Symfind: Addressing the Fragility of Subhalo Finders and Revealing the Durability of Subhalos

A major question in $\Lambda$CDM is what this theory actually predicts for the properties of subhalo populations. Subhalos are difficult to simulate and to find within simulations, and this propagates into uncertainty in theoretical predictions for satellite galaxies. We present Symfind, a new particle-tracking-based subhalo finder, and demonstrate that it can track subhalos to orders-of-magnitude lower masses than commonly used halo-finding tools, with a focus on Rockstar and consistent-trees. These longer survival mean that at a fixed peak subhalo mass, we find $\approx 15\%{-}40\%$ more subhalos within the virial radius, $R_\textrm{vir}$, and $\approx 35\%-120\%$ more subhalos within $R_\textrm{vir}/4$ in the Symphony dark-matter-only simulation suite. More subhalos are found as resolution is increased. We perform extensive numerical testing. In agreement with idealized simulations, we show that the $v_{\rm max}$ of subhalos is only resolved at high resolutions ($n_\textrm{peak}\gtrsim3\times 10^4$), but that mass loss itself can be resolved at much more modest particle counts ($n_\textrm{peak}\gtrsim4\times 10^3$). We show that Rockstar converges to false solutions for the mass function, radial distribution, and disruption masses of subhalos. We argue that our new method can trace resolved subhalos until the point of typical galaxy disruption without invoking ``orphan'' modeling. We outline a concrete set of steps for determining whether other subhalo finders meet the same criteria. We publicly release Symfind catalogs and particle data for the Symphony simulation suite at \url{http://web.stanford.edu/group/gfc/symphony}.Comment: 45 pages, 19 figure

Are Australian general practice patients appropriately screened for colorectal cancer? A cross-sectional study.

BackgroundAustralia has one of the highest rates of colorectal cancer (CRC) in the world. Data from the National Bowel Cancer Screening Program (NBCSP) suggests that only one third of Australians eligible for CRC screening are up-to-date with CRC screening; however screening occurring outside the program is not captured.AimsThis study examines the self-reported CRC screening practices of general practice patients, and the factors associated with being under-screened for CRC.Methods A cross-sectional study conducted in five general practice clinics in NSW from 2015-2017. Participants were aged 50–75 and at average risk of CRC. Participants reported whether they had a faecal occult blood test (FOBT) in the past two years, including the source of FOBT; and whether they had a colonoscopy in the past five years and the reason for colonoscopy.Results Forty-nine per cent of participants completed a FOBT in the past two years. Of these, 62 per cent sourced their FOBT from the NBCSP and 25 per cent from their general practitioner. Thirty-seven per cent of participants reported colonoscopy in the past five years. Of these, 29 per cent received potentially inappropriate colonoscopy. Thirty-two per cent of the samples were classified as under-screened. Older adults were less likely to be under-screened.ConclusionCRC screening rates were higher than those reported by the NBCSP, however a significant proportion of participants remain under-screened. Over one-quarter of participants reporting colonoscopy in the past five years may have undergone unnecessary colonoscopy. These findings indicate that more needs to be done at a general practice level to facilitate risk-appropriate CRC screening

Supporting stimulation needs in dementia care through wall-sized displays

Beside reminiscing, the increasing cognitive decline in dementia can also be addressed through sensory stimulation allowing the immediate, nonverbal engagement with the world through one’s senses. Much HCI work has prioritized cognitive stimulation for reminiscing or personhood often on small screens, while less research has explored sensory stimulation like the one enabled by large displays. We describe a year-long deployment in a residential care home of a wall-sized display, and explored its domestication through 24 contextual interviews. Findings indicate strong engagement and attachment to the display which has inspired four psychosocial interventions using online generic content. We discuss the value of these findings for personhood through residents’ exercise of choices, the tension between generic/personal content and its public/private use, the importance of participatory research approach to domestication, and the infrastructure-based prototype, illustrated by the DementiaWall and its generative quality

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Dissecting proactive control processes in task-switching: a model-based neuroscience approach

Research Doctorate - Doctor of Philosophy (PhD)Cognitive control processes support purposeful, goal-directed behaviour in the presence of conflicting demands from our environment. Given advance information, this type of control can be engaged in anticipation of a change in behaviour. The cued-trials task-switching paradigm can temporally dissociate proactive and reactive cognitive control processes involved in switching between sets of abstract task rules. Typically, there is a performance cost for switch relative to repeat trials, which is attributed partly to proactive control processes required to prepare for a switch in task and partly to reactive control processes required to deal with between-task interference. Despite two decades of research into preparatory processes in task-switching, the cognitive processes and neural substrates that support proactive control remain underspecified. This thesis uses a model-based neuroscience approach to define the temporal and spatial characteristics of cognitive processes that contribute to proactive control in task-switching. Using converging evidence from ERPs, a novel multivariate pattern misclassification analysis of EEG data and cognitive modeling, we showed that a switch-specific preparation process is temporally and spatially distinct from more general task preparation for both switch and repeat trials. Consistent with a conflict control mechanism, we show that this switch-specific preparation process is linked to a right inferior frontal source and is related to upward adjustment of response caution in anticipation of more difficult switch trials. We also used fMRI- and DWI-based analyses to examine the neural basis of these cue-related adjustments in response caution, showing that distinct cortico-basal ganglia networks are associated with the ability to flexibly adjust response caution in anticipation of easy or difficult decisions, as well as intrinsic tendencies to set overall response caution high or low. We discuss implications of these findings for our understanding of the organization and timecourse of cognitive control mechanisms

A race against time: The dementia epidemic

The global prevalence of dementia is expected to double every two decades. Consequently, there is an urgent need for high-quality research to identify effective strategies for providing optimal care to people with dementia and their carers. Currently, research in dementia care is fragmented, which has resulted in a division between the fields of diagnosis and management of dementia including end-of-life care. For example, interventions which have been developed to improve the well-being of the person with dementia and their families focus on discrete elements of the person and their family's experience, such as symptom management, dealing with emotional issues, or planning for the future. A more integrated approach is needed to address gaps in care across the trajectory, while recognizing the multitude impacts on the person affected and their families. This approach will make a meaningful difference to the well-being of people with dementia and their carers, and reduce the burden of the disease on the individual, their family, and society

Missed opportunities:general practitioner identification of their patients' smoking status.

Background: In order to provide smoking cessation support to their patients in line with clinical practice guidelines, general practitioners must first ascertain whether their patients' use tobacco. This study examined (i) the sensitivity, specificity, positive predictive value and negative predictive value of general practitioner detection of smoking. ; and (ii) the general practitioner and patient characteristics associated with detection of tobacco use. Methods: Eligible patients completed a touchscreen computer survey while waiting for an appointment with their general practitioner. Patients self-reported demographic characteristics, medical history, and current smoking status. Following the patient's consultation, their general practitioner was asked to indicate whether the patient was a current smoker (yes/no/unsure/not applicable). Smoking prevalence, sensitivity, specificity, positive predictive value and negative predictive values (with 95% confidence intervals) were calculated using patient self-report of smoking status as the gold standard. Generalised estimating equations were used to examine the general practitioner and patient characteristics associated with detection of tobacco use. Results: Fifty-one general practitioners and 1,573 patients in twelve general practices participated. Patient self-report of smoking was 11.3% compared to general practitioner estimated prevalence of 9.5%. Sensitivity of general practitioner assessment was 66% [95% CI 59-73] while specificity was 98% [95% CI 97-98]. Positive predictive value was 78% [95% CI 71-85] and negative predictive value was 96% [95% CI 95-97]. No general practitioner factors were associated with detection of smoking. Patients with a higher level of education or who responded 'Other ' were less likely to be detected as smokers than patients who had completed a high school or below level of education. Conclusion: Despite the important role general practitioners play in providing smoking cessation advice and support, a substantial proportion of general practitioners do not know their patient's smoking status. This represents a significant missed opportunity in the provision of preventive healthcare. Electronic waiting room assessments may assist general practitioners in improving the identification of smokers

Switch-related and general preparation processes in task-switching: evidence from multivariate pattern classification of EEG data

The cued-trials task-switching paradigm is used to investigate the processes involved in preparation to change task. Task switch trials typically show poorer performance than task repeat trials, suggesting that additional or more time-consuming preparation processes are required to switch tasks. However, behavioral and neuroimaging studies have so far been unable to decipher whether preparing for a switch in task involves distinct cognitive processes to those required more generally on both switch and repeat trials. The current study addresses this question using a novel multivariate pattern misclassification analysis of frequency band-specific local topographical patterns in human EEG activity that was elicited by cues varying in information value. Within the alpha frequency band, misclassification analysis produced evidence for an early switch-related preparation process over right frontal cortex, as well as a later task readiness preparation process over right parietal cortex. This represents compelling evidence for dissociable switch-related and task readiness preparation processes that show distinct time course and spatial activation patterns