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.

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.

Improved estimates of upper-ocean warming and multi-decadal sea-level rise.

Changes in the climate system's energy budget are predominantly revealed in ocean temperatures and the associated thermal expansion contribution to sea-level rise. Climate models, however, do not reproduce the large decadal variability in globally averaged ocean heat content inferred from the sparse observational database, even when volcanic and other variable climate forcings are included. The sum of the observed contributions has also not adequately explained the overall multi-decadal rise. Here we report improved estimates of near-global ocean heat content and thermal expansion for the upper 300 m and 700 m of the ocean for 1950-2003, using statistical techniques that allow for sparse data coverage and applying recent corrections to reduce systematic biases in the most common ocean temperature observations. Our ocean warming and thermal expansion trends for 1961-2003 are about 50 per cent larger than earlier estimates but about 40 per cent smaller for 1993-2003, which is consistent with the recognition that previously estimated rates for the 1990s had a positive bias as a result of instrumental errors. On average, the decadal variability of the climate models with volcanic forcing now agrees approximately with the observations, but the modelled multi-decadal trends are smaller than observed. We add our observational estimate of upper-ocean thermal expansion to other contributions to sea-level rise and find that the sum of contributions from 1961 to 2003 is about 1.5 +/- 0.4 mm yr(-1), in good agreement with our updated estimate of near-global mean sea-level rise (using techniques established in earlier studies) of 1.6 +/- 0.2 mm yr(-1).

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.

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.

Temporary sequestration of potassium by mitochondria in astrocytes.

Increases in extracellular potassium concentration ([K(+)](o)), which can occur during neuronal activity and under pathological conditions such as ischemia, lead to a variety of potentially detrimental effects on neuronal function. Although astrocytes are known to contribute to the clearance of excess K(+)(o), the mechanisms are not fully understood. We examined the potential role of mitochondria in sequestering K(+) in astrocytes. Astrocytes were loaded with the fluorescent K(+) indicator PBFI and release of K(+) from mitochondria into the cytoplasm was examined after uncoupling the mitochondrial membrane potential with carbonyl cyanide m-chlorophenylhydrazone (CCCP). Under the experimental conditions employed, transient applications of elevated [K(+)](o) led to increases in K(+) within mitochondria, as assessed by increases in the magnitudes of cytoplasmic [K(+)] ([K(+)](i)) transients evoked by brief exposures to CCCP. When mitochondrial K(+) sequestration was impaired by prolonged application of CCCP, there was a robust increase in [K(+)](i) upon exposure to elevated [K(+)](o). Blockade of plasmalemmal K(+) uptake routes by ouabain, Ba(2+), or a mixture of voltage-activated K(+) channel inhibitors reduced K(+) uptake into mitochondria. Also, reductions in mitochondrial K(+) uptake occurred in the presence of mito-K(ATP) channel inhibitors. Rises in [K(+)](i) evoked by brief applications of CCCP following exposure to high [K(+)](o) were also reduced by gap junction blockers and in astrocytes isolated from connexin43-null mice, suggesting that connexins also play a role in K(+) uptake into astrocyte mitochondria. We conclude that mitochondria play a key role in K(+)(o) handling by astrocytes.

Significant decadal-scale impact of volcanic eruptions on sea level and ocean heat content.

Ocean thermal expansion contributes significantly to sea-level variability and rise. However, observed decadal variability in ocean heat content and sea level has not been reproduced well in climate models. Aerosols injected into the stratosphere during volcanic eruptions scatter incoming solar radiation, and cause a rapid cooling of the atmosphere and a reduction in rainfall, as well as other changes in the climate system. Here we use observations of ocean heat content and a set of climate simulations to show that large volcanic eruptions result in rapid reductions in ocean heat content and global mean sea level. For the Mt Pinatubo eruption, we estimate a reduction in ocean heat content of about 3 x 10(22) J and a global sea-level fall of about 5 mm. Over the three years following such an eruption, we estimate a decrease in evaporation of up to 0.1 mm d(-1), comparable to observed changes in mean land precipitation. The recovery of sea level following the Mt Pinatubo eruption in 1991 explains about half of the difference between the long-term rate of sea-level rise of 1.8 mm yr(-1) (for 1950-2000), and the higher rate estimated for the more recent period where satellite altimeter data are available (1993-2000).

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.

Regulation of early neurite morphogenesis by the Na+/H+ exchanger NHE1.

The ubiquitously expressed Na(+)/H(+) exchanger NHE1 plays an important role in regulating polarized membrane protrusion and directional motility in non-neuronal cells. Using NGF-differentiated PC12 cells and murine neocortical neurons in vitro, we now show that NHE1 plays a role in regulating early neurite morphogenesis. NHE1 was expressed in growth cones in which it gave rise to an elevated intracellular pH in actively extending neurites. The NHE1 inhibitor cariporide reversibly reduced growth cone filopodia number and the formation and elongation of neurites, especially branches, whereas the transient overexpression of full-length NHE1, but not NHE1 mutants deficient in either ion translocation activity or actin cytoskeletal anchoring, elicited opposite effects. In addition, compared with neocortical neurons obtained from wild-type littermates, neurons isolated from NHE1-null mice exhibited reductions in early neurite outgrowth, an effect that was rescued by overexpression of full-length NHE1 but not NHE1 mutants. Finally, the growth-promoting effects of netrin-1, but not BDNF or IGF-1, were markedly reduced by cariporide in wild-type neocortical neurons and were not observed in NHE1-null neurons. Although netrin-1 failed to increase growth cone intracellular pH or Na(+)/H(+) exchange activity, netrin-1-induced increases in early neurite outgrowth were restored in NHE1-null neurons transfected with full-length NHE1 but not an ion translocation-deficient mutant. Collectively, the results indicate that NHE1 participates in the regulation of early neurite morphogenesis and identify a novel role for NHE1 in the promotion of early neurite outgrowth by netrin-1.

Do provincial drug benefit initiatives create an effective policy lab? The evidence from Canada.

Although the costs of doctors' visits and hospital stays in Canada are covered by national public health insurance, the cost of outpatient prescription drugs is not. To solve problems of access, Canadian provinces have introduced provincial prescription drug benefit programs. This study analyzes the prescription drug policymaking process in five Canadian provinces between 1992 and 2004 with a view to (1) determining the federal government's role in the area of prescription drugs; (2) describing the policymaking process; (3) identifying factors in each province's choice of a policy; (4) identifying patterns in those factors across the five provinces; and (5) assessing the federal government's influence on the policies chosen. Analysis shows that despite significant differences in policy choices, the ideological motivations of the provinces were unexpectedly similar. The findings also highlight the importance of institutional factors, for example, in provinces' decision to compete rather than to collaborate. We conclude that, to date, Canada's federalism laboratory has only partly benefited the Canadian public. Cost pressures may, however, eventually overcome barriers to cooperation between the provincial and the federal governments, enabling them to capitalize on Canada's federal structure to improve the accessibility and affordability of drugs.

Case study on nutrition labelling policy-making in Canada.

PURPOSE: In order to understand policy-making capacities, we conducted an in-depth examination of three stages of the policy cycle (agenda-setting, formulation, and decision-making) leading to mandatory nutrition labelling, nutrient content claims, and health claims regulations in Canada. METHODS: Data were collected through document review and key informant interviews (n=24) conducted with government, industry, health organizations, professional associations, academia, and consumer advocacy groups. RESULTS: The policy-making processes were complex, unpredictable, and often chaotic. In the early stages, progress was hampered by a shortage of resources and negatively affected by policy silos. In spite of formidable barriers, a high degree of stakeholder convergence was achieved, which facilitated ground-breaking policy formulation. Success factors included a common health promotion issue frame that participants adopted early in the consultative process, "champions" within the federal government's health sector, strong advocates within a broad stakeholder community, and an innovative policy-formulation process overseen by an intersectoral advisory committee. CONCLUSIONS: Authentic partnerships among government, industry, and key stakeholders strengthened policy-making processes while helping to overcome policy silos at the organizational level. Barriers were reduced through effective change management practices and collaborative advisory and communication processes. Future research should involve an examination of the population health outcomes associated with this policy initiative.

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.

Mitochondrial sensitivity and altered calcium handling underlie enhanced NMDA-induced apoptosis in YAC128 model of Huntington's disease.

Expansion of a CAG repeat in the Huntington's disease (HD) gene results in progressive neuronal loss, particularly of striatal medium-sized spiny neurons (MSNs). Studies in human HD autopsy brain tissue, as well as cellular and animal models of HD, suggest that increased activity of NMDA-type glutamate receptors and altered mitochondrial function contribute to selective neuronal degeneration. In this regard, the YAC128 mouse model, expressing full-length human huntingtin with 128 glutamine repeats, has been the focus of much interest. Although NMDA-induced apoptosis is enhanced in YAC128 MSNs, here we report that the initial steps in the death signaling pathway, including NMDA receptor (NMDAR) current and cytosolic Ca2+ loading, are similar to those observed in wild-type MSNs. In contrast, we found that the NMDAR-mediated Ca2+ load triggered a strikingly enhanced loss of mitochondrial membrane potential in YAC128 MSNs, suggesting that NMDAR signaling via the mitochondrial apoptotic pathway is altered. This effect was accompanied by impaired cytosolic Ca2+ clearance after removal of NMDA, a difference that was not apparent after high potassium-evoked depolarization-mediated Ca2+ entry. Inhibition of the mitochondrial permeability transition (mPT) reduced peak cytosolic Ca2+ and mitochondrial depolarization evoked by NMDA in YAC128 MSNs but not wild-type MSNs. Hence, in contrast to YAC models with moderate CAG expansions, the enhanced NMDA-induced apoptosis in YAC128 MSNs is predominantly determined by augmented mitochondrial sensitivity to Ca2+-induced activation of the mPT. These results suggest that the CAG repeat length influences the mechanism by which mHtt enhances NMDAR-mediated excitotoxicity.

Public policy processes and getting physical activity into Alberta's urban schools.

OBJECTIVES: Public policies impact the amount of physical activity (PA) that children receive at school. These policies are of interest because overweight and obesity among Canadian children have grown at significant rates, and increasing PA among children is one way to reverse this trend. This research investigates the public policy processes that have resulted in Alberta's education system adopting in-school daily physical activity (DPA) and not supporting walk-to-school (WTS) initiatives. METHODS: Using the policy process described by Kingdon and others as a conceptual framework, this research reviews literature and documents on public policy relating to PA in schools and interviews key individuals (N = 20) to identify the policy-related facilitators and barriers in Alberta, Canada to increasing PA in school-aged children. RESULTS: DPA was mandated because Kingdon's three policy streams (problem, solution and politics) became joined or linked. DPA was the most viable solution because literature supports and teachers believe in the educational benefits of PA. As well, a physician with personal beliefs about the benefits of PA became the minister of education and coupled the solution with the political stream through his ministerial power. Reasons that WTS programs have not become school or health policy include advocacy led by politically weak organizations, lack of a supportive policy entrepreneur and poor saliency among educators. CONCLUSIONS: This research illuminates the inner workings of the policy process shaping PA in schools, identifying the unseen forces of the policy process that move issues forward. The findings provide valuable insight for building other healthy public policies.

Shifting the lens: the introduction of population-based funding in Alberta.

This paper offers a detailed historical description of the development of Alberta's population-based funding model for Regional Health Authorities (RHAs). It focuses on key political factors that may have facilitated this transition--in particular, the role of institutions, organized interests, and ideas and values. Understanding the politics of policy change as exemplified in this case can be useful in assessing future prospects for health system reform in Canada and laying the groundwork for further comparative study.

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.

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.