-task decreases in BOLD activity in task-related areas, including the lateral occipital cortex, intraparietal cortex, and primary motor cortex. In contrast, thalamic, anterior cingulate, and medial frontal cortex areas showed overall increases irrespective of time-on-task after sleep-restriction. Furthermore, transient errors after sleep-restriction were associated with distinct transient BOLD activations in areas not involved in tracking task per se, in the right superior parietal cortex, bilateral temporal cortex, and thalamus. These results highlight the distinct cerebral underpinnings of sustained and transient modulations in alertness during increased homeostatic drive to sleep. Ability to detect neuronal changes associated with both sustained and transient changes in performance in a single task allowed us to disentangle neuronal mechanisms underlying two important aspects of sustained task performance following sleep loss.

Endometrial cancer diagnoses prompted by routine cervical cytology: a retrospective case study.

AIMS: Endometrial cancer is the commonest gynaecological cancer in New Zealand. Some women have their diagnosis of endometrial cancer prompted by an abnormal cervical cytology screening test. When high-risk human papillomavirus (hr-HPV) testing becomes the primary test for cervical screening, this avenue of incidental diagnosis will be reduced. Therefore, our aims were to estimate the proportion of women whose diagnosis of endometrial cancer follows incidental detection on routine cervical cytology, and to understand the clinicopathologic characteristics of these cases. METHODS: Retrospective analysis of patient medical records from women of cervical screening age diagnosed with endometrial cancer between 2015-2019 in the South Island of New Zealand. RESULTS: Of 334 women, 26 (7.8%) had endometrial cancer diagnosis prompted by abnormal cervical cytology. Most women had low-grade (17/26, 65.4%), low-stage (18/26, 69.2%) disease of endometrioid histologic subtype (21/26, 80.8%). The small cohort prevented significant correlations with clinicopathologic characteristics and outcomes. Overall, cervical cytology had low sensitivity (32.3%) for the detection of endometrial cancer in the 6 months before diagnosis. CONCLUSIONS: A small number of women currently have diagnoses of endometrial cancer prompted by routine cervical screening with cytology. However, the undefined clinical benefit from and poor sensitivity of cervical cytology for detecting endometrial cancer does not justify its use in screening, or opposition to hr-HPV cervical screening.

Increased cerebral activity during microsleeps reflects an unconscious drive to re-establish consciousness.

BACKGROUND: Microsleeps are brief instances of sleep, causing complete lapses in responsiveness and partial or total extended closure of both eyes. Microsleeps can have devastating consequences, particularly in the transportation sector. STUDY OBJECTIVES: Questions remain regarding the neural signature and underlying mechanisms of microsleeps. This study aimed to gain a better understanding of the physiological substrates of microsleeps, which might lead to a better understanding of the phenomenon. METHODS: Data from an earlier study, involving 20 healthy non-sleep-deprived subjects, were analysed. Each session lasted 50 min and required subjects to perform a 2-D continuous visuomotor tracking task. Simultaneous data collection included tracking performance, eye-video, EEG, and fMRI. A human expert visually inspected each participant's tracking performance and eye-video recordings to identify microsleeps. Our interest was in microsleeps of ≥4-s duration, leaving us with a total of 226 events from 10 subjects. The microsleep events were divided into four 2-s segments (pre, start, end, and post) (with a gap in the middle, between start and end segments, for microsleeps >4 s), then each segment was analysed relative to its prior segment by examining changes in source-reconstructed EEG power in the delta, theta, alpha, beta, and gamma bands. RESULTS: EEG power increased in the theta and alpha bands between the pre and start of microsleeps. There was also increased power in the delta, beta, and gamma bands between the start and end of microsleeps. Conversely, there was a reduction in power between the end and post of microsleeps in the delta and alpha bands. These findings support previous findings in the delta, theta, and alpha bands. However, increased power in the beta and gamma bands has not been previously reported. CONCLUSIONS: We contend that increased high-frequency activity during microsleeps reflects unconscious 'cognitive' activity aimed at re-establishing consciousness following falling asleep during an active task.

The High-Risk Human Papillomavirus Type Influences the Tissue Microenvironment in Cervical Intraepithelial Neoplasia Grade 2.

High-risk, cancer-causing human papillomavirus (HPV) types are associated with cervical precancer and cancer. A high proportion of high-risk HPV precancer lesions undergo immune-mediated regression. The purpose of this study was to determine if the tissue microenvironment of HPV16 and 18 (HPV16/18) cervical intraepithelial neoplasia grade 2 lesions differed from other high-risk types (HPV 'other'). Consistent with other studies, we found that progression to higher-grade disease was more frequent in HPV16/18 lesions when compared with HPV 'other' lesions. HPV16/18 lesions were significantly more likely to be indoleamine 2,3,-dioxygenase 1 (IDO1)-positive and were associated with reduced CD8 and FoxP3 T cells in the lesion. In the stroma, reduced Tbet- and CD32-positive cells and increased Blimp1-positive cells were significantly associated with HPV16/18 lesions when compared with HPV 'other' types. On analysis of the IDO1-positive tissues, lesional IDO1 was associated with significantly decreased numbers of CD4-, CD8-, and FoxP3-positive cells in the stroma compared with IDO1-negative tissues. These data suggest that IDO1 expression may impair infiltration of CD4, CD8, and FoxP3 cells into the stroma beneath the precancer lesion. Increased expression of IDO1 may contribute to immune avoidance and an increased frequency of disease progression in HPV16- and 18-positive lesions.

Blimp-1 is a prognostic indicator for progression of cervical intraepithelial neoplasia grade 2.

BACKGROUND: Progression of cervical intraepithelial neoplasia (CIN) to higher grade disease is associated with persistent human papillomavirus (HPV) infection and an absence of immune-mediated regression. However, the immune microenvironment that distinguishes progression from persistent or regressing lesions has not been well defined. METHODS: A total of 69 patients under the age of 25 with high-risk HPV-positive cytology and biopsy-confirmed p16-positive CIN2 were included in the study. Biopsies were stained using 20 antibodies to a range of immune markers. Based on a 2-year follow-up, samples were analysed in "progressor" (CIN3 +) or "persister/regressor" (CIN1, 2 or normal) groups. RESULTS: Progression was most strongly associated with Blimp-1 positive cell staining in the lesion (P = 0.0019) and with low numbers of infiltrating CD4 cells in the dermal region beneath the lesion (P = 0.0022). The presence of CD4, CD8 and T bet-positive cells in the dermal region most strongly correlated with CD11c cells in the persister/regressor but not the progressor group. CONCLUSION: High numbers of Blimp-1 + cells in CIN2 lesions may predict progression to more severe disease. Measurement of Blimp-1 may have diagnostic utility for the determination of the need to treat women with cervical pre-cancer. HIGHLIGHTS: CIN2 progression is associated with high numbers of Blimp-1 positive cells in the lesion. Detection of Blimp-1 in the lesion may have utility as a prognostic test to inform the need to treat CIN2.

Patient choice may improve adherence to follow-up in cervical screening: a randomised-control trial.

AIMS: We investigated whether patient choice of follow-up type improves health-related quality of life (HrQOL) and follow-up attendance in women who have undergone large loop excision of the transformation zone (LLETZ) for cervical intraepithelial neoplasia grade 2 to 3 (CIN 2-3). METHODS: A three-armed randomised controlled trial including women with newly diagnosed CIN 2-3 post-LLETZ treatment was performed. Consenting women were randomised (1:1:1) to either: (a) colposcopy review at the hospital, (b) follow-up with high-risk human papilloma virus (HrHPV) and smear test in the community or (c) a choice of the aforementioned follow-up options, six months post-treatment. HrQOL was measured and participants were surveyed at baseline and six months regarding preferences for follow-up. RESULTS: Sixty-eight participants were randomised to follow-up (a), 67 to follow-up (b) and 65 to follow-up (c) (n=200). At six months post-treatment, 47% of patients indicated a preference for (a), 24% for (b) and 26% for (c). We found no significant difference in HrQOL between the study arms. Attendance was greater among patients who chose their follow-up (95.5% vs 91.1%, p=0.06). CONCLUSION: Choice of follow-up was associated with greater attendance. However, larger studies examining the effects of HrQOL and attendance to different follow-ups are warranted.