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

Applicability of unmanned aerial systems to homeland defense missions

Battlefield success of Unmanned Aerial Systems (UAS) prompted Department of Defense and Department of Homeland Security leaders to examine their possible applicability to homeland defense missions within the National Strategy for Homeland Security. The National Strategy for Homeland Security incorporates all levels of government to include law enforcement agencies and the military, the predominant owner and operator of UASs. The military, however, is restricted in its domestic role by the Posse Comitatus Act, and is therefore limited in its domestic employment of UASs. In order to determine the applicability of UASs to homeland defense missions, it is necessary to examine the capabilities of available UASs, to match them with mission requirements, and determine the legality of where they can be used and who can operate them. A policy that places combat UAS capability with Title 10 military forces and homeland defense mission capability with Title 32 and law enforcement agencies will fulfill the goals stated in the national strategy and function within the current legal framework.http://archive.org/details/applicabilityofu109452509Approved for public release; distribution is unlimited

Pharmacokinetics of Trazodone and Its Major Metabolite M-Chlorophenylpiperazine in Plasma and Brain of Rats

Sprague–Dawley rats were used as models for single trazodone administration (males), continuous administration and dose proportionality experiments (males, females, pregnant females). Plasma and brain tissue were analysed for trazodone and its active metabolite, m-chlorophenylpiperazine (m-CPP). Fetal exposure to trazodone and m-CPP was assessed and differences in their steady-state plasma concentration were sought between adult males and females. Both trazodone and m-CPP rapidly appeared in plasma and brain tissue following a single intraperitoneal trazodone dose with brain concentrations exceeding those in plasma. Plasma concentrations of m-CPP were lower than those of trazodone but exceeded them in brain tissue. Chronic administration using osmotic mini-pumps revealed a significant linear relationship between trazodone concentration in plasma and brain at steady-state (r=0.96, p\u3c0.0001). No simple relationship was found between plasma and brain tissue concentration for m-CPP. In contrast to observations following single trazodone administration, m-CPP concentrations at steady-state were lower than trazodone concentrations in brain tissue, suggesting a lack of stationarity in the disposition of trazodone over time. No significant differences in plasma or brain tissue drug concentrations relative to administered trazodone dose were observed between male and female rats, nor between pregnant and non-pregnant females. Trazodone and mCPP were both detected in fetal and placental tissues, with placenta having the highest concentrations. The data suggest that neuropharmacological studies of trazodone could yield different results depending upon the route and schedule of drug administration. Maternally administered trazodone, like many other antidepressants, is distributed to fetal tissues in rodents, reaffirming the need for caution in treating pregnant women with psychoactive drugs

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

Primary Frequency Regulation with Load-Side Participation-Part I: Stability and Optimality

We present a method to design distributed generation and demand control schemes for primary frequency regulation in power networks that guarantee asymptotic stability and ensure fairness of allocation. We impose a passivity condition on net power supply variables and provide explicit steady state conditions on a general class of generation and demand control dynamics that ensure convergence of solutions to equilibria that solve an appropriately constructed network optimization problem. We also show that the inclusion of controllable demand results in a drop in steady state frequency deviations. We discuss how various classes of dynamics used in recent studies fit within our framework and show that this allows for less conservative stability and optimality conditions. We illustrate our results with simulations on the IEEE 68 bus system and observe that both static and dynamic demand response schemes that fit within our framework offer improved transient and steady state behavior compared with control of generation alone. The dynamic scheme is also seen to enhance the robustness of the system to time-delays.ER

Development of core outcome sets for studies relating to awareness and clinical management of reduced fetal movement

Objective: This study aimed to create core outcome sets (COSs) for use in research studies relating to the awareness and clinical management of reduced fetal movement (RFM). Design: Delphi survey and consensus process. Setting: International. Population: A total of 128 participants (40 parents, 19 researchers and 65 clinicians) from 16 countries. Methods: A systematic literature review was conducted to identify outcomes in studies of interventions relating to the awareness and the clinical management of RFM. Using these outcomes as a preliminary list, stakeholders rated the importance of these outcomes for inclusion in COSs for studies of: (i) awareness of RFM; and (ii) clinical management of RFM. Main outcome measures: Preliminary lists of outcomes were discussed at consensus meetings where two COSs (one for studies of RFM awareness and one for studies of clinical management of RFM). Results: The first round of the Delphi survey was completed by 128 participants, 66% of whom (n = 84) completed all three rounds. Fifty outcomes identified by the systematic review, after multiple definitions were combined, were voted on in round one. Two outcomes were added in round one, and as such 52 outcomes were voted on in two lists in rounds two and three. The COSs for studies of RFM awareness and clinical management are comprised of eight outcomes (four maternal and four neonatal) and 10 outcomes (two maternal and eight neonatal), respectively. Conclusions: These COSs provide researchers with the minimum set of outcomes to be measured and reported in studies relating to the awareness and the clinical management of RFM.</p

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

Time correlation function and finite field approaches to the calculation of the fifth order Raman response in liquid xenon

The fifth order, two-dimensional Raman response in liquid xenon is calculated via a time correlation function (TCF) theory and the numerically exact finite field method. Both employ classical molecular dynamics simulations. The results are shown to be in excellent agreement, suggesting the efficacy of the TCF approach, in which the response function is written approximately in terms of a single classical multitime TCF. (c) 2006 American Institute of Physics

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

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