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The incompressibility constraint for fluid flow was imposed by Lagrange in the so-called Lagrangian variable description using his method of multipliers in the Lagrangian (variational) formulation. An alternative is the imposition of incompressibility in the Eulerian variable description by a generalization of Dirac’s constraint method using noncanonical Poisson brackets. Here it is shown how to impose the incompressibility constraint using Dirac’s method in terms of both the canonical Poisson brackets in the Lagrangian variable description and the noncanonical Poisson brackets in the Eulerian description, allowing for the advection of density. Both cases give the dynamics of infinite-dimensional geodesic flow on the group of volume preserving diffeomorphisms and explicit expressions for this dynamics in terms of the constraints and original variables is given. Because Lagrangian and Eulerian conservation laws are not identical, comparison of the various methods is made.
Introduction: Despite recent advances in resuscitation, some patients remain in ventricular fibrillation (VF) after multiple defibrillation attempts during out-of-hospital cardiac arrest (OHCA). Vector change defibrillation (VC) and double sequential external defibrillation (DSED) have been proposed as alternate therapeutic strategies for OHCA patients with refractory VF. The primary objective was to determine the feasibility, safety and sample size required for a future cluster randomized controlled trial (RCT) with crossover comparing VC or DSED to standard defibrillation for patients experiencing refractory VF. Secondary objectives were to evaluate the intervention effect on VF termination and return of spontaneous circulation (ROSC). Methods: We conducted a pilot cluster RCT with crossover in four Canadian paramedic services and included all treated adult OHCA patients who presented in VF and received a minimum of three defibrillation attempts. In addition to standard cardiac arrest care, each EMS service was randomly assigned to provide continued standard defibrillation (control), VC or DSED. Services crossed over to an alternate defibrillation strategy after six months. Prior to the launch of the trial, 2,500 paramedics received in-person training for VC and DSED defibrillation using a combination of didactic, video and simulated scenarios. Results: Between March 2018 and September 2019, 152 patients were enrolled. Monthly enrollment varied from 1.4 to 6.1 cases per service. With respect to feasibility, 89.5% of cases received the defibrillation strategy they were randomly allocated to, and 93.1% of cases received a VC or DSED shock prior to the sixth defibrillation attempt. There were no reported cases of defibrillator malfunction, skin burns, difficulty with pad placement or concerns expressed by paramedics, patients, families, or ED staff about the trial. In the standard defibrillation group, 66.6% of cases resulted in VF termination, compared to 82.0% in VC and 76.3% of cases in the DSED group. ROSC was achieved in 25.0%, 39.3% and 40.0% of standard, VC and DSED groups, respectively. Conclusion: Findings from our pilot RCT suggest the DOSE VF protocol is feasible and safe. VF termination and ROSC were higher with VC and DSED compared to standard defibrillation. The results of this pilot trial will allow us to inform a multicenter cluster RCT with crossover to determine if alternate defibrillation strategies for refractory VF may impact patient-centered, clinical outcomes
The European Prediction of Psychosis Study (EPOS) aimed to study a large sample of young patients who are at risk of psychosis and to estimate their conversion rate to psychosis during 18 months follow-up. This presentation describes quality of life and its changes in patients at risk of psychosis.
In six European centres, 16 to 35 year old psychiatric patients were examined. Risk of psychosis was defined by occurrence of basic symptoms, attenuated psychotic symptoms, brief, limited or intermittent psychotic symptoms or familial risk plus reduced functioning. Quality of life (QoL), measured by the Modular System for Quality of Life, was assessed at baseline and at 9 and 18 months’ follow-ups. Psychiatric patients without prodromal symptoms and healthy subjects were comparison groups.
In all, 245 risk patients were included. At baseline, they reported lower QoL than non-risk patients and healthy controls. Basic symptoms associated negatively with QoL, and there were differences between the study centres. During the follow-up, QoL raised less in risk patients than in non-risk patients. Baseline QoL did not predict transition to psychosis. However, its development was poorer in patients with than in those without transition to psychosis.
Those of the psychiatric patients who are at risk of psychosis have lower QoL than other psychiatric patients or healthy controls. QoL does not predict transition to psychosis, but its changes correlates with changes in clinical state. The results indicate that there is a need for comprehensive intervention with the patients at risk of psychosis.
Both schizophrenia and ultra high risk (UHR) patients show reduced neurocognitive performance compared to matched healthy control subjects. In the current study we compared neurocognitive performance at baseline and follow up between UHR patients who made the transition to psychosis and patients who did not.
Patients were eligible for the study when they met criteria for one or more of the following groups: Attenuated symptoms or brief limited intermitted psychotic symptoms or a first degree family member with a psychotic disorder and reduced functioning or basic symptoms. We assessed 216 UHR patients (166 males, mean age: 22,6 SD 5,2) with a neuropsychological test battery composed of the National adult reading test (premorbid IQ), California verbal memory test (verbal memory), spatial working memory test, verbal fluency first letter and categories (executive functioning), finger tapping test (motor speed) and continuous performance test (sustained attention). Data were collected in 7 participating centres of EPOS. Follow up was at 9 months.
37 UHR patients made the transition to psychosis (25 males, mean age 21,5 SD 4,8). The only test that showed a significant difference between the transition and non transition group at baseline was verbal fluency categories (t= 2.79, p = 0.006).
Patients who later make the transition to psychosis perform significantly worse on verbal fluency categories than patients who do not make the transition to psychosis. Verbal fluency may contribute to an improved prediction of psychosis in UHR patients. Follow up results will also be presented.
It has long been known that cannabis can elicit an acute psychotic reaction. Recent work shows that, of the 60 cannabinoid molecules in the plant, delta-9-tetrahydrocannibinol is responsible for the central effects of cannabis. Here we aimed to investigate, in more detail, the psychological effects of synthetic intravenous THC in healthy subjects. Over 2 experimental sessions, participants (N=22) were administered 2.5mg IV THC or placebo under randomised, double-blind conditions. Psychological reactions were assessed using standard rating instruments and a battery of cognitive tests was completed.
Following THC, there was a significant increase in self-rated and observer-rated positive psychotic symptoms which were highly correlated (r=0.62, p=0.001).Phenomena centered on de-synchronisation of self-agency (ipseity disturbance) and hypersalience/paranoia. Participants also reported a significant increase in negative symptomatology under THC conditions, which was not explained by sedation. Finally, working memory/executive functioning was markedly and consistently impaired by THC.
Here we provide further evidence that THC can elicit an acute psychotic reaction in a proportion of healthy subjects. Acute THC-psychosis elicits positive, negative and cognitive symptoms. Compared with other drug models THC recreates symptomatology across 3 major dimensions of schizophrenic psychosis without sedation/clouding of consciousness. Here we also present preliminary evidence that the molecule cannabidiol (CBD) inhibits THC-elicited positive symptoms. Current work in our laboratory is exploring the underlying mechanisms.
The European Prediction of Psychosis Study (EPOS) involved a large (n=245) sample of young individuals at high-risk of developing psychosis. Participants appraisals of criticism and emotional over-involvement were described employing the Level of Expressed Emotion (LEE) measure. This presentation explores results and implications over an 18 month follow-up period.
Across six European centres, n=245 patients aged 16 – 35 years and ascertained to be at high-risk of developing psychosis were assessed over a period of eighteen months. Risk of psychosis was defined by occurrence of basic symptoms, attenuated psychotic symptoms, brief, limited or intermittent psychotic symptoms or familial risk plus reduced functioning. Appraisals of familial expressed emotion from participants towards key family members were examined for relationships to risk of transition to psychosis, psychotic symptomatology and demographical data.
Individuals at high-risk of psychosis were included and compared on the five sub-scales of LEE. Levels of Criticism, Irritability, Intrusiveness and Lack of emotional support were examined with significant correlations found between patient-perceived intrusive over-involvement and depression as well as between sub-scales of LEE and positive symptoms of psychosis. Transition to psychosis was not predicted by LEE in participants.
Perceived LEE of significant others by individuals at high-risk of developing psychosis may have a role in the maintenance of both affective and positive psychotic symptoms prior to the onset of full psychosis. Further explorations of the impact of EE appraisal on developing psychotic symptoms may inform potential targets for therapeutic intervention in both at-risk individuals and family members.
One aim of the European prediction of psychosis study (EPOS) has been to evaluate the clinical course of putatively prodromal patients in terms of psychopathology.
245 patients at risk for psychosis defined by attenuated positive symptoms, brief limited psychotic symptoms, a state/ trait combination or cognitive-perceptive basic symptoms was recruited in six centres in four countries. The Structured Interview for Prodromal Syndromes (SIPS) and the Bonn Scale for the Assessment of Basic Symptoms – Prediction List (BSABS-P) were employed. Follow-up was scheduled after 9 months (t1) and 18 months.
In total, 40 patients developed a psychosis (P). Compared to those without a transition (NP), P showed significantly higher SIPS scores at baseline. The same applied to the BSABS-P sub-scores 'cognitive perception disturbances' and 'cognitive motor disturbances'. The P sub-group developing psychosis after t1 showed no significant change of the SIPS positive (SIPS-P) sub-score or of any BSABS-P score from baseline to t1, whereas all scores improved in the NP group. At t1, SIPS-P and BSABS-P sub-score 'cognitive thought disturbances' were significantly lower in those later becoming psychotic.
Patients at risk showing a transition to psychosis during exhibited a pronounced psychopathology at baseline. Also, the positive symptom scores did not significantly improve during 1st follow-up, whereas those patients with no transition during the complete follow-up showed an improvement of all scores. As EPOS is a naturalistic study, different treatments have been performed in a considerable portion of the patients and association with course awaits further analysis.
Trauma and dissociation may be important factors contributing to the experiences of distressing voice hearing. However, there is scant mention of how to target and treat such processes when working with people with psychosis. This case study reports on an initial attempt to work with dissociation and trauma memories in a person with voices. A single case approach was used, with standardized measures used before, during and after 24 sessions of cognitive therapy, and at 6-month follow-up. In addition, session-by-session measures tracked frequency and distress associated with voices and dissociation. The participant reported significant improvements in terms of reduced frequency and distress of dissociation, and voice hearing, as well as improvement in low mood at the end of treatment. At follow-up there were enduring benefits in terms of dissociation and trauma-related experiences, as well as broad recovery but not of change in voices. This case illustrated the potential benefit of targeting dissociation and exposure to trauma memories in producing general symptom improvement and specific reductions in dissociation and voice hearing at end of treatment.
The objective of this study was to investigate the impact of the most commonly cited factors that may have influenced infants’ gut microbiota profiles at one year of age: mode of delivery, breastfeeding duration and antibiotic exposure. Barcoded V3/V4 amplicons of bacterial 16S-rRNA gene were prepared from the stool samples of 52 healthy 1-year-old Australian children and sequenced using the Illumina MiSeq platform. Following the quality checks, the data were processed using the Quantitative Insights Into Microbial Ecology pipeline and analysed using the Calypso package for microbiome data analysis. The stool microbiota profiles of children still breastfed were significantly different from that of children weaned earlier (P<0.05), independent of the age of solid food introduction. Among children still breastfed, Veillonella spp. abundance was higher. Children no longer breastfed possessed a more ‘mature’ microbiota, with notable increases of Firmicutes. The microbiota profiles of the children could not be differentiated by delivery mode or antibiotic exposure. Further analysis based on children’s feeding patterns found children who were breastfed alongside solid food had significantly different microbiota profiles compared to that of children who were receiving both breastmilk and formula milk alongside solid food. This study provided evidence that breastfeeding continues to influence gut microbial community even at late infancy when these children are also consuming table foods. At this age, any impacts from mode of delivery or antibiotic exposure did not appear to be discernible imprints on the microbial community profiles of these healthy children.
Emergency physicians are using bolus-dose vasopressors to temporize hypotensive patients until more definitive blood pressure support can be established. Despite a paucity of clinical outcome data, emergency department applications are expanding into the prehospital setting. This series presents two cases of field expedient vasopressor use by emergency medicine providers for preflight stabilization during aeromedical evacuation to a hospital ship as part of the United States Navy disaster response in Puerto Rico. A critical approach and review of the literature are discussed.
Two critically ill patients were managed in an austere environment as a result of the devastation from Hurricane Maria (Yabucoa, Puerto Rico; 2017). They both exhibited signs of respiratory distress, hemodynamic instability, and distributive shock requiring definitive airway management and hemodynamic support prior to aeromedical evacuation.
The novel use of field expedient vasopressors prior to induction for rapid sequence intubation was successfully and safely employed in both cases. Both patients had multiple risk factors for peri-induction cardiac arrest given their presenting hemodynamics. Despite their illness severity, both patients were induced, transported, and ultimately admitted to the intensive care unit (ICU) in stable condition following administration of the field expedient vasopressors.
Field expedient vasopressors were safely and effectively employed in an austere field environment during a disaster response. This case series contributes to the growing body of literature of safe bolus-dose vasopressor use by emergency physicians to temporize hypotensive patients in resource-constrained situations.
HardwickJM, MurnanSD, Morrison-PonceDP, DevlinJJ. Field Expedient Vasopressors During Aeromedical Evacuation: A Case Series from the Puerto Rico Disaster Response. Prehosp Disaster Med. 2018;33(6):668–672.
Posttraumatic stress disorder (PTSD) and stress/trauma exposure are cross-sectionally associated with advanced DNA methylation age relative to chronological age. However, longitudinal inquiry and examination of associations between advanced DNA methylation age and a broader range of psychiatric disorders is lacking. The aim of this study was to examine if PTSD, depression, generalized anxiety, and alcohol-use disorders predicted acceleration of DNA methylation age over time (i.e. an increasing pace, or rate of advancement, of the epigenetic clock).
Genome-wide DNA methylation and a comprehensive set of psychiatric symptoms and diagnoses were assessed in 179 Iraq/Afghanistan war veterans who completed two assessments over the course of approximately 2 years. Two DNA methylation age indices (Horvath and Hannum), each a weighted index of an array of genome-wide DNA methylation probes, were quantified. The pace of the epigenetic clock was operationalized as change in DNA methylation age as a function of time between assessments.
Analyses revealed that alcohol-use disorders (p = 0.001) and PTSD avoidance and numbing symptoms (p = 0.02) at Time 1 were associated with an increasing pace of the epigenetic clock over time, per the Horvath (but not the Hannum) index of cellular aging.
This is the first study to suggest that posttraumatic psychopathology is longitudinally associated with a quickened pace of the epigenetic clock. Results raise the possibility that accelerated cellular aging is a common biological consequence of stress-related psychopathology, which carries implications for identifying mechanisms of stress-related cellular aging and developing interventions to slow its pace.
Hamiltonian extended magnetohydrodynamics (XMHD) is restricted to respect helical symmetry by reducing the Poisson bracket for the three-dimensional dynamics to a helically symmetric one, as an extension of the previous study for translationally symmetric XMHD (Kaltsas et al., Phys. Plasmas, vol. 24, 2017, 092504). Four families of Casimir invariants are obtained directly from the symmetric Poisson bracket and they are used to construct Energy–Casimir variational principles for deriving generalized XMHD equilibrium equations with arbitrary macroscopic flows. The system is then cast into the form of Grad–Shafranov–Bernoulli equilibrium equations. The axisymmetric and the translationally symmetric formulations can be retrieved as geometric reductions of the helically symmetric one. As special cases, the derivation of the corresponding equilibrium equations for incompressible plasmas is discussed and the helically symmetric equilibrium equations for the Hall MHD system are obtained upon neglecting electron inertia. An example of an incompressible double-Beltrami equilibrium is presented in connection with a magnetic configuration having non-planar helical magnetic axis.
Problems of particle dynamics involving unsteady Stokes flows in confined geometries are typically harder to solve than their steady counterparts. Approximation techniques are often the only resort. Felderhof (see e.g. J. Phys. Chem. B, vol. 109 (45), 2005, pp. 21406–21412; J. Fluid Mech., vol. 637, 2009, pp. 285–303) has developed a point-particle approximation framework to solve such problems, especially in the context of Brownian motion. Despite excellent agreement with past experiments, this framework produces unsteady drag coefficients that depend on particle density. This is inconsistent, since the problem can be formulated mathematically without any reference to the particle’s density. We address this inconsistency in our work. Upon implementing our modifications, the framework passes consistency checks that it previously failed. Further, it is not obvious that such an approximation should work for short-time-scale motion. We investigate its validity by deriving it from a general formalism based on integral equations through a series of systematic approximations. We also compare results from the point-particle framework against a calculation performed using the method of reflections, for the specific case of a sphere near a full-slip plane boundary. We find from our analysis that the reasons for the success of the point-particle approximation are subtle and have to do with the nature of the unsteady Oseen tensor. Finally, we provide numerical predictions for Brownian motion near a full-slip and a no-slip plane wall based on the point-particle approximation as used by Felderhof, our modified point-particle approximation and the method of reflections. We show that our modifications to Felderhof’s framework would become significant for systems of metallic nanoparticles in liquids.
Background: Internalized stigma is a significant difficulty for those who experience psychosis, but it has never been conceptualized using cognitive theory. Aims: The aim of this paper is to outline a cognitive model conceptualizing internalized stigma experienced by people who also experience psychosis. Method: Previous literature is reviewed, critiqued and synthesized to develop the model. It draws upon previous social cognitive models of internalized stigma and integrates cognitive behavioural theory and social mentality theory. Results: This paper identifies key cognitive, behavioural and emotional processes that contribute to the development and maintenance of internalized stigma, whilst also recognizing the central importance of cultural context in creating negative stereotypes of psychosis. Moreover, therapeutic strategies to alleviate internalized stigma are identified. A case example is explored and a formulation and brief intervention plan was developed in order to illustrate the model in practice. Conclusion: An integrative cognitive model is presented, which can be used to develop individualized case formulations, which can guide cognitive behavioural interventions targeting internalized stigma in those who experience psychosis. More research is required to examine the efficacy of such interventions. In addition, it is imperative to continue to research interventions that create change in stigma at a societal level.
Introduction: High-quality cardiopulmonary resuscitation (CPR) is essential for patient survival. Typically, CPR quality is only measured during the first 10 minutes of resuscitation. There is limited research examining the quality of CPR over the entire duration of resuscitation.Objective: To examine the quality of CPR over the entire duration of resuscitation and correlate the quality of CPR to patient survival. Methods: This was a retrospective observational study using data from the Toronto RescuNET Epistry-Cardiac Arrest database. We included consecutive, adult (>18) OHCA treated by EMS between January 1, 2014 and September 30, 2015. High-quality CPR was defined, in accordance with 2015 AHA Guidelines, as a chest compression rate of 100-120/min, depth of 5.0-6.0 cm and chest compression fraction (ccf) of >0.80. We further categorized high-quality resuscitation as meeting benchmarks >80% of the time, moderate-quality between 50-80% and low-quality meeting benchmarks <50% of the resuscitation. We used multivariable logistic regression to determine association between variables of interest, including CPR quality metrics, and survival to hospital discharge. Results: A total of 5,208 OHCA met our inclusion criteria with a survival rate of 8%. The median (IQR) duration of resuscitation was 23.0 min (15.0,32.7). Overall CPR quality was considered high-quality for ccf in 81% of resuscitation episodes, 41% for rate, and 7% for depth. The percentage of resuscitations meeting the quality benchmarks differed between survivors and non-survivors for both depth (15% vs 6%) and ccf (61% vs 83%) (P value <0.001). After controlling for Utstein variables maintaining a chest compression depth within recommendations for >80% showed a trend towards improved survival (OR 1.68, 95% CI 0.96, 2.92). Other variables associated with survival were public location, initial CPR by EMS providers or bystanders, witnessed cardiac arrest (EMS or bystander), and initial shockable rhythm. Increasing age and longer duration of resuscitation were associated with decreased survival. Conclusion: Overall, EMS providers were not able to maintain rate or depth within guideline recommendations for the majority of the duration of resuscitation. Maintaining chest compression depth for greater than 80% of the resuscitation showed a trend towards increased survival from OHCA.
Angiotensin-converting enzyme (ACE) inhibitors are important agents in blood pressure (BP) management. It was recently shown that the egg-protein hydrolysate NWT-03 inhibited ACE in Zucker diabetic fatty rats. We therefore designed a dose-finding study to assess the effects of 1, 2 and 5 g NWT-03 on daytime, 36-h, and night-time systolic and diastolic BP (SBP and DBP) in ninety-two generally healthy subjects with normal BP (n 29), high-normal BP (n 34) or mild hypertension (n 29). The study had a cross-over design with six treatment arms (1 g NWT-03 or placebo in period 1 and placebo or 1 g NWT-03 in period 2, 2 g NTW-03 or placebo in period 1 and placebo or 2 g NWT-03 in period 2, or 5 g NTW-03 or placebo in period 1 and placebo or 5 g NTW-03 in period 2). A comparable number of subjects from each BP class were included in each study arm. Duration of both treatments in each arm was 7 d, separated by 5-d wash-out periods. BP was measured with an ambulatory BP monitor before and after the treatments. In mild-hypertensive subjects, 2 g NWT-03 significantly decreased daytime SBP (7·9 mmHg; P=0·006), daytime DBP (4·2 mmHg; P=0·009), 36-h SBP (6·9 mmHg; P=0·015) and 36-h DBP (3·5 mmHg; P=0·035) compared with placebo subjects. In addition, in mild-hypertensive subjects, 5 g NWT-03 significantly decreased night-time SBP (14·8 mmHg; P=0·008) and night-time DBP (8·4 mmHg; P=0·020) compared with that in placebo subjects. To conclude, we found that 2 g NWT-03 lowered daytime and 36-h BP in subjects with mild hypertension, and 5 g NWT-03 lowered night-time BP in subjects with mild hypertension. As no dose–response relationship was evident, these results should be interpreted with care, and additional studies are needed.
The Vlasov–Maxwell equations possess a Hamiltonian structure expressed in terms of a Hamiltonian functional and a functional bracket. In the present paper, the transformation (‘lift’) of the Vlasov–Maxwell bracket induced by the dynamical reduction of single-particle dynamics is investigated when the reduction is carried out by Lie-transform perturbation methods. The ultimate goal of this work is to provide an explicit pathway to the Hamiltonian formulations for the guiding-centre and gyrokinetic Vlasov–Maxwell equations, which have found important applications in our understanding of turbulent magnetized plasmas. Here, it is shown that the general form of the reduced Vlasov–Maxwell equations possesses a Hamiltonian structure defined in terms of a reduced Hamiltonian functional and a reduced bracket that automatically satisfies the standard bracket properties.