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Affective disorders are widely distributed disorders with severe social and economic effects. Strong evidence underlines that effective treatment helps to restore function and quality of life. Unfortunately, patients with major affective disorders respond variably and, at times, unpredictably to different treatments, which underline the need of alternative approaches. Due to the action of most modern antidepressant drugs, serotonergic mechanisms have traditionally been suggested to play major roles in the pathophysiology. However, recent clinical evidence strongly suggests involvement of neurodegenerative pathology in the disease. Since there is accumulating evidence that the novel neurotransmitter NO acts as a neuromodulator, and participate in several sub-cellular processes, such as cellular memory and neuronal toxicity, nitrergic pathways may have an important role in hippocampal degenerative pathology and cognitive deficits seen in patients with affective disorders.
A few clinical and several pre-clinical studies, strongly suggests involvement of the nitric oxide (NO) signalling pathway in these disorders (Harvey 1996). Several of the conventional neurotransmitters, including serotonin, glutamate and GABA, are intimately regulated by NO (Wegener et al. 2000). Interestingly, distinct classes of antidepressants (Imipramine, Tianeptine, Citalopram and Paroxetine) have been found to modulate the NO level in the living rat hippocampus in clinically relevant doses (Wegener et al. 2003). Moreover, our recent work, using selective inhibitors of phosphodiesterase 5, indicate that the whole NO signalling pathway may play a major role in the behavioural and neurochemical effects observed.
The NO system is therefore a potential target for antidepressant and anxiolytic drug action in acute therapy as well as in prophylaxis.
We have observed the G23 field of the Galaxy AndMass Assembly (GAMA) survey using the Australian Square Kilometre Array Pathfinder (ASKAP) in its commissioning phase to validate the performance of the telescope and to characterise the detected galaxy populations. This observation covers ~48 deg2 with synthesised beam of 32.7 arcsec by 17.8 arcsec at 936MHz, and ~39 deg2 with synthesised beam of 15.8 arcsec by 12.0 arcsec at 1320MHz. At both frequencies, the root-mean-square (r.m.s.) noise is ~0.1 mJy/beam. We combine these radio observations with the GAMA galaxy data, which includes spectroscopy of galaxies that are i-band selected with a magnitude limit of 19.2. Wide-field Infrared Survey Explorer (WISE) infrared (IR) photometry is used to determine which galaxies host an active galactic nucleus (AGN). In properties including source counts, mass distributions, and IR versus radio luminosity relation, the ASKAP-detected radio sources behave as expected. Radio galaxies have higher stellar mass and luminosity in IR, optical, and UV than other galaxies. We apply optical and IR AGN diagnostics and find that they disagree for ~30% of the galaxies in our sample. We suggest possible causes for the disagreement. Some cases can be explained by optical extinction of the AGN, but for more than half of the cases we do not find a clear explanation. Radio sources aremore likely (~6%) to have an AGN than radio quiet galaxies (~1%), but the majority of AGN are not detected in radio at this sensitivity.
Background: In Alberta in 2016 more people died from an opioid overdose than from motor vehicle crashes. Naloxone is an opioid antagonist - it can reverse an opioid overdose for a period of 30 to 60 minutes. Naloxone kits are available free at emergency departments and community organizations around the province with training provided at the point of pickup. It is possible that training may be refused or may be forgotten and people are often left to rely solely on the instructions included in the kit. Human centred design can improve the way people interact with overdose instructions. Aim Statement: This study will measure the effectiveness and usefulness of prototype community naloxone kit instructions over a six month period of time (2018) in Calgary and Edmonton with the aim to use human centred design principles to improve the way people interpret emergency overdose response directions. Measures & Design: Information design experts engaged people with lived experience to provide a process map outlining the current role that educational materials and instructions for community naloxone kits play in responding to an opioid overdose. Alberta Health Services (AHS) Human Factors, in collaboration with AHS harm reduction developed the protocol and administered pre- and post-questionnaire and specific ‘performance checkpoints’ intended to measure effectiveness and usefulness. A simulated overdose including a mannequin, injection trainer and anatomical paper diagram was designed and a community naloxone kit with instructions setting was provided. Participants were recruited through harm reduction nurses with pre-existing clinical relationships (experienced group), family and friends of people who use opioids and general public (non-experienced) through the University of Alberta Faculty of Art and Design. Evaluation/Results: A total of 30 voluntary participants provided their informed consent and engaged in a simulated overdose scenario using a set of prototype instructions developed by a professional information designer. Through repeated data sampling, the following points were observed and will be integrated in the next iteration of design: It isn't clear to people what opioids are. It isn't clear to people that giving a dose of naloxone will not harm a person, especially if they have not overdosed. Almost none of the participants called 911. People seem to read pictures and text equally in the non-experienced group, but in the experienced group, typically read the pictures. Many participants stated that they knew how to do rescue breaths, but did not perform them correctly. Performing the procedure is a not the same as being asked about how to perform the procedure. Discussion/Impact: Even with new instructional prototypes, many participants identified components that were unclear or confusing. The experienced group made less mistakes than the non-experienced group. They seemed to be more invested or interested in saving a friend's life. These instructions will go through another round of design to incorporate feedback from end users. The final product will be part of a larger provincial emergency medicine initiative that includes participant led design and education around emergency response in opioid overdose settings.
Suicide attempts and non-suicidal self-harm (NSSH) are major public health concerns that affect millions of young people worldwide. Consequently, there is a strong need for up-to-date epidemiological data in this population.
To provide prevalence and trend estimates of suicidal thoughts and behaviours and NSSH thoughts and behaviour in university students.
Data are from a 2018 national health survey for higher education in Norway. A total of 50 054 full-time students (69.1% women) aged 18–35 years participated (response rate 31%). Suicidal ideation, suicide attempts and NSSH were assessed with three items drawn from the Adult Psychiatric Morbidity Survey, and thoughts of NSSH were assessed with one item from the Child and Adolescent Self-Harm in Europe study.
Lifetime suicidal thoughts were reported by 21.0%, and 7.2% reported having such thoughts within the past year. In total, 4.2% reported a suicide attempt, of whom 0.4% reported attempting suicide within the past year. The prevalence of lifetime NSSH behaviour and thoughts was 19.6% and 22.6%, respectively. All four suicidal behaviour and NSSH variables were more common among students who were single, living alone and with a low annual income, as well as among immigrants. There was an increase in suicidal thoughts from 2010 (7.7%) to 2018 (11.4%), which was evident in both men and women.
The observed high and increasing prevalence of suicidal thoughts and NSSH among college and university students is alarming, underscoring the need for further research, preferably registry-linked studies, to confirm whether the reported prevalence is representative of the student population as a whole.
Patient memory for treatment contents is defined as memory for the ideas, concepts, skills, and/or insights (termed treatment points) that the therapist thinks are important for the patient to remember and implement as a part of therapy. This article reviews key findings on patient memory for treatment contents, describes the development and evaluation of the Memory Support Intervention (MSI), and outlines future directions for research. Patient memory for treatment contents is poor, and worse memory is associated with worse treatment outcome. The MSI is composed of eight memory support strategies that therapists incorporate frequently alongside treatment points delivered during treatment-as-usual. Training therapists to deliver the MSI may yield better treatment outcomes by enhancing patient memory for treatment contents. Future research is needed to understand how to best measure patient memory for treatment contents, and the mediators, moderators, and dissemination potential of the MSI.
Background: Almost all patients admitted at acute crisis to a psychiatric ward experience clinically significant symptoms of insomnia. Ward environments pose challenges to both sleep and the delivery of therapy. Despite this, there is no description of how to adapt cognitive behavioural therapy (CBT) for insomnia to overcome these challenges. Aims: (i) To describe the key insomnia presentations observed in the Oxford Ward Sleep Solution (OWLS) trial and (ii) outline key adaptations aimed to increase accessibility and hence effectiveness of CBT for insomnia for a ward setting. Methods: Trial therapists collaboratively agreed the key insomnia presentations and therapy adaptations based on their individual reflective logs used during the trial. Results: Three key insomnia presentations are outlined. These are used to illustrate the application of 10 CBT for insomnia therapy adaptations. These include use of sleep monitoring watches to engage patients in treatment, stabilizing circadian rhythms, reducing the impact of night-time observations and managing discharge as a sleep challenge. Conclusions: Whilst inpatient wards bring challenges for sleep and therapy delivery, creative adaptations can increase the accessibility of evidence based CBT for insomnia techniques. This therapy has proven popular with patients.
Chronic post-traumatic stress disorder (PTSD) behavioural symptoms and medically unexplainable somatic symptoms are reported to occur following the stressful experience of military combatants in war zones.
To determine the contribution of disordered EEG sleep physiology in those military combatants who have unexplainable physical symptoms and PTSD behavioural difficulties following war-zone exposure.
This case-controlled study compared 59 veterans with chronic sleep disturbance with 39 veterans with DSM-IV and clinician-administered PTSD Scale diagnosed PTSD who were unresponsive to pharmacological and psychological treatments. All had standardised EEG polysomnography, computerised sleep EEG cyclical alternating pattern (CAP) as a measure of sleep stability, self-ratings of combat exposure, paranoid cognition and hostility subscales of Symptom Checklist-90, Beck Depression Inventory and the Wahler Physical Symptom Inventory. Statistical group comparisons employed linear models, logistic regression and chi-square automatic interaction detection (CHAID)-like decision trees.
Veterans with PTSD were more likely than those without PTSD to show disturbances in non-rapid eye movement (REM) and REM sleep including delayed sleep onset, less efficient EEG sleep, less stage 4 (deep) non-REM sleep, reduced REM and delayed onset to REM. There were no group differences in the prevalence of obstructive sleep apnoeas/hypopnoeas and periodic leg movements, but sleep-disturbed, non-PTSD military had more EEG CAP sleep instability. Rank order determinants for the diagnosis of PTSD comprise paranoid thinking, onset to REM sleep, combat history and somatic symptoms. Decision-tree analysis showed that a specific military event (combat), delayed onset to REM sleep, paranoid thinking and medically unexplainable somatic pain and fatigue characterise chronic PTSD. More PTSD veterans reported domestic and social misbehaviour.
Military combat, disturbed REM/non-REM EEG sleep, paranoid ideation and medically unexplained chronic musculoskeletal pain and fatigue are key factors in determining PTSD disability following war-zone exposure.
Background: Our view is that sleep disturbance may be a contributory causal factor in the development and maintenance of psychotic experiences. A recent series of randomized controlled intervention studies has shown that cognitive-behavioural approaches can improve sleep in people with psychotic experiences. However, the effects of psychological intervention for improving sleep have not been evaluated in young people at ultra-high risk of psychosis. Improving sleep might prevent later transition to a mental health disorder. Aims: To assess the feasibility and acceptability of an intervention targeting sleep disturbance in young people at ultra-high risk of psychosis. Method: Patients were sought from NHS mental health services. Twelve young people at ultra-high risk of psychosis with sleep problems were offered an eight-session adapted CBT intervention for sleep problems. The core treatment techniques were stimulus control, circadian realignment, and regulating day-time activity. Participants were assessed before and after treatment and at a one month follow-up. Results: All eligible patients referred to the study agreed to take part. Eleven patients completed the intervention, and one patient withdrew after two sessions. Of those who completed treatment, the attendance rate was 89% and an average of 7.6 sessions (SD = 0.5) were attended. There were large effect size improvements in sleep. Post-treatment, six patients fell below the recommended cut-off for clinical insomnia. There were also improvements in negative affect and psychotic experiences. Conclusion: This uncontrolled feasibility study indicates that treating sleep problems in young people at ultra-high of psychosis is feasible, acceptable, and may be associated with clinical benefits.
Multi-layer reconstruction has become standard in endoscopic skull base surgery. The inlay component used can vary among autografts, allografts, xenografts and synthetics, primarily based on surgeon preference. The short- and long-term outcomes of collagen matrix in skull base reconstruction are described.
A case series of patients who underwent endoscopic skull base reconstruction with collagen matrix inlay were assessed. Immediate peri-operative outcomes (cerebrospinal fluid leak, meningitis, ventriculitis, intracranial bleeding, epistaxis, seizures) and delayed complications (delayed healing, meningoencephalocele, prolapse of reconstruction, delayed cerebrospinal fluid leak, ascending meningitis) were examined.
Of 120 patients (51.0 ± 17.5 years, 41.7 per cent female), peri-operative complications totalled 12.7 per cent (cerebrospinal fluid leak, 3.3 per cent; meningitis, 3.3 per cent; other intracranial infections, 2.5 per cent; intracranial bleeding, 1.7 per cent; epistaxis, 1.7 per cent; and seizures, 0 per cent). Delayed complications did not occur in any patients.
Collagen matrix is an effective inlay material. It provides robust long-term separation between sinus and cranial cavities, and avoids donor site morbidity, but carries additional cost.
Sleep disturbances are prominent correlates of acute mood episodes and inadequate recovery in bipolar disorder (BD), yet the mechanistic relationship between sleep physiology and mood remains poorly understood. Using a series of pre-sleep mood inductions and overnight sleep recording, this study examined the relationship between overnight mood regulation and a marker of sleep intensity (non-rapid eye movement sleep slow wave activity; NREM SWA) during the interepisode phase of BD.
Adults with interepisode BD type 1 (BD; n = 20) and healthy adult controls (CTL; n = 23) slept in the laboratory for a screening night, a neutral mood induction night (baseline), a happy mood induction night, and a sad mood induction night. NREM SWA (0.75–4.75 Hz) was derived from overnight sleep EEG recordings. Overnight mood regulation was evaluated using an affect grid pleasantness rating post-mood induction (pre-sleep) and the next morning.
Overnight mood regulation did not differ between groups following the sad or happy inductions. SWA did not significantly change for either group on the sad induction night compared with baseline. In BD only, SWA on the sad night was related to impaired overnight negative mood regulation. On the happy induction night, SWA increased relative to baseline in both groups, though SWA was not related to overnight mood regulation for either group.
These findings indicate that SWA disruption may play a role in sustaining negative mood state from the previous night in interepisode BD. However, positive mood state could enhance SWA in bipolar patients and healthy adults.
Introduction: Our tertiary care institution embarked on the Choosing Wisely campaign to reduce unnecessary testing, and selected the reduction of ankle x-rays as part of its top five priority initiatives. The Low Risk Ankle Rule (LRAR), an evidence-based decision rule, has been derived and validated to clinically evaluate ankle injuries which do not require radiography. The LRAR, is cost-effective, has 100% sensitivity for clinically important ankle injuries and reduces ankle imaging rates by 30-60% in both academic and community setting. Our objective was to significantly reduce the proportion of ankle x-rays ordered for acute ankle injuries presenting to our pediatric Emergency Department (ED). Methods: Medical records were reviewed for all patients presenting to our tertiary care pediatric ED (ages 3- 18 years) with an isolated acute ankle injury from Jan 1, 2016-Sept 30, 2016. Children with outside imaging, an injury that occurred >72 hours prior, or those who had a repeat ED visit for same injury were excluded. Quality improvement (QI) initiatives included multidisciplinary staff education about the LRAR, posters placed within the ED highlighting the LRAR, development of a new diagnostic imaging requisition for ankle x-rays requiring use of the LRAR and collaboration with the Division of Radiology to ensure compliance with new requisition. The proportion of patients presenting to the ED with acute ankle injuries who received x-rays was measured. ED length of stay (LOS), return visits to the ED and orthopedic referrals were collected as balancing measures. Results: At baseline 88% of patients with acute ankle injuries received x-rays. Following our multiple interventions, the proportion of x-rays decreased significantly to 54%, (p<0.001). This decrease in x-ray rate was not associated with an increase in ED LOS, ED return visits or orthopedic referrals. There was an increase uptake of the dedicated x-ray requisition over time to 71%. Conclusion: This QI initiative to increase uptake of the LRAR, resulted in a significant reduction of ankle x-rays rates for children presenting with acute ankle injuries in our pediatric ED without increasing LOS, return visits or need for orthopedic referrals for missed injuries. Just as in the derivation and validation studies, the reductions have been sustained and reduced unnecessary testing and ionizing radiation.
When Footlight Parade went before the cameras during the summer of 1933, the Warner Bros ‘Great Depression musicals’ template was already established, but it represents the highlight of this series. Busby Berkeley was comfortably ensconced at Warners with a crew he could trust and who understood his eccentric approach to staging dance numbers. The studio executives, while concerned about costs, mostly stayed out of his way. And for the first time in the series, a real movie star had climbed on board. Propelled by James Cagney in the lead role, Footlight Parade sports a modern, breakneck pace, as the characters fight for artistic and financial survival in the midst of economic and cultural dislocation, conditions not far removed from those that many Americans were facing during the Great Depression.
Furthermore, Footlight Parade echoed the optimism and energy generated during the initial months of Franklin D. Roosevelt's administration. Immediately upon attaining office, the new administration attacked the problems underlying the Great Depression by securing congressional enactment of an unprecedented quantity of substantive legislation during its first 100 days. The strong and speedy start made by FDR's New Deal programme inspired hopes that better times were nigh. Part of what makes the film so powerful and singular is its resistance to the usual conventions, both of its own time and the decades that followed. Very little in Footlight Parade is done by rote. As well as viscerally representing the mood of many Americans during the Great Depression, it epitomises the Warner Bros film ethos of championing the underdog struggling to get ahead in the face of amassed power, something the Warners themselves had needed to do during their ultimately successful quest to make their studio one of the majors in the 1920s. Footlight is more gritty, grimy and realistic, and quicker-paced than the typical musical – even the Warner Bros ones that preceded it. The people who populate the movie are often desperate, sometimes profane (at least by Hollywood standards), and concerned with survival. Most of the best numbers are saved for the end of the film, instead of being doled out steadily throughout. Nobody breaks into song unless it is part of a real stage number; in the world of Footlight, no orchestra arises dreamily out of nowhere to accompany a character in a fanciful romantic moment.
Tannins have long been considered ‘anti-nutritional’ factors in monogastric nutrition, shown to reduce feed intake and palatability. However, recent studies revealed that compared with condensed tannins, hydrolysable tannins (HT) appear to have far less impact on growth performance, but may be inhibitory to the total activity of caecal bacteria. This in turn could reduce microbial synthesis of skatole and indole in the hindgut of entire male pigs (EM). Thus, the objective of this study was to determine the impact of a group of dietary HT on growth performance, carcass traits and boar taint compounds of group housed EM. For the study, 36 Swiss Large White boars were assigned within litter to three treatment groups. Boars were offered ad libitum one of three finisher diets supplemented with 0 (C), 15 (T15) or 30 g/kg (T30) of HT from day 105 to 165 of age. Growth performance, carcass characteristics, boar taint compounds in the adipose tissue and cytochrome P450 (CYP) isoenzymes CYP2E1, CYP1A2 and CYP2A19 gene expression in the liver was assessed. Compared with C, feed efficiency but not daily gain and daily feed intake was lower (P<0.05) in T15 and T30 boars. Except for the percentage carcass weight loss during cooling, which tended (P<0.10) to be greater in T30 than C and T15, carcass characteristics were not affected by the diets. In line with the numerically lower androstenone level, bulbourethral and salivary glands of T30 boars were lighter (P<0.05) than of T15 with intermediate values for C. Indole level was lower (P<0.05) in the adipose tissue of T30 than C pigs with intermediate levels in T15. Skatole levels tended (P<0.10) to be lower in T30 and C than T15 pigs. Hepatic gene expression of CYP isoenzymes did not differ between-treatment groups, but was negatively correlated (P<0.05) with androstenone (CYP2E1 and CYP1A2), skatole (CYP2E1, CYP2A) and indole (CYP2A) level. In line with the numerically highest androstenone and skatole concentrations, boar taint odour but not flavour was detected by the panellists in loins from T15 compared with loins from C and T30 boars. These results provide evidence that HT affected metabolism of indolic compounds and androstenone and that they affected the development of accessory sex glands. However, the effects were too small to be detected by sensory evaluation.
Carnivores are valued by conservationists globally but protecting them can impose direct costs on rural, livestock-dependent communities. Financial incentives are increasingly used with the goal of increasing people's tolerance of predators, but the definition of tolerance has been vague and inconsistent. Empirical correlations between attitudinal and behavioural measures of tolerance imply that attitudes may be a valid proxy for behaviours. However, theoretical differences between the concepts suggest that attitudinal tolerance and behavioural intention to kill cats would have different underlying determinants. We surveyed 112 residents within a forest–farm mosaic in northern Belize inhabited by jaguars Panthera onca and four other species of wild cats. A conservation payment programme pays local landowners when camera traps record cat presence on their land. Results indicated that tolerance was associated with gender and participation in the camera-trapping programme, whereas intention to kill cats was associated with cultural group (Mennonites vs Mestizos), presence of children in the home and, to a lesser extent, tolerance. Neither dependent variable was significantly related to depredation losses or economic factors. Results suggest that monetary payments alone are unlikely to affect attitudes and behaviours towards carnivores. Payment programmes may be enhanced by accentuating non-monetary incentives, leveraging social norms and targeting specific groups with information about risks and benefits associated with carnivores. By empirically separating two concepts commonly conflated as ‘tolerance’ we clarify understanding of how social forces interact with financial incentives to shape people's relationships with predators.
Between 1964 and 1990, the notion of nonlocality in Bell's papers underwent a profound change as his nonlocality theorem gradually became detached from quantum mechanics, and referred to wider probabilistic theories involving correlations between separated beables. The proposition that standard quantum mechanics is itself nonlocal (more precisely, that it violates ‘local causality’) became divorced from the Bell theorem per se from 1976 on, although this important point is widely overlooked in the literature. In 1990, the year of his death, Bell would express serious misgivings about themathematical form of the local causality condition and leave ill-defined the issue of the consistency between special relativity and violation of the Bell-type inequality. In our view, the significance of the Bell theorem, in both its deterministic and stochastic forms, can only be fully understood by taking into account the fact that a fully Lorentz covariant version of quantum theory, free of action at a distance, can be articulated in the Everett interpretation.
John S. Bell's last word on his celebrated nonlocality theorem and its interpretation appeared in his 1990 paper ‘La nouvelle cuisine’, first published in the year of his untimely death. Bell was careful here to distinguish between the issue of ‘no superluminal signalling’ in quantum theory (both quantum field theory and quantum mechanics) and a principle he first introduced explicitly in 1976 and called ‘local causality’ . In relation to the former, Bell expressed concerns that amplify doubts he had already expressed in 1976. These concerns touch on what is now widely known as the no-signalling theorem in quantum mechanics, and ultimately have to do with Bell's distaste for what he saw as an anthropocentric element in orthodox quantum thinking. In relation to local causality, Bell emphasised that his famous factorizability (no-correlations) condition is not to be seen ‘as the formulation of local causality, but as a consequence thereof’ and stressed how difficult he found it to articulate this consequence. He left the question of any strict inconsistency between violation of factorizability and special relativity theory unresolved, a not insignificant shift from his thinking up to the early 1980s.