Commensal Escherichia coli Strains of Bovine Origin Competitively Mitigated Escherichia coli O157:H7 in a Gnotobiotic Murine Intestinal Colonization Model with or without Physiological Stress.

Cattle are a primary reservoir of enterohemorrhagic Escherichia coli (EHEC) O157:H7. Currently, there are no effective methods of eliminating this important zoonotic pathogen from cattle, and colonization resistance in relation to EHEC O157:H7 in cattle is poorly understood. We developed a gnotobiotic EHEC O157:H7 murine model to examine aspects of the cattle pathogen-microbiota interaction, and to investigate competitive suppression of EHEC O157:H7 by 18 phylogenetically distinct commensal E. coli strains of bovine origin. As stress has been suggested to influence enteric colonization by EHEC O157:H7 in cattle, corticosterone administration (±) to incite a physiological stress response was included as an experimental variable. Colonization of the intestinal tract (IT) of mice by the bovine EHEC O157:H7 strain, FRIK-2001, mimicked characteristics of bovine IT colonization. In this regard, FRIK-2001 successfully colonized the IT and temporally incited minimal impacts on the host relative to other EHEC O157:H7 strains, including on the renal metabolome. The presence of the commensal E. coli strains decreased EHEC O157:H7 densities in the cecum, proximal colon, and distal colon. Moreover, histopathologic changes and inflammation markers were reduced in the distal colon of mice inoculated with commensal E. coli strains (both propagated separately and communally). Although stress induction affected the behavior of mice, it did not influence EHEC O157:H7 densities or disease. These findings support the use of a gnotobiotic murine model of enteric bovine EHEC O157:H7 colonization to better understand pathogen-host-microbiota interactions toward the development of effective on-farm mitigations for EHEC O157:H7 in cattle, including the identification of bacteria capable of competitively colonizing the IT.

An improved method for the determination of cannabidiol in topical products using ultrasound-assisted extraction and gas chromatography-mass spectrometry.

The recent surge in the sale of cannabidiol (CBD)-based topicals has risen rapidly in recent years, as it can be used to treat a multitude of skin disorders. However, there is minimal regulation concerning actual CBD content in these products. Topicals on the market may contain various concentrations of CBD and may be combined with a range of other compounds. The concentration of CBD has to be determined before the products enter the market. For this reason, a selective analytical method was developed using a 23 factorial design; and validated to determine CBD content in various topicals based on ultrasound-assisted extraction (UAE) followed by gas chromatography coupled to mass spectrometry (GC-MS). The method showed good precision (relative standard deviation ≤ 7.7%), accuracy at three concentration levels (recovery > 97.9%) for three different matrices, acceptable linearity (R2 > 0.99), and limit of detection (0.05 µg/mg). The method was successfully applied to the analysis of five commercial topicals. The proposed method is rapid, sensitive, precise, and accurate. In addition, it does not require derivatization and it is suitable for the determination of CBD in topicals for quality control purposes.

Observed poleward freshwater transport since 1970.

Warming-induced global water cycle changes pose a significant challenge to global ecosystems and human society. However, quantifying historical water cycle change is difficult owing to a dearth of direct observations, particularly over the ocean, where 77% and 85% of global precipitation and evaporation occur, respectively1-3. Air-sea fluxes of freshwater imprint on ocean salinity such that mean salinity is lowest in the warmest and coldest parts of the ocean, and is highest at intermediate temperatures4. Here we track salinity trends in the warm, salty fraction of the ocean, and quantify the observed net poleward transport of freshwater in the Earth system from 1970 to 2014. Over this period, poleward freshwater transport from warm to cold ocean regions has occurred at a rate of 34-62 milli-sverdrups (mSv = 103 m3 s-1), a rate that is not replicated in the current generation of climate models (the Climate Model Intercomparison Project Phase 6 (CMIP6)). In CMIP6 models, surface freshwater flux intensification in warm ocean regions leads to an approximately equivalent change in ocean freshwater content, with little impact from ocean mixing and circulation. Should this partition of processes hold for the real world, the implication is that the historical surface flux amplification is weaker (0.3-4.6%) in CMIP6 compared with observations (3.0-7.4%). These results establish a historical constraint on poleward freshwater transport that will assist in addressing biases in climate models.

Reconciling global mean and regional sea level change in projections and observations.

The ability of climate models to simulate 20th century global mean sea level (GMSL) and regional sea-level change has been demonstrated. However, the Intergovernmental Panel on Climate Change (IPCC) Fifth Assessment Report (AR5) and Special Report on the Ocean and Cryosphere in a Changing Climate (SROCC) sea-level projections have not been rigorously evaluated with observed GMSL and coastal sea level from a global network of tide gauges as the short overlapping period (2007-2018) and natural variability make the detection of trends and accelerations challenging. Here, we critically evaluate these projections with satellite and tide-gauge observations. The observed trends from GMSL and the regional weighted mean at tide-gauge stations confirm the projections under three Representative Concentration Pathway (RCP) scenarios within 90% confidence level during 2007-2018. The central values of the observed GMSL (1993-2018) and regional weighted mean (1970-2018) accelerations are larger than projections for RCP2.6 and lie between (or even above) those for RCP4.5 and RCP8.5 over 2007-2032, but are not yet statistically different from any scenario. While the confirmation of the projection trends gives us confidence in current understanding of near future sea-level change, it leaves open questions concerning late 21st century non-linear accelerations from ice-sheet contributions.

Na/H exchanger NHE1 acts upstream of rho GTPases to promote neurite outgrowth.

Na+/H+ exchanger NHE1, a major determinant of intracellular pH (pHi) in mammalian central neurons, promotes neurite outgrowth under both basal and netrin-1-stimulated conditions. The small GTP binding proteins and their effectors have a dominant role in netrin-1-stimulated neurite outgrowth. Since NHE1 has been shown previously to work downstream of the Rho GTPases-mediated polarized membrane protrusion in non-neuronal cells, we examined whether NHE1 has a similar relationship with Cdc42, Rac1 and RhoA in neuronal morphogenesis. Interestingly, our results suggest the possibility that NHE1 acting upstream of Rho GTPases to promote neurite outgrowth induced by netrin-1. First, we found that netrin-1-induced increases in the activities of Rho GTPases using FRET (Forster Resonance Energy Transfer) analyses in individual growth cones; furthermore, their increased activities were abolished by cariporide, a specific NHE1 inhibitor. Second, NHE1 inhibition had no effect on neurite retraction induced by L-α-Lysophosphatidic acid (LPA), a potent RhoA activator. The regulation of Rho GTPases by NHE1 was further evidenced by reduced Rac1, Cdc42 and RhoA activities in NHE1-null neurons. Taken together, our findings suggest that NHE1-dependent neuronal morphogenesis involves the activation of Rho-family of small GTPases.

Improving Physician Accountability through Primary Care Reform in Alberta.

Like other Canadian provinces and territories, Alberta has been attempting to reform primary care since the mid-1990s. Although initially these efforts were focused almost exclusively on the method of payment for physicians, since 2003, the focus of government policy has broadened to include other aspects of practice, including governance and accountability, improved continuity, the use of a team-based approach and the use of electronic information systems. Although significant progress has been made, Alberta continues to face challenges.

Neoliberalism and Accountability Failure in the Delivery of Services Affecting the Health of the Public.

Since the 1980s, the emergence of neoliberalism as a dominant government paradigm has led to increasing instances of accountability failure, resulting in significant injuries or death. Employing a grounded theory approach, accountability failure is defined and explored through analysis of 18 public inquiries and reports in the United Kingdom and Canada. The analysis reveals that the combination of a neoliberal policy paradigm and flawed regulation, governance, culture, and performance management inevitably led to accountability failure. Neoliberal policies have precipitated uncoordinated and underfunded regulatory regimes, an oppressive culture focused on financial efficiency at the expense of quality, self-serving and willfully blind governance, and underfunded and inadequate tools for measuring performance. The evidence suggests that organizations have not learned from each other within or between countries, revealing a pattern of accountability failure in which citizens are placed at risk in their communities and hospitals for preventable injury or death within an increasingly politicized government and leadership environment.

Author Correction: Thermogenesis-triggered seed dispersal in dwarf mistletoe.

This corrects the article DOI: 10.1038/ncomms7262.

Revisiting Health Regionalization in Canada.

Twenty years ago, many of Canada's provinces began to introduce regional health authorities to address problems with their health care systems. With this action, the provinces sought to achieve advances in community decision-making, the integration of health services, and the provision of care in the home and community. The authorities were also to help restrict health care costs. An assessment of the authorities indicates, however, that over the past two decades they have been unable to meet their objectives. Community representatives continue to play little role in determining the appropriate health services for their regions. Gains have been made towards integrating health services, but the plan for a near seamless set of health services has not been realized. Funding for health services remains focused on hospital and physician care, and health care expenditures have until very recently been little affected by regional authorities. This disappointing performance has caused some provinces to abandon their regional authorities, but this article argues that the provision of greater autonomy and a better public appreciation of their role and potential may lead to more successful regional authorities. Accordingly, the objective of this article is to reveal the shortcomings of regional health authorities in Canada while at the same time arguing that changes can be made to increase the chances of more workable authorities.

The African disability scooter: efficiency testing in paediatric amputees in Malawi.

PURPOSE: The African Disability Scooter (ADS) was developed for lower limb amputees, to improve mobility and provide access to different terrains. The aim of this study was to test the efficiency of the ADS in Africa over different terrains. METHOD: Eight subjects with a mean age of 12 years participated. Energy expenditure and speed were calculated over different terrains using the ADS, a prosthetic limb, and crutches. Repeated testing was completed on different days to assess learning effect. RESULTS: Speed was significantly faster with the ADS on a level surface compared to crutch walking. This difference was maintained when using the scooter on rough terrain. Oxygen cost was halved with the scooter on level ground compared to crutch walking. There were no significant differences in oxygen consumption or heart rate. There were significant differences in oxygen cost and speed between days using the scooter over level ground, suggesting the presence of a learning effect. CONCLUSIONS: This study demonstrates that the ADS is faster and more energy efficient than crutch walking in young individuals with amputations, and should be considered as an alternative to a prosthesis where this is not available. The presence of a learning effect suggests supervision and training is required when the scooter is first issued. Implications for Rehabilitation The African Disability Scooter: is faster than crutch walking in amputees; is more energy efficient than walking with crutches; supervised use is needed when learning to use the device; is a good alternative/adjunct for mobility.

Variables affecting the emergence of untaught equivalence relations in children with and without autism.

OBJECTIVE: This study examined the formation of equivalence classes among children with ASD and typically developing children. DESIGN: A single-subject AB and BA design was used. METHODS: Two of the six equivalence relations were taught. Participants were then tested to determine whether the remaining four equivalence relations were acquired without teaching. Half of the children were taught naming responses first, then selecting responses. Half were taught in the reverse order. RESULTS: Five out of 10 participants with ASD demonstrated the emergence of all four untaught relations. The remaining five participants showed variability. Nine of the 10 typically developing children demonstrated emergence of all untaught relations. Variation in teaching conditions had no significant effect on outcomes. CONCLUSIONS: Many children with ASD are capable of generalising to untaught equivalence relations. The results fail to support the claim that acquisition of naming responses is a pre-requisite for the emergence of untaught equivalence relations.

Resistance and change: a multiple streams approach to understanding health policy making in Ghana.

Although much has been written on health policy making in developed countries, the same cannot be said of less developed countries, especially in Africa. Drawing largely on available historical and government records, newspaper publications, parliamentary Hansards, and published books and articles, this article uses John W. Kingdon's multiple streams framework to explain how the problem, politics, and policy streams converged for Ghana's National Health Insurance Scheme (NHIS) to be passed into law in 2003. The article contends that a change in government in the 2000 general election opened a "policy window" for eventual policy change from "cash-and-carry" to the NHIS.

Rapid determination of total conjugated linoleic acid content in select Canadian cheeses by (1)h NMR spectroscopy.

The application of (1)H nuclear magnetic resonance (NMR) spectroscopy to the measurement of conjugated linoleic acid (CLA) content in the lipid fraction of dairy products is both a novel and inviting alternative to traditional methods such as gas chromatography (GC), which can require time-consuming sample derivatization. In this work, a newly developed, rapid, and reliable lipid extraction protocol was combined with simple, nondestructive (1)H NMR spectroscopic analysis to measure the total CLA content in CLA standards and in various Canadian cheeses from conventional, organic, and grass-fed dairy sources. The total CLA concentrations (mg/g cheese) obtained using these new extraction and analysis methods were consistent with amounts found using the modified Folch extraction and GC analysis (correlation coefficient of 0.948). Results showed that cheeses from exclusively grass-fed dairy cows were significantly higher in total CLA content than either conventional or organic cheese.

Endosomal acidification by Na+/H+ exchanger NHE5 regulates TrkA cell-surface targeting and NGF-induced PI3K signaling.

To facilitate polarized vesicular trafficking and signal transduction, neuronal endosomes have evolved sophisticated mechanisms for pH homeostasis. NHE5 is a member of the Na(+)/H(+) exchanger family and is abundantly expressed in neurons and associates with recycling endosomes. Here we show that NHE5 potently acidifies recycling endosomes in PC12 cells. NHE5 depletion by plasmid-based short hairpin RNA significantly reduces cell surface abundance of TrkA, an effect similar to that observed after treatment with the V-ATPase inhibitor bafilomycin. A series of cell-surface biotinylation experiments suggests that anterograde trafficking of TrkA from recycling endosomes to plasma membrane is the likeliest target affected by NHE5 depletion. NHE5 knockdown reduces phosphorylation of Akt and Erk1/2 and impairs neurite outgrowth in response to nerve growth factor (NGF) treatment. Of interest, although both phosphoinositide 3-kinase-Akt and Erk signaling are activated by NGF-TrkA, NGF-induced Akt-phosphorylation appears to be more sensitively affected by perturbed endosomal pH. Furthermore, NHE5 depletion in rat cortical neurons in primary culture also inhibits neurite formation. These results collectively suggest that endosomal pH modulates trafficking of Trk-family receptor tyrosine kinases, neurotrophin signaling, and possibly neuronal differentiation.

Separation of dietary omega-3 and omega-6 fatty acids in food by capillary electrophoresis.

A lower dietary omega-6/omega-3 (n-6/n-3) fatty acid ratio (<4) has been shown to be beneficial in preventing a number of chronic illnesses. Interest exists in developing more rapid and sensitive analytical methods for profiling fatty acid levels in foods. An aqueous CE method was developed for the simultaneous determination of 15 n-3 and n-6 relevant fatty acids. The effect of pH and concentration of buffer, type and concentration of organic modifier, and additive on the separation was investigated in order to determine the best conditions for the analysis. Baseline separations of the 15 fatty acids were achieved using 40 mM borate buffer at pH 9.50 containing 50 mM SDS, 10 mM ß-cyclodextrin, and 10% acetonitrile. The developed CE method has LODs of <5 mg/L and good linearity (R(2) > 0.980) for all fatty acids studied. The proposed method was successfully applied to the determination of n-3 and n-6 fatty acids in flax seed, Udo® oils and a selection of grass-fed and grain-fed beef muscle samples.

Pursuing enterprise risk management: a local road map for Canadian healthcare leaders.

An in-depth analysis of organizational risk management in healthcare, and in particular the concepts of Enterprise Risk Management (ERM), has identified a 5-part model that can be used by Canadian healthcare leaders as an evidence-supported approach to successful organizational risk management. The Model for Organizational Risk Management, termed "the Model," has been developed as a basis for linking the components of an ERM Framework into a Canadian health organization to overcome the barriers that commonly disrupt strategic risk management. The Model addresses how an ERM Framework can fit within an existing health organization by building off and enhancing existing processes and resources to ensure familiarity, acceptance, and sustainability of the risk management program. By approaching the Model in a stepwise fashion (based on individual organizational context), healthcare leaders are provided with a road map from which to advance their own organizational risk management program.