Implementing screening and brief alcohol interventions in primary care : views from both sides of the consultation

Excessive drinking is a global health problem which is responsible for a wide range of both chronic and acute illness, and which costs the UK National Health Service (NHS) £1.7 billion annually. Current health policy aims to reduce alcohol-related problems by promoting early identification of risk followed by brief intervention to facilitate positive changes in drinking level or patterns of consumption. However, practical and philosophical barriers concerning screening and brief alcohol intervention have so far impeded its uptake in routine primary care. This qualitative study aimed to simultaneously explore and compare health professionals’ and patients’ views on the acceptability and feasibility of screening and brief alcohol intervention in primary care. Focus groups were held with (a) four primary care teams, (b) two general practitioner (GP) and two nurse groups and (c) six patient groups in the north-east of England. A thematic framework approach was used to analyse audio-taped data via transcripts. Both health professionals and patients reported that raising and discussing alcohol-related risk was acceptable in primary care, when combined with other lifestyle issues or linked to relevant health conditions. Targeted rather than universal screening was the most acceptable method of identifying alcohol-related risk and would fit well with existing practice. However, there was uncertainty among health professionals about the effectiveness of brief alcohol interventions and some disagreement with patients concerning who was best placed to deliver them. Health professionals felt that nurses were best placed for such work whilst patients reported that they would initially raise the subject with GPs. There was broad acceptance of brief intervention approaches but a lack of support and specific incentives for this work impeded its delivery in routine practice

Dietary flavonoid intakes and CVD incidence in the Framingham Offspring Cohort

This study examines the relationship between long-term intake of six flavonoid classes and incidence of CVD and CHD, using a comprehensive flavonoid database and repeated measures of intake, while accounting for possible confounding by components of a healthy dietary pattern. Flavonoid intakes were assessed using a FFQ among the Framingham Offspring Cohort at baseline and three times during follow-up. Cox proportional hazards regression was used to characterise prospective associations between the natural logarithms of flavonoid intakes and CVD incidence using a time-dependent approach, in which intake data were updated at each examination to represent average intakes from previous examinations. Mean baseline age was 54 years, and 45 % of the population was male. Over an average 14·9 years of follow-up among 2880 participants, there were 518 CVD events and 261 CHD events. After multivariable adjustment, only flavonol intake was significantly associated with lower risk of CVD incidence (hazard ratios (HR) per 2·5-fold flavonol increase = 0·86, Ptrend = 0·05). Additional adjustment for total fruit and vegetable intake and overall diet quality attenuated this observation (HR = 0·89, Ptrend = 0·20 and HR = 0·92, Ptrend = 0·33, respectively). There were no significant associations between flavonoids and CHD incidence after multivariable adjustment. Our findings suggest that the observed association between flavonol intake and CVD risk may be a consequence of better overall diet. However, the strength of this non-significant association was also consistent with relative risks observed in previous meta-analyses, and therefore a modest benefit of flavonol intake on CVD risk cannot be ruled out

Regions of the Cry1Ac toxin predicted to be under positive selection are shown to be the carbohydrate binding sites and can be altered in their glycoprotein target specificity

The cry gene family, is a large family of homologous genes from Bacillus thuringiensis. Studies have examined the structural and functional relationships of the Cry proteins. They have revealed several residues in domains II and III that are important for target recognition and receptor attachment. In 2007 Wu, Jin-Yu et al employed a maximum likelihood method to detect evidence of adaptive evolution in Cry proteins. They identified positively selected residues, which are all located in Domain II or III. Figure 1 shows a protein sequence alignment between domain II and III of Cry1Ac and Cry1Aa. This highlights the areas which are thought to be under positive selection. Cry1Ac and Cry1Aa are structurally very similar and they both bind to a variety of N-aminopeptidases (APN’s) in different insect species. However Cry1Aa has a higher specificity for the cadherin like receptor HevCalP and Cry1Ac binds to N-acetylgalactosamine (GalNAc) on the surface of APN’s. Differences in the binding of the two toxins has been shown in an in-direct toxin-binding assay where GalNAc completely abolished toxin binding of Cry1Ac but had no effect on the binding of Cry1Aa. The binding site has been shown to be located in the third domain of Cry1Ac. Some of these sites correlate with the positively selected residues found by Wu et al 2007 in Cry1Aa. Our aim was to use the comparison of the toxins to analyse the potential to alter the binding specificity of Cry1Ac and its domains. In this work we identified critical amino acid residues for this objective

The investigation of a recombinant GalNAc binding protein from bacillus thuringiensis as a tool for glycan analysis and detection

Changes in the structures of glycans on the surfaces of eukaryotic cells can be important biomarkers for developmental or disease states. Improved methods are needed for the detection and analysis of alterations in glycan structures. Carbohydrate binding proteins such as lectins have potential for the recognition of changes in glycan structure. Host-pathogen interactions frequently involve the recognition of host carbohydrates by proteins of bacteria or viruses. Many bacterial toxins have evolved to interact with host cell receptors or with a specific tissue due to lectin like properties. The toxins from Bacillus thuringiensis have been shown to have carbohydrate binding abilities, in particular N-Acetylgalactosamine (GalNAc) has been shown to inhibit the binding of the toxin Cry1Ac. GalNAc has been shown to be an important marker in many diseases such as breast cancer and colon carcinogenesis. Moreover, changes in GalNAc glycosylation have been identified in many disorders such as cystic fibrosis, neuromuscular disorders and nephropathy. Here we describe the purification of a GalNAc binding protein of bacterial origin that may have potential in the development of diagnostic assays

Gibbs Sampling with Low-Power Spiking Digital Neurons

Restricted Boltzmann Machines and Deep Belief Networks have been successfully used in a wide variety of applications including image classification and speech recognition. Inference and learning in these algorithms uses a Markov Chain Monte Carlo procedure called Gibbs sampling. A sigmoidal function forms the kernel of this sampler which can be realized from the firing statistics of noisy integrate-and-fire neurons on a neuromorphic VLSI substrate. This paper demonstrates such an implementation on an array of digital spiking neurons with stochastic leak and threshold properties for inference tasks and presents some key performance metrics for such a hardware-based sampler in both the generative and discriminative contexts.Comment: Accepted at ISCAS 201

Alcohol Screening and Brief Interventions for Offenders in the Probation Setting (SIPS Trial): a Pragmatic Multicentre Cluster Randomized Controlled Trial

Aim - To evaluate the effectiveness of different brief intervention strategies at reducing hazardous or harmful drinking in the probation setting. Offender managers were randomized to three interventions, each of which built on the previous one: feedback on screening outcome and a client information leaflet control group, 5 min of structured brief advice and 20 min of brief lifestyle counselling. Methods - A pragmatic multicentre factorial cluster randomized controlled trial. The primary outcome was self-reported hazardous or harmful drinking status measured by Alcohol Use Disorders Identification Test (AUDIT) at 6 months (negative status was a score of <8). Secondary outcomes were AUDIT status at 12 months, experience of alcohol-related problems, health utility, service utilization, readiness to change and reduction in conviction rates. Results - Follow-up rates were 68% at 6 months and 60% at 12 months. At both time points, there was no significant advantage of more intensive interventions compared with the control group in terms of AUDIT status. Those in the brief advice and brief lifestyle counselling intervention groups were statistically significantly less likely to reoffend (36 and 38%, respectively) than those in the client information leaflet group (50%) in the year following intervention. Conclusion - Brief advice or brief lifestyle counselling provided no additional benefit in reducing hazardous or harmful drinking compared with feedback on screening outcome and a client information leaflet. The impact of more intensive brief intervention on reoffending warrants further research

Human metabolism and elimination of the anthocyanin, cyanidin-3-glucoside: a 13C-tracer study

BACKGROUND: Evidence suggests that the consumption of anthocyanin-rich foods beneficially affects cardiovascular health; however, the absorption, distribution, metabolism, and elimination (ADME) of anthocyanin-rich foods are relatively unknown. OBJECTIVE: We investigated the ADME of a (13)C5-labeled anthocyanin in humans. DESIGN: Eight male participants consumed 500 mg isotopically labeled cyanidin-3-glucoside (6,8,10,3',5'-(13)C5-C3G). Biological samples were collected over 48 h, and (13)C and (13)C-labeled metabolite concentrations were measured by using isotope-ratio mass spectrometry and liquid chromatography-tandem mass spectrometry. RESULTS: The mean +/- SE percentage of (13)C recovered in urine, breath, and feces was 43.9 +/- 25.9% (range: 15.1-99.3% across participants). The relative bioavailability was 12.38 +/- 1.38% (5.37 +/- 0.67% excreted in urine and 6.91 +/- 1.59% in breath). Maximum rates of (13)C elimination were achieved 30 min after ingestion (32.53 +/- 14.24 mug(13)C/h), whereas (13)C-labeled metabolites peaked (maximum serum concentration: 5.97 +/- 2.14 mumol/L) at 10.25 +/- 4.14 h. The half-life for (13)C-labeled metabolites ranged between 12.44 +/- 4.22 and 51.62 +/- 22.55 h. (13)C elimination was greatest between 0 and 1 h for urine (90.30 +/- 15.28 mug/h), at 6 h for breath (132.87 +/- 32.23 mug/h), and between 6 and 24 h for feces (557.28 +/- 247.88 mug/h), whereas the highest concentrations of (13)C-labeled metabolites were identified in urine (10.77 +/- 4.52 mumol/L) and fecal samples (43.16 +/- 18.00 mumol/L) collected between 6 and 24 h. Metabolites were identified as degradation products, phenolic, hippuric, phenylacetic, and phenylpropenoic acids. CONCLUSION: Anthocyanins are more bioavailable than previously perceived, and their metabolites are present in the circulation fo

Development of a readiness ruler for use with alcohol brief interventions

Background A quick method of assessing readiness to change was needed for a major study of implementing screening and alcohol brief intervention in England. For this purpose, a Readiness Ruler that had been validated among a sample of male college students in the USA was adapted and applied to a sample of excessive drinkers in a general medical practice located in a deprived area of Gateshead, England. Methods 72 participants identified as excessive drinkers by health professionals completed a single-item Readiness Ruler, the 12-item Readiness to Change Questionnaire (RCQ) and the AUDIT questionnaire. Results In terms of concurrent validity, the relationships between the Readiness Ruler, on the one hand, and either stage of change allocation or a dimensional score derived from the RCQ, on the other hand, were highly significant but weaker than expected. When patients who endorsed the “maintenance” point on the Readiness Ruler were excluded from the analysis, the above relationships were considerably strengthened for reasons that are discussed. On this basis and with another small change, a final Readiness Ruler was developed. Conclusion If the validity of the Readiness Ruler is confirmed in subsequent research, a quick and simple way of measuring readiness to change will be available for research or clinical work with alcohol brief interventions

Convolutional Networks for Fast, Energy-Efficient Neuromorphic Computing

Deep networks are now able to achieve human-level performance on a broad spectrum of recognition tasks. Independently, neuromorphic computing has now demonstrated unprecedented energy-efficiency through a new chip architecture based on spiking neurons, low precision synapses, and a scalable communication network. Here, we demonstrate that neuromorphic computing, despite its novel architectural primitives, can implement deep convolution networks that i) approach state-of-the-art classification accuracy across 8 standard datasets, encompassing vision and speech, ii) perform inference while preserving the hardware's underlying energy-efficiency and high throughput, running on the aforementioned datasets at between 1200 and 2600 frames per second and using between 25 and 275 mW (effectively > 6000 frames / sec / W) and iii) can be specified and trained using backpropagation with the same ease-of-use as contemporary deep learning. For the first time, the algorithmic power of deep learning can be merged with the efficiency of neuromorphic processors, bringing the promise of embedded, intelligent, brain-inspired computing one step closer.Comment: 7 pages, 6 figure

Plasma IMS Composition Measurements for Europa and the Other Galilean Moons

NASA and ESA are planning the joint Europa Jupiter System Mission (EJSM) to the Jupiter system with specific emphasis to Europa and Ganymede, respectively. The Japanese Space Agency is also planning an orbiter mission to explore Jupiter's magnetosphere and the Galilean satellites. For NASA's Jupiter Europa Orbiter (JEO) we are developing the 3D Ion Mass Spectrometer (IMS) with two main goals which can also be applied to the other Galilean moons, 1) measure the plasma interaction between Europa and Jupiter's magnetosphere and 2) infer the 4 pi surface composition to trace elemental and significant isotopic levels. The first goal supports the magnetometer (MAG) measurements, primarily directed at detection of Europa's sub-surface ocean, while the second gives information about transfer of material between the Galilean moons, and between the moon surfaces and subsurface layers putatively including oceans. The measurement of the interactions for all the Galilean moons can be used to trace the in situ ion measurements of pickup ions back to either Europa's or Ganymede's surface from the respectively orbiting spacecraft. The IMS instrument, being developed under NASA's Astrobiology Instrument Development Program, would maximally achieve plasma measurement requirements for JEO and EJSM while moving forward our knowledge of Jupiter system composition and source processes to far higher levels than previously envisaged. The composition of the global surfaces of Europa and Ganymede can be inferred from the measurement of ejected neutrals and pick-up ions using at minimum an in situ payload including MAG and IMS also fully capable of meeting Level 1 mission requirements for ocean detection and survey. Elemental and isotopic analysis of potentially extruded oceanic materials at the moon surfaces would further support the ocean objectives. These measurements should be made from a polar orbiting spacecraft about Europa or Ganymede at height 100 km. The ejecta produced by sputtering of the surfaces of Europa and Ganymede has been shown to be representative of the surface composition. Level 2 science on surface geology and composition can then be further enhanced by addition of the following: 3D Ion Neutral Mass Spectrometer (INNS), 3D plasma electron spectrometer (ELS), and hot plasma energetic particle instrument. The measurement approach is to alternate between times measuring pickup ions and times measuring plasma and magnetic field parameters along the spacecraft trajectory. By measuring the pickup ion energy, arrival direction and mass-per-charge, the ion can be traced back along the ejection trajectory to the approximate area of origin if the 3-D electric field and magnetic field are known. In situ observations of plasma flow velocities and vector magnetic fields can be used to determine the local convective electric field (E = -VXB) along the spacecraft trajectory. By combining this information with models of the magnetospheric interaction with Europa, one can generate 3D maps of the electric and magnetic field and compute the trajectories of the pickup ions back to the surface or exospheric points of origin. In the case of Ganymede there is the additional complexity of its own internal dipole magnetic field, while Io's volcanic activity introduces the complexity of a highly structured denser atmosphere. Callisto with its less globally extended exosphere will have a simpler interaction than for Europa (i.e., more like our moon). We will discuss these differences in light of the above proposed technique. Finally, the INNS observations and neutral exosphere models are needed to estimate production rates of pickup ions. The hot plasma measurements are needed to correct for sputtering rates which can be time dependent and electron plasma observations for electron impact ionization rates. Instrument characteristics, field-of-view requirements, modes of operation and effects of radiation on instrument functionality will be discussed