Let’s celebrate recovery. Inclusive Cities working together to support social cohesion

Recovery from illicit drug and alcohol use takes place over time and is characterised by a dynamic interaction between internal and external components. An integral part of all recovery journeys is effective community reintegration. After all, recovery is not mainly an issue of personal motivation rather it is about acceptance by family, by friends and by a range of organisations and professionals across the community. Therefore to support pathways to recovery, structural and contextual endeavours are needed to supplement individually-oriented interventions and programmes. One way to do this, is by introducing Inclusive Cities. An Inclusive City promotes participation, inclusion, full and equal citizenship to all her citizens, including those in recovery, based on the idea of community capital. The aim of building recovery capital at a community level through connections and 'linking social capital' to challenge stigmatisation and exclusion, is seen as central to this idea. Inclusive Cities is an initiative to support the creation of Recovery-Oriented Systems of Care at a city level, that starts with but extends beyond substance using populations. This paper describes (and gives examples of) how it is possible to use recovery as a starting point for generating social inclusion, challenging the marginalisation of other excluded populations as well by building community connections

Global parameter search reveals design principles of the mammalian circadian clock

Background: Virtually all living organisms have evolved a circadian (~24 hour) clock that controls physiological and behavioural processes with exquisite precision throughout the day/night cycle. The suprachiasmatic nucleus (SCN), which generates these ~24 h rhythms in mammals, consists of several thousand neurons. Each neuron contains a gene-regulatory network generating molecular oscillations, and the individual neuron oscillations are synchronised by intercellular coupling, presumably via neurotransmitters. Although this basic mechanism is currently accepted and has been recapitulated in mathematical models, several fundamental questions about the design principles of the SCN remain little understood. For example, a remarkable property of the SCN is that the phase of the SCN rhythm resets rapidly after a 'jet lag' type experiment, i.e. when the light/ dark (LD) cycle is abruptly advanced or delayed by several hours. Results: Here, we describe an extensive parameter optimization of a previously constructed simplified model of the SCN in order to further understand its design principles. By examining the top 50 solutions from the parameter optimization, we show that the neurotransmitters' role in generating the molecular circadian rhythms is extremely important. In addition, we show that when a neurotransmitter drives the rhythm of a system of coupled damped oscillators, it exhibits very robust synchronization and is much more easily entrained to light/dark cycles. We were also able to recreate in our simulations the fast rhythm resetting seen after a 'jet lag' type experiment. Conclusion: Our work shows that a careful exploration of parameter space for even an extremely simplified model of the mammalian clock can reveal unexpected behaviours and non-trivial predictions. Our results suggest that the neurotransmitter feedback loop plays a crucial role in the robustness and phase resetting properties of the mammalian clock, even at the single neuron level

A weak characterization of slow variables in stochastic dynamical systems

We present a novel characterization of slow variables for continuous Markov processes that provably preserve the slow timescales. These slow variables are known as reaction coordinates in molecular dynamical applications, where they play a key role in system analysis and coarse graining. The defining characteristics of these slow variables is that they parametrize a so-called transition manifold, a low-dimensional manifold in a certain density function space that emerges with progressive equilibration of the system's fast variables. The existence of said manifold was previously predicted for certain classes of metastable and slow-fast systems. However, in the original work, the existence of the manifold hinges on the pointwise convergence of the system's transition density functions towards it. We show in this work that a convergence in average with respect to the system's stationary measure is sufficient to yield reaction coordinates with the same key qualities. This allows one to accurately predict the timescale preservation in systems where the old theory is not applicable or would give overly pessimistic results. Moreover, the new characterization is still constructive, in that it allows for the algorithmic identification of a good slow variable. The improved characterization, the error prediction and the variable construction are demonstrated by a small metastable system

Public perceptions of diabetes, healthy living and conversational agents in Singapore: a needs assessment

Background: The incidence of chronic diseases such as type 2 diabetes is on the rise in countries worldwide, including Singapore. Health professional-delivered healthy lifestyle interventions have been shown to prevent type 2 diabetes. Yet ongoing personalised guidance from health professionals is not feasible or affordable at the population level. Novel digital interventions delivered using mobile technology such as conversational agents are a potential alternative for delivery of healthy lifestyle change behavioural interventions to the public. Objective: We explored Singaporeans’ perceptions on and experience of healthy living, diabetes and mobile health interventions (apps and conversational agents). This survey was done to help inform the design and development of a conversational agent focusing on healthy lifestyle change. Methods: This qualitative study was conducted over Aug and Sept 2019. 20 participants were recruited from relevant healthy living Facebook pages and groups. Semi-structured interviews were conducted in person or over the telephone using an interview guide. Interviews were transcribed and analysed in parallel by two researchers using Burnard’s method, a structured approach for thematic content analysis. Results: The collected data was organised into four main themes: (1) use of conversational agents, (2) ubiquity of smartphone applications, (3) understanding of diabetes and (4) barriers and facilitators to a healthy living in Singapore. Most participants used health-related mobile applications as well as conversational agents unrelated to healthcare. They provided diverse suggestions for future conversational agent-delivered interventions. Participants also highlighted several knowledge gaps in relation to diabetes and healthy living. In terms of barriers to healthy living, frequent dining out, high stress levels, lack of work-life balance and dearth of free time to engage in physical activity were mentioned. In contrast, discipline, pre-planning and sticking to a routine were important for enabling a healthy lifestyle. Conclusions: Participants in our study commonly used mobile health interventions and provided important insights into their knowledge gaps and needs in relation to healthy lifestyle behaviour change. Future digital interventions like conversational agents focusing on healthy lifestyle and diabetes prevention should aim to address the barriers highlighted in our study and motivate individuals to adopt habits for healthy living

Strategies to facilitate integrated care for people with alcohol and other drug problems: a systematic review

Background: There is a growing body of research highlighting the potential benefits of integrated care as a way of addressing the needs of people with alcohol and other drug (AOD) problems, given the broad range of other issues clients often experience. However, there has been little academic attention on the strategies that treatment systems, agencies and clinicians could implement to facilitate integrated care. Methods: We synthesised the existing evidence on strategies to improve integrated care in an AOD treatment context by conducting a systematic review of the literature. We searched major academic databases for peer-reviewed articles that evaluated strategies that contribute to integrated care in an AOD context between 1990 and 2014. Over 2600 articles were identified, of which 14 met the study inclusion criteria of reporting on an empirical study to evaluate the implementation of integrated care strategies. The types of strategies utilised in included articles were then synthesised. Results: We identified a number of interconnected strategies at the funding, organisational, service delivery and clinical levels. Ensuring that integrated care is included within service specifications of commissioning bodies and is adequately funded was found to be critical in effective integration. Cultivating positive inter-agency relationships underpinned and enabled the implementation of most strategies identified. Staff training in identifying and responding to needs beyond clinicians' primary area of expertise was considered important at a service level. However, some studies highlight the need to move beyond discrete training events and towards longer term coaching-type activities focussed on implementation and capacity building. Sharing of client information (subject to informed consent) was critical for most integrated care strategies. Case-management was found to be a particularly good approach to responding to the needs of clients with multiple and complex needs. At the clinical level, screening in areas beyond a clinician's primary area of practice was a common strategy for facilitating referral and integrated care, as was joint care planning. Conclusion: Despite considerable limitations and gaps in the literature in terms of the evaluation of integrated care strategies, particularly between AOD services, our review highlights several strategies that could be useful at multiple levels. Given the interconnectedness of integrated care strategies identified, implementation of multi-level strategies rather than single strategies is likely to be preferable

Discrete Kinetic Models from Funneled Energy Landscape Simulations

A general method for facilitating the interpretation of computer simulations of protein folding with minimally frustrated energy landscapes is detailed and applied to a designed ankyrin repeat protein (4ANK). In the method, groups of residues are assigned to foldons and these foldons are used to map the conformational space of the protein onto a set of discrete macrobasins. The free energies of the individual macrobasins are then calculated, informing practical kinetic analysis. Two simple assumptions about the universality of the rate for downhill transitions between macrobasins and the natural local connectivity between macrobasins lead to a scheme for predicting overall folding and unfolding rates, generating chevron plots under varying thermodynamic conditions, and inferring dominant kinetic folding pathways. To illustrate the approach, free energies of macrobasins were calculated from biased simulations of a non-additive structure-based model using two structurally motivated foldon definitions at the full and half ankyrin repeat resolutions. The calculated chevrons have features consistent with those measured in stopped flow chemical denaturation experiments. The dominant inferred folding pathway has an “inside-out”, nucleation-propagation like character

mRNA concentrations of MIF in subcutaneous abdominal adipose cells are associated with adipocyte size and insulin action

Objective To determine whether the mRNA concentrations of inflammation response genes in isolated adipocytes and in cultured preadipocytes are related to adipocyte size and in vivo insulin action in obese individuals. Design Cross-sectional inpatient study. Subjects Obese Pima Indians with normal glucose tolerance. Measurements Adipocyte diameter (by microscope technique; n=29), expression of candidate genes (by quantitative real-time PCR) in freshly isolated adipocytes (monocyte chemoattractant protein [MCP] 1 and MCP2, macrophage inflammatory protein [MIP] 1α, MIP1β and MIP2, macrophage migration inhibitory factor [MIF], tumor necrosis factor alpha, interleukin [IL] 6 and IL8; n=22) and cultured preadipocytes (MCP1, MIP1α, MIF, IL6 and matrix metalloproteinase 2; n=33) from subcutaneous abdominal adipose tissue (by aspiration biopsy, n=34), body fat by dual-energy X-ray absorptiometry, glucose tolerance by 75-gram oral glucose tolerance test, and insulin action by euglycemic-hyperinsulinemic clamp (insulin infusion rate 40 mU/m2.min)(all n=34). Results MIF was the only gene whose expression in both freshly isolated adipocytes and cultured preadipocytes was positively associated with adipocytes diameter and negatively associated with peripheral and hepatic insulin action (all P<0.05). In multivariate analysis, the association between adipocyte MIF mRNA concentrations and adipocytes diameter was independent of percent body fat (P=0.03), whereas adipocyte MIF mRNA concentrations but not adipocytes diameter independently predicted peripheral insulin action. The mRNA expression concentrations of MIF gene in adipocytes were not associated with plasma concentrations of MIF, but were negatively associated with plasma adiponectin concentrations (P=0.004). In multivariate analysis, adipocyte MIF RNA concentrations (P=0.03) but not plasma adiponectin concentrations (P=0.4) remained a significant predictor of insulin action. Conclusions Increased expression of MIF gene in adipose cells may be an important link between obesity characterized by enlarged adipocytes and insulin resistance in normal glucose tolerant people

The Concept of Transparency in International Relations: towards a critical approach

Transparency is an important concept in International Relations. The possibility of realizing transparency in practice operates as a central analytical axis defining distinct positions on core theoretical problems within the field, from the security dilemma to the function of international institutions and beyond. As a political practice the pursuit of transparent governance is a dominant feature of global politics, promoted by a wide range of actors across a vast range of issue areas, from nuclear proliferation to Internet governance to the politics of foreign aid. Yet, despite its importance, precisely what transparency means or how the concept is understood is frequently ill-defined by academics and policy-makers alike. As a result, the epistemological and ontological underpinnings of approaches to transparency in IR often sit in tension with their wider theoretical commitments. This article will examine the three primary understandings of transparency used in IR in order to unpack these commitments. It finds that while transparency is often explicitly conceptualized as a property of information, particularly within rationalist scholarship, this understanding rests upon an unarticulated set of sociological assumptions. This analysis suggests that conceptualizing ‘transparency-as-information’ without a wider sociology of knowledge production is highly problematic, potentially obscuring our ability to recognize transparent practices in global governance. Understanding transparency as dialogue, as a social practice rooted in shared cognitive capacities and epistemic frameworks, provides a firmer analytical ground from which to examine transparency in International Relations

Hemispheric Asymmetries in Speech Perception: Sense, Nonsense and Modulations

Background: The well-established left hemisphere specialisation for language processing has long been claimed to be based on a low-level auditory specialization for specific acoustic features in speech, particularly regarding 'rapid temporal processing'.Methodology: A novel analysis/synthesis technique was used to construct a variety of sounds based on simple sentences which could be manipulated in spectro-temporal complexity, and whether they were intelligible or not. All sounds consisted of two noise-excited spectral prominences (based on the lower two formants in the original speech) which could be static or varying in frequency and/or amplitude independently. Dynamically varying both acoustic features based on the same sentence led to intelligible speech but when either or both acoustic features were static, the stimuli were not intelligible. Using the frequency dynamics from one sentence with the amplitude dynamics of another led to unintelligible sounds of comparable spectro-temporal complexity to the intelligible ones. Positron emission tomography (PET) was used to compare which brain regions were active when participants listened to the different sounds.Conclusions: Neural activity to spectral and amplitude modulations sufficient to support speech intelligibility (without actually being intelligible) was seen bilaterally, with a right temporal lobe dominance. A left dominant response was seen only to intelligible sounds. It thus appears that the left hemisphere specialisation for speech is based on the linguistic properties of utterances, not on particular acoustic features

Search for rare quark-annihilation decays, B --> Ds(*) Phi

We report on searches for B- --> Ds- Phi and B- --> Ds*- Phi. In the context of the Standard Model, these decays are expected to be highly suppressed since they proceed through annihilation of the b and u-bar quarks in the B- meson. Our results are based on 234 million Upsilon(4S) --> B Bbar decays collected with the BABAR detector at SLAC. We find no evidence for these decays, and we set Bayesian 90% confidence level upper limits on the branching fractions BF(B- --> Ds- Phi) Ds*- Phi)<1.2x10^(-5). These results are consistent with Standard Model expectations.Comment: 8 pages, 3 postscript figues, submitted to Phys. Rev. D (Rapid Communications