Phase-Induced (In)-Stability in Coupled Parametric Oscillators

We report results on a model of two coupled oscillators that undergo periodic parametric modulations with a phase difference $\theta$. Being to a large extent analytically solvable, the model reveals a rich $\theta$ dependence of the regions of parametric resonance. In particular, the intuitive notion that anti-phase modulations are less prone to parametric resonance is confirmed for sufficiently large coupling and damping. We also compare our results to a recently reported mean field model of collective parametric instability, showing that the two-oscillator model can capture much of the qualitative behavior of the infinite system.Comment: 19 pages, 8 figures; a version with better quality figures can be found in http://hypatia.ucsd.edu/~mauro/English/publications.htm

The local economic development processes in low-income countries: the case of the metropolis of Chegutu in Zimbabwe

Local authorities are widely regarded as catalysts accelerating localised processes of economic development in industrialised countries but in low-income countries they are perceived as dysfunctional, inefficient and ineffective in meeting and addressing societal demands. This abstract view is however, not grounded in empirical research. As such, utilising the case of the metropolis of Chegutu a survey was designed to empirically explicate the economic processes militating its economic development. The findings are useful to policy-makers, local government authorities and management scholars. The study's unique contribution lies in its examination of the processes of local economic development in a low-income country

How people with dementia and their families decide about moving to a care home and support their needs: development of a decision aid, a qualitative study

yesBackground: People with dementia and their relatives find decisions about the person with dementia living in a care home difficult. Methods: We interviewed 20 people with dementia or family carers around the time of this decision in order to design a decision-aid. Results: Decision-makers balanced the competing priorities of remaining somewhere familiar, family’s wish they remain at home, reduction of risk and effects on carer’s and person with dementia’s physical health. The person with dementia frequently resented their lack of autonomy as decisions about care home moves were made after insight and judgment were impaired. Family consultation usually helped carers but sometimes exacerbated tensions. Direct professional support was appreciated where it was available. There is a need for healthcare professionals to facilitate these conversations around decision-making and to include more than signposting to other organisations. Conclusions: There is a need for a healthcare professional facilitated decision-aid. This should detail what might change for the person with dementia and their carer, possible resources and alternatives and assist in facilitating discussion with the wider family; further research will develop and test a tool to facilitate decision making about place of care needs

The addition of a goal-based motivational interview to standardised treatment as usual to reduce dropouts in a service for patients with personality disorder: a feasibility study

<p>Abstract</p> <p>Background</p> <p>Rates of non-completion of treatments for personality disorder are high and there are indications that those who do not complete treatment have worse outcomes than those who do. Improving both cost-efficiency and client welfare require attention to engaging people with personality disorder in treatment. A motivational interview, based on the Personal Concerns Inventory, may have the ability to enhance engagement and retention in therapy. Here, we report the protocol for a feasibility study for a randomised controlled trial (RCT).</p> <p>Methods</p> <p>All referrals accepted to the psychological service of Nottinghamshire Healthcare NHS Trust's outpatient service for people with personality disorder are eligible for inclusion. Consenting participants are randomised to receive the Personal Concerns Inventory interview plus treatment as usual or treatment as usual only. We aim to recruit 100 participants over 11/2 years. A randomised controlled trial will be considered feasible if <abbrgrp><abbr bid="B1">1</abbr></abbrgrp> the recruitment rate to the project is 54% of all referrals (95% CI 54-64), <abbrgrp><abbr bid="B2">2</abbr></abbrgrp> 80% of clients find the intervention acceptable in terms of its practicability and usefulness (95% CI 80-91), and <abbrgrp><abbr bid="B3">3</abbr></abbrgrp> 80% of therapists report finding the intervention helpful (95% CI 80-100). In a full-scale randomised controlled trial, the primary outcome measure will be completion of treatment i.e., entry into and completion of ≥ 75% of sessions offered. Therefore, information will be collected on recruitment rates, attendance at therapy sessions, and completion of treatment. The feasibility of examining the processes of engagement will be tested by assessing the value, coherence, and attainability of goals pre-treatment, and engagement in treatment. The costs associated with the intervention will be calculated, and the feasibility of calculating the cost-benefits of the intervention will be tested. The views of clients and therapists on the intervention, collected using semi-structured interviews, will be analysed using thematic analysis.</p> <p>Discussion</p> <p>The Personal Concerns Interview as a preparation for treatment of people with personality has the potential to maximise treatment uptake, reduce unfilled places in treatment programmes, and prevent group treatments faltering through non-attendance. Most importantly, it has the potential to improve patient outcomes, helping them to function better and reduce hospitalisation.</p> <p>Trial Registration</p> <p>ClinicalTrials.Gov.UK Identifier - NCT01132976</p

Modeling Disease Vector Occurrence when Detection Is Imperfect: Infestation of Amazonian Palm Trees by Triatomine Bugs at Three Spatial Scales

Blood-sucking bugs of the genus Rhodnius are major vectors of Chagas disease. Control and surveillance of Chagas disease transmission critically depend on ascertaining whether households and nearby ecotopes (such as palm trees) are infested by these vectors. However, no bug detection technique works perfectly. Because more sensitive methods are more costly, vector searches face a trade-off between technical prowess and sample size. We compromise by using relatively inexpensive sampling techniques that can be applied multiple times to a large number of palms. With these replicated results, we estimate the probability of failing to detect bugs in a palm that is actually infested. We incorporate this information into our analyses to derive an unbiased estimate of palm infestation, and find it to be about 50% – twice the observed proportion of infested palms. We are then able to model the effects of regional, landscape, and local environmental variables on palm infestation. Individual palm attributes contribute overwhelmingly more than landscape or regional covariates to explaining infestation, suggesting that palm tree management can help mitigate risk locally. Our results illustrate how explicitly accounting for vector, pathogen, or host detection failures can substantially improve epidemiological parameter estimation when perfect detection techniques are unavailable

Collateral fattening in body composition autoregulation: its determinants and significance for obesity predisposition

Collateral fattening refers to the process whereby excess fat is deposited as a result of the body’s attempt to counter a deficit in lean mass through overeating. Its demonstration and significance to weight regulation and obesity can be traced to work on energy budget strategies in growing mammals and birds, and to men recovering from experimental starvation. The cardinal features of collateral fattening rests upon (i) the existence of a feedback system between lean tissue and appetite control, with lean tissue deficit driving hyperphagia, and (ii) upon the occurrence of a temporal desynchronization in the recovery of body composition, with complete recovery of fat mass preceeding that of lean mass. Under these conditions, persistent hyperphagia driven by the need to complete the recovery of lean tissue will result in the excess fat deposition (hence collateral fattening) and fat overshooting. After reviewing the main lines of evidence for the phenomenon of collateral fattening in body composition autoregulation, this article discusses the causes and determinants of the desynchronization in fat and lean tissue recovery leading to collateral fattening and fat overshooting, and points to their significance in the mechanisms by which dieting, developmental programming and sedentariness predispose to obesity

Identifying microRNA/mRNA dysregulations in ovarian cancer

Abstract Background MicroRNAs are a class of noncoding RNA molecules that co-regulate the expression of multiple genes via mRNA transcript degradation or translation inhibition. Since they often target entire pathways, they may be better drug targets than genes or proteins. MicroRNAs are known to be dysregulated in many tumours and associated with aggressive or poor prognosis phenotypes. Since they regulate mRNA in a tissue specific manner, their functional mRNA targets are poorly understood. In previous work, we developed a method to identify direct mRNA targets of microRNA using patient matched microRNA/mRNA expression data using an anti-correlation signature. This method, applied to clear cell Renal Cell Carcinoma (ccRCC), revealed many new regulatory pathways compromised in ccRCC. In the present paper, we apply this method to identify dysregulated microRNA/mRNA mechanisms in ovarian cancer using data from The Cancer Genome Atlas (TCGA). Methods TCGA Microarray data was normalized and samples whose class labels (tumour or normal) were ambiguous with respect to consensus ensemble K-Means clustering were removed. Significantly anti-correlated and correlated genes/microRNA differentially expressed between tumour and normal samples were identified. TargetScan was used to identify gene targets of microRNA. Results We identified novel microRNA/mRNA mechanisms in ovarian cancer. For example, the expression level of RAD51AP1 was found to be strongly anti-correlated with the expression of hsa-miR-140-3p, which was significantly down-regulated in the tumour samples. The anti-correlation signature was present separately in the tumour and normal samples, suggesting a direct causal dysregulation of RAD51AP1 by hsa-miR-140-3p in the ovary. Other pairs of potentially biological relevance include: hsa-miR-145/E2F3, hsa-miR-139-5p/TOP2A, and hsa-miR-133a/GCLC. We also identified sets of positively correlated microRNA/mRNA pairs that are most likely result from indirect regulatory mechanisms. Conclusions Our findings identify novel microRNA/mRNA relationships that can be verified experimentally. We identify both generic microRNA/mRNA regulation mechanisms in the ovary as well as specific microRNA/mRNA controls which are turned on or off in ovarian tumours. Our results suggest that the disease process uses specific mechanisms which may be significant for their utility as early detection biomarkers or in the development of microRNA therapies in treating ovarian cancers. The positively correlated microRNA/mRNA pairs suggest the existence of novel regulatory mechanisms that proceed via intermediate states (indirect regulation) in ovarian tumorigenesis.</p

Mutation analysis of the NSD1 gene in patients with autism spectrum disorders and macrocephaly

<p>Abstract</p> <p>Background</p> <p>Sotos syndrome is an overgrowth syndrome characterized by macrocephaly, advanced bone age, characteristic facial features, and learning disabilities, caused by mutations or deletions of the <it>NSD1 </it>gene, located at 5q35. Sotos syndrome has been described in a number of patients with autism spectrum disorders, suggesting that <it>NSD1 </it>could be involved in other cases of autism and macrocephaly.</p> <p>Methods</p> <p>We screened the <it>NSD1 </it>gene for mutations and deletions in 88 patients with autism spectrum disorders and macrocephaly (head circumference 2 standard deviations or more above the mean). Mutation analysis was performed by direct sequencing of all exons and flanking regions. Dosage analysis of <it>NSD1 </it>was carried out using multiplex ligation-dependent probe amplification.</p> <p>Results</p> <p>We identified three missense variants (R604L, S822C and E1499G) in one patient each, but none is within a functional domain. In addition, segregation analysis showed that all variants were inherited from healthy parents and in two cases were also present in unaffected siblings, indicating that they are probably nonpathogenic. No partial or whole gene deletions/duplications were observed.</p> <p>Conclusion</p> <p>Our findings suggest that Sotos syndrome is a rare cause of autism spectrum disorders and that screening for <it>NSD1 </it>mutations and deletions in patients with autism and macrocephaly is not warranted in the absence of other features of Sotos syndrome.</p

Addiction Treatment and Stable Housing among a Cohort of Injection Drug Users

Background: Unstable housing and homelessness is prevalent among injection drug users (IDU). We sought to examine whether accessing addiction treatment was associated with attaining stable housing in a prospective cohort of IDU in Vancouver, Canada. Methods: We used data collected via the Vancouver Injection Drug User Study (VIDUS) between December 2005 and April 2010. Attaining stable housing was defined as two consecutive ‘‘stable housing’ ’ designations (i.e., living in an apartment or house) during the follow-up period. We assessed exposure to addiction treatment in the interview prior to the attainment of stable housing among participants who were homeless or living in single room occupancy (SRO) hotels at baseline. Bivariate and multivariate associations between the baseline and time-updated characteristics and attaining stable housing were examined using Cox proportional hazard regression models. Principal Findings: Of the 992 IDU eligible for this analysis, 495 (49.9%) reported being homeless, 497 (50.1%) resided in SRO hotels, and 380 (38.3%) were enrolled in addiction treatment at the baseline interview. Only 211 (21.3%) attained stable housing during the follow-up period and of this group, 69 (32.7%) had addiction treatment exposure prior to achieving stable housing. Addiction treatment was inversely associated with attaining stable housing in a multivariate model (adjusted hazard ratio [AHR] = 0.71; 95 % CI: 0.52–0.96). Being in a partnered relationship was positively associated with the primary outcom