Extending Hybrid CSP with Probability and Stochasticity

Probabilistic and stochastic behavior are omnipresent in computer controlled systems, in particular, so-called safety-critical hybrid systems, because of fundamental properties of nature, uncertain environments, or simplifications to overcome complexity. Tightly intertwining discrete, continuous and stochastic dynamics complicates modelling, analysis and verification of stochastic hybrid systems (SHSs). In the literature, this issue has been extensively investigated, but unfortunately it still remains challenging as no promising general solutions are available yet. In this paper, we give our effort by proposing a general compositional approach for modelling and verification of SHSs. First, we extend Hybrid CSP (HCSP), a very expressive and process algebra-like formal modeling language for hybrid systems, by introducing probability and stochasticity to model SHSs, which is called stochastic HCSP (SHCSP). To this end, ordinary differential equations (ODEs) are generalized by stochastic differential equations (SDEs) and non-deterministic choice is replaced by probabilistic choice. Then, we extend Hybrid Hoare Logic (HHL) to specify and reason about SHCSP processes. We demonstrate our approach by an example from real-world.Comment: The conference version of this paper is accepted by SETTA 201

Calorie Restriction Attenuates Terminal Differentiation of Immune Cells

Immune senescence is a natural consequence of aging and may contribute to frailty and loss of homeostasis in later life. Calorie restriction increases healthy life-span in C57BL/6J (but not DBA/2J) mice, but whether this is related to preservation of immune function, and how it interacts with aging, is unclear. We compared phenotypic and functional characteristics of natural killer (NK) cells and T cells, across the lifespan, of calorie-restricted (CR) and control C57BL/6 and DBA/2 mice. Calorie restriction preserves a naïve T cell phenotype and an immature NK cell phenotype as mice age. The splenic T cell populations of CR mice had higher proportions of CD11a-CD44locells, lower expression of TRAIL, KLRG1, and CXCR3, and higher expression of CD127, compared to control mice. Similarly, splenic NK cells from CR mice had higher proportions of less differentiated CD11b-CD27+cells and correspondingly lower proportions of highly differentiated CD11b+CD27-NK cells. Within each of these subsets, cells from CR mice had higher expression of CD127, CD25, TRAIL, NKG2A/C/E, and CXCR3 and lower expression of KLRG1 and Ly49 receptors compared to controls. The effects of calorie restriction on lymphoid cell populations in lung, liver, and lymph nodes were identical to those seen in the spleen, indicating that this is a system-wide effect. The impact of calorie restriction on NK cell and T cell maturation is much more profound than the effect of aging and, indeed, calorie restriction attenuates these age-associated changes. Importantly, the effects of calorie restriction on lymphocyte maturation were more marked in C57BL/6 than in DBA/2J mice indicating that delayed lymphocyte maturation correlates with extended lifespan. These findings have implications for understanding the interaction between nutritional status, immunity, and healthy lifespan in aging populations

ERP evidence suggests executive dysfunction in ecstasy polydrug users

Background: Deficits in executive functions such as access to semantic/long-term memory have been shown in ecstasy users in previous research. Equally, there have been many reports of equivocal findings in this area. The current study sought to further investigate behavioural and electro-physiological measures of this executive function in ecstasy users. Method: Twenty ecstasy–polydrug users, 20 non-ecstasy–polydrug users and 20 drug-naïve controls were recruited. Participants completed background questionnaires about their drug use, sleep quality, fluid intelligence and mood state. Each individual also completed a semantic retrieval task whilst 64 channel Electroencephalography (EEG) measures were recorded. Results: Analysis of Variance (ANOVA) revealed no between-group differences in behavioural performance on the task. Mixed ANOVA on event-related potential (ERP) components P2, N2 and P3 revealed significant between-group differences in the N2 component. Subsequent exploratory univariate ANOVAs on the N2 component revealed marginally significant between-group differences, generally showing greater negativity at occipito-parietal electrodes in ecstasy users compared to drug-naïve controls. Despite absence of behavioural differences, differences in N2 magnitude are evidence of abnormal executive functioning in ecstasy–polydrug users

Visual adaptation alters the apparent speed of real-world actions

The apparent physical speed of an object in the field of view remains constant despite variations in retinal velocity due to viewing conditions (velocity constancy). For example, people and cars appear to move across the field of view at the same objective speed regardless of distance. In this study a series of experiments investigated the visual processes underpinning judgements of objective speed using an adaptation paradigm and video recordings of natural human locomotion. Viewing a video played in slow-motion for 30seconds caused participants to perceive subsequently viewed clips played at standard speed as too fast, so playback had to be slowed down in order for it to appear natural; conversely after viewing fast-forward videos for 30seconds, playback had to be speeded up in order to appear natural. The perceived speed of locomotion shifted towards the speed depicted in the adapting video (‘re-normalisation’). Results were qualitatively different from those obtained in previously reported studies of retinal velocity adaptation. Adapting videos that were scrambled to remove recognizable human figures or coherent motion caused significant, though smaller shifts in apparent locomotion speed, indicating that both low-level and high-level visual properties of the adapting stimulus contributed to the changes in apparent speed

Climate change and alpine-adapted insects: modelling environmental envelopes of a grasshopper radiation

Mountains create steep environmental gradients that are sensitive barometers of climate change. We calibrated 10 statistical models to formulate ensemble ecological niche models for 12 predominantly alpine, flightless grasshopper species in Aotearoa New Zealand, using their current distributions and current conditions. Niche models were then projected for two future global climate scenarios: representative concentration pathway (RCP) 2.6 (1.0°C rise) and RCP8.5 (3.7°C rise). Results were species specific, with two-thirds of our models suggesting a reduction in potential range for nine species by 2070, but surprisingly, for six species, we predict an increase in potential suitable habitat under mild (+1.0°C) or severe global warming (+3.7°C). However, when the limited dispersal ability of these flightless grasshoppers is taken into account, all 12 species studied are predicted to suffer extreme reductions in range, with a quarter likely to go extinct due to a 96-100% reduction in suitable habitat. Habitat loss is associated with habitat fragmentation that is likely to escalate stochastic vulnerability of remaining populations. Here, we present the predicted outcomes for an endemic radiation of alpine taxa as an exemplar of the challenges that alpine species, both in New Zealand and internationally, are subject to by anthropogenic climate change.fals

An algorithm to construct one-vertex triangulations of Heegaard splittings

Following work of Jaco and Rubinstein (2006), which (non-constructively) proved that any 3-manifold admits a one-vertex layered triangulation, we present an algorithm, with implementation using Regina, that uses a combinatorial presentation of a Heegaard diagram to construct a generalised notion of a layered triangulation. We show that work of Husz\'ar and Spreer (2019) extends to our construction: given a genus-$g$ Heegaard splitting, our algorithm generates a triangulation with cutwidth bounded above by $4g-2$. Beyond Heegaard splittings, our construction actually extends to a natural generalisation of Dehn fillings: given a one-vertex triangulation with a genus-$g$ boundary component $B$, we can construct a one-vertex triangulation of any 3-manifold obtained by filling $B$ with a handlebody. To demonstrate the usefulness of our algorithm, we present findings from preliminary computer searches using this algorithm.Comment: 38 pages, 36 figures. v2: Substantial updates to the expositio

Explosive Nucleosynthesis: What we learned and what we still do not understand

This review touches on historical aspects, going back to the early days of nuclear astrophysics, initiated by B$^2$FH and Cameron, discusses (i) the required nuclear input from reaction rates and decay properties up to the nuclear equation of state, continues (ii) with the tools to perform nucleosynthesis calculations and (iii) early parametrized nucleosynthesis studies, before (iv) reliable stellar models became available for the late stages of stellar evolution. It passes then through (v) explosive environments from core-collapse supernovae to explosive events in binary systems (including type Ia supernovae and compact binary mergers), and finally (vi) discusses the role of all these nucleosynthesis production sites in the evolution of galaxies. The focus is put on the comparison of early ideas and present, very recent, understanding.Comment: 11 pages, to appear in Springer Proceedings in Physics (Proc. of Intl. Conf. "Nuclei in the Cosmos XV", LNGS Assergi, Italy, June 2018

Combining PPI with qualitative research to engage ‘harder-to-reach’ populations: service user groups as co-applicants on a platform study for a trial

Abstract Background: Patient and public involvement (PPI) in all research studies is recommended from the earliest point and in as many stages as possible. Qualitative research is also recommended in the early stages of designing. complex intervention trials. Combining both together might enable inclusion of ‘harder-to-reach’ perspectives from the target population(s), particularly when the research is intended for their benefit. However, the interface between PPI and qualitative research has received little attention. Methods: In a multi-disciplinary, mixed methods study to inform the design of incentive trials for smoking cessation in pregnancy and breastfeeding, we combined PPI and qualitative research, with some overlap. Mother and baby groups from two geographically separate disadvantaged areas, with diverse experiences of the smoking and breastfeeding, but no training or previous involvement in research, were recruited as PPI research grant co-applicants. An iterative partnership approach facilitated involvement in research conduct and design across all project phases. Group PPI members were also invited to contribute to more formal qualitative data collection, as and when indicated by the research questions, and emerging analysis. Results: We engaged with ‘harder-to-reach’ women in mother and baby group settings, rather than in academic or home environments. These settings were relaxed and informal, which facilitated rapport-building, disclosures of unexpected information and maintained trust. 21 women participated in standard PPI activities: feedback on study protocols and documents; piloting questionnaires and interview schedules. PPI members voiced some different perspectives from those captured within the qualitative dataset. 19 participated in focused qualitative research. Novel aspects were audio recorded PPI discussions, which contributed qualitative data; first, to interpret systematic review findings and construct intervention vignettes for use in the qualitative research; second, to assist with recruitment to improve sample diversity in the formal qualitative dataset; and third, to translate theory and findings presented in a researcher generated logic model into a lay tool. This had face validity for potential trial participants and used the metaphor of a ladder. Conclusions: Combining and overlapping PPI and qualitative research added ‘harder-to-reach’ contributions, sample diversity, trust and engagement in creative approaches beyond what could be achieved through PPI or qualitative research alone. (350/350

Concomitant CIS on TURBT does not impact oncological outcomes in patients treated with neoadjuvant or induction chemotherapy followed by radical cystectomy

© Springer-Verlag GmbH Germany, part of Springer Nature 2018Background: Cisplatin-based neoadjuvant chemotherapy (NAC) for muscle invasive bladder cancer improves all-cause and cancer specific survival. We aimed to evaluate whether the detection of carcinoma in situ (CIS) at the time of initial transurethral resection of bladder tumor (TURBT) has an oncological impact on the response to NAC prior to radical cystectomy. Patients and methods: Patients were identified retrospectively from 19 centers who received at least three cycles of NAC or induction chemotherapy for cT2-T4aN0-3M0 urothelial carcinoma of the bladder followed by radical cystectomy between 2000 and 2013. The primary and secondary outcomes were pathological response and overall survival, respectively. Multivariable analysis was performed to determine the independent predictive value of CIS on these outcomes. Results: Of 1213 patients included in the analysis, 21.8% had concomitant CIS. Baseline clinical and pathologic characteristics of the ‘CIS’ versus ‘no-CIS’ groups were similar. The pathological response did not differ between the two arms when response was defined as pT0N0 (17.9% with CIS vs 21.9% without CIS; p = 0.16) which may indicate that patients with CIS may be less sensitive to NAC or ≤ pT1N0 (42.8% with CIS vs 37.8% without CIS; p = 0.15). On Cox regression model for overall survival for the cN0 cohort, the presence of CIS was not associated with survival (HR 0.86 (95% CI 0.63–1.18; p = 0.35). The presence of LVI (HR 1.41, 95% CI 1.01–1.96; p = 0.04), hydronephrosis (HR 1.63, 95% CI 1.23–2.16; p = 0.001) and use of chemotherapy other than ddMVAC (HR 0.57, 95% CI 0.34–0.94; p = 0.03) were associated with shorter overall survival. For the whole cohort, the presence of CIS was also not associated with survival (HR 1.05 (95% CI 0.82–1.35; p = 0.70). Conclusion: In this multicenter, real-world cohort, CIS status at TURBT did not affect pathologic response to neoadjuvant or induction chemotherapy. This study is limited by its retrospective nature as well as variability in chemotherapy regimens and surveillance regimens.Peer reviewedFinal Accepted Versio

The incidence of unpleasant dreams after sub-anaesthetic ketamine

Ketamine is an N-methyl-D-aspartate (NMDA)receptor antagonist with psychotogenic effects and for whichthere are diverse reports of whether pleasant or unpleasantdreams result during anaesthesia, post-operatively or aftersub-anaesthetic use. The aim was to assess in healthy volunteers the incidence ofunpleasant dreams over the three nights after receiving asub-anaesthetic dose of ketamine, in comparison to placebo,and with retrospective home nightmare frequency as acovariate.Thirty healthy volunteers completed questionnairesabout retrospective home dream recall and were then giveneither ketamine or placebo. Ketamine resulted in significantly more meandream unpleasantness relative to placebo and caused athreefold increase in the odds ratio for the incidence of anunpleasant dream. The number of dreams reported over thethree nights did not differ between the groups. Theincidence of unpleasant dreams after ketamine use waspredicted by retrospectively assessed nightmare frequencyat home.Ketamine causes unpleasant dreams over thethree post-administration nights. This may be evidence of aresidual psychotogenic effect that is not found on standardself-report symptomatology measures or a result of disturbedsleep electrophysiology. The results have theoretical implications for the relationship between nightmares and schizotypy