Behavioral evidence for pattern separation in human episodic memory.

An essential feature of episodic memory is the ability to recall the multiple elements relating to one event from the multitude of elements relating to other, potentially similar events. Hippocampal pattern separation is thought to play a fundamental role in this process, by orthogonalizing the representations of overlapping events during encoding, to reduce interference between them during the process of pattern completion by which one or other is recalled. We introduce a new paradigm to test the hypothesis that similar memories, but not unrelated memories, are actively separated at encoding. Participants memorized events which were either unique or shared a common element with another event (paired "overlapping" events). We used a measure of dependency, originally devised to measure pattern completion, to quantify how much the probability of successfully retrieving associations from one event depends on successful retrieval of associations from the same event, an unrelated event or the overlapping event. In two experiments, we saw that within event retrievals were highly dependent, indicating pattern completion; retrievals from unrelated events were independent; and retrievals from overlapping events were antidependent (i.e., less than independent), indicating pattern separation. This suggests that representations of similar (overlapping) memories are actively separated, resulting in lowered dependency of retrieval performance between them, as would be predicted by the pattern separation account.

Exploring international differences in ovarian cancer treatment: a comparison of clinical practice guidelines and patterns of care.

INTRODUCTION: The International Cancer Benchmarking Partnership demonstrated international differences in ovarian cancer survival, particularly for women aged 65-74 with advanced disease. These findings suggest differences in treatment could be contributing to survival disparities. OBJECTIVE: To compare clinical practice guidelines and patterns of care across seven high-income countries. METHODS: A comparison of guidelines was performed and validated by a clinical working group. To explore clinical practice, a patterns of care survey was developed. A questionnaire regarding management and potential health system-related barriers to providing treatment was emailed to gynecological specialists. Guideline and survey results were crudely compared with 3-year survival by 'distant' stage using Spearman's rho. RESULTS: Twenty-seven guidelines were compared, and 119 clinicians completed the survey. Guideline-related measures varied between countries but did not correlate with survival internationally. Guidelines were consistent for surgical recommendations of either primary debulking surgery or neoadjuvant chemotherapy followed by interval debulking surgery with the aim of complete cytoreduction. Reported patterns of surgical care varied internationally, including for rates of primary versus interval debulking, extensive/'ultra-radical' surgery, and perceived barriers to optimal cytoreduction. Comparison showed that willingness to undertake extensive surgery correlated with survival across countries (rs=0.94, p=0.017). For systemic/radiation therapies, guideline differences were more pronounced, particularly for bevacizumab and PARP (poly (ADP-ribose) polymerase) inhibitors. Reported health system-related barriers also varied internationally and included a lack of adequate hospital staffing and treatment monitoring via local and national audits. DISCUSSION: Findings suggest international variations in ovarian cancer treatment. Characteristics relating to countries with higher stage-specific survival included higher reported rates of primary surgery; willingness to undertake extensive/ultra-radical procedures; greater access to high-cost drugs; and auditing.

25 year trends in cancer incidence and mortality among adults aged 35-69 years in the UK, 1993-2018: retrospective secondary analysis.

OBJECTIVE: To examine and interpret trends in UK cancer incidence and mortality for all cancers combined and for the most common cancer sites in adults aged 35-69 years. DESIGN: Retrospective secondary data analysis. DATA SOURCES: Cancer registration data, cancer mortality and national population data from the Office for National Statistics, Public Health Wales, Public Health Scotland, Northern Ireland Cancer Registry, NHS England, and the General Register Office for Northern Ireland. SETTING: 23 cancer sites were included in the analysis in the UK. PARTICIPANTS: Men and women aged 35-69 years diagnosed with or who died from cancer between 1993 to 2018. MAIN OUTCOME MEASURES: Change in cancer incidence and mortality age standardised rates over time. RESULTS: The number of cancer cases in this age range rose by 57% for men (from 55 014 cases registered in 1993 to 86 297 in 2018) and by 48% for women (60 187 to 88 970) with age standardised rates showing average annual increases of 0.8% in both sexes. The increase in incidence was predominantly driven by increases in prostate (male) and breast (female) cancers. Without these two sites, all cancer trends in age standardised incidence rates were relatively stable. Trends for a small number of less common cancers showed concerning increases in incidence rates, for example, in melanoma skin, liver, oral, and kidney cancers. The number of cancer deaths decreased over the 25 year period, by 20% in men (from 32 878 to 26 322) and 17% in women (28 516 to 23 719); age standardised mortality rates reduced for all cancers combined by 37% in men (-2.0% per year) and 33% in women (-1.6% per year). The largest decreases in mortality were noted for stomach, mesothelioma, and bladder cancers in men and stomach and cervical cancers and non-Hodgkin lymphoma in women. Most incidence and mortality changes were statistically significant even when the size of change was relatively small. CONCLUSIONS: Cancer mortality had a substantial reduction during the past 25 years in both men and women aged 35-69 years. This decline is likely a reflection of the successes in cancer prevention (eg, smoking prevention policies and cessation programmes), earlier detection (eg, screening programmes) and improved diagnostic tests, and more effective treatment. By contrast, increased prevalence of non-smoking risk factors are the likely cause of the observed increased incidence for a small number of specific cancers. This analysis also provides a benchmark for the following decade, which will include the impact of covid-19 on cancer incidence and outcomes.

Grid-like Processing of Imagined Navigation.

Grid cells in the entorhinal cortex (EC) of rodents [1] and humans [2] fire in a hexagonally distributed spatially periodic manner. In concert with other spatial cells in the medial temporal lobe (MTL) [3-6], they provide a representation of our location within an environment [7, 8] and are specifically thought to allow the represented location to be updated by self-motion [9]. Grid-like signals have been seen throughout the autobiographical memory system [10], suggesting a much more general role in memory [11, 12]. Grid cells may allow us to move our viewpoint in imagination [13], a useful function for goal-directed navigation and planning [12, 14-16], and episodic future thinking more generally [17, 18]. We used fMRI to provide evidence for similar grid-like signals in human entorhinal cortex during both virtual navigation and imagined navigation of the same paths. We show that this signal is present in periods of active navigation and imagination, with a similar orientation in both and with the specifically 6-fold rotational symmetry characteristic of grid cell firing. We therefore provide the first evidence suggesting that grid cells are utilized during movement of viewpoint within imagery, potentially underpinning our more general ability to mentally traverse possible routes in the service of planning and episodic future thinking.

Surface-Based Display of Volume-Averaged Cerebellar Imaging Data.

The paper presents a flat representation of the human cerebellum, useful for visualizing functional imaging data after volume-based normalization and averaging across subjects. Instead of reconstructing individual cerebellar surfaces, the method uses a white- and grey-matter surface defined on volume-averaged anatomical data. Functional data can be projected along the lines of corresponding vertices on the two surfaces. The flat representation is optimized to yield a roughly proportional relationship between the surface area of the 2D-representation and the volume of the underlying cerebellar grey matter. The map allows users to visualize the activation state of the complete cerebellar grey matter in one concise view, equally revealing both the anterior-posterior (lobular) and medial-lateral organization. As examples, published data on resting-state networks and task-related activity are presented on the flatmap. The software and maps are freely available and compatible with most major neuroimaging packages.