The Porphyromonas gingivalis hemagglutinins HagB and HagC are major mediators of adhesion and biofilm formation

Porphyromonas gingivalis is a bacterium associated with chronic periodontitis that possesses a family of genes encoding hemagglutinins required for heme acquisition. In this study we generated ΔhagB and ΔhagC mutants in strain W83 and demonstrate that both hagB and hagC are required for adherence to oral epithelial cells. Unexpectedly, a double ΔhagB/ΔhagC mutant had less severe adherence defects than either of the single mutants, but was found to exhibit increased expression of the gingipain-encoding genes rgpA and kgp, suggesting that a ΔhagB/ΔhagC mutant is only viable in populations of cells that exhibit increased expression of genes involved in heme acquisition. Disruption of hagB in the fimbriated strain ATCC33277 demonstrated that HagB is also required for stable attachment of fimbriated bacteria to oral epithelial cells. Mutants of hagC were also found to form defective single and multi-species biofilms that had reduced biomass relative to biofilms formed by the wild-type strain. This study highlights the hitherto unappreciated importance of these genes in oral colonization and biofilm formation

The Pariah Patient: The Lack of Funding for Mental Health Care

In all the furor over the provision of health care in the United States-especially over who will pay for the skyrocketing costs of medical treatment-one class of patient appears to have been overlooked: the mentally ill. This oversight is not new; Anglo-American society historically has viewed the mentally ill as outsiders. In England, for example, inmates at the infamous Bedlam hospital for the insane often were displayed for the amusement of the paying public.\u27 Society\u27s disdain of the mentally ill still exists and has led to public neglect of these unfortunates, especially in the provision of mental health care. Since the process of deinstitutionalization first began, the law has been involved intimately with mental illness. In the 1960s scholars criticized the intellectual foundations of psychiatry, and numerous law- suits sought to abolish involuntary commitment.\u27 These early critics primarily wanted to protect the right to refuse treatment; specific targets were the somatic treatments for major mental illnesses, particularly psychosurgery, electroconvulsive therapy, and psychoactive drugs. Some advocates for the mentally ill continue to fight for freedom from treatment, while others have adopted a more cautious approach. As with health care in general one of the most difficult mental health care questions facing American society in the 1990s is: Who will fund the rapidly increasing cost of care? This Note examines the role of the private sector in funding emergency and longer-term care for the mentally ill. Part II describes the magnitude of the mental health problem in the United States and documents the failure of public and private insurance programs to fund mental health care adequately. Part III examines indirect funding by primary health care providers and suggests that Congress expand existing federal law to require hospitals and physicians to provide emergency care to the mentally ill who present a danger to themselves or others. Part IV examines direct funding by private insurance, focusing on the continuing validity of mental illness benefits-limitation clauses under common and federal law. Part V concludes that any alternative system likely will perpetuate the inadequate level of mental health care currently provided, unless the stigma associated with mental illness can be overcome by special recognition of the seriousness and treatability of mental illness

Fast iterative solvers for geomechanics in a commercial FE code

There is a pressing need to improve the feasibility of three-dimensional finite element (FE) methods applied to many problems in civil engineering. This is particularly the case for static analyses in geotechnical engineering: ideally, models would be 3D, follow the actual geometry, use non-linear material formulations and allow simulation of construction sequences, and all of this with a reasonable degree of accuracy. One major obstacle to improvements in this regard is the difficulty in solving of the set of (linearised) algebraic equations which arises from a typical discretisation approach. Very large systems become cumbersome for direct techniques to solve economically. This paper describes the incorporation of iterative (rather than direct) solution techniques, developed through University research, into commercial FE software for geotechnics

Surface disinfection challenges for Candida auris: an in-vitro study

The emerging pathogenic multidrug-resistant yeast Candida auris is an important source of healthcare-associated infections and of growing global clinical concern. The ability of this organism to survive on surfaces and withstand environmental stressors creates a challenge for eradicating it from hospitals. A panel of C. auris clinical isolates was evaluated on different surface environments against the standard disinfectant sodium hypochlorite and high-level disinfectant peracetic acid. C. auris was shown to selectively tolerate clinically relevant concentrations of sodium hypochlorite and peracetic acid in a surface-dependent manner, which may explain its ability to successfully persist within the hospital environment

Landsat TM and ETM+ derived snowline altitudes in the Cordillera Huayhuash and Cordillera Raura, Peru, 1986–2005

The Cordilleras Huayhuash and Raura are remote glacierized ranges in the Andes Mountains of Peru. A robust assessment of modern glacier change is important for understanding how regional change affects Andean communities, and for placing paleo-glaciers in a context relative to modern glaciation and climate. Snowline altitudes (SLAs) derived from satellite imagery are used as a proxy for modern (1986–2005) local climate change in a key transition zone in the Andes. <br><br> Clear sky, dry season Landsat Thematic Mapper (TM) and Enhanced Thematic Mapper (ETM+) satellite images from 1986–2005 were used to identify snowline positions, and their altitude ranges were extracted from an Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER) digital elevation model (DEM). Based on satellite records from 31 glaciers, average snowline altitudes (SLAs), an approximation for the equilibrium line altitude (ELA), for the Cordillera Huayhuash (13 glaciers) and Cordillera Raura (18 glaciers) from 1986–2005 were 5051 m a.s.l. from 1986–2005 and 5006 m a.s.l. from 1986–2002, respectively. During the same time period, the Cordillera Huayhuash SLA experienced no significant change while the Cordillera Raura SLA rose significantly from 4947 m a.s.l. to 5044 m a.s.l

Effects of Disturbance and Conspecific Negative Density Dependence on Forest Composition and Diversity: A Simulation-Based Approach

Forests provide a wide range of services to humans and create critical habitat for countless species. Tree species composition and diversity, key attributes of forest health and identity, are influenced by both disturbance and conspecific negative density dependence (CNDD). These factors have been thoroughly researched in isolation, but much less is known about how they interact. We present results of a simulation model constructed to investigate the interactions of variable CNDD strengths and disturbance types. We found that while CNDD consistently increased diversity, the magnitude of this effect was heavily influenced by the disturbance regime. The difference between weak and strong CNDD was most pronounced with understory disturbance, and the greatest diversity overall was achieved when strong CNDD was paired with understory disturbance. Empirical studies of CNDD have yielded widely divergent results. Our study suggests a comprehensive understanding of forest ecosystems may require simultaneous consideration of both disturbance and CNDD

Functional outcomes following ileal pouch-anal anastomosis (IPAA) in older patients: a systematic review

Aim Ileal pouch-anal anastomosis (IPAA) is performed in ulcerative colitis or familial adenomatous polyposis with a view to restoration of GI continuity and prevention of permanent faecal diversion. Debate exists as to its safety in older patients. This review aims to assess functional outcomes and safety of restorative proctocolectomy (RPC) in older compared to younger patients. Methods Literature search was performed for age-stratified studies which assessed functional outcomes of IPAA. Twelve papers were included overall. Patients were categorized into ‘older’ and ‘younger’ groups. Analysis was split into three separate parts: 1. Age cut-off of 50 ± 5 years (with sensitivity analysis); 2. Age cut-off of 65 ± years; 3. Long-term outcomes (>10 years). Results With an age cut-off of 50 years (4327 versus 513 patients), complication rates were comparable with the exception of an increased rate of small-bowel obstruction in the younger patients (p = 0.034). At 1 year, 24-h stool frequency was significantly higher in the older patient group (p < 0.0001). Daytime (p < 0.0001) and night-time (p < 0.0001) incontinence rates were also significantly higher in older patients. Overall, function deteriorated with time across all ages; however, after 10 years, there was no significant difference in incontinence rates between age groups. Dehydration and electrolyte loss was a significant problem in patients over 65 (p < 0.0001). Despite differences in postoperative function, quality of life was comparable between groups; however, only a few studies reported quality of life data. Conclusion IPAA is safe in older patients, although treating clinicians should bear in mind the increased risk of dehydration. Postoperative function is worse in older patients, but seems to level out with time and does not appear to significantly impact on overall quality of life and patient satisfaction. Assessment for suitability for RPC should not be based on chronological age in isolation. It is imperative that the correct support is given to older patients with worsened postoperative function in order to maintain patient satisfaction and adequate quality of life

Data Portraits and Intermediary Topics: Encouraging Exploration of Politically Diverse Profiles

In micro-blogging platforms, people connect and interact with others. However, due to cognitive biases, they tend to interact with like-minded people and read agreeable information only. Many efforts to make people connect with those who think differently have not worked well. In this paper, we hypothesize, first, that previous approaches have not worked because they have been direct -- they have tried to explicitly connect people with those having opposing views on sensitive issues. Second, that neither recommendation or presentation of information by themselves are enough to encourage behavioral change. We propose a platform that mixes a recommender algorithm and a visualization-based user interface to explore recommendations. It recommends politically diverse profiles in terms of distance of latent topics, and displays those recommendations in a visual representation of each user's personal content. We performed an "in the wild" evaluation of this platform, and found that people explored more recommendations when using a biased algorithm instead of ours. In line with our hypothesis, we also found that the mixture of our recommender algorithm and our user interface, allowed politically interested users to exhibit an unbiased exploration of the recommended profiles. Finally, our results contribute insights in two aspects: first, which individual differences are important when designing platforms aimed at behavioral change; and second, which algorithms and user interfaces should be mixed to help users avoid cognitive mechanisms that lead to biased behavior.Comment: 12 pages, 7 figures. To be presented at ACM Intelligent User Interfaces 201

Hsp90 governs dispersion and drug resistance of fungal biofilms

Fungal biofilms are a major cause of human mortality and are recalcitrant to most treatments due to intrinsic drug resistance. These complex communities of multiple cell types form on indwelling medical devices and their eradication often requires surgical removal of infected devices. Here we implicate the molecular chaperone Hsp90 as a key regulator of biofilm dispersion and drug resistance. We previously established that in the leading human fungal pathogen, Candida albicans, Hsp90 enables the emergence and maintenance of drug resistance in planktonic conditions by stabilizing the protein phosphatase calcineurin and MAPK Mkc1. Hsp90 also regulates temperature-dependent C. albicans morphogenesis through repression of cAMP-PKA signalling. Here we demonstrate that genetic depletion of Hsp90 reduced C. albicans biofilm growth and maturation in vitro and impaired dispersal of biofilm cells. Further, compromising Hsp90 function in vitro abrogated resistance of C. albicans biofilms to the most widely deployed class of antifungal drugs, the azoles. Depletion of Hsp90 led to reduction of calcineurin and Mkc1 in planktonic but not biofilm conditions, suggesting that Hsp90 regulates drug resistance through different mechanisms in these distinct cellular states. Reduction of Hsp90 levels led to a marked decrease in matrix glucan levels, providing a compelling mechanism through which Hsp90 might regulate biofilm azole resistance. Impairment of Hsp90 function genetically or pharmacologically transformed fluconazole from ineffectual to highly effective in eradicating biofilms in a rat venous catheter infection model. Finally, inhibition of Hsp90 reduced resistance of biofilms of the most lethal mould, Aspergillus fumigatus, to the newest class of antifungals to reach the clinic, the echinocandins. Thus, we establish a novel mechanism regulating biofilm drug resistance and dispersion and that targeting Hsp90 provides a much-needed strategy for improving clinical outcome in the treatment of biofilm infections

Biofilm formation is a risk factor for mortality in patients with Candida albicans bloodstream infection-Scotland, 2012-2013

Acknowledgements This work was supported by the Wellcome Trust Strategic Award for Medical Mycology and Fungal Immunology 097377/Z/11/Z. Data collection was supported by a grant from Pfizer. G. Ramage was also supported by a research fellowship grant from Gilead Sciences. We are grateful to microbiology colleagues throughout Scotland for submitting isolates.Peer reviewedPublisher PD