Probability of noise- and rate-induced tipping

We propose an approximation for the probability of tipping when the speed of parameter change and additive white noise interact to cause tipping. Our approximation is valid for small to moderate drift speeds and helps to estimate the probability of false positives and false negatives in early-warning indicators in the case of rate- and noise-induced tipping. We illustrate our approximation on a prototypical model for rate-induced tipping with additive noise using Monte-Carlo simulations. The formula can be extended to close encounters of rate-induced tipping and is otherwise applicable to other forms of tipping. We also provide an asymptotic formula for the critical ramp speed of the parameter in the absence of noise for a general class of systems undergoing rate-induced tipping.Comment: 14 pages, 9 figures https://link.aps.org/doi/10.1103/PhysRevE.95.05220

Inverse-square law between time and amplitude for crossing tipping thresholds

A classical scenario for tipping is that a dynamical system experiences a slow parameter drift across a fold tipping point, caused by a run-away positive feedback loop. We study what happens if one turns around after one has crossed the threshold. We derive a simple criterion that relates how far the parameter exceeds the tipping threshold maximally and how long the parameter stays above the threshold to avoid tipping in an inverse-square law to observable properties of the dynamical system near the fold. For the case when the dynamical system is subject to stochastic forcing we give an approximation to the probability of tipping if a parameter changing in time reverses} near the tipping point. The derived approximations are valid if the parameter change in time is sufficiently slow. We demonstrate for a higher dimensional system, a model for the Indian Summer Monsoon, how numerically observed escape from the equilibrium converge to our asymptotic expressions. The inverse-square law between peak of the parameter forcing and the time the parameter spends above a given threshold is also visible in the level curves of equal probability when the system is subject to random disturbances.Comment: 20 pages, 6 figures, 1 table, Supplementary Material found at https://figshare.com/articles/Monsoon_supplementary_material_final_pdf/760582

Award for Best Oral Presentation by a First Timer - Hunting zebra: retrieving rare disease guidelines

The EAHIL 2014 conference provided the opportunity to present a piece of work carried out by a team of informationprofessionals for RARE-Bestpractices (RBP), an international project to promote exchange of information andknowledge in rare disease. The authors work for Healthcare Improvement Scotland (HIS), a publicly fundedorganisation which uses evidence, scrutiny and improvement science to facilitate the delivery of safe, effective andpatient-centred healthcare. HIS is one of fifteen European partners contributing to RBP with our team providing thecore information professional support for the project. Work to develop a rare disease guideline search protocol waspresented in order to raise awareness of RARE-Bestpractices, and to demonstrate the engagement of informationprofessionals in multidisciplinary research projects

A case of bowel entrapment after penetrating injury of the pelvis: don't forget the omentumplasty

Bowel entrapment within a pelvic injury is rare and difficult to diagnose. Usually, it is diagnosed late because of concomitant abdominal injuries. It may present itself as an acute intestinal obstruction or, more commonly, as a prolonged or intermittent ileus. Therefore, one should be aware of this late complication and primarily take measures for avoiding bowel entrapment. This report describes an unusual case of bowel entrapment within a pelvic fracture after a penetrating injury, and discusses options for preventing such a complication

Improving the retrieval and dissemination of rare disease guidelines and research recommendations: a RARE-Bestpractices initiative

No abstract available

Recent developments in targeting access to high cost medicines in Australia

BACKGROUND: In Australia, the Pharmaceutical Benefits Scheme (PBS) has developed a set of arrangements to control access to high-cost medicines to ensure their use is cost-effective. These medicines include the tumour necrosis factor-alpha inhibitors (TNFIs) for the treatment of rheumatoid arthritis. The aim of this first phase of a qualitative study was to explore basic views on the restricted access to TNFIs in order to confirm where further investigation should take place in the next phase. METHODS: Semi-structured interviews were conducted in 2004 with a member of the four relevant stakeholder groups. Participants were asked their opinions about features of the establishment, process and effects of the system of restricted access to TNFIs. Views on the collaboration between stakeholder groups in the decision-making process were also collected. RESULTS: The principle of 'controlled access' to TNFIs was supported in general. There were concerns regarding some of the specific eligibility criteria. Wider and more transparent stakeholder consultation was judged desirable. Some flexibility around prescribing of TNFIs by physicians, and regular review of the arrangements were proposed. These themes will inform the next phase of the study. CONCLUSION: This first phase highlighted a range of issues associated with the PBS arrangements restricting access to TNFIs. Timely review and report of issues and concerns associated with such policy developments that arose in practice are essential. There is a need for a more comprehensive exploration across a wide range of stakeholders with different perspectives that will in turn be helpful in guiding policy and practice around national arrangements to manage access to high-cost medicines

Directing mesenchymal stem cells to bone to augment bone formation and increase bone mass.

Aging reduces the number of mesenchymal stem cells (MSCs) that can differentiate into osteoblasts in the bone marrow, which leads to impairment of osteogenesis. However, if MSCs could be directed toward osteogenic differentiation, they could be a viable therapeutic option for bone regeneration. We have developed a method to direct MSCs to the bone surface by attaching a synthetic high-affinity and specific peptidomimetic ligand (LLP2A) against integrin α4β1 on the MSC surface to a bisphosphonate (alendronate, Ale) that has a high affinity for bone. LLP2A-Ale induced MSC migration and osteogenic differentiation in vitro. A single intravenous injection of LLP2A-Ale increased trabecular bone formation and bone mass in both xenotransplantation studies and in immunocompetent mice. Additionally, LLP2A-Ale prevented trabecular bone loss after peak bone acquisition was achieved or as a result of estrogen deficiency. These results provide proof of principle that LLP2A-Ale can direct MSCs to the bone to form new bone and increase bone strength

Community perceptions of mental health needs: a qualitative study in the Solomon Islands

<p>Abstract</p> <p>Background</p> <p>Psychosocial and mental health needs in the aftermath of conflict and disaster have attracted substantial attention. In the Solomon Islands, the conceptualisation of mental health, for several decades regarded by policy makers as primarily a health issue, has broadened and been incorporated into the national development and social policy agendas, reflecting recognition of the impact of conflict and rapid social change on the psychosocial wellbeing of the community as a whole. We sought to understand how mental health and psychosocial wellbeing were seen at the community level, the extent to which these issues were identified as being associated with periods of 'tension', violence and instability, and the availability of traditional approaches and Ministry of Health services to address these problems.</p> <p>Methods</p> <p>This article reports the findings of qualitative research conducted in a rural district on the island of Guadalcanal in the Solomon Islands. Key informant interviews were conducted with community leaders, and focus groups were held with women, men and young people. Wellbeing was defined broadly.</p> <p>Results</p> <p>Problems of common concern included excessive alcohol and marijuana use, interpersonal violence and abuse, teenage pregnancy, and lack of respect and cooperation. Troubled individuals and their families sought help for mental problems from various sources including chiefs, church leaders and traditional healers and, less often, trauma support workers, health clinic staff and police. Substance-related problems presented special challenges, as there were no traditional solutions at the individual or community level. Severe mental illness was also a challenge, with few aware that a community mental health service existed. Contrary to our expectations, conflict-related trauma was not identified as a major problem by the community who were more concerned about the economic and social sequelae of the conflict.</p> <p>Conclusion</p> <p>Communities identify and are responding to a wide range of mental health challenges; the health system generally can do more to learn about how this is being done, and build more comprehensive services and policy on this foundation. The findings underscore the need to promote awareness of those services which are available, to extend mental health care beyond urban centres to rural villages where the majority of the population live, and to promote community input to policy so as to ensure that it 'fits' the context.</p

Genetic and biochemical characterization of an acquired subgroup B3 metallo-β-lactamase gene, blaAIM-1, and its unique genetic context in Pseudomonas aeruginosa from Australia

Three clinical Pseudomonas aeruginosa isolates (WCH2677, WCH2813, and WCH2837) isolated from the Women's and Children's Hospital, Adelaide, Australia, produced a metallo-β-lactamase (MBL)-positive Etest result. All isolates were PCR negative for known MBL genes. A gene bank was created, and an MBL gene, designated bla, was cloned and fully characterized. The encoded enzyme, AIM-1, is a group B3 MBL that has the highest level of identity to THIN-B and L1. It is chromosomal and flanked by two copies (one intact and one truncated) of an ISCR element, ISCR15. Southern hybridization studies indicated the movement of both ISCR15 and bla within the three different clinical isolates. AIM-1 hydrolyzes most β-lactams, with the exception of aztreonam and, to a lesser extent, ceftazidime; however, it possesses significantly higher k values for cefepime and carbapenems than most other MBLs. AIM-1 was the first mobile group B3 enzyme detected and signals further problems for already beleaguered antimicrobial regimes to treat serious P. aeruginosa and other Gram-negative infections