Internet Applications for Screening and Brief Interventions for Alcohol in Primary Care Settings-Implementation and Sustainability

Screening and brief interventions head the list of effective evidence-based interventions for the prevention and treatment of alcohol use disorders in healthcare settings. However, healthcare professionals have been reluctant to engage with this kind of activity both because of the sensitive nature of the subject and because delivery is potentially time-consuming. Digital technologies for behavioral change are becoming increasingly widespread and their low delivery costs make them highly attractive. Internet and mobile technologies have been shown to be effective for the treatment of depression, anxiety, and smoking cessation in healthcare settings, and have the potential to add substantial value to the delivery of brief intervention for alcohol. Online alcohol questionnaires have been shown to elicit reliable responses on alcohol consumption and compared with conventional prevention techniques, digital alcohol interventions delivered in various settings have been found to be as effective in preventing alcohol-related harms. The last decade has seen the emergence of a range of approaches to the implementation in health care settings of referral to Internet-based applications for screening and brief interventions (eSBI) for alcohol. Research in this area is in its infancy, but there is a small body of evidence providing early indications about implementation and sustainability, and a number of studies are currently underway. This paper examines some of the evidence emerging from these and other studies and assesses the implications for the future of eSBI delivery in primary care settings

The Effect of Question Order on Outcomes in the Core Outcome Set for Brief Alcohol Interventions Among Online Help-Seekers: Protocol for a Factorial Randomized Trial

Background: A core outcome set (COS) for trials and evaluations of the effectiveness and efficacy of alcohol brief interventions (ABIs) has recently been established through international consensus to address the variability of outcomes evaluated. / Objective: This is a protocol for studies to assess if there are order effects among the questions included in the COS. / Methods: The 10 items of the COS are organized into 4 clusters. A factorial design will be used with 24 arms, where each arm represents 1 order of the 4 clusters. Individuals searching online for help will be asked to complete a questionnaire, and consenting participants will be randomized to 1 of the 24 arms (double-blind with equal allocation). Participants will be included if they are 18 years or older. The primary analyses will (1) estimate how the order of the clusters of outcomes affects how participants respond and (2) investigate patterns of abandonment of the questionnaire. / Results: Data collection is expected to commence in November 2020. A Bayesian group sequential design will be used with interim analyses planned for every 50 participants completing the questionnaire. Data collection will end no more than 24 months after commencement, and the results are expected to be published no later than December 2023. / Conclusions: Homogenizing the outcomes evaluated in studies of ABIs is important to support synthesis, and the COS is an important step toward this goal. Determining whether there may be issues with the COS question order may improve confidence in using it and speed up its dissemination in the research community. We encourage others to adopt the protocol as a study within their trial as they adopt the ORBITAL (Outcome Reporting in Brief Intervention Trials: Alcohol) COS to build a worldwide repository and provide materials to support such analysis. / Trial Registration: ISRCTN Registry ISRCTN17954645; http://www.isrctn.com/ISRCTN17954645 / International Registered Report Identifier (IRRID): PRR1-10.2196/2417

The Effect of Question Order on Outcomes in the Core Outcome Set for Brief Alcohol Interventions Among Online Help-Seekers: Protocol for a Factorial Randomized Trial

Background: A core outcome set (COS) for trials and evaluations of the effectiveness and efficacy of alcohol brief interventions (ABIs) has recently been established through international consensus to address the variability of outcomes evaluated. / Objective: This is a protocol for studies to assess if there are order effects among the questions included in the COS. / Methods: The 10 items of the COS are organized into 4 clusters. A factorial design will be used with 24 arms, where each arm represents 1 order of the 4 clusters. Individuals searching online for help will be asked to complete a questionnaire, and consenting participants will be randomized to 1 of the 24 arms (double-blind with equal allocation). Participants will be included if they are 18 years or older. The primary analyses will (1) estimate how the order of the clusters of outcomes affects how participants respond and (2) investigate patterns of abandonment of the questionnaire. / Results: Data collection is expected to commence in November 2020. A Bayesian group sequential design will be used with interim analyses planned for every 50 participants completing the questionnaire. Data collection will end no more than 24 months after commencement, and the results are expected to be published no later than December 2023. / Conclusions: Homogenizing the outcomes evaluated in studies of ABIs is important to support synthesis, and the COS is an important step toward this goal. Determining whether there may be issues with the COS question order may improve confidence in using it and speed up its dissemination in the research community. We encourage others to adopt the protocol as a study within their trial as they adopt the ORBITAL (Outcome Reporting in Brief Intervention Trials: Alcohol) COS to build a worldwide repository and provide materials to support such analysis. / Trial Registration: ISRCTN Registry ISRCTN17954645; http://www.isrctn.com/ISRCTN17954645 / International Registered Report Identifier (IRRID): PRR1-10.2196/2417

Kinase inhibition leads to hormesis in a dual phosphorylation-dephosphorylation cycle

This is the final version of the article. Available from the publisher via the DOI in this record.Many antimicrobial and anti-tumour drugs elicit hormetic responses characterised by low-dose stimulation and high-dose inhibition. While this can have profound consequences for human health, with low drug concentrations actually stimulating pathogen or tumour growth, the mechanistic understanding behind such responses is still lacking. We propose a novel, simple but general mechanism that could give rise to hormesis in systems where an inhibitor acts on an enzyme. At its core is one of the basic building blocks in intracellular signalling, the dual phosphorylation-dephosphorylation motif, found in diverse regulatory processes including control of cell proliferation and programmed cell death. Our analytically-derived conditions for observing hormesis provide clues as to why this mechanism has not been previously identified. Current mathematical models regularly make simplifying assumptions that lack empirical support but inadvertently preclude the observation of hormesis. In addition, due to the inherent population heterogeneities, the presence of hormesis is likely to be masked in empirical population-level studies. Therefore, examining hormetic responses at single-cell level coupled with improved mathematical models could substantially enhance detection and mechanistic understanding of hormesis.Funding bodies: BBSRC (BB/J010340/1); EPSRC (EP/I00503X/1); Wellcome Trust (ISSF to University of Exeter)

Fuel Optimization in Multiple Diesel Driven Generator Power Plants

This paper presents two fuel optimization approaches for independent power producer (IPP) power plants consisting of multiple diesel driven generator sets (DGs). The optimization approaches utilize assumed information about the fuel consumption characteristics of each DG in an effort to demonstrate the potential benefits of acquiring such information. Reasonable variations in fuel consumption characteristics are based on measurements of a DG during restricted air filter flow operation. The two approaches are: (i) a gradient search approach capable of finding the optimal power generation for each DG in a fixed selection of DGs accommodating a given plant power reference and (ii) a genetic algorithm approach further capable of determining the optimal selection of DGs to operate in an IPP power plant. Both approaches show notable potential benefits, in terms of fuel savings, compared to current market-leading solutions

Fuel Optimization in Multiple Diesel Driven Generator Power Plants

This paper presents two fuel optimization approaches for independent power producer (IPP) power plants consisting of multiple diesel driven generator sets (DGs). The optimization approaches utilize assumed information about the fuel consumption characteristics of each DG in an effort to demonstrate the potential benefits of acquiring such information. Reasonable variations in fuel consumption characteristics are based on measurements of a DG during restricted air filter flow operation. The two approaches are: (i) a gradient search approach capable of finding the optimal power generation for each DG in a fixed selection of DGs accommodating a given plant power reference and (ii) a genetic algorithm approach further capable of determining the optimal selection of DGs to operate in an IPP power plant. Both approaches show notable potential benefits, in terms of fuel savings, compared to current market-leading solutions

X-Ray Computed Tomography: Semiautomated Volumetric Analysis of Late-Stage Lung Tumors as a Basis for Response Assessments

Background. This study presents a semiautomated approach for volumetric analysis of lung tumors and evaluates the feasibility of using volumes as an alternative to line lengths as a basis for response evaluation criteria in solid tumors (RECIST). The overall goal for the implementation was to accurately, precisely, and efficiently enable the analyses of lesions in the lung under the guidance of an operator. Methods. An anthropomorphic phantom with embedded model masses and 71 time points in 10 clinical cases with advanced lung cancer was analyzed using a semi-automated workflow. The implementation was done using the Cognition Network Technology. Results. Analysis of the phantom showed an average accuracy of 97%. The analyses of the clinical cases showed both intra- and interreader variabilities of approximately 5% on average with an upper 95% confidence interval of 14% and 19%, respectively. Compared to line lengths, the use of volumes clearly shows enhanced sensitivity with respect to determining response to therapy. Conclusions. It is feasible to perform volumetric analysis efficiently with high accuracy and low variability, even in patients with late-stage cancer who have complex lesions

Spring bloom dynamics in a subarctic fjord influenced by tidewater outlet glaciers (Godthåbsfjord, SW Greenland)

In high-latitude fjord ecosystems, the spring bloom accounts for a major part of the annual primary production and thus provides a crucial energy supply to the marine food web. However, the environmental factors that control the timing and intensity of these spring blooms remain uncertain. In 2013, we studied the spring bloom dynamics in Godthåbsfjord, a large fjord system adjacent to the Greenland Ice Sheet. Our surveys revealed that the spring bloom did not initiate in the inner stratified part of the fjord system but only started farther away from tidewater outlet glaciers. A combination of out-fjord winds and coastal inflows drove an upwelling in the inner part of the fjord during spring (April–May), which supplied nutrient-rich water to the surface layer. This surface water was subsequently transported out-fjord, and due to this circulation regime, the biomass accumulation of phytoplankton was displaced away from the glaciers. In late May, the upwelling weakened and the dominant wind direction changed, thus reversing the direction of the surface water transport. Warmer water was now transported toward the inner fjord, and a bloom was observed close to the glacier terminus. Overall, our findings imply that the timing, intensity, and location of the spring blooms in Godthåbsfjord are controlled by a combination of upwelling strength and wind forcing. Together with sea ice cover, the hydrodynamic regime hence plays a crucial role in structuring food web dynamics of the fjord ecosystem

Childhood maltreatment and attention deficit hyperactivity disorder symptoms in adults: a large twin study

BACKGROUND: Childhood maltreatment (CM) has been associated with increased risk of attention deficit hyperactivity disorder (ADHD) in children and adults. It is, however, unclear whether this association is causal or due to familial confounding. Method Data from 18 168 adult twins, aged 20-46 years, were drawn from the population-based Swedish twin registry. Retrospective self-ratings of CM (emotional and physical neglect, physical and sexual abuse and witnessing family violence), and self-ratings for DSM-IV ADHD symptoms in adulthood were analysed. Possible familial confounding was investigated using a within twin-pair design based on monozygotic (MZ) and dizygotic (DZ) twins. RESULTS: CM was significantly associated with increased levels of ADHD symptom scores in adults [regression coefficient: 0.40 standard deviations, 95% confidence interval (CI) 0.37-0.43]. Within twin-pair analyses showed attenuated but significant estimates within DZ (0.29, 95% CI 0.21-0.36) and MZ (0.18, 95% CI 0.10-0.25) twin pairs. Similar results emerged for hyperactive/impulsive and inattentive ADHD symptom scores separately in association with CM. We conducted sensitivity analyses for early maltreatment, before age 7, and for abuse and neglect separately, and found similarly reduced estimates in DZ and MZ pairs. Re-traumatization after age 7 did not significantly influence results. CONCLUSIONS: CM was significantly associated with increased ADHD symptoms in adults. Associations were partly due to familial confounding, but also consistent with a causal interpretation. Our findings support cognitive neuroscience studies investigating neural pathways through which exposure to CM may influence ADHD. Clinicians treating adults with ADHD should be aware of the association with maltreatment