The evolution and comparative neurobiology of endocannabinoid signalling

CB(1)- and CB(2)-type cannabinoid receptors mediate effects of the endocannabinoids 2-arachidonoylglycerol (2-AG) and anandamide in mammals. In canonical endocannabinoid-mediated synaptic plasticity, 2-AG is generated postsynaptically by diacylglycerol lipase alpha and acts via presynaptic CB(1)-type cannabinoid receptors to inhibit neurotransmitter release. Electrophysiological studies on lampreys indicate that this retrograde signalling mechanism occurs throughout the vertebrates, whereas system-level studies point to conserved roles for endocannabinoid signalling in neural mechanisms of learning and control of locomotor activity and feeding. CB(1)/CB(2)-type receptors originated in a common ancestor of extant chordates, and in the sea squirt Ciona intestinalis a CB(1)/CB(2)-type receptor is targeted to axons, indicative of an ancient role for cannabinoid receptors as axonal regulators of neuronal signalling. Although CB(1)/CB(2)-type receptors are unique to chordates, enzymes involved in biosynthesis/inactivation of endocannabinoids occur throughout the animal kingdom. Accordingly, non-CB(1)/CB(2)-mediated mechanisms of endocannabinoid signalling have been postulated. For example, there is evidence that 2-AG mediates retrograde signalling at synapses in the nervous system of the leech Hirudo medicinalis by activating presynaptic transient receptor potential vanilloid-type ion channels. Thus, postsynaptic synthesis of 2-AG or anandamide may be a phylogenetically widespread phenomenon, and a variety of proteins may have evolved as presynaptic (or postsynaptic) receptors for endocannabinoids

Performance Comparison of Different Load Balancing Algorithms in Cloud Computing

Cloud computing offers economical, scalable, and instantaneous computing resources to enterprises, allowing them to manage substantial traffic volumes and cater to a multitude of users. But the need for effective load balancing techniques has grown significantly as cloud computing becomes more and more popular. To guarantee the best possible performance, availability, and dependability of apps and services, load balancing is a crucial component of cloud computing. This paper offers a comparative study of different cloud computing technologies and load balancing strategies. We present a performance comparison of software-based load balancing; our analysis compares various service broker policies, such as closest distance, optimized, and reconfigurable, with algorithms such as round robin, throttled, and equally spread. Overall, this paper helps readers understand load balancing mechanisms in cloud computing

Receiving Aphasia Intervention in a Virtual Environment: The Participants’ Perspective

Background: Digital technology is making an increasing contribution to aphasia therapy. However applications of virtual reality are rare. EVA Park is a virtual island developed with and for people with aphasia. It is a multi-user environment, which enables people with aphasia to interact with support workers, therapists and each other. The first study to use EVA Park in aphasia rehabilitation demonstrated significant gains in functional communication. This paper augments the findings of that study, by reporting results from qualitative interviews conducted with the 20 study participants. Aims: This study aimed to determine the views of participants about the intervention that they received in EVA Park, and the impacts of that intervention. Long-term retrospective views were also explored. Methods & Procedures: Participants took part in 1:1, semi-structured interviews two weeks before (Entry) and to weeks after (Exit) the intervention. Questions focussed on activities undertaken by participants, communication, changes since the stroke and uses of technology. Exit interviews additionally explored participants’ views and experiences of EVA Park and any perceived impacts of the intervention. A sub-set of 5 participants was interviewed at least one year later, to explore long term recollections of the EVA Park intervention and any perceived long term impacts. Interview data were transcribed and subject to framework analysis. Outcomes & Results: The thematic framework comprised 10 parent themes and 33 sub-themes. Following ‘affect’, the largest single theme related to EVA Park, with 636 coded references. Comments were overwhelmingly positive. EVA Park intervention was strongly associated with fun and enjoyment. Participants particularly valued their relationship with the support workers who delivered the intervention. The virtual locations and activities in EVA Park were also appreciated, together with the contact with other participants. Perceived impacts related to communication, activity, computer use and confidence. Most participants in the long term interviews described maintained impacts. Conclusions: These interview results indicate that the first intervention delivered in EVA Park was highly acceptable to participants and perceived as beneficial. They augment the findings of our experimental study and suggest that EVA Park could be a valuable addition to the resources available to practising clinician

Codesign for People with Aphasia Through Tangible Design Languages

Codesign techniques encourage designers and end-users to work together in the creation of design solutions, but often make assumptions about the ways in which participants will be able to communicate. This can lead to the unwitting exclusion of people with communication impairments from the design of technologies that have the potential to transform their lives. This paper reports our research into codesign techniques for people whose communication skills are impaired. A variety of techniques were explored on two projects; some were adaptations of existing codesign techniques, others were created specially. In both cases, the emphasis was on creating tangible design languages. The results illustrate how people with communication impairments can be given a voice in design and demonstrate the benefits of doing so

Donepezil Effects on Mood in Patients with Schizophrenia and Schizoaffective Disorder

Donepezil, 5 mg/d for 6 wk then 10 mg/d for 6 wk, and placebo daily for 12 wk in a double-blind cross-over paradigm, was added to the therapeutic regimen of 13 patients with schizophrenia or schizoaffective disorders, clinically stable on atypical antipsychotic medications. Patients had varying degrees of depressive symptoms, ranging from no depression to clinically significant depression. There was no worsening or induction of depression in individual patients or the group as a whole. In addition there was a statistically significant antidepressant effect in the group as a whole during the donepezil condition and a clinically significant antidepressant effect in the patients with clinically significant depressive symptoms, although there were not enough depressed patients in the group to conclude that donepezil may have antidepressant effects. Thus, in this study, donepezil did not induce or worsen depressive symptoms in schizophrenic and schizoaffective disorder patients

A Randomised Trial of Social Support Group Intervention for People with Aphasia: A Novel Application of Virtual Reality

About a third of strokes cause aphasia, or language loss, with profound consequences for the person’s social participation and quality of life. These problems may be mitigated by group social support. But this intervention is not available to all individuals. This study investigated whether it is feasible to deliver group social support to people with aphasia via a multi-user, virtual reality platform. It also explored the indicative effects of intervention and the costs. Intervention aimed to promote wellbeing and communicative success. It enabled participants to form new social connections and share experiences of living with aphasia. It comprised 14 sessions delivered over 6 months and was led by community based co-ordinators and volunteers. Feasibility measures comprised: recruitment and retention rates, compliance with intervention and assessment of treatment fidelity. Effects of intervention were explored using a waitlist randomised controlled design, with outcome measures of wellbeing, communication, social connectedness and quality of life. Two intervention groups were randomised to an immediate condition and two were randomised to a delayed condition. The main analysis explored scores on the measures between two time points, between which those in the immediate condition had received intervention, but those in the delayed group had not (yet). A comprehensive approach to economic data collection ensured that all costs of treatment delivery were recorded. Feasibility findings showed that the recruitment target was met (N = 34) and 85.3% (29/34) of participants completed intervention. All groups ran the 14 sessions as planned, and participants attended a mean of 11.4 sessions (s.d. 2.8), which was 81.6% of the intended dose. Fidelity checking showed minimal drift from the manualised intervention. No significant change was observed on any of the outcome measures, although the study was not powered to detect these. Costs varied across the four groups, from £7,483 - £12,562 British Pounds Sterling ($10,972 -$18,419 US dollars), depending on travel costs, the relative contributions of volunteers and the number of hardware loans that were needed. The results suggest that a larger trial of remote group support, using virtual reality, would be merited. However the treatment content and regime, and the selection of outcome measures should be reviewed before conducting the trial

Delivering word retrieval therapies for people with aphasia in a virtual communication environment

Background: Delivering therapy remotely, via digital technology, can enhance provision for people with aphasia. EVA Park is a multi-user virtual island that can be used for such delivery. The first EVA Park study showed that daily language stimulation delivered via the platform improved functional communication and was positively received by users (Marshall et al, 2016; Amaya et al, 2018). This paper reports two single case studies, evaluating its capacity to deliver targeted language interventions. The first employed therapy for noun retrieval, using cued picture naming and modified Sematic Feature Analysis. The second employed modified Verb Network Strengthening Treatment (VNeST). Aims: This study aimed to determine if treatment delivery was feasible in EVA Park, as assessed by participant compliance, treatment fidelity and participants’ views. It explored the impact of the therapies on treated and untreated word production, connected speech and functional communication. Methods & Procedures: Two participants with aphasia each received 20 sessions of individual therapy in EVA Park, delivered over 5 weeks. Feasibility was assessed by measuring compliance with the therapy regime, recording and checking the fidelity of 20% of treatment sessions, and using post therapy interviews to explore participant views. Treatment outcomes were evaluated via repeated measures single case designs, in which assessments were administered twice before therapy, immediately post therapy and five weeks later. Outcome measures included Object Picture Naming (study 1), Sentence Elicitation Pictures (study 2), Naming 84 items from the Object and Action Naming Battery (study 2), Narrative Production (Study 2), the Northwestern Assessment of Verb and Sentences: Argument Structure Production Test (Study 2) and Communication Activities of Daily Living – 2 (Study 1 & 2). Outcomes & Results: Feasibility results were excellent. Both participants were fully compliant with the therapy regime. There was at least 90% fidelity with the treatment protocols and participant views were positive. Outcomes varied across the studies. The noun therapy significantly improved the naming of treated words, with good maintenance. Lexical gains were less evident on the Sentence Elicitation Pictures used in the VNeST study. Neither study demonstrated generalisation to untreated words, connected speech or functional communication. Conclusions: Two treatment approaches, designed for face to face delivery, could be delivered remotely in EVA Park. Outcomes for the noun treatment were comparable to previous evaluations. Comparisons with previous research were more challenging for VNeST, owing to differences in methodology. Further evaluations of other treatment approaches are warranted

Factors that impact on recruitment to randomised trials in health care : a qualitative evidence synthesis (Review)

Peer reviewedPublisher PD

Integrative Literature Review of Factors Related to Breastfeeding in African American Women: Evidence for a Potential Paradigm Shift

Background: Human milk has widespread health benefits for infants, mothers, and society. However, not all populations of women, particularly African American women, engage in human milk feeding at high rates. Research aim: The purpose of this integrative literature review is twofold: (a) to examine factors that influence low rates of human milk feeding among African American women and (b) to introduce a need for a methodological paradigm shift to develop culturally relevant and effective interventions. Methods: The authors searched four electronic social science databases for peer-reviewed journal articles pertaining to human milk among African American women published from 1990 to 2015. Both coauthors independently assessed these articles using thematic analysis and validation. The database search yielded 47 peer-reviewed articles. Results: Three main themes emerged explaining the human milk feeding disparity: (a) the social characteristics of women likely not to feed human milk (e.g., low socioeconomic status, single); (b) women's perceptions of human milk feeding; and (c) the quality of human milk feeding information provided by health care providers (i.e., limited human milk information). Conclusion: Current literature does include sociohistorical factors that have shaped current norms. Adding sociohistorical frameworks, paying particular attention to the embodied experience of historical trauma, could lead to the development of new evidence-based, culturally sensitive interventions to enhance human milk feeding in the African American community

Core Outcome Set-STAndards for Reporting The COS-STAR Statement

Background Core outcome sets (COS) can enhance the relevance of research by ensuring that outcomes of importance to health service users and other people making choices about health care in a particular topic area are measured routinely. Over 200 COS to date have been developed, but the clarity of these reports is suboptimal. COS studies will not achieve their goal if reports of COS are not complete and transparent. Methods and Findings In recognition of these issues, an international group that included experienced COS developers, methodologists, journal editors, potential users of COS (clinical trialists, systematic reviewers, and clinical guideline developers), and patient representatives developed the Core Outcome Set–STAndards for Reporting (COS-STAR) Statement as a reporting guideline for COS studies. The developmental process consisted of an initial reporting item generation stage and a two-round Delphi survey involving nearly 200 participants representing key stakeholder groups, followed by a consensus meeting. The COS-STAR Statement consists of a checklist of 18 items considered essential for transparent and complete reporting in all COS studies. The checklist items focus on the introduction, methods, results, and discussion section of a manuscript describing the development of a particular COS. A limitation of the COS-STAR Statement is that it was developed without representative views of low- and middle-income countries. COS have equal relevance to studies conducted in these areas, and, subsequently, this guideline may need to evolve over time to encompass any additional challenges from developing COS in these areas. Conclusions With many ongoing COS studies underway, the COS-STAR Statement should be a helpful resource to improve the reporting of COS studies for the benefit of all COS users