Exploring barriers and enablers to the delivery of Making Every Contact Count brief behavioural interventions in Ireland: A cross-sectional survey study

Objectives The public health impact of the Irish Making Every Contact Count (MECC) brief intervention programme is dependent on delivery by health care professionals. We aimed to identify enablers and modifiable barriers to MECC intervention delivery to optimize MECC implementation. Design Online cross-sectional survey design. Methods Health care professionals (n = 4050) who completed MECC eLearning were invited to complete an online survey based on the Theoretical Domains Framework (TDF). Multiple regression analysis identified predictors of MECC delivery (logistic regression to predict delivery or not; linear regression to predict frequency of delivery). Data were visualized using Confidence Interval-Based Estimates of Relevance (CIBER). Results Seventy-nine per cent of participants (n = 283/357) had delivered a MECC intervention. In the multiple logistic regression (Nagelkerke's R2 = .34), the significant enablers of intervention delivery were ‘professional role’ (OR = 1.86 [1.10, 3.15]) and ‘intentions/goals’ (OR = 4.75 [1.97, 11.45]); significant barriers included ‘optimistic beliefs about consequences’ (OR = .41 [.18, .94]) and ‘negative emotions’ (OR = .50 [.32, .77]). In the multiple linear regression (R2 = .29), the significant enablers of frequency of MECC delivery were ‘intentions/goals’ (b = 10.16, p = .02) and professional role (b = 6.72, p = .03); the significant barriers were ‘negative emotions’ (b = −4.74, p = .04) and ‘barriers to prioritisation’ (b = −5.00, p = .01). CIBER analyses suggested six predictive domains with substantial room for improvement: ‘intentions and goals’, ‘barriers to prioritisation’, ‘environmental resources’, ‘beliefs about capabilities’, ‘negative emotions’ and ‘skills’. Conclusion Implementation interventions to enhance MECC delivery should target intentions and goals, beliefs about capabilities, negative emotions, environmental resources, skills and barriers to prioritization

Cloning and characterization of the ecto-nucleotidase NTPDase3 from rat brain: Predicted secondary structure and relation to other members of the E-NTPDase family and actin

The protein family of ecto-nucleoside triphosphate diphosphohydrolases (E-NTPDase family) contains multiple members that hydrolyze nucleoside 5’-triphosphates and nucleoside 5’-diphosphates with varying preference for the individual type of nucleotide. We report the cloning and functional expression of rat NTPDase3. The rat brain-derived cDNA has an open reading frame of 1590 bp encoding 529 amino acid residues, a calculated molecular mass of 59.1 kDa and predicted N- and C-terminal hydrophobic sequences. It shares 94.3% and 81.7% amino acid identity with the mouse and human NTPDase3, respectively, and is more closely related to cell surface-located than to the intracellularly located members of the enzyme family. The NTPDase3 gene is allocated to chromosome 8q32 and organized into 11 exons. Rat NTPDase3 expressed in CHO cells hydrolyzed both nucleoside triphosphates and nucleoside diphosphates with hydrolysis ratios of ATP:ADP of 5:1 and UTP:UDP of 8:1. After addition of ATP, ADP is formed as an intermediate product that is further hydrolyzed to AMP. The enzyme is preferentially activated by Ca2+ over Mg2+ and reveals an alkaline pH optimum. Immunocytochemistry confirmed expression of heterologously expressed NTPDase3 to the surface of CHO cells. PC12 cells express endogenous surface-located NTPDase3. An immunoblot analysis detects NTPDase3 in all rat brain regions investigated. An alignment of the secondary structure domains of actin conserved within the actin/HSP70/sugar kinase superfamily to those of all members of the NTPDase family reveals apparent similarity. It infers that NTPDases share the two-domain structure with members of this enzyme superfamily

Measurement of the Bottom-Strange Meson Mixing Phase in the Full CDF Data Set

We report a measurement of the bottom-strange meson mixing phase \beta_s using the time evolution of B0_s -> J/\psi (->\mu+\mu-) \phi (-> K+ K-) decays in which the quark-flavor content of the bottom-strange meson is identified at production. This measurement uses the full data set of proton-antiproton collisions at sqrt(s)= 1.96 TeV collected by the Collider Detector experiment at the Fermilab Tevatron, corresponding to 9.6 fb-1 of integrated luminosity. We report confidence regions in the two-dimensional space of \beta_s and the B0_s decay-width difference \Delta\Gamma_s, and measure \beta_s in [-\pi/2, -1.51] U [-0.06, 0.30] U [1.26, \pi/2] at the 68% confidence level, in agreement with the standard model expectation. Assuming the standard model value of \beta_s, we also determine \Delta\Gamma_s = 0.068 +- 0.026 (stat) +- 0.009 (syst) ps-1 and the mean B0_s lifetime, \tau_s = 1.528 +- 0.019 (stat) +- 0.009 (syst) ps, which are consistent and competitive with determinations by other experiments.Comment: 8 pages, 2 figures, Phys. Rev. Lett 109, 171802 (2012

Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure fl ux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defi ned as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (inmost higher eukaryotes and some protists such as Dictyostelium ) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the fi eld understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation it is imperative to delete or knock down more than one autophagy-related gene. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways so not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

Microtopographic drivers of vegetation patterning in blanket peatlands recovering from erosion

Blanket peatlands are globally rare, and many have been severely eroded. Natural recovery and revegetation (‘self-restoration’) of bare peat surfaces are often observed but are poorly understood, thus hampering the ability to reliably predict how these ecosystems may respond to climatic change. We hypothesised that morphometric/topographic-related microclimatic variables may be key controls on successional pathways and vegetation patterning in self-restoring blanket peatlands. We predicted the occurrence probability of four common peatland plant species (Calluna vulgaris, Eriophorum vaginatum, Eriophorum angustifolium, and Sphagnum spp.) using a digital surface model (DSM) generated from drone imagery at a pixel size of 20 cm, a suite of variables derived from the DSM, and an ensemble learning method (random forests). All four species models provided accurate fine-scale predictions of habitat suitability (accuracy > 90%, area under curve (AUC) > 0.9, recall and precision > 0.8). Mean elevation (within a 1 m radius) was often the most influential variable. Topographic position, wind exposure, and the heterogeneity or ruggedness of the surrounding surface were also important for all models, whilst light-related variables and a wetness index were important in the Sphagnum model. Our approach can be used to improve prediction of future responses and sensitivities of peatland recovery to climatic changes and as a tool to identify areas of blanket peatlands that may self-restore successfully without management intervention

Characteristics of Indigenous primary health care service delivery models: a systematic scoping review

Published online: 25 January 2018Background: Indigenous populations have poorer health outcomes compared to their non-Indigenous counterparts. The evolution of Indigenous primary health care services arose from mainstream health services being unable to adequately meet the needs of Indigenous communities and Indigenous peoples often being excluded and marginalised from mainstream health services. Part of the solution has been to establish Indigenous specific primary health care services, for and managed by Indigenous peoples. There are a number of reasons why Indigenous primary health care services are more likely than mainstream services to improve the health of Indigenous communities. Their success is partly due to the fact that they often provide comprehensive programs that incorporate treatment and management, prevention and health promotion, as well as addressing the social determinants of health. However, there are gaps in the evidence base including the characteristics that contribute to the success of Indigenous primary health care services in providing comprehensive primary health care. This systematic scoping review aims to identify the characteristics of Indigenous primary health care service delivery models. Method: This systematic scoping review was led by an Aboriginal researcher, using the Joanna Briggs Institute Scoping Review Methodology. All published peer-reviewed and grey literature indexed in PubMed, EBSCO CINAHL, Embase, Informit, Mednar, and Trove databases from September 1978 to May 2015 were reviewed for inclusion. Studies were included if they describe the characteristics of service delivery models implemented within an Indigenous primary health care service. Sixty-two studies met the inclusion criteria. Data were extracted and then thematically analysed to identify the characteristics of Indigenous PHC service delivery models. Results: Culture was the most prominent characteristic underpinning all of the other seven characteristics which were identified – accessible health services, community participation, continuous quality improvement, culturally appropriate and skilled workforce, flexible approach to care, holistic health care, and self-determination and empowerment. Conclusion: While the eight characteristics were clearly distinguishable within the review, the interdependence between each characteristic was also evident. These findings were used to develop a new Indigenous PHC Service Delivery Model, which clearly demonstrates some of the unique characteristics of Indigenous specific models.Stephen G. Harfield, Carol Davy, Alexa McArthur, Zachary Munn, Alex Brown and Ngiare Brow

Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease

BACKGROUND: Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization. RESULTS: During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events. CONCLUSIONS: Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .)